@article {pmid41550042, year = {2026}, author = {Liu, S and Liu, H and Li, Z and Huang, T and Zhu, X and Che, I and Zhan, H and Chio, LH and Tang, F and Ran, M and Lin, X and Wen, S and Li, H and Li, J and Li, Z}, title = {Transformer-Based Multi-Channel K-Complex Detection Algorithm Tailored for Elderly Patients With Amnestic Mild Cognitive Impairment.}, journal = {Journal of sleep research}, volume = {}, number = {}, pages = {e70285}, doi = {10.1111/jsr.70285}, pmid = {41550042}, issn = {1365-2869}, support = {JCYJ20220530141215033//Shenzhen Science and Technology Program/ ; 2024C01//Fund for Creative Research of The Second People's Hospital of Foshan/ ; HL46380/NH/NIH HHS/United States ; RR00080-39/NH/NIH HHS/United States ; T32-HL07567/NH/NIH HHS/United States ; RO1-46380/NH/NIH HHS/United States ; R01HL62252/HL/NHLBI NIH HHS/United States ; R24 HL114473/HL/NHLBI NIH HHS/United States ; 75N92019R002/HL/NHLBI NIH HHS/United States ; R01AG036838//National Institute on Ageing/ ; R01AG058680//National Institute on Ageing/ ; 1UL1RR025011/RR/NCRR NIH HHS/United States ; }, abstract = {K-complexes (KCs) are hallmark waveforms of non-rapid eye movement stage 2 (NREM2) sleep, associated with sleep maintenance and memory consolidation. KC density and amplitude decline with ageing and are further altered in amnestic mild cognitive impairment (aMCI). Manual scoring, while considered the gold standard, is labour intensive and subjective. Existing automated KC detectors, often trained on small public datasets of young healthy subjects using single-channel electroencephalography (EEG), may underperform in elderly aMCI individuals whose KC morphology is more variable. Hence, the goal of this study is to develop and validate AdaPatchFormer, an automated multi-channel Transformer-based KC detection algorithm optimised for elderly individuals with aMCI. AdaPatchFormer integrates a period embedding module, which adaptively identifies physiologically relevant rhythms across multiple frequency bands, with a multi-granularity encoder that progressively fuses temporal features across channels. The model was trained on full-night polysomnography (PSG) recordings from 268 elderly aMCI patients and evaluated against expert-labelled gold standards on four independent test datasets: private aMCI and cognitively normal cohorts, plus two public elderly cohorts. Across all datasets, AdaPatchFormer outperformed the two open-access detectors by Chambon et al. and Lechat et al., achieving higher recall, precision, specificity, accuracy, F1 score, Matthews correlation coefficient (MCC) and a well-balanced recall-precision profile. Moreover, the KC density and amplitude detected by AdaPatchFormer closely mirrored expert annotations. These results suggest that AdaPatchFormer is a robust, accurate, and objective algorithm for KC detection in elderly individuals, with the potential for supporting early and cost-effective identification of aMCI in real-world settings.}, }
@article {pmid41545383, year = {2026}, author = {Wang, X and Liu, Y and Jiang, C and Huang, Z and Yan, H and Wong, SH and Johnson, CH and Zhang, J and Ge, Y and Zhang, F and Zhang, J and Lai, R and Gao, P and Zhang, X and Shen, X}, title = {TidyMass2: advancing LC-MS untargeted metabolomics through metabolite origin inference and metabolic feature-based functional module analysis.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-026-68464-7}, pmid = {41545383}, issn = {2041-1723}, support = {025402-00001//Ministry of Education - Singapore (MOE)/ ; }, abstract = {Untargeted metabolomics provides a direct window into biochemical activities but faces critical challenges in determining metabolite origins and interpreting unannotated metabolic features. Here, we present TidyMass2, an enhanced computational framework for Liquid Chromatography-Mass Spectrometry (LC-MS) untargeted metabolomics that addresses these limitations. TidyMass2 introduces three major innovations compared to its predecessor, TidyMass: (1) a comprehensive metabolite origin inference capability that traces metabolites to human, microbial, dietary, pharmaceutical, and environmental sources through integration of 11 metabolite databases containing 532,488 metabolites with source information; (2) a metabolic feature-based functional module analysis approach that bypasses the annotation bottleneck by leveraging metabolic network topology to extract biological insights from unannotated metabolic features; and (3) a graphical interface that makes advanced metabolomics analyses accessible to researchers without programming expertise. Applied to longitudinal urine metabolomics data from human pregnancy, TidyMass2 identified diverse metabolites originating from human, microbiome, and environment, and uncovered 27 dysregulated metabolic modules. It increased the proportion of biologically interpretable metabolic features from 5.8% to 58.8%, revealing coordinated changes in steroid hormone biosynthesis, carbohydrate metabolism, and amino acid processing. By expanding biological interpretation beyond MS[2] spectra-based annotated metabolites, TidyMass2 enables more comprehensive metabolic phenotyping while upholding open-source principles of reproducibility, traceability, and transparency.}, }
@article {pmid41542943, year = {2026}, author = {Broderick, C and Poulsen, CS and Hjelmsø, MH and Marrs, T and Radulovic, S and Logan, K and Li, X and Wu, Z and Sørensen, SJ and Ezzamouri, B and Alexander, H and Fyhrquist, N and Alenius, H and Bhattacharyya, M and Neumann, AU and Lack, G and Perkin, M and Bønnelykke, K and Stokholm, J and Flohr, C}, title = {Associations between early-life exposures and the infant skin microbiome.}, journal = {The British journal of dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1093/bjd/ljaf524}, pmid = {41542943}, issn = {1365-2133}, abstract = {BACKGROUND: Factors influencing the early-life skin microbiome, and the association with atopic dermatitis (AD), are relatively unexplored.<br><br>OBJECTIVE: To evaluate associations with the infant skin microbiome during the first year of life.<br><br>METHODS: 3-month-old infants from the Enquiring About Tolerance (EAT) birth cohort were examined for AD at enrolment, 1 and 3 years of age. Parent-completed questionnaires, trans-epidermal water loss (TEWL), and filaggrin mutation status were evaluated. Bacterial swabs were collected from the elbow crease and volar forearm in 148 infants at 3 months and 1 year of age, and the microbiome composition was characterized using 16S rRNA gene sequencing (V3-V4 region).<br><br>RESULTS: Shannon diversity was significantly higher at the forearm compared to the elbow. Staphylococcus, Acinetobacter, and Streptococcus were the most abundant genera across time and body-site. Microbiome community composition was primarily associated with body-site and age (p&#x2264;0.001, both). Other significant associations were found with ethnicity (p=0.009), filaggrin status (p&#x2264;0.001), urban-vs-rural residence (p=0.005), older siblings (p=0.041), bath product usage at 3 months (p=0.011), but not with pets (p=0.159), systemic antibiotics (p=0.27) nor with bathing frequency (p=0.109). The microbiome was associated with elevated TEWL (3-months p=0.004, 1-year p&#x2264;0.001) and with concurrent AD (3-months p=0.027, 1-year p&#x2264;0.001). Streptococcus parasanguinis was significantly less abundant in non-lesional skin of infants with AD at 3 months.<br><br>CONCLUSION: In addition to age and body-site, the infant skin microbiome is associated with heritable factors, the home environment, hygiene practices, and with the presence of AD.}, }
@article {pmid41530288, year = {2026}, author = {Huang, Z and Liu, Y and Wu, Y and Zhang, F and Yu, L and Gao, S and Wen, W and Wang, G and Su, R and Xia, P and Zhou, Q and Bie, Y and Hu, P and Burgermeister, E and Lan, P and Wu, X and Zhang, H and Zhang, F and El-Omar, EM and Zuo, T}, title = {Publisher Correction: Gut mucosal mycobiome profiling in Crohn's disease uncovers an AMP-mediated anti-inflammatory effect of Cladosporium sphaerospermum.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1038/s42255-026-01460-9}, pmid = {41530288}, issn = {2522-5812}, }
@article {pmid41527254, year = {2026}, author = {London, RE}, title = {Microbiome-generated antifolates.}, journal = {FEBS letters}, volume = {}, number = {}, pages = {}, doi = {10.1002/1873-3468.70252}, pmid = {41527254}, issn = {1873-3468}, support = {ZIA ES050111/ES/NIEHS NIH HHS/United States ; }, abstract = {The folate biosynthesis activity of the human microbiome provides reduced folate metabolites that are readily absorbed from the gastrointestinal (GI) tract. The bacterial folate biosynthesis enzyme dihydropteroate synthase (DHPS), which adds p-aminobenzoate (pABA) to an activated pterin precursor, is an important antibiotic target. Both the broad-spectrum p-aminobenzenesulfonamide antibiotics, and the drug p-aminosalicylate (PAS, 2-hydroxy-pABA) with high selectivity for Mycobacterium tuberculosis, are competitive DHPS substrates. The adducts formed from these drugs, DHP-sulfonamides (sulfapterins) and 2'-hydroxyfolate metabolites, respectively, have been reported to exhibit antifolate activity in studies of microorganisms. The presence of these DHP-adducts and their effects on the host organism are largely undetermined; however, their close structural relationship to dihydrofolate (DHF) suggests that they are likely to mediate some side effects reported for these antibiotics. Naturally occurring pABA analogs that probably function similar to DHPS-targeted antibiotics have been identified in carrots and bacteria. Impact statement pABA analogs represent an important class of antibiotics, that are converted into dihydrofolate analogs by organisms present in the human microbiome. These analogs may mediate reported side-effects associated with these antibiotics. Several naturally occurring pABA mimics have been identified that are likely to exhibit antibiotic activity.}, }
@article {pmid41526636, year = {2026}, author = {Neff, HA and Yıldız-Altay, &#xdc; and Salam, N and Ward, DV and Shepard, D and Ramirez-Ortiz, ZG and Richmond, JM}, title = {Gut dysbiosis in a murine model of cutaneous lupus erythematosus correlates with antigen-specific T cells and antigen-presenting cells in skin.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-34741-6}, pmid = {41526636}, issn = {2045-2322}, support = {Mechanisms &amp; Targets Award//Lupus Research Alliance/ ; Mechanisms &amp; Targets Award//Lupus Research Alliance/ ; }, abstract = {The commensal organisms constituting the human microbiome are increasingly appreciated to fortify epithelial barriers and modulate host immunity. Dysbiosis of both single strains and communities can contribute to inflammatory conditions. Here, we sought to characterize potential dysbiosis in our inducible mouse model of cutaneous lupus erythematosus (CLE). We hypothesized that gut dysbiosis would occur based on several studies that found lower Firmicutes/Bacteroidetes (F/B) ratios and decreased diversity in systemic lupus erythematosus (SLE) cohorts compared to healthy counterparts, a mouse study that identified Ro60 commensal orthologs that can trigger onset of lupus-like disease, and a study of CLE that identified outgrowth of Staphylococcus aureus in the skin. Using whole genome shotgun sequencing, we identified differences in pre- and post-irradiation cohorts, particularly an increase in Duncaniella, a decrease in Prevotella, and a reduction in alpha diversity following irradiation. Baseline alterations in CLE mice gut bacteria compared to littermate controls were also extant, including trends toward increased Parabacterides distasonis and Bacteroides acidifaciens in CLE mice. Importantly, we noted an increase in Phocaeicola sartorii in CLE mice compared to littermate controls post-disease induction. We examined the mycobiome in our mice and noted a reduction of Colletotrichum tofieldiae specifically in CLE mice post-disease induction, and a trend towards increased Periglandula ipomoeae. Last, we correlated abundance of genera and species with flow cytometry data obtained from the skin, lymph node and spleen, and identified specific strains that correlated with presence of antigen-specific T cells and different antigen presenting cell populations. Thus, our model exhibits similar changes to other models of lupus-like disease, and our data identify potential novel strains/species that could be modified for CLE and/or SLE treatment such as through generation of probiotics or specific antimicrobial agents.}, }
@article {pmid41525625, year = {2026}, author = {Weng, Q and Hu, M and Peng, G and Lu, W and Wang, H and Zhu, J}, title = {Variational Bayesian Multi-Output Gaussian Process Regression for Metabolic Profiles Prediction with Microbiome Data.}, journal = {IEEE transactions on computational biology and bioinformatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TCBBIO.2026.3653067}, pmid = {41525625}, issn = {2998-4165}, abstract = {Understanding the pivotal role of the human microbiome in health necessitates accurate metabolite prediction, which is crucial for unraveling the intricate interplay between the gut microbiome and human health. This study introduces an innovative approach, Variational Bayesian Multi-Output Gaussian Process Regression (VBMOGPR), to address the challenges posed by the complex, high-dimensional nature of microbiome data. VBMOGPR predicts microbial metabolites, quantifies the model confidence, and incorporates uncertainty estimates. Employing a Bayesian framework with Automatic Relevance Determination (ARD) for feature selection enhances interpretability and performance. Comparative analysis across 14 datasets within a meta-database demonstrated the superiority of VBMOGPR, marking a significant advancement in metabolite prediction and its implications for microbiome impact on human health. In addition, we confirmed that VBMOGPR could tap the potential microbial metabolic association.}, }
@article {pmid41524397, year = {2026}, author = {Kozik, AJ}, title = {Out of the box: toward new frameworks for understanding human microbiomes.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0100024}, doi = {10.1128/msphere.01000-24}, pmid = {41524397}, issn = {2379-5042}, abstract = {The study of the human microbiome (mirroring broader practice across biomedical science), has historically defaulted to the use of simplified, socially constructed "boxes," such as racial and ethnic labels, that fail to accurately capture human variation and fundamentally misdirect the search for mechanisms to explain differences in health outcomes. Five years ago, I proposed a "frameshift," a fundamental conceptual shift away from relying on these categories and toward a more nuanced, careful approach to the complexity of human variation. Moving "out of the box" means tackling the difficult but essential work of analyzing microbial variation through a systems lens, connecting large-scale ecosocial drivers to individual mechanisms and outcomes. In this Full Circle review, I discuss rapid progress in the field toward this new framework and argue that by adopting transdisciplinary methods, we can generate more accurate, actionable, and equitable solutions for human health.}, }
@article {pmid41519338, year = {2026}, author = {Vacca, M and Cavaliere, M and Celano, G and Pinto, D and De Stradis, A and Spagnuolo, M and Brunetti, G and De Mastro, F and Di Bari, B and Vona, D and De Angelis, M}, title = {Addressing bacteria with tannins chemistry: an innovative food inspired organic lauryl-gallate-based coating to increase probiotics resistance.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {150164}, doi = {10.1016/j.ijbiomac.2026.150164}, pmid = {41519338}, issn = {1879-0003}, abstract = {Functional foods and various applications based on beneficial effect provided by probiotics have gained increasing attention due to the well-established link with human health. Probiotics are pivotally involved in regulating the intestinal microbiota, influencing various physiological processes that impact the overall well-being of hosts. However, ensuring probiotic survival and, after delivery, keeping a residual biological activity remains one of the most major challenges. To address this issue, various encapsulation strategies have been developed to protect probiotics. In this study, we investigated an innovative approach of single-cell coating to enhance probiotic resistance under stress conditions, including simulated digestion, heat exposure, and refrigerated storage. The methodology employs the natural antioxidant lauryl gallate (LG), entrapped at molecular lever in probiotics membranes via hydrophobic insertion, which can be further involved in the synthesis of the macromolecular coating using (and comparing) 3 defined methodologies: oxidative polymerization, cross-linking and metal:organic chelation. All the coated products exhibited the ability to preserve probiotic viability. Our findings demonstrated that coated probiotics showed significantly higher survival rates compared to uncoated controls, particularly under harsh gastric (+2 log) and intestinal conditions (+1 log), as well as during heat treatment (+ 1.5 log) and long-term cold storage (+3 log). Therefore, the present study highlights the potential of single-cell coatings as an alternative way to encapsulate probiotics enhancing the protection against environmental stressors. These findings provide valuable insights for the development of advanced probiotic delivery systems, including the plausible future applications in functional foods and personalized biomedicine.}, }
@article {pmid41511159, year = {2026}, author = {Paone, P and Petitfils, C and Puel, A and Latousakis, D and de Vos, WM and Delzenne, NM and Juge, N and Van Hul, M and Cani, PD}, title = {Akkermansia muciniphila modulates intestinal mucus composition to counteract high-fat diet-induced obesity in mice.}, journal = {Gut microbes}, volume = {18}, number = {1}, pages = {2612580}, doi = {10.1080/19490976.2025.2612580}, pmid = {41511159}, issn = {1949-0984}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Obesity/metabolism/microbiology/etiology/therapy ; Mice, Inbred C57BL ; Mice ; *Intestinal Mucosa/metabolism/microbiology ; Male ; Mucins/metabolism/genetics ; *Probiotics/administration &amp; dosage ; Gastrointestinal Microbiome ; *Mucus/metabolism/chemistry ; Akkermansia ; *Verrucomicrobia ; }, abstract = {OBJECTIVE: This study investigates whether live Akkermansia muciniphila Muc[T] supplementation can counteract obesity and metabolic dysfunctions induced by a high-fat diet (HFD) by modulating intestinal mucus production, secretion and composition.<br><br>DESIGN: C57BL/6J mice were fed an HFD with or without live A. muciniphila Muc[T] (2&#x2009;&#xd7;&#x2009;10[8] CFU per day) supplementation or a control diet for 6 weeks. Body weight, fat mass gain and metabolic markers were measured. Intestinal mucus characteristics were assessed via gene expression analysis of mucins and analysed mucin glycosylation by tandem mass spectrometry (MS/MS).<br><br>RESULTS: Mice receiving live A. muciniphila Muc[T] exhibited reduced body weight gain and fat mass accumulation compared to HFD controls, without changes in muscle mass. A. muciniphila improved gut barrier integrity by increasing antimicrobial peptide expression in the jejunum and in the colon of HFD-fed mice. Furthermore, live A. muciniphila Muc[T] influenced markers of goblet cell differentiation and restored the expression of mucin markers altered by HFD. Specifically, live A. muciniphila Muc[T] counteracted HFD-induced mucin 3 (Muc3) expression depletion in the colon. Although the overall mucus thickness was not affected by live A. muciniphila Muc[T], the bacteria significantly modulated mucin glycans composition. Live A. muciniphila Muc[T] did not change the gut microbiota composition.<br><br>CONCLUSION: These findings highlight the protective effects of live A. muciniphila Muc[T] against diet-induced metabolic dysfunctions by modulating adiposity, mucus layer composition, and glycan profiles. This reinforces its potential as a therapeutic strategy for metabolic disorders associated with gut microbiota alterations.}, }
@article {pmid41509038, year = {2026}, author = {Xu, T and Wei, Z and Zeng, Q and Feng, Q and Zhi, M}, title = {Unveiling potential driver taxa in subgingival plaque and their roles in mediating periodontitis progression.}, journal = {Journal of oral microbiology}, volume = {18}, number = {1}, pages = {2609452}, pmid = {41509038}, issn = {2000-2297}, abstract = {BACKGROUND: Periodontitis progression is accompanied by a succession of the oral microbiome. However, the dynamic microbial transitions that link different disease stages and contribute to disease progression remain incompletely understood.<br><br>OBJECTIVE: This study aims to identify microbial taxa that may serve as potential drivers underlying increasing severity of periodontitis.<br><br>DESIGN: Subgingival sample 16S rRNA gene sequencing data were reprocessed for quality control and taxonomic annotation. MaAsLin2 was used to identify microbial differences between groups, and co-occurrence networks were built based on the differential taxa. NetMoss algorithm was applied to identify key microbes driving the transition from health to periodontitis. Correlation and mediation analyses were used to assess the associations between these driver taxa and periodontal clinical indicators.<br><br>RESULTS: Putative novel pathogens (e.g. Filifactor alocis, Slackia exigua) were markedly enriched in periodontitis, whereas potential protective taxa (e.g. Haemophilus and Rothia) had higher relative abundance in the health group. The microbial co-occurrence networks in the periodontitis groups were progressively disrupted, characterized by reduced network robustness and heightened vulnerability in the Stage III and IV groups. The driver taxa probably influenced the severity of periodontitis through modulation of periodontal clinical indicators, with positive or negative correlations observed between these taxa and periodontal clinical indicators.<br><br>CONCLUSIONS: Capnocytophaga, Paludibacter, Dialister pneumosintes, Eubacterium minutum and Phocaeicola abscessus are proposed as key driver taxa across different periodontal health conditions, and exhibited significant correlations with periodontal clinical indicators.}, }
@article {pmid41504222, year = {2026}, author = {Li, T and Huang, M and Cai, J and Li, X and Xing, Y and He, R and Wan, Z and Gan, Y and Li, Z and Weng, J and Xie, Y and Wu, Y and Liu, X and Wang, X and Luo, Y and Huang, M and Lin, J and Yu, H}, title = {m[1]A-Dependent TRMT6/61A-ARG2 Axis Drives Protumorigenic Senescence by Remodeling the Tumor Microenvironment.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e18536}, doi = {10.1002/advs.202518536}, pmid = {41504222}, issn = {2198-3844}, support = {82372715//National Natural Science Foundation of China/ ; 82173067//National Natural Science Foundation of China/ ; 82272965//National Natural Science Foundation of China/ ; 82473456//National Natural Science Foundation of China/ ; 2022A1515012656//Natural Science Foundation of Guangdong Province/ ; 2025A04J5297//Science and Technology Program of Guangzhou/ ; 2023A04J1817//Science and Technology Program of Guangzhou/ ; 1010CG(2022)-02//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research-'1010' Program/ ; A2023094//Medical Scientific Research Foundation of Guangdong Province/ ; R2021217202512965//Excellent Talent Training Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; 2022JBGS07//Scientific Research Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; 23ykbj007//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; //Program of Introducing Talents of Discipline to Universities, Sun Yat-sen University/ ; 2020B1111170004//Program of Guangdong Provincial Clinical Research Center for Digestive Diseases/ ; 2012//National Key Clinical Discipline/ ; }, abstract = {Cellular senescence, a fundamental hallmark of aging, plays a paradoxical, often pro-tumorigenic role in cancer. This malignancy is largely driven by the senescence-associated secretory phenotype (SASP), yet the mechanisms that govern the production of a pro-tumorigenic SASP remain poorly understood. This study uncovers an epitranscriptomic axis in colorectal cancer (CRC) where the TRMT6/TRMT61A tRNA N[1]-methyladenosine (m[1]A) methyltransferase complex is aberrantly elevated, driving a senescent state in malignant cells. Mechanistically, TRMT6/61A-dependent m[1]A deposition on specific tRNAs enhances the translational efficiency of their cognate codons. This codon-biased translational control selectively boosts the synthesis of ARG2. Accumulation of ARG2 subsequently activates mTOR and NF-κB signaling and thereby establishes a robust SASP, which actively reprograms the tumor microenvironment by promoting the growth and invasiveness of neighboring cancer cells, activating cancer-associated fibroblasts, and polarizing immunosuppressive M2 macrophages. Collectively, these findings define the TRMT6/61A-ARG2 pathway as a driver for pro-tumorigenic senescence in an m[1]A-dependent manner, revealing a new layer of translational control in aging-associated pathology and offering a compelling rationale for developing senomorphic therapies.}, }
@article {pmid41501528, year = {2026}, author = {Huang, Z and Liu, Y and Wu, Y and Zhang, F and Yu, L and Gao, S and Wen, W and Wang, G and Su, R and Xia, P and Zhou, Q and Bie, Y and Hu, P and Burgermeister, E and Lan, P and Wu, X and Zhang, H and Zhang, F and El-Omar, EM and Zuo, T}, title = {Gut mucosal mycobiome profiling in Crohn's disease uncovers an AMP-mediated anti-inflammatory effect of Cladosporium sphaerospermum.}, journal = {Nature metabolism}, volume = {}, number = {}, pages = {}, pmid = {41501528}, issn = {2522-5812}, support = {82172323//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32100134//National Natural Science Foundation of China (National Science Foundation of China)/ ; 823B2010//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32372334//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82304144//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Crohn's disease (CD) is a subtype of inflammatory bowel disease that most commonly affects the terminal ileum and is associated with abnormal gut microbiome composition. However, the fungi of the small bowel mucosa and their metabolic functions, particularly protective ones, remain largely unexplored. We enrolled patients with CD and healthy individuals from three independent cohorts and conducted multi-omics profiling of the ileal mucosal mycobiome and bacteriome, along with the faecal mycobiome, bacteriome and metabolome. We show that compared to a healthy mucosa, the fungus Cladosporium sphaerospermum is remarkably depleted in the mucosa of patients with CD, yet remains unchanged in faeces. Subsequent causality studies reveal that C. sphaerospermum occupies the intestinal crypt niche and counteracts intestinal inflammation partly by adenosine 5'-monophosphate (AMP) production, as demonstrated in mice, in vitro and in fungal cultures. Mechanistically, C. sphaerospermum upregulates epithelial cell junctions and the Wnt signalling pathway. Our study unveils a mucosa-associated beneficial fungus, suggesting potential novel microbial intervention strategies for CD.}, }
@article {pmid41501499, year = {2026}, author = {Li, P and Li, T and Huang, M and Liu, Y and Liu, P and Wu, Y and Li, X and He, R and Gan, Y and Hong, Y and Wang, P and Lin, J and Huang, M}, title = {Harnessing early postoperative MRD and VAF dynamics for precision prognosis in resected colorectal liver metastases.}, journal = {Journal of cancer research and clinical oncology}, volume = {152}, number = {1}, pages = {28}, pmid = {41501499}, issn = {1432-1335}, support = {No. 23ykbj007, HY//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; 2022007, MH//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; 1010PY(2022)-10, JL//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research - '1010' Program/ ; 1010CG(2022)-02, MH; 1010CG(2022)-03, YL;//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research - '1010' Program/ ; A2023094, JL//Medical Scientific Research Foundation of Guangdong Province/ ; 202201011004, HY; 2023A04J1817, JL//Science and Technology Program of Guangzhou/ ; No. 82372715, YL; No. 81972245, YL; No. 82173067, YL; No. 82272965, HY//National Natural Science Foundation of China/ ; No. 2022A1515012656, HY//Natural Science Foundation of Guangdong Province/ ; 2022JBGS07//Scientific Research Project of the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; No. P20150227202010251, YL//Talent Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; No. R2021217202512965, YL//Excellent Talent Training Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; }, abstract = {BACKGROUND: Circulating tumor DNA (ctDNA) shows promise for predicting recurrence in colorectal cancer liver metastases (CRLM) patients. We investigated the prognostic value of perioperative ctDNA, particularly 2 week postoperative minimal residual disease (MRD), in CRLM patients undergoing liver resection.<br><br>METHODS: We prospectively collected blood samples from 94 CRLM patients before (after neoadjuvant therapy, if any) and 2&#xa0;weeks after liver metastasectomy. 63 patients had both assessments. ctDNA status and variant allele fraction (VAF) were determined using targeted sequencing. Disease-free survival (DFS) was analyzed using Kaplan-Meier curves and Cox regression. Baseline characteristics were compared based on ctDNA status.<br><br>RESULTS: Preoperative ctDNA status was not associated with DFS (p&#x2009;=&#x2009;0.77). However, postoperative 2&#xa0;week MRD status was a strong predictor; MRD-positive patients (N&#x2009;=&#x2009;31) had significantly worse DFS than MRD-negative patients (N&#x2009;=&#x2009;32) (p&#x2009;<&#x2009;0.001). In multivariate analysis, postoperative MRD positivity (HR&#x2009;=&#x2009;5.52, 95% CI: 2.46-12.39, p&#x2009;<&#x2009;0.001) and multiple metastases (HR&#x2009;=&#x2009;3.42, 95% CI: 1.42-8.25, p&#x2009;=&#x2009;0.006) were independent predictors of DFS. Postoperative MRD positivity showed a trend towards association with higher primary tumor T stage (p&#x2009;=&#x2009;0.095). Among MRD-negative patients, a higher maximum absolute VAF change (Max&#x394;VAF) suggested potentially worse DFS (p&#x2009;=&#x2009;0.053), while it held no prognostic value in MRD-positive patients (p&#x2009;=&#x2009;0.99).<br><br>CONCLUSIONS: Postoperative 2&#xa0;week ctDNA (MRD) status is a potent, independent predictor of DFS in resected CRLM patients and outperforms preoperative ctDNA. Early MRD assessment should be considered for risk stratification and may help guide adjuvant treatment decisions. VAF dynamics might further refine prognosis, especially in MRD-negative cases.}, }
@article {pmid41500802, year = {2026}, author = {Lee, CH and Bui, TPN and Petitfils, C and Jian, C and Wong, GC and Puel, A and Le Roy, T and Bellais, S and Ben Abdallah, B and Nehlich, M and Leicht, T and Jia, M and Hoyles, L and Federici, M and Fernández-Real, JM and Burcelin, R and Dumas, ME and Delzenne, NM and Clavel, T and Boeren, S and Troise, AD and Scaloni, A and Muccioli, GG and De Vos, WM and Van Hul, M and Cani, PD}, title = {Novel myo-inositol to butyrate fermentation pathway in the prevalent human gut species Dysosmobacter welbionis, a bacterium associated with improved metabolic and liver health.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-336617}, pmid = {41500802}, issn = {1468-3288}, abstract = {BACKGROUND: Dysosmobacter welbionis is a recently discovered butyrate producer whose presence in stool correlates with improved metabolic health. Whether its abundance is reduced in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. Mechanistic insight into its butyrate production from myo-inositol, a dietary compound from fruits, beans, grains and nuts with metabolic benefits, is also limited.<br><br>OBJECTIVE: To assess population-level distribution, relative abundance and strain diversity of D. welbionis in humans, and to elucidate its metabolic capacity to ferment myo-inositol into butyrate.<br><br>DESIGN: We analysed several human cohorts for associations with liver health and evaluated D. welbionis J115[T] supplementation in a diet-induced steatosis mouse model. An antibody-guided anaerobic cell-sorting strategy enabled isolation of distinct strains. We combined [13]C-labelled inositol isotopes with NMR, mass spectrometry, genomics and proteomics.<br><br>RESULTS: We found that D. welbionis and two related species (D. hominis and D. segnis) are prevalent gut bacteria in the human gut. D. welbionis abundance was reduced in MASLD across two cohorts and inversely correlated with fibrosis score in a third cohort. Treatment with D. welbionis J115[T] improved glycaemia and hepatic steatosis in high-fat diet fed mice. We identified a non-canonical myo-inositol-to-butyrate fermentation pathway. 19 human strains were isolated, comparative genomics of 23 strains revealed an open pangenome (about 2100 core genes) including the full myo-inositol fermentation pathway.<br><br>CONCLUSION: D. welbionis possesses a unique, conserved route to convert dietary myo-inositol into butyrate, distinguishing it from other commensals and supporting its potential as a next-generation probiotic for metabolic and liver health.}, }
@article {pmid41498552, year = {2026}, author = {Schussman, MK and Feng, S and Schmoldt, A and Bootsma, MJ and Dennis, K and Janssen, KH and McLellan, SL}, title = {Environmental reservoirs account for high levels of carbapenem resistance genes in wastewater.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0173725}, doi = {10.1128/spectrum.01737-25}, pmid = {41498552}, issn = {2165-0497}, abstract = {UNLABELLED: Wastewater surveillance has moved to the forefront as a practical and informative public health tool for assessing viral and bacterial pathogens in the human population; however, the usefulness for tracking antimicrobial-resistance genes (ARGs) of clinical concern is not straightforward given the large reservoir of free-living bacteria within sewer systems. In this study, we examined six high-priority carbapenem resistance gene targets and common host organisms in wastewater collected from two treatment plants. Polymerase chain reaction (PCR)-based assays demonstrated an extremely high abundance of blaKPC, blaOXA-24/40, and blaOXA-48 with mean concentrations as high as 3.55E+06 copy number (cn)/L for blaKPC. In addition, blaVIM and blaIMP were detectable in ~99% of samples at lower levels of ~1.5E+05 cn/L and 1.0E+04 cn/L, respectively. The target blaNDM was readily detected but quantifiable in only 49% of samples with levels of ~1.0E+03 cn/L. Each PCR target showed one to two dominant sequence types that matched exactly to reported clinical strains, indicating that high levels could not be attributed to non-specific amplification. Select ARG targets showed moderate-to-weak correlations to human fecal markers and Klebsiella pneumoniae or Escherichia coli, whereas blaOXA-24/40 most closely correlated to Acinetobacter baumannii. The two treatment plants showed different dynamics, suggesting that the inherent characteristics of the individual conveyance systems influence concentrations. Culture on selective media revealed an abundance of Aeromonas in addition to sporadic Enterobacteriaceae carrying blaKPC. Understanding the ecological dynamics of bacteria harboring ARGs will be important for understanding reservoirs and interpreting wastewater surveillance data.<br><br>IMPORTANCE: Wastewater surveillance for carbapenem-resistant bacteria has been proposed as a potentially valuable tool for assessing the human burden, but their distribution in environmental reservoirs is not well understood. Untreated sewage contains a high density of resident organisms mixed with human inputs, which are transported through the complex environment of sewer conveyance systems. In addition to resident microbial community members, organisms seeded into the system from the human microbiome have the potential to grow. This work shows that environmental bacteria may be a significant source of carbapenem resistance genes collected from sewer systems, making wastewater surveillance data difficult to interpret or use for public health actions. More knowledge is needed to unravel the ecology of these systems and identify targets for surveillance that are meaningful to clinicians. This work sheds light on the complex dynamics and confounding factors for antimicrobial-resistance gene wastewater surveillance, which will improve the interpretation of wastewater surveillance data.}, }
@article {pmid41490313, year = {2025}, author = {Mahnoor,  and Ullah, R and Sonyia,  and Khan, R and Bahadar, A and Elbatel, I and Khan, I and Alnahari, AA and Haider, A and Jamal, SB and Khan, R}, title = {A modified targeted culturing approach provided a snapshot into interdependencies and resistome among core anaerobic bacteria of the healthy human gut.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0318225}, doi = {10.1128/spectrum.03182-25}, pmid = {41490313}, issn = {2165-0497}, abstract = {The core anaerobic component of the human microbiome plays a critical role in preserving the overall structure and function of the microbiome. However, how these core strains interact with each other and with other gut microbes is largely unknown. We employed a modified culturomics approach to selectively culture these core genera from the human gut and provided a snapshot into their ecological interactions, clinically relevant resistome, and whole genome sequence (WGS)-based insights into their observed phenotypes. This strategy successfully isolated representatives of the targeted 21 core genera, with some isolates reported for the first time. Cross-interactions and resistome-based profiling revealed important insights. Out of the 440 interaction assessments, a significant proportion exhibited either cooperative or competitive effects on other core genera. Interestingly, Bacteroides thetaiotaomicron displayed dual roles, inhibiting potential pathogens while enhancing the growth of beneficial probiotic strains. Moreover, resistome profiling revealed variable resistance and susceptibility toward various antibiotics. WGS analysis revealed the ability of the selected organism to produce metabolites consistent with the observed phenotype. Our unique culturomics approach successfully isolated key anaerobic genera and revealed their complex interdependencies and clinically relevant resistance. Furthermore, our approach lays the foundation for exploring larger-scale microbial community dynamics in terms of interdependencies and for assessing how clinically significant antibiotics impact the key microbiome, something that may be important when making therapy decisions. In summary, our research improves our knowledge of the interactions present among core gut microorganisms and hints at possible mechanisms responsible for sustaining gut microbial homeostasis and rehabilitation. IMPORTANCE This study presents a unique strategy for the targeted isolation and characterization of key interaction dynamics as well as the resistome of core anaerobic bacteria in the healthy human gut. By utilizing this targeted single, optimized core anaerobe-specific growth medium approach, we were able to culture a major proportion of the core anaerobic gut species, where some of those were cultured for the first time. Through the combinatorial approach of cross-interaction, antimicrobial resistance profiling, and whole genome sequencing (WGS) resolved functional insights, we uncovered interesting insights into interdependencies and competition among these core strains as well as their ecological flexibilities. Moreover, we observed that some strains, such as Bacteroides thetaiotaomicron and Bifidobacterium angulatum, are capable of either inhibiting or promoting the growth of certain strains, depending on the pairing. Such findings go against the traditional binary view of microbes as being purely commensal or pathogenic and suggest that microbial behavior is highly context-dependent. Furthermore, WGS analysis provided useful insights into the potential genomic basis of the observed phenotype. Taken together, our findings provide valuable data and enhance our current understanding of how core anaerobes interact with each other, survive, and adapt within the gut environment. Moreover, our work also lays the critical basis for a more rational design of synthetic microbial communities as well as precision-based microbiome aimed at targeted gut health rehabilitation, both with accuracy and sensitivity.}, }
@article {pmid41473293, year = {2025}, author = {Estrada, KB and Mancera Azamar, KM and Wang, C and Sudi, SD and Friday-Saunders, K and Márquez, V and Quintanilla-Carvajal, MX and Acosta-González, A and Conde-Martinez, N and Porras, AM and Alviña, K}, title = {Supplementation with a Limosilactobacillus fermentum K73 synbiotic modulates gut microbiota function and behavior in gnotobiotic mice transplanted with microbiota from children diagnosed with autism spectrum disorder.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41473293}, issn = {2692-8205}, abstract = {BACKGROUND: Gut dysbiosis has been implicated in numerous pathological conditions, including neurodevelopmental and neurodegenerative disorders. Recently, dietary interventions targeted at restoring microbial balance have therefore gained attention as potential therapeutic strategies. We recently demonstrated that an encapsulated synbiotic containing high-oleic palm oil and Limosilactobacillus fermentum K73 can modulate the metabolic activity and composition of human-derived gut microbiota in an in vitro batch bioreactor. Here, we extended this work through an in vivo supplementation pilot study using gnotobiotic mice colonized with gut microbiota from Colombian pediatric patients diagnosed with autism spectrum disorder (ASD) or age-matched neurotypical (NT) donors. Behavioral assessments and analyses of gut microbiota composition and function were performed before and after synbiotic supplementation.<br><br>RESULTS: First, we found that the gut microbiota from Colombian ASD patients exhibited significantly reduced richness relative to NT donors, consistent with reports from other geographical regions, and displayed distinct compositional features unique to this population. Humanization of the gnotobiotic mice with this donor microbiota was successful, with murine gut communities reflecting features of their corresponding donor microbiota. Notably, synbiotic supplementation induced significant increases in the abundance of beneficial taxa and the production of short chain fatty acids that were more pronounced in mice colonized with ASD-derived microbiota, with concurrent behavioral changes associated with beneficial modulation of gut microbiota.<br><br>CONCLUSIONS: Overall, we provide evidence that supports synbiotic supplementation as a viable strategy to positively modulate gut microbiome in conditions of dysbiosis. Our study also expands the body of knowledge of gut microbiome to understudied populations such as Latin America.}, }
@article {pmid41488762, year = {2025}, author = {Zhao, Y and Hu, X and Li, C and Huang, J and Guo, K and Pan, Q and Yu, Z}, title = {Comprehensive Analysis of Vaginal and Gut Microbiome Alterations in Endometriosis Patients.}, journal = {International journal of women's health}, volume = {17}, number = {}, pages = {5775-5786}, pmid = {41488762}, issn = {1179-1411}, abstract = {PURPOSE: Endometriosis (EMS) is a chronic gynecological disorder with unclear pathogenesis. While the vaginal and gut microbiomes are known to influence EMS, few studies have analyzed both microbiomes integrally. This study aims to characterize the vaginal and gut microbiome profiles in EMS patients and evaluate their diagnostic potential.<br><br>PATIENTS AND METHODS: We conducted metagenomic sequencing on 22 paired vaginal and fecal samples from EMS patients and controls. Microbial composition, diversity, and metabolic pathways were analyzed. Machine learning models were employed to assess the predictive performance of microbiome features in EMS diagnosis.<br><br>RESULTS: EMS patients exhibited pronounced shifts in the vaginal microbiome, characterized by reduced Lactobacillus and increased Bifidobacterium and Gardnerella, which correlated with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. The gut microbiome displayed decreased diversity, with a depletion of beneficial taxa such as Ruminococcus and Prevotella, alongside an enrichment of Dialister. Metabolic pathways in both microbial communities were significantly altered. Machine learning analyses demonstrated that gut microbiome features outperformed both vaginal microbiome and hormonal indices in predicting EMS, highlighting their strong diagnostic potential.<br><br>CONCLUSION: This study underscores the pivotal role of the gut microbiota in EMS and elucidates the complex interplay between microbial dysbiosis and disease pathogenesis. Our findings indicate that gut microbiome signatures may serve as superior diagnostic biomarkers for EMS, thereby paving the way for microbiome-based diagnostic and therapeutic strategies.}, }
@article {pmid41480158, year = {2026}, author = {Khawaja, T and Kajova, M and Kantele, A}, title = {Improving antibiotic prescribing in LMICs: Insights from an outpatient clinic in Pakistan.}, journal = {New microbes and new infections}, volume = {69}, number = {}, pages = {101680}, pmid = {41480158}, issn = {2052-2975}, abstract = {BACKGROUND: Most human antibiotic use occurs in outpatient care and is a key driver of antimicrobial resistance (AMR). Although sales statistics suggest that high-income countries consume more antibiotics overall, the steepest growth is seen in low- and middle-income countries. Sales data - incomplete and non-transparent - reveal little about prescriptions to individual patients. Detailed, clinic-level data are essential for identifying targets for stewardship.We investigated antibiotic use and prescription appropriateness in an outpatient clinic in Pakistan - a country with some of the world's highest reported AMR prevalences.<br><br>METHODS: Patients attending an outpatient clinic near Lahore were interviewed immediately after their clinic visit and again one month later. Clinical data were collected through patient interviews, and antibiotic prescriptions were extracted from patient records.<br><br>RESULTS: Of the 983 participants, 398 (40.5&#xa0;%) were prescribed antibiotics at the primary visits. Metronidazole was the single most common agent, followed by first-generation cephalosporins, fluoroquinolones, and amoxicillin-clavulanate; phenoxymethylpenicillin and amoxicillin were only minimally prescribed. One-third of prescriptions (33.2&#xa0;%) were combination regimens, 90.2&#xa0;% of which included metronidazole. Guideline-concordant first- or second-line choices accounted for only 23.4&#xa0;% of prescriptions.Of all patients, 493 (50.2&#xa0;%) attended a one-month control visit. Of these, 233 (47.3&#xa0;%) also saw a practitioner during the visit; 73 of them (31.3&#xa0;%) were prescribed antibiotics.<br><br>CONCLUSIONS: Antibiotic prescribing was excessive and discordant with recommended first-line therapies, favouring broad-spectrum agents and combination treatments - practices likely influenced by the negligible time available per patient. Our findings highlight the need to adapt antimicrobial stewardship interventions to limited-resource contexts.}, }
@article {pmid41476963, year = {2025}, author = {Ma, S and Zheng, L and Zhuang, X and Wang, M and Zou, Y}, title = {Pathogenic mechanisms and therapeutic potential of the microbiome in premature ovarian insufficiency.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1734367}, pmid = {41476963}, issn = {1664-3224}, mesh = {Humans ; *Primary Ovarian Insufficiency/therapy/microbiology/metabolism/etiology ; Female ; Animals ; *Microbiota ; Ovary/metabolism/microbiology ; Probiotics/therapeutic use ; }, abstract = {The postponement of childbearing age has become a global issue. Factors such as increased work pressures on women and environmental changes have led to a rising incidence and younger onset of premature ovarian insufficiency (POI). POI not only impacts patients' reproductive function but also heightens the risk of depression, anxiety, cognitive decline, premature mortality, osteoporosis, and cardiovascular disease. Exploring effective prevention and treatment strategies for POI can slow ovarian ageing and safeguard female reproductive health. Microbiome research confirms that most human tissues and organs form dynamic, interactive systems with symbiotic microbes that play a crucial role in female reproductive function. Previous studies on the microbiome and female reproductive health have rarely focused on POI. The proposed 'Microbiota-Ovary Axis' aims to establish an integrated regulatory framework. This theoretical model systematically elucidates how microbial signals influence ovarian function through four core pathways: the hypothalamic-pituitary-ovarian (HPO) axis, metabolism and endocrine regulation, immunoregulation, and oxidative stress. Evaluating the efficacy of dietary modifications, probiotics, and microbiota transplantation in animal models and preliminary clinical studies will establish a robust theoretical foundation for developing microbiota-targeted innovative diagnostic and therapeutic strategies for POI, thereby enhancing reproductive health throughout the female lifespan.}, }
@article {pmid41470806, year = {2025}, author = {Black, EG and Bugarcic, A and Lauche, R and El-Omar, E and El-Assaad, F}, title = {The Effects of Kefir on the Human Oral and Gut Microbiome.}, journal = {Nutrients}, volume = {17}, number = {24}, pages = {}, pmid = {41470806}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Kefir/microbiology ; *Mouth/microbiology ; Probiotics ; Functional Food ; }, abstract = {Kefir, a fermented probiotic drink made from milk, water, or plant-based ingredients, has gained significant attention as a dietary supplement. Originating from the Caucasus Mountains over three thousand years ago, kefir is believed to harbor a range of health benefits through its ability to alter the composition of microbial niches within the human body. These microbial niches are called microbiomes and encompass the collective community of microbial organisms, their genomes and environment. The modern commercialization of kefir has driven the need for high-quality research into its impact on the human microbiome and associated health outcomes; however, there is currently very limited scientific evidence supporting effects of kefir consumption on the human oral and gut microbiome. High-quality human clinical trials are essential to establish the safety and effectiveness of kefir before it can be advised for use in treating conditions linked to the oral and gut microbiota or metabolic health. This literature review aims to critically analyze recent studies investigating the effect of kefir consumption on the oral and gut microbiome, as well as its potential implications for human health. By examining kefir's effects on these interconnected microbial ecosystems, we can better understand its potential and limitations as a functional food for promoting systemic health.}, }
@article {pmid41465000, year = {2025}, author = {Torreggiani, A and Caponio, M and Pinto, D and Mondadori, G and Verardo, V and Gómez-Caravaca, AM and Verni, M and Rizzello, CG}, title = {Upcycling Grape Pomace in a Plant-Based Yogurt Alternative: Starter Selection, Phenolic Profiling, and Antioxidant Efficacy on Human Keratinocytes.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {24}, pages = {}, pmid = {41465000}, issn = {2304-8158}, abstract = {Due to its appealing composition, grape pomace (GP), the major by-product of the wine industry, could be considered an ideal candidate for innovative functional foods development. In this study, a rice/GP-yogurt alternative, also known as gurt, fermented with selected lactic acid bacteria, was designed. An extensive characterization of the gurts led to the selection of the one fermented with Lactiplantibacillus plantarum T0A10. The strains showed good pro-technological performances (fast acidification and growth up to 9 log cfu/g in the specific plant-based composite substrate), as well as the ability to increase DPPH radical scavenging activity compared to the unfermented control (57% against 40%). Then, an in-depth focus on the effect of fermentation on phenolic compounds and their related antioxidant efficacy on human keratinocytes was provided, elucidating a compound/function relationship. Fermentation significantly modified the phenolic profile of the gurt, reducing glycosylated forms of flavonols and phenolic acids and increasing the content of catechin and pyrogallol (more than 100 mg/kg combined). Such modification was responsible for significantly up-regulating (p < 0.05) the expression of the antioxidant enzyme superoxide dismutase 2, thus protecting NCTC 2544 cells against oxidative stress. Overall, these findings provide a foundation for developing value-added products from GP, supporting both circular economy initiatives and functional ingredient innovation.}, }
@article {pmid41461310, year = {2025}, author = {Sun, C and Zhu, J and Sun, X and Zhang, Z and Sun, Y and Jin, Y and Wu, T}, title = {Targeting the human gut microbiome: a comparative review of probiotics, prebiotics, synbiotics, and postbiotics.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.12.032}, pmid = {41461310}, issn = {2090-1224}, abstract = {BACKGROUND: The human gut microbiome plays a central role in regulating host health, serving as a core hub for systemic physiological interactions. Dysregulation of the gut microbiome is implicated in a wide spectrum of local and systemic diseases. Research has evolved from establishing associations to elucidating the mechanistic roles of gut microbes and developing targeted strategies for their modulation, with a growing emphasis on their bidirectional communication with other organ systems.<br><br>AIM OF REVIEW: This review aims to synthesize current knowledge on the composition and function of the gut microbiome, its functional crosstalk with the host, and its integral role in both health and disease. A major focus is placed on critically evaluating the mechanisms, efficacy, and applications of key microbiome-directed interventions-probiotics, prebiotics, synbiotics, and postbiotics-in maintaining or restoring gut-centric ecological balance.<br><br>The gut microbiome acts as a dynamic microbial organ essential for digestion, immune maturation, and metabolic homeostasis. Dysbiosis, characterized by a loss of beneficial microbes and an overgrowth of potential pathogens, is a critical factor in the pathogenesis of gastrointestinal disorders, metabolic diseases, and other systemic conditions. The gut microbiome engages in continuous bidirectional communication with distant organs, including the oral cavity, lungs, skin, and urinary tract, via specific axes (e.g., gut-oral, gut-lung, gut-skin), thereby exerting widespread influence on host physiology. Probiotics, prebiotics, synbiotics, and postbiotics represent complementary strategies to counteract dysbiosis and reestablish gut ecological integrity, ranging from introducing live beneficial bacteria to utilizing inactivated microbial cells and their bioactive metabolites. Enhancing the translational potential of these interventions requires deeper mechanistic insights and robust clinical validation.}, }
@article {pmid41461285, year = {2025}, author = {Bharathi, S and Soundara Rajan, YAPA and Prakash, S and Immanuel, G and Ramasubburayan, R}, title = {Pathobionts in the Microbiome: Drivers of Disease and Targets for Treatment.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {108268}, doi = {10.1016/j.micpath.2025.108268}, pmid = {41461285}, issn = {1096-1208}, abstract = {Pathobionts are commensal inhabitants of the human microbiome that can transition to a pathogenic state under specific genetic or environmental conditions. They have recently gained attention for their impact on various clinical conditions. This review discusses the key factors behind pathobiont emergence, including microbial dysbiosis, antibiotic use, dietary influences, immune dysfunction and host genetics. It provides a comprehensive overview of pathobionts associated with the gut, oral cavity, and vaginal microbiomes highlighting their roles in disease pathogenesis. A significant focus is also placed on the involvement of pathobiont in immune-related disorders. Furthermore, current and advanced therapeutic strategies aimed at mitigating the effects of pathobionts, such as faecal microbiota transplantation, phage therapy, probiotics and prebiotics, along with their advantages and limitations, were highlighted. Thus, the integrated perspective combining microbial ecology, host immunity, and therapeutic strategies outlines the need for targeted, microbiome-based interventions to address the complex behaviour of pathobionts.}, }
@article {pmid41459433, year = {2025}, author = {Bhojiya, AA and Saurabh, A and Jain, D}, title = {Editorial: Microbial therapeutics: harnessing the human microbiome for disease treatment and prevention.}, journal = {Frontiers in medical technology}, volume = {7}, number = {}, pages = {1751147}, doi = {10.3389/fmedt.2025.1751147}, pmid = {41459433}, issn = {2673-3129}, }
@article {pmid41458698, year = {2025}, author = {Darwish, S and Razdolsky, N and Ditty, K and Torres, A and Mathew, S and Ali, S and Izhar, A and Ghazzawi, J and Phillips, C and Braun, A and Costin, JM}, title = {The Effects of Vaginal Virome on Women's Health: A Scoping Review.}, journal = {Cureus}, volume = {17}, number = {11}, pages = {e97876}, pmid = {41458698}, issn = {2168-8184}, abstract = {While research on the vaginal microbiome (VMB) has focused mainly on its bacteriome, the role of viral communities remains largely understudied. Given the vaginal virome's potential influence on disease susceptibility and progression, understanding its exact role in different health outcomes is crucial. The objective of this scoping review was to analyze studies on the vaginal virome's influence on women's health, the virome's interactions with other microbes, assess the limitations of these studies, and highlight gaps to guide future studies and treatments in the field of gynecological health. The review was conducted using previously gathered literature on the impact of the vaginal virome among reproductive-aged women in developed countries. Articles were sourced from Ovid MEDLINE, Embase, and World of Science using the following search string: vaginal virome AND reproductive health OR infections OR pregnancy outcomes. Articles were screened using the PCC framework as follows: influence of the vaginal virome on women's health (Concept) in women aged 18 and older (Population) in developed countries (Context). Of the 352 articles originally identified, 10 studies met the inclusion criteria and were utilized in this scoping review. The vaginal virome contains a diverse array of viruses and bacteriophages that impact human papillomavirus (HPV) infection persistence and subsequent progression to cervical cancer, pregnancy outcomes, and the inflammatory response. In bacterial vaginosis, reductions in Lactobacillus-targeting bacteriophages have the potential to contribute to dysbiosis. Hormonal fluctuations throughout the menstrual cycle influence both bacterial and viral populations, potentially affecting infection susceptibility and overall vaginal health. During pregnancy, higher viral diversity is associated with preterm birth risk, and immune modulation by the virome may impact susceptibility to infections like HPV. Analysis of the included studies indicates the need for continued investigation of the manner in which the vaginal virome interacts with other aspects of the microenvironment to influence women's health. This scoping review highlights the new and emerging role of the vaginal virome in women's health, highlighting its relationship with other microbes and clinical significance. These findings underscore the importance of the vaginal virome in reproductive health, suggesting that further research is needed to better understand its role and guide effective prevention and treatment strategies.}, }
@article {pmid41456646, year = {2025}, author = {Yang, X and Li, C and He, J and Xie, B and Lv, L and Xu, J and Lin, Y and Zhou, C and Li, M and Zeng, Z and Tan, J and Chen, S and Cui, G and Liu, G and Suo, S and Peng, G and Liang, X}, title = {Spatial and single-cell transcriptomics landscape of adenomyosis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2025.12.042}, pmid = {41456646}, issn = {2090-1224}, abstract = {INTRODUCTION: Adenomyosis is a prevalent gynaecological disorder affecting women of reproductive age, yet the underlying etiology and cellular-molecular mechanisms driving its pathogenesis remain poorly understood. Gonadotropin-releasing hormone agonists (GnRHa) are commonly used to improve clinical pregnancy rates in affected patients; however, their effects on specific cellular niches within the diseased uterus have not been fully elucidated.<br><br>OBJECTIVE: This study aimed to profile adenomyosis at both the single-cell and spatial transcriptomic levels to examine various cell populations and systematically evaluate the effects of GnRHa treatment.<br><br>METHODS: To characterize in depth the cellular and molecular landscape of adenomyosis, we employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (Geo-seq) to profile 15 participants, including 11 patients with adenomyosis (three untreated and eight treated with GnRHa) and four control participants. For validation using immunofluorescence and immunohistochemistry, we included an additional two control subjects and 11 patients with adenomyosis. Furthermore, publicly available scRNA-seq datasets from samples collected during the proliferative phase of the menstrual cycle were incorporated for comparison.<br><br>RESULTS: Our analysis revealed that ectopic endometrial glands in adenomyosis were enriched with ciliated epithelial cells, a feature that persisted following GnRHa treatment, suggesting a potential role of these cells in disease pathogenesis. Immune-inflammatory signatures, including elevated CD4[+] T cells and LYVE1[+] macrophages, were prominent in untreated adenomyosis, contributing to a pro-angiogenic microenvironment. This inflammatory and angiogenic activity was partially mitigated by GnRHa therapy. Notably, mast cells were found to be concentrated in the junctional zone, implicating this region as a potential site of disease initiation.<br><br>CONCLUSION: Our findings provide evidence for the invagination theory, highlighting the involvement of ciliated epithelial cells and immune-angiogenic crosstalk in adenomyosis pathogenesis. Moreover, this study demonstrates that GnRHa exerts therapeutic effects through the normalization of immune cell composition and restoration of epithelial-stromal interaction, offering novel mechanistic insights into its mode of action.}, }
@article {pmid41455545, year = {2025}, author = {Zhang, JS and Zhang, Y and Huang, S and Chu, CH and Jakubovics, NS and Yu, OY}, title = {High-Resolution Microbial Changes in Root Caries Revealed by Type IIB Restriction-site Associated DNA for Microbiome.}, journal = {Journal of dentistry}, volume = {}, number = {}, pages = {106319}, doi = {10.1016/j.jdent.2025.106319}, pmid = {41455545}, issn = {1879-176X}, abstract = {OBJECTIVES: This study aimed to characterize the species-level microbial and functional alterations in the dental biofilms associated with root caries leveraging the high-resolution sequencing.<br><br>METHODS: Twenty-five older adults with active root caries (Patients) and 31 older adults without untreated caries (Healthy controls) were enrolled. Site-specific supragingival plaque was collected from spatially-matched carious (CC) and caries-free (CH) root surfaces from patients, and from caries-free root surfaces of healthy controls (HH). Plaque samples were analysed using Type IIB Restriction-site Associated DNA for Microbiome (2bRAD-M). Microbial diversity, species-level relative abundance, and predicted functional pathways were compared across groups using nonparametric tests.<br><br>RESULTS: No significant differences in overall microbial diversity were observed between groups. The microbial divergence between paired carious (CC) and caries-free (CH) root microbiota from patients was significantly greater than that between paired caries-free (HH) root microbiota in healthy controls. Several species showed increased abundance in CC microbiota compared to CH microbiota, with Propionibacterium acidifaciens, Prevotella multisaccharivorax, Mitsuokella sp000469545, and Parascardovia denticolens exhibiting the highest level of abundance difference. Predicted metagenomic analysis indicated that nine KEGG pathways, primarily involved in alternative carbohydrate metabolism, were positively associated with root caries status.<br><br>CONCLUSION: Within-subject comparison revealed a significant difference in microbiota between carious and caries-free root surfaces. These differences were characterized by shifts in specific species and their associated metabolic potentials, rather than by broad changes in community diversity.<br><br>CLINICAL SIGNIFICANCE: This study underscores the importance of tooth-level resolution in investigating the microbial etiology of root caries and revealed the species-level changes in carious root microbiota.}, }
@article {pmid41455148, year = {2025}, author = {Uoti, A and Neulasalmi, O and Hiippala, K and Oksanen, T and Arkkila, P and Puustinen, L and Satokari, R and Sjöstedt, N}, title = {Characterization of fecal deglucuronidation activity in healthy subjects and in patients treated with fecal microbiota transplantation.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {53}, number = {12}, pages = {100205}, doi = {10.1016/j.dmd.2025.100205}, pmid = {41455148}, issn = {1521-009X}, abstract = {Gut bacterial β-glucuronidase (GUS) enzymes contribute to the intestinal toxicity and/or enterohepatic recycling of glucuronidated compounds by cleaving glucuronide conjugates excreted into the intestinal lumen. The activities and substrate specificities of several GUS isoforms have been recently described. However, the extent of intraindividual and interindividual variability in gut microbial deglucuronidation activity has remained poorly characterized. In this study, we used pan-GUS reporter substrates as well as drug and steroid glucuronides to study the deglucuronidation activities of fecal lysates produced from individual fecal samples from healthy donors (n = 12), and sequential samples collected from fecal microbiota transplantation (FMT) donors (n = 3) and patients with recurrent Clostridioides difficile infection who underwent FMT (n = 7). To determine relationships between fecal deglucuronidation activity and gut microbiota composition, we used 16S rRNA gene sequencing to characterize the healthy donors' fecal microbiotas. Although we observed considerable interindividual variability specifically in the processing of steroid glucuronides, intraindividual variability in the fecal deglucuronidation activity of FMT donors was relatively modest. We observed the female sex and Alistipes, Faecalibacterium, and Gemmiger taxa to be associated with higher deglucuronidation activity, whereas the abundance of Roseburia correlated negatively with deglucuronidation activity. In addition, the baseline deglucuronidation activity of patients with recurrent C. difficile infection was low but increased by FMT treatment. The results of this study further highlight deglucuronidation as a function of a healthy gut microbiota. Moreover, these results improve our understanding of deglucuronidation activity as a source of individual variability in the pharmacokinetics and pharmacodynamics of glucuronidated drugs that undergo enterohepatic recycling. SIGNIFICANCE STATEMENT: Gut microbial deglucuronidation rates of specific compounds may vary considerably between individuals. Deglucuronidation activity is relatively stable within healthy individuals for ≥1 year, but fecal microbiota transplantation can significantly alter the deglucuronidation activity of an individual.}, }
@article {pmid41452451, year = {2025}, author = {Zhang, X and Li, C and Feng, X and Yuan, X}, title = {The interplay of microbiome, molecular mechanisms, and fertility -an integrated review.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {41452451}, issn = {1874-9356}, support = {LBH-Z21218//Postdoctoral funding of Heilongjiang Province/ ; }, abstract = {The human microbiome, particularly the gut and reproductive tract microbiota, plays a critical role in regulating fertility through complex molecular and immunological mechanisms. This review synthesizes emerging evidence on the bidirectional communication along the gut-reproductive axis, emphasizing how microbial-derived metabolites, such as short-chain fatty acids (butyrate), bile acids, and indoles, modulate systemic inflammation, immune tolerance, hormone metabolism, and energy homeostasis. Dysbiosis, or microbial imbalance, is strongly associated with a range of reproductive pathologies, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, impaired spermatogenesis, and recurrent implantation failure. Furthermore, site-specific microbiomes, such as Lactobacillus-dominated vaginal and uterine communities, are vital for successful implantation and pregnancy maintenance. External factors including diet, environmental toxins, and antibiotic use can disrupt these microbial ecosystems, whereas interventions like probiotics like Lactobacillus and Clostridium butyricum, prebiotics, postbiotics, and fecal microbiota transplantation offer promising avenues for restoring microbial and reproductive health. However, translational challenges remain, including methodological heterogeneity in microbiome research and the need to establish causal mechanisms beyond correlation. Future efforts should prioritize multi-omics integration, randomized controlled trials, and personalized microbiome-based diagnostics and therapeutics to effectively address infertility.}, }
@article {pmid41446056, year = {2025}, author = {Wang, T and Ahmad, S and Rosa, RSL and Binion, B and Fernandez-Materan, FV and Igbalaye, JO and Chung, D and Bushra, A and Perez, V and Biedak, MA and Tang, E and Barnick, B and Olukoya, D and Mbuvi, P and Dutta, D and Erdman, JW and Gaskins, HR and Yang, G and Irudayaraj, J and Bernardi, RC and Ridlon, JM}, title = {The urinary pathobiont Actinobaculum massiliense generates androgens via the dirAB pathway.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.64898/2025.12.18.695155}, pmid = {41446056}, issn = {2692-8205}, abstract = {While overlooked during the Human Microbiome Project, characterizing the urinary microbiota in health and disease is a new frontier in microbiome science. Recent studies have associated differential abundance of bacterial taxa including Propionimicrobium lymphophilum and Actinobaculum / Actinotignum spp. with prostate cancer. In this study, we collected urine from subjects prior to prostate biopsy and applied a novel H uman S terolbiome D iscovery H igh-throughput (HSDH) assay to identify culturable urinary bacteria with the ability to generate androgens. Application of the HSDH assay to urine samples led to the isolation of eight P. lymphophilum strains positive for cortisol side-chain cleavage (steroid-17,20-desmolase), 17β-HSDH activity, or both. In addition, we isolated three strains of Actinobaculum massiliense that encode D HEA isomerase reductase (dir) genes. The dirA gene encodes a novel 3β/17β-hydroxysteroid dehydrogenase/Δ [4,5] -isomerase and the dirB gene encodes a novel 17β-hydroxysteroid dehydrogenase isoform. Structural prediction and molecular dynamics reveal probable catalytic mechanisms based on the shared catalytic triad but distinct binding pocket geometries of the DirA and DirB that describe their respective reactions. Phylogenetic analysis of DirA and DirB revealed homologs in urinary tract commensals as well as bacteria associated with steroid degradation found in aquatic and terrestrial environments. Taken together, the development of the HSDH assay and the identification of the dir pathway genes is a significant advance in microbial endocrinology, laying the methodological foundation and providing the molecular basis for understanding the role of urinary tract bacteria in host endocrine physiology.}, }
@article {pmid41438742, year = {2025}, author = {Chen, PJ and Devkota, S and Shiao, S and Hendifar, A and Yang, JD}, title = {Gut microbiome, a novel precision medicine biomarker for hepatocellular carcinoma.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1568962}, pmid = {41438742}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Hepatocellular/therapy/immunology/microbiology/metabolism ; *Liver Neoplasms/therapy/immunology/microbiology/metabolism ; *Gastrointestinal Microbiome/immunology ; Precision Medicine/methods ; Biomarkers, Tumor ; Animals ; Immune Checkpoint Inhibitors/therapeutic use ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Immunotherapy/methods ; }, abstract = {Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have transformed systemic therapy, durable responses are achieved in only a subset of patients, highlighting the need for reliable predictive biomarkers. The gut-liver axis, a bidirectional network linking intestinal microbiota, microbial metabolites, and hepatic immune pathways, has emerged as a key regulator of liver immunity and tumor progression. Growing evidence indicates that the gut microbiome modulates ICI efficacy by shaping immune activation, cytokine signaling, and drug metabolism. This review summarizes current insights into how gut microbial composition and metabolites influence immunotherapy outcomes in HCC and discusses microbiome-targeted strategies, including fecal microbiota transplantation (FMT), prebiotics, probiotics, and dietary interventions. Further research and clinical validation are needed before these insights can be effectively integrated into HCC management.}, }
@article {pmid41436448, year = {2025}, author = {Manghi, P and Antonello, G and Schiffer, L and Golzato, D and Wokaty, A and Beghini, F and Mirzayi, C and Long, K and Gravel-Pucillo, K and Piccinno, G and Gamboa-Tuz, SD and Bonetti, A and D'Amato, G and Azhar, R and Eckenrode, K and Zohra, F and Giunchiglia, V and Keller, M and Pedrotti, A and Likhotkin, I and Elsafoury, S and Geistlinger, L and Blanco-Miguez, A and Thomas, AM and Zolfo, M and Ramos, M and Valles-Colomer, M and Tamburini, S and Asnicar, F and Jones, HE and Huttenhower, C and Carey, V and Davis, S and Pasolli, E and Oh, S and Segata, N and Waldron, L}, title = {Meta-analysis of 22,710 human microbiome metagenomes defines an oral-to-gut microbial enrichment score and associations with host health and disease.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-66888-1}, pmid = {41436448}, issn = {2041-1723}, support = {5R01CA230551//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; 5R01CA230551//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; }, abstract = {Large public datasets of the human microbiome now exist but combining them for large-scale analysis is difficult due to a lack of standardization. We developed curatedMetagenomicData (cMD) 3, a uniformly processed collection of over 22,000 human microbiome samples with manually curated metadata from 94 studies and 42 countries. This large and diverse resource allows for meta-analysis of the links between microbes and human health. Through meta-analysis, we identified hundreds of microbial species and thousands of microbial functions significantly associated with a person's sex, age, body mass index, and disease status, and catalog these as references. We developed an "oral enrichment score" (OES) based on the relative abundance of bacteria typically found in the oral cavity and not in the gut. Higher OES in the gut is a consistent feature in individuals with disease, suggesting that the relative abundance of oral bacteria in the gut is a simple and quantifiable signal of altered microbiome health. These analyses identify modest but widely shared patterns in human microbiomes, serving as a reproducible and readily updatable reference.}, }
@article {pmid41434948, year = {2025}, author = {Kaiyrlykyzy, A and Zholdasbekova, G and Alzhanova, D and Kozhakhmetov, S and Kushugulova, A and Askarova, S}, title = {Basic Science and Pathogenesis.}, journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association}, volume = {21 Suppl 1}, number = {}, pages = {e097791}, doi = {10.1002/alz70855_097791}, pmid = {41434948}, issn = {1552-5279}, mesh = {Humans ; Male ; Female ; *Alzheimer Disease/genetics/epidemiology ; Aged ; Kazakhstan/epidemiology ; Polymorphism, Single Nucleotide/genetics ; Gastrointestinal Microbiome ; Cytokines/blood ; Risk Factors ; Cohort Studies ; Middle Aged ; Apolipoproteins E/genetics ; }, abstract = {BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia and a critical social issue. Its multifactorial nature necessitates evaluating risk factors in diverse populations.<br><br>METHODS: This study analyzed 181 AD patients and 244 controls in Kazakhstan, comparing clinical, genetic, and microbial traits.<br><br>RESULTS: In our cohort, significant dementia-associated variables included smoking, depression, dyslipidemia, insulin resistance, and liver dysfunction. AD patients had higher HDL, bilirubin, AST/ALT ratios, and lower ALT. Genetic analysis identified 13 SNPs linked to AD, notably in APOE, TOMM40, and MED12L genes involved in lipid metabolism, mitochondrial function, and gene transcription. APOE4 increased AD risk 1.9x, with higher prevalence in northern Kazakhstan (Astana). We also found specific alterations in the gut microbiome, specifically, a decreased Firmicutes/Bacteroidetes ratio, a reduced Bifidobacterium, and increased proteobacteria and inflammatory bacteria. The investigation of cytokine profiles demonstrated that pro-inflammatory cytokines such as IFN-&#x3b3;, IL-6, TNF-&#x3b2;, MCP-1, and IL-17A were significantly elevated in AD patients, along with anti-inflammatory cytokines IL-4 and IL-1RA, suggesting a dysregulated inflammatory response in AD. Additionally, elevated serum adiponectin levels, observed at three times higher than in controls, were strongly correlated with multiple cytokines and specific microbial taxa, such as Actinobacteria and Acidomicrobiia, indicating a potential interplay between gut microbiota, adipose tissue, and neuroinflammation in AD.<br><br>CONCLUSION: These findings underscore the importance of considering bio-geographic and environmental factors in AD research. The study's outcomes may aid in further research and the development of personalized approaches for managing and treating AD in distinct geographical regions. Research support: Nazarbayev University Collaborative Research Program Grant [Funder Project Reference: 20122022CRP1602] and the Ministry of Higher Education and Science of the Republic of Kazakhstan Grant [Funder Project Reference: AP14871338].}, }
@article {pmid41428468, year = {2025}, author = {Li, Z and Hong, X and Zhang, X and Li, Z and Liu, Y}, title = {Association between dietary nutrient density patterns and cognitive function: A latent class analysis of NHANES 2011-2014.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {}, number = {}, pages = {13872877251407108}, doi = {10.1177/13872877251407108}, pmid = {41428468}, issn = {1875-8908}, abstract = {BackgroundAlzheimer's disease (AD) and cognitive decline are major global health challenges. The impact of dietary nutrient density, particularly in the context of ultra-processed, fortified foods, on cognitive function remains uncertain.ObjectiveTo examine associations between dietary nutrient density patterns and cognitive performance in U.S. older adults and to evaluate effect modification by key subgroups.MethodsWe analyzed data from 2991 adults aged ≥60 years in NHANES 2011-2014. Nutrient density patterns were derived by latent class analysis of 24-h dietary recalls. Cognitive function was assessed with the CERAD Word Learning, Animal Fluency, and Digit Symbol Substitution Tests. Multivariable linear regression estimated associations between nutrient density patterns and cognitive scores, adjusting for sociodemographic, lifestyle, and clinical factors; stratified analyses assessed effect modification.ResultsFour distinct nutrient density patterns were identified. A High-Nutrient, Ultra-Processed pattern, characterized by high intake of processed foods and relatively lower plant-based nutrients, was associated with poorer cognitive performance, particularly on memory tasks (β = -0.43, p = 0.018), and these associations persisted after full adjustment. Associations were stronger among participants with hypertension or diabetes.ConclusionsDietary nutrient density patterns are independently associated with cognitive function in older adults, with ultra-processed, fortified dietary profiles linked to worse performance, especially in those with cardiometabolic conditions. Targeted dietary strategies that emphasize nutrient-dense, minimally processed foods may help preserve cognitive health in vulnerable subgroups.}, }
@article {pmid41423295, year = {2025}, author = {Jeong, H and Seo, H and Kim, S and Rahim, MA and Barman, I and Shuvo, MSH and Jo, S and Hossain, MS and Yoo, JJ and Kim, YH and Jung, SS and Song, HY and Jeon, CH}, title = {Alterations in the Gut Microbiome in Ankylosing Spondylitis and Their Correlation with Disease Activity.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2508043}, doi = {10.4014/jmb.2508.08043}, pmid = {41423295}, issn = {1738-8872}, mesh = {Humans ; *Spondylitis, Ankylosing/microbiology ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Male ; Adult ; Female ; Feces/microbiology ; *Bacteria/classification/genetics/isolation &amp; purification ; Middle Aged ; Dysbiosis/microbiology ; C-Reactive Protein/analysis ; Biomarkers ; DNA, Bacterial/genetics ; Case-Control Studies ; }, abstract = {The microbiome significantly influences immune dysfunction and gut dysbiosis in patients with ankylosing spondylitis (AS). This study focuses on defining the distinct microbial characteristics within AS and biomarkers associated with disease activity. 44 patients with AS and 50 healthy controls (HC) were recruited. 16S rRNA sequencing was conducted to assess the microbiome of stool samples. The Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) was calculated for all AS patients; scores ≥ 2.1 indicated high disease activity, while < 2.1 indicated low disease activity. Similar alpha diversity profiles were maintained in both AS and HC cohorts, whereas significant differences were identified in beta diversity. The compositional prevalence of Proteobacteria, particularly Gammaproteobacteria, and Enterobacterales, including Escherichia spp., in the AS group was significantly increased. On the other hand, beneficial taxa, including Firmicutes, Clostridia, Clostridiales, Lachnospiraceae, Ruminococcaceae, and Faecalibacterium, were highly abundant in the HC group. Among patients with AS, alpha diversity decreased in the high disease activity group compared to the low disease activity group, while beta diversity did not differ significantly. Moreover, Coprobacter spp. abundance positively correlated with the Bath Ankylosing Spondylitis Disease Activity Index (p = 0.032) and the ASDAS-CRP (p = 0.023). Patients with AS exhibit distinct gut microbiota profiles, with increased Proteobacteria and decreased beneficial taxa such as Firmicutes. Greater disease activity is accompanied by reduced alpha diversity, while Coprobacter spp. abundance correlates with disease activity, suggesting its potential as a biomarker.}, }
@article {pmid41421426, year = {2025}, author = {Nam, J and Lee, Y and Lee, S and Choi, H and Lee, SY and Yang, D}, title = {Synthetic biology strategies for engineering probiotics and commensal bacteria for diagnostics and therapeutics.}, journal = {Biotechnology advances}, volume = {}, number = {}, pages = {108782}, doi = {10.1016/j.biotechadv.2025.108782}, pmid = {41421426}, issn = {1873-1899}, abstract = {Microorganisms inhabit diverse environments, including nearly every organ in the human body. The human microbiome-a complex community of microorganisms residing in the human body-has gained increasing attention as a key contributor to human health and disease, making it an important target for the development of diagnostic and therapeutic strategies. However, the inherent complexity of microbial communities and the challenges of engineering diverse, non-model microorganisms present significant barriers. To address these challenges, synthetic biology has provided powerful tools and strategies to engineer microorganisms capable of sensing disease-specific environments and performing targeted therapeutic functions. In particular, the development of synthetic genetic circuits has significantly improved the precision and reliability of disease diagnosis and treatment, enabling real-time disease monitoring, therapeutic, and even preventive interventions. This review highlights state-of-the-art synthetic biology tools and strategies for engineering the probiotics and commensal bacteria aimed at the diagnosis and treatment of human diseases, with accompanying examples. Future challenges and prospects are also discussed.}, }
@article {pmid41420149, year = {2025}, author = {Arazi, P and Skurnik, M and Mohsenipour, Z and Abtahi, HR and Jahanbin, B and Kianian, F and Feizabadi, MM}, title = {Genomic and functional characterization of a novel lytic phage vB-AbaM-fThrA with anti-biofilm activity against CR-MDR Acinetobacter baumannii.}, journal = {BMC microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1186/s12866-025-04525-z}, pmid = {41420149}, issn = {1471-2180}, abstract = {BACKGROUND: Multidrug-resistant Acinetobacter baumannii causes increasingly fat5al infections in humans. Phage therapy is considered as a promising approach to treat the infections.<br><br>METHODS: Here we present the isolation and characterization of a new lytic A. baumannii specific phage vB-AbaM-fThrA (fThrA for short) originating from hospital wastewater.<br><br>RESULTS: Phage fThrA has a myovirus morphology with a relatively broad host range. The phage forms large and transparent plaques with a halo and showed high lysis power in in-vitro laboratory studies. Based on the genome sequence analysis phage fThrA is a new member of the Obolenskvirus genus with about 75.6% genomic similarity to its closest relative. The phage, tolerated well pH range from 4 to 10, and heating at 50&#xa0;&#xb0;C, but not 80&#xa0;&#xb0;C. At pH 2 ca. 50% of the phage survived for 1&#xa0;h, an indication that the phage would be suitable for oral administration and phage therapy of the digestive tract. Phage fThrA was highly active against formation of biofilm and in destruction of the formed biofilm, an asset when used as a supplement to antibiotics in severe infections. Also, in genomic studies, no genes related to pathogenicity and lysogenicity were observed in the whole phage sequence.<br><br>CONCLUSIONS: These features make phage fThrA as a promising candidate for phage therapy in-vivo.}, }
@article {pmid41418718, year = {2025}, author = {Dwivedi, J and Shukla, MM and Upadhyay, A and Wal, A and Sharma, KK and Gasmi, A}, title = {From 16S rRNA to deep learning: Evolution of computational approaches in human microbiome studies.}, journal = {Computational biology and chemistry}, volume = {121}, number = {}, pages = {108852}, doi = {10.1016/j.compbiolchem.2025.108852}, pmid = {41418718}, issn = {1476-928X}, abstract = {The human microbiome plays a vital role in maintaining physiological balance and influencing immunity, metabolism, and disease development. Over the past decade, the field has witnessed a remarkable transition from traditional 16S rRNA sequencing and culture-based assays to advanced computational frameworks that integrate multiomics datasets. Modern computational tools now enable researchers to move beyond descriptive taxonomy toward functional, predictive, and mechanistic insights, with techniques such as network modeling, genome-scale metabolic reconstruction, and deep learning algorithms facilitating the accurate profiling of microbial communities and the identification of biomarkers associated with complex disorders. AI-based platforms including QIIME, MetaPhlAn, and DeepMicro have further strengthened microbiome analysis by integrating genomic, proteomic, and metabolomic data to model host-microbe interactions. Despite these advances, challenges such as data heterogeneity, limited interpretability of AI models, and ethical issues in data sharing continue to impede clinical translation. Future progress will rely on explainable AI, federated learning, and standardized data frameworks to promote transparency, reproducibility, and applicability in precision medicine. Overall, the integration of AI-driven bioinformatics marks a paradigm shift in human microbiome research, transforming it from an observational discipline into a predictive and translational science with the potential to revolutionize personalized healthcare.}, }
@article {pmid41412124, year = {2025}, author = {Deng, L and Fehr, K and Toe, LC and Allen, LH and Bode, L and Hampel, D and Manus, MB and Mertens, A and Robertson, B and Yonemitsu, C and Meulenaer, B and Lachat, C and Sonnenburg, JL and Azad, MB and Dailey-Chwalibóg, T}, title = {Time-specific bidirectional links between the maternal microbiome, milk composition, and infant gut microbiota.}, journal = {Cell host &amp; microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2025.11.014}, pmid = {41412124}, issn = {1934-6069}, abstract = {Early-life gut microbiome development is shaped by complex maternal and nutritional influences, yet the temporal and directional structure of these interactions remains unclear. In a longitudinal study of 152 mother-infant dyads in rural Burkina Faso, we examine how maternal gut and milk microbiomes, alongside milk components, influence infant gut microbiome development during the first 6 months. At 1-2 months, the infant gut microbiome clusters into three types: Escherichia-dominated, Bifidobacterium-dominated, and a diverse, pathogen-prevalent profile, which become less distinct by 5-6 months. Early infant gut microbiomes associate with maternal prenatal gut microbiota and early milk microbiome and oligosaccharides, while later variation links to other milk nutrients. Furthermore, early infant gut profiles predict subsequent milk composition, suggesting potential bidirectional communication between infant needs and maternal lactational physiology. These findings offer insights into early-life microbial development and inform future mechanistic studies and microbiome-targeted interventions, particularly in low-resource settings.}, }
@article {pmid41411654, year = {2025}, author = {Zhang, L and Xu, W and Meng, HYH and Ching, JYL and Liu, Y and Wang, S and Yan, S and Lin, L and Cheong, PK and Ip, KL and Peng, Y and Zhu, J and Cheung, CP and Leung, TF and Leung, ASY and Tam, WH and Leung, TY and Chan, PKS and Chang, EB and Rubin, DT and Claud, EC and Wu, WKK and Tun, HM and Chan, FKL and Ng, SC}, title = {Impacts of COVID-19 pandemic on early life gut microbiome.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2443117}, doi = {10.1080/19490976.2024.2443117}, pmid = {41411654}, issn = {1949-0984}, mesh = {Humans ; *COVID-19/epidemiology ; *Gastrointestinal Microbiome/genetics ; Infant ; Female ; SARS-CoV-2 ; Infant, Newborn ; China/epidemiology ; Pandemics ; Male ; Bacteria/genetics/classification/isolation &amp; purification/drug effects ; Cohort Studies ; Hygiene ; Anti-Bacterial Agents/pharmacology ; Feces/microbiology ; Drug Resistance, Bacterial/genetics ; }, abstract = {Increased hygiene and sanitation are theorized to predispose to developing atopic diseases, a process potentially mediated by the gut microbiome. We hypothesized that the gut microbiome maturation has been altered by COVID-19 lockdown measures during the first year of life, a critical period when environmental exposure shapes human microbiome development. The two large pre- and during-COVID-19 mother-baby pairs cohorts in the Greater Bay Area of China provided the unique opportunity to assess the effect of increased hygiene standards on early gut microbiome maturation. Our results showed that the gut microbiome diversity, composition, and developmental trajectory were significantly altered between pre- and during-COVID-19 cohorts. Functionally, there was decreased richness in both antimicrobial peptide resistance genes and antibiotic resistance genes in the during-COVID cohort. Specially, Staphylococcus epidermidis carried a lower copy number of fluoroquinolone and beta-lactam antibiotics resistance genes while Klebsiella pneumoniae possessed a higher copy number of fluoroquinolone antibiotic resistance genes in gut microbiota of infants born during the COVID-19 pandemic. Our study underscores the importance of considering the microbiome when evaluating hygiene measures and the need for future research to ascertain the role of the gut microbiome in disease development.}, }
@article {pmid41279291, year = {2025}, author = {Camargo, AP and Baltoumas, FA and Ndela, EO and Fiamenghi, MB and Merrill, BD and Carter, MM and Pinto, Y and Chakraborty, M and Andreeva, A and Ghiotto, G and Shaw, J and Proal, AD and Sonnenburg, JL and Bhatt, AS and Roux, S and Pavlopoulos, GA and Nayfach, S and Kyrpides, NC}, title = {A genomic atlas of the human gut virome elucidates genetic factors shaping host interactions.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41279291}, issn = {2692-8205}, abstract = {Viruses are key modulators of human gut microbiome composition and function. While metagenomic sequencing has enabled culture-independent discovery of gut bacteriophage diversity, existing genomic catalogues suffer from limited geographic representation, sparse taxonomic classification, and insufficient functional annotation, hindering detailed investigation into phage biology. Here, we present the Unified Human Gastrointestinal Virome (UHGV), a collection of 873,994 viral genomes from globally diverse populations that addresses these limitations. UHGV provides high-quality virome references with extensive host predictions, comprehensive functional annotations, protein structures, a classification framework for comparative analysis, and a web portal to facilitate data access. Using UHGV to profile worldwide metagenomes, we found that host range breadth is strongly associated with phage prevalence. Additionally, we identified diversity-generating retroelements and DNA methyltransferases as key factors enabling phage populations to access diverse hosts, revealing how specific genomic features contribute to global phage distribution patterns. UHGV is available at http://uhgv.jgi.doe.gov.}, }
@article {pmid41408251, year = {2025}, author = {Liu, Z and Shi, H and Li, N and Xu, Z and Zhao, X and Liu, G and Liang, X and Yang, X}, title = {Couples exposure to neonicotinoid insecticides and its influence on in vitro fertilization/intracytoplasmic sperm injection outcomes.}, journal = {Environmental health : a global access science source}, volume = {24}, number = {1}, pages = {93}, pmid = {41408251}, issn = {1476-069X}, support = {82571898//Natural Science Foundation of China/ ; 2023A1515012940//Natural Science Foundation of Guangdong Province/ ; 2023WST04//Key laboratory start-up project (Sixth Affiliated Hospital of Sun Yat-sen University)/ ; }, }
@article {pmid41404442, year = {2025}, author = {Lee, M and Hwang, SY and Wi, K and Kim, J and Lee, MH and Hwang, IH}, title = {Pharmacological evaluation of 1-acetyl-β-carboline, a naturally occurring compound with anti-skin cancer potential.}, journal = {Molecular therapy. Oncology}, volume = {33}, number = {4}, pages = {201093}, pmid = {41404442}, issn = {2950-3299}, abstract = {The human microbiome comprises microbial communities that reside in the human body and contribute to host health through molecular mediators. Lactobacillus spp. are frequently used as probiotics to restore microbial balance, and L. gasseri has been reported to exert a wide range of beneficial effects. In this study, 1-acetyl-β-carboline (ABC) was identified in L. gasseri cultures and subsequently synthesized via the Pictet-Spengler reaction followed by palladium-catalyzed oxidation. ABC exhibited significant anticancer activity by reducing colony formation and growth of epidermal growth factor-induced JB6 cells and by inhibiting the proliferation of SK-MEL-5 and SK-MEL-28 melanoma cells. Mechanistic studies revealed that ABC induced G2/M phase cell-cycle arrest and promoted apoptosis by regulating related markers, including p27 and caspases-3 and -7. Additionally, ABC significantly inhibited the mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling pathway by reducing phosphorylated MEK and phosphorylated ERK levels. ABC also downregulated cyclooxygenase-2 expression, targeting inflammation-related pathways in melanoma cells. In a mouse model, ABC effectively mitigated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal hyperplasia and reduced inflammation. These findings highlight the pharmacological significance of ABC, independent of its origin, and suggest that this naturally occurring compound possesses preventive and therapeutic potential against skin cancer.}, }
@article {pmid41396889, year = {2025}, author = {Chowdhury, R and Maiti, U and Devi, S and Pasanna, RM and Taneja, S and Majumder, PP and Strand, TA and Pandey, RM and Kurpad, AV and Mukherjee, S and Bhandari, N}, title = {Impact of an integrated intervention package during preconception, pregnancy, and early childhood on inflammation, IGF-1, IGFBP3 during first 6 months of life: Findings from the WINGS randomized controlled trial.}, journal = {PLOS global public health}, volume = {5}, number = {12}, pages = {e0005118}, doi = {10.1371/journal.pgph.0005118}, pmid = {41396889}, issn = {2767-3375}, abstract = {Early-life interventions targeting maternal and child health, nutrition, and psychosocial care may influence infant growth and immune development by modulating systemic inflammation and growth factor pathways. However, causal evidence on comprehensive, integrated interventions initiated during early life remains limited. This study was nested in a factorial randomized controlled trial involving women aged 18-30 years. Participants were randomized to receive either a preconception intervention package or routine care until early childhood. The intervention included health care for growth-related conditions, nutrition, WASH (water, sanitation, and hygiene), and psychosocial care. The primary study demonstrated a substantial effect of the intervention on child growth and development. Blood samples from 381 infants (178 in intervention and 203 in control group) were analyzed at 3 and 6 months of age for inflammatory and growth-related biomarkers: C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), insulin-like growth factor 1 (IGF-1), and IGF binding protein 3 (IGFBP3). Generalized linear models were used to estimate mean differences and relative risks for the outcomes. The trial was registered at the Clinical Trials Registry-India: CTRI/2020/10/028770. Baseline maternal characteristics were similar between the two groups. At 3 and 6 months, the proportions of infants with CRP levels > 5 mg/L were similar in both groups. No significant differences were observed in AGP or IGF-1 concentrations at either time point. IGFBP3 was lower in the intervention group at 3 months [adjusted mean difference: [30.8(-55.3, -6.3)] ng/mL, but this effect was not sustained at 6 months. An integrated intervention delivered from preconception through pregnancy and early childhood did not reduce systemic inflammation markers or produce sustained improvements in growth factor profiles during the first six months of life. These findings highlight the complexity of early-life inflammatory processes and underscore the need for further research on long-term effects of early-life interventions in low-resource settings.}, }
@article {pmid41387308, year = {2025}, author = {Zhao, Z and Li, Q and Bai, X and Zhai, E and Dai, W and Qian, Y and Zhang, T and Huang, Z and Huang, Z and Meng, F and Chen, J and Zuo, T and Cai, S and Zhao, R}, title = {Gut Bacterium Lysinibacillus Sphaericus Exacerbates Aspirin-induced Intestinal Injury by Production of Carboxylesterase EstB.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e17747}, doi = {10.1002/advs.202517747}, pmid = {41387308}, issn = {2198-3844}, support = {82100626//National Natural Science Foundation of China/ ; 82173239//National Natural Science Foundation of China/ ; 32470958//National Natural Science Foundation of China/ ; 82403246//National Natural Science Foundation of China/ ; 823B2010//National Natural Science Foundation of China/ ; 202206010014//Special Project of Guangzhou Science and Technology Innovation Development/ ; }, abstract = {Aspirin provides long-term health benefits but can cause gastrointestinal toxicity, and the role of gut microbiota in aspirin metabolism and enterotoxicity remains unclear. In this study, the contribution and mechanisms of microbiota-aspirin interactions in intestinal injury are investigated. In a mouse model, aspirin-induced enteropathy is found to be more severe in microbiota-replete than in microbiota-depleted mice, implicating a detrimental role of gut microbiota. Co-cultivation experiments revealed that gut microbes facilitated the biotransformation of aspirin into salicylic acid, a metabolite more harmful than aspirin itself in disrupting epithelial cell integrity and renewal, both in vitro and in vivo. Through metagenomic screening, selective bacterial interrogation, and functional validation, Lysinibacillus sphaericus is identified as the culprit bacterium, and its secreted carboxylesterase EstB as the key enzyme catalyzing aspirin hydrolysis to salicylic acid. Importantly, inhibition of microbial EstB with the dietary compound flavanomarein abrogated aspirin biotransformation and prevented intestinal injury. Together, these findings reveal L. sphaericus and EstB as central drivers of aspirin enterotoxicity, highlight the functional importance of gut microbiota in drug metabolism, and suggest microbiota- and metabolite-guided precision prevention strategies.}, }
@article {pmid41384120, year = {2025}, author = {Li, X and Guo, G and Shi, Q and Chen, Q and Li, L}, title = {Association study between intestinal microbiota dysbiosis in inflammatory bowel disease and the global disease burden growth trend.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1635242}, pmid = {41384120}, issn = {2296-858X}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a group of chronic intestinal inflammatory diseases. Its incidence and prevalence have been on the rise globally, imposing a heavy burden on patients' health and social medical resources. Intestinal microbiota dysbiosis is believed to play a crucial role in the occurrence and development of IBD, but the association between them and the global disease burden growth trend remains unclear.<br><br>METHODS: By searching the Global Burden of Disease (GBD) study database, we collected IBD disease burden data from 180 countries and regions between 1990 and 2023, including key indicators such as incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Intestinal microbiota data were sourced from two parts: (1) Independent collection: A total of 20,000 healthy individuals and IBD patients were selected as research subjects from 180 countries and regions using a stratified random sampling method. Fecal samples (2-5 grams per person) were collected and immediately stored in a -80 &#xb0;C ultra-low temperature refrigerator to avoid changes in the microbial community structure; (2) Supplementary data from public databases: Published intestinal microbiota sequencing data of corresponding regions from 1990 to 2023 were extracted from the MGnify (https://www.ebi.ac.uk/metagenomics/), Human Microbiome Project (HMP), and GMrepo (https://gmrepo.humangut.info/) databases. The sample size for each country and region was no less than 500 to cover populations of different ages (18-70&#x202f;years), genders (male/female ratio approximately 1:1), and dietary habits (high-fiber diet, high-sugar and high-fat diet). Technologies like metagenomic sequencing and 16S rRNA gene sequencing were used to obtain data on the composition, abundance, and diversity of the intestinal microbiota of the corresponding regional populations. For metagenomic sequencing, the Illumina HiSeq or NovaSeq platform was used. Linear regression models, time-series analysis, and causal inference methods were applied to evaluate the correlation between intestinal microbiota dysbiosis and the growth trends of various disease burden indicators, and to explore the potential impact mechanisms.<br><br>RESULTS: The global incidence of IBD increased from 12.3 per 100,000 in 1990 to 25.6 per 100,000 in 2023, the prevalence rose from 396 per 100,000 to 523 per 100,000, and the DALY value also increased significantly (from 230 per 100,000 in 1990 to 380 per 100,000 in 2023). The average annual growth rates of the above indicators were 2.8% (95% CI: 2.5-3.1%, p <&#x202f;0.001), 1.0% (95% CI: 0.8-1.2%, p <&#x202f;0.001), and 1.5% (95% CI: 1.3-1.7%, p <&#x202f;0.001), respectively. Further analysis showed that intestinal microbiota dysbiosis was closely related to the growth of the disease burden. In regions with severe microbiota dysbiosis, the annual growth rate of the IBD incidence was 3.2 times higher than that in balanced regions (&#x3b2; =&#x202f;3.2, 95% CI: 2.8-3.6, p <&#x202f;0.001); when the average abundance of beneficial bacteria such as Bifidobacterium and Lactobacillus in the intestine decreased by 40% (relative to the average abundance of healthy populations) and the abundance of harmful bacteria such as Escherichia coli increased by 60%, the annual growth rate of IBD incidence in this region was as high as 8.5% (95% CI: 7.9-9.1%, p <&#x202f;0.001); in regions where the Shannon index decreased by 10%, the incidence of IBD increased by an average of 15% (&#x3b2; =&#x202f;0.15, 95% CI: 0.12-0.18, p <&#x202f;0.001). A positive correlation was observed between the degree of intestinal microbiota dysbiosis and disease severity (measured by DALYs): in regions where the intestinal F/B ratio deviated from the normal range by more than 30%, DALYs were 40% higher than those in regions with a normal ratio (&#x3b2; =&#x202f;0.40, 95% CI: 0.35-0.45, p <&#x202f;0.001); in regions where the content of short-chain fatty acids (SCFAs) decreased by 20%, DALYs increased by approximately 25% (&#x3b2; =&#x202f;0.25, 95% CI: 0.21-0.29, p <&#x202f;0.001). Among IBD patients with different severity levels in the Asian region, the abundance of specific bacterial genera related to inflammation regulation (e.g., Faecalibacterium) in the intestines of severe patients decreased by more than 50% compared with healthy populations, and their DALY values were 60% higher than those of mild patients (95% CI: 55-65%, p <&#x202f;0.001). Additionally, the SCFA levels of severe patients were significantly lower than those of mild patients and healthy populations (median SCFA level: 2.1&#x202f;mmol/L in severe patients; 4.5&#x202f;mmol/L in mild patients; 6.8&#x202f;mmol/L in healthy populations, p <&#x202f;0.001).<br><br>CONCLUSION: This study confirms a close association between intestinal microbiota dysbiosis in inflammatory bowel disease and the global disease burden growth trend. Intestinal microbiota dysbiosis can be used as a key indicator to predict the growth of the IBD disease burden, providing an important theoretical basis for formulating targeted prevention, control strategies, and treatment methods.}, }
@article {pmid41384118, year = {2025}, author = {Bautista, J and Cardona-Maya, WD and Gancino-Guevara, K and López-Cortés, A}, title = {Reprogramming prostate cancer through the microbiome.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1690498}, pmid = {41384118}, issn = {2296-858X}, abstract = {Prostate cancer (PCa) is a major global public health challenge, driven by a multifactorial interplay of genetic, epigenetic, hormonal and environmental determinants. In recent years, the human microbiome has emerged as a critical and previously underappreciated contributor to PCa initiation, progression, and therapeutic response. Emerging high-resolution multi-omics studies have demonstrated that microbial communities across the gut, urinary tract and prostate form a functional axis that shapes immune surveillance, hormonal metabolism, inflammatory tone and epigenetic regulation. Dysbiosis in these compartments promotes chronic inflammation, modulates androgen receptor signaling, and produces bioactive metabolites, including short-chain fatty acids, that activate oncogenic IGF-1/MAPK/PI3K and NF-κB/JAK/STAT pathways. Cross-compartmental trafficking of bacterial taxa and metabolites reinforces tumor-promoting circuits, while specific commensals such as Akkermansia muciniphila enhance antitumor immunity and improve responses to androgen deprivation therapy. Importantly, microbiota-derived factors also modulate microRNA (miRNAs) expression and epigenetic signatures, thereby affecting tumor plasticity and resistance to therapy. These mechanistic insights have catalyzed interest in microbiome-based therapeutic approaches, including probiotics, prebiotics, fecal microbiota transplantation, dietary modulation and bacteriophage therapy, which hold promise for restoring eubiosis and enhancing treatment efficacy. Nevertheless, clinical translation remains limited by inter-individual variability and the need for well-designed, longitudinal studies integrating shotgun metagenomics, metabolomics and host-microbe interactomics. Overall, the prostate, urinary and gut microbiomes represent interconnected targets that may inform precision diagnostics and novel therapeutic strategies in PCa.}, }
@article {pmid41380667, year = {2025}, author = {Insel, RA and Jarman, JB and Torres, PJ and Van Dien, S and Culler, SJ and de Vos, WM}, title = {Restoring a gut Bifidobacterium community in early infancy.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {12}, pages = {2012-2016}, doi = {10.1016/j.chom.2025.10.017}, pmid = {41380667}, issn = {1934-6069}, mesh = {Humans ; *Bifidobacterium/growth &amp; development/genetics ; *Gastrointestinal Microbiome ; Infant ; *Dysbiosis/microbiology/prevention &amp; control ; Oligosaccharides/metabolism ; Milk, Human/chemistry/metabolism ; Probiotics/administration &amp; dosage ; Infant, Newborn ; }, abstract = {An early-life microbiota with increased Bifidobacterium and human milk oligosaccharide (HMO) utilization genes has been linked to decreased risk of childhood allergic disease. As infant microbiomes increasingly have reduced Bifidobacterium, we examine early-life dysbiosis and interventions that potentially prevent or reverse this dysbiotic state, thus mitigating noncommunicable diseases.}, }
@article {pmid41292759, year = {2025}, author = {Van Egeren, D and Schenck, RO and Khan, A and Horning, AM and Mo, S and Weiß, CL and Esplin, ED and Becker, WR and Wu, S and Hanson, C and Barapour, N and Jiang, L and Contrepois, K and Lee, H and Nevins, SA and Guha, TK and Zhang, H and He, Z and Ma, Z and Monte, E and Karathanos, TV and Laquindanum, R and Mills, MA and Chaib, H and Chiu, R and Jian, R and Chan, J and Ellenberger, M and Bahmani, B and Michael, B and Weimer, AK and Esplin, DG and Lancaster, S and Shen, J and Ladabaum, U and Longacre, TA and Kundaje, A and Greenleaf, WJ and Hu, Z and Ford, JM and Snyder, MP and Curtis, C}, title = {Polyclonal origins of human premalignant colorectal lesions.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {41292759}, issn = {2692-8205}, abstract = {Cancer is generally thought to be caused by expansion of a single mutant cell[1]. However, analyses of early colorectal cancer lesions suggest that tumors may instead originate from multiple, genetically distinct cell populations[2,3]. Detecting polyclonal tumor initiation is challenging in patients, as it requires profiling early-stage lesions before clonal sweeps obscure diversity. To investigate this, we analyzed normal colorectal mucosa, benign and dysplastic premalignant polyps, and malignant adenocarcinomas (123 samples) from six individuals with familial adenomatous polyposis (FAP). Individuals with FAP have a germline heterozygous APC mutation, predisposing them to colorectal cancer and numerous premalignant polyps by early adulthood[4]. Whole-genome and/or whole-exome sequencing revealed that many premalignant polyps-40% with benign histology and 28% with dysplasia-were composed of multiple genetic lineages that diverged early, consistent with polyclonal origins. This conclusion was reinforced by whole-genome sequencing of single crypts from multiple polyps in additional patients which showed limited sharing of mutations among crypts within the same lesion. In some cases, multiple distinct APC mutations co-existed in different lineages of a single polyp, consistent with polyclonality. These findings reshape our understanding of early neoplastic events, demonstrating that tumor initiation can arise from the convergence of diverse mutant clones. They also suggest that cell-intrinsic growth advantages alone may not fully explain tumor initiation, highlighting the importance of microenvironmental and tissue-level factors in early cancer evolution.}, }
@article {pmid41373536, year = {2025}, author = {Mascellino, MT}, title = {Special Issue: "Molecular Research in Human Microbiome 2.0".}, journal = {International journal of molecular sciences}, volume = {26}, number = {23}, pages = {}, doi = {10.3390/ijms262311379}, pmid = {41373536}, issn = {1422-0067}, mesh = {Humans ; *Microbiota ; Gastrointestinal Microbiome ; }, abstract = {The human microbiome is crucial to the health and welfare of the global population; a healthy microbiome protects us against pathogens while preserving beneficial organisms, assists immune system development and generally maintains a good level of well-being [...].}, }
@article {pmid41366581, year = {2025}, author = {Alimoradi, E and Hashemnejad, MA and Etemad, S and Arabi, M and Bereimipour, A}, title = {Investigation of Transcriptome and Kinome in Non Metastatic and Metastatic Renal Clear Cancer Stem Cells and Their Relationship with Gut Microbiota.}, journal = {Molecular biotechnology}, volume = {}, number = {}, pages = {}, pmid = {41366581}, issn = {1559-0305}, abstract = {Evidence for the microbiome's role in human health and disease has been piling up ever since the human microbiome project. The composition of one's microbiome can have a major effect on one's risk of developing cancer and the nature of how cancer develops. Several estimates suggest the percentage of cancer cases that can be attributed to microorganisms at around 15%. In addition, researchers are still trying to figure out how the microbiota, and the gut microbiota in particular, affects how a patient responds to chemotherapy, immunotherapy, and radiotherapy. In this light, we conducted an in-depth bioinformatics analysis of the gut microbiota- RCCstem cells axis, utilizing python-based programme and enrichment databases to analyses data from many sources, including clinical data, transcription factors, kinases and gene expression profile of RCCstem cells. Five genes, including SLC16A6, CPNE5, AFAP1L1, SCARF1, and NOTCH4, were shown to be shared by the hub gut microbiota and extracellular proteins. Patients with RCCstem cells had a disproportionately high number of certain types of bacteria. In patients expression profile have high CPNE5, AFAP1L1, SCARF1, and NOTCH4 expression. RCCsurvival rates are reduced by roughly 50% due to all of the genes involved. Also, the Actinobacteria and Gammaproteobacteria possible role in renal cancer development via relation to cancer stem cells. The gut microbiota and its components were considered for their possible relevance in the development of RCC.}, }
@article {pmid41366180, year = {2025}, author = {Fernandez-Ibanez, R and Moreno, S and Fernandez, M}, title = {A Review of Doxycycline Post-Exposure Prophylaxis and Its Implications for Antimicrobial Resistance and the Human Microbiome.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, pmid = {41366180}, issn = {2193-8229}, abstract = {Sexually transmitted infections (STIs) remain a major global health burden, with rising incidence of Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. Doxycycline post-exposure prophylaxis (DoxyPEP), consisting of a single 200 mg dose within 72 h after condomless sex, has emerged as a promising intervention. Randomized controlled trials demonstrate consistent efficacy in reducing chlamydia and syphilis, while protection against gonorrhea is variable, being strongly influenced by baseline tetracycline resistance and anatomical site. Surveillance data from San Francisco and King County confirm that high-frequency use can drive rapid increases in gonococcal tetracycline resistance. Although no cephalosporin resistance has yet been linked to DoxyPEP, genomic correlations raise concern for co-selection of multidrug-resistant strains, particularly FC428-like clones with mosaic penA alleles. C. trachomatis remains uniformly susceptible, with resistance limited to theoretical horizontal transfer from C. suis. T. pallidum shows no evidence of resistance, supported by genomic constraints and experimental studies. Mycoplasma genitalium demonstrates low intrinsic susceptibility to doxycycline, but no acquired tetracycline resistance has been confirmed. Beyond target pathogens, DoxyPEP alters the functional resistome of the human microbiome, amplifying tetracycline resistance gene expression in gut, skin, and oropharyngeal flora, and selecting for resistant Staphylococcus aureus and commensal Neisseria. These ecological shifts underscore the importance of molecular surveillance to monitor resistance spillover. Overall, DoxyPEP provides substantial benefit in controlling chlamydia and syphilis and conditional utility against gonorrhea in low-resistance settings. Its deployment should be coupled with antimicrobial stewardship, local resistance data, and strengthened genomic surveillance to balance individual protection with population-level risks.}, }
@article {pmid41365903, year = {2025}, author = {Szrinivasan, R and Trontti, K and Mathieu, R and Draia-Nicolau, T and Chazal, G and Loukasmäki, S and Bodington Celma, S and Achim, K and Uvarov, P and Khirug, S and Ludwig, A and Lauri, SE and de Chevigny, A and Pietiläinen, O and Rivera, C}, title = {Functional KCC2 expression marks an evolutionarily conserved population of early-maturing interneurons in the perinatal cortex.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-67270-x}, pmid = {41365903}, issn = {2041-1723}, abstract = {The developmental shift from depolarizing to hyperpolarizing GABA responses is a pivotal step in the maturation of GABAergic transmission and cortical circuits; classically documented in principal neurons during the first postnatal week in the mouse cortex. Surprisingly, whether maturation of GABA-mediated responses follows the same temporal pattern in cortical interneurons (INs) remains unresolved. Leveraging an array of methods, a high-resolution cortical development mouse atlas and single-cell RNA sequencing, we identify and comprehensively characterize a population of early-maturing cortical INs in mice, distinguished by KCC2 expression at embryonic stages and concomitant hyperpolarizing GABAA responses at birth. These early KCC2-expressing INs exhibit precocious intrinsic excitability, synaptic integration, and dendritic complexity at birth, contrasting delayed maturation in principal neurons and other INs. Spatial transcriptomics and differential gene expression (DGE) analyses reveal early KCC2-expressing INs localize predominantly to layer 5, express somatostatin, and show upregulation of synaptogenic genes, consistent with the recorded elevated synaptic activity. Crucially, evolutionary conservation of early KCC2-expressing INs in humans was demonstrated with analogous genetic profiles enriched for signaling and synaptic maturation pathways. This work resolves a critical gap in developmental neurobiology, demonstrating heterogenous GABAergic functional maturation within IN subpopulations and establishing KCC2 as a marker of early-maturing INs.}, }
@article {pmid41362424, year = {2025}, author = {Zhang, N and Karkman, A and Hiippala, K and Satokari, R and Takala, TM and Saris, PEJ}, title = {Comparative genomics and characterization of highly adhesive and stress resistant Lacticaseibacillus paracasei strain E.}, journal = {Current research in food science}, volume = {11}, number = {}, pages = {101245}, pmid = {41362424}, issn = {2665-9271}, abstract = {Lacticaseibacillus paracasei strains have a long history of safe use in food products, particularly fermented foods such as yogurt and cheese. These strains are known for their health-promoting probiotic attributes. Recently, we de novo assembled the whole genome of Lacticaseibacillus paracasei subsp. paracasei strain E, originally isolated from cheese and later studied as an adjunct starter in cheesemaking. In this study, the strain's probiotic properties and their potential genetic basis were analyzed using the combination of in vitro and in silico methods. This analysis particularly focused on correlating specific phenotypic traits with the presence or absence of specific gene sets. The strain E harbours two copies of the same spaCBA-srtC1 pilus gene cluster as L. rhamnosus GG, and it expresses more SpaC pilins, even though the overall adhesion to mucus was found to be somewhat lower than that of LGG. The strain E exhibited better tolerance to simulated gastrointestinal condition and remarkably higher cell surface hydrophobicity than LGG, suggesting distinct surface properties and hence a different preference for binding to host cells. Taken together, these findings indicate that L. paracasei E has potential as a probiotic strain.}, }
@article {pmid41358022, year = {2025}, author = {Tiemblo-Martin, M and Mercogliano, M and Hiippala, K and De Simone Carone, L and Campanero-Rhodes, MA and Masiello, M and Cangiano, A and Molinaro, A and Paduano, L and Solís, D and Satokari, R and Di Lorenzo, F and Silipo, A}, title = {Odoribacter splanchnicus lipooligosaccharide: an uncommon structure with weak immunostimulatory activity.}, journal = {Chemical science}, volume = {}, number = {}, pages = {}, pmid = {41358022}, issn = {2041-6520}, abstract = {Odoribacter splanchnicus, a prominent member of the human gut microbiota, has emerged as a promising next-generation probiotic due to its anti-inflammatory properties and association with intestinal health. While previous studies have demonstrated its ability to attenuate inflammation and protect epithelial integrity, the molecular basis underlying these effects remained elusive. In this study, we provide the first comprehensive structural and functional characterization of the O. splanchnicus lipooligosaccharide (LOS), a major immunomodulatory surface component. NMR spectroscopy and mass spectrometry revealed a heterogeneous LOS structure composed of a mono-phosphorylated tetra- and penta-acylated lipid A backbone and a highly branched, short core oligosaccharide featuring unique residues such as 4-lactylmannose and galactosaminuronic acid. Small-angle X-ray scattering demonstrated that the LOS self-assembles into core-shell spherical micelles, with a large oligosaccharide corona shielding the lipid A, thereby limiting its accessibility to the innate immunity TLR4/MD-2 receptor complex. Accordingly, the O. splanchnicus LOS exhibited minimal TLR4 activation and failed to induce IL-8 secretion in enterocyte cell lines, in stark contrast to proinflammatory Escherichia coli LPS; in addition, it potently antagonized E. coli LPS-induced inflammation. These findings identify the LOS as a key effector of the O. splanchnicus anti-inflammatory phenotype and support its further development as a live biotherapeutic agent.}, }
@article {pmid41354223, year = {2025}, author = {Adhikary, P and Maddheshiya, A and Takkar, B and Das, T and Mukherjee, S}, title = {Differential gut microbiome profiles in diabetic retinopathy: A comparative study across continental populations.}, journal = {Diabetes research and clinical practice}, volume = {}, number = {}, pages = {113043}, doi = {10.1016/j.diabres.2025.113043}, pmid = {41354223}, issn = {1872-8227}, abstract = {Gut dysbiosis damages gut barrier, stimulates inflammation, endotoxemia, and breakdown of blood-retina barrier, promoting diabetic retinopathy (DR). Most microbiome studies on DR relied on 16S rRNA gene sequencing, documenting altered microbial richness, diversity, and shifts in dominant phyla and genera, though these findings remain inconsistent across populations. The only shotgun metagenomic study to date identified species Eubacterium hallii, Firmicutes bacterium and Alistipes finegoldii enriched in DR, with altered metabolic pathways. The β-diversity showed distinct inter-individual variations in diseased individuals compared to healthy controls (HC). The objective of this narrative review is to highlight the key microbial biomarkers, metabolic pathways, and putative microbiota-gut-retina axis integrating both 16S rRNA and shotgun data to compare microbial alterations across HC, T2DM, and DR. The review concludes with a comprehensive understanding of dysbiotic gut taxa associated with DM and DR in different populations showing wide variability in results mostly due to small sample size, geography, antidiabetic medications, lack of demographic and clinical data and limited taxonomic classification by 16S sequencing. This emphasizes the need of a large scale, multi-ethnic shotgun metagenomic sequencing study with systematically collected medical data and dietary information to understand the contributions of gut microbiome in the progression of DR.}, }
@article {pmid41352809, year = {2026}, author = {Shazad, A and Tlais, AZA and Trossolo, E and Casagrande Bacchiocchi, S and Filannino, P and Pinto, D and Gobbetti, M and Di Cagno, R}, title = {Pre-digestion of soybeans, fermentation with fructophilic lactic acid bacteria, and in silico analyses to uncover psychobiotic potential.}, journal = {Food research international (Ottawa, Ont.)}, volume = {223}, number = {Pt 1}, pages = {117904}, doi = {10.1016/j.foodres.2025.117904}, pmid = {41352809}, issn = {1873-7145}, mesh = {*Fermentation ; *Glycine max/metabolism/chemistry/microbiology ; Computer Simulation ; *Lactobacillales/metabolism ; *Digestion ; *Prebiotics ; Gastrointestinal Microbiome ; Humans ; Isoflavones ; }, abstract = {Psychobiotics are emerging as key players in gut-brain axis research, yet the role of Fructophilic Lactic Acid Bacteria (FLAB) remains largely unexplored. To address this gap, we employed a comprehensive strategy that first simulated gastrointestinal pre-digestion of soybeans to mimic host conditions, then harnessed FLAB fermentation to reshape the soybean metabolite landscape and finally applied in silico prediction to assess the neuroactive potential of the resulting compounds. Six strains were initially screened for gastrointestinal resistance, with only Apilactobacillus kunkeei (BEE4, PL34) and Fructobacillus fructosus (FCS3, PL22) showing high tolerance. Selected strains showed varied but notable functional and pre-technological enzymatic activities. When inoculated into pre-digested soybean, they showed high adaptation, with efficient acidification and short chain fatty acids release. While in vitro digestion alone enriched the amino acid profile, FLAB fermentation further enhanced it, particularly increasing gamma-aminobutyric acid in PL34_DS. Although digestion reduced most phenolic compounds, fermentation not only restored but also diversified the metabolite pool, yielding higher levels of daidzein, genistein, dihydrokaempferol, biochanin A, sinapic acid, caftaric acid, and naringenin. Similarly, peptide abundance rose after digestion and was further boosted by fermentation, especially with A. kunkeei PL34 and F. fructosus PL22, which increased low-molecular-weight peptides and generated novel sequences. Importantly, PL34_DS consistently showed superior antioxidant activity and the strongest reduction of antinutritional factors, highlighting its functional potential. In silico analyses further revealed that several released phenolics (e.g., daidzein) and peptides have gastrointestinal absorption and blood-brain barrier permeability, targeting neurotransmitter receptors, cytokine networks, and cholinergic enzymes. Taken together, these findings indicate that FLAB-driven soybean fermentation can enrich neuroactive metabolite profiles with promising psychobiotic potential, providing a foundation for future in vivo studies aimed at mental health modulation.}, }
@article {pmid41352125, year = {2025}, author = {Taki, AG and Shareef, A and Arora, V and Oweis, R and Jyothi, SR and Singh, U and Sahoo, S and Chauhan, AS and Alimova, F and Sameer, HN and Yaseen, A and Athab, ZH and Adil, M}, title = {Unraveling the microbiome's role in breast cancer progression and treatment response.}, journal = {Current problems in cancer}, volume = {60}, number = {}, pages = {101264}, doi = {10.1016/j.currproblcancer.2025.101264}, pmid = {41352125}, issn = {1535-6345}, abstract = {The human microbiome, encompassing microbial communities in the gut and breast tissue, has emerged as a critical modulator of breast cancer (BC) initiation, progression, and treatment response. This review synthesizes current evidence on the microbiome's role in BC, highlighting its influence on tumorigenesis, tumor microenvironment (TME), and therapeutic outcomes. Breast cancer, the most prevalent malignancy among women globally, exhibits significant heterogeneity across its molecular subtype's hormone receptor-positive, HER2-enriched, and triple-negative-each with distinct clinical challenges. Recent studies reveal that microbial dysbiosis in the gut and breast tissue can drive oncogenesis through mechanisms such as immune modulation, estrogen metabolism, and inflammation. Gut microbes, via the "estrobolome," regulate circulating estrogen levels, impacting hormone-driven BC, while breast tissue microbiota contributes to local inflammation and DNA damage, promoting tumor progression. Specific microbial taxa, including Bacillus, Staphylococcus, and Escherichia coli, are enriched in BC patients, whereas beneficial species like Lactobacillus and Bifidobacterium are diminished. The microbiome also influences treatment efficacy, with gut microbial diversity linked to enhanced chemotherapy and immunotherapy responses, while antibiotic-induced dysbiosis may impair outcomes. Emerging research suggests microbiome signatures as potential biomarkers for predicting therapeutic success, with Akkermansia muciniphila and short-chain fatty acids showing promise in enhancing anti-tumor immunity. Probiotics, prebiotics, and fecal microbiota transplantation offerel therapeutic avenues, though challenges such as standardization, interindividual variability, and safety concerns remain. Integrating multi-omics and machine learning could elucidate microbiome-host interactions, paving the way for precision oncology. This review underscores the transformative potential of microbiome-based diagnostics and interventions in improving BC management, emphasizing the need for large-scale, longitudinal studies to validate these findings and address existing research gaps.}, }
@article {pmid41350302, year = {2025}, author = {Sieskind, R and Missoury, S and Bonhomme, F and Nogaret, P and Lucas-Staat, S and Monot, M and Skurnik, M and Baudoux, AC and Delarue, M}, title = {Exploitation of phage Carin-5's own DNA polymerase to sequence its T-hypermodified genome.}, journal = {Scientific reports}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41598-025-26930-0}, pmid = {41350302}, issn = {2045-2322}, abstract = {The bacteriophage Carin-5, which infects Cobetia marina, presented significant challenges for genome sequencing due to DNA modifications that hindered efficient amplification of its DNA. Initial attempts using an optimized Illumina library preparation protocol yielded only a partial genome. Among the obtained contigs, the gene encoding the replicative DNA polymerase was identified. This gene was subsequently cloned into an expression vector and the encoded DNA polymerase protein was purified. The purified DNA polymerase was used to replicate the Carin-5 genomic DNA in vitro, effectively bypassing the modification-induced amplification barriers. This approach enabled the amplification of the entire Carin-5 genomic DNA and the use of a standard NGS library preparation protocol and allowed to obtain the complete sequence of the Carin-5 genome. The DNA modifications were characterized by mass spectrometry, and they showed a clear analogy with the oligosaccharide-hypermodified thymidines of bacteriophage SP-15. The annotated genome of Carin-5 carried a gene block encoding enzymes for nucleotide sugar modifications and glycosyltransferases.}, }
@article {pmid41350154, year = {2025}, author = {Vonaesch, P and Garneau, JR and Dominguez-Bello, MG}, title = {From global to local: rethinking the design of probiotic intervention strategies.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2025.11.009}, pmid = {41350154}, issn = {1878-4380}, abstract = {The human microbiome plays a crucial role in maintaining homeostasis and influencing disease development, yet its composition varies across geography, age, and lifestyle. These differences challenge the efficacy of universal probiotic treatments and call for more personalized or regionally adapted approaches. In this review we examine the limitations of universal probiotics, emphasizing the importance of considering host-microbe co-adaptation, local dietary practices, and ecological context. We argue that probiotic design must account for microbial diversity, strain-level adaptation, and functional redundancy, and we explore how these factors affect colonization success and therapeutic potential. Finally, we discuss ways to re-center microbiome knowledge within diverse ecological, cultural, and epistemic traditions for a global, inclusive approach allowing for microbiome-targeted therapies that are both effective and accessible.}, }
@article {pmid41348839, year = {2025}, author = {Fan, S and Ma, N and Li, J and Wang, B and Zhao, Y and Yao, Y and Chai, X and Zhou, Z}, title = {Oral Icariin Nanoparticles Ameliorate Nonalcoholic Fatty Liver Disease by Alleviating Oxidative Stress.}, journal = {ACS applied materials &amp; interfaces}, volume = {}, number = {}, pages = {}, doi = {10.1021/acsami.5c17806}, pmid = {41348839}, issn = {1944-8252}, abstract = {Chronic inflammatory liver conditions, such as nonalcoholic fatty liver disease (NAFLD), are frequently exacerbated by oxidative stress, rendering the neutralization of reactive oxygen species (ROS) crucial for their amelioration. Oral administration of nanoparticles (NPs) presents an optimal strategy for NAFLD management due to its convenience. This research aimed to overcome the poor water solubility and low bioavailability of icariin (ICA) by engineering an oral nanosystem, ICA-loaded poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA) NPs with chitosan (CS) and mannose surface modification (ICA-NPs), to augment ICA's antioxidant potency against NAFLD. Methods involved comprehensive in vitro characterization of ICA-NPs (including dispersibility, biocompatibility, HepG2 targeting, and ROS scavenging capabilities) and in vivo studies in high-fat diet (HFD)-induced NAFLD mice, assessing liver accumulation, ROS scavenging, and antiobesity effects across multiple experimental groups. Results demonstrated that this targeted oral NP system significantly amplified ICA's therapeutic impact, leading to substantial reductions in body weight, diminished white adipose tissue accumulation, decreased hepatic lipid content, improved hepatic function, and a notable suppression of ROS in the livers of NAFLD-afflicted mice. In conclusion, by harnessing the precision of targeted delivery, this oral nanosystem not only enhances ICA's therapeutic efficacy but also establishes a safe and effective platform for the oral administration of herbal remedies for liver conditions, suggesting a promising avenue for advancing herbal medicine in liver disease treatment.}, }
@article {pmid41335477, year = {2025}, author = {Riskumäki, M and Ruuskanen, MO and Mäenpää, K and Ruokolainen, L and Mäkelä, MJ and Jousilahti, P and Vartiainen, E and Ottman, N and Laatikainen, T and Haahtela, T and Alenius, H and Fyhrquist, N and Sinkko, H}, title = {Shotgun metagenomics reveals distinct skin microbial species in allergen-sensitized individuals.}, journal = {Microbial genomics}, volume = {11}, number = {12}, pages = {}, doi = {10.1099/mgen.0.001527}, pmid = {41335477}, issn = {2057-5858}, mesh = {Humans ; *Metagenomics/methods ; *Allergens/immunology ; *Skin/microbiology/virology ; Finland ; Adolescent ; *Microbiota/genetics ; Male ; Russia ; Female ; *Hypersensitivity/microbiology/immunology ; Malassezia/genetics/isolation &amp; purification ; Immunoglobulin E/immunology ; Bacteria/genetics/classification ; Child ; }, abstract = {The Karelian region, which spans the border between Finland and Russia, presents distinct environmental exposures and lifestyles on either side of the governmental border. In the more urbanized Finnish Karelia, allergic diseases are markedly more prevalent than in the more rural Russian Karelia. Prior studies, based on amplicon sequencing, have demonstrated major differences in skin microbiotas between the two populations. However, compositional differences in microbiota between sensitized and non-sensitized (NS) individuals have not been characterized. Here, in a selected population of 112 allergen-sensitized and NS adolescents, we used shotgun metagenomics to characterize the prokaryotic, eukaryotic and viral species in the skin potentially involved in allergic sensitization via distinct environmental exposures. In the more urban Finnish Karelia, the microbiome species composition was associated with IgE-mediated allergen sensitization status, while in the more rural Russian Karelia, the composition was associated with exposure to furry pets. Finnish participants showing high IgE-mediated sensitization to common allergens (allergen-specific IgE >7.5 kU/L) had less Cutibacterium acnes and Malassezia in their skin and displayed weaker interconnectedness of the microbial co-occurrence network compared with NS participants. Moreover, Malassezia restricta strain-level differences were related to allergen sensitization in both Finnish and Russian participants. In summary, we found distinct skin microbiomes between allergen-sensitized and NS participants and tracked the bacterial and fungal species associated with the degree of allergic sensitization in the more urbanized part of the Karelian region. These findings provide new insights into the factors that shape the human skin microbiome and influence allergic diseases.}, }
@article {pmid41331251, year = {2025}, author = {Zhao, Y and Chen, H and Huang, J and Chistoserdova, L and Yu, Z}, title = {The gut methanotroph Methylocystis intestini modulates intestinal peristalsis and fat metabolism via reducing methane levels.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-66596-w}, pmid = {41331251}, issn = {2041-1723}, support = {32300051//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Methane, a predominant component of human intestinal gas, has been reported to be associated with a reduction in intestinal transit speed, as well as correlations with elevated body mass index. While the gut methanogenic archaea that produce this gas have been studied, the countervailing role of methane-consuming bacteria (methanotrophs) within the human gut ecosystem remains a critical, under-explored area. The potential for these bacteria to act as a built-in sink for intestinal methane and thereby mitigate its negative physiological effects is unknown. Here, we isolate an unreported methanotroph from human fecal samples, classified as Methylocystis intestini. Using a mouse model, we observe that methane challenge is associated with gastrointestinal motility and fat metabolism. We then demonstrate that the administration of Methylocystis intestini effectively reverses these dysfunctional processes, restoring motility and metabolic parameters. Additional analysis of methane-oxidation genes abundance in 1207 public metagenomic sequences from individuals with varying health statuses, including obesity and constipation, provides consistent correlative support for our experimental conclusions. Expanding this view to a global scale, we conducted a metagenomic survey of 550 human fecal samples from populations across five continents. This broader analysis reveals that methane-oxidizing genes are not a rarity but a common feature of the human gut microbiome, being detectable in over 91% of samples. This ubiquity underscores their fundamental role in human biology. Collectively, our findings establish gut methanotrophs as key mediators of intestinal methane level. Their presence is widespread across global populations, and their functional capacity can balance the effects of methane on host physiology. This work elucidates a crucial component of gut homeostasis and opens a promising avenue for developing microbiome-based therapeutic strategies aimed at managing methane-related gastrointestinal disorders by harnessing the power of these native methane-consuming bacteria.}, }
@article {pmid41328030, year = {2025}, author = {Hickman, B and Korpela, K}, title = {Impact of data compositionality on the detection of microbiota responses.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2590841}, doi = {10.1080/19490976.2025.2590841}, pmid = {41328030}, issn = {1949-0984}, mesh = {*High-Throughput Nucleotide Sequencing/methods ; *Bacteria/classification/genetics/isolation &amp; purification ; *Microbiota ; Humans ; Computer Simulation ; *Gastrointestinal Microbiome ; Computational Biology/methods ; *Metagenomics/methods ; }, abstract = {Next-generation sequencing (NGS) data usage is widespread, but its compositional nature poses challenges. We evaluated four normalization methods (relative abundance, CLR, TMM, DESeq2) for identifying true signals in compositional microbiota data using simulations. Two experiments were conducted: one with only increases in specific taxa, and a 1:1 increase/decrease in specific taxa. Simulated sequencing produced compositional data, which were normalized using the four methods. The study compared absolute abundance data and the normalized compositional data using variance explained and false discovery rates. All normalization methods showed decreased variance explained and increased false positives and negatives compared to absolute abundance data. CLR, TMM, and DESeq2 did not improve over relative abundance data and sometimes worsened false discovery rates. The study highlights that false positives and negatives are common in compositional NGS datasets, and current normalization methods do not consistently address these issues. Compositionality artefacts should be considered when interpreting NGS results and obtaining absolute abundances of features/taxa is recommended to distinguish biological signals from artefacts.}, }
@article {pmid41326814, year = {2025}, author = {Kelliher, JM and Mirzayi, C and Bordenstein, SR and Oliver, A and Kellogg, CA and Hatcher, EL and Berg, M and Baldrian, P and Aljumaah, M and Miller, CML and Mungall, C and Novak, V and Palucki, A and Smith, E and Tabassum, N and Bonito, G and Brister, JR and Chain, PSG and Chen, M and Degregori, S and Dundore-Arias, JP and Emerson, JB and Moreira C Fernandes, V and Flores, R and Gonzalez, A and Hansen, ZA and Jackson, SA and Moustafa, AM and Northen, TR and Pariente, N and Pett-Ridge, J and Record, S and Reji, L and Reysenbach, AL and Rich, VI and Richardson, L and Roux, S and Schriml, LM and Shabman, RS and Sierra, MA and Sullivan, MB and Sundaramurthy, P and Thibault, KM and Thompson, LR and Tighe, S and Vereen, E and ,  and Eloe-Fadrosh, EA}, title = {STREAMS guidelines: standards for technical reporting in environmental and host-associated microbiome studies.}, journal = {Nature microbiology}, volume = {10}, number = {12}, pages = {3059-3068}, pmid = {41326814}, issn = {2058-5276}, abstract = {The interdisciplinary nature of microbiome research, coupled with the generation of complex multi-omics data, makes knowledge sharing challenging. The Strengthening the Organization and Reporting of Microbiome Studies (STORMS) guidelines provide a checklist for the reporting of study information, experimental design and analytical methods within a scientific manuscript on human microbiome research. Here, in this Consensus Statement, we present the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines. The guidelines expand on STORMS and include 67 items to support the reporting and review of environmental (for example, terrestrial, aquatic, atmospheric and engineered), synthetic and non-human host-associated microbiome studies in a standardized and machine-actionable manner. Based on input from 248 researchers spanning 28 countries, we provide detailed guidance, including comparisons with STORMS, and case studies that demonstrate the usage of the STREAMS guidelines. STREAMS, like STORMS, will be a living community resource updated by the Consortium with consensus-building input of the broader community.}, }
@article {pmid41322070, year = {2025}, author = {Amirinia, F and Motamedi, M and Ardi, P and Jabrodini, A}, title = {Evaluating the Role of Candida albicans as a Potential Oral Carcinogen.}, journal = {Interdisciplinary perspectives on infectious diseases}, volume = {2025}, number = {}, pages = {4057977}, pmid = {41322070}, issn = {1687-708X}, abstract = {Oral cavity cancers, especially oral squamous cell carcinoma (OSCC), are a major subset of head and neck malignancies. Increasing evidence indicates that oral microbiota, particularly Candida albicans (C. albicans), plays a significant role in OSCC development and progression. While C. albicans is normally a commensal organism in the human microbiome, it can become pathogenic under certain conditions. The carcinogenic potential of C. albicans contributes to oral cancer by acting both as a co-factor and a direct pathogen. This involves complex interactions with the host immune system and the expression of multiple virulence factors. The dynamic relationship between C. albicans and its host influences disease outcomes and cancer progression. This review focuses on key virulence mechanisms of C. albicans, including adhesion to host cells, secretion of hydrolytic enzymes, production of carcinogenic metabolites, induction of chronic inflammation, and release of candidalysin, a cytolytic peptide toxin. Understanding these factors is essential to clarify how C. albicans promotes OSCC initiation and progression. Improved knowledge of C. albicans virulence may lead to targeted therapies, preventive strategies, and novel biomarkers for early detection, ultimately enhancing treatment outcomes and prognosis for patients with oral cavity cancers.}, }
@article {pmid40953220, year = {2025}, author = {Liu, C and Lai, P and Hu, J and Yin, S and Guo, S and Liu, D and Yu, J and Liang, D and Chen, G and Xing, M and Luo, Z and He, X and Gong, J and Lan, P and He, Z}, title = {Lactobacillus johnsonii Synthesizes Chenodeoxycholic Acid to Reduce Susceptibility to High-Fat Diet-Induced Colorectal Cancer.}, journal = {Cancer research}, volume = {85}, number = {23}, pages = {4600-4615}, doi = {10.1158/0008-5472.CAN-25-0879}, pmid = {40953220}, issn = {1538-7445}, support = {2022YFA1304000//National Key Research and Development Program of China (NKPs)/ ; 2024B1111150001//Guangdong Provincial Department of Science and Technology (GDSTC)/ ; 2021B1212040017//Guangdong Provincial Department of Science and Technology (GDSTC)/ ; 2020B1111170004//Guangdong Gastrointestinal Disease Research Center/ ; 82273346//National Natural Science Foundation of China (NSFC)/ ; U21A20344//National Natural Science Foundation of China (NSFC)/ ; 2023WST03//Sun Yat-sen University (SYSU)/ ; //National Key Clinical Specialty Discipline Construction Program of China (National Key Clinical Specialty Construction Programs of China)/ ; //Guangdong Cheung Kong Foundation/ ; B2302036//Shenzhen Government ()/ ; }, mesh = {Animals ; *Colorectal Neoplasms/etiology/prevention &amp; control/microbiology/pathology/metabolism ; *Diet, High-Fat/adverse effects ; Mice ; Gastrointestinal Microbiome ; *Chenodeoxycholic Acid/metabolism/biosynthesis ; *Lactobacillus johnsonii/metabolism ; Mice, Inbred C57BL ; Humans ; Probiotics ; Male ; Disease Susceptibility ; Apoptosis ; Oxidative Stress ; }, abstract = {UNLABELLED: High-fat diet (HFD) is positively correlated with colorectal cancer, but there are notable interindividual differences in susceptibility to the tumor-promoting effects of HFD. A better understanding of the mechanisms that modulate the outcomes of HFD could help inform precision prevention strategies for colorectal cancer. In this study, we found a key role for the gut microbiota in the individual differences observed in the tumor-promoting effects of HFD. Analysis of the gut bacteria enriched in mice resistant to HFD-induced cancer identified Lactobacillus johnsonii as an effective protector. Colonization of L. johnsonii increased intestinal chenodeoxycholic acid (CDCA) concentrations in HFD-exposed mice, which decelerated HFD-induced colorectal cancer progression. Mechanistically, L. johnsonii converted conjugated bile acid to CDCA via bile salt hydrolase, and CDCA induced mitochondrial dysfunction and oxidative stress to promote apoptosis, effectively suppressing tumor development. These results establish the gut microbiota as a mediator of interindividual differences in cancer susceptibility induced by HFD and reveal a probiotic strategy with the ability to inhibit tumorigenesis, suggesting a possible route to reduce HFD-induced colorectal cancer progression.<br><br>SIGNIFICANCE: Investigation of bacteria-host interactions that alter cancer susceptibility uncovers suppression of high-fat diet-induced colorectal cancer by Lactobacillus johnsonii, offering a translational approach to improve cancer prevention. See related commentary by Dalal and Shah, p. 4579.}, }
@article {pmid41320324, year = {2025}, author = {Liu, C and Gong, J and Luo, Z and Lai, P and Guo, S and Liang, D and Chen, G and Xing, M and Yu, J and Xie, Y and Liu, D and Zeng, W and He, Z and Lan, P}, title = {Gut microbe alleviates stress-related cancer metastasis by oleic acid degradation.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-335627}, pmid = {41320324}, issn = {1468-3288}, abstract = {BACKGROUND: Chronic stress is a known risk factor for cancer metastasis. However, the underlying mechanisms, particularly those involving the gut microbiota and their metabolites, remain unclear.<br><br>OBJECTIVE: To investigate whether gut microbiota dysbiosis and metabolic alterations mediate the sustained pro-metastatic effects of chronic stress, even after normalisation of stress hormone levels.<br><br>DESIGN: Multiple metastatic models were performed after stress cessation. Shotgun metagenomics and metabolomics were performed to assess changes in microbiota and metabolites. The effects of Bifidobacterium animalis and oleic acid (OA) on metastasis were evaluated in vivo and in vitro. Moreover, we explored how B. animalis degraded OA. Mechanistically, we discovered the interaction between corticosteroids and gut bacteria through guanine metabolism assays. Human samples were collected from patients with colorectal cancer (CRC) with varying perceived stress scores and metastatic status for validation.<br><br>RESULTS: Mice that underwent chronic stress exhibited increased metastasis even after hormone levels recovered. The gut microenvironment was altered, with a significant reduction in B. animalis and an increase in OA. B. animalis administration reduced OA levels and suppressed metastasis, while OA supplementation had the opposite effect. B. animalis expresses oleate hydratase, an enzyme that degrades OA. Stress hormones inhibited B. animalis by altering guanine metabolism in the intestinal epithelium. In patients, high stress was associated with more OA, lower B. animalis levels and increased metastasis.<br><br>CONCLUSIONS: Chronic stress promotes metastasis by altering microbiota and increasing OA. Targeting B. animalis and OA may help prevent stress-related tumour progression.}, }
@article {pmid41318317, year = {2025}, author = {Liu, WC and Kuo, HY and Tsai, HW and Lin, YJ and Ruan, JW and Lee, CC and Sun, HY and Wu, IC and Chang, TT}, title = {Intratumoral microbiome composition and its role in tumor recurrence in primary liver cancer.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2025.11.031}, pmid = {41318317}, issn = {0929-6646}, abstract = {BACKGROUND: The human microbiome is increasingly recognized as a factor in cancer development, though its role in primary liver cancer (PLC) remains unclear. This retrospective cohort study examines tissue-specific microbiota differences between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), and explores their association with tumor recurrence in PLC.<br><br>METHODS: Clinical data from 116 patients (85 HCC and 31 age-matched CCA) were analyzed. Fresh frozen samples underwent RNAscope&#x2122; ISH assay for microbial RNA detection, while the MiSeq platform targeted 16&#xa0;S ribosomal RNA. Microbiome functional pathways were explored with Tax4Fun2, and predictors of recurrence were identified through logistic regression analysis.<br><br>RESULTS: Microbial RNA was detected within liver sinusoids, the basal lamina of intrahepatic bile ducts, and hepatocyte cytosol. 16&#xa0;S ribosomal RNA analysis revealed differences in microbiome composition, including a distinct Firmicutes/Bacteroidetes ratio between CCA and HCC patients. Specific functional pathways were differentially enriched between the two groups. LEfSe and logistic regression analyses identified Aquabacterium spp. as a potential marker for HCC recurrence (OR, 14.77; 95&#xa0;% CI, 1.07-203.94; p&#xa0;=&#xa0;0.044). Increased abundances of Brevundimonas spp. (OR, 3.1&#xa0;E+17; 95&#xa0;% CI, 4.3&#xa0;E+3-2.2&#xa0;E+31; p&#xa0;=&#xa0;0.013), Novosphingobium spp. (OR, 3.5&#xa0;E+20; 95&#xa0;% CI, 4.4&#xa0;E+5-2.8&#xa0;E+35; p&#xa0;=&#xa0;0.007), and Pelomonas spp. (OR, 3.3&#xa0;E+21; 95&#xa0;% CI, 3.0&#xa0;E+8-3.5&#xa0;E+34; p&#xa0;=&#xa0;0.001), along with decreased Staphylococcus spp. (OR 0.00; 95&#xa0;% CI, 0.00-0.06; p&#xa0;=&#xa0;0.003), were independent predictors of CCA occurrence.<br><br>CONCLUSION: This study reveals that intratumoral microbiota help distinguish PLC subtypes and are associated with recurrence, identifying Aquabacterium as a potential marker for HCC recurrence and microbiome-based management.}, }
@article {pmid41316695, year = {2025}, author = {Liong, O and Palosuo, K and Hinkkanen, V and Fortino, V and Mäkelä, MJ and Karisola, P}, title = {Oral Immunotherapy Induces Shift in lncRNA Expression Modulating Allergen-Specific Immune Responses.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.70173}, pmid = {41316695}, issn = {1398-9995}, support = {190150//Pediatric Research Foundation/ ; //Finnish Society of Allergology and Immunology/ ; TYH2019313//Helsinki University Hospital Research Fund/ ; TYH2020322//Helsinki University Hospital Research Fund/ ; //Allergy Research Foundation/ ; //Helsingin Yliopisto/ ; 338325//Academy of Finland/ ; //Finnish Cultural Foundation/ ; //Magnus Ehrnrooth Foundation/ ; //Sigrid Jus&#xe9;lius Foundation/ ; }, abstract = {BACKGROUND: Previously, we reported the success of egg oral immunotherapy (OIT) in liberating most participants from dietary restrictions. The diminishing symptoms and declining inflammation were accompanied by differential expression of genes in peripheral blood mononuclear cells (PBMCs) of 50 egg-allergic children following 8 months of OIT.<br><br>METHODS: Here, we explore the impact of OIT on long non-coding RNA (lncRNA) expression and its downstream effects on allergen-specific immune response with the help of PBMC transcriptome, co-expression gene module identification, pathway enrichment analyses and in&#xa0;vitro stimulation in both PBMC and THP1 cells.<br><br>RESULTS: We observed 17 lncRNAs which correlated positively with genes involved in IL-13, IL-4, and IL-10 signaling pathways. The same set of lncRNAs correlated negatively with genes playing a role in neutrophil degranulation, phagosome formation, and pyroptosis signaling. The expression of one of the most important lncRNAs, LOC644727, was found to align with CXCL8 expression in egg extract-stimulated PBMCs and LPS-stimulated THP1-derived macrophages.<br><br>CONCLUSIONS: Our results highlight the involvement of lncRNA in the regulation of gene expression during OIT. LOC644727 may serve as a potential marker for inflammatory responses and it may offer a therapeutic target for future desensitization protocols.}, }
@article {pmid41316495, year = {2025}, author = {Liu, Z and Yu, W and Sun, T and Li, M and Li, X and Qin, L and Liu, X and Bian, Y and Zhao, S and Zhao, Q and Zhao, H and Feng, Q}, title = {Ambient temperature affects the composition of the vaginal microbiome, and temperature-sensitive vaginal microbes influence assisted reproductive technology outcomes.}, journal = {Microbiome}, volume = {}, number = {}, pages = {}, doi = {10.1186/s40168-025-02212-9}, pmid = {41316495}, issn = {2049-2618}, support = {2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 2021YFC2700400//National Key Research and Development Program of China/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 31988101//the Basic Science Center Program of NSFC/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; 32370916//the National Natural Science Foundation of China/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; ZR2023YQ061//the Natural Science Foundation of Shandong Province for Excellent Youth Scholars/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2021-I2M-5-001//CAMS Innovation Fund for Medical Sciences/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; 2020ZLYS02//Shandong Provincial Key Research and Development Program/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; Q2022144//the Program for Chang Jiang Scholars/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; ts20190988//the Taishan Scholars Program of Shandong Province/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; 2023QNTD004//the Fundamental Research Funds of Shandong University/ ; }, abstract = {OBJECTIVE: To investigate the influence of environmental factors on the composition and structure of the vaginal microbiome and to explore the interaction among environmental factors, vaginal microbiome, and outcomes of assisted reproductive technology (ART).<br><br>METHODS: Adonis test was utilized to evaluate the impact of 33 host/environmental variables on vaginal microbiome. Distributed lag nonlinear model analysis (DLNM), Mfuzz analysis, and linear mixed effect model were employed to establish the correlations between ambient temperature and vaginal microbes.<br><br>RESULTS: Ambient temperature was one of the most important environmental factors associated with vaginal microbiome. As the temperature increased, succession of vaginal microbes showed four patterns of abundance variation. Furthermore, a group of vaginal microbes showed a preference for certain temperatures, and these microbes' varying interactions partly drove the shift of microbial networks at different temperatures. The community assembly process of vaginal microbiome deviated from neutral model and exposure to ambient temperature did not affect the role of stochastic processes in shaping vaginal microbial community. Notably, vaginal microbiome prior to embryo transfer was significantly associated with preterm birth. Preterm women exhibited higher abundance of Lactobacillus iners and lower abundance of Lactobacillus crispatus.<br><br>CONCLUSIONS: Ambient temperature change can affect the structure and composition of the vaginal microbiome and correlate with the abundance of certain vaginal microbes. Temperature-sensitive vaginal bacteria may affect the risk of future preterm births. Video Abstract.}, }
@article {pmid41315289, year = {2025}, author = {Thinnes, CC and Waschkowitz, R and Courtney, E and Culligan, E and Fahy, K and Ferrazza, RAM and Ferris, C and Lagali, A and Lane, R and Maye, C and Murphy, O and Noone, D and Ryan, S and Bet, M and Corr, MC and Cummins, H and Hackett, D and Healy, E and Kulczycka, N and Lang, N and Madden, L and McHugh, L and Pyne, I and Varley, C and Harkin, N and Meade, R and O'Donnell, G and Nap, B and Martinelli, F and Heinken, A and Thiele, I}, title = {MicroMap: a network visualisation resource for human microbiome metabolism.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {222}, pmid = {41315289}, issn = {2055-5008}, support = {757922/ERC_/European Research Council/International ; 859890//H2020 Marie Sk&#x142;odowska-Curie Actions/ ; 1RF1AG058942/NH/NIH HHS/United States ; 12/RC/2273-P2/SFI_/Science Foundation Ireland/Ireland ; }, mesh = {Humans ; *Microbiota ; *Metabolic Networks and Pathways ; *Software ; *Computational Biology/methods ; *Bacteria/metabolism/genetics/classification ; Computer Simulation ; }, abstract = {The human microbiome critically influences metabolism and thereby our health. Constraint-based reconstruction and analysis (COBRA) is a proven framework for generating mechanism-derived hypotheses along the nutrition-host-microbiome-disease axis. However, no large-scale microbiome metabolism visualisation has been available. Therefore, we created the MicroMap, a manually curated network visualisation, which captures the metabolism of over a quarter million microbial genome-scale metabolic reconstructions. The MicroMap contains 5064 unique reactions and 3499 unique metabolites, including for 98 drugs. Users can intuitively explore microbiome metabolism, inspect metabolic capabilities, and visualise computational modelling results. Further, the MicroMap may serve as an educational tool to help diversify the computational modelling community. We generated 257,429 visualisations, covering all our current microbiome reconstructions, to visually compare metabolic capabilities between microbes. The MicroMap integrates with the Virtual Metabolic Human (VMH, www.vmh.life), the COBRA Toolbox (https://opencobra.github.io), and is freely accessible at the MicroMap dataverse (https://dataverse.harvard.edu/dataverse/micromap), along with all the generated reconstruction visualisations.}, }
@article {pmid41313023, year = {2025}, author = {Adam, D and Bensaada, D and Stulanovic, N and Focant, J-F and Stefanuto, P-H and Rigali, S}, title = {Comparative volatilomics identifies ubiquitous sulfur compounds inhibiting the fungal pathogen Rasamsonia argillacea.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0266625}, doi = {10.1128/spectrum.02666-25}, pmid = {41313023}, issn = {2165-0497}, abstract = {UNLABELLED: Members of the phylum Actinomycetota, particularly Streptomyces species, are prolific producers of bioactive metabolites, and bioprospecting in unique environments may uncover novel species producing previously undescribed antifungal compounds. In previous work, Streptomyces strains isolated from cave moonmilk deposits completely inhibited the growth of Rasamsonia argillacea, an emerging fungal pathogen associated with chronic granulomatous disease (CGD) and cystic fibrosis (CF). Cross-streak and bipartite Petri dish assays revealed that R. argillacea inhibition occurred specifically when bacteria were cultivated on Mueller-Hinton agar (MHA) and was mediated by volatile compounds rather than diffusible metabolites. This antifungal effect was not strain specific, as it was reproduced by phylogenetically diverse bacteria grown on MHA, suggesting the involvement of ubiquitous volatile molecules. Similar inhibitory effects were observed on MHA against other fungi and yeasts relevant to CGD and CF, supporting the hypothesis that these volatiles are broadly toxic rather than species-specific. To identify candidate ubiquitous antifungal VCs, we conducted comparative volatilomics of two phylogenetically distant bacterial strains that consistently inhibited fungal growth. Among the 143 VCs detected, only dimethyl trisulfide (DMTS) and dimethyl disulfide (DMDS) showed consistent presence in both bacterial volatilomes, with significantly increased production under conditions that promoted fungal inhibition. Exposure assays with pure compounds confirmed that both DMDS and DMTS strongly inhibited R. argillacea growth, with DMTS exhibiting greater potency. Our findings position these ubiquitous sulfur compounds as valuable models for exploring novel agents against human pathogens.<br><br>IMPORTANCE: Our findings suggest that antifungal activity against human pathogens may arise from common metabolic pathways shared across diverse microbes rather than from unique biosynthetic systems. Because dimethyl disulfide and dimethyl trisulfide can also be generated through microbial and dietary sulfur metabolism, it is plausible that the human microbiome may produce similar volatiles depending on diet composition, particularly following consumption of sulfur-rich foods. This study, therefore, underscores the critical influence of culture conditions on revealing bioactive volatile production and opens intriguing perspectives on the ecological and physiological roles of ubiquitous microbial metabolites in regulating fungal colonization and microbiome-host interactions.}, }
@article {pmid41311358, year = {2025}, author = {Niaz, H and Skurnik, M and Adnan, F}, title = {Molecular Cloning and Functional Analysis of Holin and Endolysin From Escherichia Phage UE-M6 as Potential Antibacterial Agents.}, journal = {MicrobiologyOpen}, volume = {14}, number = {6}, pages = {e70150}, doi = {10.1002/mbo3.70150}, pmid = {41311358}, issn = {2045-8827}, support = {//We gratefully acknowledge the Higher Education Commission (HEC) of Pakistan for the award of the International Research Support Initiative Program (IRSIP) for the University of Helsinki, Finland./ ; }, mesh = {*Endopeptidases/genetics/pharmacology/metabolism/chemistry ; *Anti-Bacterial Agents/pharmacology/metabolism ; Escherichia coli/virology/drug effects ; Cloning, Molecular ; *Viral Proteins/genetics/pharmacology/metabolism ; *Coliphages/genetics/enzymology ; Microbial Sensitivity Tests ; Recombinant Proteins/pharmacology/genetics/metabolism/isolation &amp; purification ; *Bacteriophages/genetics ; Staphylococcus aureus/drug effects ; }, abstract = {The rise of antibiotic-resistant bacteria has intensified the search for alternative antibacterial strategies. Bacteriophage (phage) therapy is gaining attention as a promising approach, utilizing phage-derived proteins such as holins and endolysins to combat bacterial infections. In this study, the endolysin (UE-lysin) and holin (UE-holin) genes from Escherichia phage UE-M6 were characterized, and their antimicrobial activity was evaluated. In silico analysis revealed that UE-lysin has a modular architecture, with the N-terminal enzymatic activity domain that contains an N-acetylmuramidase of the glycoside hydrolase family GH108, and the C-terminal cell wall-binding domain that contains the peptidoglycan binding family PG_binding_3 domain. UE-holin was predicted to belong to class II holins, featuring two transmembrane helices. Furthermore, the genes encoding the UE-lysin and UE-holin were cloned and their expression optimized in Escherichia coli BL21 (DE3). The purified recombinant UE-lysin (27 kDa) and UE-holin (15 kDa) exhibited antibacterial activity against the E. coli host strain PSU-5266 (UE-17). The addition of the outer membrane permeabilizer ethylenediaminetetraacetic acid further enhanced their activity. Notably, the combined application of UE-holin and UE-lysin demonstrated greater antibacterial efficacy than either enzyme alone, highlighting a synergistic effect. Furthermore, UE-lysin and UE-holin exhibited high lytic activity against E. coli, Bacillus, and Staphylococcus aureus strains, underscoring their potential as candidates for treating both Gram-negative and Gram-positive bacterial infections.}, }
@article {pmid41305578, year = {2025}, author = {Rehner, J and Gund, M and Becker, SL and Hannig, M and Rupf, S and Schattenberg, JM and Keller, A and The Imagine Consortium,  and Molano, LG and Keller, V}, title = {Joint Bacterial Traces in the Gut and Oral Cavity of Obesity Patients Provide Evidence for Saliva as a Rich Microbial Biomarker Source.}, journal = {Nutrients}, volume = {17}, number = {22}, pages = {}, doi = {10.3390/nu17223527}, pmid = {41305578}, issn = {2072-6643}, support = {469073465//DFG/ ; }, mesh = {Humans ; *Saliva/microbiology ; *Obesity/microbiology ; *Gastrointestinal Microbiome ; Feces/microbiology ; *Mouth/microbiology ; Male ; Female ; Biomarkers/analysis ; Middle Aged ; Adult ; Dental Plaque/microbiology ; *Bacteria/isolation &amp; purification/classification/genetics ; Metagenome ; }, abstract = {Background: The human microbiome holds promise for identifying biomarkers and therapeutic targets. In obesity, interactions between oral and gut communities are increasingly implicated and end in organ injury. Methods: From the IMAGINE study, we analyzed 418 shotgun metagenomes from three specimen types (dental plaque (n = 143; 65 non-obese, 78 obese), saliva (n = 166; 75 non-obese, 91 obese), and stool (n = 109; 57 non-obese, 52 obese)) to compare site-specific microbial shifts between obese (BMI > 30 kg/m[2]) and non-obese individuals. Differential abundance was assessed with ANCOM-BC; effect sizes were summarized as Cohen's d. Results: Across all samples, we detected 240 bacterial species in plaque, 229 in saliva, and 231 in stool, with 46 species present across all three sites. Absolute effect sizes were significantly larger in plaque (mean |d| = 0.26) and saliva (0.25) than in stool (0.21; p = 9 × 10[-3]). Several taxa showed an opposite directionality between oral and gut sites, including Streptococcus salivarius and Bifidobacterium longum, indicating site-specific associations. Notably, Actinomyces sp. and Streptococcus sp. exhibited promising effect sizes as diagnostic markers. Conclusions: The oral and gut microbiomes capture complementary obesity-related signals, with stronger shifts observed in oral sites. We suggest that integrating oral and gut profiling could enhance diagnostic and therapeutic strategies in obesity.}, }
@article {pmid41305349, year = {2025}, author = {Ruden, DM}, title = {The Human Archaeome: Commensals, Opportunists, or Emerging Pathogens?.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/pathogens14111111}, pmid = {41305349}, issn = {2076-0817}, support = {5P42ES030991-07/NH/NIH HHS/United States ; 5P30ES036084-06/NH/NIH HHS/United States ; }, mesh = {Humans ; *Archaea/physiology/pathogenicity/classification ; *Microbiota ; *Symbiosis ; }, abstract = {Archaea, one of the three domains of life, are increasingly recognized as consistent, though often underappreciated, members of the human microbiome, yet their roles in health and disease remain poorly understood. Unlike bacteria, no archaeal species have been conclusively identified as primary mammalian pathogens, but their widespread presence across diverse body sites suggests potential indirect contributions to host physiology and pathology. Current evidence is synthesized on archaeal diversity and habitat specificity across multiple human-associated sites, encompassing the gastrointestinal, aerodigestive, and urogenital tracts as well as the skin. Methanogens dominate the lower gastrointestinal tract (LGT), where they influence fermentation dynamics and methane production, while members of the class Nitrososphaeria are prevalent on the skin and upper aerodigestive tract (UAT), reflecting ecological specialization. Variability in archaeal composition across niches highlights possible links to disease processes: methanogens have been associated with irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), obesity, and colorectal cancer (CRC); Methanobrevibacter oralis is enriched in periodontal disease; and archaea have been detected in the lungs of cystic fibrosis patients. Although archaea lack canonical bacterial virulence factors, they may contribute indirectly through metabolic cross-feeding, immune modulation, synergy in polymicrobial infections, and alteration of host-microbiome network dynamics. This review explores the emerging concept of the human "archaeome", evaluates current evidence for archaeal involvement in disease, and highlights emerging technologies, such as bacteria-MERFISH and multi-omics profiling, that enable translational applications including microbiome diagnostics, therapeutic targeting, and microbiome engineering.}, }
@article {pmid41301648, year = {2025}, author = {Kurt, KC and Tokuç, E and Kurt, H and Akın, DN and Sait, A and Aydın, S and Skurnik, M and Bahar Tokman, H}, title = {Characterization and Genomic Analysis of a New Bacteriophage Klebsiella pneumoniae CTF-1 from Turkey.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/antibiotics14111153}, pmid = {41301648}, issn = {2079-6382}, support = {34517//IUC-BAP/ ; }, abstract = {Background/Objectives:Klebsiella pneumoniae is a clinically important pathogen that causes respiratory tract infections, pneumonia, wound infections, urinary tract infections, and sepsis. It is on the World Health Organization (WHO) priority pathogen list as it causes antimicrobial-resistant infections. The aim of this study was to isolate bacteriophages against pan-resistant K. pneumoniae isolated from clinical wound infections. Results: One of the isolated phages, CTF-1, possesses a linear double-stranded DNA genome that is 40,841 base pairs (bp) long and contains 44 predicted genes. Functional assignments were made for 31 of the predicted gene products, which are associated with genome replication, phage packaging, structural proteins, and host lysis, leaving 13 annotated as hypothetical proteins. Based on sequencing analysis, phage CTF-1 is a new member of the genus Przondovirus within the order Autographivirales. Phage CTF-1 was effective against 22 of 25 (88%) pan-resistant K. pneumoniae isolates. The latent period and lytic cycle of the phage were approximately 40 min, with a burst size of about 92 PFU/mL. Conclusions: Our findings suggest that Klebsiella phage CTF-1 is an excellent candidate for phage therapy due to its high lytic activity against pan-resistant K. pneumoniae strains and lack of genes encoding antibiotic resistance, toxins, virulence factors, or integrases.}, }
@article {pmid41301521, year = {2025}, author = {Chen, S and Chen, X and Zhou, J and Wang, J and Li, K and Xie, W and Long, C and Wu, G}, title = {The Synaptic and Intrinsic Cellular Mechanisms of Persistent Firing in Neurogliaform Cells.}, journal = {Biomolecules}, volume = {15}, number = {11}, pages = {}, doi = {10.3390/biom15111603}, pmid = {41301521}, issn = {2218-273X}, support = {32371065 and 31671059//National Natural Science Foundation of China/ ; 2023A1515010899//Natural Science Foundation of the Guangdong Province/ ; }, mesh = {Animals ; Mice ; Mice, Inbred C57BL ; *Hippocampus/cytology/physiology/metabolism ; *Synapses/physiology/metabolism ; *Action Potentials/drug effects ; Male ; Calcium Channels, T-Type/metabolism ; *Interneurons/physiology/metabolism/drug effects ; Receptors, Serotonin/metabolism ; Olanzapine/pharmacology ; Synaptic Transmission ; Patch-Clamp Techniques ; *Neuroglia/physiology/metabolism ; }, abstract = {While persistent firing in glutamatergic neurons has been well-characterized, the intrinsic and synaptic mechanisms driving this phenomenon in neurogliaform cells (NGFCs), a subtype of GABAergic interneurons, remain unclear. This study investigates the mechanisms underlying persistent firing in hippocampal NGFCs. Whole-cell current-clamp recordings were performed on acute brain slices from C57BL/6J mice to examine the electrophysiological properties of NGFCs in the hippocampal stratum lacunosum-moleculare (SLM). Pharmacological interventions, including T-type calcium channel blocker ML218 and 5-hydroxytryptamine (5-HT) receptor antagonist olanzapine, were used to dissect the mechanisms of persistent firing. Biocytin labeling and confocal microscopy were employed to confirm neuronal morphology and location. The study revealed that persistent firing in NGFCs is induced by a long-lasting delayed afterdepolarization (L-ADP), which depends on T-type calcium channels (intrinsic mechanism) and is modulated by 5-HT receptors (synaptic mechanism). Persistent firing was observed in 62.96% of SLM neurons and was abolished by ML218 or olanzapine. The findings bridge a gap in understanding how inhibitory interneurons contribute to memory processes. The dual-mechanism framework (T-type channels and 5-HT receptors) aligns with prior work on glutamatergic systems but highlights unique features of GABAergic persistent firing. These insights advance the understanding of inhibitory circuit dynamics and their potential role in cognitive functions, paving the way for further research into interneuron-specific memory encoding.}, }
@article {pmid41300382, year = {2025}, author = {Sulas, F and Favero, G and Bonini, SA and Lonati, C and Pinto, D and Memo, M and Rinaldi, F and Rezzani, R}, title = {Melatonin Improves Intestinal Barrier Impairment in a Mouse Model of Autism Spectrum Disorder.}, journal = {Biology}, volume = {14}, number = {11}, pages = {}, doi = {10.3390/biology14111594}, pmid = {41300382}, issn = {2079-7737}, support = {ex 60% grants//University of Brescia-Italy/ ; Donation//FLAMMA S.p.A.-Italy/ ; Donation.//Franchini Acciai S.p.A.-Italy/ ; }, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental condition mainly characterized by social impairments and repetitive behaviors. An altered intestinal barrier morphology and increased transmucosal leaks have also been implicated in ASD; in fact, comorbidities such as gastrointestinal problems (leaky gut) have frequently been reported in these patients. The regulation of tight junctions (TJs) is essential in maintaining intestinal barrier morphology and in regulating the delicate balance of trafficking between the intestinal lumen and the submucosa. To date, there are no definitive treatments for ASD comorbidities; however, melatonin (MLT) represents a well-validated and tolerated treatment for sleep disorders in ASD patients. The potential beneficial effects of MLT on this disorder have been and continue to be better investigated. In this context, the present study examines the effects of oral MLT administration (10 mg/kg/day for 16 weeks) on the intestinal barrier in BTBR T + Itpr3tf/J (BTBR) mice, a validated ASD model. Morphological analyses of the ileum of these animals reveal modified villus height (Vh), crypt depth (Cd), and Vh-Cd ratios; an inflammatory state; and a decrease in Paneth cells. Moreover, these mice showed altered TJ expression compared to the control animals (C57BL6/J mice). Notably, MLT normalizes morphological indices and TJ expression, consistent with an improved gut barrier morphology. These data collectively suggest that orally administered MLT can promote the remodeling of the intestinal barrier; thus, we can suppose that MLT reduces gastrointestinal barrier leaks. The overall safety and economy of MLT use suggest that this indolamine could be efficacious as an adjuvant therapy to reduce the condition known as leaky gut.}, }
@article {pmid41298564, year = {2025}, author = {Qu, T and Koch, L and Mukherjee, R and Tu, Y and Seidel, AL and Püttmann, LD and Winkel, A and Yang, I and Grischke, J and Liu, D and Wolkers, WF and Kittler, S and Chichkov, B and Stiesch, M and Szafrański, SP}, title = {Laser-assisted microbial culturomics.}, journal = {Nature communications}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41467-025-66804-7}, pmid = {41298564}, issn = {2041-1723}, support = {German Cluster of Excellence Ex62/2 Rebirth//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; German Cluster of Excellence Ex62/2 Rebirth//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; SFB/TRR 298 SIIRI - Project-ID 426335750//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; EXC 2155 - project number 390874280//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; Laser-Tissue-Perfude, 101054009//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, abstract = {Even though metagenomics have revolutionized the characterization of the human microbiome, detailed mechanistic studies are impracticable, as there is a dearth of robust culture collections. We now describe the development and use of a laser-assisted culturomics platform, incorporating the elements of a bioprinter, the culture conditions, the methods to characterize the microorganisms and a biobank. With laser-assisted bioprinting, the microorganisms can be rapidly and precisely transferred from clinical biofilms to highly organized arrays of microbial colonies, which are suitable for co-culturing and molecular analyses. The presented technique has propagated 99 of 100 microbial species and recovered 79% of abundant species from dental plaque in accordance with full 16S rRNA gene profiling of 691,199 sequences. Microscopy, spectroscopy and enzyme assays have been used to guide isolations. Processing of oral biofilms from four individuals has yielded 249 representative isolates, from 14 classes and 124 species in total. Functional profiling with bioprinting has indicated commensals which could potentially contribute to disease development. Isolates from peri-implantitis cover 85.4% of the transcriptionally active clinical biofilms at genus level. Taken together, this work provides the basis for generating on-demand culture collections and biofilms for research and clinical use.}, }
@article {pmid41297880, year = {2025}, author = {Chue, KM and Wong, SH and Zuo, T and Ali, Y}, title = {The Role of the Gut Non-Bacterial Microbiome (Virome, Mycobiome, Archaeome) and its Impact on Obesity.}, journal = {Molecular metabolism}, volume = {}, number = {}, pages = {102289}, doi = {10.1016/j.molmet.2025.102289}, pmid = {41297880}, issn = {2212-8778}, abstract = {The epidemic of obesity and metabolic syndrome is a major public health concern internationally. There is increasing knowledge and research in areas of appetite regulation and drivers of obesity but there is still a gap on how the interactomes are altered in a metabolically dysregulated human body. The human microbiome has been implicated in the pathogenesis of obesity. While the association of gut bacteriome dysbiosis is well described in obesity and metabolic syndrome, there is a lack of an integrative understanding about the roles of the non-bacterial microbiome (virome, mycobiome, and archaeome) in the pathogenesis and protection of obesity and metabolic syndrome. Accumulating studies have revealed that the non-bacterial microbes in the gut, including viruses/ phages, fungi, and archaea, are profoundly altered in obesity, and impact host adiposity and physiology in nuanced manners. In this review, we aim to provide a comprehensive view on the role and the mechanisms of the gut virome, mycobiome, and archaeome in obesity. These insights will shed light on the translational value as well as the future research directions for harnessing the gut non-bacterial microbial entities in the therapeutics and prevention of metabolic diseases.}, }
@article {pmid41295160, year = {2025}, author = {Wright, E and Valand, N and Venkatraman Girija, U}, title = {Harnessing Probiotics to Combat Candidiasis: Mechanisms, Evidence, and Future Directions.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, doi = {10.3390/jof11110779}, pmid = {41295160}, issn = {2309-608X}, abstract = {Candida species are common commensals within the human microbiome but can transition opportunistically to pathogenic states when host-microbe homeostasis is disrupted. Their ability to adhere to mucosa and implanted medical devices, form thick biofilms, and invade epithelial tissues makes candidiasis particularly harmful in immunocompromised and elderly populations. This review examines the reported antifungal activity of common probiotic genera such as Lactobacillus, Bacillus, Bifidobacterium, and Saccharomyces across the oral cavity, gastrointestinal tract, and vaginal tract. The probiotic mechanisms of action, such as competitive exclusion, secretion of antifungal metabolites, and immunomodulation, are explored in detail, and research methodologies are scrutinised to assess the robustness of current evidence. This review compiles evidence from a variety of studies and clinical trials showing certain probiotic strains and formulations have the ability to significantly decrease Candida colonisation and reduce candidiasis symptom prevalence. Although outcomes vary greatly between probiotic strains tested, species of Candida targeted, and specific site of infection, it is clear that selected probiotic species and their secreted substances can have prominent anti-Candida effects and promote tangible clinical improvements. Future directions for the field of probiotic study are suggested, including the roles of prebiotics, postbiotics, and synbiotic formulations to enhance probiotic efficacy against candidiasis.}, }
@article {pmid41294086, year = {2026}, author = {Vu, D and de Vries, M and van den Ende, BG and Houbraken, J and Nilsson, RH and Brankovics, B and Hernández-Restrepo, M and Groenewald, JZ and Crous, PW and Hagen, F and Meyer, W and Verkley, GJM and Groenewald, M}, title = {Advancing Yeast Identification Using High-Throughput DNA Barcode Data From a Curated Culture Collection.}, journal = {Molecular ecology resources}, volume = {26}, number = {1}, pages = {e70082}, doi = {10.1111/1755-0998.70082}, pmid = {41294086}, issn = {1755-0998}, mesh = {*DNA Barcoding, Taxonomic/methods ; *Yeasts/classification/genetics/isolation &amp; purification ; DNA, Fungal/genetics/chemistry ; High-Throughput Nucleotide Sequencing/methods ; DNA, Ribosomal Spacer/genetics/chemistry ; Sequence Analysis, DNA ; }, abstract = {Yeast identification is essential in fields ranging from microbiology and biotechnology to food science and medicine. While DNA barcoding has become the standard for identifying cultured strains, environmental DNA (eDNA) metabarcoding has revolutionised microbial community profiling, providing deeper insights into yeast communities across diverse ecosystems. A major challenge in DNA (meta)barcoding remains the limited availability of high-quality reference sequences, which are critical for accurate species identification and comprehensive taxonomic profiling of both environmental and clinical samples. To address this gap, the Westerdijk Fungal Biodiversity Institute (WI) launched a DNA barcoding initiative in 2006 to generate high-quality, often type-derived ITS and LSU barcodes for all ~100,000 fungal strains preserved in the CBS culture collection, including approximately 15,000 yeasts. Building on the yeast barcode dataset released in 2016, we now present an expanded set of 2856 ITS and 3815 LSU sequences, representing 911 and 1137 yeast species, respectively. Notably, 27%-29% of these sequences are derived from ex-type cultures. Using both newly generated and previously published barcodes, we assess the taxonomic resolution of commonly used yeast metabarcoding markers (ITS, ITS1, ITS2 and LSU) and propose marker-specific similarity cutoffs for different yeast taxonomic groups. These results provide actionable guidance for marker selection and improve the interpretation of metabarcoding data. We further demonstrate the impact of well-curated reference databases with up-to-date taxonomy by reanalyzing Human Microbiome Project data, revealing how diet and environment shape the gut mycobiota.}, }
@article {pmid41291291, year = {2025}, author = {Van Egeren, D and Schenck, RO and Khan, A and Horning, AM and Mo, S and Weiß, CL and Esplin, ED and Becker, WR and Wu, S and Hanson, C and Barapour, N and Jiang, L and Contrepois, K and Lee, H and Nevins, SA and Guha, TK and Zhang, H and He, Z and Ma, Z and Monte, E and Karathanos, TV and Laquindanum, R and Mills, MA and Chaib, H and Chiu, R and Jian, R and Chan, J and Ellenberger, M and Bahmani, B and Michael, B and Weimer, AK and Esplin, DG and Lancaster, S and Shen, J and Ladabaum, U and Longacre, TA and Kundaje, A and Greenleaf, WJ and Hu, Z and Ford, JM and Snyder, MP and Curtis, C}, title = {Polyclonal origins of human premalignant colorectal lesions.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41586-025-09930-y}, pmid = {41291291}, issn = {1476-4687}, abstract = {Cancer is generally thought to be caused by expansion of a single mutant cell[1]. However, analyses of early colorectal cancer lesions suggest that tumors may instead originate from multiple, genetically distinct cell populations[2,3]. Detecting polyclonal tumor initiation is challenging in patients, as it requires profiling early-stage lesions before clonal sweeps obscure diversity. To investigate this, we analyzed normal colorectal mucosa, benign and dysplastic premalignant polyps, and malignant adenocarcinomas (123 samples) from six individuals with familial adenomatous polyposis (FAP). Individuals with FAP have a germline heterozygous APC mutation, predisposing them to colorectal cancer and numerous premalignant polyps by early adulthood[4]. Whole-genome and/or whole-exome sequencing revealed that many premalignant polyps-40% with benign histology and 28% with dysplasia-were composed of multiple genetic lineages that diverged early, consistent with polyclonal origins. This conclusion was reinforced by whole-genome sequencing of single crypts from multiple polyps in additional patients which showed limited sharing of mutations among crypts within the same lesion. In some cases, multiple distinct APC mutations co-existed in different lineages of a single polyp, consistent with polyclonality. These findings reshape our understanding of early neoplastic events, demonstrating that tumor initiation can arise from the convergence of diverse mutant clones. They also suggest that cell-intrinsic growth advantages alone may not fully explain tumor initiation, highlighting the importance of microenvironmental and tissue-level factors in early cancer evolution.}, }
@article {pmid41287874, year = {2025}, author = {Zhu, Y and Zhi, M and Liang, X and Li, L and Dong, M and Zhang, G and Wang, L and Wang, P and Zhong, N and Feng, Q and Li, Z}, title = {Microbial variations in the multibody sites of the pancreatic ductal adenocarcinoma patients.}, journal = {International journal of surgery (London, England)}, volume = {}, number = {}, pages = {}, doi = {10.1097/JS9.0000000000003799}, pmid = {41287874}, issn = {1743-9159}, abstract = {OBJECTIVES: We aimed to investigate microbial characteristics across multibody sites of pancreatic ductal adenocarcinoma (PDAC) and identify novel microbial markers for PDAC.<br><br>METHOD: We conducted 16S ribosomal RNA (rRNA) amplicon sequencing on saliva, duodenal fluid, and pancreatic tissue obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) from 63 PDAC patients and 22 benign controls.<br><br>RESULTS: From controls to PDAC patients, the contribution of salivary and duodenal microbes to the assembly of pancreatic microbes increased. In PDAC patients and controls, duodenal microbes contributed more significantly to the pancreatic microbial assembly than salivary microbes. Prevotella dentalis, Peptoanaerobacter stomatis, Slackia exigua, etc. were enriched, whereas Loigolactobacillus coryniformis, Akkermansia muciniphila, Faecalibacterium prausnitzii, etc., were reduced in pancreatic tissue, duodenal fluid, and saliva of PDAC patients (P < 0.05). We developed microbial classifiers for discriminating PDAC based on the differential species shared among the three sites with the areas under the curves (AUCs) of 0.946, 0.991, and 0.971 in pancreatic tissue, duodenal fluid, and saliva, respectively. Faecalibacterium prausnitzii in duodenal fluid, Prevotella dentalis and Slackia exigua in saliva, and Anaeroglobus geminatus and Propionibacterium acidifaciens across all three sites were "driver" microbes contributing to the variations from controls to PDAC patients.<br><br>CONCLUSIONS: Salivary and duodenal microbes were significant contributors to the pancreatic microbial composition associated with PDAC. Novel microbial markers with high discriminative power were identified, underscoring their potential for PDAC detection.}, }
@article {pmid41283667, year = {2025}, author = {Zhang, J and Meng, F and Sun, Y and Xu, W and Wu, S and Su, X}, title = {Phylo-Spec: a phylogeny-fusion deep learning model advances microbiome status identification.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0145325}, doi = {10.1128/msystems.01453-25}, pmid = {41283667}, issn = {2379-5077}, abstract = {The human microbiome is crucial for health regulation and disease progression, presenting a valuable opportunity for health state classification. Traditional microbiome-based classification relies on pre-trained machine learning (ML) or deep learning (DL) models, which typically focus on microbial distribution patterns, neglecting the underlying relationships between microbes. As a result, model performance can be significantly affected by data sparsity, misclassified features, or incomplete microbial profiles. To overcome these challenges, we introduce Phylo-Spec, a phylogeny-driven deep learning algorithm that integrates multi-aspect microbial information for improved status recognition. Phylo-Spec fuses convolutional features of microbes within a phylogenetic hierarchy via a bottom-up iteration and significantly alleviates the challenges due to sparse data and inaccurate profiling. Additionally, the model dynamically assigns unclassified species to virtual nodes on the phylogenetic tree based on higher-level taxonomy, minimizing interferences from unclassified species. Phylo-Spec also captures the feature importance via an information gain-based mechanism through the phylogenetic structure propagation, enhancing the interpretability of classification decisions. Phylo-Spec demonstrated superior efficacy in microbiome status classification across two in silico synthetic data sets that simulate the aforementioned cases, outperforming existing ML and DL methods. Validation with real-world metagenomic and amplicon data further confirmed the model's performance in multiple status classification, establishing a powerful framework for microbiome-based health state identification and microbe-disease association. The source code is available at https://github.com/qdu-bioinfo/Phylo-Spec.IMPORTANCEThe human microbiome profoundly influences health and disease, but current computational tools often overlook the evolutionary relationships among microbes, leading to incomplete or inaccurate interpretations of complex microbial data. Phylo-Spec provides a new way to understand the microbiome by combining microbial abundance, taxonomy, and phylogeny within a unified deep learning framework. This model not only improves the accuracy of health status classification but also highlights key microbial contributors linked to disease. By capturing both microbial diversity and evolutionary context, Phylo-Spec bridges the gap between bioinformatics and biological insight, offering a powerful and interpretable approach for advancing microbiome-based diagnostics and precision medicine.}, }
@article {pmid41279900, year = {2025}, author = {Li, L and Smardz, M and Soh, D and Marsh, PD and Hoare, A and Diaz, PI}, title = {The Impact of Serum on a Complex Synthetic Community Model of the Subgingival Microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.10.07.681017}, pmid = {41279900}, issn = {2692-8205}, abstract = {Despite rapid advances in characterizing the human microbiome, the ecological pressures shaping its transitions from healthy to diseased states remain poorly resolved. This is particularly true for periodontitis, a slow-progressing chronic inflammatory disease associated with well-defined shifts in the subgingival microbiome. Here, we report the development of a complex synthetic community model of the subgingival microbiome, designed for systematic interrogation of ecological factors that drive community restructuring. The model includes 22 prevalent and abundant subgingival species maintained in mucin-rich medium under microaerophilic, continuous culture conditions, in a chemostat. Using this system, we interrogated the impact of serum, as a surrogate for the inflammatory exudate, on community structure and function. Through integrated 16S rRNA gene sequencing, metatranscriptomics, and metabolomics, we found that serum was not required for a community with a periodontitis-like configuration to establish, but its presence intensified features of dysbiosis. Serum increased total biomass, promoted polymicrobial aggregate formation, promoted nitrogen and protein metabolism thereby modifying the environmental pH towards alkalinity, and introduced nitrosative stress. Serum also modified the community metatranscriptome in ways that paralleled microbiome activities in human periodontitis. Serum, however, decreased community diversity by disproportionally conferring a competitive advantage to the pathogen Porphyromonas gingivalis . This synthetic community model has revealed serum as a key nutritional pressure that modulates subgingival microbiome ecology and may perpetuate dysbiosis.}, }
@article {pmid41273085, year = {2025}, author = {Kruger, R and Oler, E and Saha, S and Poelzer, J and Han, S and Punsalan, MP and Green, B and Bushra, F and Kyes, M and Disu, F and Wakoli, J and Woudstra, R and Tejol, E and Fakutan, O and Wang, F and Lee, BL and Sajed, T and Tian, S and Torres-Calzada, C and Berjanskii, M and MacKay, S and Karu, N and Kadurrah-Daouk, R and Wishart, DS}, title = {MiMeDB 2.0: the Human Microbial Metabolome Database for 2026.}, journal = {Nucleic acids research}, volume = {}, number = {}, pages = {}, doi = {10.1093/nar/gkaf1272}, pmid = {41273085}, issn = {1362-4962}, support = {//NIH/ ; AG063744/AG/NIA NIH HHS/United States/AG/NIA NIH HHS/United States ; CFI MSIF 42495//Canada Foundation for Innovation/ ; CRC TIER1 100628//Canada Research Chairs/ ; //Genome Alberta, a division of Genome Canada/ ; ALLRP 597259-24//Natural Sciences and Engineering Research Council of Canada/ ; UBC F23-05862 WFF//Weston Family Foundation/ ; 2007-2024-1003//Social Sciences and Humanities Research Council of Canada/ ; //Genome Alberta/ ; }, abstract = {The Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, freely accessible resource linking human-associated microbes to the metabolites they produce, along with their connections to human health, disease, and diet. Since the release of MiMeDB 1.0 in 2023, the database has been substantially expanded and redesigned. Major updates include the systematic addition of millions of newly annotated genes and pathways, thousands of new metabolites, significantly expanded pathway and reaction coverage, along with broader representation of eukaryotic gut microbes. MiMeDB 2.0 now contains >12.9 million annotated microbial genes, over 23.1 million microbial pathways, 29 295 metabolites, 21 829 metabolic reactions, 3725 microbial species and strains, and 514 076 new experimental and predicted nuclear magnetic resonance and mass spectrometry spectra of microbial metabolites. New features, such as detailed microbial descriptions, metabolite origin tags, refined search filters, and species-specific reaction queries, have been added to enhance usability. Likewise, redesigned network and genome viewers have been implemented to support more comprehensive, intuitive, and integrated visualization of complex, multi-omic relationships. The significant addition of more metabolite spectral data and improved spectral search capabilities further strengthen metabolite identification and discovery. Together, these improvements make MiMeDB 2.0 one of the most comprehensive and user-friendly platforms for investigating the human microbiome at a molecular level and exploring the roles of microbes and microbial metabolites in human health, diet, and disease.}, }
@article {pmid41270950, year = {2025}, author = {Yuan, S and Bremmer, A and Yang, X and Hu, Q}, title = {Microbiota Metabolism and Immune Regulation: From Mechanisms to Immunotherapeutic Applications in Cancer.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2025.11.023}, pmid = {41270950}, issn = {1096-3650}, abstract = {The human microbiome plays a pivotal role in shaping immune responses by producing bioactive metabolites such as bile acids (BAs) and short-chain fatty acids (SCFAs). These microbial metabolites influence a broad range of cell types, including innate and adaptive immune cells and non-immune cells. Emerging evidence suggests that microbiome metabolism is a crucial factor affecting the success of cancer immunotherapy. Promising therapeutic approaches, such as the use of probiotics, engineered bacteria, metabolite supplementation, and bile acid sequestrants, are being explored to enhance immunotherapeutic outcomes. This review critically evaluates current insights into how microbiome-derived metabolites modulate cellular functions, with a particular focus on immune cells within the tumor microenvironment, and highlights their potential to improve the efficacy of cancer immunotherapy.}, }
@article {pmid41270740, year = {2025}, author = {Yi, X and Cai, H and Liu, H and Xu, S and Meng, R and Rao, J and Wu, M and Yang, L and Shi, Y and Zhang, J and Zhu, T and Yang, Y and Wen, P and Qin, Y and Song, W and Li, JT and Shu, W and Dai, J and Sun, J and Lin, L and Guan, WJ and Brightling, CE and Zheng, XY and Wang, Z}, title = {Environmental exposure augments the abundance and transferability of antibiotic resistance genes in the respiratory tract.}, journal = {Cell reports}, volume = {}, number = {}, pages = {116517}, doi = {10.1016/j.celrep.2025.116517}, pmid = {41270740}, issn = {2211-1247}, abstract = {Exposure to environmental pollutants has been linked to increased antibiotic resistance, a critical global health challenge. The respiratory microbiome constitutes a key reservoir of antibiotic resistance genes (ARGs). Here, we constructed a respiratory ARG catalog from sputum metagenomes of 1,128 individuals. We demonstrate that exposures, particularly to cigarette smoke and biofuels, are associated with increased abundance and enhanced mobility of respiratory ARGs. These resistome alterations correlate inversely with lung function, with elevated mobile ARG abundance detectable even in individuals with mild airflow limitation within normal spirometry. Specific ARGs, including opmD and tet(K), interact with smoking in relation to lung function impairment. Murine experiments recapitulate these findings, showing exposure-induced increases in homologous ARGs that confer heightened phenotypic resistance in cultured respiratory bacteria. Our results elucidate a pathway through which environmental pollutants augment the respiratory resistome, suggesting the need for actions to mitigate the antimicrobial resistance burden by addressing environmental pollution.}, }
@article {pmid41266796, year = {2025}, author = {Weng, Y and Guccione, C and McDonald, D and Oles, R and Devkota, S and Kopylova, E and Sepich-Poore, GD and Salido, RA and Din, MO and Song, SJ and Curtius, K and Chu, H and Bartko, A and Hasty, J and Knight, R}, title = {Calculating fast differential genome coverages among metagenomic sources using micov.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1624}, pmid = {41266796}, issn = {2399-3642}, abstract = {Breadth of coverage, the proportion of a reference genome covered by at least one sequencing read, is critical for interpreting metagenomic data, informing analyses from genome assembly to taxonomic profiling. However, existing tools typically summarize coverage breadth at the whole-genome or aggregate-sample level, missing informative variation along genomes and between sample groups. Here we introduce MIcrobiome COVerage (micov), a tool that computes and compares per-sample breadth of coverage across many genomes and samples. micov offers two key advances: (1) rapid cumulative coverage breadth calculations specific to each sample type, and (2) detection of differential coverage breadth along genomes. Applying micov to three metagenomic datasets, we show that it identifies a genomic region in Prevotella copri that explains variation in community composition independent of host country of origin, uncovers dietary association with a partially annotated region in an uncharacterized Lachnospiraceae genome, enabling hypothesis generation for genes of unknown function, and improves sensitivity in low-biomass settings by detecting a single genomic copy of enteropathogenic Escherichia coli (EPEC) in wastewater and distinguishing Mediterraneibacter gnavus across specimen types.}, }
@article {pmid41254344, year = {2025}, author = {Distante, A and Garino, D and Cerrato, C and Perez-Ardavin, J and Flores, FQ and Lopetuso, L and Mir, MC}, title = {The role of the human microbiome in prostate cancer: a systematic review from diagnosis to treatment.}, journal = {Prostate cancer and prostatic diseases}, volume = {}, number = {}, pages = {}, pmid = {41254344}, issn = {1476-5608}, abstract = {BACKGROUND: Prostate cancer (PC) heterogeneity and treatment resistance remain major clinical challenges, with emerging evidence implicating the microbiome as a key modulator of disease pathogenesis. While microbial dysbiosis has been linked to PC diagnosis, progression, and therapeutic outcomes, the mechanisms underlying these associations are poorly understood. This review synthesizes current evidence on the diagnostic, prognostic, and therapeutic potential of the microbiome in PC.<br><br>METHODS: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials (through April 2024) was conducted following PRISMA guidelines (PROSPERO: CRD42024534899). Controlled and observational studies investigating microbial roles in PC diagnosis (e.g., ISUP grading group), prognosis, or treatment response were included. Data extraction and quality assessment used the QUIPS tool. From 810 screened records, 42 studies met inclusion criteria.<br><br>RESULTS: Distinct microbial profiles differentiated PC from controls, with Mycoplasma genitalium and Staphylococcus spp. enriched in prostate tumors (3.1- and 2.7-fold, respectively) and correlated with inflammation (IL-6: r&#x2009;=&#x2009;0.38, p&#x2009;=&#x2009;0.002). Urinary microbiota showed diagnostic potential (sensitivity: 58-82%), though sampling methods influenced variability. Prognostically, Betaproteobacteria gut enrichment predicted earlier castration-resistant progression (5.2 months; HR 1.8, 95% CI 1.3-2.5), while ADT-induced dysbiosis (e.g., Klebsiella overgrowth) accelerated resistance (2.1-fold risk). Therapies altered microbial ecology: radiotherapy depleted Bacteroides (linked to proctitis; OR 3.1), and immunotherapy responders harbored higher Akkermansia muciniphila. Microbial androgen synthesis and endotoxin production emerged as resistance mechanisms.<br><br>CONCLUSIONS: The microbiome influences PC detection, aggressiveness, and treatment efficacy through direct (tissue-resident) and indirect (gut-derived) mechanisms. Standardized profiling and microbiome-modulating strategies (e.g., probiotics during ADT) may personalize management. Prospective trials are needed to validate causality and translate microbial biomarkers into clinical practice.}, }
@article {pmid41247142, year = {2025}, author = {Wang, Y and Hou, Q and Wei, F and Liu, B and Feng, Q}, title = {MNetClass: a control-free microbial network clustering framework for identifying central subcommunities across ecological niches.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0098925}, doi = {10.1128/msystems.00989-25}, pmid = {41247142}, issn = {2379-5077}, abstract = {Investigating microbiome subnetworks and identifying central microbes in specific ecological niches is a critical issue in human microbiome studies. Traditional methods typically require control samples, limiting the ability to study microbiomes at distinct body sites without matched controls. Moreover, some clustering methods are not well-suited for microbial data and fail to identify central subcommunities across ecological niches after clustering. In this study, we present MNetClass, a novel microbial network clustering analysis framework. It utilizes a random walk algorithm and a rank-sum ratio-entropy weight evaluation model to classify key subnetworks and identify central microbes at any body site, without the need for control samples. We demonstrate its capabilities on both simulated and real microbiome data sets. Simulation results indicate that MNetClass outperforms current unsupervised microbial clustering methods. In applied case studies, the analysis of microbiome data from five distinct oral sites revealed site-specific microbial communities. Furthermore, MNetClass demonstrated superior predictive performance on cross-cohort Autism Spectrum Disorder data and identified age-related microbial communities across different oral sites, underscoring its broad applicability in microbiome research.IMPORTANCEMNetClass provides a valuable tool for microbiome network analysis, enabling the identification of key microbial subcommunities across diverse ecological niches. Implemented as an R package (https://github.com/YihuaWWW/MNetClass), it offers broad accessibility for researchers. Here, we systematically benchmarked MNetClass against existing microbial clustering methods on synthetic data using various performance metrics, demonstrating its superior efficacy. Notably, MNetClass operates without the need for control groups and effectively identifies central microbes, highlighting its potential as a robust framework for advancing microbiome research.}, }
@article {pmid40568082, year = {2025}, author = {Hu, J and Peng, B and Pankajam, AV and Xu, B and Deshpande, VA and Bueckle, A and Herr, BW and Börner, K and Dupont, C and Scheuermann, RH and Zhang, Y}, title = {Benchmarking single cell transcriptome matching methods for incremental growth of reference atlases.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40568082}, issn = {2692-8205}, support = {OT2 OD026671/OD/NIH HHS/United States ; OT2 OD033756/OD/NIH HHS/United States ; R03 OD036499/OD/NIH HHS/United States ; }, abstract = {BACKGROUND: The advancement of single cell technologies has driven significant progress in constructing a multiscale, pan-organ Human Reference Atlas (HRA) for healthy human cells, though challenges remain in harmonizing cell types and unifying nomenclature. Multiple machine learning and artificial intelligence methods, including pre-trained and fine-tuned models on large-scale atlas data, are publicly available for the single cell community users to computationally annotate and match their cell clusters to the reference atlas.<br><br>RESULTS: This study benchmarks four computational tools for cell type annotation and matching - Azimuth, CellTypist, scArches, and FR-Match - using two lung atlas datasets, the Human Lung Cell Atlas (HLCA) and the LungMAP single-cell reference (CellRef). Despite achieving high overall performance while comparing algorithmic cell type annotations to expert annotated data, variations in accuracy were observed, especially in annotating rare cell types, underlining the need for improved consistency across cell type prediction methods. The benchmarked methods were used to cross-compare and incrementally integrate 61 cell types from HLCA and 48 cell types from CellRef, resulting in a meta-atlas of 41 matched cell types, 20 HLCA-specific cell types, and 7 CellRef-specific cell types.<br><br>CONCLUSION: This study reveals complementing strengths of the benchmarked methods and presents a framework for incremental growth of the cell type inventory in the reference atlases, leading to 68 unique cell types in the meta-atlas across CellRef and HLCA. The benchmarking analysis contributes to improving the coverage and quality of HRA construction by assessing the reliability and performance of cell type annotation approaches for single cell transcriptomics datasets.}, }
@article {pmid41233921, year = {2025}, author = {Naga, NG and Taha, RM and Hamed, EA and Nawar, EA and Jaheen, HO and Mobarak, AA and Radwan, YM and Faramawy, AG and Arayes, MA}, title = {The silent microbial shift: climate change amplifies pathogen evolution, microbiome dysbiosis, and antimicrobial resistance.}, journal = {Tropical diseases, travel medicine and vaccines}, volume = {11}, number = {1}, pages = {43}, pmid = {41233921}, issn = {2055-0936}, abstract = {Climate change is a primary driver of new infectious diseases. It affects pathogen evolution, vector ecology, and human susceptibility. Rising temperatures, changed rainfall patterns, and extreme weather events contributed to the spread of vector-borne, food-borne, and water-borne diseases. Furthermore, climate stressors promote antimicrobial resistance (AMR) and disrupt the human microbiome. This increases susceptibility to infections and chronic diseases. This review explores the complex relationships between climate change, microbial ecosystems, and public health focusing on how microbial dysbiosis and environmental changes interact to influence disease dynamics. We also highlight long-term solutions, such as One Health approaches, probiotics, and AI-powered early warning systems, as strategies for reducing future risks. Addressing these challenges requires global collaboration, climate-resilient health systems, and proactive actions to mitigate the health consequences of a rapidly changing environment.}, }
@article {pmid41237775, year = {2025}, author = {Van Hul, M and Cani, PD}, title = {From microbiome to metabolism: Bridging a two-decade translational gap.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2025.10.011}, pmid = {41237775}, issn = {1932-7420}, abstract = {The mapping of the human genome sparked high expectations for biomedical breakthroughs, yet attention has since shifted toward the human microbiome as a key player in health and disease. Pioneering studies revealed striking inter-individual variability and numerous associations between gut microbiota and a wide range of conditions (i.e., obesity, diabetes, cardiovascular and inflammatory bowel diseases, autism, allergies, neurodegenerative diseases, and cancers). However, the field has faced a deluge of correlative "dysbiosis" studies with limited causal evidence. Although animal models have provided crucial mechanistic insights, translating these findings to humans has proven challenging. Interventions such as fecal microbiota transplantation, prebiotics, probiotics, and postbiotics often yield inconsistent or modest effects in clinical trials. This gap highlights the need for precision, functional profiling, and integration of multi-omics , for instance, through artificial intelligence. In this perspective, we discuss what microbiome research offers as a transformative shift and how we conceptualize disease, favoring systems biology and personalized interventions over reductionist approaches.}, }
@article {pmid41237539, year = {2025}, author = {Karisola, P and Sinkko, H and Nieminen, A and Laatikainen, T and Yang, Y and Paalanen, L and Jousilahti, P and Vartiainen, E and Mäkelä, MJ and Fyhrquist, N and Haahtela, T and Alenius, H}, title = {Serum metabolites link immune-microbiota interaction in children and young adults from Russian Karelia and Finnish Karelia with contrasting lifestyle and environment.}, journal = {Environment international}, volume = {205}, number = {}, pages = {109911}, doi = {10.1016/j.envint.2025.109911}, pmid = {41237539}, issn = {1873-6750}, abstract = {BACKGROUND: Environmental exposureregulates the immune, circulatory, and nervous systems, thereby affecting health. We investigated the associations between serum metabolite profiles, skin microbiota, and immune-related gene expression of peripheral blood mononuclear cells in children and young adults from Russian Karelia (RUS) and Finnish Karelia (FIN), two regions with contrasting environmental exposures and lifestyles.<br><br>METHODS: Serum metabolites (n&#xa0;=&#xa0;278) from 15 to 20-year-old participants from RUS (n&#xa0;=&#xa0;162) and FIN (n&#xa0;=&#xa0;116) were profiled. Using integrative analysis, a subset of metabolomics was combined with skin microbiota (n&#xa0;=&#xa0;143) and blood transcriptomics (n&#xa0;=&#xa0;144) to characterize environment-linked metabolic and immune signatures.<br><br>RESULTS: Serum metabolite profiles differed significantly between the RUS and FIN subjects, reflecting divergent metabolic states. Citrulline and glutamate/glutamine metabolism were prominent in the RUS subjects while tryptophan catabolism was enhanced in the FIN subjects. Transcriptomic network analysis identified co-expression modules associated with metabolites, skin microbial taxa and key immune traits. A strongly RUS-associated module was dominated by epigenetic long non-coding RNAs and associated positively with anti-inflammatory metabolites such as circulating short-chain fatty acids (SCFAs) and betaine - both present at reduced levels in the FIN subjects. In contrast, FIN-associated modules were linked to inflammatory metabolites such as xanthurenic acid and L-cystine, as well as gene pathways involved in interferon (anti-viral) signaling and neutrophil responses. Across all omics layers, RUS subjects exhibited a more tightly integrated molecular network, with stronger correlations between circulating metabolites, microbial taxa and immune-related gene regulation.<br><br>CONCLUSIONS: Multi-omics integration revealed a more coordinated and responsive immune-metabolic network in RUS youth, potentially shaped by environmental exposures typical of their living context. In contrast, the FIN cohort exhibited metabolic patterns more closely linked to inflammatory gene expression.}, }
@article {pmid41236809, year = {2025}, author = {Shuvo, MSH and Kim, S and Jo, S and Rahim, MA and Barman, I and Hossain, MS and Jeong, Y and Jeong, H and Kim, S and Seo, H and Song, HY}, title = {Characterization of Gut Microbiota of Honey Bees in Korea.}, journal = {Polish journal of microbiology}, volume = {}, number = {}, pages = {}, doi = {10.33073/pjm-2025-025}, pmid = {41236809}, issn = {2544-4646}, abstract = {Korea's unique climate and agricultural environment suggest that the gut microbiome of honey bees may possess distinctive compositions influenced by regional factors. With the decline in honey bee populations and rising health challenges, understanding the role of gut microbiomes is essential for enhancing honey bee health and their resilience to environmental stressors. To explore caste-specific gut microbiota and identify microbial signatures associated with honey bee health, this study examined the gut microbial composition of worker bees, queen bees, and drones of Apis mellifera using 16S rRNA gene amplicon sequencing. Analysis of beta diversity and species richness demonstrated significant differences between worker bees and both drones and queens, with no significant differences identified between drones and queens. Notably, Lactobacillus dominated all groups, comprising 98.6% of the drones, 95.4% of the queens, and 68.3% of the workers. Additionally, Bombella was prominent in queens (4%), whereas Gilliamella (23%) and Frischella (4.7%) were notably enriched in workers. Drones and queens exhibited similar gut microbiome profiles, while workers displayed distinctly different compositions. These findings underscore the variation in gut microbiota composition and potential functional roles across honey bee castes. Such microbial distinctions may reflect caste-specific roles and physiological demands within the colony. Future research should investigate the physiological roles of gut microbiota and their contributions to environmental resilience, paving the way for microbiome-based strategies to promote honey bee health. This study lays a crucial scientific foundation for conserving the honey bee ecosystem and promoting sustainable agriculture.}, }
@article {pmid41236171, year = {2025}, author = {Shi, H and Li, L and Liu, Z and Zhao, X and Wang, Y and Yang, X and Chen, P}, title = {Impact of female sexual dysfunction on assisted reproductive technology outcome.}, journal = {The journal of sexual medicine}, volume = {}, number = {}, pages = {}, doi = {10.1093/jsxmed/qdaf317}, pmid = {41236171}, issn = {1743-6109}, support = {2023A1515012940//Natural Science Foundation of Guangdong Province/ ; 2023WST04//Sixth Affiliated Hospital of Sun Yat-sen University/ ; GZC20233216//Postdoctoral Fellowship Program of CPSF/ ; }, abstract = {BACKGROUND: Despite its high prevalence in infertile women and known impact on natural conception, the specific influence of female sexual dysfunction (FSD) on assisted reproductive technology (ART) outcomes, which bypass intercourse, remains unclear.<br><br>AIM: To investigate the association between female sexual function and ART outcomes, including live birth.<br><br>METHODS: In this prospective cohort study, 300 women undergoing their first ART cycle completed the Female Sexual Function Index (FSFI) prior to treatment. Multivariable regression models were used to assess the association between FSFI measures (FSD status, total score, and domain scores) and ART outcomes, adjusting for key clinical confounders.<br><br>OUTCOMES: The primary outcome was live birth rate following in vitro fertilization or intracytoplasmic sperm injection treatment, with secondary outcomes including biochemical pregnancy, clinical pregnancy rate, ovarian response, and embryology parameters.<br><br>RESULTS: Participants with FSD (n&#x2009;=&#x2009;200) exhibited significantly lower biochemical pregnancy rates (55.5% vs. 82%, P&#x2009;<&#x2009;.01), clinical pregnancy rates (51% vs. 78%, P&#x2009;<&#x2009;.01), and live birth rates (36.5% vs. 54%, P&#x2009;<&#x2009;.01) compared to those without (n&#x2009;=&#x2009;100). After adjusting for confounders, female sexual function, as measured by FSFI, held independent predictive value for these critical pregnancy outcomes. Furthermore, when analyzed as a continuous variable, higher total FSFI scores positively correlated with indicators of improved parameters of embryo development and increased pregnancy success rates. Notably, all six FSFI domains also demonstrated significant positive associations with key ART outcomes. Compared to the standard 26.55 threshold, a data-driven FSFI threshold of 20.70 showed higher Youden index values for predicting ART outcomes.<br><br>CLINICAL IMPLICATIONS: Evaluating FSD should be considered part of routine infertility treatment, as addressing it may offer a novel strategy to improve ART outcomes.<br><br>STRENGTHS &amp; LIMITATIONS: Key strengths are the prospective cohort design establishing temporality and use of a validated FSFI scale. However, as an observational study, it cannot establish causality; other limitations include the single-center design, potential unmeasured confounders, and the subjective nature of self-reported FSFI scores.<br><br>CONCLUSION: Lower female sexual function is significantly associated with poorer outcomes following ART, including substantially reduced live birth rates.}, }
@article {pmid41231122, year = {2025}, author = {Brandl, P and Lüthy, L and Pultar, F and Hansen, ME and Jelmini, N and Faris, J and Yasmin, SO and Kamenik, AS and Arnold, R and Ebert, MO and Wolfrum, S and Lokey, RS and Riniker, S and Carreira, EM}, title = {Mutanobactin D from the Human Microbiome: Chemistry, Biology, and Molecular Dynamics Studies.}, journal = {Journal of the American Chemical Society}, volume = {}, number = {}, pages = {}, doi = {10.1021/jacs.5c08850}, pmid = {41231122}, issn = {1520-5126}, abstract = {Mutanobactin D is an interkingdom communicator derived from the human oral microbiome. The lipopeptide prevents yeast-to-hyphae morphogenesis in Candida albicans, notably without fungicidal or fungistatic activity. The mode of action and structure-activity relationship of mutanobactin D are unknown and prompt an interdisciplinary program of study. Stereoselective synthesis of designed mutanobactin D analogs reveals that the C26 configuration is crucial for bioactivity associated with inhibition of pathogenesis, or yeast-to-hyphae transition, in C. albicans. To shed light on this finding, we employ molecular dynamics (MD) simulations of mutanobactin D and selected analogs in increasingly complex environments: Monophasic (water or CHCl3), interfacial (water/CHCl3), and explicit lipid membrane (phosphatidylcholine) models. Monophasic MD simulations do not distinguish between bioactive and inactive compounds. In contrast, at a polar/apolar interphase, a dominant, stable conformation emerges for mutanobactin D and bioactive analogs. Explicit lipid membrane simulations reinforce these results and further reveal the formation of a continuous, structured water cushion, which is not found for inactive analogs. Our studies collectively reveal how the stereodefined attachment of the lipid in the C26-C28 motif governs activity against C. albicans and provide a framework for understanding the membrane behavior of mutanobactin D, which may be coupled to its role in the human oral microbiome. The approach described herein, consisting of synthesis and evaluation of designed analogs complemented by MD simulations, provides a blueprint for the study of bioactive natural products in various contexts, including the human microbiome.}, }
@article {pmid41230977, year = {2025}, author = {Zhong, G and Yang, X and Deng, R and Zeng, J and Pu, J and Shen, C and Zhao, S and Yang, T and Liu, H and Luo, M and Li, S and Chen, C and Huang, B}, title = {Succinate-driven virulence enhancement in hypervirulent Klebsiella pneumoniae via DcuSR two-component system.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0145325}, doi = {10.1128/spectrum.01453-25}, pmid = {41230977}, issn = {2165-0497}, abstract = {UNLABELLED: Hypervirulent Klebsiella pneumoniae (hvKP) primarily colonizes the mammalian gastrointestinal tract, and it is prone to causing invasive infections under specific conditions. To establish infection, hvKP must compete with the resident gut microbiota for essential nutrients. This study focuses on the C4-dicarboxylate (C4-DC) succinate, which has been reported to accumulate in the gut under specific pathological conditions. We demonstrate that hvKP utilizes succinate as a signaling molecule to enhance virulence gene expression. Specifically, extracellular succinate activates type VI secretion system gene expression via the DcuSR two-component system (TCS), thereby increasing cytotoxicity toward intestinal epithelial cells and enhancing competitiveness against commensal Escherichia coli. Additionally, succinate facilitates the expression of type III fimbriae via the DcuSR TCS, promoting hvKP adherence to intestinal epithelial cells. Beyond its signaling role, succinate functions as a metabolic substrate and contributes to adenosine 5'-triphosphate (ATP) synthesis, potentially through C4-dicarboxylic acid transporters DctA or DcuB to boost energy synthesis. This study focuses on elucidating the impact of succinate in regulating hvKP virulence, with particular attention to the potential role of the DcuSR TCS in hvKP pathogenesis.<br><br>IMPORTANCE: Succinate, a C4-DC, is produced by the host and the gut microbiota and can accumulate in the intestinal environment under various pathological conditions, such as diabetes and inflammatory bowel disease. It acts as a pivotal regulator of virulence traits and metabolic pathways in Enterobacteriaceae. Our findings highlight the significant impact of succinate on hvKP pathogenesis: (i) functioning through the DcuSR TCS to activate virulence programs and (ii) serving as a metabolic substrate that fuels bioenergetic adaptation through ATP synthesis.}, }
@article {pmid41221507, year = {2025}, author = {Clinton, CK and Jackson, FLC}, title = {Persistent human-associated microbial signatures in burial soils from the 17th and 18th century New York African burial ground.}, journal = {ISME communications}, volume = {5}, number = {1}, pages = {ycaf181}, pmid = {41221507}, issn = {2730-6151}, abstract = {Understanding the long-term persistence of human-associated microbial signatures in burial soils offers a untapped insights into historical human health, decomposition, and ecological transformation. This study investigates whether centuries-old burial soils retain distinguishable microbial evidence of human decomposition using 16S rRNA gene sequencing on 81 samples from the New York African Burial Ground (NYABG), a 17th and 18th century cemetery for free and enslaved Africans. Comparative analyses against six control soils from nearby urban parks were conducted using QIIME2, ALDEx2, and ANCOM. Burial soils exhibited significantly greater alpha diversity (Faith's PD, Shannon, observed ASVs; P < .01) and distinct beta diversity patterns (Bray-Curtis, UniFrac; PERMANOVA P = .001). Enrichment of Firmicutes, Actinobacteriota, and gut-associated genera such as Bacillus and Ruminococcus characterized burial soils, whereas oligotrophic taxa dominated controls. Tentative identifications of human-associated pathogenic genera (e.g. Fusobacterium periodonticum, Prevotella pleuritidis) were observed exclusively in burial soils, suggesting their origin from the interred individuals but requiring further validation. These findings demonstrate that soil microbiomes reflect host-associated microbial communities long after decomposition, providing a scalable, nondestructive approach for reconstructing ancient microbial communities and host-associated health signatures. This work establishes the NYABG burial soil microbiome as a valuable model for microbial archaeology and introduces a replicable framework for integrating environmental microbiology, bioarchaeology, and historical epidemiology through the lens of postmortem microbial ecology.}, }
@article {pmid41217181, year = {2025}, author = {Weinberger, V and Neumann, C and Kumpitsch, C and Duller, S and Shinde, T and Mantaj, P and Schmidberger, L and Zurabishvili, T and Halmer, I and Cecovini, M and Vrbancic, S and Pepper, K and Schmon, E and Wenninger, J and Kamolz, L-P and Sendlhofer, G and Koskinen, K and Moissl-Eichinger, C and Mahnert, A}, title = {Colonizing the clinic: tracking bacterial succession and longitudinal dynamics in five new hospital departments over an entire year.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0217825}, doi = {10.1128/spectrum.02178-25}, pmid = {41217181}, issn = {2165-0497}, abstract = {The development of hospital-associated microbial communities over time remains poorly characterized, particularly in terms of how microbial populations dynamically respond to changes in building function, the integration of molecular and cultivation-based data, and the early identification of intervention points for flexible, adaptive microbial control strategies. In this longitudinal study, we investigated microbiome dynamics across five newly built departments at the University Hospital of Graz, Austria, over one year. Surface samples were collected at seven time points: before and after hospital operation started. Alpha and beta diversity analyses revealed a distinct two-phase microbial transition, marked by an initial disruption followed by a gradual homogenization of microbial communities. The strongest driver of community change was the arrival of patients, which led to a significant shift in both diversity and taxonomic composition. While early time points were dominated by environmental taxa such as Acinetobacter and Pseudomonas, human-associated genera like Staphylococcus and Corynebacterium became more prevalent over time, particularly on frequently touched surfaces. Department-specific and surface-specific microbial signatures were observed, with outpatient and transplant departments showing more variability than surgical and intensive care units (ICUs). Propidium monoazide treatment indicated that Pseudomonas and Acinetobacter may persist as viable community members, whereas Staphylococcus and Corynebacterium likely reflect frequent human deposition. Cultivation data supported these findings, showing episodic contamination primarily linked to human contact. Phenotypic predictions revealed a decline in aerobic, Gram-negative, and potentially pathogenic bacteria over time, although these trends were less pronounced in the ICU. Together, our findings reveal a longitudinal homogenization of hospital microbiomes driven by human activity and highlight key taxa and surfaces that warrant targeted monitoring to improve hygiene protocols and infection control strategies.IMPORTANCEThis study provides crucial insights into how hospital environments transform microbially after new departments open, a process poorly understood until now. We reveal a two-phase microbial shift, starting with environmental bacteria like Acinetobacter and Pseudomonas before the hospital opens, then rapidly transitioning to human-associated microbes such as Staphylococcus and Corynebacterium once patients and staff arrive. Our findings highlight that human activity is the strongest driver of these changes, especially on frequently touched surfaces. This work is vital for developing targeted and adaptive hygiene concepts, improving infection control, and ultimately making hospital environments safer for patients and staff by focusing on specific surfaces and microbial groups that warrant continuous monitoring.}, }
@article {pmid41211619, year = {2025}, author = {Ermolenko, E and Sitkin, S and Alferova, L and Ilyushonok, S and Beltyukov, P and Babakov, V and Novikova, N and Gladyshev, N and Berdichevskiy, G and Demchenko, E and Suvorov, A}, title = {Health Reversion Effects of Autoprobiotics on Serum and Urine Metabolomes in Patients With Metabolic Syndrome: A Pilot Study.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e70273}, doi = {10.1002/mnfr.70273}, pmid = {41211619}, issn = {1613-4133}, abstract = {The effectiveness of oral administration of autoprobiotic (nonpathogenic, indigenous) Enterococcus faecium or Enterococcus hirae for 20 days in patients with metabolic syndrome (MetS), characterized by obesity and impaired carbohydrate and lipid metabolism, was investigated. The dynamics of changes in anthropometric, biochemical parameters, and metabolism were monitored 14 and 28 days after the end of therapy. Clinical and laboratory changes after using autoprobiotics indicate a decrease in the severity of MetS. In the reversed-phase high-performance liquid chromatography-mass spectrometry analysis of blood serum metabolome, a significant decrease in the levels of all identified long-chain acylcarnitines - palmitoyl-L-carnitine (C16:0), stearoyl-L-carnitine (C18:0), and oleoyl-L-carnitine (C25), trimethylamine-N-oxide, and homocysteine 14 and 28 days after the end of therapy, and, conversely, a significant increase in L-histidine levels. The targeted gas-liquid chromatography showed an increase in the concentrations of hippuric, glycolic, methylmalonic acids, and 5-oxoproline at the same time. The effectiveness of therapy is confirmed by changes in serum and urinary metabolism, primarily aimed at correcting these and reducing signs characteristic of patients with obesity and impaired energy metabolism. The revealed positive changes in the concentration of individual serum and urine metabolites allow for their further use in a targeted study to predict the severity of MetS and the effectiveness of its therapy.}, }
@article {pmid41210964, year = {2025}, author = {Haller, N and Widauer, HL and Strepp, T and Nunes, N and Blumkaitis, JC and Wenger, M and Stöggl, T and Aglas, L}, title = {How intense is high-intensity interval training? Biomarker responses and associations with training load and fitness.}, journal = {iScience}, volume = {28}, number = {11}, pages = {113738}, pmid = {41210964}, issn = {2589-0042}, abstract = {High-intensity interval training (HIIT) enhances physical performance but requires close monitoring to avoid illnesses/injuries. We monitored physiological responses at rest during and up to 14 days following a 7-day HIIT intervention to identify chronic physiological changes and to explore correlations between blood biomarkers (blood count, cytokines, creatine kinase [CK], urea, ferritin, and transferrin), training load, cardiorespiratory fitness (VO2max), and muscle soreness. Thirty participants were randomly allocated to either HIIT shock cycle (10× HIIT in 7 days) (1) with or (2) without additional low-intensity training after each HIIT session or (3) control group. Repeated HIIT resulted in a chronic decrease of hemoglobin, hematocrit, red blood cells, CK, interleukin [IL]-2, -4, -9, -17A, -17F, tumor necrosis factor alpha (TNF-α), and ferritin. CK showed highest positive correlation with training load and muscle soreness, while VO2max correlated with cytokines IL-5, -6, -10, -17F, -22. The present study revealed reliable biomarkers reflecting training load and VO2max, suitable for personalized monitoring of health and recovery and performance optimization.}, }
@article {pmid41207298, year = {2025}, author = {Zhai, Z and Che, X and Shen, W and Zhang, Z and Li, Y and Pan, J}, title = {HLRMDB: a comprehensive database of the human microbiome with metagenomic assembly, taxonomic classification, and functional annotation by analysis of long-read and hybrid sequencing data.}, journal = {Nucleic acids research}, volume = {}, number = {}, pages = {}, doi = {10.1093/nar/gkaf1152}, pmid = {41207298}, issn = {1362-4962}, support = {32470699//National Natural Science Foundation of China/ ; //Chongqing Medical University/ ; }, abstract = {The human microbiome harbours an immense diversity of uncultivated microbes; short-read metagenomic sequencing has elucidated much of this diversity, but fragment repeats and mobile elements constrain strain-level resolution. Fortunately, long-read metagenomic sequencing can generate reads spanning tens of kilobases with single-molecule accuracies exceeding 99%, enabling near-complete genome and gene cluster recovery in a cultivation-independent manner. However, systematic resources that aggregate and standardise long-read outputs remain limited. Here, we present HLRMDB (http://www.inbirg.com/hlrmdb/), a comprehensive database of human microbiome datasets derived from long-read and hybrid metagenomic sequencing. We curated 1672 publicly available metagenomes (1291 long reads; 381 hybrids) spanning 38 studies, 39 sampling contexts and 42 host health states. A uniform assembly and binning pipeline reconstructed >98 Gb of contigs and yielded 18 721 metagenome-assembled genomes (MAGs). These MAGs span 21 phyla and 1323 bacterial species, with 6339 classified as near-complete and 5609 as medium-quality. HLRMDB integrates these genome-resolved data with extensive gene-centric functional profiles and antimicrobial resistance annotations. An interactive web interface supports flexible access to both sample-level and genome-level results, with multiple visualisations linking raw reads to assembled genomes. Overall, HLRMDB offers a harmonised, long-read-oriented repository that supports reproducible, strain-resolved comparative genomics and context-sensitive ecological investigations of the human microbiome.}, }
@article {pmid41205405, year = {2025}, author = {Reinholm, A and Khan, H and Laakso, T and Maljanen, S and Jalkanen, P and Gunell, M and Kallonen, T and Österlund, P and Ritvos, O and Nousiainen, A and Häkkinen, HK and Pakkanen, SH and Välimaa, H and Kantele, A and Lempainen, J and Julkunen, I and Kolehmainen, P and Kakkola, L}, title = {Corrigendum to "Long-term neutralization capacity of vaccine and breakthrough infection induced SARS-CoV-2 specific antibodies against omicron subvariants BA.2, XBB.1.5, and JN.1" [Vaccine 68 (2025) 127894].}, journal = {Vaccine}, volume = {68}, number = {}, pages = {127939}, doi = {10.1016/j.vaccine.2025.127939}, pmid = {41205405}, issn = {1873-2518}, }
@article {pmid41205302, year = {2025}, author = {Camille, E and Sébastien, B and Virginie, B}, title = {The hidden players: The mycobiome of pancreatic ductal adenocarcinoma tumors.}, journal = {Microbiological research}, volume = {303}, number = {}, pages = {128392}, doi = {10.1016/j.micres.2025.128392}, pmid = {41205302}, issn = {1618-0623}, abstract = {The microorganisms that inhabit the human body are known to play a role in human health and disease. Continuing to elucidate their specific role in disease progression is, however, necessary. The imbalance of these microorganisms-known as dysbiosis-has been linked to a myriad of intestinal diseases, and more recently to cancer. Despite making up less than 0.1 % of the human microbiome, dysbiosis of the fungal component of the microbiome-the mycobiome-has been found to contribute to the tumorigenesis and progression of certain types of tumors, pancreatic ductal adenocarcinoma (PDAC) included. The quantity and composition of the mycobiome was found to differ between healthy pancreatic tissue, the gut mycobiome of PDAC patients and PDAC tissue. Moreover, in a murine model of PDAC, it was shown that fungal ablation had a protective effect on tumor growth, and that specific fungal species, such as Malassezia globosa, contribute to tumor growth as well as to the inflammatory environment observed in PDAC tumors which promotes tumor progression. Research shows that fungal presence contributes to shaping the immune microenvironment through the activation of the complement system and/or by eliciting a type 2 immune response. Despite these preliminary findings, given the novelty of the field and of the bioinformatics pipelines used to analyze sequencing data, standardized approaches are still under development, thus leading to disagreement on the reliability of these results. The purpose of this review is to provide an up-to-date overview of the current research regarding the contribution of the fungal mycobiome in PDAC tumor progression and the overall tumor microenvironment (TME) of PDAC tumors.}, }
@article {pmid41202150, year = {2025}, author = {Champagne-Jorgensen, K and Gommerman, JL}, title = {Two of a kind, one with MS: Gut microbes tip the balance.}, journal = {Science immunology}, volume = {10}, number = {113}, pages = {eaed4910}, doi = {10.1126/sciimmunol.aed4910}, pmid = {41202150}, issn = {2470-9468}, mesh = {*Gastrointestinal Microbiome/immunology ; Humans ; Animals ; *Multiple Sclerosis/immunology/microbiology ; Mice ; Fecal Microbiota Transplantation ; }, abstract = {An MS twin study links ileal Lachnospiraceae to spontaneous CNS autoimmunity in mice receiving a human microbiome transplant.}, }
@article {pmid41197755, year = {2025}, author = {Wang, XX and Liang, JJ and Duan, X and Chen, G}, title = {Microbial Metabolites for Cancer Immunotherapy: Current Evidence and Future Directions.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2025.10.005}, pmid = {41197755}, issn = {1096-3650}, abstract = {Immune checkpoint blockade (ICB) therapy has transformed cancer treatment by activating the body's immune defenses to combat malignancies, offering substantial therapeutic outcomes for patients with advanced cancers. However, its efficacy varies considerably across different tumor types and individual patients. Recent studies have identified the human microbiome as a pivotal regulator of host homeostasis and systemic immunity and also found that it is essential for regulating immunotherapy's efficacy. Beyond direct microbial-host interactions, microbiota-derived immunomodulatory products, including metabolites, extracellular vesicles, and polysaccharides, have been shown to profoundly influence tumorigenesis, disease progression, and therapeutic responses. These microbial-derived immunomodulatory products can reshape the tumor microenvironment (TME) and modulate tumor immunity. Notably, emerging therapeutic strategies targeting or utilizing microbial immunomodulators have demonstrated promising efficacy in both preclinical and clinical models. This review provides a comprehensive overview of current research on microbiota-derived immunomodulatory products in cancer immunotherapy, highlighting their mechanistic roles and potential as innovative adjuncts in future tumor treatment strategies.}, }
@article {pmid41197754, year = {2025}, author = {Xia, F and Yi, Q and Xu, Z and Zhou, Z and Tang, H and Zhang, K and Yan, Y}, title = {Microbial Modulation as a Game Changer: Boosting Immunotherapy Efficacy in Breast Cancer.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2025.10.006}, pmid = {41197754}, issn = {1096-3650}, abstract = {Breast cancer is generally regarded as an immunologically cold tumor, characterized by limited T cell infiltration and poor responsiveness to immune checkpoint inhibitors. Increasing evidence suggests that the human microbiome, including both gut and tumor-associated microbial communities, serves as a critical regulator of systemic and local antitumor immunity, with potential to convert inert tumors into immune-responsive states. Gut microbiota influence systemic immune homeostasis through metabolites such as lipids, lactic acid, and trimethylamine N-oxide, which modulate T lymphocytes, dendritic cells, leukocytes, and stromal components. Tumor-resident microbiota further shape the tumor immune microenvironment by regulating CD4[+] and CD8[+] T cells, NKT cells, Tregs, and macrophages, thereby impacting the efficacy of immune checkpoint blockade. Emerging strategies to sensitize cold breast tumors through microbiome modulation include dietary phytochemicals, bariatric surgery induced microbial shifts, probiotics and postbiotics, polyvalent microbial antigen vaccines, and nanotechnology-based platforms. Clinical challenges remain, particularly interindividual microbial heterogeneity, safety and regulatory considerations, and the need for reliable microbial and immune biomarkers. This review summarizes current advances in microbiota-immune interactions in breast cancer and discusses opportunities for microbiome-targeted strategies to enhance immunotherapy outcomes.}, }
@article {pmid41194223, year = {2025}, author = {Peng, B and Ma, B and Lu, H and Chen, Z and Xiong, W and Wang, H and Cai, Z and Shi, X and Huang, R}, title = {Ultrasound-responsive Janus patch with mechanical anisotropy, pro-healing, and anti-adhesion properties for abdominal wall defect repair.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {702}, pmid = {41194223}, issn = {1477-3155}, support = {2021YFC2101700//National Key Research Development Program of China/ ; 22371312//National Natural Science Foundation of China/ ; 52203112//National Natural Science Foundation of China/ ; 22271320//National Natural Science Foundation of China/ ; 2017008//Sun Yat-sen University Clinical Research 5010 Program/ ; RCBS20221008093103014//Shenzhen Science and Technology Program/ ; 23qnpy155//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; 23yxqntd002//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; FTWS2025001//the Futian Healthcare Research Project/ ; 2023B0303000025//Guangdong Major Project of Basic and Applied Basic Research/ ; 2021-M04//CIFST-Abbott Foundation of Food Nutrition and Safety/ ; }, abstract = {Abdominal wall exhibits a complex anisotropic architecture with region-specific mechanical gradients, essential for maintaining biomechanical integrity during physiological deformations. However, most clinical patches possess isotropic structures and fail to meet the mechanical anisotropy requirements of abdominal wall. Herein, inspired by the hierarchical structure of abdominal wall, an innovative ultrasound-responsive Janus patch (JPLCL/ZnO) is designed by constructing a poly (2-methacryloyloxyethyl phosphorylcholine) (PMPC) coating on the top surface of a fibrous anisotropic patch (PLCL/ZnO) via multi-channel electrospinning and in situ photocuring technologies. By adjusting fiber orientation, our patch achieves tunable anisotropy ratios (1-14), matching the mechanical gradients of abdominal wall (1-9). The PMPC-coated side prevents tissue adhesion, while the anisotropic PLCL/ZnO side promotes directional cell growth and tissue regeneration under ultrasound stimulation. Moving toward clinical translation, we developed a large mammal defect model in pigs with abdominal wall resection. By integrating excellent mechanical anisotropy, pro-healing, anti-adhesion, and immune regulation properties, our JPLCL/ZnO patch demonstrates a significant advancement for abdominal wall defect repair.}, }
@article {pmid41190871, year = {2025}, author = {Liang, W and Chen, G and Zheng, B and Zhou, H and Ouyang, Y and Wang, X and He, Z and Wu, D and Lan, P and Huang, R}, title = {Biocompatible Nanozyme Shell-Armed Probiotic with Inflammation Targeting and Scavenging Properties Enables Effective Treatment of Colitis.}, journal = {Advanced materials (Deerfield Beach, Fla.)}, volume = {}, number = {}, pages = {e08532}, doi = {10.1002/adma.202508532}, pmid = {41190871}, issn = {1521-4095}, support = {2022YFA1304000//National Key Research and Development Program of China/ ; 22271320//National Natural Science Foundation of China/ ; 52372057//National Natural Science Foundation of China/ ; 2021B1212040017//Science and Technology Planning Project of Guangdong Province/ ; 2023B0303000025//Guangdong Major Project of Basic and Applied Basic Research/ ; //Fundamental Research Funds for the Central Universities/ ; 23yxqntd002//Sun Yat-sen University/ ; JCYJ20240813150654069//Shenzhen Science and Technology Program/ ; //Guangdong Basic Research Center of Excellence for Functional Molecular Engineering/ ; //National Key Clinical Discipline/ ; }, abstract = {Coupling probiotics with lesion targeting and inflammation control properties without complex chemical modifications is crucial for preserving their native bioactivity, but remains challenging. Herein, metformin as a functional self-modulated alkaline reagent is incorporated to achieve the rapid and biocompatible construction of a polydopamine-based nanozyme shell (DMCe) on the surface of probiotics, thus avoiding the biological toxicity caused by traditional triggering methods. DMCe can not only serve as a robust physical barrier to protect probiotics from the invasion of digestive juices and antibiotics, but also synergistically scavenge reactive oxygen species (ROS) at colitis lesions via the intrinsic antioxidant property of catechol and the catalase-mimicking activity of cerium oxide. It is worth noting that during the process of scavenging ROS, the originally harmful ROS can be utilized by DMCe as reactive components to facilitate chemical reactions between the modified probiotics and colitis lesions, thus achieving prolonged inflammation targeting for up to 7 days. In addition, nanozyme shell-armed probiotics can improve microbial community composition and increase the levels of short-chain fatty acids. By integrating inflammation targeting, ROS scavenging, and microbiome remodeling, nanozyme shell-armed probiotics can significantly reduce inflammation levels and promote healing of the mucosal barrier in a mouse colitis model.}, }
@article {pmid41184906, year = {2025}, author = {Singh, H and Balusamy, SR and Sukweenadhi, J and Saravanan, M and Aruchamy, M and Mijakovic, I and Singh, P}, title = {Smart hybrid nanomaterials for chronic infections: microbiome-responsive and sustainable therapeutic platforms.}, journal = {Journal of nanobiotechnology}, volume = {23}, number = {1}, pages = {698}, pmid = {41184906}, issn = {1477-3155}, abstract = {UNLABELLED: Chronic wounds remain a persistent clinical challenge due to their complex pathology involving prolonged inflammation, microbial biofilms, and impaired tissue regeneration. Emerging research highlights the dynamic role of the human microbiome in modulating immune responses and influencing wound healing outcomes. Disruptions to this microbial balance, termed dysbiosis, not only exacerbate infection but also hinder therapeutic efficacy. Recent advances in smart and sustainable nanotechnology offer promising avenues to address these challenges. By integrating microbiome-sensitive mechanisms with targeted delivery systems, bio-based nanomaterials can overcome multidrug resistance, modulate inflammation, and accelerate healing. This review explores the molecular interplay between chronic infections and host immunity, highlights next-generation nanomaterials for regenerative applications, and proposes a sustainable paradigm that bridges clinical effectiveness with environmental responsibility.<br><br>GRAPHICAL ABSTRACT: [Image: see text]}, }
@article {pmid41187758, year = {2025}, author = {Yilmaz, B and Baertschi, I and Meier, KHU and Le Gac, C and Jordi, SBU and Black, C and Li, J and Lindholm, AK and ,  and König, B and Sauer, U and Stelling, J and Macpherson, AJ}, title = {A global survey of taxa-metabolic associations across mouse microbiome communities.}, journal = {Cell host &amp; microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2025.10.010}, pmid = {41187758}, issn = {1934-6069}, abstract = {Host-microbiota mutualism is rooted in the exchange of dietary and metabolic molecules. Microbial diversity broadens the metabolite pool, with each taxon contributing distinct compounds in varying proportions. In the human microbiome, high variability in consortial composition is largely compensated by similar metabolic functions across different taxa. However, the extent of compensation in lower diversity mouse models, and whether vivaria are metabolically equivalent, is unknown. We provide a searchable resource of microbiome composition variability across 51 murine vivaria and 12 wild mouse colonies worldwide, with vivarium-specific variants mapped according to predicted 3D structures for each microbial species. Our matched metabolomics data show that realized metabolic potential has relatively low variability, providing functional evidence for metabolic compensation. Additionally, variability is related to taxonomic composition rather than vivarium, revealing taxa-metabolite associations that are potentially relevant to phenotypic differences between vivaria. Collectively, this resource offers tools to strengthen microbiome studies and collaborative science.}, }
@article {pmid41182672, year = {2025}, author = {El-Demerdash, FE and Mohammed, OA and Mohamed, HH and Doghish, AS}, title = {Microbiome alterations in healthy pregnancy and pregnancy disorders in association with autoimmune diseases.}, journal = {Folia microbiologica}, volume = {}, number = {}, pages = {}, pmid = {41182672}, issn = {1874-9356}, abstract = {Pregnancy induces significant alterations in the maternal microbiome, which are critical for fetal development and maternal health. Gynecological diseases, along with infertility, have increased due to excessive personal care product usage, which contains endocrine-disrupting chemicals (EDCs). Mammalian immune systems develop during pregnancy and after birth owing to crucial inputs from the environment. The growing incidence of autoimmune diseases (AIMDs) emphasizes the need to understand the environmental elements that play a role in their development, with the microbiome emerging as a key player. Exposure to EDCs with oxidative stress (OS) induces microbiome disruptions to promote AIMDs and negatively impacts female reproductive health and fetuses. Because the body changes in a number of ways to provide ideal conditions for fetal growth, pregnancy is a special moment in a woman's life. All microorganisms undergo changes, and their quantity and composition vary over the three trimesters of pregnancy. Recent research suggests a connection between pregnancy issues and the microorganisms present during pregnancy. This review explores the pivotal role of the human microbiome in pregnancy health, emphasizing how microbiome dynamics influence immune development and long-term immunity in offspring. It examines the impact of environmental factors, particularly EDCs, on maternal microbiota and their association with pregnancy complications such as hypertensive disorders and autoimmune diseases. The manuscript highlights current research findings and discusses potential microbiome-targeted interventions to promote maternal and fetal well-being.}, }
@article {pmid41181176, year = {2025}, author = {Abidov, A and Bayer, DK}, title = {Atopic dermatitis, primary atopic disorders, and the cutaneous microbiome: current understanding of an expanding field.}, journal = {Frontiers in pediatrics}, volume = {13}, number = {}, pages = {1670623}, pmid = {41181176}, issn = {2296-2360}, abstract = {Atopic dermatitis is a common inflammatory skin disease with rapidly expanding worldwide prevalence. Increasingly, cases of severe and early-onset dermatitis have been identified and found to be due to underlying monogenic mutations, leading to immune dysregulation. These conditions, called primary atopic disorders, have become an area of extensive study over the last 30 years. Simultaneously, our understanding of the human microbiome has steadily grown, and there is clear evidence that dysbiosis plays a major role in atopic dermatitis, not only in severity of disease and as a potential trigger but also offering clues for targeted treatment strategies. Unfortunately, despite our growing understanding of the cutaneous microbiome and the expanding availability of genetic testing allowing for diagnosis of primary atopic disorders, there remains very limited understanding regarding the microbiomics changes that underlie these disorders. Here we review the current research regarding atopic dermatitis in the setting of primary atopic disorders, understanding regarding primary atopic disorders and associated cutaneous dysbiosis, and identify specific gaps in knowledge.}, }
@article {pmid41177823, year = {2025}, author = {Zuo, T}, title = {Pushing the frontier of gut microbiome health cross-kingdom and cross-organ.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, pmid = {41177823}, issn = {1759-5053}, }
@article {pmid41175426, year = {2025}, author = {Meher, MM and Afrin, M}, title = {Global surge of human metapneumovirus (hMPV) and its interactions with microbiome to disease severity.}, journal = {Journal of infection and public health}, volume = {19}, number = {1}, pages = {103024}, doi = {10.1016/j.jiph.2025.103024}, pmid = {41175426}, issn = {1876-035X}, abstract = {Human metapneumovirus (hMPV) is a significant virus of the lungs that causes diversified symptoms such as mild colds to severe pneumonia in people of all ages, especially in children, the elderly, and immunosuppressed individuals. The review highlights the global escalation of hMPV and explores how the human microbiome may shape the susceptibility of infections, immune responses and disease severity. The virus can form inclusion bodies inside the host cells and increase hMPV virulence to induce severe viral infection. hMPV also exploits immune-evasion strategy that weaken the host-body's defenses. Disturbances of gut-lung-microbiota can weaken the host immunity and worsen the disease severity. Nevertheless, intestinal microbes may promote the lung health through the compounds e.g., short-chain fatty acids. Although no particular treatment exists, there is an increasing concern in microbiome-based therapeutic approaches and personalized medicine. Understanding the microbiome interaction to hMPV may develop strategies to predict, prevent, and manage the hMPV infections.}, }
@article {pmid41171140, year = {2025}, author = {Zhang, Z and Zhao, H and Wang, T}, title = {PRIME: a database for 16S rRNA microbiome data with phenotypic reference and comprehensive metadata.}, journal = {Nucleic acids research}, volume = {}, number = {}, pages = {}, doi = {10.1093/nar/gkaf1057}, pmid = {41171140}, issn = {1362-4962}, support = {12222111//National Natural Science Foundation of China/ ; 12331009//National Natural Science Foundation of China/ ; 12571306//National Natural Science Foundation of China/ ; //Fundamental Research Funds for the Central Universities/ ; //Shanghai Jiao Tong University/ ; //National Natural Science Foundation of China/ ; }, abstract = {PRIME (Phenotypic Reference for Integrated Microbiome Enrichment) is a curated and standardized database of human microbiome 16S rRNA amplicon sequencing data, designed to facilitate cross-study analysis, reproducibility, and phenotype-driven discovery. PRIME aggregates 53 449 samples from 111 public studies, covering 93 body sites and 101 phenotypic categories, with detailed harmonization of sample-level metadata such as disease status, demographics, body sites, sequencing protocols, and experimental design. Each sample includes taxonomic abundance profiles generated via a consistent pipeline using both SILVA (138.2) and Greengenes2 (2024.09) reference databases, with results reported at multiple taxonomic levels as observed abundances (read counts) and relative abundances (proportions). A major strength of PRIME is its extensive manual curation, which standardizes phenotypic and contextual metadata across studies, enabling precise querying and robust phenotype-based comparisons. Users can interactively explore the database through a modern web interface, filter and visualize data by metadata fields, and download customized subsets. Programmatic access is supported via RESTful APIs and R package. PRIME aims to advance microbiome data integration and is continuously updated to incorporate new studies and features. The database is freely available at https://primedb.sjtu.edu.cn.}, }
@article {pmid41171074, year = {2025}, author = {Zhou, Y and Wang, Y and Xiao, B and Wang, S and Zhang, Z and Wang, X and Liu, B and Yang, Y and Wang, C and Zhou, C and Liao, M and Song, F and Luo, H}, title = {Predicting age from binarized human oral microbial data combined with an ensemble of classifiers.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0118225}, doi = {10.1128/msystems.01182-25}, pmid = {41171074}, issn = {2379-5077}, abstract = {It is well established that the composition of the human microbiome changes with age; however, limited research has explored the association between the oral microbiome and aging, as well as its potential for age prediction. In this study, we investigated the correlation between the oral microbiome and age by analyzing samples from 150 individuals across a wide age range (6-78 years). The observed species richness and Chao1 index significantly increased with age. Permutational multivariate analysis of variance (PERMANOVA), using both Bray-Curtis and Jaccard distances, identified age as a major factor influencing microbial variation. After a comprehensive comparison of four different oral microbiome data processing approaches, we then developed an ensemble model based on binarized oral microbial data, incorporating an eXtreme Gradient Boosting (XGBoost) algorithm with 32 classifiers. This ensemble model achieved a mean absolute error (MAE) of 7.20 years in the independent validation set (n = 15) and 4.33 years in the 20-59 age subgroup (n = 12), significantly outperforming traditional models. When the sample size increased to 2,550, the MAE in the independent validation set (n = 255) was reduced to 4.80 years, with the 20-59 age subgroup (n = 232) achieving an MAE of 3.76 years, highlighting its generalizability and robustness. Additionally, compared to the previously published model for age prediction based on oral microbiome, our model demonstrated significantly superior performance. These findings support the potential of integrating binarized microbial data with ensemble modeling as a promising direction for human age prediction based on the microbiome.IMPORTANCEPERMANOVA analysis with Jaccard distances revealed age as a major determinant of variation in microbial composition, highlighting the potential of binarized oral microbial data as a novel predictor for human age prediction. Furthermore, we developed an ensemble model combining an XGBoost algorithm and 32 classifiers to predict age from binarized oral microbial data. The model achieved an MAE of 7.20 years in the independent validation set (n = 15) and 4.33 years in the 20-59 age subgroup (n = 12). When applied to predict age in 2,550 samples from previous studies, the ensemble model outperformed the prior model, achieving an MAE of 4.44 years compared to the previous model's 4.94 years. These findings demonstrate that binarized oral microbial data, along with the ensemble model we developed, can effectively predict human age and provide a solid foundation for future age-related research.}, }
@article {pmid41165334, year = {2025}, author = {Horvath, M and Kang, HG and Wu, T-C and Aiken, E and Castaneda, DC and Akkurt, S and Marches, F and Anczuków, O and Palucka, K and Oh, J}, title = {Host-specific bacterial modulation of airway gene expression and alternative splicing.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0057725}, doi = {10.1128/msphere.00577-25}, pmid = {41165334}, issn = {2379-5042}, abstract = {The human microbiome varies extensively between individuals. While there are numerous studies investigating the effects of inter-individual differences on microbiome composition, there are few studies investigating inter-individual effects on microbial modulation of the host or host-specific effects. To address this knowledge gap, we colonized human bronchial epithelial air-liquid interface tissue cultures generated from six different adults with one of three phylogenetically diverse bacteria and compared how each microbe differentially modulated host gene expression in each of the six donors. Microbial treatment had the strongest effect on transcription, followed by donor-specific effects. Gene pathways differed markedly in their donor and microbe specificity; interferon expression was highly donor-dependent, while transcription of epithelial barrier and antibacterial innate immunity genes was predominantly microbially driven. Moreover, we evaluated whether microbial regulation of alternative splicing was modulated by the donor. Strikingly, we found significant nonredundant, donor-specific regulation of alternative splicing exclusively in the gram-positive commensal microbes. These findings highlight that microbial effects on the human airway epithelium are not only species-specific but also deeply individualized, underscoring the importance of the host context in shaping microbe-induced transcriptional and splicing responses.IMPORTANCEMicrobiota are integral regulators of host gene expression, utilizing diverse mechanisms that are shaped by the interplay between microbiome composition and inter-individual differences, i.e., host-specific factors. While previous studies have characterized inter-individual variation in microbiome composition and the effects of variable microbiome composition on the host, the extent to which host-specificity itself regulates host-microbe interactions remains poorly understood. In this study, we address this gap by characterizing changes in epithelial gene expression from six different human donors following colonization with one of three phylogenetically diverse bacteria. By systematically comparing donor-specific responses, we demonstrate that host specificity is a key determinant of the host transcriptional response to microbial colonization. Importantly, we demonstrate that the effects of host specificity are not uniform, but instead are dependent on the colonizing microbe. Our findings underscore the complexity of host-microbe relationships and establish host specificity as a significant factor shaping host-microbe interactions.}, }
@article {pmid41165062, year = {2025}, author = {Senar, N and Zwinderman, AH and Hof, MH}, title = {Sparse Canonical Correlation Analysis for Multiple Measurements With Latent Trajectories.}, journal = {Biometrical journal. Biometrische Zeitschrift}, volume = {67}, number = {6}, pages = {e70090}, doi = {10.1002/bimj.70090}, pmid = {41165062}, issn = {1521-4036}, mesh = {*Biometry/methods ; Humans ; Correlation of Data ; Models, Statistical ; }, abstract = {Canonical correlation analysis (CCA) is a widely used multivariate method in omics research for integrating high-dimensional datasets. CCA identifies hidden links by deriving linear projections of observed features that maximally correlate datasets. An important requirement of standard CCA is that observations are independent of each other. As a result, it cannot properly deal with repeated measurements. Current CCA extensions dealing with these challenges either perform CCA on summarized data or estimate correlations for each measurement. While these techniques factor in the correlation between measurements, they are suboptimal for high-dimensional analysis and exploiting this data's longitudinal qualities. We propose a novel extension of sparse CCA that incorporates time dynamics at the latent variable level through longitudinal models. This approach addresses the correlation of repeated measurements while drawing latent paths, focusing on dynamics in the correlation structures. To aid interpretability and computational efficiency, we implement an ℓ 0 $\ell _0$ penalty to enforce fixed sparsity levels. We estimate these trajectories fitting longitudinal models to the low-dimensional latent variables, leveraging the clustered structure of high-dimensional datasets, thus exploring shared longitudinal latent mechanisms. Furthermore, modeling time in the latent space significantly reduces computational burden. We validate our model's performance using simulated data and show its real-world applicability with data from the Human Microbiome Project. This application highlights the model's ability to handle high-dimensional, sparsely, and irregularly observed data. Our CCA method for repeated measurements enables efficient estimation of canonical correlations across measurements for clustered data. Compared to existing methods, ours substantially reduces computational time in high-dimensional analyses as well as provides longitudinal trajectories that yield interpretable and insightful results.}, }
@article {pmid41163402, year = {2025}, author = {Szóstak, N and Kozłowski, P and Zuo, T and Philips, A}, title = {The role of gut mycobiome in responses to cancer immunotherapy.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2571433}, doi = {10.1080/19490976.2025.2571433}, pmid = {41163402}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Mycobiome ; *Neoplasms/therapy/immunology/microbiology ; *Immunotherapy ; Animals ; Tumor Microenvironment/immunology ; *Fungi/classification/immunology ; Dysbiosis/microbiology/immunology ; Immune Checkpoint Inhibitors/therapeutic use ; }, abstract = {The gut microbiome has emerged as an important modulator of cancer progression and therapy response, yet the role of its fungal component, the gut mycobiome, remains poorly understood. In this review, we summarize current knowledge on the relationship between intestinal fungi and cancer, with a particular focus on the potential influence of the gut mycobiome on the efficacy of immune checkpoint inhibitors (ICIs). Drawing from both human studies and preclinical models, we discuss evidence linking fungal dysbiosis to altered immune responses and therapy outcomes in cancer patients. Specific fungal taxa, such as Candida and Malassezia, have been associated with changes in the tumor microenvironment and modulation of host immunity. We also review the proposed mechanisms through which fungi may impact antitumor immunity, including interactions with immune receptors and production of bioactive metabolites. Although research in this field is still in its early stages, emerging data suggest that the gut mycobiome may serve as a biomarker for immunotherapy response and a potential target for therapeutic intervention. A better understanding of host-fungus interactions in the gut could contribute to the development of personalized strategies to improve the effectiveness and safety of cancer immunotherapy.}, }
@article {pmid41163171, year = {2025}, author = {Qiu, X and Zhang, M and Zhang, L and Chen, H and Gao, M and Li, W and Yu, Z and Hou, Z}, title = {Peculiarities of vaginal microbiota in perimenopausal and postmenopausal women with type 2 diabetes mellitus.}, journal = {Annals of clinical microbiology and antimicrobials}, volume = {24}, number = {1}, pages = {59}, pmid = {41163171}, issn = {1476-0711}, support = {H2020206490//Natural Science Foundation of Hebei Province,China/ ; 20230095//Medical Science Research Subject Plan of Hebei/ ; PD2023002//Clinical Medicine Postdoctoral Research Support Program of Hebei Medical University/ ; B2024003014//Hebei Province Yanzhao Golden Talent Program/ ; 2024YFC2510600//Key R&amp;D Program of the China Ministry of Science and Technology/ ; }, mesh = {Humans ; Female ; *Vagina/microbiology ; *Diabetes Mellitus, Type 2/microbiology ; Middle Aged ; *Postmenopause ; *Microbiota ; *Perimenopause ; Aged ; *Bacteria/classification/genetics/isolation &amp; purification ; Metagenomics ; Dysbiosis/microbiology ; }, abstract = {BACKGROUND: The changes in the vaginal microbiota and potential dysbiosis adjustment strategies in diabetic patients remain inconclusive. This study was designed to investigate the impact of Type 2 diabetes mellitus (T2DM) on the ecological dynamics of the vaginal microbiota in perimenopausal and postmenopausal women, with a focus on microbial community structure and functional homeostasis.<br><br>METHODS: Vaginal secretion samples from 22 T2DM patients (DM group) and 23 healthy controls (CT group) under perimenopausal and postmenopausal conditions were analyzed via metagenomic sequencing. Alpha diversity (Observe, ACE, Shannon-Weaver, Gini-Simpson indices) and beta diversity (PCoA, NMDS) were assessed. Taxonomic profiling, LEfSe analysis, and co-occurrence network construction were performed to identify differential species and microbial interactions. Neutral community modeling evaluated stochastic vs. deterministic assembly processes.<br><br>RESULTS: No significant differences were observed in age (62.22&#x2009;&#xb1;&#x2009;5.74 vs. 58.23&#x2009;&#xb1;&#x2009;7.55, p&#x2009;=&#x2009;0.052) or perimenopausal/ postmenopausal status (3/19 vs. 5/18, p&#x2009;=&#x2009;0.748) between the DM and CT groups. The DM group exhibited significantly higher alpha diversity (p&#x2009;<&#x2009;0.05) and distinct beta diversity clustering (p&#x2009;<&#x2009;0.05), marked by reduced Lactobacillus relative abundance (28.7% in CT vs. 6.3% in DM) and increased abundance of opportunistic pathogenic genera (Klebsiella, Gardnerella, Staphylococcus). LEfSe identified Firmicutes as CT biomarkers, while the relative abundance of Bacteroidetes and Prevotella increased in DM group. Both fasting blood glucose and HbA1c levels significantly influenced the relative abundance of vaginal Lactobacillus crispatus, Lactobacillus gasseri, and Lactobacillus iners, showing a significant negative correlation. Co-occurrence networks revealed greater complexity and more integrated in the DM group (more triangles, lower modularity, higher node degrees, higher clustering coefficients, p&#x2009;<&#x2009;0.0001). Neutral modeling indicated stochastic assembly (R&#xb2; >0.5), with Lactobacillus species and opportunistic pathogens deviating from neutral predictions in DM.<br><br>CONCLUSION: Under perimenopausal and postmenopausal conditions, T2DM disrupts vaginal microbiota homeostasis by diminishing protective Lactobacillus populations and promoting pathogen proliferation.}, }
@article {pmid41162426, year = {2025}, author = {Zhao, Y and Yao, S and Umar, A and Huang, J and Chen, S and Yu, Z}, title = {Comprehensive multi omics explore the microbial function in metabolic pathway flow during altered diet.}, journal = {NPJ science of food}, volume = {9}, number = {1}, pages = {212}, pmid = {41162426}, issn = {2396-8370}, support = {82270564//National Natural Science Foundation of China/ ; 32170071//National Natural Science Foundation of China/ ; 2022JJ30916//Natural Science Foundation of Hunan Province/ ; 2022M713521//China Postdoctoral Science Foundation/ ; 2023CXQD059//Central South University Innovation-Driven Research Programme/ ; }, abstract = {High-protein diet (HPD) and high-fiber diet (HFiD) are two common types of diet, and the transition from HPD to HFiD frequently happens in people who perform diet control. Gut microbiota provide a bridge between diet and health. However, most of the research left out the metabolic landscape change and gut microbial influence under this kind of altered diet. Here, we examined gut microbiome and metabolites change using multi-omics (16S rRNA gene sequencing, shotgun metagenomics, LC-MS/MS metabolomics), and machine-learning methods were introduced to capture the response of gut microbiota to altered diet and associate the variable metabolites and microbial factors. The results suggest that the conversion from HPD to HFiD improves the gut microbial diversity and promotes the pathways of tryptophan, galactose, fructose, and mannose metabolism, which are associated with different gut microbiota and special metabolites. Among them, Faecalibacterium rodentium and Akkermansia muciniphila indicate potential roles in the multi-metabolism. Although these findings are exploratory and hypothesis-generating, they provide a foundation for future mechanistic investigations and emphasize the importance of diverse diets.}, }
@article {pmid41162403, year = {2025}, author = {Kowal, M and Sorokowski, P and David, O and Iuga, IA and Renwick, S and Sorokowska, A}, title = {Microbiome and well-being: a meta-analysis.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {201}, pmid = {41162403}, issn = {2055-5008}, support = {PNRR-III-C9-2023-I8-CF 32/28.07.2023//European Union/ ; PNRR-III-C9-2023-I8-CF 32/28.07.2023//European Union/ ; PNRR-III-C9-2023-I8-CF 32/28.07.2023//European Union/ ; PNRR-III-C9-2023-I8-CF 32/28.07.2023//European Union/ ; PNRR-III-C9-2023-I8-CF 32/28.07.2023//European Union/ ; }, mesh = {Humans ; *Microbiota ; Male ; Female ; *Bacteria/classification/genetics/isolation &amp; purification ; *Mental Health ; }, abstract = {The human microbiome may play a significant role in both health and disease. However, most studies to date have focused on the microbiome's role in pathogenesis, while its potential role in promoting well-being remains underexplored. We conducted the first meta-analysis synthesizing empirical evidence on associations between the human microbiome and psychological well-being. Based on eight analyzed studies (N = 2526 participants), we found that both microbial diversity and taxonomic abundance were positively associated with psychological well-being, with diversity emerging as the stronger predictor. Notably, these associations appeared consistent across sex and age. This study provides preliminary evidence that microbiome composition may support salutogenic processes and offers a foundation for future integration of microbiome science into psychological and clinical interventions. However, given the small number of empirical studies included in the meta-analysis, the generalizability of these findings remains limited. Further research is required to strengthen and refine our understanding of the microbiome-well-being relationship.}, }
@article {pmid41162165, year = {2025}, author = {Ghorbanian, F and Seo, H and Sarafraz, F and Atashi, A and Shuvo, MSH and Chae-Eun, P and Hossain, MS and Tajdozian, H and Kim, S and Song, HY and Yang, H}, title = {In Vivo Therapeutic Potential of Next-Generation Probiotic Akkermansia muciniphila and Butyrate Combination Therapy in Diabetes.}, journal = {Journal of microbiology and biotechnology}, volume = {35}, number = {}, pages = {e2506025}, doi = {10.4014/jmb.2506.06025}, pmid = {41162165}, issn = {1738-8872}, mesh = {Animals ; *Probiotics/administration &amp; dosage/therapeutic use ; *Diabetes Mellitus, Experimental/therapy/drug therapy ; Mice ; Rats, Sprague-Dawley ; Mice, Inbred C57BL ; Rats ; Male ; Blood Glucose/drug effects ; Gastrointestinal Microbiome/drug effects ; *Butyrates/therapeutic use/administration &amp; dosage ; *Butyric Acid/therapeutic use/administration &amp; dosage ; Akkermansia ; Streptozocin ; }, abstract = {Recent studies have found that gut microbiota is closely related to the initiation and progression of T1DM. This study aimed to examine the effects of sodium butyrate and Akkermansia muciniphila (AKK), both individually and combined, on T1DM models. To optimize a T1DM model, a single high dose of streptozotocin (STZ) was administered to C57BL/6J mice to determine the appropriate dose (150 mg/kg). Mice were divided into four groups: a control group, a diabetic group, a diabetic group treated with butyrate, and a diabetic group treated with AKK. The groups treated with butyrate and AKK reduced blood glucose levels, prevented body weight loss, and normalized food and water intake. To explore the synergistic effects of AKK and butyric acid, Sprague-Dawley (SD) rats were assigned to control, diabetic, and treatment groups including butyrate, AKK, and combination therapy. Two weeks of oral treatment showed improved metabolic parameters in the treatment groups. The combination therapy exhibited the most improvements. In the in vitro experiment, the cytotoxic effects of STZ on 3T3-L1 cells treated with both AKK and butyric acid were measured, indicating their protective effects on cell viability. GC-MS/MS analysis was also performed to assess changes and correlations in systemic short-chain fatty acids (SCFAs). SCFAs were significantly increased in the liver after probiotic treatment, especially in the combination therapy group. These findings demonstrate the microbiota-regulating and therapeutic effects of AKK and butyrate, particularly highlighting the potential of combination therapy as an alternative to standard diabetic treatments.}, }
@article {pmid41161045, year = {2025}, author = {Reinholm, A and Khan, H and Laakso, T and Maljanen, S and Jalkanen, P and Gunell, M and Kallonen, T and Österlund, P and Ritvos, O and Nousiainen, A and Häkkinen, HK and Pakkanen, SH and Välimaa, H and Kantele, A and Lempainen, J and Julkunen, I and Kolehmainen, P and Kakkola, L}, title = {Long-term neutralization capacity of vaccine and breakthrough infection induced SARS-CoV-2 specific antibodies against omicron subvariants BA.2, XBB.1.5, and JN.1.}, journal = {Vaccine}, volume = {68}, number = {}, pages = {127894}, doi = {10.1016/j.vaccine.2025.127894}, pmid = {41161045}, issn = {1873-2518}, abstract = {The long-term effectiveness of COVID-19 vaccines remains a critical area of study, especially with the emergence of new SARS-CoV-2 subvariants. In this study, we investigated the long-term neutralization capacity of SARS-CoV-2 -specific antibodies induced by the third, fourth and fifth vaccine doses, and by SARS-CoV-2 breakthrough infections. Spike (S)-specific antibodies decline relatively rapidly after each vaccine dose, with an estimated half-life of 3-4 months. However, after the third vaccine dose, S-specific serum antibody levels remained comparable at 12 and 24 months post-vaccination. Antibody levels induced by the fourth and fifth vaccine doses were higher, and the decay was slower than after the third vaccine dose. Additionally, nucleocapsid (N)-specific antibody levels increased significantly following multiple breakthrough infections. The neutralization capacity of the antibodies against Omicron XBB.1.5 and JN.1 subvariants were significantly increased by the fifth, XBB.1.5 subvariant specific, mRNA vaccine dose. Our findings strongly indicate that updated booster vaccines based on the latest s of concern are necessary to sustain high neutralizing antibody levels against emerging variants. No exhaustion of vaccine-induced antibody response was observed after repeated COVID-19 vaccinations.}, }
@article {pmid41159234, year = {2025}, author = {Blanes Hernández, R and de Cossio Tejido, S and Puchades Gimeno, F and García-Bustos, V and Salavert Lletí, M}, title = {Legends, dogmas, presumptions, and demystifications in antibiotic therapy.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {38 Suppl 1}, number = {}, pages = {70-79}, doi = {10.37201/req/s01.11.2025}, pmid = {41159234}, issn = {1988-9518}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use/administration &amp; dosage ; Antimicrobial Stewardship ; Inappropriate Prescribing ; }, abstract = {Suboptimal antimicrobial use is a global challenge driven by entrenched misconceptions and dogmas. This article aims to critically evaluate and debunk several widespread myths in infectious disease management that lead to overdiagnosis and overtreatment. Through a nonsystematic literature review, this manuscript examines key misconceptions across various aspects of antimicrobial therapy, including administration routes, drug mechanisms, treatment duration, and the interplay with infection source control. It also explores the influence of evolving concepts like long-acting antimicrobials and the human microbiome. We challenge the dogmas that intravenous antibiotics are superior to oral agents, that longer courses are always better, and that bactericidal drugs are more effective than bacteriostatic ones. The review highlights the paramount importance of source control and surgical intervention in treating severe infections and cautions against misinformation surrounding the human microbiome. The medical community must critically re-evaluate long-standing clinical practices to improve antibiotic stewardship. By debunking these myths, we can promote a more precise, safe, and effective approach to antimicrobial use, ultimately reducing unnecessary prescribing and combating antimicrobial resistance.}, }
@article {pmid41155245, year = {2025}, author = {Ukraincev, NI and Kashutina, MI and Kasatkina, LI and Abduraimov, AB and Zhernov, YV}, title = {Mammary Gland Microbiota in Benign Breast Diseases.}, journal = {International journal of molecular sciences}, volume = {26}, number = {20}, pages = {}, doi = {10.3390/ijms26209951}, pmid = {41155245}, issn = {1422-0067}, support = {25-18-00901//Russian Science Foundation/ ; }, mesh = {Humans ; Female ; *Microbiota ; *Mammary Glands, Human/microbiology ; *Breast Diseases/microbiology ; Dysbiosis/microbiology ; Mastitis/microbiology ; Breast Neoplasms/microbiology ; }, abstract = {The human microbiome is a critical factor in health and disease. While its association with breast cancer (BC) has been increasingly studied, this review provides a dedicated synthesis of the microbiota's role in benign breast diseases (BBDs)-a common yet microbiologically overlooked spectrum of conditions. The primary aim of this work is to consolidate the current understanding of the composition, origins, and functional mechanisms of the mammary gland (MG) microbiota specifically in the context of BBD and to evaluate its potential for novel diagnostic and therapeutic targets. We detail the distinct MG microbiota, formed via exogenous (e.g., cutaneous, translocation) and endogenous (e.g., enteromammary, lymphohematogenous) pathways, and its interaction with the host through estrogen metabolism, immunomodulation, and epigenetic modifications. This narrative review reveals unique dysbiotic patterns in BBD, characterized by distinct microbial signatures, such as the enrichment of Corynebacterium kroppenstedtii in granulomatous mastitis and the presence of Staphylococcus aureus in fibroadenomas and lactational mastitis. Furthermore, specific gut microbial profiles are identified in BBD patients, including an increased abundance of genera such as Clostridium and Faecalibacterium, alongside a decrease in Collinsella and Alistipes compared to healthy controls. These specific taxa represent compelling candidates for diagnostic biomarkers. We conclude that microbial dysbiosis is a significant component of BBD pathogenesis. A paradigm shift toward multi-omics approaches and mechanistic studies is now essential to translate these associations into clinical applications. Understanding the BBD-specific microbiome holds the promise of revolutionizing patient care through microbiota-based diagnostics for differentiating benign subtypes and novel, personalized therapeutic strategies aimed at restoring microbial homeostasis.}, }
@article {pmid41155038, year = {2025}, author = {Yang, T and Dai, M and Zhang, F and Wen, W}, title = {Integrative Bioinformatics-Guided Analysis of Glomerular Transcriptome Implicates Potential Therapeutic Targets and Pathogenesis Mechanisms in IgA Nephropathy.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {12}, number = {10}, pages = {}, doi = {10.3390/bioengineering12101040}, pmid = {41155038}, issn = {2306-5354}, support = {82304144//National Natural Science Foundation of China/ ; 32372334//National Natural Science Foundation of China/ ; }, abstract = {(1) Background: IgA nephropathy (IgAN) is a leading cause of chronic kidney disease worldwide. Despite its prevalence, the molecular mechanisms of IgAN remain poorly understood, partly due to limited research scale. Identifying key genes involved in IgAN's pathogenesis is critical for novel diagnostic and therapeutic strategies. (2) Methods: We identified differentially expressed genes (DEGs) by analyzing public datasets from the Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to elucidate the biological roles of DEGs. Hub genes were screened using weighted gene co-expression network analysis combined with machine learning algorithms. Immune infiltration analysis was conducted to explore associations between hub genes and immune cell profiles. The hub genes were validated using receiver operating characteristic curves and area under the curve. (3) Results: We identified 165 DEGs associated with IgAN and revealed pathways such as IL-17 signaling and complement and coagulation cascades, and biological processes including response to xenobiotic stimuli. Four hub genes were screened: three downregulated (FOSB, SLC19A2, PER1) and one upregulated (SOX17). The AUC values for identifying IgAN in the training and testing set ranged from 0.956 to 0.995. Immune infiltration analysis indicated that hub gene expression correlated with immune cell abundance, suggesting their involvement in IgAN's immune pathogenesis. (4) Conclusion: This study identifies FOSB, SLC19A2, PER1, and SOX17 as novel hub genes with high diagnostic accuracy for IgAN. These genes, linked to immune-related pathways such as IL-17 signaling and complement activation, offer promising targets for diagnostic development and therapeutic intervention, enhancing our understanding of IgAN's molecular and immune mechanisms.}, }
@article {pmid41153658, year = {2025}, author = {Dubli, K and Balasundaram, P and Chaudhari, R and Vettrivelan, S and Borawake, A and Kapoor, R and Kovalchuk, I and Kapoor, A and Singh, R and Tripathi, MB}, title = {Exploring the Impact of Skin Care Routines on the Skin Microbiome and Possible Skin Disease Risk-A Pilot Study.}, journal = {Biomedicines}, volume = {13}, number = {10}, pages = {}, doi = {10.3390/biomedicines13102371}, pmid = {41153658}, issn = {2227-9059}, support = {IT33301//Mitacs/ ; }, abstract = {Background/Objectives: Unceasing exposure of skin and its microbiome to various external and internal factors influences its health. Any imbalance ensuing may result in dysbiosis and consequently skin diseases. Thus, it becomes critical to identify and recognize the influence of several factors on the skin microbiome and various disorders associated with it. Methods: In the current investigation, we studied the skin microbiomes of 37 subjects using the next-generation shotgun sequencing method and compared them with 48 healthy subjects from the Human Microbiome Project (HMP). This work focused on the analysis of the impact of different skin care routines-use of sunscreen and moisturizers-on the skin microbiome and related skin diseases. Results: Differences were observed between the microbiomes of subjects who were using only moisturizer (p = 3.1 × 10[-5]) or moisturizer with sunscreen (p = 3.2 × 10[-13]) and those who did not use these products at all. We also observed differences in the skin microbiomes of males vs. females with respect to the use of moisturizer. The composition of the skin microbiomes of female participants showed a higher difference in diversity in comparison to males. The current investigation also found that usage of sunscreen might help in retaining skin-protecting species in the skin microbiome. Conclusions: This work allowed us to understand the impact of moisturizer and sunscreen on skin health. The present evaluation shall pave the way for personalized skin care product development.}, }
@article {pmid41151427, year = {2025}, author = {Hernández-Villamor, D and Jeaidi, A and Boydens, R and Rabaey, K and Van de Wiele, T and Prévoteau, A}, title = {Mediated electron transfer in five prevalent human oral microbial species.}, journal = {Bioelectrochemistry (Amsterdam, Netherlands)}, volume = {168}, number = {}, pages = {109149}, doi = {10.1016/j.bioelechem.2025.109149}, pmid = {41151427}, issn = {1878-562X}, abstract = {An increasing number of microbial species within the human body, many of which are pathogenic, are being reported as "electroactive". However, the mechanisms and kinetics of extracellular electron transfer (EET) and its putative ecological relevance remain understudied. We utilized rotating disk electrodes (RDEs) to assess mediated electron transfer (MET) in five oral species via their ability to reduce riboflavin and ferricyanide. The use of both mediators was confirmed in Streptococcus mutans, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, while A. viscosus only reduced riboflavin. Kinetics of EET (turnover rate per cell) were slow with riboflavin (kcat, RF< 10[4] s[-1]) in all species but F. nucleatum, whereas ferricyanide resulted in fast kinetics (kcat, Ferri(app)> 10[4] s[-1]) in all but S. mutans. Due to its central role in oral biofilms and association to systemic diseases, MET was further characterized in F. nucleatum. Apparent Michaelis-Menten kinetics showed Km values of (0.57 ± 0.16 and 10.43 ± 0.91) μM for ferricyanide and riboflavin. The presence of mediators enhanced acetate production compared to mediator-free controls; when ferricyanide was used, butyrate and formate production was triggered only after its depletion. Finally, the putative molecular mechanisms enabling MET in F. nucleatum are discussed.}, }
@article {pmid41148698, year = {2025}, author = {Appel, A and Velazco, L and Alreja, AB and LeClair, K and Duggal, AP and Vashee, I and Taal, AM and Gonzalez-Juarbe, N and Fouts, DE}, title = {In Silico Identification and Molecular Characterization of Lentilactobacillus hilgardii Antimicrobial Peptides with Activity Against Carbapenem-Resistant Acinetobacter baumannii.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, doi = {10.3390/antibiotics14101004}, pmid = {41148698}, issn = {2079-6382}, support = {U54CK000603/CC/CDC HHS/United States ; }, abstract = {BACKGROUND/OBJECTIVES: Biofilm formation by Acinetobacter baumannii contributes to its persistence in clinical settings and resistance to antibiotic treatment. This study aims to identify and characterize antimicrobials from lactic acid bacteria (LAB) using molecular and in silico approaches that can prevent and disrupt A. baumannii biofilms, assess their antimicrobial host range, and define their synergy with current antibiotics.<br><br>METHODS: Thirteen LAB isolates from the Human Microbiome Project were screened for anti-biofilm activity against A. baumannii. Conditioned media was further tested against six ESKAPE pathogens and three skin commensals. Lentilactobacillus hilgardii was selected for detailed study and antimicrobial peptide (AMP) prediction analysis due to limited toxicity toward commensals. In silico identified peptides were synthesized and tested individually and in combination with sub-MIC doses of an antibiotic.<br><br>RESULTS: Conditioned media from five LAB species (Lentilactobacillus hilgardii, Lentilactobacillus buchneri, Ligilactobacillus ruminis, Limosilactobacillus fermentum, and Limosilactobacillus antri) significantly inhibited A. baumannii biofilm formation and reduced biomass of mature biofilms. LAB-conditioned media also exhibited broad-spectrum activity against ESKAPE pathogens, though effects on commensals varied. Bioinformatically predicted AMPs from L. hilgardii inhibited planktonic A. baumannii growth but showed no direct biofilm activity even at high doses. However, AMPs were found to synergize with sub-MIC doses of meropenem against mature biofilms leading to decolonization.<br><br>CONCLUSIONS: Our study provides a comprehensive platform for the discovery and characterization of AMPs and supports using commensal bacteria to reduce, prevent, and decolonize biofilms from pathogenic bacteria in community and nosocomial settings.}, }
@article {pmid41147308, year = {2025}, author = {Scaglioni, M}, title = {Negotiated Categories: The Co-Construction of the Tunisian Population in Human Microbiome Science and Its Historical Entanglements.}, journal = {Medical anthropology}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/01459740.2025.2581072}, pmid = {41147308}, issn = {1545-5882}, abstract = {The analysis of the intersection between race and microbiome science is a growing area in the social sciences, but little scholarly attention has been given to how population categories, that often have a racial subtext when applied to the Global South, are constructed, or how they intersect with or diverge from local conceptions of race. Drawing on research on an EU-funded human microbiome project involving Italian and Tunisian researchers, I argue that population categories in microbiome research are not merely imposed, but are continuously negotiated and co-constructed with local, homegrown racial categories.}, }
@article {pmid41146567, year = {2025}, author = {Bhowmik, B and Hossain, MN and Afrin, S and Jui, AH and Naumovski, N}, title = {Heavy metal detoxification of gut environment: potential application of probiotic supplementation and challenges.}, journal = {Journal of the science of food and agriculture}, volume = {}, number = {}, pages = {}, doi = {10.1002/jsfa.70280}, pmid = {41146567}, issn = {1097-0010}, abstract = {The human microbiome is a diverse group of microbes that regulates the host's environment and health. Probiotic microorganisms improve gastrointestinal microbial balance. However, frequent exposure to heavy metals (HMs) such as arsenic, lead, cadmium, chromium and mercury can disrupt the delicate balance gut microbiota, altering its composition. Exopolysaccharide (EPS) from probiotics can effectively reduce HM toxicity and mobility in the environment, potentially enhancing the gut microbiota's ability to regulate the host's environment. The current paper discusses the role of probiotic supplementation on HM biosorption to build awareness about the health effects of HMs on human metabolism and raises concerns about their sources, distribution and the potential effects on human gut health. HM toxicity occurs through reactive oxygen species which can cause damage to cellular components such as DNA, proteins and lipids. This oxidative damage can lead to various health issues, including neurodegenerative diseases, cardiovascular problems and impaired immune function. EPS biopolymers have shown promising results in the removal of HMs from contaminated environments through binding with metal ions, preventing their harmful effects on living organisms. Thus, EPS biopolymers have been found to enhance the growth and activity of probiotic microorganisms, further aiding in the bioremediation process. Vigorous research is needed to understand the underlying mechanism and cell surface morphology of bacteria for better sorption and removal of HMs. © 2025 Society of Chemical Industry.}, }
@article {pmid41144790, year = {2025}, author = {Luo, H and Bai, D and Zhu, Z and Yousuf, S and Yang, H and Xun, J and Zeng, M and Wang, Y and Gao, Y and Peng, K and Xu, S and Zhou, Y and Zhang, T and Ma, C and Hou, H and Wan, X and Zhou, Y and Jia, B and Huang, S and Gan, R and Wen, T and Chen, T and Chen, X and Li, X and Liu, YX}, title = {EasyAmplicon 2: Expanding PacBio and Nanopore Long Amplicon Sequencing Analysis Pipeline for Microbiome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e12447}, doi = {10.1002/advs.202512447}, pmid = {41144790}, issn = {2198-3844}, support = {32522001//Natural Science Foundation of China/ ; 32470055//Natural Science Foundation of China/ ; CAAS-BRC-CB-2025-01//Agricultural Science and Technology Innovation Program/ ; }, abstract = {In the past decade, third-generation sequencing technologies (such as PacBio (Pacific Biosciences) and Nanopore) have become gradually matured and are widely used for microbial taxonomy and quantification. Compared with Illumina sequencing, PacBio or Nanopore has advantages with long reads and high resolution in taxonomic classification. However, there is currently a lack of an easy-to-use, reproducible, and community-supported pipeline for PacBio or Nanopore amplicon sequencing data analysis. To address this shortcoming, the highly cited EasyAmplicon is updated to version 2, a pipeline fully supporting third-generation full-length amplicon data. EasyAmplicon 2 is a user-friendly pipeline that embraces data analysis and visualization options for data obtained from various sequencing technologies (Illumina, BGI (Beijing Genomics Institution), PacBio, Nanopore or Qitan). It integrates popular tools such as DADA2 and Emu, and provides a workflow from raw data to publication-ready visualizations. EasyAmplicon 2 inherits the advantages of the previous version and further optimizes the visualization part. The updated version of the pipeline includes data preprocessing, annotation, and quantification of amplicon sequence variants, intergroup comparison, and visualization for third-generation sequencing. EasyAmplicon 2 provides a simple and easy-to-use analysis environment for long-read amplicon sequencing data analysis. It is available for free on GitHub (https://github.com/YongxinLiu/EasyAmplicon).}, }
@article {pmid41136898, year = {2025}, author = {Junier, T and Palmieri, F and Ubags, ND and Trompette, A and Koutsokera, A and Junier, P and Pagni, M and Neuenschwander, S}, title = {Prevalence of oxalotrophy in the human microbiome.}, journal = {BMC genomics}, volume = {26}, number = {1}, pages = {954}, pmid = {41136898}, issn = {1471-2164}, support = {40B2-0_194701//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; GRS-064/18//Gebert R&#xfc;f Stiftung/ ; }, abstract = {BACKGROUND: Incomplete degradation of oxalate, a compound commonly found in the diet, can lead to disease in humans, particularly affecting the kidneys. The concentration of oxalate in the body depends on several factors, one of which is intestinal absorption-an aspect influenced by oxalotrophy among enteric bacteria. Despite its potential significance, oxalotrophy in the human microbiome remains poorly understood.<br><br>RESULTS: In this study, we conducted a systematic search for the co-occurrence of three key oxalotrophy genes-frc, oxc, and oxlT. We developed and validated specific conservation models for each gene and applied them to genomes and metagenomes associated with the human digestive tract, oral cavity, and lungs. Our analysis revealed that oxalotrophy, defined as the capacity to use oxalate as an energy source, is a rare metabolic trait predominantly confined to the gut. We also found evidence that this capacity can be acquired via horizontal gene transfer.<br><br>CONCLUSIONS: While oxalotrophy is relatively uncommon, the broader capacity for oxalate degradation is more widespread. Notably, the genes frc and oxc are frequently found in close proximity within genomes, suggesting a selective advantage for organisms possessing this capability. Incomplete degradation of oxalate, a compound commonly found in the diet, can cause disease in humans, particularly affecting the kidney. Its concentration in the body depends on several factors, one of which is intestinal absorption, which is itself affected by oxalotrophy among enteric bacteria. Oxalotrophy in the human microbiome is poorly known. In this study, we perform a systematic search for the simultaneous presence of the three oxalotrophy genes, namely frc, oxc and oxlT. Thanks to the construction and validation of specific conservation models for all three genes, we were able to search for oxalotrophy in genomes and metagenomes associated with the human digestive tract, oral cavity, and lungs. We report that oxalotrophy-the capacity to use oxalate as an energy source-is a rare metabolic trait, mostly confined to the gut, and also find evidence that it can be acquired by horizontal gene transfer. By contrast, the capacity for oxalate degradation is more widespread, and two genes responsible for it (frc and oxc) are almost always close together in the genome, suggesting selection pressure.}, }
@article {pmid41136386, year = {2025}, author = {Rodríguez-Daza, MC and Boeren, S and Tytgat, HLP and Desjardins, Y and de Vos, WM}, title = {Akkermansia muciniphila Muc[T] harnesses dietary polyphenols as xenosiderophores for enhanced iron uptake.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {9428}, pmid = {41136386}, issn = {2041-1723}, support = {Grant 024.002.002//Stiftelsen Siamon/ ; }, mesh = {*Iron/metabolism ; *Polyphenols/metabolism/pharmacology ; *Siderophores/metabolism ; *Akkermansia/metabolism/genetics ; Gastrointestinal Microbiome/drug effects ; *Verrucomicrobia/metabolism/genetics ; Proteomics ; Zinc/metabolism ; ATP-Binding Cassette Transporters/metabolism ; }, abstract = {Dietary proanthocyanidins (PACs) are polyphenols that promote a healthy gut microbiome. PACs are notable for their rich catechol moieties with high affinity for iron, enabling them to interfere with pathogens' iron uptake. PACs selectively increase the abundance of Akkermansia muciniphila, a symbiont known for supporting metabolic and immune health. We discovered that A. muciniphila Muc[T] utilizes distinct iron-acquisition systems to take up iron sequestered by PACs, supporting its metabolic activity. Integrative proteomics and transcriptomics revealed that A. muciniphila has an active catechol-type siderophore-mediated iron uptake (Fe[3+]) system, involving membrane ATP-binding cassette transporters and lipocalins. Simultaneously, the expression of ferrous iron (Fe[2+]) transporters, zinc uptake, and iron storage proteins was upregulated. Administering iron-laden PACs in an iron-depleted medium restored the A. muciniphila growth to levels comparable to those in iron-amended conditions. This was associated with an increased expression of the A. muciniphila siderophore operon and lipocalin genes, indicating that iron-laden PACs are recognized as xenosiderophores to cope with iron depletion. Hence, we identified novel signaling mechanisms for iron acquisition and siderophore uptake regulation in A. muciniphila Muc[T] upon exposure to PACs, enhancing our understanding of the role of dietary PACs in selectively promoting this gut symbiont and potentially outcompeting pathogenic bacteria.}, }
@article {pmid41135513, year = {2025}, author = {Zhang, F and Zhou, G and Schewe, M and Kulling, SE and Ding, Y and Mozaffarian, D and Zuo, T}, title = {Dietary urbanization destabilizes host-gut microbiome homeostasis and informs precision nutrition for human health.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2025.09.013}, pmid = {41135513}, issn = {1932-7420}, abstract = {Since the industrial revolution, human dietary habits have invariably trended toward dietary urbanization, during which the human gut microbiota has rapidly changed. However, the human genome cannot change substantially over one generation, leaving it potentially ill-equipped to adapt to evolving microbial functions associated with rising non-communicable diseases (NCDs). In this review, we map the chronological alterations in dietary patterns and incidences of NCDs during global urbanization while emphasizing the gut microbiome as the centerpiece. We then illustrate losses and acquisitions of gut microbes during worldwide urbanization and delineate the mechanisms by which urbanized diets may disrupt host-microbiome interactions, linking to the onset of NCDs. Building on this, we further propose a microbiome-directed precision-nutrition framework that integrates both inter-population and intra-population variations to promote diet-fueled host-microbiome synergism and hence to counteract urbanization-associated diseases. These insights will instruct future microbiome-targeted diets to thwart NCDs.}, }
@article {pmid41121269, year = {2025}, author = {Haque, S and Bantun, F and Jalal, NA and Faidah, H and Babalghith, AO and Alobaidy, MA and Aldairi, AF and Ahmad, F}, title = {Gut microbiota alterations and their association with tumorigenic pathways in colorectal cancer: insights from a pooled analysis of 109 microbiome datasets.}, journal = {Gut pathogens}, volume = {17}, number = {1}, pages = {82}, pmid = {41121269}, issn = {1757-4749}, abstract = {BACKGROUND: Colorectal cancer (CRC) is a significant global health burden, ranking amongst the top causes of cancer-associated mortality. Emerging evidences implicate gut microbiota as a prominent mediator of cell signalling, immune, and metabolic pathways in the pathophysiology of CRC.<br><br>METHODS: We analysed 16S rRNA amplicon sequencing data (PRJEB7774) from faecal samples of 46 CRC patients and 63 healthy controls to assess shifts in microbial composition, diversity, and biomarker taxa. Differential abundances of microbiota were determined using Linear Discriminant Analysis Effect Size (LEfSe) and Random Forest (RF) models. Host-microbiota interactions were explored using the Human Microbiome Affect the Host Epigenome (MIAOME) and Host Genetic and Immune Factors Shaping Human Microbiota (GIMICA) databases, with key host genes validated using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) datasets. Functional enrichment analyses were performed to uncover associated biological processes and pathways.<br><br>RESULTS: CRC samples exhibited significantly reduced alpha diversity and distinct beta diversity profiles, compared to controls. Taxonomic profiling revealed an enrichment of potentially pathogenic bacteria, including Prevotella copri, Methanobrevibacter smithii, Bacteroides eggerthii, and Dialister invisus, and depletion of beneficial microbes such as Bifidobacterium animalis and Ruminococcus sp. Predicted host-microbe interactions highlighted associations between key microbial biomarkers and inflammation-related genes (CD44, CXCL8, DUSP16, FOXP3, IFNGR2, IL18), all significantly overexpressed in CRC samples. Enrichment analyses linked these genes to immune pathways, including NF-&#x3ba;B, TLR and cytokine signalling.<br><br>CONCLUSIONS: Our study reveals a distinct gut microbiota signature in CRC and suggests functional interactions between microbial dysbiosis and host inflammatory responses. These findings emphasize the potential of microbiota-based interventions and microbial metabolites as adjunctive strategies for the management of CRC.}, }
@article {pmid41120038, year = {2025}, author = {Kajova, M and Khawaja, T and Kainulainen, K and Kantele, A}, title = {Travel-Associated Carbapenemase-Producing Enterobacterales: Epidemiology and Risk Factors in a Finnish Cohort.}, journal = {Travel medicine and infectious disease}, volume = {}, number = {}, pages = {102926}, doi = {10.1016/j.tmaid.2025.102926}, pmid = {41120038}, issn = {1873-0442}, abstract = {BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are increasing worldwide and are associated with difficult-to-treat infections. We previously reported that international travel is a major source of CPE acquisition in the Helsinki region, Finland. To clarify the extent of importation, we investigated the epidemiology and associated risk factors of foreign-acquired CPEs.<br><br>METHODS: We revisited two earlier cohorts. Cohort A (n=187 after a one-year extension) comprised patients from 2010 through 2024 presumed to have acquired CPE abroad; CPE types were categorized by travel region. Cohort B included 3,029 patients screened for CPE from 2010 through 2019 within 12 months after hospitalization abroad. Multivariable analysis identified factors that predispose to colonization.<br><br>RESULTS: Among patients hospitalized abroad (Cohort B), CPE rates were particularly high for South Asia (14.6%) and North Africa (13.7%). Across the 24 individual countries with data, the highest CPE colonization risks were observed for Egypt (20.8%) and India (16.4%). In addition to destination, independent risk factors included antibiotic use, travel type, short interval between discharge from a foreign hospital and screening (within one week or one month) and male sex. For South/Southeast Asia and sub-Saharan Africa, over 70% of CPE carriers (Cohort A) had metallo-&#x3b2;-lactamase-producing Enterobacterales, predominantly NDM, whereas OXA-48-like enzymes predominated in North Africa and the Middle East.<br><br>CONCLUSIONS: Hospitalization in high-prevalence countries and antibiotic use emerged as key risk factors for CPE acquisition. Regional variation was evident: OXA-48-like enzymes dominated among CPEs linked to the Middle East and North Africa, whereas NDM was prevalent elsewhere in Eurasia and Africa.}, }
@article {pmid41118314, year = {2025}, author = {Yue, X and Wang, H and Xu, YN and Chu, CC and Chen, L}, title = {Microbiome network: a robust biomarker of skin health.}, journal = {The British journal of dermatology}, volume = {193}, number = {Supplement_2}, pages = {ii1-ii5}, doi = {10.1093/bjd/ljaf230}, pmid = {41118314}, issn = {1365-2133}, support = {T2341007//Natural Science Foundation of China/ ; T2350003//Natural Science Foundation of China/ ; 12131020//Natural Science Foundation of China/ ; 42450084//Natural Science Foundation of China/ ; 42450135//Natural Science Foundation of China/ ; 12326614//Natural Science Foundation of China/ ; 12426310//Natural Science Foundation of China/ ; 23JS1401300//Science and Technology Commission of Shanghai Municipality/ ; 2025C01114//Science and Technology Commission of Shanghai Municipality/ ; //Institute for advanced study/ ; 2024HIAS-P004//UCAS/ ; //Unilever/ ; }, mesh = {Humans ; *Microbiota/physiology ; *Skin/microbiology ; Biomarkers/metabolism ; *Skin Diseases/microbiology ; Host Microbial Interactions/physiology ; }, abstract = {The skin microbiome is an integral part of the skin barrier. Its activity is shaped by microbe-microbe and microbe-host interactions. Understanding such interactions is an evolving field essential for uncovering the ecology and functions of a human microbiome community. Various studies have adapted network theory to explore the relationships of the microbiome community and its functional importance in health and diseases. The microbiome network is described as a biomarker depicting the interaction or correlation between two species, rather than their concentrations or abundances as in traditional molecular biomarkers. In skin diseases, the collapse of microbial community network structure has been reported in patients with atopic dermatitis, vitiligo and seborrhoeic dermatitis. More recently, we have reported that a fragile skin microbiome network is becoming a marker consistently observed across skin conditions, such as acne, in preclinical concerns like dry skin and premature ageing, as well as in pollution-compromised skin. In this review, we describe how advanced microbiome networks are constructed to reveal hidden microbiome features based on the nature of polymicrobial interaction from a systems perspective. We discuss the skin microbiome network as a robust network biomarker by capturing skin-microbiome interactions, specifically in conditions where a differential abundance of microbial species is absent, and further as a dynamic network biomarker by capturing skin microbiome dynamics.}, }
@article {pmid41112578, year = {2025}, author = {Chen, J and Xu, Q and Zhang, L and Zhang, D and Wu, X}, title = {Enrichment of prevotella melaninogenica in the lower respiratory tract links to checkpoint inhibitor pneumonitis and radiation pneumonitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1594460}, pmid = {41112578}, issn = {2235-2988}, mesh = {Humans ; Male ; Female ; Middle Aged ; Aged ; Bronchoalveolar Lavage Fluid/microbiology ; *Radiation Pneumonitis/microbiology ; *Prevotella/isolation &amp; purification/genetics/classification ; Microbiota ; Lung Neoplasms/drug therapy ; *Immune Checkpoint Inhibitors/adverse effects ; High-Throughput Nucleotide Sequencing ; Metagenomics ; *Pneumonia/microbiology ; Lung/microbiology ; }, abstract = {BACKGROUND: Checkpoint inhibitor pneumonitis (CIP) and radiation pneumonitis (RP) lead to anti-cancer therapy discontinuation and poor diagnosis. The human microbiome is related to various respiratory diseases. However, the role of the lung microbiome in CIP and RP remains unknown. Our study aimed to explore the lower respiratory tract (LRT) microbiome in CIP/RP patients.<br><br>METHODS: The study enrolled 61 patients with pneumonitis or pneumonia, including 23 with CIP/RP, and 38 with lung cancer with pneumonia (LC-P). Metagenomic next-generation sequencing (mNGS) was performed to identify the microbiota in bronchoalveolar lavage fluid (BALF), and bioinformatics methods were used to compare the microbial differences between CIP/RP and LC-P groups. Correlation analysis was conducted to explore the relationship between LRT microbiota and clinical features.<br><br>RESULTS: The Prevotella was the dominant genus in both groups. The Prevotella melaninogenica, which belongs to the Prevotella genus, was the dominant species in the CIP/RP group and the second most abundant species in the LC-P group. Compared to the LC-P group, the CIP/RP group had significantly high levels of Prevotella melaninogenica species and lymphocyte percentage in BALF but significantly low levels of lymphocytes, eosinophils and albumin in peripheral blood. In addition, the Prevotella melaninogenica species had a negative correlation with peripheral blood lymphocytes.<br><br>CONCLUSION: The enrichment of Prevotella melaninogenica species in LRT and a decreased level of peripheral blood lymphocytes are associated with CIP/RP.}, }
@article {pmid41112283, year = {2025}, author = {Pei, X and Yu, M and Wang, Y and Zong, S and Qi, F and Wang, K}, title = {What is the relationship between microorganisms in the human body and upper tract urothelial carcinoma?.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1636782}, pmid = {41112283}, issn = {1664-3224}, mesh = {Humans ; *Microbiota/immunology ; *Urologic Neoplasms/microbiology ; Tumor Microenvironment/immunology ; *Carcinoma, Transitional Cell/microbiology ; }, abstract = {Upper Tract Urothelial Carcinoma (UTUC) is a highly malignant tumor originating from the epithelium of the upper urinary tract with diverse pathogenesis, but currently available diagnostic and therapeutic strategies have some limitations. In recent years, human microbiome-related studies have provided new ideas for the exploration of the pathogenesis and treatment of UTUC. In this paper, we review the research progress of human microbiome related to UTUC. Focusing on the urinary microbiome, the role of the microbiome in the pathogenesis of UTUC is investigated through the mechanisms of chronic inflammation, genotoxic damage, immune microenvironmental imbalance and metabolic reprogramming. The pyelo-ureteric microbiome of healthy populations is dominated by commensal bacteria such as Lactobacillus and Streptococcus, whereas pathogenic bacteria such as Escherichia coli (E. coli) and Enterococcus faecalis are significantly enriched in patients with UTUC, which results in the development of DNA damage, inflammatory response and immunosuppression. In addition, microbiome metabolites (e.g., short-chain fatty acids, tryptophan derivatives) can influence tumor progression by modulating immune checkpoints (e.g., PD-1/PD-L1, B7-H4) and metabolic pathways (e.g., Warburg effect). In diagnostic and therapeutic applications, urinary microbial markers (e.g., E. coli-specific gene clusters) can be combined with circulating tumor DNA (ctDNA) assays to improve diagnostic sensitivity and specificity, and indices of intestinal flora diversity (e.g., Simpson's index) are significantly correlated with the response rate to chemotherapy and prognostic course. In the future, we need to overcome the challenges of difficult sample acquisition, unknown causal mechanisms, and etiologic heterogeneity interference, and promote multi-omics joint modeling as well as cross-ethnicity and geographic research, and bidirectional regulation mechanisms of the gut-kidney axis in order to develop more accurate UTUC diagnosis and treatment strategies.}, }
@article {pmid41112053, year = {2025}, author = {Li, P and Xie, L and Zheng, H and Feng, Y and Mai, F and Tang, W and Wang, J and Lan, Z and Lv, S and Jayawardana, T and Koentgen, S and Xu, S and Wan, Z and Chen, Y and Xu, H and Shen, S and Zhang, F and Yang, Y and Hold, G and He, F and El-Omar, EM and Yu, G and Chen, X}, title = {Gut microbial-derived 3,4-dihydroxyphenylacetic acid ameliorates reproductive phenotype of polycystic ovary syndrome.}, journal = {iMeta}, volume = {4}, number = {5}, pages = {e70065}, pmid = {41112053}, issn = {2770-596X}, abstract = {Polycystic ovary syndrome (PCOS) is a prevalent endocrine and reproductive disorder affecting women of reproductive age. While the gut microbiota has been implicated in PCOS pathophysiology, the role of microbial-derived metabolites as mediators of host-microbe interactions remains poorly defined. Here, we integrated untargeted gut metabolomics with metagenomic profiling in patients with PCOS and identified a marked depletion of 3,4-dihydroxyphenylacetic acid (DHPAA), a flavonoid-derived microbial catabolite. Oral administration of DHPAA ameliorated PCOS-like phenotypes in two mouse models by suppressing bone morphogenetic protein signaling and reducing anti-Müllerian hormone (AMH) levels. We found that DHPAA production depends on gut microbial degradation of dietary flavonoids. We further identified a bacterial species, Streptococcus thermophilus, consistently depleted in PCOS across two human cohorts and a mouse model, restored DHPAA levels and improved reproductive outcomes in mice. Conversely, a β-galactosidase-deficient mutant of S. thermophilus failed to confer these benefits, highlighting β-galactosidase as a critical enzyme in DHPAA biosynthesis. Our findings establish DHPAA as a key microbial metabolite linking diet, microbiota, and reproductive health, and propose its potential as a novel therapeutic candidate for PCOS.}, }
@article {pmid41112042, year = {2025}, author = {Lin, A and Xiong, M and Jiang, A and Huang, L and Wong, HZH and Feng, S and Zhang, C and Li, Y and Chen, L and Chi, H and Zhang, P and Ye, B and Zhang, H and Zhang, N and Zhu, L and Mou, W and Shen, J and Li, K and Xu, W and Ying, H and Zhang, C and Zeng, D and Xie, J and Deng, X and Wang, Q and Xu, J and Shi, W and Qi, C and Qu, C and Huang, X and Hajdu, A and Li, C and Peng, C and Cao, X and Pei, G and Zhang, L and Huo, Y and Xu, J and Glaviano, A and Szöllősi, AG and Bian, S and Li, Z and Tang, H and Tang, B and Liu, Z and Zhang, J and Miao, K and Cheng, Q and Wei, T and Yuan, S and Luo, P}, title = {The microbiome in cancer.}, journal = {iMeta}, volume = {4}, number = {5}, pages = {e70070}, pmid = {41112042}, issn = {2770-596X}, abstract = {The human microbiome is now recognized as a central regulator of cancer biology, intricately shaping tumor development, immune dynamics, and therapeutic response. This comprehensive review delineates the multifaceted roles of bacteria, viruses, and fungi in modulating the tumor microenvironment and systemic immunity across diverse cancer types. We synthesize current evidence on how microbial dysbiosis promotes carcinogenesis via chronic inflammation, metabolic reprogramming, genotoxic stress, immune evasion, and epigenetic remodeling. This review emphasizes organ-specific microbiome signatures and highlights their potential as non-invasive biomarkers for early detection, treatment stratification, and prognosis. Furthermore, we explore the impact of intratumoral microbiota on cancer therapies, uncovering how microbial metabolites and host-microbe interactions shape therapeutic efficacy and resistance. Finally, advances in microbiome-targeted strategies, such as probiotics, fecal microbiota transplantation, and engineered microbes offer new avenues for adjunctive cancer therapy. This review provides a roadmap for future investigation and underscores the transformative promise of microbiome modulation in cancer prevention and treatment.}, }
@article {pmid41110780, year = {2025}, author = {Sreekutti, S and Ndomondo, S and Sharma, P and Patel, R and Mevada, V}, title = {Forensic application of metagenomics: Methods and future directions.}, journal = {Journal of microbiological methods}, volume = {}, number = {}, pages = {107300}, doi = {10.1016/j.mimet.2025.107300}, pmid = {41110780}, issn = {1872-8359}, abstract = {The microbial communities are found commonly in our environment, making it impossible to touch any surface without interfering with them. The human microbiome, primarily bacteria in the saliva, skin, and gut, can be used for forensic purposes. Human-associated and environmental samples, such as soil, water, etc., carry the microbiome, which can be used for geolocation inference. These microbiomes have considerable potential for use in forensic investigations, including many instances of sexual violence, post-mortem examinations, individual identification, and location identification. Recent developments in metagenomic sequencing have greatly contributed to microbial analysis. Yet, because of certain issues and challenges, the forensic application of microbiomes is still in its infancy. This article reviewed the use of metagenomics in forensic science and some of the main obstacles that are faced by experts in this area. The first and foremost issues noted were the lack of standardization protocols and a poor reference database for research studies. Some limitations, such as storage sensitivity and limited samples, are also indicated. Future research studies should concentrate on more standardized investigations to overcome these difficulties and explore the enormous potential of microbiomes for beneficial applications in forensic contexts.}, }
@article {pmid41106731, year = {2025}, author = {Kamath, S and Ariaee, A and Abdelhafez, A and Asif, Z and Chan, NSL and Collins, K and Hunter, A and Joyce, P}, title = {Microbiome-active drug delivery systems (MADDS): Leveraging microbial stimuli for controlled drug release.}, journal = {Advanced drug delivery reviews}, volume = {}, number = {}, pages = {115720}, doi = {10.1016/j.addr.2025.115720}, pmid = {41106731}, issn = {1872-8294}, abstract = {The human microbiome comprises diverse microbial communities that inhabit tissues and biofluids throughout the body, including the gastrointestinal tract, lungs, vagina, and skin. These sites create dynamic microenvironments rich in enzymes, metabolites, and chemical gradients that act both as biological barriers and as localised targets for drug delivery. This review provides an overview of Microbiome-Active Drug Delivery Systems (MADDS), an emerging class of platforms that exploit microbial stimuli for site-specific therapeutic release. Unlike conventional systems that simply coexist with the microbiome, MADDS harness resident microbes and their metabolites to trigger drug activation, retention, or release. This enables spatially precise delivery of small molecules, biologics, and live biotherapeutic products (LBPs). Key strategies include enzyme-, environment-, metabolite-, biofilm-, and receptor-responsive designs, each tailored to microbial niches and applied across infectious, inflammatory, and metabolic disorders. However, challenges remain, including microbiome variability between individuals, regulatory uncertainty around hybrid biologic-material systems, and the need for scalable GMP-compliant manufacturing. This review therefore outlines the current approaches for engineering MADDS and the future steps required for clinical translation. By exploiting microbial cues for controlled drug release, MADDS offer a practical route to more targeted and patient-specific therapies.}, }
@article {pmid41106704, year = {2025}, author = {Heckmann, ND and Culler, M and Atallah, LM and Mont, MA and Lieberman, JR and Parvizi, J}, title = {Emerging Concepts in Periprosthetic Joint Infection Research: Infection Recurrence and Microbe Persistence.}, journal = {The Journal of arthroplasty}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.arth.2025.10.033}, pmid = {41106704}, issn = {1532-8406}, abstract = {Recurrent periprosthetic joint infection (PJI) is a highly morbid complication following total joint arthroplasty (TJA). Despite appropriate medical and surgical management with targeted antimicrobial therapies, many patients who suffer from a PJI experience clinically relevant episodes of recurrence. Though the majority of these recurrent infections are due to microbes that are different from the species initially isolated at the index infection, approximately 15 to 50% of subsequent PJIs are attributed to recurrence with the same causative organism. Treatment resistance, contamination during revision surgery, hematogenous spread of bacteria from a distant source, and the presence of resilient biofilms have long been implicated in these recurrent infections. However, recent preclinical and clinical evidence has demonstrated that certain organisms that commonly cause PJI, namely staphylococcal species, can undergo phenotypic transformation into viable, but non-culturable (VBNC) and quasi-dormant small colony variant (SCV) forms that may persist intracellularly and lead to recurrent infection. Moreover, some organisms are known to infiltrate the osteocyte lacuno-canalicular network (OLCN) and invade eukaryotic cells to avoid targeting by the host immune system and antimicrobial agents. In doing so, they create microbial reservoirs that may be capable of reactivating to cause symptomatic infection locally or after being transported to the joint by circulating phagocytic cells. Commensal species present in the human microbiome may also become pathogenic and lead to recurrent PJI. Evidence suggests dysbiosis, a pathological imbalance in the composition and function of the microbiome, may induce the translocation of resident organisms from the gut into the bloodstream. Recent studies have also identified joint microbiota signatures that vary in accordance with the presence or absence of certain pathologies, including PJI.}, }
@article {pmid41103759, year = {2025}, author = {Khelfaoui, I and Wang, W and Meskher, H and Shehata, AI and El Basuini, MF and Abouelenein, MF and Degha, HE and Alhoshy, M and Teiba, II and Mahmoud, SS}, title = {Beyond just correlation: causal machine learning for the microbiome, from prediction to health policy with econometric tools.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1691503}, pmid = {41103759}, issn = {1664-302X}, abstract = {The human microbiome is increasingly recognized as a key mediator of health and disease, yet translating microbial associations into actionable interventions remains challenging. This review synthesizes advances in machine learning (ML) and causal inference applied to human microbiome research, emphasizing policy-relevant applications. Explainable ML approaches, have identified microbial drivers, guiding targeted strategies. Econometric tools, including instrumental variables, difference-in-differences, and panel data models, provide robust frameworks for validating causal relationships, while hybrid methods like Double Machine Learning (Double ML) and Deep Instrumental Variables (Deep IV) address high-dimensional and non-linear effects, enabling precise evaluation of microbiome-mediated interventions. Policy translation is further enhanced by federated learning, standardized analytical pipelines, and model visualization frameworks, which collectively improve reproducibility, scalability, and data privacy compliance. By integrating predictive power with causal rigor, microbiome research can move beyond observational associations to generate interventions that are biologically grounded, clinically actionable, and policy-ready. This roadmap provides a blueprint for translating mechanistic microbial insights into real-world health solutions, emphasizing interdisciplinary collaboration, standardized reporting, and evidence-based policymaking.}, }
@article {pmid41099014, year = {2025}, author = {Vázquez-González, L and Peña-Reyes, C and Regueira-Iglesias, A and Balsa-Castro, C and Tomás, I and Carreira, MJ}, title = {EPheClass: ensemble-based phenotype classifier from 16S rRNA gene sequences.}, journal = {Frontiers in bioinformatics}, volume = {5}, number = {}, pages = {1514880}, pmid = {41099014}, issn = {2673-7647}, abstract = {One area of bioinformatics that is currently attracting particular interest is the classification of polymicrobial diseases using machine learning (ML), with data obtained from high-throughput amplicon sequencing of the 16S rRNA gene in human microbiome samples. The microbial dysbiosis underlying these types of diseases is particularly challenging to classify, as the data is highly dimensional, with potentially hundreds or even thousands of predictive features. In addition, the imbalance in the composition of the microbial community is highly heterogeneous across samples. In this paper, we propose a curated pipeline for binary phenotype classification based on a count table of 16S rRNA gene amplicons, which can be applied to any microbiome. To evaluate our proposal, raw 16S rRNA gene sequences from samples of healthy and periodontally affected oral microbiomes that met certain quality criteria were downloaded from public repositories. In the end, a total of 2,581 samples were analysed. In our approach, we first reduced the dimensionality of the data using feature selection methods. After tuning and evaluating different machine learning (ML) models and ensembles created using Dynamic Ensemble Selection (DES) techniques, we found that all DES models performed similarly and were more robust than individual models. Although the margin over other methods was minimal, DES-P achieved the highest AUC and was therefore selected as the representative technique in our analysis. When diagnosing periodontal disease with saliva samples, it achieved with only 13 features an F1 score of 0.913, a precision of 0.881, a recall (sensitivity) of 0.947, an accuracy of 0.929, and an AUC of 0.973. In addition, we used EPheClass to diagnose inflammatory bowel disease (IBD) and obtained better results than other works in the literature using the same dataset. We also evaluated its effectiveness in detecting antibiotic exposure, where it again demonstrated competitive results. This highlights the importance and generalisation aspect of our classification approach, which is applicable to different phenotypes, study niches, and sample types. The code is available at https://gitlab.citius.usc.es/lara.vazquez/epheclass.}, }
@article {pmid41098769, year = {2025}, author = {Li, Y and Xin, Y and Zong, W and Li, X}, title = {The role of oral microbiota in digestive system diseases: current advances and perspectives.}, journal = {Journal of oral microbiology}, volume = {17}, number = {1}, pages = {2566403}, pmid = {41098769}, issn = {2000-2297}, abstract = {The oral microbiota is intimately linked to human health and various disease states. With the advent of the Human Microbiome Project, our comprehension of the oral microbiota has substantially improved. This microbial community is not only associated with a range of oral diseases, such as dental caries and periodontal diseases, but also with numerous digestive disorders, as demonstrated by recent clinical studies. Specific bacteria residing in the oral cavity, such as Porphyromonas gingivalis, Fusobacterium species and Streptococcus species, have been shown to translocate to the gastrointestinal tract, thereby establishing a potential connection between the oral and gut microbiota. The transfer and ectopic colonization of oral microbiota within the gastrointestinal tract may contribute to both the onset and exacerbation of gastrointestinal diseases. Following the principles of dysregulation characteristics, mechanism research and innovative treatment, this paper systematically reviews the association between the oral microbiota and various digestive system diseases. This paper explores how specific oral microbiota drive digestive system diseases mechanisms and evaluates treatments including probiotics, prebiotics, fecal microbiota transplantation, and targeted antimicrobial therapies. By clarifying the oral-gut microbiota-disease link, it highlights oral microbiota monitoring as a promising tool for early detection, diagnosis, and therapy.}, }
@article {pmid41094150, year = {2025}, author = {Zhang, Y and Bhosle, A and Bae, S and Eckenrode, K and Huang, X and Tang, J and Lavrentovich, D and Awad, L and Hua, J and Wang, Y and Morgan, XC and Li, B and Krueger, A and Garrett, WS and Franzosa, EA and Huttenhower, C}, title = {Predicting functions of uncharacterized gene products from microbial communities.}, journal = {Nature biotechnology}, volume = {}, number = {}, pages = {}, pmid = {41094150}, issn = {1546-1696}, support = {R24DK110499//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; U19AI110820//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; }, abstract = {The majority of genes in microbial communities remain uncharacterized. Here we develop a method to infer putative function for microbial proteins at scale by assessing community-wide multiomics data. We predict high-confidence functions for >443,000 protein families (~82.3% previously uncharacterized), including >27,000 protein families with weak homology to known proteins and >6,000 protein families without homology. These were drawn from 1,595 gut metagenomes and 800 metatranscriptomes from the Integrative Human Microbiome Project (HMP2/iHMP). Integrating additional information such as sequence similarity, genomic proximity and domain-domain interactions improves performance of the method. Our method's implementation, FUGAsseM, is generalizable and predicts protein function in both well-studied and undercharacterized communities. FUGAsseM achieves similar levels of accuracy in the context of microbial communities when compared to state-of-the-art approaches designed for application to single organisms while simultaneously providing much greater breadth of coverage. This initial study expands the functional landscape of the human gut microbiome and allows for exploration of microbial proteins in undercharacterized communities.}, }
@article {pmid41091222, year = {2025}, author = {Tajdozian, H and Seo, H and Kim, S and Rahim, MA and Park, HA and Sarafraz, F and Yoon, Y and Kim, H and Barman, I and Park, CE and Ghorbanian, F and Lee, S and Jeong, HR and Song, HY}, title = {Microbiome therapeutic PMC101 inhibits the translocation of carbapenem-resistant Klebsiella while enhancing eubiosis in antibiotic-induced dysbiosis mice.}, journal = {Medical microbiology and immunology}, volume = {214}, number = {1}, pages = {49}, pmid = {41091222}, issn = {1432-1831}, support = {No. RS-2023-00219563//Ministry of Science and ICT, South Korea/ ; P248400003//Korea Institute for Advancement of Technology/ ; }, mesh = {Animals ; *Dysbiosis/chemically induced/microbiology/therapy ; *Carbapenem-Resistant Enterobacteriaceae/drug effects/physiology ; *Anti-Bacterial Agents/adverse effects/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; *Klebsiella Infections/microbiology/therapy ; *Bacterial Translocation/drug effects ; Carbapenems/pharmacology ; Humans ; Mice, Inbred C57BL ; Feces/microbiology ; }, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE), known for their extensive antibiotic resistance, pose a severe global medical threat. Therefore, developing novel therapeutics beyond conventional antibiotics is urgently needed, and the importance of microbiome therapeutics is increasingly being recognized. This study explores the expanded systemic efficacy of PMC101, a microbiome therapeutic, beyond intestinal CRE infections and investigates its mechanism of action from a microbiome perspective. First, the genetic characteristics of the novel strain were identified through whole-genome analysis, and a scalable cultivation process was established as part of the overall development of this microbiome therapeutic. PMC101 increased the survival rate to 100%, significantly reduced disease severity scores, and prevented weight loss in CRE-infected mice treated with antibiotics. These effects are attributed to the inhibition of CRE growth in stool and the reduced detection of CRE in the lungs and kidneys, indicating suppression of systemic translocation. Metagenomic analysis revealed that PMC101 prevented the reduction in microbial population caused by antibiotics and CRE infection, restored species diversity indices, and mitigated dysbiosis while promoting eubiosis. This CRE translocation suppression was closely associated with increased CRE translocation-microbiome index, defined as the ratio of Bacteroidetes to Proteobacteria. This relationship was further confirmed through simulations using a human intestinal microbial ecosystem model. Additionally, increases in short-chain fatty acids, reductions in excessive inflammatory responses, and decreases in tissue damage were observed, all of which contribute to preventing CRE translocation. Finally, pathogen inhibition effects and safety tests were conducted, confirming the prophylactic potential of PMC101 as a microbiome therapeutic. These findings strongly support PMC101 as a promising candidate for future microbiome-based therapies against CRE infections.}, }
@article {pmid41076098, year = {2025}, author = {Karisola, P and Alenius, H}, title = {Environmental determinants of immune tolerance in asthma and allergy.}, journal = {Immunology letters}, volume = {}, number = {}, pages = {107102}, doi = {10.1016/j.imlet.2025.107102}, pmid = {41076098}, issn = {1879-0542}, abstract = {Prevalence of allergic diseases has increased globally, reflecting environmental and behavioral changes. The exposome concept encompasses cumulative chemical, microbial, nutritional, psychosocial, and physical exposures across the life course, offering a unifying framework to understand how immune tolerance is shaped or disrupted. Emerging evidence highlights that early-life exposures are particularly critical. Pollutants, endocrine disruptors, microbial deprivation, dietary shifts, and psychosocial stress contribute to barrier dysfunction, dysbiosis, and immune dysregulation, favoring Th2 dominance and allergy development. In contrast, exposures that enhance biodiversity, microbial diversity, pollution-free air, and balanced nutrition support active tolerance development, especially via regulatory T cells. Mechanistic insights point to the barrier-microbiota-immune axis as central pathways linking the environment to allergic outcomes. Translational studies, including biodiversity enrichment interventions, maternal and infant dietary strategies, and microbiome-based therapies, illustrate the potential of exposome-informed approaches to allergy prevention. However, major challenges remain in measuring complex exposure mixtures, identifying causal pathways, and integrating exposome data with systems immunology. This review synthesizes current knowledge on how the exposome modulates immune tolerance and outlines future research directions toward precision prevention. A deeper understanding of these interactions is essential to address the rising global allergy burden.}, }
@article {pmid41060894, year = {2025}, author = {Rosas-Plaza, S and Mainou, L and Delgado, G and Morales, R and Aguilar-Romero, A and Escalante, AE and Cerritos, R}, title = {Microbiome characterization of a pre-Hispanic man from Zimapán, Mexico: Insights into ancient gut microbial communities.}, journal = {PloS one}, volume = {20}, number = {10}, pages = {e0331137}, doi = {10.1371/journal.pone.0331137}, pmid = {41060894}, issn = {1932-6203}, mesh = {Humans ; Male ; *Gastrointestinal Microbiome/genetics ; Mexico ; RNA, Ribosomal, 16S/genetics ; *Bacteria/genetics/classification/isolation &amp; purification ; Phylogeny ; Mummies/microbiology ; }, abstract = {The research of microbiome derived from mummified human remains, coprolites and paleofeces has gained significant interest over several decades, aiming to elucidate the evolution of microbial interactions and shed light on the lifestyles of past populations. In this study, we analyzed the gut microbiome of a pre-Hispanic male individual referred to as the Zimapán man, dated to 936 BP, discovered on the border between Mesoamerica and Aridoamerica. Employing high-throughput 16S rRNA gene sequencing on both the paleofeces and mummified intestinal tissue, we conducted a comprehensive characterization of the Zimapán man's gut microbiome. The bacterial community was described, and a weighted UniFrac-based principal coordinates analysis (PCoA) was performed. The multivariate analysis incorporated microbiome samples from diverse environments, such as soils, compost, and both contemporary and ancient human gut microbiota. The analysis revealed bacterial groups associated with the human microbiome, including families such as Peptostreptococcaceae, Clostridiaceae, Enterobacteriaceae, and Enterococcaceae. Notably, a high abundance of the Clostridiaceae group was found, similar to those discovered in the intestinal tissue of mummies from other geographic regions. Additionally, unique groups such as Romboutsia hominis, exclusively isolated from human intestines and not previously reported in ancient human microbiomes, were identified. Furthermore, our analysis demonstrated that the bacterial composition did not resemble soil and compost environments. This initial characterization successfully achieved the goal of identifying bacterial groups of the gut microbiome in the Zimapán samples. Consequently, this study contributes to the ongoing expansion of knowledge regarding ancient microbiomes across diverse temporal, historical, geographical, and environmental contexts.}, }
@article {pmid41057417, year = {2025}, author = {Manoharan-Basil, S and Gestels, Z and Abdellati, S and Vanbaelen, T and Van Den Bossche, D and van Alebeek, L and Van Herrewege, Y and Poppe, L and Vandenhove, L and Bracke, S and Smekens, B and Jacobs, B and Genbrugge, E and Kenyon, C}, title = {Concentrations of ciprofloxacin in food defined as safe alter the gut microbiome and ciprofloxacin susceptibility in humans: an interventional clinical study.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {34908}, pmid = {41057417}, issn = {2045-2322}, mesh = {Humans ; *Ciprofloxacin/pharmacology/administration &amp; dosage ; *Gastrointestinal Microbiome/drug effects ; Escherichia coli/drug effects ; Male ; Female ; *Anti-Bacterial Agents/pharmacology/administration &amp; dosage ; Adult ; Microbial Sensitivity Tests ; Middle Aged ; Young Adult ; Enrofloxacin ; Drug Resistance, Bacterial ; }, abstract = {It is unknown if the low residual concentrations of ciprofloxacin/enrofloxacin allowed in food could influence the human microbiome. The European Medicines Agency reports that it is safe for an average human to ingest 372 µg of enrofloxacin/ciprofloxacin daily. We randomized 30 individuals to either 372 µg of ciprofloxacin or placebo daily for 27 days in a 2:1 fashion and measured the effect on the gut microbiome and the susceptibility of Escherichia coli to ciprofloxacin. After 27 days the E. coli of the individuals in the ciprofloxacin, but not the placebo arm, had reduced ciprofloxacin susceptibility. The receipt of ciprofloxacin was also associated with a reduction in the number of E. coli colony forming units in the gut. The low concentration of antimicrobials allowed in food may have an impact on the composition of the gut microbiome and antimicrobial susceptibility.}, }
@article {pmid41050662, year = {2025}, author = {Wierzbińska, W and Kuźmycz, O and Kowalczyk, A and Stączek, P}, title = {The role of dysbiosis in shaping host immunity in endometrial cancer development.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1627285}, pmid = {41050662}, issn = {1664-3224}, mesh = {Humans ; *Dysbiosis/immunology/microbiology ; *Endometrial Neoplasms/immunology/microbiology/pathology/etiology ; Female ; Tumor Microenvironment/immunology ; Animals ; Microbiota/immunology ; Carcinogenesis/immunology ; }, abstract = {In recent years, research into the background of carcinogenic processes has increasingly focused on the role of the tumor microenvironment (TME) in tumorigenesis. In addition to the presence of tumor cells and non-malignant components, which include immune cells, extracellular matrix elements, stroma, and endothelial cells, the microbiome is now increasingly being classified as an integral part of the TME. The establishment of the Human Microbiome Project (HMP) in 2007 along with the development of next-generation sequencing (NGS) techniques proved to be a breakthrough in terms of human microbiota research, shedding new light on the existing knowledge of microorganisms inhabiting various niches of the human body and their functions. Emerging scientific evidence from preclinical and clinical studies indicates significant differences in the microbiome composition between tumor tissues and benign controls. The presence of specific pathogenic strains within a tissue may play a key role in the initiation and progression of inflammation, which not only may be directly responsible for the stimulation of tumorigenic processes but may also affect the destabilization of the host genome, causing significant disruption of its metabolism. The role of microorganisms in the induction and promotion of pathological processes, including cancer, has been confirmed in many studies to date. Recent years of research on the microbiota of the female reproductive tract (FRT) have not only indicated that the endometrium has its unique microbial composition but have also made it possible to point out differences in composition between the microbiome of healthy and tumor-lesioned tissue, suggesting a potential role for dysbiotic disorders in the pathogenesis of endometrial cancer (EC). In this review, we aim to highlight the complex interplay between bacterial interactions and host immunity, and how this phenomenon contributes to the development and progression of endometrial cancer.}, }
@article {pmid41047836, year = {2025}, author = {Reddy, LB and Saier, MH}, title = {Microbiome: Friend or Friendly Foe.}, journal = {Microbial physiology}, volume = {}, number = {}, pages = {}, doi = {10.1159/000548748}, pmid = {41047836}, issn = {2673-1673}, abstract = {The human microbiome is a dynamic, polymicrobial ecosystem that plays an essential role in nutrition, immune development, barrier integrity, and host physiology, acting as a mutualistic partner under balanced conditions. However, its ecological complexity, genetic adaptability through horizontal gene transfer, and interactions with other prokaryotes as well as protozoan and metazoan parasites can transform commensals into pathobionts, resulting in weakened host's barriers, immunity declines with the progression of age, and community composition shifts toward dysbiosis. Factors such as diet, genetics, aging, immune-senescence, impaired autophagy, and environmental exposure, all influence this delicate balance, determining whether the microbiome remains protective or becomes an opportunistic source of inflammation and disease. This review focuses on the study of the intestinal microbiome in humans. Maintaining microbiome homeostasis is promoted through (a) dietary diversity, (b) limited antimicrobial use, (c) use of probiotics, (d) support for gut barrier function, and (e) healthy lifestyle improvements. These actions and considerations are critical to prevent the emergence of pathogenic states and preserving the microbiome's vital role in host health throughout life.}, }
@article {pmid41047724, year = {2025}, author = {de Groen, P and Fuhri Snethlage, CM and Wortelboer, K and Tokgöz, S and Davids, M and Verdoes, X and Westerbeke, FHM and Meijer, RI and Gotthardt, M and de Vos, WM and Herrema, H and Nieuwdorp, M and Hanssen, NMJ}, title = {Autologous fecal microbiota capsules are safe and potentially preserve beta-cell function in individuals with type 1 diabetes.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2563155}, doi = {10.1080/19490976.2025.2563155}, pmid = {41047724}, issn = {1949-0984}, mesh = {Humans ; *Diabetes Mellitus, Type 1/therapy ; *Insulin-Secreting Cells/physiology/metabolism ; Male ; Female ; Adult ; *Feces/microbiology ; Pilot Projects ; Capsules/administration &amp; dosage ; *Fecal Microbiota Transplantation/adverse effects/methods ; Young Adult ; Middle Aged ; C-Peptide/blood/metabolism ; Adolescent ; Gastrointestinal Microbiome ; }, abstract = {This study investigated the safety and feasibility of daily ingestion of autologous lyophilized fecal microbiota capsules (a-LFMCs) for preserving beta-cell function in individuals with type 1 diabetes (T1D). We evaluated a-LFMC in an open-label, single-arm pilot study (NCT05323162) with 10 individuals with T1D. The study included a 3-month run-in period, 3 months of daily a-LFMC treatment, and a 3-month follow-up. Beta-cell function was assessed using mixed-meal stimulated C-peptide area under the curve (AUC). During the run-in period, beta-cell function significantly declined (mean ΔAUC -12.02 ± 5.09 nmol/L*min, p = 0.025). There was no decrease in beta-cell function during the a-LFMC treatment period (mean ΔAUC 0.76 ± 5.09 nmol/L*min, p = 0.88) and the follow-up period (mean ΔAUC 0.96 ± 5.09 nmol/L*min, p = 0.85). No serious adverse events occurred, though constipation increased during the treatment period (0% vs. 30%, p = 0.021). a-LFMC treatment was found to be safe and potentially contributes to preserving beta-cell function in T1D patients. A larger randomized placebo-controlled trial is needed to confirm these promising findings.}, }
@article {pmid41046872, year = {2025}, author = {Yang, S and Yang, M and Jennings, M and Timek, H and Haley, AE and Romee, R and Li, J}, title = {Repurposing the bacterial surface display technology for drug delivery.}, journal = {Advanced drug delivery reviews}, volume = {}, number = {}, pages = {115701}, doi = {10.1016/j.addr.2025.115701}, pmid = {41046872}, issn = {1872-8294}, abstract = {Bacteria have emerged as versatile platforms for therapeutic delivery, owing to their inherent adaptability, genetic tractability, and ability to interface with the human microbiome and immune system. This review explores the evolution of bacterial engineering for medical applications, emphasizing drug delivery strategies enabled by bacterial surface display technologies. We outline the advantages of surface display-such as enhanced localization, prolonged therapeutic activity, and reduced systemic toxicity-over conventional bacterial secretion and lysis-based delivery methods. The review details key biological mechanisms of surface display in both Gram-negative and Gram-positive bacteria, including outer membrane proteins, sortase-mediated anchoring, and spore-based systems. We also highlight emerging applications of surface-displayed cytokines, nanobodies, and immunomodulatory proteins in cancer therapy, vaccine development, microbiome engineering, and animal health. Innovative approaches combining bacterial display with conjugation systems and biosensors expand the potential of these living therapeutics for precise, responsive, and programmable interventions. Furthermore, we propose a future roadmap that leverages computational tools such as AlphaFold and in silico screening to rationally identify optimal outer membrane anchors, accelerating the design of next-generation surface display platforms. While challenges remain-including regulatory hurdles and microbial stability-continued interdisciplinary innovation with synthetic biology promises to transform engineered bacteria into clinically viable therapeutic agents. This review positions bacterial surface display as a powerful and underexplored modality for targeted drug delivery, bridging synthetic biology, immune engineering, and translational medicine.}, }
@article {pmid41039266, year = {2025}, author = {Tavanaeian, S and Feizabadi, MM and Falsafi, S and Aghdaei, HA and Houri, H}, title = {Oral and fecal microbiome alterations in pancreatic cancer: insights into potential diagnostic biomarkers.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {624}, pmid = {41039266}, issn = {1471-2180}, abstract = {BACKGROUND: The human microbiome plays a pivotal role in pancreatic cancer (PC). This study investigates the abundance of specific gut and oral microbes in PC patients compared to healthy controls.<br><br>METHODS: A cohort of 20 diagnosed PC patients and an equivalent control group were recruited. Comprehensive lifestyle data, such as overall food consumption, were collected. Saliva and stool samples were prepared. Microbial DNA was extracted from stool and saliva samples using specialized kits. Primers were designed targeting the conserved regions of the 16&#xa0;S rRNA genes from Neisseria elongata, Granulicatella adiacens, Fusobacterium nucleatum, Roseburia intestinalis, and Bifidobacterium bifidum. The quantities of selected bacterial species were evaluated using real-time quantitative PCR.<br><br>RESULTS: Granulicatella adiacens and Fusobacterium nucleatum were significantly increased in the PC group (medians: 7.35 and 4.37 log10 CFU/g, respectively) compared to controls (medians: 2.43 and 1.20 log10 CFU/g ; P&#x2009;<&#x2009;0.001 for both). Conversely, Neisseria elongata, Roseburia intestinalis, and Bifidobacterium bifidum levels were significantly lower in PC patients (medians: 2.37, 2.34, and 3.45 log10 CFU/g, respectively) compared to controls (medians: 5.63, 5.07, and 4.34 log10 CFU/g; P&#x2009;<&#x2009;0.001). The principal component analysis confirmed distinct clustering of microbiota profiles between the two groups, with key microorganisms associated with PC. The discriminatory performance of clinical and microbiota variables demonstrated notable accuracy in classifying PC, particularly metrics such as hemoglobin and hematocrit, achieving an area under the curve (AUC) of 1.00.<br><br>CONCLUSIONS: In summary, these findings highlight the significant association between microbiome composition and PC, underscoring the potential of microbiota profiles as non-invasive diagnostic biomarkers that warrant further investigation for early detection and therapeutic targeting in clinical practice.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04344-2.}, }
@article {pmid41043678, year = {2025}, author = {Kumar, P and Gulati, M and Kapoor, B and Yadav, AK and Hussain, MS and Kumar, R}, title = {Beyond the HCG test: Microbiome-based diagnosis of pregnancy.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {}, number = {}, pages = {120639}, doi = {10.1016/j.cca.2025.120639}, pmid = {41043678}, issn = {1873-3492}, abstract = {The complex but definitive relationship between pregnancy and the body microbiota offers a significant opportunity for novel diagnostic techniques. This work proposes a new diagnostic method that correlates the significant changes in the gut, vaginal, and oral microbiota composition that occur in the early stages of pregnancy. The main premise is identification of those microbial indicators that are strongly linked to early pregnancy by describing the periodic shifts in these microbial ecosystems. Early and precise pregnancy identification may be made possible by these biomarkers' potential as highly sensitive and precise indicators. More importantly, understanding of the fundamental processes by which the microbiota in various organs affects pregnancy outcomes, tailored therapies to enhance the health of both the mother and the foetus may be considered as a long-term goal. Analysis of vaginal swabs or saliva is proposed as a non-invasive method that might transform prenatal care. Healthcare professionals might monitor pregnancy progress, understand and mitigate the expected problems, and initiate prompt measures by identifying early pregnancy indicators. Finding microbiome-based indicators of pregnancy complications may also make it possible to identify at-risk patients early and implement individualised treatment plans. We may get fresh understanding of the intricacies of pregnancy and create creative methods to enhance the health of both mothers and children by utilizing the potential of the human microbiome.}, }
@article {pmid41043219, year = {2025}, author = {Gugescu, L and Yang, Y and Kool, JF and Fyhrquist, N and Wincent, E and Alenius, H}, title = {Microbiota modulates compound-specific toxicity of environmental chemicals: A multi-omics analysis in zebrafish embryos.}, journal = {Environment international}, volume = {204}, number = {}, pages = {109828}, doi = {10.1016/j.envint.2025.109828}, pmid = {41043219}, issn = {1873-6750}, abstract = {Interactions between gut microbiota and environmental chemicals critically influence toxicological outcomes, yet mechanistic insights remain limited. Here, we combine developmental toxicity with full-length 16S rRNA gene sequencing, transcriptomic, and metabolomic analyses in germ-free (GF) and conventionally colonized wild-type (WT) zebrafish embryos to elucidate the microbiota's role in modulating chemical toxicity. Using representative compounds from major classes of environmental contaminants, we show that microbial presence significantly alters toxicity profiles in a compound-specific manner. The perfluorinated contaminant PFOS (perfluorooctanesulfonic acid) induced the strongest microbiota-dependent effects, with a greater number of differentially expressed genes in WT embryos and pronounced changes in immune and stress-related pathways. The pesticide boscalid and bisphenol F elicited distinct microbiota-modulated transcriptional and metabolic responses. Gene network analysis identified baseline microbial regulation of immune and metabolic programs, while metabolomics showed PFOS-dependent changes in L-tryptophan and its microbe-associated metabolites, including inosine, indoxyl sulfate and indole acetaldehyde, exclusively in WT embryos. These findings establish a mechanistically grounded framework for microbiota-chemical interactions and highlight the importance of integrating microbiome context into environmental health assessments.}, }
@article {pmid41036626, year = {2025}, author = {Xia, Y and Liang, L and Wang, X and Chen, Z and Liu, J and Yang, Y and Xie, H and Ding, Z and Huang, X and Long, S and Wang, Z and Xu, X and Ding, C and Chen, Q and Feng, Q}, title = {MetaflowX: a scalable and resource-efficient workflow for multi-strategy metagenomic analysis.}, journal = {Nucleic acids research}, volume = {53}, number = {18}, pages = {}, doi = {10.1093/nar/gkaf954}, pmid = {41036626}, issn = {1362-4962}, support = {2022YFA1304100//National Key R&amp;D Program of China/ ; 82&#xa0;270&#xa0;980//National Natural Science Foundation of China/ ; 82071122//National Natural Science Foundation of China/ ; 82&#xa0;202&#xa0;539//National Natural Science Foundation of China/ ; 2023ZD0501406//National Science and Technology Major Program/ ; 2019//National Young Scientist Support Foundation/ ; ZR2021JQ29//Excellent Young Scientist Foundation of Shandong Province/ ; 2019//Taishan Young Scientist Project of Shandong Province/ ; 2021GXRC021//Periodontitis innovation team of Jinan City/ ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; 2021ZDSYS18//Shandong Province Key Research and Development Program/ ; #202412A001//horizontal cooperation project with Shenzhen 01 Life Institute/ ; #202112E401//horizontal cooperation project with Shenzhen 01 Life Institute/ ; }, mesh = {*Metagenomics/methods ; Workflow ; *Software ; *Metagenome/genetics ; *Microbiota/genetics ; Humans ; }, abstract = {Microbiomes play crucial roles in diverse ecosystems, spanning environmental, agricultural, and human health domains. However, in-depth metagenomic data analysis presents significant technical and resource challenges, particularly at scale. Existing computational pipelines are typically limited to either reference-based or reference-free approaches and exhibit inefficiencies in process large datasets. Here, we introduce MetaflowX (https://github.com/01life/MetaflowX), an open-resource workflow integrating both analytical paradigms for enhanced metagenomic investigations. This modular framework encompasses short-read quality control, rapid microbial profiling, hybrid contig assembly and binning, high-quality metagenome-assembled genome (MAG) identification, as well as bin refinement and reassembly. Benchmarking tests showed that MetaflowX completed full metagenomic analyses up to 14-fold faster and with 38% less disk usage than existing workflows. It also recovered the highest number of high-quality and taxonomically diverse MAGs. A dedicated reassembly module further improved MAG quality, increasing completeness by 5.6% and reducing contamination by 53% on average. Functional annotation modules enable detection of key features, including virulence and antibiotic resistance genes. Designed for extensibility, MetaflowX provides an efficient solution addressing current and emerging demands in large-scale metagenomic research.}, }
@article {pmid41035896, year = {2025}, author = {Bautista, J and Echeverría, CE and Maldonado-Noboa, I and Ojeda-Mosquera, S and Hidalgo-Tinoco, C and López-Cortés, A}, title = {The human microbiome in clinical translation: from bench to bedside.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1632435}, pmid = {41035896}, issn = {1664-302X}, abstract = {The human microbiome, once regarded as a passive passenger, is now recognized as a dynamic and essential determinant of human physiology, shaping immunity, metabolism, neurodevelopment, and therapeutic responsiveness across the lifespan. Advances in multi-omic technologies, experimental models, and computational approaches have revealed mechanistic insights into how microbial communities modulate host systems across diverse body sites, including the gut, skin, lungs, oral cavity, and reproductive tract. The clinical translation of this knowledge has begun to redefine early-life programming, cardiometabolic regulation, immune homeostasis, neuropsychiatric resilience, and cancer therapy response. Innovative strategies such as phage therapy, live biotherapeutics, precision nutrition, and microbiota transplantation illustrate the therapeutic potential of harnessing microbial functions to prevent or treat disease. In parallel, large-scale initiatives cataloging the microbiome of underexplored niches, such as the vagina and skin, are advancing health equity by broadening representation in microbial reference datasets. Yet significant challenges persist, including interindividual variability, incomplete functional annotation of microbial "dark matter," and the absence of validated biomarkers. Addressing these gaps requires standardized methodologies, harmonized regulatory frameworks, and longitudinal studies across diverse populations. This review outlines the progress and remaining hurdles in translating microbiome science into clinical practice and concludes that the microbiome now stands at the forefront of a paradigm shift, transforming concepts of disease etiology, therapeutic design, and the future of individualized medicine.}, }
@article {pmid41025644, year = {2025}, author = {Saito, D and Saito, CPB and Cannavan, FDS and Tsai, SM}, title = {Draft genome sequences of six Rothia mucilaginosa strains assembled from the human oral microbiome.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0050825}, doi = {10.1128/mra.00508-25}, pmid = {41025644}, issn = {2576-098X}, abstract = {We report draft metagenome-assembled genomes (MAGs) of six Rothia mucilaginosa strains recovered from the oral microbiome of distinct human subjects. MAGs were retrieved according to a species-specific genome mapping approach, displaying high average nucleotide identities (≥95.85%) to R. mucilaginosa ATCC 25296's genome and minimal contamination levels (≤3.75%).}, }
@article {pmid41023926, year = {2025}, author = {Chen, Y and Chen, Z and Xu, D and Li, S and Chen, F and Yu, X and Cai, S and Zeng, C and Ye, X and Yang, J and Liu, J and Lin, J and Xiao, S}, title = {Early prediction of bloodstream infections in ICU patients using machine learning methods based on routine laboratory parameters.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {1196}, pmid = {41023926}, issn = {1471-2334}, }
@article {pmid41023588, year = {2025}, author = {Nascimento, T and Inácio, J and Guerreiro, D and Patrício, P and Proença, L and Toscano, C and Barroso, H}, title = {Exploring the skin mycobiome in intensive care patients: a pilot study on fungal diversity from axillary and groin swabs.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {589}, pmid = {41023588}, issn = {1471-2180}, support = {10.54499/UIDB/04585/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Humans ; Pilot Projects ; *Skin/microbiology ; *Mycobiome ; Male ; *Fungi/classification/isolation &amp; purification/genetics ; Female ; Intensive Care Units ; Middle Aged ; Aged ; *Axilla/microbiology ; *Groin/microbiology ; DNA, Fungal/genetics ; Adult ; Critical Illness ; Biodiversity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {The skin mycobiome is a largely unexplored component of the human microbiome, especially in critically ill patients. Fungal colonisation in the Intensive Care Unit (ICU) may be influenced by underlying comorbidities and hospital-related risk factors, potentially impacting patient outcomes. This pilot study aimed to characterize the diversity and abundance of skin fungi in ICU patients during their first week of hospitalization. A total of 35 ICU patients were recruited and divided into two groups: Group 1 (patients with 1-2 comorbidities and ICU risk factors) and Group 2 (patients with more than 2 comorbidities and ICU risk factors). Bilateral axillary-groin swabs were collected on admission day (D1) and after one week of ICU stay (D8) for fungal identification. Culture-based methods and MALDI-TOF MS were initially used, followed by Internal Transcribed Spacer 2 (ITS2) sequencing via the Illumina MiSeq platform for in-depth analysis of fungal communities. Fungal diversity and relative abundance were assessed using standard alpha and beta diversity metrics. Culture and MALDI-TOF MS identified only Candida spp., suggesting limited diversity. ITS2 sequencing revealed that Candida (69.3%) was the most prevalent genus, followed by Penicillium (10.3%) and Cladosporium (4.0%), with Malassezia being rare (0.7%). Diversity analysis indicated a relatively stable fungal community throughout the first week (ANOSIM, p = 0.499), with no significant changes in species richness or community structure. By Day 8, Candida spp. represented 79.9% and 78.9% of the mycobiome in Groups 1 and 2, respectively. Preliminary data suggest that the ICU skin mycobiome is dominated by Candida spp. and exhibits low fungal diversity. These findings provide foundational insight into the skin mycobiome of critically ill patients and underscore the need for further research to elucidate its clinical significance and potential role in patient management.}, }
@article {pmid41022221, year = {2025}, author = {Delic, M and Butorova, I and Kuskov, A}, title = {Chitosan application in cosmetics and dermatology - antimicrobial and prebiotic potential to control human microbiome.}, journal = {Journal of biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jbiotec.2025.09.014}, pmid = {41022221}, issn = {1873-4863}, abstract = {The human microbiome has become a critically important field of study, with recent advances continuously revealing new aspects of its functional roles. A deeper understanding of the complex metabolic interactions between the microbiome, therapeutic agents, and the human host is now developing. A key challenge is the development of effective novel antimicrobial compounds, particularly those targeting biofilm-related infections implicated in a wide range of chronic diseases, to better control the human microbiota and treat typical skin diseases. Chitosan, a polysaccharide derived from various natural sources, possesses a unique set of biological properties, making it a promising base for numerous cosmetic and medicinal products aimed at managing dermatological diseases and modulating the microbiome. By altering its characteristics, chitosan's properties can be tuned to produce biomacromolecules with optimized activity beneficial to human microbiota. This review summarizes the sources and mechanisms underlying chitosan's antimicrobial activity, its immunomodulatory and anti-pathogenic effects, and critically evaluates its dual potential as both an antimicrobial and a prebiotic agent. Special emphasis is placed on chitosan-based formulations for treating skin diseases and promoting microbiome health - an emerging and promising area of research.}, }
@article {pmid41015042, year = {2025}, author = {Fang, S and Qin, Y and Lian, H and Zhong, Y and Yang, Y and Yu, XD and Yang, S and Liang, J and Xiao, W and Wen, S and Zhang, XM and Li, B and Huang, L}, title = {Reduced oxytocin signaling in the dBNST drives the transition from acute pain to persistent anxiety.}, journal = {Current biology : CB}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cub.2025.09.012}, pmid = {41015042}, issn = {1879-0445}, abstract = {Transient sensory experiences can trigger sustained emotional disturbances, yet the underlying neural mechanisms remain unclear. Here, we show that acute pain induces persistent anxiety in male mice, independent of ongoing nociceptive input, through reduced oxytocin signaling in the dorsal bed nucleus of the stria terminalis (dBNST). Reactivating oxytocin receptors (Oxtrs) in the dBNST markedly alleviated anxiety-like behaviors following pain resolution. Mechanistically, chemogenetic inhibition of somatostatin-expressing (SST) neurons in the dBNST (dBNST[SST] neurons) abolished oxytocin's anxiolytic effects, while pharmacological blockade or selective knockdown of Oxtrs in these neurons increased anxiety-like behaviors. Transcriptomic and electrophysiological analyses further revealed that alterations in synaptic transmission and intrinsic excitability participate in this anxiety state. Together, these findings define a multilevel framework-spanning molecular, cellular, and circuit mechanisms-by which acute sensory input induces long-term emotional dysregulation. This study advances our understanding of pain-related affective disorders and highlights oxytocin signaling and dBNST[SST] neurons as promising therapeutic targets.}, }
@article {pmid41013188, year = {2025}, author = {Xuan, P and Wang, R and Gu, J and Cui, H and Zhang, T}, title = {Structure-sensitive transformer and multi-view graph contrastive learning enhanced prediction of drug-related microbes.}, journal = {BMC bioinformatics}, volume = {26}, number = {1}, pages = {231}, pmid = {41013188}, issn = {1471-2105}, support = {2024A1515010176//Guangdong Basic and Applied Basic Research Foundation/ ; 62372282, 62172143//Natural Science Foundation of China/ ; 62372282, 62172143//Natural Science Foundation of China/ ; NTF22032//STU Scientific Research Initiation Grant/ ; }, mesh = {Humans ; *Machine Learning ; *Microbiota/drug effects ; *Computational Biology/methods ; Algorithms ; Semantics ; }, abstract = {BACKGROUND: The human microbiome plays a crucial role in regulating the efficacy and toxicity of drugs as well as in developing the drugs. Therefore, predicting the drug-related microbes is beneficial for analyzing the functional mechanisms of drugs. Recently, the graph learning based methods demonstrated their advantages in extracting the node features from the biological heterogeneous graphs. However, the previous methods failed to completely preserve the intrinsic structures of biological data and did not fully utilize the topological and positional information for predicting the drug-microbe associations.<br><br>RESULTS: We propose a new prediction model, structure-sensitive transformer and multi-view graph contrastive learning for microbe-drug association prediction (SMMDA), to encode and integrate the topological structures, semantics, and multiple-view embedding features of the drugs and microbes. Considering the sparsity of the original features of drugs and microbes, the learnable data augmentation strategy is designed to learn their global representations. Since similar drugs are more likely to associate with the similar microbes, a structure-sensitive transformer is proposed to integrate the topology structures composed of drugs (microbes) to form the multi-view embedding features. We design two contrastive learning strategies to exploit the complementary semantics across multiple views. As the embedding features from multiple views have various semantics, we design view-level attention to adaptively integrate these features.<br><br>CONCLUSIONS: The extensive experimental results show that SMMDA outperforms several state-of-the-art methods for predicting the drug-related candidate microbes. The ablation studies show the effectiveness of the major innovations which include the learnable data augmentation, structure-sensitive transformer-based node feature learning, and multi-view contrastive learning. The case studies on three drugs also demonstrate SMMDA's capability in retrieving the potential microbe candidates for the drugs.}, }
@article {pmid41011478, year = {2025}, author = {Cortés, M and Olate, P and Rodriguez, R and Diaz, R and Martínez, A and Hernández, G and Sepulveda, N and Paz, EA and Quiñones, J}, title = {Human Microbiome as an Immunoregulatory Axis: Mechanisms, Dysbiosis, and Therapeutic Modulation.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13092147}, pmid = {41011478}, issn = {2076-2607}, support = {N&#xb0; 21231033//Agencia Nacional de Investigaci&#xf3;n y Desarrollo/ ; }, abstract = {The human microbiome plays a central role in modulating the immune system and maintaining immunophysiological homeostasis, contributing to the prevention of immune-mediated diseases. In particular, the gut microbiota is a key ecosystem for immune system maturation, especially in early life. This review aimed to analyze the molecular and cellular mechanisms linking the microbiome to immune and neuronal functions, as well as the impact of dysbiosis and emerging therapeutic strategies targeting the microbiome. The analysis was based on scientific databases, prioritizing studies published since 2000, with special emphasis on the past decade. The microbiome influences immune signaling through microorganism-associated molecular patterns (MAMPs) and pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). Additionally, microbial metabolites-such as short-chain fatty acids (SCFAs), tryptophan derivatives, and secondary bile acids-exert significant immunomodulatory effects. The intestinal epithelial barrier is also described as an active immunological interface contributing to systemic regulation. The literature highlights innovative therapies, including fecal microbiota transplantation (FMT), probiotics, and microbiome editing with CRISPR-Cas technologies. These strategies aim to restore microbial balance and improve immune outcomes. The growing body of evidence positions the microbiome as a valuable clinical and diagnostic target, with significant potential for application in personalized medicine.}, }
@article {pmid41011312, year = {2025}, author = {Corona-Angeles, JA and Martínez-Pulido, RL and Oregon-Romero, E and Palafox-Sánchez, CA}, title = {Role of the Microbiome and Its Metabolites in Primary Sjögren's Syndrome.}, journal = {Microorganisms}, volume = {13}, number = {9}, pages = {}, doi = {10.3390/microorganisms13091979}, pmid = {41011312}, issn = {2076-2607}, abstract = {Primary Sjögren's syndrome (pSS) is a chronic, autoimmune rheumatic disease characterized by progressive lymphocytic infiltration of the exocrine glands, leading to inflammation and subsequent tissue damage. As a multifactorial disease, its etiology is complex, making it difficult to predict disease progression. Among the environmental factors implicated in pSS, the involvement of microorganisms has gained increasing attention. Since the launch of the Human Microbiome Project, growing evidence has highlighted the role of dysbiosis in the pathogenesis of various autoimmune diseases, including pSS. Shifts in the abundance of specific bacterial phyla can lead to corresponding changes in the levels of key microbial metabolites involved in tissue homeostasis and immune regulation-such as short-chain fatty acids (SCFAs), choline, taurine, serine, lactate, and tryptophan and their metabolites. Understanding the mechanisms by which these metabolites influence immune processes may provide deeper insights into the progression of the disease. Therefore, this review aims to explore the mechanisms through which microbiota-derived metabolites contribute to the pathophysiology of primary Sjögren's syndrome.}, }
@article {pmid41009770, year = {2025}, author = {Pita-Galeana, MA and Ruhle, M and López-Vázquez, L and de Anda-Jáuregui, G and Hernández-Lemus, E}, title = {Computational Metagenomics: State of the Art.}, journal = {International journal of molecular sciences}, volume = {26}, number = {18}, pages = {}, doi = {10.3390/ijms26189206}, pmid = {41009770}, issn = {1422-0067}, mesh = {*Metagenomics/methods ; Humans ; *Microbiota/genetics ; *Computational Biology/methods ; Machine Learning ; Metagenome ; }, abstract = {Computational metagenomics has revolutionized our understanding of the human microbiome, enabling the characterization of microbial diversity, the prediction of functional capabilities, and the identification of associations with human health outcomes. This review provides a concise yet comprehensive overview of state-of-the-art computational approaches in metagenomics, alongside widely used methods and tools employed in amplicon-based metagenomics. It is intended as an introductory resource for new researchers, outlining key methodologies, challenges, and future directions in the field. We discuss recent advances in bioinformatics pipelines, machine learning (ML) models, and integrative frameworks that are transforming our understanding of the microbiome's role in health and disease. By addressing current limitations and proposing innovative solutions, this review aims to outline a roadmap for future research and clinical translation in computational metagenomics.}, }
@article {pmid41000747, year = {2025}, author = {Tripp, AD and Qu, EB and Balogun, I and Brodsky, J and Baker, JS and Mancuso, CP and Roux, S and Hussain, FA and Lieberman, TD}, title = {Phage-mediated lysis does not determine Cutibacterium acnes colonization on human skin.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.09.09.675206}, pmid = {41000747}, issn = {2692-8205}, abstract = {Despite Cutibacterium acnes being the most abundant and prevalent bacteria on human skin, only a single type of phage has been identified that infects this host. Here, we leverage this one-to-one system to systematically characterize how the phage-bacteria arms race shapes C. acnes evolution and community composition on individual people. Our analysis reveals a surprising lack of phage-mediated selection despite global prevalence of C. acnes phages. Analysis of anti-phage defense systems across 3,205 bacterial genomes revealed a limited, phylogenetically restricted defense repertoire under weak selective pressure to diversify or be maintained. Functional assays did not reveal alternative phage resistance mechanisms or fitness costs associated with defense gene carriage that could explain this limited immune arsenal. This lack of pressure to maintain phage resistance could not be explained by lack of phage colonization, as examination of 471 global human facial skin metagenomes demonstrated that even in samples with high virus-to-microbe ratio, phage-sensitive clades dominate on-person populations. Together, these findings indicate that phage pressure, while present, does not play a critical role in determining strain fitness and success within C. acnes populations on human skin. We propose that this observed weak phage-mediated selective pressure can be explained by the anatomy of skin: C. acnes growth is thought to occur at the bottom of pores, where exposure to phage may be limited by physical barriers. Together, this portrait of a static arms race provides a strong contrast with other microbial species in different ecosystems and expands understanding of phage-bacteria interactions in the human microbiome.}, }
@article {pmid40999889, year = {2025}, author = {Tu, Z and Lin, J and Li, Z and Zhu, Y and Xu, C and Qiu, Z and Wang, Q and Ye, Y and Wen, Y and Li, J and Leong, KW and Wen, W}, title = {Tackling Allergic Airway Inflammation with Organic Sheet-Like Nanoplatforms by Targeted Elimination of Epithelial Small Extracellular Vesicles.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e04197}, doi = {10.1002/advs.202504197}, pmid = {40999889}, issn = {2198-3844}, support = {82271188//National Natural Science Foundation of China/ ; 82020108009//National Natural Science Foundation of China/ ; 81900918//National Natural Science Foundation of China/ ; 2022QNRC001//Young Elite Scientists Sponsorship Program by CAST/ ; 2025A04J7163//Funding by Science and Technology Projects in Guangzhou/ ; 2023P-ZD06//Key Clinical Technique of Guangzhou/ ; 2023B1111040004//Guangdong Natural Science Foundation of China/ ; 2022A1515010002//Guangdong Natural Science Foundation of China/ ; 2022A1515010506//Guangdong Natural Science Foundation of China/ ; }, abstract = {Allergic airway inflammatory disorders, such as allergic rhinitis (AR) and asthma, affect the health of more than one billion people worldwide, yet therapeutic outcomes remain unsatisfactory. 2D nanomaterials are extensively adopted in biomedical research, but their inorganic components often limit clinical applications. To address these challenges, functionalized "inorganic-free" nanosheets PNSE are developed as a potential strategy for alleviating allergic inflammation via targeted elimination of epithelial small extracellular vesicles (sEVs). PNSE are prepared using template-based synthesis technology and modified with epidermal growth factor receptor aptamers, which exhibit low cytotoxicity, mild protein adsorption, and potent epithelial sEVs binding efficacy. PNSE suppresses sEVs-triggered stimulator of interferon genes activation, alleviating the dendritic cell maturation and eosinophil extracellular trap formation in vitro. In addition, PNSE displays exceptional biocompatibility, preferential airway localization, and robust modulation for allergic airway inflammation in vivo. Transcriptome analysis and multi-channel flow cytometry of airway tissues further confirm the alleviation of dysregulated airway inflammation in house dust mite-stimulated animal models. These results highlight the pivotal feature of the organic sheet-like nanoplatforms for targeted clearance of epithelial sEVs, which can be exploited as a nanomedicine for the treatment of allergic airway inflammation and also other allergic disorders.}, }
@article {pmid40997670, year = {2025}, author = {Cho, HS and Lee, JW and Cha, HE and Seo, J and Lim, SK}, title = {Comparative analysis of skin microbiome across 10 sites in Koreans for forensic applications: a pilot study.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {78}, number = {}, pages = {102706}, doi = {10.1016/j.legalmed.2025.102706}, pmid = {40997670}, issn = {1873-4162}, abstract = {Various microorganisms have a symbiotic relationship with human skin cells, influenced by intrinsic and extrinsic factors. The composition of the human microbiome varies based on the skin site. To investigate the microbial characteristics of different skin sites in Koreans, microbiome samples were collected from the scalp, forehead, cheek, retroauricular crease, cervical vertebrae, axilla, palm, lateral finger, femur, and plantar skin. The concentrations of human and bacterial DNA were quantified, and QIIME2 and MicrobiomeAnalyst platforms were used for microbial analysis. Forehead and cheek microbiome compositions were similar, with higher proportions of Streptococcus than that at other sites. Palm and lateral finger microbiome compositions were also similar, with higher proportions of Haemophilus than that at other sites. Lawsonella was specifically observed on the scalp, while Mycoplasma was found on cervical vertebrae. Staphylococcus, observed on all sites, was particularly predominant on axilla. The microbial composition of plantar was distinct, with no prevalent genus compared to that at other sites. Further research analyzing skin microbiomes from forensic evidence could help identify the origin of skin samples, aiding in crime scene reconstruction. Comparing our findings from Korean participants with international studies, it suggests that expanding research to include diverse populations could reveal regional and national differences in skin microbiomes, providing valuable insights for forensic science.}, }
@article {pmid40996703, year = {2025}, author = {Sierra, MA and Ryon, K and Arikatla, MR and Elshafey, R and Bhaskar, H and Proszynski, J and Bhattacharya, C and Shaaban, H and Danko, DC and Ambrose, P and Spaulding, SA and Zambrano, MM and Consortium, TMD and Mason, CE}, title = {The Microbe Directory: a centralized database for biological interpretation of microbiome data.}, journal = {Database : the journal of biological databases and curation}, volume = {2025}, number = {}, pages = {}, doi = {10.1093/database/baaf060}, pmid = {40996703}, issn = {1758-0463}, support = {U01DA053941/NH/NIH HHS/United States ; U54AG089334/NH/NIH HHS/United States ; R01AI151059/NH/NIH HHS/United States ; 80NSSC24K0728/NASA/NASA/United States ; 80NSSC24K1052/NASA/NASA/United States ; //WorldQuant Foundation/ ; }, mesh = {*Microbiota/genetics ; Humans ; *Databases, Genetic ; Data Curation ; Metadata ; Animals ; Metagenomics ; }, abstract = {The Microbe Directory (TMD) is a centralized database of metadata for microbes from all domains that helps with the biological interpretation of metagenomic data. The database comprises phenotypical and ecological traits of microorganisms, which have been verified by independent manual annotations. This effort has been possible by the help of a community of volunteer students worldwide who were trained in manual curation of microbiology data. To summarize this information, we have built an interactive browser that makes the database accessible to everyone, including non-bioinformaticians. We used the TMD data to analyse microbiome samples from different projects such as MetaSUB, TARA Oceans, Human Microbiome Project, and Sponge Microbiome Project, showcasing the utility of TMD. Furthermore, we compare our microbial annotations with annotations collected by artificial intelligence (AI) and demonstrate that despite the high speed of AI in reviewing and collecting microbial data, annotation requires domain knowledge and therefore manual curation. Collectively, TMD provides a unique source of information that can help to interpret microbiome data and uncover biological associations. Database URL: www.themicrobedirectory.com/.}, }
@article {pmid40996271, year = {2025}, author = {Wong, MK and Armstrong, E and Heirali, AA and Schneeberger, PHH and Chen, H and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Siu, LL and Spreafico, A and Coburn, B}, title = {Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.}, journal = {mBio}, volume = {}, number = {}, pages = {e0190425}, doi = {10.1128/mbio.01904-25}, pmid = {40996271}, issn = {2150-7511}, abstract = {Composition and function of the gut microbiome are associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models in recapitulating ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure, and their ecological features were compared to human donors by metagenomic sequencing. HMA mice resembled other mice more than their respective human donors in gut microbial composition and function, with taxa including Akkermansia muciniphila and Bacteroides spp. enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse data sets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice was more like other mice than their human donor. Our data suggest that HMA mice are limited models for assessing the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overshadow ecological effects of treatments in humans that HMA models aim to recapitulate.IMPORTANCEHMA mice are models that better represent human gut ecology compared to conventional laboratory mice and are commonly used to test the effects of the gut microbiome on disease or treatment response. We evaluated the fidelity of using HMA mice as avatars of ecological response to a human microbial consortium, Microbial Ecosystem Therapeutic 4. Our results show that HMA mice in our cohort and across other published studies are more similar to each other than the human donors or inoculum they are derived from and harbor a taxonomically restricted gut microbiome. These findings highlight the limitations of HMA mice in evaluating the ecological effects of complex human microbiome-targeting interventions, such as microbial consortia.}, }
@article {pmid40990521, year = {2025}, author = {Robinson, JM and Breed, MF}, title = {Beyond microbial exposure and colonization: multisensory shaping of the gut microbiome.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0110725}, doi = {10.1128/msystems.01107-25}, pmid = {40990521}, issn = {2379-5077}, abstract = {Microorganisms play a fundamental role in human health, contributing to digestion, immune regulation, and metabolic processes. While direct colonization by environmental microbes through ingestion, inhalation, and dermal contact has been documented, evidence suggests that multisensory interactions with nature-via visual, auditory, tactile, gustatory, and olfactory stimuli-also influence the gut microbiome through psychophysiological and immune-mediated pathways. Exposure to natural environments can regulate stress and immune responses, activate the parasympathetic nervous system, and modulate the hypothalamic-pituitary-adrenal and gut-brain axes, which in turn may alter gut microbiome composition and function. Furthermore, sensory interactions with nature may induce epigenetic changes that impact immune function and microbiome dynamics over time. Here, we review evidence for nature-based indirect shaping of the human microbiome (including multisensory and exposure-immunoregulation pathways) and suggest that after the early-life critical window of microbiome development (0-3 years), these indirect effects likely have a greater influence on gut microbiome dynamics than direct colonization by environmental microbiota (e.g., ingested directly from the air). However, this concept remains to be comprehensively tested. Therefore, understanding the relative contributions of direct microbial colonization versus indirect effects-such as multisensory stimulation and immune modulation-demands more integrated, transdisciplinary research. Integrating these insights into public health strategies, urban design, and nature-based interventions could promote microbiome eubiosis, ultimately improving human (and non-human animal) well-being in an era of increasing environmental and health challenges.}, }
@article {pmid40986279, year = {2025}, author = {Korsurat, S and Koslovsky, MD}, title = {A Bayesian semiparametric mixture model for clustering zero-inflated microbiome data.}, journal = {Biometrics}, volume = {81}, number = {3}, pages = {}, doi = {10.1093/biomtc/ujaf125}, pmid = {40986279}, issn = {1541-0420}, support = {DMS-2245492//National Science Foundation/ ; }, mesh = {Bayes Theorem ; Humans ; Cluster Analysis ; *Models, Statistical ; Computer Simulation ; *Microbiota ; *Gastrointestinal Microbiome ; Diarrhea/microbiology ; }, abstract = {Microbiome research has immense potential for unlocking insights into human health and disease. A common goal in human microbiome research is identifying subgroups of individuals with similar microbial composition that may be linked to specific health states or environmental exposures. However, existing clustering methods are often not equipped to accommodate the complex structure of microbiome data and typically make limiting assumptions regarding the number of clusters in the data which can bias inference. Designed for zero-inflated multivariate compositional count data collected in microbiome research, we propose a novel Bayesian semiparametric mixture modeling framework that simultaneously learns the number of clusters in the data while performing cluster allocation. In simulation, we demonstrate the clustering performance of our method compared to distance- and model-based alternatives and the importance of accommodating zero-inflation when present in the data. We then apply the model to identify clusters in microbiome data collected in a study designed to investigate the relation between gut microbial composition and enteric diarrheal disease.}, }
@article {pmid40985730, year = {2025}, author = {Farmer, NM and Benezra, A and Maki, KA and Ishaq, SL and Kozik, AJ}, title = {Prioritizing precision: guidelines for the better use of population descriptors in human microbiome research.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0064025}, doi = {10.1128/msystems.00640-25}, pmid = {40985730}, issn = {2379-5077}, abstract = {Microbiome science is a celebration of the connections between humans, our environment, and microbial organisms. We are continually learning more about our microbial fingerprint, how each microbiome may respond to identical stimuli differently, and how the quality of the environmental conditions around us influences the microorganisms we encounter and acquire. However, in this process of self-discovery, we have utilized socially constructed ideas about ourselves as biological factors, potentially obscuring the true nature of our relationships to each other, microbes, and the planet. The concept of race, which has continuously changing definitions over hundreds of years, is frequently operationalized as a proxy for biological variation and suggested to have a real impact on the microbiome. Scientists across disciplines and through decades of research have misused race as a biological determinant, resulting in falsely scientific justifications for social and political discrimination. However, concepts of race and ethnicity are highly nuanced, inconsistent, and culturally specific. Without training, microbiome researchers risk continuing to misconstrue these concepts as fixed biological factors that have direct impacts on our microbiomes and/or health. In 2023, the National Academies of Sciences, Engineering, and Medicine released recommendations on the use of population descriptors such as race and ethnicity in genetic science. In this paper, we posit similar recommendations that can and must be translated into microbiome science to avoid re-biologizing race and that push us toward the goal of understanding the microbiome as an engine of adaptation to help us thrive in a dynamic world.}, }
@article {pmid40985585, year = {2025}, author = {Imre, A and Crook, N}, title = {The emerging roles of non-Saccharomyces yeasts in fermented foods and human health.}, journal = {FEMS yeast research}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsyr/foaf056}, pmid = {40985585}, issn = {1567-1364}, abstract = {Yeasts play a crucial role in the maturation of fermented foods, with Saccharomyces cerevisiae standing out as the most prominent among them. However, in recent years, there has been a growing interest in the roles and applications of non-Saccharomyces yeasts in fermented products. Their contribution to shape the characteristics of fermented foods like wine, beer, sourdough bread, cheese, and kombucha is undeniable, yet our understanding of the specific effects of each species remains incomplete in certain cases. In this mini-review, we collected and summarized studies that aimed to gain deeper understanding of the microbial dynamics and roles of non-Saccharomyces yeasts during the fermentation and development of alcoholic and non-alcoholic fermentations, as well as highlight that non-Saccharomyces yeasts are recently also recognized for benefiting the human microbiome as probiotics, further expanding their potential contributions to human health and supplementation.}, }
@article {pmid40983700, year = {2025}, author = {Xiang, G and Wang, Y and Ni, K and Luo, H and Liu, Q and Song, Y and Miao, P and He, L and Jian, Y and Yang, Z and Chen, T and Xu, K and Sun, X and Shen, Z and Ji, C and Zhao, N and He, M and Pan, Y and Luo, Y and Hu, J and Otto, M and Li, M}, title = {Nasal Staphylococcus aureus carriage promotes depressive behaviour in mice via sex hormone degradation.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {40983700}, issn = {2058-5276}, support = {AI000904//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ ; 82472288//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82302595//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82172325//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The human microbiome has a pronounced impact on human physiology and behaviour. Despite its unique anatomical connection to the brain, the role of the nasal microbiome in neurological diseases is understudied. Here, using human data and experiments in mice, we show that nasal Staphylococcus aureus is linked to depression. Nasal microbiome analyses revealed a positive correlation between depression scores and S. aureus abundance among patients with depression and healthy controls. Metabolomics of the nasal cavity showed decreased sex hormones, estradiol and testosterone in patients with depression versus controls. Nasal microbiota transplants from patients reproduced depression-like behaviour in mice with differential abundance of S. aureus. Further homology and mutational analysis uncovered an S. aureus sex hormone-degrading enzyme, 17b-hydroxysteroid dehydrogenase (Hsd12), which degraded testosterone and estradiol in mice, leading to lower levels of dopamine and serotonin in the murine brain. These findings reveal a nasal commensal that influences depressive behaviour and provides insights into the nose-brain axis.}, }
@article {pmid40983504, year = {2025}, author = {Zhou, T and Zhao, F}, title = {AI-empowered human microbiome research.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2025-335946}, pmid = {40983504}, issn = {1468-3288}, abstract = {Recent advances in high-throughput microbiome profiling have generated expansive data sets that offer unprecedented opportunities to investigate the role of microbes in human health. However, the complexity and high dimensionality of these data present significant analytical challenges that often exceed the capabilities of traditional computational methods. Artificial intelligence (AI), encompassing both classical machine learning and modern deep learning approaches, has emerged as a powerful solution to these challenges. In this review, we systematically explore AI-driven methodologies in microbiome research, including clustering algorithms, dimensionality reduction techniques, convolutional and recurrent neural networks, and emerging large language models. We assess how these approaches enable the extraction of meaningful biological patterns from complex microbial data from a multiscale perspective, facilitating insights into community dynamics, host-microbe interactions and functional genomics. Additionally, we explore the transformative impact of AI on translational applications across both academic research and real-world clinical settings, including disease diagnostics, therapeutic development and precision microbiome engineering. By critically evaluating the current capabilities and limitations of AI in this context, this review aims to chart a path forward for the integration of AI into microbiome research, ultimately accelerating innovations in personalised medicine and deepening our understanding of host-microbiome relationships.}, }
@article {pmid40982389, year = {2025}, author = {Pizzini, JD and Midani, FS and Britton, RA}, title = {Updated Protocol for the Assembly and Use of the Minibioreactor Array (MBRA).}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {223}, pages = {}, doi = {10.3791/68788}, pmid = {40982389}, issn = {1940-087X}, mesh = {*Bioreactors/microbiology ; *Microbiota/physiology ; Humans ; }, abstract = {The human microbiome comprises diverse and dynamic microbial communities that play essential roles in host health. Understanding these communities and their responses to environmental factors is critical for advancing microbiome-based therapeutics. Traditional in vitro models for cultivating human-derived microbiota often lack scalability and require extensive technical expertise, limiting their accessibility and throughput. To address these limitations, we developed the Minibioreactor Array (MBRA) system -- a modular, single-stage, continuous-flow platform for high-throughput cultivation of microbial communities. This system enables parallel cultivation of up to 48 distinct microbial communities, supporting experimental flexibility while maintaining the stable growth of complex ecosystems. This protocol provides detailed guidance on MBRA fabrication, assembly, sterilization, and operation. The system's modular design allows for easy integration into anaerobic chambers and supports customization for a wide range of experimental applications. It has been used to study microbial responses to antibiotics, dietary compounds, and pathogen invasion, and to screen for pathogen-resistant communities. With its accessibility, scalability, and reproducibility, the MBRA represents a powerful model system for investigating microbial interactions and advancing microbiome research.}, }
@article {pmid40981537, year = {2025}, author = {Nichter, M}, title = {Public Understanding of Gut Health and the Human Microbiome in the USA: An Exploratory Study.}, journal = {Medical anthropology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/01459740.2025.2558836}, pmid = {40981537}, issn = {1545-5882}, abstract = {At a time of rising public interest in the human microbiome and calls for increased microbe literacy in public health, few studies have explored how different segments of the US public understand gut health. To address this gap, An exploratory ethnographic study was conducted in Southern Arizona. The study identified five themes that encompass Pasteurian militaristic and post-Pasteurian ecological perceptions of gut health, gut adaptability, and probiotic/antibiotic influence on" natural immunity." Future microbe literacy programs will need to engage with local ideas about gut health, build upon points of convergence with bioscience, and identify points of divergence that challenge public health initiatives.}, }
@article {pmid40981416, year = {2025}, author = {Mulay, SA and Vishnivetskaya, TA and Hochanadel, LH and Klingeman, DM and Lloyd, KG and Pelletier, DA and Podar, M}, title = {BONCAT-Live for isolation and cultivation of active environmental bacteria.}, journal = {mBio}, volume = {}, number = {}, pages = {e0238925}, doi = {10.1128/mbio.02389-25}, pmid = {40981416}, issn = {2150-7511}, abstract = {In diverse environments, microbes drive a myriad of processes, from geochemical and nutrient cycling to interspecies interactions, including associations with plants and animals. Their physiological state is dynamic and impacted by abiotic and biotic conditions, responding to environmental fluctuations by changes in cellular metabolism, according to their genetic potential. Molecular, cellular, and genomic approaches can identify and measure microbial responses and adaptation to environmental changes in native communities. However, isolating individual microbial cells that respond to specific changes for cultivation has been difficult. To address this, we implemented a novel bacterial isolation approach (BONCAT-Live) by integrating bio-orthogonal non-canonical amino acid tagging (BONCAT) in diverse native communities, with isolation and cultivation of cells responding to specific stimuli, at different time scales. In frozen Arctic permafrost samples, we identified and isolated dormant bacteria that become active after thawing under native or nutrient-enriched conditions. From the Populus tree rhizosphere, we isolated strains that thrive under high concentrations of root exudates that act as defense compounds and nutrients. In the human microbiome, we identified and isolated bacteria that rapidly proliferated when exposed to metabolites provided by the host or other co-occurring microbes. Further characterization of isolated bacterial strains will provide opportunities for in-depth determination of how these microbes adapt to changes in their environments, individually and as part of model communities.IMPORTANCEDynamic microbial activity transforms environments and impacts health and disease in associations with plants and animals, including humans. Identifying the contribution of individual microbes to those processes in real time has not been generally compatible with their selective cultivation. BONCAT-Live tracks which bacteria in environmental samples are translationally active and couples it with single-cell isolation and cultivation. By studying the response of individual community members to specific natural or induced physical or chemical changes in the environment and culturing those organisms, BONCAT-Live enables further insights into microbial metabolic strategies, community dynamics, and environmental adaptations.}, }
@article {pmid40972768, year = {2025}, author = {Dhakal, B and Kishore, LS and Sayed, K}, title = {Integrating multi-compartment microbiome data with clinical parameters enhances mortality prediction using autoencoder.}, journal = {Journal of microbiological methods}, volume = {}, number = {}, pages = {107267}, doi = {10.1016/j.mimet.2025.107267}, pmid = {40972768}, issn = {1872-8359}, abstract = {The human microbiome, a complex ecosystem of microorganisms residing in different body compartments, significantly influences health outcomes and disease progression, however, leveraging this data for developing clinical prediction models remains challenging due to its high dimensionality, sparsity, and compositional nature. Traditional machine learning approaches often struggle to capture the intricate microbial interactions that contribute to mortality risk, particularly when analyzing data across multiple compartments with distinct microbial compositions. To address these limitations, we introduce a novel framework utilizing an autoencoder-based model trained on high-dimensional microbiome data collected from oral, lung, and gut compartments. Our approach encodes microbiome data into a low-dimensional latent space while preserving essential microbial community characteristics, enabling more effective feature extraction and pattern recognition than conventional dimensionality reduction techniques. Through systematic evaluation of three data configurations-microbiome taxa only, clinical data only, and an integrated model combining both-we demonstrated that the integrated approach consistently achieved superior prediction accuracy (98 % in lung microbiome) compared to using either data source independently. Clinical data alone provided reasonable but inconsistent performance (70-90 %), while microbiome taxa alone yielded the weakest results (53-65 %). Furthermore, our investigation of preprocessing techniques revealed that applying z-score normalization to the taxa data significantly enhanced performance and substantially improved recall metrics across all compartments. By analyzing compartment-specific microbial contributions, our study reveals distinct predictive roles of the oral and lung microbiomes compared to the gut microbiome, underscoring of body-site specificity in microbiome-based predictive modeling.}, }
@article {pmid40970967, year = {2025}, author = {Lee, Y and Seo, H and Lee, S and Choi, D and Kim, S and Rahim, MA and Song, HY}, title = {Therapeutic potential of Bacillus sonorensis PMC204 membrane vesicles against drug-resistant Mycobacterium tuberculosis.}, journal = {Medical microbiology and immunology}, volume = {214}, number = {1}, pages = {43}, pmid = {40970967}, issn = {1432-1831}, support = {RS-2023-00219563//Ministry of Science and ICT, South Korea/ ; }, mesh = {*Mycobacterium tuberculosis/drug effects ; Mice ; Animals ; RAW 264.7 Cells ; *Probiotics/pharmacology ; *Bacillus/physiology/metabolism ; Macrophages/microbiology ; *Tuberculosis, Multidrug-Resistant/therapy ; Proteomics ; *Extracellular Vesicles/chemistry ; Antitubercular Agents/pharmacology ; Flagellin/metabolism ; }, abstract = {Tuberculosis remains a severe global health threat, exacerbated by the rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis. Despite the urgent need for effective interventions, the development of anti-tuberculosis drugs has been slow, and the emergence of pan-drug-resistant strains underscores the critical need for innovative therapeutic strategies. This study introduces Bacillus sonorensis PMC204, a novel probiotic strain with potent anti-tuberculosis properties identified through extensive screening. PMC204 significantly reduced M. tuberculosis H37Rv and XDR strains within Raw 264.7 macrophage cells. Moreover, membrane vesicles (MVs) derived from this strain exhibited superior inhibitory effects against both standard and XDR strains of M. tuberculosis. Proteomic analysis of the isolated MVs revealed a high abundance of flagellin proteins, which are hypothesized to play a pivotal role in the observed anti-tuberculosis effects. These findings also suggest a close link between the therapeutic efficacy of PMC204 and autophagy activation. Safety assessments further demonstrated the feasibility of PMC204 as a potential anti-tuberculosis therapeutic. The anti-tuberculosis activity of bacterial MVs represents an innovative approach in microbiome therapeutics, positioning PMC204 as a next-generation probiotic distinct from conventional strains. This study contributes to advancing the field of microbiome-based therapeutics and presents promising avenues for managing drug-resistant tuberculosis.}, }
@article {pmid40967861, year = {2025}, author = {Ma, Y and Si, JH and Sun, DJY and Yu, CQ and Pang, YJ and Lyu, J and Li, LM}, title = {[Progress in population-based research of human microbiome and cardiovascular diseases].}, journal = {Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi}, volume = {46}, number = {9}, pages = {1680-1687}, doi = {10.3760/cma.j.cn112338-20241219-00816}, pmid = {40967861}, issn = {0254-6450}, support = {2023ZD0510101, 2023ZD0510100//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; }, mesh = {Humans ; *Cardiovascular Diseases/microbiology ; *Microbiota ; Metagenomics ; }, abstract = {The human microbiome encompasses a diverse array of microorganisms and their functional interactions within the human body. It exhibits a vast diversity of species and complex roles across various body environments. Advanced sequencing technologies, such as 16S amplicon sequencing and metagenomic sequencing, facilitate in-depth analysis on this microbial community. Recent researches have suggested that characteristics of the human microbiome (such as diversity and composition of microbiome, involving metabolic pathways and metabolites) might be associated with the onset and progression of cardiovascular diseases. These findings provide valuable insights into the etiology of chronic diseases and might aid in the development of novel disease biomarkers and intervention strategies. This paper summarizes the designs, current status and key findings of current population-based research in this field, and introduce the future development and analyze the existing critical problems that need further investigations.}, }
@article {pmid40955307, year = {2025}, author = {Li, W and Liu, Q and Chen, S and Zhi, M and Yang, P and Zhang, Y and Wu, Z and Zhang, J and Feng, Q}, title = {Salidroside Improves Periodontitis by Mitigating Inflammatory Reactions and Enhancing Osteogenic Differentiation of Human Periodontal Ligament Stem Cells.}, journal = {Drug design, development and therapy}, volume = {19}, number = {}, pages = {8097-8114}, pmid = {40955307}, issn = {1177-8881}, mesh = {*Periodontal Ligament/drug effects/cytology/pathology ; *Glucosides/pharmacology/administration &amp; dosage ; Humans ; *Osteogenesis/drug effects ; *Periodontitis/drug therapy/pathology/metabolism ; *Phenols/pharmacology/administration &amp; dosage ; *Cell Differentiation/drug effects ; Animals ; Rats ; *Stem Cells/drug effects/metabolism ; *Inflammation/drug therapy/metabolism/pathology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Male ; Rats, Sprague-Dawley ; Lipopolysaccharides/antagonists &amp; inhibitors/pharmacology ; Disease Models, Animal ; }, abstract = {PURPOSE: Salidroside (Sal), a significant bioactive compound found in Rhodiola rosea, is documented to possess various pharmacological properties. This study investigated the effects of Sal in alleviating periodontitis.<br><br>METHODS: The rat periodontitis model was utilized to assess the therapeutic impact of Sal on periodontitis. Human periodontal ligament stem cells (hPDLSCs) were used to investigate the effect of Sal on lipopolysaccharide (LPS)-inhibited osteogenic differentiation. RNA sequencing (RNA-seq), and Western blot were employed to analyze the genes and proteins impacted by Sal treatment.<br><br>RESULTS: Sal significantly alleviated the alveolar bone loss and gingival inflammation in rats periodontitis model. Sal demonstrated a dose-dependent pattern of promoting osteogenesis on hPDLSCs. A concentration of 0.5&#xa0;&#x3bc;M Sal could effectively counteract the impact of LPS on osteogenic differentiation. Mechanically, Sal inhibited the ratios of phospho-I&#x3ba;B&#x3b1;(p-I&#x3ba;B&#x3b1;)/I&#x3ba;B&#x3b1; and phospho-p65(p-p65)/p65 in Nuclear Factor kappa-B (NF-&#x3ba;B) pathway and reduced the expressions of interleukin-6 (IL-6) and interleukin-8 (IL-8). Sal increased the expression of lymphoid enhancer-binding factor 1 (LEF1).<br><br>CONCLUSION: Sal promoted the osteogenic differentiation by inhibiting the activation of the NF-&#x3ba;B pathway and increasing the expression of LEF1.}, }
@article {pmid40946177, year = {2025}, author = {Shi, JH and Tang, QL and Wang, JH and Long, YL and Zhao, SF and Zhao, Z and Xie, WT and Li, ZM and Lu, HM and Gao, TX and Fang, ZZ and Zhou, T and Li, BX and Yang, X and Gao, GQ and Qi, WW}, title = {Pigment Epithelium-Derived Factor Deficiency Impairs Hippocampal Glutamate Homeostasis and Cognitive Function by Downregulating Astrocytic GLT-1.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e00402}, doi = {10.1002/advs.202500402}, pmid = {40946177}, issn = {2198-3844}, support = {82273116//National Natural Science Foundation of China/ ; 82203661//National Natural Science Foundation of China/ ; 2024A1515010149//Guangdong Natural Science Fund/ ; 2023A1515010214//Guangdong Natural Science Fund/ ; 202102100004//Guangzhou Key Laboratory for Metabolic Diseases/ ; }, abstract = {Maintenance of glutamate homeostasis is essential for synaptic plasticity and cognition. Disrupted glutamate-glutamine cycling causes chronic excitotoxicity, a key driver of cognitive deficits in Alzheimer's disease (AD), though regulatory mechanisms remain unclear. Pigment epithelium-derived factor (PEDF), a neuroprotective protein declining with age, is demonstrated here to play a novel role in synaptic glutamate clearance. Analysis of peripheral blood samples from 19 patients with AD and 75 non-dementia control subjects revealed lower levels of PEDF in patients, and loss of PEDF correlates with cognitive decline. PEDF-deficient mice exhibit defective learning and memory, and higher susceptibility to AD. Furthermore, PEDF deficiency impaired synaptic plasticity and dendritic spine morphology. Mechanistically, PEDF inhibits ubiquitin-proteasome-dependent degradation of astrocytic glutamate transporter-1 (GLT-1) and normally guarantees elimination of synaptic glutamate by modulating the protein kinase C signaling pathway. Strikingly, restoring PEDF rescued cognitive deficits in a mouse model of AD, and upregulation of GLT-1 rescued cognitive impairment in PEDF-deficient mice. Collectively, these findings reveal PEDF is a physiologic regulator of synaptic glutamate homeostasis. Targeting PEDF deficiency-induced neural impairment may provide a novel avenue for the development of new therapeutic applications for neurodegenerative diseases associated with glutamate-induced excitotoxicity.}, }
@article {pmid40944126, year = {2025}, author = {Napier, BA and Allegretti, JR and Feuerstadt, P and Kelly, CR and Van Hise, NW and Jäger, R and Kassam, Z and Reid, G}, title = {Multi-Species Synbiotic Supplementation Enhances Gut Microbial Diversity, Increases Urolithin A and Butyrate Production, and Reduces Inflammation in Healthy Adults: A Randomized, Placebo-Controlled Trial.}, journal = {Nutrients}, volume = {17}, number = {17}, pages = {}, doi = {10.3390/nu17172734}, pmid = {40944126}, issn = {2072-6643}, support = {N/A//Seed Health, Inc./ ; }, abstract = {Background: In healthy adults, probiotic supplementation alone does not increase Urolithin A (UroA) and rarely increases butyrate, both microbiome-derived metabolites that influence key biological functions involved in regulating gastrointestinal symptoms. Accordingly, this clinical trial evaluated key biological functions of a multi-species synbiotic with 24 probiotic strains and a polyphenol-based prebiotic using capsule-in-capsule delivery technology. Methods: We conducted a randomized, placebo-controlled trial among healthy participants (n = 32). Participants were administered a daily synbiotic (53.6 billion AFU multi-species probiotic and 400 mg Indian pomegranate extract; DS-01) or matching placebo for 91 days. Samples were obtained at baseline Day 0, and Days 7, 14, 49, and 91. Endpoints included changes in fecal microbiome composition, urinary UroA, fecal butyrate, serum CRP, and safety. Results: The synbiotic significantly increased alpha-diversity of Bifidobacterium and Lactobacillus spp. at all timepoints, including at end-of-study (Day 91, p < 0.0001) and increased native beneficial microbes. UroA production was significantly increased in the synbiotic arm at short-term (Day 7, 12-fold, p < 0.02) and long-term (Day 91, 49-fold, p < 0.001) timepoints. A higher proportion of synbiotic participants were capable of converting polyphenols into UroA (Day 91, 100% vs. 44.4%; p < 0.01). Mechanistically, synbiotic participants showed an increased abundance of Lactobacillus species involved in UroA precursor metabolism and UroA-producing Gordonibacter species. The synbiotic also significantly increased fecal butyrate levels (p < 0.03), and butyrate-producing species, in low-baseline butyrate producers, through Day 91, and was associated with reduced systemic inflammation. Conclusions: This multi-species synbiotic significantly increases diversity and abundance of key beneficial bacteria, enhances UroA production and butyrate levels, and is associated with lowered systemic inflammation. This is the first synbiotic to increase both UroA and butyrate.}, }
@article {pmid40943494, year = {2025}, author = {Barraza-Ortega, E and Gómez-Gil, B and García-Gasca, T and Lizárraga, D and Díaz, N and García-Gasca, A}, title = {The Impact of Lifestyle on Reproductive Health: Microbial Complexity, Hormonal Dysfunction, and Pregnancy Outcomes.}, journal = {International journal of molecular sciences}, volume = {26}, number = {17}, pages = {}, doi = {10.3390/ijms26178574}, pmid = {40943494}, issn = {1422-0067}, abstract = {Endocrine dysfunctions refer to alterations in hormone production, release, or regulation that can significantly impact health. In pregnant women or those planning pregnancy, these conditions may manifest as disorders such as polycystic ovary syndrome, hypothyroidism, endometriosis, gestational diabetes mellitus, and other metabolic issues, which could potentially cause infertility or pregnancy complications. Research and clinical experience indicate that hormones play a crucial role in basic physiology and are essential for overall health and well-being. At the same time, lifestyle-defined as daily habits related to nutrition, exercise, sleep, stress management, and other factors-directly influences microbial composition and hormonal regulation. The human microbiome, a diverse community of microorganisms residing within the human body, plays essential roles in supporting overall health. The increasing prevalence of hormonal disorders, especially in urban populations, has heightened interest in how modern lifestyles-characterised by sedentary habits, chronic stress, imbalanced diets, and inadequate sleep-may contribute to the development or aggravation of these conditions, leading to higher infertility rates or pregnancy complications if untreated. This review investigates the interaction between hormonal dysfunction, the human microbiome, and lifestyle factors, with a focus on their effects on pregnant women and those seeking to conceive. Its purpose is to provide a comprehensive overview of the underlying pathophysiological mechanisms and to examine preventative and therapeutic approaches that could alter these patterns.}, }
@article {pmid40938107, year = {2025}, author = {Stinson, LF and Pang, WW and Rea, A and Fok, D and Chua, MC and Tan, KH and Yap, F and Godfrey, KM and Shek, LP and Eriksson, JG and Chong, Y-S and Chan, S-Y and Wlodek, M and Geddes, DT}, title = {Composition of the human milk microbiome in the GUSTO cohort is shaped by intrapartum antibiotic prophylaxis and breastfeeding exclusivity.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0067725}, doi = {10.1128/msystems.00677-25}, pmid = {40938107}, issn = {2379-5077}, abstract = {Human milk contains a low biomass microbiome, which is thought to contribute to mammary and infant health. However, the determinants of the human milk microbiome across populations are poorly understood. Here, we characterized the microbiome of 266 milk samples collected from 208 mothers at 3 weeks and 3 months postpartum from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) study, a multi-ethnic Asian cohort. Full-length 16S rRNA gene sequencing showed a substantial level of inter-individual variation, as well as temporal variation, highlighting the need for broad-scale longitudinal sampling in this field. Milk microbiome composition and diversity were associated with maternal, socioeconomic, and breastfeeding factors. In particular, intrapartum antibiotic prophylaxis and breastfeeding exclusivity modulated milk bacterial composition and diversity, even at 3 months postpartum. These results highlight the dynamic nature of the human milk microbiome and its relationship with clinical and breastfeeding factors, with potential implications for infant health.IMPORTANCEHuman milk exposes infants to a constant source of maternal bacteria that may influence the development of the infant immune system and gut microbiome. However, compared to other body niches, the human milk microbiome is relatively under-studied, and there is limited consensus on the factors driving variance in these bacterial communities. In this study, we performed in-depth microbiome profiling of milk samples from 208 mothers in a diverse Asian population, finding a high level of variation between individuals and over time. We found that factors such as delivery-related antibiotics, breastfeeding practices, and maternal lifestyle can influence which bacteria are present in milk. These findings suggest that the milk microbiome is not static, but dynamic and shaped by both medical and social factors. Understanding what drives variance in the milk microbiome could help inform strategies to support maternal and infant health, especially in the critical early months of life when microbial exposures can have long-term effects.}, }
@article {pmid40930165, year = {2025}, author = {Chen, L and Zhang, Z and Yang, S and Tang, Y and Wang, X and Li, W and Yang, L and Guo, C and Fang, S and Xiao, W and Yan, M and Li, Y and Peng, T and Li, B and Zhang, XM and Huang, L}, title = {Developmental Neuroplasticity Enables Recovery from Anesthetic-Induced Synaptic Perturbations in the Immature Brain.}, journal = {Neurochemistry international}, volume = {}, number = {}, pages = {106051}, doi = {10.1016/j.neuint.2025.106051}, pmid = {40930165}, issn = {1872-9754}, abstract = {General anesthetics are essential in pediatric medicine, yet concerns persist regarding their potential neurotoxic effects on the developing brain. Whether transient synaptic disruptions caused by anesthesia lead to long-term deficits or are mitigated by endogenous plasticity remains unresolved. Here, we use longitudinal in vivo two-photon imaging in awake mice to investigate the structural and functional consequences of a single, clinically relevant exposure to sevoflurane at postnatal day 20. We find that sevoflurane induces transient behavioral hyperactivity and suppresses filopodia elimination. Remarkably, these effects are fully reversed within 24 hours. Across a 10-day follow-up, we observe no persistent alterations in synaptogenesis, neuronal activity, motor learning, or anxiety-like behavior. Electrophysiological recording and calcium imaging further confirm the restoration of normal firing and synaptic transmission in layer 5 pyramidal neurons. These findings reveal a dual-phase recovery mechanism-acute plasticity followed by chronic convergence-highlighting the developing brain's intrinsic resilience to transient anesthetic insults. Our study redefines sevoflurane not as a source of irreversible neurotoxicity but as a temporary challenge that can be effectively buffered by developmental neuroplasticity, offering important reassurance for its continued use in pediatric anesthesia.}, }
@article {pmid40928632, year = {2025}, author = {Mafe, AN and Smart, OO and Edo, GI and Akpoghelie, PO and Gaaz, TS and Yousif, E and Isoje, EF and Igbuku, UA and Ismael, SA and Essaghah, AEA and Ahmed, DS and Ozsahin, DU and Umar, H}, title = {Genesis, Health Benefits, and Future Perspectives of Probiotics: Exploring Endogenous and Exogenous Classes, Innovations, and Research Gaps.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40928632}, issn = {1867-1314}, abstract = {Probiotics are live beneficial microorganisms that confer health benefits to the host when administered in adequate amounts, have gained considerable scientific and commercial interest for their ability to support gut health, strengthen immunity, and reduce disease risk. This review traces the genesis of probiotic science from its origins in traditional fermented foods to contemporary clinical applications, offering a conceptual understanding of its evolution. A clear distinction is drawn between endogenous probiotics, naturally resident in the human microbiome, and exogenous probiotics, introduced via dietary supplements and functional foods. The broad spectrum of documented health benefits is examined, encompassing digestive, immune, metabolic, neurological, and dermatological outcomes. Recent innovations are highlighted, including bioengineered probiotic strains with targeted therapeutic functions, the integration of probiotics with prebiotics as synbiotics, and advanced delivery systems such as microencapsulation and nanotechnology. Special attention is given to regulatory frameworks, with global comparisons and a focused case study on Argentina, alongside a structured roadmap for translating research into market-ready products. The review also addresses inclusivity in probiotic use, emphasizing safety considerations across diverse populations, and underscores the strain-specific nature of probiotic effects. Current challenges such as commercialization gaps, regulatory inconsistencies, and underexplored applications in non-digestive health domains are critically discussed. The conclusion calls for interdisciplinary collaboration among microbiologists, nutritionists, clinicians, and technologists to accelerate innovation, ensure equitable access, and maximize the potential of probiotics in promoting health and preventing disease.}, }
@article {pmid40928232, year = {2025}, author = {Allman, HM and Bernate, EP and Franck, E and Oliaro, FJ and Hartmann, EM and Crofts, TS}, title = {Preparation of functional metagenomic libraries from low biomass samples using METa assembly and their application to capture antibiotic resistance genes.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0103925}, doi = {10.1128/msystems.01039-25}, pmid = {40928232}, issn = {2379-5077}, abstract = {A significant challenge in the field of microbiology is the functional annotation of novel genes from microbiomes. The increasing pace of sequencing technology development has made solving this challenge in a high-throughput manner even more important. Functional metagenomics offers a sequence-naive and cultivation-independent solution. Unfortunately, most methods for constructing functional metagenomic libraries require large input masses of metagenomic DNA, putting many sample types out of reach. Here, we show that our functional metagenomic library preparation method, METa assembly, can be used to prepare useful libraries from much lower input DNA quantities. Standard methods of functional metagenomic library preparation generally call for 5-60 µg of input metagenomic DNA. We demonstrate that the threshold for input DNA mass can be lowered at least to 30.5 ng, a 3-log decrease from prior art. We prepared functional metagenomic libraries using between 30.5 ng and 100 ng of metagenomic DNA and found that despite their limited input mass, they were sufficient to link MFS transporters lacking substrate-specific annotations to tetracycline resistance and capture a gene encoding a novel GNAT family acetyltransferase that represents a new streptothricin acetyltransferase, satB. Our preparation of functional metagenomic libraries from aquatic samples and a human stool swab demonstrates that METa assembly can be used to prepare functional metagenomic libraries from microbiomes that were previously incompatible with this approach.IMPORTANCEBacterial genes in microbial communities, including those that give resistance to antibiotics, are often so novel that sequencing-based approaches cannot predict their functions. Functional metagenomic libraries offer a high-throughput, sequence-naive solution to this problem, but their use is often held back due to their need for large quantities of metagenomic DNA. We demonstrate that our functional metagenomic library preparation method, METa assembly, can prepare these libraries using as little as ~30 ng of DNA, approximately 1,000-fold less than other methods. We use METa assembly to prepare functional metagenomic libraries from low-biomass aquatic and fecal swab microbiomes and show that they are home to novel tetracycline efflux pumps and a new family of streptothricin resistance gene, respectively. The efficiency of the METa assembly library preparation method makes many otherwise off-limits, low-biomass microbiome samples compatible with functional metagenomics.}, }
@article {pmid40927450, year = {2025}, author = {Montecillo, JAV and Lee, JH and Yoo, HJ and Lee, YY and Park, CM and Cho, A and Lee, H and Kim, JM and Lee, NY and Park, SH and Park, NJ and Han, HS and Chong, GO and Seo, I}, title = {Characterization of Streptococcus mitis subsp. carlssonii isolated from human vagina: prevalence, phenotypic, and genomic insights.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1625724}, pmid = {40927450}, issn = {1664-302X}, abstract = {The genus Streptococcus is a heterogenous group of commensal and pathogenic bacteria. Members of this genus are classified into two major groups, the pyogenic group and the viridans group streptococci (VGS). VGS are frequently found as normal members of the human microbiome and are regarded as commensals. In this work, we characterized a VGS strain isolated from the vaginal swab sample of a Korean patient diagnosed with endometrial cancer. Phylogenetic, phenotypic, and genome-based analyses confirmed the classification of the strain K0074 as a member of the S. mitis complex. Based on the phylogenetic analyses, the species belonged to the recently established Streptococcus mitis subsp. carlssonii. The strain was found to be rare in the vaginal microbiome, but prevalent in the oral and nasal microbiome samples. K0074 neither triggered an inflammatory response nor caused cytolytic and cytotoxic effects on human cervical cancer cell line. Genome analysis uncovered the genetic basis of the strain's metabolism, virulence factors, and potential antimicrobial resistance phenotypes. Moreover, comparative genomics of the strain and closely related species and subspecies highlighted their striking differences in gene properties and biological functions. Overall, the new strain exhibited low virulence and pathogenic potentials and thus, is regarded as a commensal member of the human microflora. The genetic divergence of K0074 from closely related strains offers a compelling foundation for future investigations into the strain's potential functional specialization and its adaptation within the vaginal microbiome.}, }
@article {pmid40925462, year = {2025}, author = {Eggestein, A and Urban, S and Hümmer, E and Nunes, N and Zenk, J and Reiger, M and Aglas, L and Traidl-Hoffmann, C and Gilles, S}, title = {Towards real life exposure: nasal epithelial cell stimulation with pollen particle aerosols.}, journal = {Environmental research}, volume = {}, number = {}, pages = {122762}, doi = {10.1016/j.envres.2025.122762}, pmid = {40925462}, issn = {1096-0953}, abstract = {BACKGROUND: Currently, most researchers apply pollen extracts or -suspensions to assess the effects of pollen exposure on airway epithelia. How respiratory epithelia respond to pollen aerosols is not well studied because standardised methods to aerosolize pollen were not available until recently.<br><br>AIM OF STUDY: To develop and test a near-natural exposure model for pollen grains based on differentiated human nasal epithelial cells and a novel particle aerosoliser.<br><br>METHODS: Primary human nasal epithelial cells were differentiated at the air-liquid interface and exposed to birch, timothy grass and ragweed pollen, either as aqueous extract, suspension, or particle aerosol generated with the VitroCell PowderX device. Morphology, physical barrier function, and cytokine responses were compared.<br><br>RESULTS: The cells responded to pollen aerosol exposure with strong mucus production and coordinated ciliary beating in attempt to clear the pollen grains. Pollen aerosols did not affect the transepithelial electrical resistance (TEER), whereas grass pollen extracts led to a significant TEER decrease. Extract exposure resulted in apical and basolateral cytokine release; aerosol exposure led to a directed, predominantly basolateral dose-dependent cytokine response. Cytokine responses to birch, grass and ragweed pollen differed, with birch pollen inducing lower levels of inflammatory cytokines, while timothy and ragweed pollen induced high levels of inflammatory cytokines and alarmins.<br><br>CONCLUSION: We were able to establish and characterize a biologically relevant pollen aerosol exposure system characterized by a directed cytokine response. The differences in response patterns to different pollen types likely reflect differential sensitization mechanisms, warranting further research.}, }
@article {pmid40920071, year = {2025}, author = {Dallon, E and Moran, HM and Chidambaran, SR and Kian, A and Huang, BYH and Fried, SD and DiRuggiero, J}, title = {Investigation of the global translational response to oxidative stress in the model archaeon Haloferax volcanii reveals untranslated small RNAs with ribosome occupancy.}, journal = {mSphere}, volume = {}, number = {}, pages = {e0034325}, doi = {10.1128/msphere.00343-25}, pmid = {40920071}, issn = {2379-5042}, abstract = {Oxidative stress induces a wide range of cellular damage, often causing disease and cell death. While many organisms are susceptible to the effects of oxidative stress, haloarchaea have adapted to be highly resistant. Several aspects of the haloarchaeal oxidative stress response have been characterized; however, little is known about the impacts of oxidative stress at the translation level. Using the model archaeon Haloferax volcanii, we performed RNA-seq and ribosome profiling (Ribo-seq) to characterize the global translation landscape during oxidative stress. We identified 281 genes with differential translation efficiency (TE). Downregulated genes were enriched in ribosomal and translation proteins, in addition to peroxidases and genes involved in the TCA cycle. We also identified 42 small noncoding RNAs (sRNAs) with ribosome occupancy. Size distributions of ribosome footprints revealed distinct patterns for coding and noncoding genes, with 12 sRNAs matching the pattern of coding genes, and mass spectrometry confirming the presence of seven small proteins encoded by these sRNAs. However, the majority of sRNAs with ribosome occupancy had no evidence of coding potential. Of these ribosome-associated sRNAs, 12 had differential ribosome occupancy or TE during oxidative stress, suggesting that they may play a regulatory role during the oxidative stress response. Our findings on ribosomal regulation during oxidative stress, coupled with potential roles for ribosome-associated noncoding sRNAs and sRNA-derived small proteins in H. volcanii, revealed additional regulatory layers and underscored the multifaceted architecture of stress-responsive regulatory networks.IMPORTANCEArchaea are found in diverse environments, including as members of the human microbiome, and are known to play essential ecological roles in major geochemical cycles. The study of archaeal biology has expanded our understanding of the evolution of eukaryotes, uncovered novel biological systems, and revealed new opportunities for applications in biotechnology and bioremediation. Many archaeal systems, however, remain poorly characterized. Using Haloferax volcanii as a model, we investigated the global translation landscape during oxidative stress. Our findings expand current knowledge of translational regulation in archaea and further illustrate the complexity of stress-responsive gene regulation.}, }
@article {pmid40915424, year = {2025}, author = {Mancera Azamar, KM and Sudi, SD and Mohammadalizadeh, Z and Coffin, C and Parker, IK and Porras, AM}, title = {Innovative engineering approaches to model host-microbiome interactions in vitro.}, journal = {Advanced drug delivery reviews}, volume = {}, number = {}, pages = {115677}, doi = {10.1016/j.addr.2025.115677}, pmid = {40915424}, issn = {1872-8294}, abstract = {The human microbiome plays a critical role in health and disease. Disruptions in microbiota composition or function have been implicated not only as markers but also as drivers of diverse pathologies, creating opportunities for targeted microbiome interventions. Advancing these therapies requires experimental models that can unravel the complex, bidirectional interactions between human tissue and microbial communities. This scoping review examines emerging engineering approaches to design in vitro platforms that successfully integrate host and microbial components to model these interactions. Compared to traditional in vitro and in vivo approaches, these advanced microphysiological systems offer greater experimental control, human-specific biology, and reduced cost and ethical concerns. Here, we identify key challenges in the creation of these in vitro models and innovative solutions to address them by leveraging microfluidics, biomaterials, and organoid technologies, among others. These strategies have enabled the development of co-culture systems that replicate critical features of host-microbiome interfaces, including mucosal barriers, oxygen and pH gradients, mechanical stimuli, and host cell diversity. We also describe how these physiologically relevant models are uncovering new insights into epithelial-microbiota crosstalk, immune modulation by commensal microbes, and systemic effects of microbiota and their metabolites across multiple body sites. We conclude by discussing opportunities to expand these systems in scale, complexity, and clinical relevance. As these models continue to evolve, they hold the potential to transform our ability to mechanistically probe microbiome interactions, personalize therapeutic strategies, and accelerate the translation of microbiome science into clinical practice.}, }
@article {pmid40915391, year = {2025}, author = {Suvi T, J and Anh, NN and Xiaobo, H and Kirsten, N and Leo, H and Lari, P and Pirkka T, P and Pia, D and Tinja, L and Nelli, H and Santtu, H and Sini M, L and Anu, K and Olli, V and Tomas, S and Jussi, H and Maria F, P and Eliisa, K}, title = {B cell dysregulation during acute COVID-19 is transient.}, journal = {Immunology letters}, volume = {}, number = {}, pages = {107086}, doi = {10.1016/j.imlet.2025.107086}, pmid = {40915391}, issn = {1879-0542}, abstract = {BACKGROUND: COVID-19 is still a significant health concern worldwide. B cell responses to COVID-19 have been extensively studied in acute severe disease, but less so during extended follow-up or mild disease. Persisting immunological changes together with herpesvirus reactivations during acute COVID-19 have been suggested as contributing factors for post-acute sequelae of COVID-19 (PASC). Here, we evaluated the natural kinetics of B cell subpopulations together with serological markers of increased B cell activity during acute COVID-19 and long-term follow-up. We also measured human herpesvirus reactivations during acute COVID-19.<br><br>METHODS: We collected plasma and peripheral blood mononuclear cell samples from 120 SARS-CoV-2 positive patients (outpatients&#x202f;=&#x202f;56, inpatients&#x202f;=&#x202f;64) at up to five timepoints during acute disease and recovery (up to 460 days since symptom onset, dsso). We determined circulating B cell and Th cell subpopulations using flow cytometry, and measured free light chains, in addition to Epstein-Barr virus (EBV) serology, and herpesvirus qPCR from the plasma samples. The presence of anosmia as a proxy for PASC was self-reported at 3-12 months post-COVID.<br><br>RESULTS: All changes in B cell subpopulation proportions normalized within 200 dsso. Likewise, the acute alterations observed in circulating T follicular helper and T follicular regulatory cell proportions stabilized soon after. Free light chains were high in acute COVID-19, especially in inpatients, but normalized during follow-up. EBV and human herpesvirus 6B (HHV-6B) reactivations were significantly more common in inpatients than outpatients, with reactivation in 47 and 19% of inpatients and 4.3 and 0% of outpatients respectively. Anosmia was not significantly associated with any herpesvirus reactivation.<br><br>CONCLUSIONS: The circulating B cell and Th cell subpopulations experience transitional changes during SARS-CoV-2 infection, but these changes recover in follow-up. EBV and HHV-6B reactivations are common in inpatients, but they are not associated with persisting anosmia.}, }
@article {pmid40913709, year = {2025}, author = {Jamal, A and Kamal, MA and Alqurashi, YE and Al-Malki, ES and Naiyer, MM and Hussain, SA and Hattiwale, HM}, title = {The microbiome-cancer axis as a hidden contributor to early-onset tumorigenesis.}, journal = {Medical oncology (Northwood, London, England)}, volume = {42}, number = {10}, pages = {464}, pmid = {40913709}, issn = {1559-131X}, mesh = {Humans ; *Neoplasms/microbiology ; *Carcinogenesis/pathology ; *Gastrointestinal Microbiome ; *Microbiota ; Dysbiosis/microbiology ; Age of Onset ; }, abstract = {The global incidence of early-onset cancer has surged by nearly 80% over the past three decades, yet the underlying causes remain poorly understood. While genetics and lifestyle are among the traditional risk factors, emerging evidence implicates the human microbiome as a potent and overlooked contributor to early tumorigenesis. Increases in the studies that are exploring the tissue-specific microbiome signatures such as the enrichment of Actinomyces and Bacteroidia in early-onset colorectal cancer, or Enterobacter and Neisseria in pancreatic tumors offer compelling evidence for age-stratified microbial contributions. Additionally, the recent works on the establishment of gut-testis, oral-gut, and gut-liver microbial axes are being explored to understand the modulation of systemic immune and endocrine landscapes in younger individuals that might unravel their unique predisposition to malignancy. Further, the microbiome-cancer axis has been regarded as a hidden driver in the initiation and progression of early-onset malignancies across diverse tissue types. Understanding this link will provide the missing mechanistic insights showcasing how microbial dysbiosis, biofilm formation, and microbially derived metabolites promote oncogenic inflammation, DNA damage, and immune evasion contributing to early-onset cancers. Considering the potential of these studies, microbial biomarkers with diagnostic promises that include probiotics, fecal microbiota transplantation, and diet have also been explored as emerging tools for prevention and therapy. Through this study, we aim to understand early-onset cancer through a patient microbiota and underscore an urgent need to integrate microbial dynamics into cancer surveillance and intervention strategies, especially for young and largely asymptomatic populations.}, }
@article {pmid40904056, year = {2025}, author = {Dassanayake, P and Diksha, D and Varela-Mattatall, G and Sun, Q and Donnelly, SC and Suchy, M and Bartolome, D and Furlong, S and Deans, L and Biernaski, H and Huston, Y and Thompson, RT and Burton, JP and Moran, G and Gelman, N and Prato, FS and Kovacs, MS and Thiessen, JD and Goldhawk, DE and Schellenberg, J and Fox, MS}, title = {Biodistribution and dosimetry of [89]Zirconium-labeled microbiota transplants in the pig gut.}, journal = {Medical physics}, volume = {52}, number = {9}, pages = {e18087}, doi = {10.1002/mp.18087}, pmid = {40904056}, issn = {2473-4209}, mesh = {Animals ; *Zirconium/chemistry ; *Radioisotopes/chemistry ; Swine ; Tissue Distribution ; Radiometry ; Female ; Escherichia coli ; *Gastrointestinal Microbiome ; Positron-Emission Tomography ; Magnetic Resonance Imaging ; Isotope Labeling ; }, abstract = {BACKGROUND: The gastrointestinal (GI) microbiota, composed of diverse microbial communities, is essential for physiological processes, including immune modulation. Strains such as Escherichia coli Nissle 1917 support gut health by reducing inflammation and resisting pathogens. Microbial therapies using such strains may restore GI balance and offer alternatives to antibiotics, whose overuse contributes to antibiotic resistance. However, effective treatment will require optimizing delivery and understanding microbial dissemination and engraftment.<br><br>PURPOSE: We developed a method to monitor microbial migration and GI permeability post-ingestion using hybrid PET/MRI. To simulate probiotic therapy, bacteria were radiolabeled with [89]Zr, encapsulated, and administered to pigs. Organ level and whole-body dosimetry was determined from the time activity curves recorded over 7 days post ingestion.<br><br>METHODS: We administered [89]Zr-labeled Lactobacillus crispatus ATCC33820 (Gram-positive) to six female Duroc pigs (weight&#xa0;=&#xa0;33.3&#xa0;&#xb1;&#xa0;4.6&#xa0;kg) and E. coli Nissle 1917 (Gram-negative). Scans were performed between 6&#xa0;h and 7 days post-ingestion using a hybrid PET/MRI system. The mean administered dose was 74.7&#xa0;&#xb1;&#xa0;12.9 MBq. Whole-body PET scans were acquired simultaneously with MRI using a T2-weighted HASTE sequence. Images were processed using 3D-Slicer co-registering PET with MRI and semi-automated organ segmentation was performed. Gender-averaged human equivalent organ-level effective doses (ED) and whole body ED were calculated using OLINDA.<br><br>RESULTS: PET imaging showed [89]Zr-labeled L. crispatus and E. coli post-ingestion localized primarily within the GI tract before excretion within feces. The highest mean ED for [89]Zr-labeled L. crispatus and E. coli were in the distal colon (26.8&#xa0;&#xb1;&#xa0;4.9 &#xb5;Sv/MBq and 28.4&#xa0;&#xb1;&#xa0;7.9 &#xb5;Sv/MBq, respectively) and proximal colon (17.9&#xa0;&#xb1;&#xa0;3.7 &#xb5;Sv/MBq and 18.4&#xa0;&#xb1;&#xa0;5.1 &#xb5;Sv/MBq, respectively). EDs in other organs were low. Whole body ED were 60.5&#xa0;&#xb1;&#xa0;9.5 &#xb5;Sv/MBq (L. crispatus) and 66.7&#xa0;&#xb1;&#xa0;14.9 &#xb5;Sv/MBq (E. coli).<br><br>CONCLUSIONS: The whole-body ED for L. crispatus and E. coli is lower than reported values for ingested tracers, such as that from [89]Zr labelled antibodies and [111]In labelled "meals" used to determine gut transit times. Hence ingestion of [89]Zr labelled bacteria shows promise for becoming a human nuclear-medicine procedure to determine the effectiveness of probiotic therapies.}, }
@article {pmid40903859, year = {2025}, author = {Sugawara, K and Hozumi, K and Mizuma, H and Sasaki, D and Shinohara, M and Kondo, A and Watanabe, Y and Ogawa, W}, title = {Similarities and differences in the intestinal actions of metformin and imeglimin.}, journal = {Diabetes, obesity &amp; metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.70075}, pmid = {40903859}, issn = {1463-1326}, support = {//Boehringer Ingelheim Japan/ ; //Suzuken Memorial Foundation/ ; //Cell Science Research Foundation/ ; 22K18393//Japan Society for the Promotion of Science/ ; 23K08007//Japan Society for the Promotion of Science/ ; //Japan Diabetes Foundation/ ; 24ek0210192h0002//Japan Agency for Medical Research and Development/ ; }, abstract = {AIMS: Imeglimin is a novel antidiabetic drug that shares structural similarity with metformin. While the intestinal effects of metformin have attracted widespread attention, those of imeglimin remain underexplored.<br><br>MATERIALS AND METHODS: C57BL/6J mice were treated with metformin or imeglimin for RNA sequencing of intestinal tissue. Gut microbiota composition was evaluated in KK-A[y] mice by 16S rRNA sequencing of faecal samples. To assess direct effects on the human microbiome, a gut simulator was used with faecal samples from healthy and diabetic individuals. Intestinal glucose dynamics were assessed in C57BL/6J mice following administration of [[18]F]fluorodeoxyglucose, with subsequent analysis of tissue distribution.<br><br>RESULTS: Bulk RNA-sequencing of colonic tissue revealed that both drugs induced similar patterns of gene expression changes, including a prominent upregulation of Gdf15. However, single-cell RNA-sequencing uncovered distinct effects of the two drugs, with metformin having a pronounced impact on the functional properties of enterocytes and imeglimin increasing the proportion of IgA-producing plasma cells. Metformin reduced gut microbial diversity and induced substantial changes in microbial composition, whereas imeglimin exerted less pronounced effects. Gut simulator analysis with human faecal samples showed that both drugs directly altered gut microbial populations but in different ways. Finally, metformin promoted glucose excretion into the intestinal lumen, whereas imeglimin had a minimal effect on this process.<br><br>CONCLUSIONS: In conclusion, although metformin and imeglimin exerted similar effects on gene expression in the colon at the whole-tissue level, they showed distinct cell type-specific actions, and they differed in their influence on gut microbiota and intestinal glucose dynamics.}, }
@article {pmid40902606, year = {2025}, author = {Zhang, D and Zou, Y and Shi, Y and Zhang, J and Liu, J and Wu, G and Zhang, J and Gao, Y and Chen, M and Li, YX}, title = {Systematically investigating and identifying bacteriocins in the human gut microbiome.}, journal = {Cell genomics}, volume = {}, number = {}, pages = {100983}, doi = {10.1016/j.xgen.2025.100983}, pmid = {40902606}, issn = {2666-979X}, abstract = {Human gut microbiota produces unmodified bacteriocins, natural antimicrobial peptides that protect against pathogens and regulate host physiology. However, current bioinformatic tools limit the comprehensive investigation of bacteriocins' biosynthesis, obstructing research into their biological functions. Here, we introduce IIBacFinder, a superior analysis pipeline for identifying unmodified class II bacteriocins. Through large-scale bioinformatic analysis and experimental validation, we demonstrate their widespread distribution across the bacterial kingdom, with most being habitat specific. Analyzing over 280,000 bacterial genomes, we reveal the diverse potential of human gut bacteria to produce these bacteriocins. Guided by meta-omics analysis, we synthesized 26 hypothetical bacteriocins from gut commensal species, with 16 showing antibacterial activities. Further ex vivo tests show minimal impact of narrow-spectrum bacteriocins on human fecal microbiota. Our study highlights the huge biosynthetic potential of unmodified bacteriocins in the human gut, paving the way for understanding their biological functions and health implications.}, }
@article {pmid40897518, year = {2025}, author = {Salihoglu, R}, title = {The Microbiome Shaping Cancer Development, Progression, and Therapeutic Response.}, journal = {Physiological genomics}, volume = {}, number = {}, pages = {}, doi = {10.1152/physiolgenomics.00091.2025}, pmid = {40897518}, issn = {1531-2267}, abstract = {The human microbiome is emerging as a key regulator of cancer biology, modulating tumor development, immune dynamics, and therapeutic responses across diverse malignancies. In this review, recent insights are synthesized regarding how microbial communities (bacterial, fungal, and viral) shape oncogenic signaling, immune checkpoint blockade (ICB) efficacy, and metabolic reprogramming in lung, pancreatic, colorectal, breast, cervical, melanoma, and gastric cancers. Mechanistic links between microbial metabolites, intratumoral colonization, and host immune phenotypes are highlighted proposing that the microbiome constitutes a programmable axis within the tumor immune-metabolic ecosystem. Drawing on multi-omics integration and translational studies, a shift from associative profiling toward causal, spatially resolved, and intervention-ready frameworks is proposed. This perspective positions the microbiome not as a passive bystander, but as a co-evolving participant in tumor progression and treatment response, with the potential to reshape diagnostics, prognostics, and therapeutic strategies in precision oncology.}, }
@article {pmid40897178, year = {2025}, author = {Xu, T and Jiao, X and Liu, G and Chen, X and Luo, Q and Zhang, G and Li, B and Zhang, Y and Li, X and Cheung, Y and Chai, X and Huang, Y and Wu, H and Deng, F and Chen, F and Liang, G}, title = {Oral virome metagenomic catalog links Porphyromonas gingivalis phages to obesity and type 2 diabetes.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102325}, doi = {10.1016/j.xcrm.2025.102325}, pmid = {40897178}, issn = {2666-3791}, abstract = {The human microbiota has a critical role in maintaining human microbiome homeostasis and health, yet the viral component of the oral microbiome remains largely unidentified. We establish the Human Oral Virome Database (HOVD) catalog, a freely accessible online resource cataloging 24,440 bacteriophage viral operational taxonomic units and 83 eukaryotic viral genomes. Utilizing HOVD, we investigate oral virome variation and its correlation with oral bacteria and gut virome in 220 obese individuals with or without type 2 diabetes mellitus (T2D). Obese individuals with T2D exhibit reduced oral viral diversity, lower correlations with clinical features, disrupted viral-bacterial correlations, and enhanced oral-gut virome transmission. Furthermore, we computationally identify bacteriophages that infect Porphyromonas gingivalis and screen six putative endolysins. Experimental validation reveals that a mixture of three endolysins significantly inhibits Porphyromonas gingivalis growth. These findings highlight the potential of phage-derived endolysins for periodontitis with T2D, offering a path toward oral and systemic disease intervention.}, }
@article {pmid40892293, year = {2025}, author = {Chen, C and Krzyżewska-Dudek, E and Patpatia, S and Dulipati, V and Mapelli, SN and Meral, A and Kotimaa, J and Kiljunen, S and Meri, S}, title = {Antibiotic-resistant Acinetobacter baumannii can be killed by a combination of bacteriophages and complement.}, journal = {Medical microbiology and immunology}, volume = {214}, number = {1}, pages = {40}, pmid = {40892293}, issn = {1432-1831}, mesh = {*Acinetobacter baumannii/virology/drug effects/immunology/genetics ; *Bacteriophages/physiology/growth &amp; development/immunology ; *Complement System Proteins/immunology ; *Drug Resistance, Multiple, Bacterial ; Acinetobacter Infections/therapy/microbiology ; Bacterial Capsules/metabolism ; Humans ; Anti-Bacterial Agents/pharmacology ; Lipopolysaccharides ; DNA Transposable Elements ; Microbial Viability ; }, abstract = {Infections caused by multidrug-resistant Acinetobacter baumannii are an emerging global health threat. Although phages have shown promising results in treating bacterial infections, the mechanisms of the combined effect of phages and innate immunity on clearing A. baumannii remain unclear. Here, we report a synergistic effect of the complement system and phages on clearing multidrug-resistant A. baumannii. We show that A. baumannii rapidly adapts and becomes resistant to phage or serum complement by modifying the expression of capsule and lipooligosaccharides, which can be regulated through reversible transposon mutagenesis in the K locus. Compared to the encapsulated phenotype, the non-encapsulated, phage-resistant A. baumannii showed a higher level of membrane attack complex deposition and were susceptible to killing by complement. In contrast, the encapsulated phenotype escaped the complement system by shedding the membrane attack complex to the environment. Thus, while the complement system targets the non-encapsulated phenotype, the phage infects and eliminates the encapsulated subpopulation. These results suggest means of combatting antibiotic-resistant A. baumannii by a simultaneous treatment with phages and complement, a combination which can be supplemented further with antibacterial antibodies.}, }
@article {pmid40891819, year = {2025}, author = {De Boeck, I and Spacova, I and Cauwenberghs, E and Eilers, T and Gehrmann, T and Van den Bossche, K and Martens, K and Condori-Catachura, S and Michiels, K and De Winter, F and Kumar-Singh, S and Bruffaerts, N and Packeu, A and Hellings, PW and Vroegop, A and Van Gool, K and Vanderveken, OM and Lebeer, S}, title = {Lacticaseibacillus rhamnosus GG in a chewable colonizes the nose and facilitates local immune benefits in allergic rhinoconjunctivitis patients.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0077325}, doi = {10.1128/spectrum.00773-25}, pmid = {40891819}, issn = {2165-0497}, abstract = {Current treatments fall short in managing allergic rhinitis (AR), emphasizing the need for additional strategies. Beneficial bacteria application shows promise in AR; however, most studies focus on oral probiotic administration without monitoring the applied strains in the upper respiratory tract (URT) and their local effects. In this randomized, double-blind, placebo-controlled trial, the probiotic Lacticaseibacillus rhamnosus GG was administered via chewable tablets in seasonal AR patients, randomized to probiotic (n = 33) or placebo (n = 31) groups. Per-protocol analysis of the URT microbiome, immune markers, and AR symptoms was performed. L. rhamnosus GG trafficked from chewables to the oropharynx (77%, P = 0.02) and nasopharynx (41%, P < 0.0001). Control of self-reported AR symptoms via validated questionnaires under grass pollen exposure was observed after 2 weeks of probiotic administration and not upon placebo. A local decrease in salivary interleukin-4 (P < 0.05) and nasal IL-13 (P < 0.0001) was observed in the probiotic group. These data indicate that L. rhamnosus GG chewables can target the URT and exert local effects on key allergy cytokines after temporal probiotic engraftment.IMPORTANCEAllergic rhinitis (AR) or hay fever is a highly prevalent condition, impacting nearly half the population in some countries. Supplementation of beneficial bacteria or probiotics has gained increasing attention in AR, and a key innovative way to do this is direct administration to the upper airways. Our study shows for the first time that the model probiotic strain Lacticaseibacillus rhamnosus GG can traffic to the nose in AR patients when administered via a slow-releasing chewable tablet. This trafficking is associated with local benefits in the airways, including on grass pollen-induced nasal symptoms and allergy-related cytokines.}, }
@article {pmid40884907, year = {2025}, author = {Sanati, S and Bakhti, A and Mohammadipanah, F}, title = {Long-term toxic effects of nanoparticles on human microbiota.}, journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)}, volume = {91}, number = {}, pages = {127723}, doi = {10.1016/j.jtemb.2025.127723}, pmid = {40884907}, issn = {1878-3252}, abstract = {Synthetic nanomaterials can penetrate various organs, such as the skin, lungs, and gastrointestinal tract, enter systemic circulation, and ultimately reach tissues and human cells. Nanomaterials used in medicine, food, cosmetics, and agricultural processes can accumulate in our intestines and cause dysbiosis. The direct and indirect detrimental impacts of nanomaterials on humans by altering our cells and microbiota are discussed in this paper. These adverse effects of nanomaterials can be slightly reduced by changing their physicochemical characteristics. Some of the gut microbiota can reduce or mitigate the toxicity of nanomaterials through various strategies providing approaches for pro- or postbiotics with detoxifying function. Moreover, nanomaterials influence the rate of horizontal gene transfer. The use of nanomaterials in food, water, and medicines needs to be legitimized based on the duration, dose, type, and level of toxicity. The negative implications of nanomaterials in human cells and their microbiota are surveyed in this paper.}, }
@article {pmid40884571, year = {2025}, author = {Brindangnanam, P and Coumar, MS}, title = {Integrated Microbiome Data Analysis Reveals Potential Pneumonia Microbial Biomarkers in ICU Patients: A Machine Learning Approach.}, journal = {Current microbiology}, volume = {82}, number = {10}, pages = {483}, pmid = {40884571}, issn = {1432-0991}, mesh = {Humans ; *Machine Learning ; Intensive Care Units ; Biomarkers/analysis ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; *Pneumonia/microbiology/diagnosis ; Bacteria/genetics/classification/isolation &amp; purification ; Lung/microbiology ; Data Analysis ; }, abstract = {The human microbiome is pivotal in maintaining health and managing diseases. By examining the core microbiome in intensive care units (ICU) patients with pneumonia, we can gain valuable insights into the microbial communities associated with disease conditions. Pneumonia is the second most common infection in ICU settings, and recent research has highlighted the significance of endotracheal aspirate (ETA) microbiota in influencing pneumonia. Analysis of 16S rRNA sequencing data from lung microbiota of ICU patients revealed Pseudomonas as a key microbial biomarker, with machine learning model (xgbTree) achieving high predictive accuracy (prAUC: 0.98 and 0.7 log loss). Functional profile analysis revealed that the ATP-binding cassette (ABC) transporters and tetracycline-resistant ribosomal protection (Tet RPPs) proteins were possible molecular biomarkers that can be targeted to address the abundant pathogenic microbiome in pneumonia patients. These findings provide critical insights into pneumonia-specific microbiome signatures, highlighting Pseudomonas as a diagnostic marker and resistance-associated functional pathways as potential intervention targets. This study contributes to the development of precision medicine strategies for pneumonia management in ICU settings.}, }
@article {pmid40879391, year = {2025}, author = {Devotta, H and Lavelle, A and Korpela, K and Hurley, S and Shannon, E and Lunjani, N and Ambikan, A and Neogi, U and Venter, C and Walter, J and Hourihane, J and O'Mahony, L}, title = {Microbial Sharing Between Siblings Supports Metabolic Functions Protective Against Allergy.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.70033}, pmid = {40879391}, issn = {1398-9995}, support = {/SFI_/Science Foundation Ireland/Ireland ; //Royal College of Surgeons in Ireland/ ; //Temple Street Hospital Foundation/ ; //Clemens Von Pirquet Foundation/ ; 12/RC/2273_P2//Research Ireland/ ; 21/FFP-A/10000//Research Ireland Frontiers for the Future Awards/ ; 23/FFP-A/12076//Research Ireland Frontiers for the Future Awards/ ; }, }
@article {pmid40871739, year = {2025}, author = {Lupu, A and Adam-Raileanu, A and Bozomitu, LI and Gimiga, N and Forna, L and Anton, CR and Sasaran, MO and Nedelcu, AH and Ghica, DC and Anton, E and Morariu, ID and Fotea, S and Beser, OF and Lupu, VV}, title = {Helicobacter pylori and Compositional Patterns of Digestive Tract Microbiome in Children: A Literature Review.}, journal = {Nutrients}, volume = {17}, number = {16}, pages = {}, doi = {10.3390/nu17162711}, pmid = {40871739}, issn = {2072-6643}, mesh = {Humans ; *Helicobacter pylori ; *Gastrointestinal Microbiome ; Child ; *Helicobacter Infections/microbiology/drug therapy ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {Helicobacter pylori (H. pylori) represents a major healthcare problem, colonizing more than half of the population worldwide. Usually acquired during childhood, it has a significant impact on human health. After forty years of extensive research, there are aspects of the complex H. pylori-human organism interplay that require further investigation. A comprehensive review was conducted after an extensive literature search in the PubMed/Medline, Web of Science, and EMBASE databases concerning H. pylori and human microbiota reports. Although the exact nature of H. pylori's relation with the human microbiome remains elusive, its presence as well as its eradication treatment are associated with the alteration of bacterial communities' composition not only in the gastric microenvironment but also in all digestive tract levels, with particular changes in both children and adults. Understanding microbiota composition is a step towards personalized medicine. Although the current literature on pediatric patients related to this topic is scarce, the available positive results reported in adult studies encourage pediatric research on microbiota manipulation, promising beneficial outcomes.}, }
@article {pmid40868571, year = {2025}, author = {Aldawood, E and Alzamil, L and Faqih, L and Almuhayya, S}, title = {Knowledge of Vaginal Microbiota and Its Association with Perceptions of Vulvovaginal Aesthetic Procedures Among Saudi Women.}, journal = {Healthcare (Basel, Switzerland)}, volume = {13}, number = {16}, pages = {}, doi = {10.3390/healthcare13161955}, pmid = {40868571}, issn = {2227-9032}, support = {ORF-2025-1475//Ongoing Research Funding program, King Saud University, Riyadh, Saudi Arabia./ ; }, abstract = {BACKGROUND: The human microbiome includes trillions of microorganisms, with the vaginal microbiota playing a vital role in women's reproductive health. Concurrently, interest in vulvovaginal esthetic procedures (VVEP) is increasing. This study aimed to compare single and married or previously married women in terms of their knowledge of the human microbiome, particularly the vaginal microbiota, and their perceptions of VVEP. It also examined associations between microbiota awareness, attitudes toward VVEP, and sociodemographic factors.<br><br>METHODS: A cross-sectional, online survey was distributed to women aged 18 years and older in Saudi Arabia. A total of 1019 responses were collected. Chi-square tests compared knowledge responses between marital groups, while linear regression was used to explore associations between microbiota knowledge and participant characteristics.<br><br>RESULTS: Single women showed greater awareness of general microbiome concepts, with 42% correctly identifying the term "microbiome" compared to 29.89% of married or previously married women. In contrast, married or previously married women demonstrated better knowledge of vaginal microbiota and the effects of antibiotic misuse. Of the participants, 6.6% had undergone one or more VVEP. Furthermore, 19.7% of single women and 18.3% of married or previously married women expressed future interest in undergoing such procedures. Marital status influenced perceptions of specific procedures, with married or previously married women more likely to justify interventions such as augmentation of the labia minora/"G-spot" augmentation and vaginal rejuvenation. Justification for augmentation of the labia minora/"G-spot" augmentation in this group was associated with lower vaginal microbiota knowledge. Healthcare professionals exhibited significantly higher microbiota awareness.<br><br>CONCLUSION: Enhancing women's knowledge of vaginal microbiota can enhance informed decision-making and reduce unnecessary esthetic interventions among Saudi women, thereby supporting better reproductive health outcomes.}, }
@article {pmid40868183, year = {2025}, author = {Kim, JH and Seo, H and Kim, S and Rahim, MA and Jo, S and Barman, I and Tajdozian, H and Sarafraz, F and Shuvo, MSH and Song, HY and Song, YS}, title = {Association of Intratumoral Microbiota Modulation with Prostate Cancer Progression: A Microbiome Analysis of Prostatic Tissue.}, journal = {Biomedicines}, volume = {13}, number = {8}, pages = {}, doi = {10.3390/biomedicines13081929}, pmid = {40868183}, issn = {2227-9059}, support = {RS-2024-00333544, RS-2023-00219563//Ministry of Science and ICT/ ; NA//National Research Foundation of Korea (NRF)/ ; NA//Soonchunhyang University Research Fund/ ; }, abstract = {Background: The involvement of the intratumoral microbiome in prostate cancer progression is becoming increasingly acknowledged. This study analyzed the microbiome of prostate cancer tissues from patients with localized prostate cancer (LPC, stages 1-2) and advanced prostate cancer (APC, stages 3-4) to determine its association with cancer progression. Methods: Paraffin-embedded tissue samples obtained during radical prostatectomy underwent 16S rRNA amplicon-based profiling. Results: The profile of the bacterial communities in LPC and APC differed remarkably. While species diversity remained stable, species richness (as determined by the ACE analysis) was significantly lower in APC, correlating with a decrease in Enhydrobacter (which is more abundant in LPC) and an increase in Lautropia (enriched in APC). The role of Lautropia in the progression of cancer was confirmed by in vitro studies employing cell lines from prostate cancer. Conclusions: These findings demonstrate the potential of microbiome-targeted interventions in the management of prostate cancer.}, }
@article {pmid40867601, year = {2025}, author = {Jin, S and Ku, C and Kim, HJ and Kim, JG and Kim, SH and Han, H and Kang, HC and Hwang, JS and Kim, MJ}, title = {The Role of miRNA167 in Skin Improvement: Insight from Extracellular Vesicles Derived from Rock Samphire (Crithmum maritimum).}, journal = {Biomolecules}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/biom15081157}, pmid = {40867601}, issn = {2218-273X}, mesh = {*Extracellular Vesicles/metabolism/genetics ; *MicroRNAs/genetics/metabolism ; Humans ; *Skin/metabolism ; Wound Healing ; Fibroblasts/metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism ; Collagen Type I/genetics/metabolism ; Matrix Metalloproteinase 1/genetics/metabolism ; Collagen Type I, alpha 1 Chain ; Regeneration ; }, abstract = {Samphire (Crithmum matrimum), a halophyte, thrives in saline environments due to its salt tolerance, which is partly attributed to miR167. However, the functional role of miR167 in human cells is unclear. This study explores the role of extracellular vesicles (EVs) derived from C. matrimum callus in skin regeneration, highlighting the potential of miRNA tae-miR167c-5p (miR167). Calluses were successfully induced and scaled for EV isolation. Characterization confirmed the presence of plant EV biomarkers and EVs with an average size of 136.6 nm. Cm-callus EVs enhanced wound healing and skin regeneration in human fibroblasts (HFF cells and CCD-986Sk cells) by modulating key genes, in particular, by downregulating MMP1 and upregulating COL1A1 and VEGFA. Small RNA sequencing revealed an enrichment of miR167 in Cm-callus EVs. Transfection with an miR167 mimic replicated these regenerative effects. Computational predictions identified PPP3R2, which is linked to the MAPK and NFAT pathways, as a potential target of miR167. This study demonstrates the efficacy of Cm-callus EVs and miR167 in promoting skin regeneration without cytotoxicity, providing insights into their therapeutic potential and calling for further experimental validation of target interactions.}, }
@article {pmid40867553, year = {2025}, author = {Jin, S and Kim, JG and Kim, HJ and Kim, JY and Kim, SH and Kang, HC and Kim, MJ}, title = {miRNA408 from Camellia japonica L. Mediates Cross-Kingdom Regulation in Human Skin Recovery.}, journal = {Biomolecules}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/biom15081108}, pmid = {40867553}, issn = {2218-273X}, mesh = {Humans ; *Camellia/genetics/chemistry/metabolism ; *MicroRNAs/genetics/metabolism ; *Wound Healing/drug effects/genetics ; *Skin/metabolism ; Fibroblasts/metabolism/drug effects ; Extracellular Vesicles/metabolism ; Keratinocytes/metabolism/drug effects ; }, abstract = {Wound healing is a complex and dynamic process involving several stages of tissue repair. This study has shown that extracellular vesicles (EVs) derived from the callus of Camellia japonica L. and their associated microRNAs (miRNAs) possess significant wound healing activities. In human fibroblasts, EVs from C. japonica L. stimulated wound healing and upregulated collagen gene expression. The EVs also decreased inflammation levels in human keratinocytes, supporting wound healing. Among the miRNAs identified, miR408, one of the abundant miRNAs in the EVs, also showed similar wound healing efficacy. These findings suggest that both EVs and miR408 from the callus of C. japonica L. play a pivotal role in promoting wound healing. Additionally, this study shows that the regulation of miRNAs between different kingdoms can be achieved and suggests a new direction for the utilization of plant-derived components.}, }
@article {pmid40866318, year = {2025}, author = {Inoue, N and Shibata, T and Sawada, R and Yamanishi, Y}, title = {Human Microbiome-Based Prediction of Health Effects of Foods via Machine Learning.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.5c06318}, pmid = {40866318}, issn = {1520-5118}, abstract = {Food absorption is dependent on the activities of internal microorganisms. When exploring food functionality, considering the food compounds and their metabolites produced by microbial metabolism is crucial. In this study, we developed a machine learning method to predict food functionalities using microorganism and metabolic data. The prediction was performed on the chemical properties of 70,478 constituent compounds and 24,255 metabolites and their interactions with target proteins in disease-related pathways. This identified potential functional associations between 941 foods and 83 diseases, providing insights into the mechanisms involved, particularly those related to microorganisms. The effects of microorganism-mediated foods on diseases can be categorized based on food type. For example, the microorganisms associated with diseases within each food category indicated the potential involvement of the Bacteroidetes phylum in dyslipidemia and the Firmicutes phylum in Parkinson's disease. This method could aid in identifying disease-associated microorganisms, identifying prebiotic foods, and highlighting the potential of food interventions in the preventive medicine field. Furthermore, this approach is expected to be useful for elucidating novel mechanisms of food-disease interactions mediated by microbial metabolites.}, }
@article {pmid40856313, year = {2025}, author = {Klier, K and Mehrjerd, A and Fässler, D and Franck, M and Weihs, A and Budde, K and Bahls, M and Frost, F and Henning, AK and Heinken, A and Völzke, H and Dörr, M and Nauck, M and Grabe, HJ and Friedrich, N and Hertel, J}, title = {Integrating population-based metabolomics with computational microbiome modelling identifies methanol as a urinary biomarker for protective diet-microbiome-host interactions.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d5fo00761e}, pmid = {40856313}, issn = {2042-650X}, abstract = {Background: Diet-microbiome interactions are core to human health, in particular through bacterial fibre degradation pathways. However, biomarkers reflective of these interactions are not well described. Methods: Using the population-based SHIP-START-0 cohort (n = 4017), we combined metabolome-wide screenings with elastic net machine learning models on 33 food items captured using a food frequency questionnaire (FFQ) and 43 targeted urine nuclear magnetic resonance (NMR) metabolites, identifying methanol as a marker of plant-derived food items. We utilised the independent SHIP-START-0 cohort for the replication of food-metabolite associations. Moreover, constraint-based microbiome community modelling using the Human Microbiome data (n = 149) was performed to predict and analyse the contribution of the microbiome to the human methanol pools through bacterial fibre degradation. Finally, we employed prospective survival analysis in the SHIP-START-0 cohort, testing urinary methanol on its predictive value for mortality. Results: Among 21 metabolites associated with 17 dietary FFQ variables after correction for multiple testing, urinary methanol emerged as the top hit for a range of plant-derived food items. In line with this, constraint-based community modelling demonstrated that gut microbiomes can produce methanol via pectin degradation with the genera Bacteroides (68.9%) and Faecalibacterium (20.6%) being primarily responsible. Moreover, microbial methanol production capacity was a marker of high microbiome diversity. Finally, prospective survival analysis in SHIP-START-0 revealed that higher urinary methanol is associated with lower all-cause mortality in fully adjusted Cox regressions. Conclusion: Integrating population-based metabolomics and computational microbiome modelling identified urinary methanol as a promising biomarker for protective diet-microbiome interactions linked to microbial pectin degradation.}, }
@article {pmid40852123, year = {2025}, author = {Linehan, K and Healy, K and Hurley, E and O'Shea, CA and Ryan, CA and Ross, RP and Stanton, C and Dempsey, EM}, title = {Perinatal factors influencing the earliest establishment of the infant microbiome.}, journal = {Microbiome research reports}, volume = {4}, number = {2}, pages = {24}, pmid = {40852123}, issn = {2771-5965}, abstract = {Background: While extensive research exists on the human microbiome, a number of outstanding questions remain regarding the infant microbiome in the initial stages of life. This study aimed to determine the timing of very early microbial colonization in humans, assess the contribution of maternal microbial sources to their offspring and examine the effects of perinatal factors such as delivery mode, gestational age, and feeding practices on the maternal and infant microbiota in early life. Methods: Using a cohort of 18 healthy mother-infant dyads, maternal saliva (within 24 h postpartum), vaginal (1 h prepartum), and placental (1 h postpartum) samples were collected. From their corresponding infants, saliva (within 24 h postpartum) and meconium (within 96 h postpartum) samples were collected. 16S rRNA amplicon sequencing was utilized to assess the taxonomic and inferred functional compositions of the bacterial communities from both mothers and infants. Results: Our results consolidate and corroborate recent findings addressing the existence of a meconium microbiome and the absence of a placental microbiome. We show that significant sharing of microbiota, primarily Streptococcus and Veillonella species, between the maternal oral cavity and the infant oral cavity occurs in early life. Perinatal factors such as vaginal delivery and exclusive breastfeeding were strongly associated with enhanced microbial richness and diversity in infants. Conclusions: This study provides information on the relationship between health and delivery factors and the first establishment of the infant microbiota. These findings could offer valuable guidance to clinicians and mothers in optimizing the infant microbiota toward health during infancy and later life.}, }
@article {pmid40850975, year = {2025}, author = {Yeo, LF and Lee, AWY and Tee, PYE and Chin, JSF and Lee, BKB and Lim, J and Teo, SH and Pan, JW}, title = {Characterization of intra-tumoral microbiota from transcriptomic sequencing of Asian breast cancer.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {31147}, pmid = {40850975}, issn = {2045-2322}, mesh = {Humans ; *Breast Neoplasms/microbiology/genetics/pathology/immunology ; Female ; *Microbiota/genetics ; *Transcriptome ; Middle Aged ; Tumor Microenvironment/genetics/immunology ; Malaysia ; Asian People/genetics ; Gene Expression Profiling ; Adult ; Aged ; }, abstract = {The human microbiome has garnered significant interest in recent years as an important driver of human health and disease. Likewise, it has been suggested that the intra-tumoral microbiome may be associated with specific features of cancer such as tumour progression and metastasis. However, additional research is needed to validate these findings in diverse populations. In this study, we characterized the intra-tumoral microbiota of 883 Malaysian breast cancer patients using transcriptomic data from bulk tumours and investigated their association with clinical variables and immune scores. We found that the tumour microbiome was not associated with breast cancer molecular subtype, cancer stage, tumour grade, or patient age, but was weakly associated with immune scores. We also found that the tumour microbiome was associated with immune scores in our cohort using random forest models, suggesting the possibility of an interaction between the tumour microbiome and the tumour immune microenvironment in Asian breast cancer.}, }
@article {pmid40846688, year = {2025}, author = {Ding, SQ and Lei, Y and Zhao, ZM and Li, XY and Lang, JX and Zhang, JK and Li, YS and Zhang, CD and Dai, DQ}, title = {Crosstalk Between Microbiome and Ferroptosis in Diseases: From Mechanism to Therapy.}, journal = {Comprehensive Physiology}, volume = {15}, number = {4}, pages = {e70042}, doi = {10.1002/cph4.70042}, pmid = {40846688}, issn = {2040-4603}, support = {81972322//National Natural Science Foundation of China/ ; JYTMS20230108//Scientific Study Project for Institutes of Higher Learning, Ministry of Education, Liaoning Province/ ; RXXM202302//Young Backbone Talents of China Medical University/ ; 2023-MS-163//Liaoning Provincial Natural Science Foundation/ ; }, mesh = {*Ferroptosis/physiology ; Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Iron/metabolism ; Dysbiosis/metabolism ; Reactive Oxygen Species/metabolism ; *Microbiota/physiology ; Lipid Peroxidation ; }, abstract = {The human microbiome is a unique organ and maintains host immunomodulation and nutrient metabolism. Structural and functional microbiome alterations are commonly known as dysbiosis, which is strongly associated with disease progression. Ferroptosis is a novel iron-dependent cell death mode characterized by intracellular iron accumulation, increased reactive oxygen species (ROS), and lipid peroxidation (LPO). Importantly, the complex crosstalk between the microbiome and ferroptosis in disease has attracted considerable research attention. The microbiome influences ferroptosis by regulating host iron homeostasis, mitochondrial metabolism, and LPO, among many other pathways. Thus, the in-depth analysis of microbiome-ferroptosis crosstalk and associated mechanisms could provide new strategies to treat human diseases. Therefore, understanding this crosstalk is critical. Here, we systematically explore the associations between gut microbiome and ferroptosis across multiple diseases. We show that the oral microbiome also influences disease progression by regulating ferroptosis. Furthermore, we provide a potential for certain disease therapies by targeting the crosstalk between the microbiome and ferroptosis.}, }
@article {pmid40842971, year = {2025}, author = {Fukuyo, M and Takahashi, N and Hanada, K and Ishikawa, K and Venclovas, &#x10c; and Yahara, K and Yonezawa, H and Terabayashi, T and Katsura, Y and Osada, N and Kaneda, A and Camargo, MC and Rabkin, CS and Uchiyama, I and Osaki, T and Kobayashi, I}, title = {Helicobacter pylori base-excision restriction enzyme in stomach carcinogenesis.}, journal = {PNAS nexus}, volume = {4}, number = {8}, pages = {pgaf244}, pmid = {40842971}, issn = {2752-6542}, abstract = {Many recent lines of evidence from the human microbiome and other fields indicate bacterial involvement in various types of cancer. Helicobacter pylori has been recognized as the major cause of stomach cancer (gastric cancer), but the mechanism by which it destabilizes the human genome to cause cancer remains unclear. Our recent studies have identified a unique family of toxic restriction enzymes that excise a base (A: adenine) from their recognition sequence (5'-GTAC). At the resulting abasic sites (5'-GT_C), its inherent endonuclease activity or that of a separate endonuclease may yield atypical strand breaks that resist repair by ligation. Here, we present evidence demonstrating involvement of its H. pylori member, HpPabI, in stomach carcinogenesis: (i) Association of intact HpPabI gene with gastric cancer in the global H. pylori Genome Project and the open genomes; (ii) Frequent mutations at A in 5'-GTAC in the gastric cancer genomes as well as in H. pylori genomes; (iii) Its induction of chromosomal double-strand breaks in infected human cells and of mutagenesis in bacterial test systems. In addition, its unique regions that interact with DNA exhibit signs of diversifying selection. Our further analysis revealed similar oncogenic bacterium-restriction-enzyme pairs for other types of cancer. These results set another stage for cancer research and medicine around oncogenic restriction enzymes.}, }
@article {pmid40839108, year = {2025}, author = {Mukherjea, N and Khandelwal, A and Saluja, R and Kalra, N}, title = {The Role of the human microbiome in neurodegenerative diseases: A Perspective.}, journal = {Current genetics}, volume = {71}, number = {1}, pages = {17}, pmid = {40839108}, issn = {1432-0983}, mesh = {Humans ; *Neurodegenerative Diseases/microbiology ; *Microbiota ; Parkinson Disease/microbiology ; *Gastrointestinal Microbiome ; Alzheimer Disease/microbiology ; Inflammasomes ; Inflammation/microbiology ; }, abstract = {Advances in diagnostics, therapeutics, and large-scale clinical studies have significantly expanded our understanding how human health is shaped by the microorganisms that colonize the body since birth. This article explores the rapidly evolving field of human microbiome research, focusing upon how microbial communities influence neurological health and contribute to the development of neurodegenerative diseases (NDs). Multiple factors, including age, lifestyle, and immunological memory, are recognized as major determinants of an individual's microbiome composition, which in turn can influence the onset and the progression of disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These conditions have been linked to mechanisms including the aggregation of pathogenic proteins (e.g., amyloid-β and α-synuclein), inflammation driven by activation of the Toll-like receptor (TLR) signaling pathway, the NLRP3 inflammasome, as well as the modulatory effect of microbial metabolites such as short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS). The article also highlights ongoing research and emerging strategies aimed at leveraging the human microbiome for better diagnosis, and management of NDs.}, }
@article {pmid40836109, year = {2025}, author = {Hyvönen, S and Saarikivi, A and Mälkönen, J and Solasaari, T and Korpela, K and de Vos, WM and Salonen, A and Ruuska-Loewald, T and Kolho, KL}, title = {The association of maternal and infant early gut microbiota with respiratory infections in infants.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, pmid = {40836109}, issn = {1530-0447}, support = {200141/WT_/Wellcome Trust/United Kingdom ; 210168//the Foundation for Pediatric research/ ; grant not numbered//the Foundation for Pediatric research/ ; 5044//Signe ja Ane Gyllenbergin S&#xe4;&#xe4;ti&#xf6;/ ; 329/31/2015//Tekes/ ; grant not numbered//Juho Vainion S&#xe4;&#xe4;ti&#xf6;/ ; 5851//the Finnish Medical Foundation/ ; }, abstract = {BACKGROUND: There are limited data on the proposed association of early gut microbiota composition and the risk of respiratory tract infections (RTI) in infants from prospective studies.<br><br>METHODS: We investigated the maternal and infant gut microbiota in infants prospectively followed up for their RTIs in the HELMi cohort from Helsinki, Finland. The 16S rRNA gene amplicon data was assessed at weeks 3 and 6 from 461 infants, of whom 178 developed RTIs within 3 and 6 months of life. Fecal samples collected near the due date were available from 261 mothers.<br><br>RESULTS: There was no difference in the maternal or early infant gut microbiota in the overall microbiota composition in alpha or beta diversity between infants with or without RTIs within the first 3 and 6 months of life. The relative abundances of adult-type butyrate producers and some Enterobacteriaceae were significantly more higher at 3 and to some extent also at 6 weeks of age in the infection group compared to controls, while their mothers' microbiota was significantly enriched with Enterococcus, Citrobacter, and Enterobacter spp., and Clostridium being less abundant.<br><br>CONCLUSION: The maternal and early-life infant gut microbiota may play a role in predisposition to RTIs in infants.<br><br>IMPACT: The maternal and early-life infant gut microbiota profile was associated with infants' respiratory tract infections within the first 6 months of life. In infants, the higher abundance of adult-type butyrate producers and some Enterobacteriaceae were associated with respiratory tract infections, while mothers' microbiota was significantly enriched with Enterococcus, Citrobacter, and Enterobacter spp. in the group of infants with infections. The results indicate that maternal and infant gut microbiota may play a role in predisposing an infant to infections during early life. Further studies are warranted on how this link is mediated.}, }
@article {pmid40835787, year = {2025}, author = {Nguyen, TT and Kim, YK and Nguyen, TVT and Kwon, J and Bang, YJ}, title = {Metabolic profiling and genetic tool development in the mucosal bacterium Selenomonas sputigena.}, journal = {Genes &amp; genomics}, volume = {}, number = {}, pages = {}, pmid = {40835787}, issn = {2092-9293}, support = {Creative-Pioneering Researchers Program//Seoul National University/ ; RS-2023-00217157//Ministry of Education, Science and Technology/ ; 800-20240293//College of Medicine, Seoul National University/ ; }, abstract = {BACKGROUND: Selenomonas sputigena is an anaerobic mucosa-associated bacterium with dual roles in human health-acting as a pathobiont in periodontal disease and exhibiting protective effects in allergic airway inflammation. Despite its clinical significance, its metabolic functions and underlying mechanisms remain poorly defined.<br><br>OBJECTIVE: This study aimed to systematically characterize S. sputigena's metabolic capacity and develop genetic tools for functional studies.<br><br>METHODS: We reconstructed central carbon metabolic networks through in silico analysis. Growth kinetics, substrate utilization, and fermentation profiles were evaluated experimentally across five carbon sources: glucose, gluconate, glycerol, glutamate, and succinate. Expression of key metabolic genes was quantified by qRT-PCR. Native promoter constructs were developed and tested for GFP reporter expression.<br><br>RESULTS: Selenomonas sputigena displayed glucose-preferential growth with rapid consumption (0.70&#x2009;&#xb1;&#x2009;0.05&#xa0;mM&#xa0;h&#x207b;[1]) and substantial acetate production (17.76&#x2009;&#xb1;&#x2009;2.05&#xa0;mM). Gluconate and glycerol supported moderate growth, while glutamate and succinate were poorly utilized. Gene expression analysis revealed strong substrate-dependent regulation of glycolytic genes, with gap expression correlating with growth performance, while TCA cycle genes maintained constitutive basal expression. Four native promoters successfully drove reporter expression, with Pgap demonstrating superior performance as a growth-responsive reporter.<br><br>CONCLUSIONS: This study establishes the first comprehensive metabolic and genetic framework for S. sputigena, revealing glucose-dependent fermentation with high acetate production that may contribute to host interactions. The validated promoter system enables future investigations of host-microbe interactions and therapeutic applications in mucosal environments.}, }
@article {pmid40830911, year = {2025}, author = {Qi, Q and Gao, C and Meng, X and Liu, W and Xue, Y and Yan, Y}, title = {Oral Microbiota Dynamics Across the Lifespan: Age, Sex, Race and Socioeconomic Influences in the US Population.}, journal = {Journal of clinical periodontology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jcpe.70016}, pmid = {40830911}, issn = {1600-051X}, support = {82473650//National Natural Science Foundation of China/ ; 82073572//National Natural Science Foundation of China/ ; 20230484467//Beijing Nova Program/ ; }, abstract = {AIM: The oral microbiota, a complex and dynamic ecosystem, plays a crucial role in human health, yet systematic studies across the lifespan remain limited. This study aimed to investigate variations in the oral microbiota and the effects of key influencing factors on the oral microbiota at different age groups.<br><br>MATERIALS AND METHODS: In this study, we analysed the oral microbiota of 9662 individuals aged 14-69&#x2009;years from the US National Health and Nutrition Examination Survey (NHANES) to explore the impact of demographic, lifestyle and environmental factors on microbial diversity and composition. Microbiological characterisation was done using the participants' oral rinses by 16S ribosomal RNA gene sequencing.<br><br>RESULTS: Our findings revealed a clear age-related trend in microbial diversity, with Shannon diversity peaking in middle-aged and declining in older adults. The composition of the oral microbiota also varied significantly with age, as different genera exhibited distinct abundance patterns across the lifespan. Gender and race emerged as key influencing factors, with males showing greater Shannon diversity and greater relative abundances of Atopobium, Megasphaera and Porphyromonas spp., and Whites were enriched in Rothia and Veillonella. Socioeconomic factors and lifestyle, particularly smoking, were strongly associated with shifts in microbial communities.<br><br>CONCLUSIONS: These findings provide a comprehensive overview of the dynamic changes in the oral microbiota throughout life and underscore the intricate interplay between host and environmental factors in shaping microbial composition, offering a foundation for future research on microbiota-related health interventions.}, }
@article {pmid40828642, year = {2025}, author = {Davies, RG and Wood, LA and Hengist, A and O'Donovan, C and Barton, W and Crispie, F and Walhin, JP and Valdivia-Garcia, MA and Garcia-Perez, I and Frost, G and O'Sullivan, O and Cotter, PD and Gonzalez, JT and Betts, JA and Koumanov, F and Thompson, D}, title = {Effects of a combined energy restriction and vigorous-intensity exercise intervention on the human gut microbiome: A randomised controlled trial.}, journal = {The Journal of physiology}, volume = {}, number = {}, pages = {}, doi = {10.1113/JP287424}, pmid = {40828642}, issn = {1469-7793}, support = {MR/P002927/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Metabolic health improvements in response to exercise and energy restriction may be mediated by the gut microbiome, yet causal evidence in humans remains limited. We used a 3-week exercise and energy restriction intervention to examine changes to the gut microbiome in otherwise healthy sedentary men and postmenopausal women with overweight/obesity. Intervention participants (n = 18) reduced habitual energy intake by 5000 kcal/week and expended 2000 kcal/week in addition to habitual physical activity through treadmill walking at 70% V̇O2Peak. Control participants (n = 12) maintained their usual lifestyle. Participants underwent dual-energy X-ray absorptiometry (DEXA), and samples of faeces, fasted venous blood, subcutaneous adipose tissue and skeletal muscle were collected. Faecal DNA was sequenced and profiled using shotgun metagenomics, Kraken2/Bracken and Human Microbiome Project Unified Metabolic Analysis Network 2 (HUMAnN2). The intervention significantly reduced body mass (mean Δ ± SD: -2.6 ± 1.5 kg), fat mass (-1.5 ± 1.3 kg), fasted insulin (-23.5 ± 38.1 pmol/l), leptin (-10.6 ± 7.3 ng/ml) and total cholesterol (-0.70 ± 0.42 mmol/l) concentrations, and also improved insulin sensitivity (HOMA2%S (homeostatic model of assessment)). Despite these significant metabolic changes the gut microbiome was unchanged in terms of α and β diversity and relative abundance. Thus, despite clinically meaningful improvements in body composition and metabolic health, we found no evidence for changes to the gut microbiome. In conclusion early metabolic changes with weight loss in humans are unlikely to be mediated by changes to the gut microbiome. KEY POINTS: Changes to the gut microbiome could contribute to metabolic improvements associated with weight loss in humans, but there have been limited attempts to address this question using robust randomised controlled trials (RCTs). We used a parallel-group RCT to examine whether a 3-week combined energy intake restriction and vigorous-intensity exercise intervention in people with overweight and obesity was temporally associated with changes to gut microbiome taxonomic composition and functional potential, short-chain fatty acid concentrations and expression of genes related to host-microbiome interactions in skeletal muscle and subcutaneous adipose tissue. We found that the human gut microbiome remains unchanged in the face of an intensive energy intake restriction and vigorous exercise intervention that significantly improved body composition and metabolic health in people with overweight/obesity. These findings indicate that early metabolic changes with weight loss in humans are unlikely to be mediated by changes to the gut microbiome.}, }
@article {pmid40827925, year = {2025}, author = {Caffrey, EB and Olm, MR and Kothe, CI and Wastyk, HC and Evans, JD and Sonnenburg, JL}, title = {MiFoDB, a workflow for microbial food metagenomic characterization, enables high-resolution analysis of fermented food microbial dynamics.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0014125}, doi = {10.1128/msystems.00141-25}, pmid = {40827925}, issn = {2379-5077}, abstract = {Fermented foods, which contain a diversity of microbes and microbial metabolites, have been used for millennia to increase food security, flavor, and nutritional content; more recently, they have been recognized as potential mediators of human health. Metagenomics is a powerful approach to characterize microbes in fermented foods, providing high taxonomic resolution and functional insights. Here, we introduce the Microbial Food DataBase, a metagenomics-based approach designed for the identification of fermentation-associated microbes. Using this primary database of metagenome-assembled genomes and relevant deposited genomes of prokaryotes, eukaryotes, and common food-relevant substrates, we investigated 89 fermented food samples. We present a streamlined high-confidence characterization of microbial diversity in fermented food, identifying previously undiscovered genomes and facilitating strain-level tracking across food environments. The easy and robust functionality of the workflow has significant implications for advancing food safety, promoting desired microbial communities, and increasing sustainability in food production.IMPORTANCEFermented foods have microbial communities that influence food safety, flavor, and human health. Microbial Food DataBase (MiFoDB), an alignment-based sequencing workflow and database, addresses the limitations of existing tools by enabling strain-level resolution, identifying novel genomes, and providing functional insights into microbial communities. Applying MiFoDB to fermented food samples, we demonstrate its ability to uncover novel species, track microbial strains across substrates, and integrate functional annotations. Additionally, the outlined workflow is highly customizable and can be used to generate alignment-based databases for other microbial ecosystems. This work highlights the importance of fermentation-specific workflows for studying microbial food ecosystems, advancing food safety, sustainability, and innovation in fermented food research.}, }
@article {pmid40827869, year = {2025}, author = {Allen, JM}, title = {Rediscovering the wild: MiFoDB brings fermented food microbiomes into focus.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0059925}, doi = {10.1128/msystems.00599-25}, pmid = {40827869}, issn = {2379-5077}, abstract = {Fermented foods have sustained human societies for thousands of years, with their microbial communities subtly shaping flavor, nutrient preservation, and health. Yet despite this long-standing relationship, much of the microbial complexity within fermented foods remains unresolved. In recent work, Caffrey et al. (E. B. Caffrey, M. R. Olm, C. I. Kothe, H. C. Wastyk, et al., mSystems 10:e00141-25, 2025, https://doi.org/10.1128/msystems.00141-25) put forth a new tool, MiFoDB, a metagenomic workflow that offers a promising alternative for advancing food microbiome science. By enabling strain-level resolution, functional gene annotation, and microbial tracking across substrates and time, MiFoDB provides a clearer view into the ecological and functional landscape of the fermented food microbiota. This work also bridges gaps between food and human microbiome research and brings us closer to a mechanistic understanding of how fermented foods influence health, helping transform ancient dietary practices into actionable and targeted nutritional strategies for improving human health and well-being.}, }
@article {pmid40823863, year = {2025}, author = {Glowacki, RW and Engelhart, MJ and Till, JM and Kadam, A and Nemet, I and Sangwan, N and Ahern, PP}, title = {Identification of strain-specific cues that regulate biofilm formation in Bacteroides thetaiotaomicron.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0341924}, doi = {10.1128/spectrum.03419-24}, pmid = {40823863}, issn = {2165-0497}, abstract = {Members of the gut microbiome encounter a barrage of host- and microbe-derived microbiocidal factors that must be overcome to maintain fitness in the intestine. The long-term stability of many gut microbiome strains within the microbiome suggests the existence of strain-specific strategies that have evolved to foster resilience to such insults. Despite this, little is known about the mechanisms that mediate this resistance. Biofilm formation represents one commonly employed defense strategy against stressors like those found in the intestine. Here, we demonstrate strain-level variation in the capacity of the gut symbiont Bacteroides thetaiotaomicron to form biofilms. Despite the potent induction of biofilm formation by bile in most strains, we show that the specific bile acid species driving biofilm formation differs among strains and uncover that a secondary bile acid, lithocholic acid, and its conjugated forms potently induce biofilm formation in a strain-specific manner. Additionally, we found that the short-chain fatty acid, acetic acid, could suppress biofilm formation. Thus, our data define molecular components of bile that can promote biofilm formation in B. thetaiotaomicron and reveal that distinct molecular cues trigger the induction or inhibition of this process. Moreover, we uncover strain-level variation in these responses, thus identifying that both shared and strain-specific determinants govern biofilm formation in this species.IMPORTANCEIn order to thrive within the intestine, it is imperative that gut microbes resist the multitude of insults derived from the host immune system and other microbiome members. As such, they have evolved strategies that ensure their survival within the intestine. We investigated one such strategy, biofilm formation, in Bacteroides thetaiotaomicron, a common member of the human microbiome. We uncovered significant variation in natural biofilm formation in the absence of an overt stimulus among different B. thetaiotaomicron strains and revealed that different strains adopted a biofilm lifestyle in response to distinct molecular stimuli. Thus, our studies provide novel insights into factors mediating gut symbiont resiliency, revealing strain-specific and shared strategies in these responses. Collectively, our findings underscore the prevalence of strain-level differences that should be factored into our understanding of gut microbiome functions.}, }
@article {pmid40818485, year = {2025}, author = {Shah, ND and Staudacher, HM}, title = {Cultural competence in the delivery of nutrition and symptom care in irritable bowel syndrome.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2468-1253(25)00236-5}, pmid = {40818485}, issn = {2468-1253}, }
@article {pmid40813370, year = {2025}, author = {Rakoff-Nahoum, S and Debelius, J and Valles-Colomer, M and Noordzij, HT and Esteban-Torres, M and Zhernakova, A and Brusselaers, N and Pettersen, VK}, title = {A reconceptualized framework for human microbiome transmission in early life.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7546}, pmid = {40813370}, issn = {2041-1723}, abstract = {Human development and physiology are fundamentally linked with the microbiome. This is particularly true during early life, a critical period for microbiome assembly and its impact on the host. Understanding microbial acquisition in early life is thus central to both our basic understanding of the human microbiome and strategies for disease prevention and treatment. Here, we review the historical approaches to categorize microbial transmission originating from the fields of infectious disease epidemiology and evolutionary biology and discuss how this lexicon has influenced our approach to studying the early-life microbiome, often leading to confusion and misinterpretation. We then present a conceptual framework to capture the multifaceted nature of human microbiome acquisition based on four key components: what, where, who, and when. We present ways these parameters may be assigned, with a particular focus on the 'transmitted strain' through metagenomics to capture these elements. We end with a discussion of approaches for implementing this framework toward defining each component of microbiome acquisition.}, }
@article {pmid40791541, year = {2025}, author = {Horvath, M and Kang, HG and Wu, TC and Aiken, E and Cadena Castaneda, D and Akkurt, S and Marches, F and Anczuków, O and Palucka, K and Oh, J}, title = {Host-specific bacterial modulation of airway gene expression and alternative splicing.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.07.18.665426}, pmid = {40791541}, issn = {2692-8205}, abstract = {The human microbiome varies extensively between individuals. While there are numerous studies investigating the effects of inter-individual differences on microbiome composition, there are few studies investigating inter-individual effects on microbial modulation of the host, or host-specific effects. To address this knowledge gap, we colonized human bronchial epithelial air-liquid interface tissue cultures generated from six different adults with one of three phylogenetically diverse bacteria and compared how each microbe differentially modulated host gene expression in each of the six donors. Microbial treatment had the strongest effect on transcription, followed by donor-specific effects. Gene pathways differed markedly in their donor- and microbe-specificity; interferon expression was highly donor-dependent while transcription of epithelial barrier and antibacterial innate immunity genes were predominantly microbially driven. Moreover, we evaluated whether microbial regulation of alternative splicing was modulated by donor. Strikingly, we found significant non-redundant, donor-specific regulation of alternative splicing exclusively in the Gram-positive commensal microbes. These findings highlight that microbial effects on the human airway epithelium are not only species-specific but also deeply individualized, scoring the importance of host context in shaping microbe-induced transcriptional and splicing responses.}, }
@article {pmid40653354, year = {2025}, author = {Gupta, R and Gaur, S}, title = {Effect of diet and lifestyle on microbiome composition.}, journal = {International review of cell and molecular biology}, volume = {395}, number = {}, pages = {157-174}, doi = {10.1016/bs.ircmb.2024.12.008}, pmid = {40653354}, issn = {1937-6448}, mesh = {Humans ; *Life Style ; *Diet ; *Microbiota ; Animals ; }, abstract = {Microbes are major drivers of many important physiological pathways in the human body. A well-adapted and established microbial community at key body sites performs a wide range of functions, including digestive and immunological roles. However, the structure of these microbial communities depends on numerous factors, both genetic and external. Diet and lifestyle are the most common external factors influencing microbiome composition. A healthy diet and lifestyle promote the growth of beneficial microbes, while disturbances in these factors can alter the entire microbial dynamics, potentially leading to pathogenesis. These perturbations can occur at any stage of life, from birth to old age, and may result in serious clinical conditions such as obesity, diabetes, cancers, metabolic syndromes, and many others. Therefore, it is essential to identify the dietary and lifestyle factors that support a healthy microbiome and prevent dysbiosis. This chapter aims to discuss the role of various component of diet and life style that can ultimately shape the human microbiome.}, }
@article {pmid40623763, year = {2025}, author = {Agrawal, P and Mendhey, P and Kumar, R and Patel, S and Kaushik, PK and Dadsena, A and Kumar, S}, title = {Introduction to microbiomes in health and diseases.}, journal = {International review of cell and molecular biology}, volume = {394}, number = {}, pages = {1-42}, doi = {10.1016/bs.ircmb.2024.12.010}, pmid = {40623763}, issn = {1937-6448}, mesh = {Humans ; *Microbiota ; *Health ; *Disease ; Animals ; }, abstract = {The human microbiome is a complex ecological system of commensal, symbiotic, and pathogenic microorganisms that plays a crucial role in human health and disease. The microbiome includes both the living microorganisms also called microbiota and their synthesized metabolites and structural components. It is distributed to the gastrointestinal tract, skin, respiratory system, and oral cavity, each with a distinct microbial composition. Dysbiosis, or imbalance in the microbiome is linked to numerous diseases such as eczema, gastric ulcers, cardiovascular diseases, and cancer. The axes of microbial activity and their connections to disease, including the gut-skin, gut-lung, gut-brain, and gut-kidney play a crucial role in health and disease conditions. Also, the role of the microbiome in cancer development and response to therapy is examined. This book chapter underscores the importance of maintaining a balanced microbiome for overall health and the potential for microbiome-based interventions in disease prevention and treatment.}, }
@article {pmid40586419, year = {2025}, author = {Dason, MS and Corà, D and Re, A}, title = {Sequence modeling tools to decode the biosynthetic diversity of the human microbiome.}, journal = {mSystems}, volume = {10}, number = {7}, pages = {e0033325}, pmid = {40586419}, issn = {2379-5077}, support = {P2022AFS8P//Next Generation EU - MUR/ ; }, mesh = {Humans ; *Microbiota/genetics ; *Biosynthetic Pathways/genetics ; Multigene Family ; *Computational Biology/methods ; Bacteria/genetics/metabolism ; }, abstract = {Understanding the biosynthetic potential of the human microbiome remains a significant challenge with far-reaching scientific and translational implications. Analyses of human-associated (meta)genomic sequencing data undeniably show that the biosynthetic diversity encoded in these genomes is largely underexplored. A crucial step in studying specialized metabolites involves the sequence-based identification of genes encoding biosynthetic pathways, typically organized into biosynthetic gene clusters (BGCs). In this review, we provide a concise and updated overview of the widening range of computational approaches that have effectively addressed the sequence-based identification of BGCs across both isolated genomes and complex microbial communities. These advancements are set to deepen our understanding of the biosynthetic potential and diversity of microorganisms residing in different human body sites.}, }
@article {pmid40448869, year = {2025}, author = {Dash, HR and Al-Snan, NR}, title = {DNA forensics at forty: the way forward.}, journal = {International journal of legal medicine}, volume = {139}, number = {5}, pages = {2023-2046}, pmid = {40448869}, issn = {1437-1596}, abstract = {Forensic DNA analysis has transformed criminal investigations since its inception in 1985. Over four decades, this field has evolved through various phases-from the early stages of exploration to today's highly sophisticated methodologies. Key advancements such as the development of rapid DNA analysis techniques, microchip-based systems, and next-generation sequencing have improved the speed, reliability, and utility of DNA forensics. However, despite these technological advances, the field still faces considerable challenges, particularly with increasing case backlogs, limited population-specific databases, and the difficulties associated with analyzing degraded or challenging samples like bones and touch DNA. Emerging technologies such as single-cell genomic analysis, lineage markers, proteomics, and human microbiome analysis offer promising solutions to these challenges. Furthermore, the integration of artificial intelligence (AI) and machine learning (ML) in forensic workflows is enhancing the ability to analyze complex DNA samples efficiently, paving the way for faster and more accurate results. As forensic DNA analysis enters its next phase, the focus will be on expanding databases, refining quality control and assurance protocols, and standardizing training for forensic professionals worldwide. The journey of forensic DNA analysis over the past 40 years demonstrates a field in continuous development. Although significant progress has been made, there remain opportunities for further innovation, particularly in overcoming the current limitations and addressing ethical and legal concerns. By doing so, forensic DNA analysis will continue to play a pivotal role in the future of criminal justice.}, }
@article {pmid40411594, year = {2025}, author = {Dash, HR and Patel, A}, title = {Genealogically bewildered individuals and forensic identification: a review of current and emerging solutions.}, journal = {International journal of legal medicine}, volume = {139}, number = {5}, pages = {2001-2021}, pmid = {40411594}, issn = {1437-1596}, abstract = {The increasing use of assisted reproductive technologies (ART) with donor gametes is driven by rising infertility rates, delayed parenthood, and the need to prevent hereditary diseases. Greater social acceptance of diverse family structures, advancements in reproductive medicine, and improving success rates also contribute. Accessibility, affordability, and cross-border reproductive care further expand ART's reach, making donor gametes a preferred option for many individuals and couples worldwide. The widespread application of ART has led to an increasing number of donor-conceived individuals, many of whom are now reaching reproductive maturity. This demographic shift introduces significant challenges for traditional forensic genetic identification methods, which rely on biological reference samples from genetically related individuals. The absence of such samples complicates the identification process, particularly for individuals conceived via gamete donation or adoption, where biological and legal parentage are incongruent. Conventional forensic genetic analyses, including short tandem repeat (STR) and single nucleotide polymorphism (SNP) profiling of autosomal, Y-chromosome, X-chromosome, and mitochondrial DNA, exhibit limited efficacy in these scenarios. While these methods can sometimes identify individuals conceived using a single donor gamete, they are insufficient for cases involving dual donor gametes or mitochondrial replacement therapy. Emerging methodologies such as forensic genetic genealogy, DNA methylation profiling, and human microbiome analysis offer innovative approaches but necessitate further clinical validation and standardization.}, }
@article {pmid40363959, year = {2025}, author = {Gullo, G and Satullo, M and Billone, V and De Paola, L and Petousis, S and Kotlik, Y and Margioula-Siarkou, C and Perino, A and Cucinella, G}, title = {The Role of the Genital Tract Microbiome in Human Fertility: A Literature Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {9}, pages = {}, pmid = {40363959}, issn = {2077-0383}, abstract = {Background/Objectives: Infertility is a multifactorial condition influenced by various factors, including dysbiosis and alterations in the genital tract microbiome. Recent studies emphasize the microbiome's significant role in influencing a woman's fertility potential, thereby affecting the chances of spontaneous conception and the outcomes of assisted reproductive treatments. Understanding the microbial characteristics and unique features of a healthy genital microbiome, as well as how changes in its composition can impact fertility, would allow for a more comprehensive and personalized approach to managing assisted reproductive treatments. The microbiome also influences pregnancy outcomes, and restoring its balance has been shown to improve fertility in infertile couples. The human microbiome plays a key role in maintaining the body's overall health. Disruptions in microbiome balance among women of reproductive age can contribute to a range of pregnancy-related complications, with notable consequences for both maternal and fetal well-being. Emerging research has highlighted a connection between the reproductive tract microbiome and outcomes of assisted reproductive technologies (ART), suggesting that re-establishing a healthy microbial environment may enhance fertility in couples facing infertility. Methods: We conducted a search on PubMed using the keywords "microbiome", "infertility", and "ART" over the past 10 years. This article aims to provide an updated overview of the role of the microbiome in female reproductive health, with a focus on its implications for fertility treatment. Results: The microbiome has a significant role in influencing women's fertility. Conclusions: Understanding the microbiome's impact on fertility and pregnancy outcomes may lead to more effective and personalized approaches in fertility treatments, improving the chances of successful conception and pregnancy.}, }
@article {pmid40297591, year = {2025}, author = {Pei, X and Liu, L and Han, Y}, title = {Advances in human microbiome and prostate cancer research.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1576679}, pmid = {40297591}, issn = {1664-3224}, mesh = {Humans ; *Prostatic Neoplasms/microbiology/therapy/immunology/metabolism/etiology ; Male ; *Microbiota ; *Gastrointestinal Microbiome ; Tumor Microenvironment/immunology ; Animals ; }, abstract = {Prostate cancer (PCa) is the second most common malignant tumor in men worldwide, and its metastatic and heterogeneous nature makes it significantly more difficult to treat. Recent studies have revealed the critical role of microbiota in PCa occurrence, progression, and treatment. Accumulating evidence from 16S rRNA and metagenomic sequencing suggests the presence of specific microbiota in prostate tissues and macrogenomics techniques: cancerous tissues are enriched with pro-inflammatory genera (e.g., Fusobacterium, Propionibacterium acnes), whereas commensal bacteria (e.g., Pseudomonas) are more common in paracancerous tissues. The microbiota drive tumor progression through activation of the NF-κB/STAT3 pathway to induce chronic inflammation, modulation of the immune microenvironment (e.g., Treg/Th17 imbalance and M2-type macrophage polarization), and metabolite (e.g., LPS, short-chain fatty acids)-mediated hormonal and epigenetic regulation. In terms of clinical translation, urinary microbiota characterization combined with metabolomics analysis may enhance diagnostic specificity, while gut flora modulation (e.g., probiotic interventions or fecal transplants) may improve resistance to androgen deprivation therapy. Current challenges include sequencing accuracy of low-biomass samples, limitations of causal mechanism validation models, and large cohort heterogeneity. In the future, it will be necessary to integrate multi-omics technologies to explore the bidirectional regulation of the "gut-prostate axis" and develop personalized therapeutic strategies targeting microorganisms. In this paper, we systematically review the interactions between microbiota and PCa and their clinical potentials to provide a theoretical basis for precision diagnosis and treatment.}, }
@article {pmid40166302, year = {2025}, author = {Walker, AR and Pham, DN and Noeparvar, P and Peterson, AM and Lipp, MK and Lemos, JA and Zeng, L}, title = {FRUCTOSE ACTIVATES A STRESS RESPONSE SHARED BY METHYLGLYOXAL AND HYDROGEN PEROXIDE IN STREPTOCOCCUS MUTANS.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.10.26.620100}, pmid = {40166302}, issn = {2692-8205}, abstract = {Fructose catabolism by Streptococcus mutans is initiated by three PTS transporters yielding either fructose-1-phoshate (F-1-P) or fructose-6-phosphate (F-6-P). Deletion of one such F-1-P-generating PTS, fruI, has been shown to reduce the cariogenicity of S. mutans in rats fed a high-sucrose diet. Moreover, a recent study linked fructose metabolism in S. mutans to a reactive electrophile species (RES) methylglyoxal. Here, we conducted a comparative transcriptomic analysis of exponentially grown S. mutans shocked with 50 mM fructose, 50 mM glucose, 5 mM methylglyoxal, or 0.5 mM hydrogen peroxide (H2O2). The results revealed a striking overlap between the fructose and methylglyoxal transcriptomes, totaling 176 genes, 61 of which were also shared with the H2O2 transcriptome. This core of 61 genes encompassed many of the same pathways affected by exposure to low pH or zinc intoxication. Consistent with these findings, fructose negatively impacted metal homeostasis of a mutant deficient in zinc expulsion and the growth of a mutant of the major oxidative stress regulator SpxA1. We further demonstrated the induction of the superoxide dismutase (sodA) and the fruRKI operon by different levels of fructose. Finally, fructose metabolism lowered culture pH at a faster pace, allowed better survival under acidic and nutrient-depleted conditions, and enhanced the competitiveness of S. mutans against Streptococcus sanguinis, although a moderated level of F-1-P might further boost some of these benefits. In conclusion, fructose metabolism is integrated into the stress core of S. mutans and regulates critical functions required for survival in both the oral cavity and during systemic infections. Importance. Fructose is a common monosaccharide in the biosphere, yet its overconsumption has been linked to various health problems in humans including insulin resistance, obesity, diabetes, and non-alcoholic liver diseases. These effects are in large part attributed to the unique biochemical characteristics and metabolic responses associated with the degradation of fructose. Yet, an understanding of the effects of fructose on the physiology of bacteria and its implications to the human microbiome is severely lacking. Here we performed a series of analyses on the gene regulation of a dental pathogen Streptococcus mutans by exposing it to fructose and other important stress agents. Further supported by growth, persistence, and competition assays, our findings revealed the ability of fructose to activate a set of cellular functions that may prove critical to the ability of the bacterium to persist and cause diseases both within and without of the oral cavity.}, }
@article {pmid40119155, year = {2025}, author = {Heidrich, V and Valles-Colomer, M and Segata, N}, title = {Human microbiome acquisition and transmission.}, journal = {Nature reviews. Microbiology}, volume = {23}, number = {9}, pages = {568-584}, pmid = {40119155}, issn = {1740-1534}, abstract = {As humans, we host personal microbiomes intricately connected to our biology and health. Far from being isolated entities, our microbiomes are dynamically shaped by microbial exchange with the surroundings, in lifelong microbiome acquisition and transmission processes. In this Review, we explore recent studies on how our microbiomes are transmitted, beginning at birth and during interactions with other humans and the environment. We also describe the key methodological aspects of transmission inference, based on the uniqueness of the building blocks of the microbiome - single microbial strains. A better understanding of human microbiome transmission will have implications for studies of microbial host regulation, of microbiome-associated diseases, and for effective microbiome-targeting strategies. Besides exchanging strains with other humans, there is also preliminary evidence we acquire microorganisms from animals and food, and thus a complete understanding of microbiome acquisition and transmission can only be attained by adopting a One Health perspective.}, }
@article {pmid40111698, year = {2025}, author = {Vernon, JJ}, title = {Modulation of the Human Microbiome: Probiotics, Prebiotics, and Microbial Transplants.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {277-294}, pmid = {40111698}, issn = {0065-2598}, mesh = {Humans ; *Probiotics/therapeutic use/administration &amp; dosage ; *Prebiotics/administration &amp; dosage ; *Microbiota/physiology ; *Mouth/microbiology ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {The balance between health and disease is intrinsically linked to the interactions between microbial communities and the host. This complex environment of antagonism and synergy involves both prokaryotic and eukaryotic cells, whose collaborative metabolic pathways and immunomodulatory elements influence system homeostasis. As with the gut and other niches, the oral microbiome has the capacity to affect distal host sites. The ability to manipulate this environment holds the potential to impact local and systemic disease.With the increasing threat of antimicrobial resistance, novel approaches to reduce the burden of disease are essential. The use of probiotics and prebiotics is one such strategy. Probiotics introduce non-pathogenic bacteria into the environment to compete with pathogens for nutrients and attachment sites, or to produce metabolites that counteract disease aetiologies. Prebiotic compounds enhance the growth of health-associated organisms, offering additional benefits, whilst a conjunctive approach with probiotics potentially holds even greater promise. Though widely studied in the gastrointestinal context, their potential for treating oral diseases, such as dental caries and periodontitis, is less understood. Additionally, the use of microbial transplantations has demonstrated efficacy in other areas, reducing systemic inflammation and recolonising with commensal bacteria. Here we evaluate their use in the oral context and their modulatory impact on overall health.In this chapter, we discuss how pro- and prebiotic strategies seek to modulate both the oral and gut environments to promote oral health and prevent disease. We assess novel approaches for utilising health-associated microorganisms to combat oral disorders, either administered locally in the mouth or imparting influence through immune modulation via the oral-gut axis. By examining available clinical trial data, we aim to further understand the intricacies involved in this discipline. Furthermore, we consider the challenges facing the research community, including optimal candidate organism/compound selection and colonisation retention, as well as considerations for future research.}, }
@article {pmid40072555, year = {2025}, author = {Shah, H and Patel, P and Nath, A and Shah, U and Sarkar, R}, title = {Role of human microbiota in facilitating the metastatic journey of cancer cells.}, journal = {Naunyn-Schmiedeberg's archives of pharmacology}, volume = {398}, number = {8}, pages = {9767-9796}, pmid = {40072555}, issn = {1432-1912}, abstract = {Cancer continues to be the leading cause of mortality worldwide, with metastasis being the primary contributor to cancer-related deaths. Despite significant advancements in cancer therapies, metastasis remains a major challenge in effective cancer management. Metastasis, the process by which cancer cells spread from the primary tumor to distant organs, is a complex phenomenon influenced by multiple factors, including the human microbiota. The human body encompasses various microorganisms, comprising bacteria, viruses, fungi, and protozoa, collectively known as microbiota. In fact, the microbiota is more abundant than human cells, and its disruption, leading to an imbalance in host-microbiota interactions (dysbiosis), has been linked to various diseases, including cancer. Among all microbiota, bacteria are one of the key contributors to cancer progression. Bacteria and bacteria-derived components such as secondary metabolites, QSPs, and toxins play a pivotal role in the metastatic progression of cancers. This review explores the intricate relationship between the human microbiota and cancer progression, focusing on different bacterial species which have been implicated in tumorigenesis, immune evasion, and metastasis. The present review explores the role of the human microbiome, specifically of bacteria in promoting metastasis in different types of cancers, demonstrating its ability to impact both the spread of tumors and their underlying mechanisms. This review also highlights the therapeutic potential and challenges of microbiome-based interventions in combating metastatic cancers. By addressing these challenges and by integrating microbiome-targeted strategies into clinical cancer treatment could represent a transformative approach in the fight against metastasis.}, }
@article {pmid39298326, year = {2024}, author = {Gordon, JI and Barratt, MJ and Hibberd, MC and Rahman, M and Ahmed, T}, title = {Establishing human microbial observatory programs in low- and middle-income countries.}, journal = {Annals of the New York Academy of Sciences}, volume = {1540}, number = {1}, pages = {13-20}, doi = {10.1111/nyas.15224}, pmid = {39298326}, issn = {1749-6632}, support = {//Fondazione Internazionale Premio Balzan/ ; //Bill and Melinda Gates Foundation/ ; /NH/NIH HHS/United States ; /NH/NIH HHS/United States ; }, mesh = {Humans ; *Developing Countries ; Global Health ; *Microbiota ; }, abstract = {Studies of the human microbiome are progressing rapidly but have largely focused on populations living in high-income countries. With increasing evidence that the microbiome contributes to the pathogenesis of diseases that affect infants, children, and adults in low- and middle-income countries (LMICs), and with profound and rapid ongoing changes occurring in our lifestyles and biosphere, understanding the origins of and developing microbiome-directed therapeutics for treating a number of global health challenges requires the development of programs for studying human microbial ecology in LMICs. Here, we discuss how the establishment of long-term human microbial observatory programs in selected LMICs could provide one timely approach.}, }
@article {pmid39217206, year = {2024}, author = {Duller, S and Vrbancic, S and Szydłowski, &#x141; and Mahnert, A and Blohs, M and Predl, M and Kumpitsch, C and Zrim, V and Högenauer, C and Kosciolek, T and Schmitz, RA and Eberhard, A and Dragovan, M and Schmidberger, L and Zurabischvili, T and Weinberger, V and Moser, AM and Kolb, D and Pernitsch, D and Mohammadzadeh, R and Kühnast, T and Rattei, T and Moissl-Eichinger, C}, title = {Targeted isolation of Methanobrevibacter strains from fecal samples expands the cultivated human archaeome.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {7593}, pmid = {39217206}, issn = {2041-1723}, support = {P 30796//Austrian Science Fund (Fonds zur F&#xf6;rderung der Wissenschaftlichen Forschung)/ ; SFB F-83//Austrian Science Fund (Fonds zur F&#xf6;rderung der Wissenschaftlichen Forschung)/ ; COE 7//Austrian Science Fund (Fonds zur F&#xf6;rderung der Wissenschaftlichen Forschung)/ ; }, mesh = {*Methanobrevibacter/genetics/isolation &amp; purification/metabolism ; Humans ; *Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; *Genome, Archaeal ; Methane/metabolism ; Phylogeny ; Adult ; Male ; Female ; Gastrointestinal Tract/microbiology ; }, abstract = {Archaea are vital components of the human microbiome, yet their study within the gastrointestinal tract (GIT) is limited by the scarcity of cultured representatives. Our study presents a method for the targeted enrichment and isolation of methanogenic archaea from human fecal samples. The procedure combines methane breath testing, in silico metabolic modeling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyzes include the co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits. Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which are absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from individual donors revealed features potentially associated with gastrointestinal diseases. Our work broadens available archaeal representatives for GIT studies, and offers insights into Candidatus Methanobrevibacter intestini genomes' adaptability in critical microbiome contexts.}, }
@article {pmid39167930, year = {2024}, author = {Mohamed, KA and Kruf, S and Büll, C}, title = {Putting a cap on the glycome: Dissecting human sialyltransferase functions.}, journal = {Carbohydrate research}, volume = {544}, number = {}, pages = {109242}, doi = {10.1016/j.carres.2024.109242}, pmid = {39167930}, issn = {1873-426X}, mesh = {Humans ; *Sialyltransferases/metabolism ; Polysaccharides/metabolism/chemistry ; }, abstract = {Human glycans are capped with sialic acids and these nine-carbon sugars mediate many of the biological functions and interactions of glycans. Structurally diverse sialic acid caps mark human cells as self and they form the ligands for the Siglec immune receptors and other glycan-binding proteins. Sialic acids enable host interactions with the human microbiome and many human pathogens utilize sialic acids to infect host cells. Alterations in sialic acid-carrying glycans, sialoglycans, can be found in every major human disease including inflammatory conditions and cancer. Twenty sialyltransferase family members in the Golgi apparatus of human cells transfer sialic acids to distinct glycans and glycoconjugates. Sialyltransferases catalyze specific reactions to form unique sialoglycans or they have shared functions where multiple family members generate the same sialoglycan product. Moreover, some sialyltransferases compete for the same glycan substrate, but create different sialic acid caps. The redundant and competing functions make it difficult to understand the individual roles of the human sialyltransferases in biology and to reveal the specific contributions to pathobiological processes. Recent insights hint towards the existence of biosynthetic rules formed by the individual functions of sialyltransferases, their interactions, and cues from the local Golgi environment that coordinate sialoglycan biosynthesis. In this review, we discuss the current structural and functional understanding of the human sialyltransferase family and we review recent technological advances that enable the dissection of individual sialyltransferase activities.}, }
@article {pmid39166876, year = {2024}, author = {de Palma, TH and Powers, C and McPartland, MJ and Mark Welch, J and Ramsey, M}, title = {Essential genes for Haemophilus parainfluenzae survival and biofilm growth.}, journal = {mSystems}, volume = {9}, number = {9}, pages = {e0067424}, pmid = {39166876}, issn = {2379-5077}, support = {R01 DE027958/DE/NIDCR NIH HHS/United States ; 1017848//U.S. Department of Agriculture (USDA)/ ; R01DE027958//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; }, mesh = {*Biofilms/growth &amp; development ; *Haemophilus parainfluenzae/genetics ; *Genes, Essential/genetics ; Humans ; Genome, Bacterial/genetics ; DNA Transposable Elements/genetics ; Microbial Viability/genetics ; }, abstract = {Haemophilus parainfluenzae (Hp) is a Gram-negative, highly prevalent, and abundant commensal in the human oral cavity, and an infrequent extraoral opportunistic pathogen. Hp occupies multiple niches in the oral cavity, including the supragingival plaque biofilm. Little is known about how Hp interacts with its neighbors in healthy biofilms nor its mechanisms of pathogenesis as an opportunistic pathogen. To address this, we identified the essential genome and conditionally essential genes in in vitro biofilms aerobically and anaerobically. Using transposon insertion sequencing (TnSeq) with a highly saturated mariner transposon library in two strains, the ATCC33392 type-strain (Hp 392) and oral isolate EL1 (Hp EL1), we show that the essential genomes of Hp 392 and Hp EL1 are composed of 395 (20%) and 384 (19%) genes, respectively. The core essential genome, consisting of 341 (17%) essential genes conserved between both strains, was composed of genes associated with genetic information processing, carbohydrate, protein, and energy metabolism. We also identified conditionally essential genes for aerobic and anaerobic biofilm growth, which were associated with carbohydrate and energy metabolism in both strains. RNAseq analysis determined that most genes upregulated during anaerobic growth are not essential for Hp 392 anaerobic survival. The completion of this library and analysis under these conditions gives us a foundational insight into the basic biology of H. parainfluenzae in differing oxygen conditions, similar to its in vivo habitat. This library presents a valuable tool for investigation into conditionally essential genes for an organism that lives in close contact with many microbial species in the human oral habitat.IMPORTANCEHaemophilus parainfluenzae is a highly abundant human commensal microbe, present in most healthy individuals where it colonizes the mouth. H. parainfluenzae correlates with good oral health and may play a role in preservation of healthy host status. Also, H. parainfluenzae can cause opportunistic infections outside of the oral cavity. To date, little is known about how H. parainfluenzae colonizes the human host, despite being such a frequent and abundant part of our human microbiome. Here, we demonstrate the creation and use of a powerful tool, a TnSeq library, used to identify genes necessary for both the outright growth of this organism and also genes conditionally essential for growth in varying oxygen status which it can encounter in the human host. This tool and these data serve as a foundation for further study of this relatively unknown organism that may play a role in preserving human health.}, }
@article {pmid39136453, year = {2024}, author = {Etlin, S and Rose, J and Bielski, L and Walter, C and Kleinman, AS and Mason, CE}, title = {The human microbiome in space: parallels between Earth-based dysbiosis, implications for long-duration spaceflight, and possible mitigation strategies.}, journal = {Clinical microbiology reviews}, volume = {37}, number = {3}, pages = {e0016322}, pmid = {39136453}, issn = {1098-6618}, mesh = {Humans ; *Space Flight ; *Dysbiosis/microbiology ; *Astronauts ; Microbiota/physiology ; Gastrointestinal Microbiome/physiology ; }, abstract = {SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats.}, }
@article {pmid39101047, year = {2024}, author = {Liu, J and Zhang, X and Lin, T and Chen, R and Zhong, Y and Chen, T and Wu, T and Liu, C and Huang, A and Nguyen, TT and Lee, EE and Jeste, DV and Tu, XM}, title = {A New Paradigm for High-dimensional Data: Distance-Based Semiparametric Feature Aggregation Framework via Between-Subject Attributes.}, journal = {Scandinavian journal of statistics, theory and applications}, volume = {51}, number = {2}, pages = {672-696}, pmid = {39101047}, issn = {0303-6898}, support = {K23 MH118435/MH/NIMH NIH HHS/United States ; K23 MH119375/MH/NIMH NIH HHS/United States ; R01 MH094151/MH/NIMH NIH HHS/United States ; R01 MH135147/MH/NIMH NIH HHS/United States ; }, abstract = {This article proposes a distance-based framework incentivized by the paradigm shift towards feature aggregation for high-dimensional data, which does not rely on the sparse-feature assumption or the permutation-based inference. Focusing on distance-based outcomes that preserve information without truncating any features, a class of semiparametric regression has been developed, which encapsulates multiple sources of high-dimensional variables using pairwise outcomes of between-subject attributes. Further, we propose a strategy to address the interlocking correlations among pairs via the U-statistics-based estimating equations (UGEE), which correspond to their unique efficient influence function (EIF). Hence, the resulting semiparametric estimators are robust to distributional misspecification while enjoying root-n consistency and asymptotic optimality to facilitate inference. In essence, the proposed approach not only circumvents information loss due to feature selection but also improves the model's interpretability and computational feasibility. Simulation studies and applications to the human microbiome and wearables data are provided, where the feature dimensions are tens of thousands.}, }
@article {pmid38974672, year = {2024}, author = {Castaño-Henao, L and Mendez, DFG and Egan, S and Sanabria, J}, title = {Changes in groundwater and surface water bacterial communities under disinfection processes: Chlorination, ozonization, photo-fenton and ultraviolet radiation.}, journal = {Current research in microbial sciences}, volume = {7}, number = {}, pages = {100244}, pmid = {38974672}, issn = {2666-5174}, abstract = {Pathogenic bacteria, introduced in water sources through faecal contamination, have traditionally been investigated as individual species, leading to the establishment of microbial, sanitary, and environmental quality indicators. Recent advancements in our understanding of the microbiome and its intricate interactions within the human-microbiome-environment network advocate for a broader evaluation of the impact of disinfection on the entire microbial community. In this study, we conducted a comprehensive screening experiment involving four disinfection processes; ozone, ultraviolet radiation with wavelengths between 200 - 280 nm (UV-C), photo-Fenton, and chlorination, applied to two distinct water sources; surface (SW) and groundwater (GW). The cells that remained viable after treatment were recovered using Brain Heart Infusion (BHI) broth, and 16S rRNA gene sequencing was used for their identification. Our findings confirmed the presence of faecal contamination in the water sources and revealed distinct effects of each treatment on the recovered bacterial populations. The chlorination of groundwater samples likely had a greater impact on bacteria in a vegetative state than on spores. Consequently, this led to a higher abundance in the BHI cultures of sporulating bacteria such as Bacillus (increasing from 0.36 to 93.62 %), while ozonation led to an elevated recovery of Pseudomonas (increasing from 45.2 to 69.9 %). Conversely, in surface water, calcium hypochlorite and ozone treatments favored the selection of Staphylococcus and Bacillus, whose relative abundance in the cultures increased from 0 to 39.22 % and from 0.35 to 96.6 %, respectively. In groundwater, Pseudomonas was resistant to UV-C radiation and their relative abundance increased from 45.2 % to 93.56 %, while photo-Fenton was effective against this bacterial group decreasing its relative abundance to 0.46 %. However, other genera such as Bacteroides, Aeromonas, and Citrobacter seemed to be less injured by this disinfection process. BHI broth was successful in recovering various bacterial groups that exhibited resistance to sublethal water disinfection.}, }
@article {pmid38850297, year = {2024}, author = {Hoisington, AJ and Stamper, CE and Ellis, JC and Lowry, CA and Brenner, LA}, title = {Quantifying variation across 16S rRNA gene sequencing runs in human microbiome studies.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {367}, pmid = {38850297}, issn = {1432-0614}, support = {U.S. Department of Veterans Affairs//U.S. Department of Veterans Affairs/ ; 140755//Mindsource Brain Injury Network/ ; }, mesh = {Humans ; *RNA, Ribosomal, 16S/genetics ; *Feces/microbiology ; *Microbiota/genetics ; *Sequence Analysis, DNA/methods ; *DNA, Bacterial/genetics ; Bacteria/genetics/classification/isolation &amp; purification ; Reproducibility of Results ; Mouth/microbiology ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {Recent microbiome research has incorporated a higher number of samples through more participants in a study, longitudinal studies, and metanalysis between studies. Physical limitations in a sequencing machine can result in samples spread across sequencing runs. Here we present the results of sequencing nearly 1000 16S rRNA gene sequences in fecal (stabilized and swab) and oral (swab) samples from multiple human microbiome studies and positive controls that were conducted with identical standard operating procedures. Sequencing was performed in the same center across 18 different runs. The simplified mock community showed limitations in accuracy, while precision (e.g., technical variation) was robust for the mock community and actual human positive control samples. Technical variation was the lowest for stabilized fecal samples, followed by fecal swab samples, and then oral swab samples. The order of technical variation stability was inverse of DNA concentrations (e.g., highest in stabilized fecal samples), highlighting the importance of DNA concentration in reproducibility and urging caution when analyzing low biomass samples. Coefficients of variation at the genus level also followed the same trend for lower variation with higher DNA concentrations. Technical variation across both sample types and the two human sampling locations was significantly less than the observed biological variation. Overall, this research providing comparisons between technical and biological variation, highlights the importance of using positive controls, and provides semi-quantified data to better understand variation introduced by sequencing runs. KEY POINTS: • Mock community and positive control accuracy were lower than precision. • Samples with lower DNA concentration had increased technical variation across sequencing runs. • Biological variation was significantly higher than technical variation due to sequencing runs.}, }
@article {pmid38830853, year = {2024}, author = {Kitsios, GD and Sayed, K and Fitch, A and Yang, H and Britton, N and Shah, F and Bain, W and Evankovich, JW and Qin, S and Wang, X and Li, K and Patel, A and Zhang, Y and Radder, J and Dela Cruz, C and Okin, DA and Huang, CY and Van Tyne, D and Benos, PV and Methé, B and Lai, P and Morris, A and McVerry, BJ}, title = {Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4708}, pmid = {38830853}, issn = {2041-1723}, support = {R03 HL162655/HL/NHLBI NIH HHS/United States ; COVID-19 Respiratory Virus Research//American Lung Association (Lung Association)/ ; IK2 BX004886/BX/BLRD VA/United States ; IK2BX004886//U.S. Department of Veterans Affairs (Department of Veterans Affairs)/ ; P01 HL114453/HL/NHLBI NIH HHS/United States ; T32 HL116275/HL/NHLBI NIH HHS/United States ; T32 HL007563/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Female ; Male ; *Dysbiosis/microbiology ; Middle Aged ; *Lung/microbiology ; *COVID-19/microbiology/virology ; Aged ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Host Microbial Interactions/genetics ; Longitudinal Studies ; RNA, Ribosomal, 16S/genetics ; Respiratory Insufficiency/microbiology ; SARS-CoV-2/genetics/isolation &amp; purification ; Adult ; Respiration, Artificial ; Bacteria/genetics/classification/isolation &amp; purification ; Critical Illness ; Metagenomics/methods ; }, abstract = {Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.}, }
@article {pmid38076985, year = {2023}, author = {Jain, R and Hadjigeorgiou, A and Harkos, C and Mishra, A and Morad, G and Johnson, S and Ajami, N and Wargo, J and Munn, L and Stylianopoulos, T}, title = {Dissecting the Impact of the Gut Microbiome on Cancer Immunotherapy.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38076985}, issn = {2693-5015}, support = {F32 CA260769/CA/NCI NIH HHS/United States ; R01 NS118929/NS/NINDS NIH HHS/United States ; U01 CA224348/CA/NCI NIH HHS/United States ; R01 CA259253/CA/NCI NIH HHS/United States ; R21 EB031982/EB/NIBIB NIH HHS/United States ; R35 CA197743/CA/NCI NIH HHS/United States ; R01 CA208205/CA/NCI NIH HHS/United States ; R01 CA247441/CA/NCI NIH HHS/United States ; R01 CA219896/CA/NCI NIH HHS/United States ; U01 CA261842/CA/NCI NIH HHS/United States ; }, abstract = {The gut microbiome has emerged as a key regulator of response to cancer immunotherapy. However, there is a gap in our understanding of the underlying mechanisms by which the microbiome influences immunotherapy. To this end, we developed a mathematical model based on i) gut microbiome data derived from preclinical studies on melanomas after fecal microbiota transplant, ii) mechanistic modeling of antitumor immune response, and iii) robust association analysis of murine and human microbiome profiles with model-predicted immune profiles. Using our model, we could distill the complexity of these murine and human studies on microbiome modulation in terms of just two model parameters: the activation and killing rate constants of immune cells. We further investigated associations between specific bacterial taxonomies and antitumor immunity and immunotherapy efficacy. This model can guide the design of studies to refine and validate mechanistic links between the microbiome and immune system.}, }
@article {pmid37637212, year = {2023}, author = {Li, W and Mirone, J and Prasad, A and Miolane, N and Legrand, C and Dao Duc, K}, title = {Orthogonal outlier detection and dimension estimation for improved MDS embedding of biological datasets.}, journal = {Frontiers in bioinformatics}, volume = {3}, number = {}, pages = {1211819}, pmid = {37637212}, issn = {2673-7647}, abstract = {Conventional dimensionality reduction methods like Multidimensional Scaling (MDS) are sensitive to the presence of orthogonal outliers, leading to significant defects in the embedding. We introduce a robust MDS method, called DeCOr-MDS (Detection and Correction of Orthogonal outliers using MDS), based on the geometry and statistics of simplices formed by data points, that allows to detect orthogonal outliers and subsequently reduce dimensionality. We validate our methods using synthetic datasets, and further show how it can be applied to a variety of large real biological datasets, including cancer image cell data, human microbiome project data and single cell RNA sequencing data, to address the task of data cleaning and visualization.}, }
@article {pmid37457284, year = {2023}, author = {Lugones-Sánchez, C and Santos-Mínguez, S and Salvado, R and González-Sánchez, S and Tamayo-Morales, O and Hoya-González, A and Ramírez-Manent, JI and Magallón-Botaya, R and Quesada-Rico, JA and Garcia-Cubillas, MD and Rodríguez-Sánchez, E and Gómez-Marcos, MA and Benito-Sanchez, R and Mira, A and Hernandez-Rivas, JM and Garcia-Ortiz, L and , }, title = {Lifestyles, arterial aging, and its relationship with the intestinal and oral microbiota (MIVAS III study): a research protocol for a cross-sectional multicenter study.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1164453}, pmid = {37457284}, issn = {2296-2565}, mesh = {Humans ; Middle Aged ; Aged ; Cross-Sectional Studies ; *Cardiovascular Diseases/epidemiology ; Blood Pressure/physiology ; Pulse Wave Analysis/methods ; RNA, Ribosomal, 16S ; Aging ; Life Style ; *Diet, Mediterranean ; *Microbiota ; Multicenter Studies as Topic ; }, abstract = {BACKGROUND: The microbiota is increasingly recognized as a significant factor in the pathophysiology of many diseases, including cardiometabolic diseases, with lifestyles probably exerting the greatest influence on the composition of the human microbiome. The main objectives of the study are to analyze the association of lifestyles (diet, physical activity, tobacco, and alcohol) with the gut and oral microbiota, arterial aging, and cognitive function in subjects without cardiovascular disease in the Iberian Peninsula. In addition, the study will examine the mediating role of the microbiome in mediating the association between lifestyles and arterial aging as well as cognitive function.<br><br>METHODS AND ANALYSIS: MIVAS III is a multicenter cross-sectional study that will take place in the Iberian Peninsula. One thousand subjects aged between 45 and 74 years without cardiovascular disease will be selected. The main variables are demographic information, anthropometric measurements, and habits (tobacco and alcohol). Dietary patterns will be assessed using a frequency consumption questionnaire (FFQ) and the Mediterranean diet adherence questionnaire. Physical activity levels will be evaluated using the International Physical Activity Questionnaire (IPAQ), Marshall Questionnaire, and an Accelerometer (Actigraph). Body composition will be measured using the Inbody 230 impedance meter. Arterial aging will be assessed through various means, including measuring medium intimate carotid thickness using the Sonosite Micromax, conducting analysis with pulse wave velocity (PWA), and measuring pulse wave velocity (cf-PWV) using the Sphygmocor System. Additional cardiovascular indicators such as Cardio Ankle Vascular Index (CAVI), ba-PWV, and ankle-brachial index (Vasera VS-2000[&#xae;]) will also be examined. The study will analyze the intestinal microbiota using the OMNIgene GUT kit (OMR-200) and profile the microbiome through massive sequencing of the 16S rRNA gene. Linear discriminant analysis (LDA), effect size (LEfSe), and compositional analysis, such as ANCOM-BC, will be used to identify differentially abundant taxa between groups. After rarefying the samples, further analyses will be conducted using MicrobiomeAnalyst and R v.4.2.1 software. These analyses will include various aspects, such as assessing &#x3b1; and &#x3b2; diversity, conducting abundance profiling, and performing clustering analysis.<br><br>DISCUSSION: Lifestyle acts as a modifier of microbiota composition. However, there are no conclusive results demonstrating the mediating effect of the microbiota in the relationship between lifestyles and cardiovascular diseases. Understanding this relationship may facilitate the implementation of strategies for improving population health by modifying the gut and oral microbiota.<br><br>TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT04924907, ClinicalTrials.gov, identifier: NCT04924907. Registered on 21 April 2021.}, }
@article {pmid36464584, year = {2023}, author = {Villemin, C and Six, A and Neville, BA and Lawley, TD and Robinson, MJ and Bakdash, G}, title = {The heightened importance of the microbiome in cancer immunotherapy.}, journal = {Trends in immunology}, volume = {44}, number = {1}, pages = {44-59}, doi = {10.1016/j.it.2022.11.002}, pmid = {36464584}, issn = {1471-4981}, mesh = {Humans ; *Microbiota ; *Neoplasms/therapy/microbiology ; Immunotherapy ; Bacteria ; }, abstract = {The human microbiome is recognized as a key factor in health and disease. This has been further corroborated by identifying changes in microbiome composition and function as a novel hallmark in cancer. These effects are exerted through microbiome interactions with host cells, impacting a wide variety of developmental and physiological processes. In this review, we discuss some of the latest findings on how the bacterial component of the microbiome can influence outcomes for different cancer immunotherapy modalities, highlighting identified mechanisms of action. We also address the clinical efforts to utilize this knowledge to achieve better responses to immunotherapy. A refined understanding of microbiome variations in patients and microbiome-host interactions with cancer therapies is essential to realize optimal clinical responses.}, }
@article {pmid36270683, year = {2022}, author = {Mahapatra, S and Mohanty, S and Mishra, R and Prasad, P}, title = {An overview of cancer and the human microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {83-139}, doi = {10.1016/bs.pmbts.2022.07.007}, pmid = {36270683}, issn = {1878-0814}, mesh = {Humans ; *Microbiota ; Symbiosis ; *Neoplasms ; }, abstract = {Mutual beneficial associations with the microbial consortia are an essential requisite of human life. Microbial communities have both a symbiotic and a pathogenic standpoint, which portrays a context-dependent scenario of the human microbiome. The symbiotic assemblage works to develop indispensable functions of the human body such as immune system, digestive system, defense against colonization by pathobionts and their toxins, etc. Furthermore, any deviation in the resource utilization by the symbionts due to host factors comprising lifestyle changes, diet, drugs, immunocompromised states, and co-morbidities could perturb beneficial microbes communities and promote the invasion by opportunistic pathogens thus, disrupting the homeostatic state. Microbial infestations have proved to be carcinogenic but this does not spontaneously establish a cancer hallmark, rather they initiate a cascade of events that disturbs the normal cellular activities finally these defective machineries invade distant sites of the body, submitting to a devastative transformed internal milieu. Significant technological and system biology advances have been made in elucidating a lucid but complex basis of such microbe-associated malignancies. This chapter discusses the recent advances, without compromising the concepts of the inception studies, including a brief version of the microbial status in cancer generation, mechanistic approaches adapted, therapeutic interventions, system biology approaches with special mention on the study design gaps, challenges in addressing the drawbacks and finally with a perspective of the future targeted studies, has been a focus of this piece of work.}, }
@article {pmid36109831, year = {2022}, author = {Roussel, C and Anunciação Braga Guebara, S and Plante, PL and Desjardins, Y and Di Marzo, V and Silvestri, C}, title = {Short-term supplementation with ω-3 polyunsaturated fatty acids modulates primarily mucolytic species from the gut luminal mucin niche in a human fermentation system.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2120344}, pmid = {36109831}, issn = {1949-0984}, mesh = {Akkermansia ; Docosahexaenoic Acids/pharmacology ; Eicosapentaenoic Acid/pharmacology ; Expectorants/pharmacology ; *Fatty Acids, Omega-3/pharmacology ; Fatty Acids, Volatile ; Fermentation ; Firmicutes ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Mucins ; Prebiotics ; Propionates/pharmacology ; Verrucomicrobia ; }, abstract = {Consumption of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provides multifaceted health benefits. Recent studies suggest that ω-3 PUFAs modulate the gut microbiota by enhancing health-promoting bacteria, such as the mucin specialist Akkermansia muciniphila. However, these prebiotic properties have been poorly investigated and direct effects on the gut microbiome have never been explored dynamically across gut regions and niches (lumen vs. mucus-associated microbiota). Thus, we studied the effects of 1 week EPA- and DHA-enriched ω-3 fish-oil supplementation on the composition and functionality of the human microbiome in a Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME®). Gut microbial communities derived from one individual harvested in two different seasons were tested in duplicate. Luminal and outer mucus-associated microbiota of the ileum, ascending, transverse and descending colons were cultivated over 28 d from fecal inoculates and supplemented with ω-3 PUFAs for the last 7 d. We show that ω-3 PUFA supplementation modulates the microbiota in a gut region- and niche-dependent fashion. The outer mucus-associated microbiota displayed a higher resilience than the luminal mucin habitat to ω-3 PUFAs, with a remarkable blooming of Akkermansia muciniphila in opposition to a decrease of Firmicutes-mucolytic bacteria. The ω-3 PUFAs also induced a gradual and significant depletion of non-mucolytic Clostridia members in luminal habitats. Finally, increased concentrations of the short chain fatty acids (SCFA) propionate in colon regions at the end of the supplementation was associated positively with the bloom of Akkermansia muciniphila and members of the Desulfovibrionia class.}, }
@article {pmid36068270, year = {2022}, author = {Ke, S and Weiss, ST and Liu, YY}, title = {Dissecting the role of the human microbiome in COVID-19 via metagenome-assembled genomes.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5235}, pmid = {36068270}, issn = {2041-1723}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; RF1 AG067744/AG/NIA NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {*COVID-19 ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome/genetics ; *Microbiota ; SARS-CoV-2/genetics ; }, abstract = {Coronavirus disease 2019 (COVID-19), primarily a respiratory disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is often accompanied by gastrointestinal symptoms. However, little is known about the relation between the human microbiome and COVID-19, largely due to the fact that most previous studies fail to provide high taxonomic resolution to identify microbes that likely interact with SARS-CoV-2 infection. Here we used whole-metagenome shotgun sequencing data together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from 514 COVID-19 related nasopharyngeal and fecal samples in six independent cohorts. We reconstructed a total of 11,584 medium-and high-quality microbial MAGs and obtained 5403 non-redundant MAGs (nrMAGs) with strain-level resolution. We found that there is a significant reduction of strain richness for many species in the gut microbiome of COVID-19 patients. The gut microbiome signatures can accurately distinguish COVID-19 cases from healthy controls and predict the progression of COVID-19. Moreover, we identified a set of nrMAGs with a putative causal role in the clinical manifestations of COVID-19 and revealed their functional pathways that potentially interact with SARS-CoV-2 infection. Finally, we demonstrated that the main findings of our study can be largely validated in three independent cohorts. The presented results highlight the importance of incorporating the human gut microbiome in our understanding of SARS-CoV-2 infection and disease progression.}, }
@article {pmid36014818, year = {2022}, author = {Lane, MM and Lotfaliany, M and Forbes, M and Loughman, A and Rocks, T and O'Neil, A and Machado, P and Jacka, FN and Hodge, A and Marx, W}, title = {Higher Ultra-Processed Food Consumption Is Associated with Greater High-Sensitivity C-Reactive Protein Concentration in Adults: Cross-Sectional Results from the Melbourne Collaborative Cohort Study.}, journal = {Nutrients}, volume = {14}, number = {16}, pages = {}, pmid = {36014818}, issn = {2072-6643}, mesh = {Adult ; *C-Reactive Protein/analysis ; Cohort Studies ; Cross-Sectional Studies ; Diet ; *Energy Intake ; Fast Foods/adverse effects/analysis ; Food Handling ; Humans ; }, abstract = {Background: Few studies have examined associations between ultra-processed food intake and biomarkers of inflammation, and inconsistent results have been reported in the small number of studies that do exist. As such, further investigation is required. Methods: Cross-sectional baseline data from the Melbourne Collaborative Cohort Study (MCCS) were analysed (n = 2018). We applied the NOVA food classification system to data from a food frequency questionnaire (FFQ) to determine ultra-processed food intake (g/day). The outcome was high-sensitivity C-reactive protein concentration (hsCRP; mg/L). We fitted unadjusted and adjusted linear regression analyses, with sociodemographic characteristics and lifestyle- and health-related behaviours as covariates. Supplementary analyses further adjusted for body mass index (kg/m2). Sex was assessed as a possible effect modifier. Ultra-processed food intake was modelled as 100 g increments and the magnitude of associations expressed as estimated relative change in hsCRP concentration with accompanying 95% confidence intervals (95%CIs). Results: After adjustment, every 100 g increase in ultra-processed food intake was associated with a 4.0% increase in hsCRP concentration (95%CIs: 2.1−5.9%, p < 0.001). Supplementary analyses showed that part of this association was independent of body mass index (estimated relative change in hsCRP: 2.5%; 95%CIs: 0.8−4.3%, p = 0.004). No interaction was observed between sex and ultra-processed food intake. Conclusion: Higher ultra-processed food intake was cross-sectionally associated with elevated hsCRP, which appeared to occur independent of body mass index. Future prospective and intervention studies are necessary to confirm directionality and whether the observed association is causal.}, }
@article {pmid35876529, year = {2022}, author = {Kitrinos, C and Bell, RB and Bradley, BJ and Kamilar, JM}, title = {Hair Microbiome Diversity within and across Primate Species.}, journal = {mSystems}, volume = {7}, number = {4}, pages = {e0047822}, pmid = {35876529}, issn = {2379-5077}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Phylogeny ; Primates ; *Microbiota/genetics ; Hair ; }, abstract = {Primate hair and skin are substrates upon which social interactions occur and are host-pathogen interfaces. While human hair and skin microbiomes display body site specificity and immunological significance, little is known about the nonhuman primate (NHP) hair microbiome. Here, we collected hair samples (n = 158) from 8 body sites across 12 NHP species housed at three zoological institutions in the United States to examine the following: (1) the diversity and composition of the primate hair microbiome and (2) the factors predicting primate hair microbiome diversity and composition. If both environmental and evolutionary factors shape the microbiome, then we expect significant differences in microbiome diversity across host body sites, sexes, institutions, and species. We found our samples contained high abundances of gut-, respiratory-, and environment-associated microbiota. In addition, multiple factors predicted microbiome diversity and composition, although host species identity outweighed sex, body site, and institution as the strongest predictor. Our results suggest that hair microbial communities are affected by both evolutionary and environmental factors and are relatively similar across nonhuman primate body sites, which differs from the human condition. These findings have important implications for understanding the biology and conservation of wild and captive primates and the uniqueness of the human microbiome. IMPORTANCE We created the most comprehensive primate hair and skin data set to date, including data from 12 nonhuman primate species sampled from 8 body regions each. We find that the nonhuman primate hair microbiome is distinct from the human hair and skin microbiomes in that it is relatively uniform-as opposed to distinct-across body regions and is most abundant in gut-, environment-, and respiratory-associated microbiota rather than human skin-associated microbiota. Furthermore, we found that the nonhuman primate hair microbiome varies with host species identity, host sex, host environment, and host body site, with host species identity being the strongest predictor. This result demonstrates that nonhuman primate hair microbiome diversity varies with both evolutionary and environmental factors and within and across primate species. These findings have important implications for understanding the biology and conservation of wild and captive primates and the uniqueness of the human microbiome.}, }
@article {pmid35536006, year = {2022}, author = {Oliver, A and Xue, Z and Villanueva, YT and Durbin-Johnson, B and Alkan, Z and Taft, DH and Liu, J and Korf, I and Laugero, KD and Stephensen, CB and Mills, DA and Kable, ME and Lemay, DG}, title = {Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults.}, journal = {mBio}, volume = {13}, number = {3}, pages = {e0010122}, pmid = {35536006}, issn = {2150-7511}, support = {F32 HD093185/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology ; Diet ; Dietary Fiber ; Drug Resistance, Bacterial/genetics ; *Gastrointestinal Microbiome ; Humans ; Phylogeny ; }, abstract = {Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). Diet is one method of intervention, and yet little is known about the association between diet and antimicrobial resistance. To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24[®]] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. These data suggest diet may be a potential method for reducing the burden of AMR. IMPORTANCE Antimicrobial resistance (AMR) represents a considerable burden to health care systems, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. Humans carry antibiotic resistance in the microbes that live in and on us, collectively known as the human microbiome. Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance, and yet little is known about the relationship between diet and AMR. We examined this relationship in healthy individuals who contained various abundances of antibiotic resistance genes and found that individuals who consumed diverse diets that were high in fiber and low in animal protein had fewer antibiotic resistance genes. Dietary interventions may be useful for lessening the burden of antimicrobial resistance and might ultimately motivate dietary guidelines which will consider how nutrition can reduce the impact of infectious disease.}, }
@article {pmid35005176, year = {2021}, author = {McGee, JS and Huttenhower, C}, title = {Of mice and men and women: Sexual dimorphism of the gut microbiome.}, journal = {International journal of women's dermatology}, volume = {7}, number = {5Part A}, pages = {533-538}, pmid = {35005176}, issn = {2352-6475}, abstract = {The gut microbiome plays a critical role in developing and educating our immune system. Therefore, its now well-established role in autoimmunity and immune disorders is in some ways not surprising. However, it is well-documented in the literature that there is a female predisposition to autoimmune disorders, while sexual dimorphisms in the human microbiome have been confined largely to areas outside of the gut. Herein, we will review the evidence of sexual dimorphism in the gut microbiome in both mice and humans, how this differs in animal models versus humans, and how such dimorphisms may be established and influenced by both host and environmental factors. We will conclude with a discussion on how these aspects of the gut microbiome may contribute to both the study and pathogenesis of gender-specific autoimmunity and immune disorders.}, }
@article {pmid34525957, year = {2021}, author = {Wang, C and Hu, J and Blaser, MJ and Li, H}, title = {Microbial trend analysis for common dynamic trend, group comparison, and classification in longitudinal microbiome study.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {667}, pmid = {34525957}, issn = {1471-2164}, support = {R01 DK110014/DK/NIDDK NIH HHS/United States ; R01DK110014//foundation for the national institutes of health/ ; U01AI22285//foundation for the national institutes of health/ ; 1P20CA252728//foundation for the national institutes of health/ ; P20 CA252728/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Computational Biology ; Longitudinal Studies ; Mice ; *Microbiota ; }, abstract = {BACKGROUND: The human microbiome is inherently dynamic and its dynamic nature plays a critical role in maintaining health and driving disease. With an increasing number of longitudinal microbiome studies, scientists are eager to learn the comprehensive characterization of microbial dynamics and their implications to the health and disease-related phenotypes. However, due to the challenging structure of longitudinal microbiome data, few analytic methods are available to characterize the microbial dynamics over time.<br><br>RESULTS: We propose a microbial trend analysis (MTA) framework for the high-dimensional and phylogenetically-based longitudinal microbiome data. In particular, MTA can perform three tasks: 1) capture the common microbial dynamic trends for a group of subjects at the community level and identify the dominant taxa; 2) examine whether or not the microbial overall dynamic trends are significantly different between groups; 3) classify an individual subject based on its longitudinal microbial profiling. Our extensive simulations demonstrate that the proposed MTA framework is robust and powerful in hypothesis testing, taxon identification, and subject classification. Our real data analyses further illustrate the utility of MTA through a longitudinal study in mice.<br><br>CONCLUSIONS: The proposed MTA framework is an attractive and effective tool in investigating dynamic microbial pattern from longitudinal microbiome studies.}, }
@article {pmid33846857, year = {2021}, author = {Classen, AY and Henze, L and von Lilienfeld-Toal, M and Maschmeyer, G and Sandherr, M and Graeff, LD and Alakel, N and Christopeit, M and Krause, SW and Mayer, K and Neumann, S and Cornely, OA and Penack, O and Weißinger, F and Wolf, HH and Vehreschild, JJ}, title = {Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO).}, journal = {Annals of hematology}, volume = {100}, number = {6}, pages = {1603-1620}, pmid = {33846857}, issn = {1432-0584}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antineoplastic Agents/therapeutic use ; Drug Resistance, Bacterial ; Fluoroquinolones/therapeutic use ; Germany ; Hematologic Neoplasms/*complications/drug therapy ; Hematology ; Humans ; Medical Oncology ; Microbiota/drug effects ; Pneumocystis carinii/*drug effects ; Pneumonia, Pneumocystis/complications/*prevention &amp; control ; Societies, Medical ; }, abstract = {Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). It gives an overview about current strategies for antibacterial prophylaxis in cancer patients while taking into account the impact of antibacterial prophylaxis on the human microbiome and resistance development. Current literature published from January 2012 to August 2020 was searched and evidence-based recommendations were developed by an expert panel. All recommendations were discussed and approved in a consensus conference of the AGIHO prior to publication. As a result, we present a comprehensive update and extension of our guideline for antibacterial and PcP prophylaxis in cancer patients.}, }
@article {pmid33517907, year = {2021}, author = {Blaustein, RA and Michelitsch, LM and Glawe, AJ and Lee, H and Huttelmaier, S and Hellgeth, N and Ben Maamar, S and Hartmann, EM}, title = {Toothbrush microbiomes feature a meeting ground for human oral and environmental microbiota.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {32}, pmid = {33517907}, issn = {2049-2618}, support = {TL1 TR001423/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; *Built Environment ; Drug Resistance, Microbial/drug effects/genetics ; Humans ; Metagenome/drug effects/genetics ; *Microbiota/drug effects/genetics ; Middle Aged ; Mouth/drug effects/*microbiology ; *Toothbrushing ; Triclosan/pharmacology ; Young Adult ; }, abstract = {BACKGROUND: While indoor microbiomes impact our health and well-being, much remains unknown about taxonomic and functional transitions that occur in human-derived microbial communities once they are transferred away from human hosts. Toothbrushes are a model to investigate the potential response of oral-derived microbiota to conditions of the built environment. Here, we characterize metagenomes of toothbrushes from 34 subjects to define the toothbrush microbiome and resistome and possible influential factors.<br><br>RESULTS: Toothbrush microbiomes often comprised a dominant subset of human oral taxa and less&#xa0;abundant or&#xa0;site-specific environmental strains. Although toothbrushes contained lower taxonomic diversity than oral-associated counterparts (determined by comparison with the Human Microbiome Project), they had relatively broader antimicrobial resistance gene (ARG) profiles. Toothbrush resistomes were enriched with a variety of ARGs, notably those conferring multidrug efflux and putative resistance to triclosan, which were primarily attributable to versatile environmental taxa. Toothbrush microbial communities and resistomes correlated with a variety of factors linked to personal health, dental hygiene, and bathroom features.<br><br>CONCLUSIONS: Selective pressures in the built environment may shape the dynamic mixture of human (primarily oral-associated) and environmental microbiota that encounter each other on toothbrushes. Harboring a microbial diversity and resistome distinct from human-associated counterparts suggests toothbrushes could potentially serve as a reservoir that may enable the transfer of ARGs. Video abstract.}, }
@article {pmid33436100, year = {2021}, author = {Silverstein, RB and Mysorekar, IU}, title = {Group therapy on in utero colonization: seeking common truths and a way forward.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {7}, pmid = {33436100}, issn = {2049-2618}, support = {R01 HD091218/HD/NICHD NIH HHS/United States ; }, mesh = {*Consensus ; Female ; Fetus/*microbiology ; Humans ; Microbiota/*physiology ; Uncertainty ; Uterus/*microbiology ; }, abstract = {The human microbiome refers to the genetic composition of microorganisms in a particular location in the human body. Emerging evidence over the past many years suggests that the microbiome constitute drivers of human fate almost at par with our genome and epigenome. It is now well accepted after decades of disbelief that a broad understanding of human development, health, physiology, and disease requires understanding of the microbiome along with the genome and epigenome. We are learning daily of the interdependent relationships between microbiome/microbiota and immune responses, mood, cancer progression, response to therapies, aging, obesity, antibiotic usage, and overusage and much more. The next frontier in microbiome field is understanding when does this influence begin? Does the human microbiome initiate at the time of birth or are developing human fetuses already primed with microbes and their products in utero. In this commentary, we reflect on evidence gathered thus far on this question and identify the unknown common truths. We present a way forward to continue understanding our microbial colleagues and our interwoven fates.}, }
@article {pmid33323129, year = {2020}, author = {Utter, DR and Borisy, GG and Eren, AM and Cavanaugh, CM and Mark Welch, JL}, title = {Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {293}, pmid = {33323129}, issn = {1474-760X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DE022586/DE/NIDCR NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Chromosome Mapping ; Haemophilus parainfluenzae/genetics ; Humans ; *Metagenome ; Microbiota/*genetics ; Micrococcaceae/genetics ; Mouth/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The increasing availability of microbial genomes and environmental shotgun metagenomes provides unprecedented access to the genomic differences within related bacteria. The human oral microbiome with its diverse habitats and abundant, relatively well-characterized microbial inhabitants presents an opportunity to investigate bacterial population structures at an ecosystem scale.<br><br>RESULTS: Here, we employ a metapangenomic approach that combines public genomes with Human Microbiome Project (HMP) metagenomes to study the diversity of microbial residents of three oral habitats: tongue dorsum, buccal mucosa, and supragingival plaque. For two exemplar taxa, Haemophilus parainfluenzae and the genus Rothia, metapangenomes reveal distinct genomic groups based on shared genome content. H. parainfluenzae genomes separate into three distinct subgroups with differential abundance between oral habitats. Functional enrichment analyses identify an operon encoding oxaloacetate decarboxylase as diagnostic for the tongue-abundant subgroup. For the genus Rothia, grouping by shared genome content recapitulates species-level taxonomy and habitat preferences. However, while most R. mucilaginosa are restricted to the tongue as expected, two genomes represent a cryptic population of R. mucilaginosa in many buccal mucosa samples. For both H. parainfluenzae and the genus Rothia, we identify not only limitations in the ability of cultivated organisms to represent populations in their native environment, but also specifically which cultivar gene sequences are absent or ubiquitous.<br><br>CONCLUSIONS: Our findings provide insights into population structure and biogeography in the mouth and form specific hypotheses about habitat adaptation. These results illustrate the power of combining metagenomes and pangenomes to investigate the ecology and evolution of bacteria across analytical scales.}, }
@article {pmid32430415, year = {2020}, author = {Gosens, R and Hiemstra, PS and Adcock, IM and Bracke, KR and Dickson, RP and Hansbro, PM and Krauss-Etschmann, S and Smits, HH and Stassen, FRM and Bartel, S}, title = {Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease.}, journal = {The European respiratory journal}, volume = {56}, number = {2}, pages = {}, pmid = {32430415}, issn = {1399-3003}, mesh = {Humans ; Lung ; *Lung Diseases/therapy ; *Microbiota ; *Respiration Disorders ; *Respiratory Tract Diseases ; }, abstract = {Chronic respiratory diseases are highly prevalent worldwide and will continue to rise in the foreseeable future. Despite intensive efforts over recent decades, the development of novel and effective therapeutic approaches has been slow. However, there is new and increasing evidence that communities of micro-organisms in our body, the human microbiome, are crucially involved in the development and progression of chronic respiratory diseases. Understanding the detailed mechanisms underlying this cross-talk between host and microbiota is critical for development of microbiome- or host-targeted therapeutics and prevention strategies. Here we review and discuss the most recent knowledge on the continuous reciprocal interaction between the host and microbes in health and respiratory disease. Furthermore, we highlight promising developments in microbiome-based therapies and discuss the need to employ more holistic approaches of restoring both the pulmonary niche and the microbial community.}, }
@article {pmid31848308, year = {2019}, author = {Wang, C and Li, P and Yan, Q and Chen, L and Li, T and Zhang, W and Li, H and Chen, C and Han, X and Zhang, S and Xu, M and Li, B and Zhang, X and Ni, H and Ma, Y and Dong, B and Li, S and Liu, S}, title = {Characterization of the Pig Gut Microbiome and Antibiotic Resistome in Industrialized Feedlots in China.}, journal = {mSystems}, volume = {4}, number = {6}, pages = {}, pmid = {31848308}, issn = {2379-5077}, abstract = {To characterize the diversity and richness and explore the function and structure of swine gut microbiome and resistome in common pig-farming feedlots, we sampled and metagenomic sequenced the feces of pigs from four different industrialized feedlots located in four distant provinces across China. Surprisingly, more than half of the nonredundant genes (1,937,648, 54.3%) in the current catalogue were newly found compared with the previously published reference gene catalogue (RGC) of the pig gut microbiome. Additionally, 16 high-completeness draft genomes were obtained by analyzing the dominant species on each feedlot. Notably, seven of these species often appeared in the human body sites. Despite a smaller number of nonredundant genes, our study identified more antibiotic resistance genes than those available in the RGC. Tetracycline, aminoglycoside, and multidrug resistance genes accounted for nearly 70% of the relative abundance in the current catalogue. Slightly higher sharing ratios were shown between the industrialized feedlot pig gut microbiomes and human gut microbiomes than that between the RGC and human counterpart (14.7% versus 12.6% in genes and 94.1% versus 87.7% in functional groups, respectively). Furthermore, a remarkably high number of the antibiotic resistance proteins (n =141) were identified to be shared by the pig, human, and mouse resistome, indicating the potential for horizontal transfer of resistance genes. Of the antibiotic resistance proteins shared by pigs and humans, 50 proteins were related to tetracycline resistance, and 49 were related to aminoglycoside resistance.IMPORTANCE The gut microbiota is believed to be closely related to many important physical functions in the host. Comprehensive data on mammalian gut metagenomes has facilitated research on host-microbiome interaction mechanisms, but less is known about pig gut microbiome, especially the gut microbiome in industrialized feedlot pigs, compared with human microbiome. On the other hand, pig production, as an important source of food, is believed to exacerbate the antibiotic resistance in humans due to the abuse of antibiotics in pig production in various parts of the world. This study delineates an intricate picture of swine gut microbiome and antibiotic resistome in industrialized feedlots and may provide insight for the pig producing industry.}, }
@article {pmid31113222, year = {2019}, author = {Lew, KN and Starkweather, A and Cong, X and Judge, M}, title = {A Mechanistic Model of Gut-Brain Axis Perturbation and High-Fat Diet Pathways to Gut Microbiome Homeostatic Disruption, Systemic Inflammation, and Type 2 Diabetes.}, journal = {Biological research for nursing}, volume = {21}, number = {4}, pages = {384-399}, doi = {10.1177/1099800419849109}, pmid = {31113222}, issn = {1552-4175}, mesh = {Animals ; Diabetes Mellitus, Type 2/*metabolism ; Diet, High-Fat ; Dietary Fats/*metabolism ; *Gastrointestinal Microbiome ; Humans ; Inflammation/*metabolism ; Insulin Resistance ; Lipopolysaccharides/metabolism ; Obesity/*metabolism ; }, abstract = {Type 2 diabetes (T2D) is a highly prevalent metabolic disease, affecting nearly 10% of the American population. Although the etiopathogenesis of T2D remains poorly understood, advances in DNA sequencing technologies have allowed for sophisticated interrogation of the human microbiome, providing insight into the role of the gut microbiome in the development and progression of T2D. An emerging body of research reveals that gut-brain axis (GBA) perturbations and a high-fat diet (HFD), along with other modifiable and nonmodifiable risk factors, contribute to gut microbiome homeostatic imbalance. Homeostatic imbalance or disruption increases gut wall permeability and facilitates translocation of endotoxins (lipopolysaccharides) into the circulation with resultant systemic inflammation. Chronic, low-grade systemic inflammation ensues with pro-inflammatory pathways activated, contributing to obesity, insulin resistance (IR), pancreatic β-cell decline, and, thereby, T2D. While GBA perturbations and HFD are implicated in provoking these conditions, prior mechanistic models have tended to examine HFD and GBA pathways exclusively without considering their shared pathways to T2D. Addressing this gap, this article proposes a mechanistic model informed by animal and human studies to advance scientific understanding of (1) modifiable and nonmodifiable risk factors for gut microbiome homeostatic disruption, (2) HFD and GBA pathways contributing to homeostatic disruption, and (3) shared GBA and HFD pro-inflammatory pathways to obesity, IR, β-cell decline, and T2D. The proposed mechanistic model, based on the extant literature, proposes a framework for studying the complex relationships of the gut microbiome to T2D to advance study in this promising area of research.}, }
@article {pmid33149747, year = {2018}, author = {Vlasova, AN and Rajashekara, G and Saif, LJ}, title = {Interactions between human microbiome, diet, enteric viruses and immune system: Novel insights from gnotobiotic pig research.}, journal = {Drug discovery today. Disease models}, volume = {28}, number = {}, pages = {95-103}, pmid = {33149747}, issn = {1740-6757}, abstract = {Studies over the past few decades demonstrated that gnotobiotic (Gn) pigs provide an unprecedented translational model to study human intestinal health and diseases. Due to the high degree of anatomical, physiological, metabolic, immunological, and developmental similarity, the domestic pig closely mimics the human intestinal microenvironment. Also, Gn piglets can be efficiently transplanted with human microbiota from infants, children and adults with resultant microbial profiles remarkably similar to the original human samples, a feat consistently not achievable in rodent models. Finally, Gn and human microbiota-associated (HMA) piglets are susceptible to human enteric viral pathogens (including human rotavirus, HRV) and can be fed authentic human diets, which further increases the translational potential of these models. In this review, we will focus on recent studies that evaluated the pathophysiology of protein malnutrition and the associated dysbiosis and immunological dysfunction in neonatal HMA piglets. Additionally, we will discuss studies of potential dietary interventions that moderate the effects of malnutrition and dysbiosis on antiviral immunity and HRV vaccines in HMA pigs. Such studies provide novel models and novel mechanistic insights critical for development of drug interventions.}, }
@article {pmid28988258, year = {2017}, author = {Wagner Mackenzie, B and Waite, DW and Hoggard, M and Taylor, MW and Biswas, K and Douglas, RG}, title = {Moving beyond descriptions of diversity: clinical and research implications of bacterial imbalance in chronic rhinosinusitis.}, journal = {Rhinology}, volume = {55}, number = {4}, pages = {291-297}, doi = {10.4193/Rhin17.135}, pmid = {28988258}, issn = {0300-0729}, mesh = {Bacterial Physiological Phenomena ; Chronic Disease ; Discriminant Analysis ; Ecosystem ; Humans ; Machine Learning ; *Microbiota ; Paranasal Sinuses/*microbiology ; Rhinitis/*microbiology/therapy ; Sinusitis/*microbiology/therapy ; }, abstract = {Chronic rhinosinusitis (CRS) is a debilitating disease which affects 5-16% of the general population and involves long-term inflammation of the sinonasal cavity. While microbial involvement in the pathogenesis of CRS has long been suspected, the exact role of microbes remains unclear. Recent application of cultivation-independent, molecular methods has provided much new information, taking advantage of developments in both laboratory- and bioinformatics-based analyses. The aim of this mini-review is to present a variety of available bioinformatics approaches, such as data classification techniques and network analyses, with proven applications in other aspects of human microbiome health and disease research. The uses of molecular techniques in the clinical setting are still in its infancy, but these tools can further our understanding of microbial imbalance during chronic disease and help guide effective patient treatment. The mini-review emphasises ways in which CRS bacterial gene-targeted sequencing data can progress beyond descriptive summaries and toward unlocking the mechanisms by which bacterial communities can be markers for sinus health.}, }
@article {pmid25755488, year = {2013}, author = {Bawa, M and Saraswat, VA}, title = {Gut-liver axis: role of inflammasomes.}, journal = {Journal of clinical and experimental hepatology}, volume = {3}, number = {2}, pages = {141-149}, pmid = {25755488}, issn = {0973-6883}, abstract = {Inflammasomes are large multiprotein complexes that have the ability to sense intracellular danger signals through special NOD-like receptors or NLRs. They include NLRP3, NLRC4, AIM2 and NLRP6. They are involved in recognizing diverse microbial (bacteria, viruses, fungi and parasites), stress and damage signals, which result in direct activation of caspase-1, leading to secretion of potent pro-inflammatory cytokines and pyroptosis. NLRP3 is the most studied antimicrobial immune response inflammasome. Recent studies reveal expression of inflammasomes in innate immune response cells including monocytes, macrophages, neutrophils, and dendritic cells. Inflammasome deficiency has been linked to alterations in the gastrointestinal microflora. Alterations in the microbiome population and/or changes in gut permeability promote microbial translocation into the portal circulation and thus directly to the liver. Gut derived lipopolysaccharides (LPS) play a significant role in several liver diseases. Recent advancements in the sequencing technologies along with improved methods in metagenomics and bioinformatics have provided effective tools for investigating the 10(14) microorganisms of the human microbiome that inhabit the human gut. In this review, we examine the significance of inflammasomes in relation to the gut microflora and liver. This review also highlights the emerging functions of human microbiota in health and liver diseases.}, }
@article {pmid40819811, year = {2025}, author = {H, L and L, T and J, L and H, S and R, K}, title = {Ketogenic diet influences the renin-angiotensin-aldosterone system components in the healthy and inflamed intestine of male mice.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {110079}, doi = {10.1016/j.jnutbio.2025.110079}, pmid = {40819811}, issn = {1873-4847}, abstract = {Inhibiting the overexpression of the renin-angiotensin-aldosterone system (RAAS) alleviates intestinal inflammation. Recently, we and others reported that a high-fat, low carbohydrate, ketogenic diet (KD), shown to downregulate the conventional RAAS components in rat lung and adipose tissue, can protect mice from experimental colitis. Here we assessed whether the proinflammatory angiotensin-converting enzyme - angiotensin receptor type 1 (ACE-AT1R) axis and the anti-inflammatory angiotensin-converting enzyme 2- MAS1 receptor (ACE2-MAS1) axis RAAS components are influenced by the consumption of a KD rich either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) in healthy and inflamed intestine of C57BL/6J male mice. In healthy jejunum, KD increased the AT2R protein level and decreased Ace2 level regardless of the fat source, whereas in the healthy colon, the RAAS components were unaffected by the dietary interventions. In colon, administration of 2.5 % (w/v) dextran sodium sulfate (DSS) for 5 days upregulated ACE protein while downregulating Agtr2 gene expression. These DSS-induced changes were absent in both KD groups. Furthermore, the DSS-SFA-KD group exhibited lower angiotensinogen gene expression than the DSS animals. Additionally, LA-KD mitigated the DSS-induced decrease in Ace2 gene expression. In conclusion, intestinal RAAS component expression is influenced by KDs, and the DSS-induced upregulation of proinflammatory RAAS components were not observed in DSS-KD groups.}, }
@article {pmid40815467, year = {2025}, author = {Wang, X and Liang, T and Liang, Z and Jiang, T and Chen, Y and Chen, T and Dong, B and Wu, Q and Gao, Y}, title = {Increased vaginal Gardnerella vaginalis abundance and reduced D-galactose metabolism are associated with preterm birth in older mothers with columnar ectopy in South China.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0082525}, doi = {10.1128/msystems.00825-25}, pmid = {40815467}, issn = {2379-5077}, abstract = {Advanced maternal age is associated with adverse pregnancy outcomes. However, the impact of changes in maternal physiology, biochemistry, vaginal microbiome, and its metabolites related to reproductive age on pregnancy outcomes is uncertain. Multi-omics were used to analyze vaginal samples collected from 195 pregnant women of different age groups to characterize the factors affecting the occurrence of adverse pregnancy outcomes in older mothers. Results showed that advanced maternal age is associated with a higher risk of premature birth. Furthermore, columnar ectopy may also contribute to premature birth. Moreover, older mothers with columnar ectopy exhibited vaginal microbiome dysbiosis, characterized by an increase in Gardnerella vaginalis and a reduction in Lactobacillus crispatus. Functional analysis of the microbiome revealed that disruptions in the vaginal microbiome might contribute to columnar ectopy by influencing carbohydrate metabolism in the host, such as galactose metabolism. Finally, galactose-degrading enzymes of L. crispatus were enriched in older mothers with non-columnar ectopies. In addition, G. vaginalis promoted the occurrence of columnar ectopy, whereas the dominance of galactosidase in L. crispatus was protective against columnar ectopy. Our findings demonstrate that L. crispatus is a target to prevent columnar ectopy or age-associated premature birth. G. vaginalis and galactose can be diagnostic markers for the occurrence of adverse pregnancy outcomes in older mothers.IMPORTANCEAdvanced maternal age poses a growing challenge to maternal health globally, yet the mechanisms linking age-related physiological changes to adverse pregnancy outcomes remain unclear. This study identifies vaginal microbiome dysbiosis, characterized by increased Gardnerella vaginalis and reduced Lactobacillus crispatus, as a critical mediator of age-associated preterm birth in mothers with columnar ectopy. By integrating multi-omics analyses, we reveal that disruptions in galactose metabolism driven by microbial shifts may contribute to columnar ectopy development. Notably, L. crispatus galactosidase activity emerges as a protective factor, while G. vaginalis and galactose accumulation serve as potential diagnostic markers. These findings provide actionable targets for microbiome-based interventions to mitigate age-related pregnancy complications, advancing personalized strategies for maternal care.}, }
@article {pmid40801368, year = {2025}, author = {West, SR and Adekoya, AE and Arriaga, SK and Rajagopol, S and Varriale, SL and Planet, PJ and Ibberson, CB}, title = {Genomic analysis of eight clinical Rothia isolates.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0015325}, doi = {10.1128/mra.00153-25}, pmid = {40801368}, issn = {2576-098X}, abstract = {Here, we report the genome sequences of eight clinical isolates of Rothia, seven of which were isolated from the upper respiratory tract of people with cystic fibrosis (pwCF). Analyzing the genomes of members of the respiratory microbiome in pwCF can elucidate possible interactions among microbial community members.}, }
@article {pmid40788100, year = {2025}, author = {Nooij, S and Sanders, IMJG and Schout, L and Vossen, RHAM and Kloet, SL and Smits, WK and Ducarmon, QR}, title = {Draft and complete genome sequences of 17 Streptococcus species.}, journal = {Microbiology resource announcements}, volume = {}, number = {}, pages = {e0019025}, doi = {10.1128/mra.00190-25}, pmid = {40788100}, issn = {2576-098X}, abstract = {We present 17 near-complete or complete genomes of Streptococcus spp. obtained from eight mixed cultures of presumed Ruminococcus gnavus isolates. The genomes are classified as eight different Streptococcus spp., and three currently have no representative available in databases.}, }
@article {pmid40775187, year = {2025}, author = {Zhang, Z and Zhao, Z and Huang, X and Zhou, L and Jiang, X and Wu, H and Liu, C and Huang, K and Wen, J and Liu, Y and Miller, MC and Zhao, Z and He, Z and Wang, Y and Liu, S and Huang, L and Yuan, L and Zeng, R and Cen, Z and Chen, A and Chen, Y and Zeng, G and Liu, W and Hong, X and Ren, M and Yan, L and Zhang, Y and Guan, D and Tian, X and Cai, W and Tai, G and Mayo, KH and Zhou, Y and Li, Z and Chen, S}, title = {Galectin-3-integrin α5β1 phase separation disrupted by advanced glycation end-products impairs diabetic wound healing in rodents.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {7287}, pmid = {40775187}, issn = {2041-1723}, mesh = {*Wound Healing/physiology ; *Diabetic Foot/blood/pathology/physiopathology ; Angiogenesis/physiology ; *Galectin 3/blood/genetics/metabolism ; *Integrin alpha5beta1/genetics/metabolism ; Insulin Resistance ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Phosphorylation ; Phase Separation ; *Glycation End Products, Advanced/metabolism ; Humans ; Male ; Animals ; Mice ; Rats ; Skin/blood supply/pathology/physiopathology ; Rats, Sprague-Dawley ; Female ; Mice, Inbred C57BL ; Diabetes Mellitus, Experimental/blood/chemically induced/complications/physiopathology ; Streptozocin/administration &amp; dosage/toxicity ; Mice, Transgenic ; Gene Knockdown Techniques ; }, abstract = {Diabetic foot ulcers are severe diabetic complications, and promoting impaired angiogenesis is essential for wound healing. Pro-angiogenic galectin-3 is elevated in diabetic serum and promotes systemic insulin resistance that may impair wound healing. However, the exact role of galectin-3 in the regulation of diabetic wound healing remains unclear. Here, we demonstrate that galectin-3 promotes skin wound healing and angiogenesis via binding to its receptor integrin α5β1, and enhances downstream focal adhesion kinase phosphorylation by forming a liquid-liquid phase separation with integrin α5β1. Under diabetic conditions, aberrant accumulated advanced glycation end-products bind to galectin-3, blocking its interaction with integrin α5β1 and impairing angiogenesis. Topical treatment of recombinant galectin-3 in hydrogels promotes diabetic wound healing in rodents without causing systemic insulin resistance and synergizes with insulin. This study clarifies the binding of galectin-3 to integrin α5β1, instead of advanced glycation end-products, forming phase separation to promote angiogenesis and diabetic wound healing, laying the foundation for local galectin-3 therapy to treat diabetic foot ulcers.}, }
@article {pmid40770074, year = {2025}, author = {Myers, T and Song, SJ and Chen, Y and De Pessemier, B and Khatib, L and McDonald, D and Huang, S and Gallo, R and Callewaert, C and Havulinna, AS and Lahti, L and Roeselers, G and Laiola, M and Shetty, SA and Kelley, ST and Knight, R and Bartko, A}, title = {Chronological age estimation from human microbiomes with transformer-based Robust Principal Component Analysis.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {1159}, pmid = {40770074}, issn = {2399-3642}, mesh = {Humans ; *Aging ; *Biometry/methods ; *Deep Learning ; *Gastrointestinal Microbiome ; *Principal Component Analysis/methods ; *Skin Microbiome ; Software Validation ; }, abstract = {Deep learning for microbiome analysis has shown potential for understanding microbial communities and human phenotypes. Here, we propose an approach, Transformer-based Robust Principal Component Analysis(TRPCA), which leverages the strengths of transformer architectures and interpretability of Robust Principal Component Analysis. To investigate benefits of TRPCA over conventional machine learning models, we benchmarked performance on age prediction from three body sites(skin, oral, gut), with 16S rRNA gene amplicon(16S) and whole-genome sequencing(WGS) data. We demonstrated prediction of age from longitudinal samples and combined classification and regression tasks via multi-task learning(MTL). TRPCA improves age prediction accuracy from human microbiome samples, achieving the largest reduction in Mean Absolute Error for WGS skin (MAE: 8.03, 28% reduction) and 16S skin (MAE: 5.09, 14% reduction) samples, compared to conventional approaches. Additionally, TRPCA's MTL approach achieves an accuracy of 89% for birth country prediction across 5 countries, while improving age prediction from WGS stool samples. Notably, TRPCA uncovers a link between subject and error prediction through residual analysis for paired samples across sequencing method (16S/WGS) and body site(oral/gut). These findings highlight TRPCA's utility in improving age prediction while maintaining feature-level interpretability, and elucidating connections between individuals and microbiomes.}, }
@article {pmid40766783, year = {2025}, author = {Kim, BR and Rha, MS and Cho, HJ and Yoon, JH and Kim, CH}, title = {Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function.}, journal = {Frontiers in cell and developmental biology}, volume = {13}, number = {}, pages = {1550845}, pmid = {40766783}, issn = {2296-634X}, abstract = {INTRODUCTION: Olfaction is important for the quality of life; however, in Kallmann syndrome (KS), defective development results in olfactory dysfunction. Notably, the mechanism underlying olfactory development, especially in the olfactory epithelium (OE), which detects olfactory signals, remains unclear. Mutations in PROK2, which encodes prokineticin-2, have been identified in approximately 9% of the KS patients with olfactory defects.<br><br>METHODS: We examined olfactory function and analyzed the causes of olfactory dysfunction based on spatiotemporal development and gene expression changes in Prok2 knockout (KO) model mice with KS.<br><br>RESULTS: The ability of the OE to detect olfactory signals was diminished in adult Prok2 KO mice. Maturation of olfactory sensory neurons (OSNs) in the OE and formation of glomeruli in the olfactory bulb (OB) in adult Prok2 KO mice were disrupted, thus causing olfactory dysfunction. Furthermore, molecular analysis of Prok2 KO mice during embryonic development revealed abnormal development of OB layers and diminished differentiation to mature OSNs in the OE at the later stage, which caused defects in the entire olfactory system. Remarkably, downstream signaling genes of Prok2, including intermediate filament genes and genes expressed in the putative OB, were found to mediate olfactory system organization.<br><br>DISCUSSION: Overall, these findings reveal the role of Prok2 in olfactory system organization and elucidate how olfactory development defects translate to olfactory function.}, }
@article {pmid40763745, year = {2025}, author = {Ho, PY and Huang, KC}, title = {Challenges in interpreting functional redundancy and quantifying functional selection in microbial communities.}, journal = {Cell systems}, volume = {}, number = {}, pages = {101350}, doi = {10.1016/j.cels.2025.101350}, pmid = {40763745}, issn = {2405-4720}, abstract = {Microbiomes often show similar functional profiles despite highly variable taxonomic compositions, a phenomenon attributed to "functional redundancy" and presumed selection for functional traits. However, this link between functional variability and selection remains vaguely defined. We demonstrate that reduced functional variability can arise from statistical averaging when aggregating taxonomic abundances and does not necessarily imply selection. We introduce an empirical null model that accounts for this statistical averaging effect. Applying this model to microbial communities from bromeliad foliage, we find no evidence of functional selection. In contrast, soil and human gut communities grown in vitro exhibit selection for metabolic functions. We also find that correlations between functions and taxonomic abundances can produce misleading signals of selection. Using an extended null model, we show that apparent functional selection in Human Microbiome Project data is artifactual. Our framework clarifies the conditions under which functional selection can be meaningfully inferred from microbiome data.}, }
@article {pmid40762804, year = {2025}, author = {do Carmo Greier, M and Hofauer, BG}, title = {[Prebiotics, probiotics and postbiotics-An introduction].}, journal = {HNO}, volume = {}, number = {}, pages = {}, pmid = {40762804}, issn = {1433-0458}, abstract = {The human microbiome consists of a diverse array of microorganisms that perform essential functions for health. In particular, the oral microbiome plays a crucial role in maintaining oral health by preventing the colonization of pathogenic bacteria and regulating pH balance. Dysbiosis of the oral microbiome has been linked to the development of caries, periodontal diseases and oral squamous cell carcinoma. Moreover, a bidirectional interaction between the oral and intestinal microbiomes is mediated through the so-called oral-gut axis. In recent years, prebiotics, probiotics and especially postbiotics have been extensively studied for their potential in microbiome modulation. Postbiotics represent a promising alternative as they do not contain viable microorganisms but bioactive metabolites, cell wall fragments or enzymes that exert immunomodulatory, anti-inflammatory and antimicrobial effects. Particularly in the context of oral health, postbiotics show potential benefits by inhibiting the growth of pathogenic microbes, regulating immune responses and reducing inflammatory processes. Recent research results suggest that postbiotics can sustainably improve oral health. Furthermore, preliminary studies indicate their potential application as an adjunct therapy for oral cancer due to their antitumor properties.}, }
@article {pmid40758911, year = {2025}, author = {Blaser, MJ and Dominguez-Bello, MG}, title = {The Invisible Extinction.}, journal = {Annual review of microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-micro-051024-092416}, pmid = {40758911}, issn = {1545-3251}, abstract = {The characterization of the human microbiome has opened a new chapter in understanding human biology and its relationship to health and disease. Yet we also have learned that our ancient coevolved microbiome has been changing across recent human generations; we have been losing a substantial amount of its diversity. This is especially concerning because the microbiota that we acquire early in life has important bearing on our developmental trajectory, especially with regard to metabolism, immunity, and cognition. Collectively, the early-life microbiota is a partner in our human developmental biology. We detail the medical, public health, and dietary phenomena bearing on the acquisition, maintenance, and loss of members of the microbiota and then consider the linkages between the altered microbiome and the diseases that have been emerging in recent years. Finally, we highlight ways to address and solve these problems associated with modernization.}, }
@article {pmid40757859, year = {2025}, author = {Adekoya, AE and West, SR and Arriaga, SK and Ibberson, CB}, title = {Infections as ecosystems: community metabolic interactions in microbial pathogenesis.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {e0053024}, doi = {10.1128/iai.00530-24}, pmid = {40757859}, issn = {1098-5522}, abstract = {Microbes rarely exist alone; instead, they live in dynamic multi-species communities with a range of metabolic capacities. To establish within a polymicrobial community, an organism must compete with the other members of the community for space and nutrients. In addition, microbes form complex metabolic interdependencies in polymicrobial environments, and these nutrient exchanges are central to overall community function. Interactions between microbial community members dictate key processes, including nutrient cycling, tolerance to disturbances, and disease progression, and these interactions are known to depend on the environment in which they are measured. Therefore, understanding these ecological interactions is fundamental to our understanding of community composition, function, and impacts on disease. In this mini-review, we will describe the mechanisms microbes use to exchange nutrients in host-associated environments, with a focus on the oral and respiratory tracts. We will particularly emphasize the environmental factors that influence community composition and how interactions between organisms, ranging from cooperation to competition, impact nutrient bioavailability and overall community function during infection.}, }
@article {pmid40752380, year = {2025}, author = {Sendo, S and Vela, AJ and Ro, M and Thiruppathy, D and Wilkinson, EL and Zhao, Z and Hsieh, WC and Yang, S and Coras, R and Bergot, AS and Guma, M and Nguyen, A and McBride, DA and Devkota, S and Thomas, R and Shah, NJ and Svensson, MND and Zengler, K and Stanford, SM and Bottini, N}, title = {Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.}, journal = {Journal of autoimmunity}, volume = {156}, number = {}, pages = {103452}, doi = {10.1016/j.jaut.2025.103452}, pmid = {40752380}, issn = {1095-9157}, abstract = {Gut dysbiosis is observed in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), however, how it promotes disease in interaction with other environmental and genetic risk factors remains unclear. Here we assessed interactions between gut dysbiosis and RA/JIA-associated loss of function haplotypes of the RA/JIA-associated PTPN2 gene by inducing mannan-induced arthritis in germ-free PTPN2[+/+] and PTPN2 haploinsufficient (PTPN2[+/-]) SKG mice reconstituted with fecal microbiota from six patients with seropositive RA. Mannan-induced arthritis and lymph node T cell immunophenotypes were identical in germ free PTPN2[+/+] vs PTPN2[+/-] SKG mice. While no difference in arthritis severity was seen among PTPN2[+/+] mice recipient of RA gut microbiota, two microbiomes (RA#02 and RA#86) enhanced arthritis in PTPN2[+/-] mice. The microbiome of RA patient microbiota recipient mice exclusively clustered by patient of origin and the RA#86 microbiome was found to carry a significant expansion of Prevotella genera, which is associated with RA dysbiosis. RA#86 microbiota-recipient PTPN2[+/-] mice selectively displayed increased joint GM-CSF expression and an expansion of CD4[+]RORγt[+]FoxP3[-] T cells in the joints, without evidence of increased intestinal inflammation, gut barrier leakage or expansion of P. copri in post-mannan fecal samples. Monocolonization with P. copri caused enhanced arthritis and CD4[+]RORγt[+]FoxP3[-] T cells expansion in PTPN2[+/-] vs PTPN2[+/+] mice. Our data support current views about P. copri promotion of autoimmune arthritis and suggest that its pathogenicity can be amplified via interaction with a dysbiotic context and risk factors that enhance gut mucosa immune responses.}, }
@article {pmid40751875, year = {2025}, author = {Malik, YS and Pathania, A and De, UK and M, M and Panwar, H and Kaur, J and Mishra, A and Kumar, N and Ghosh, S and Sarkar, VK and Sakshi, }, title = {Exploring the Therapeutic Landscape of Probiotics in Enteric and Respiratory Viral Infections.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40751875}, issn = {1867-1314}, abstract = {In recent times, the understanding of the human microbiome and its impact on health and disease has undergone a paradigm shift, leading to ground-breaking discoveries in the field of probiotics. Probiotics, live microorganisms known for conferring health benefits when administered adequately, have garnered significant interest for their potential to modulate the immune system's response to viral infections in both humans and animals. The emergence of enteric and respiratory viruses as significant global health threats has prompted intensive research efforts to identify novel therapeutic strategies. Traditional antiviral therapies often face challenges such as drug resistance, limited efficacy and adverse effects, underscoring the urgent need for alternative approaches. In this context, probiotics have emerged as a promising avenue for the prevention and treatment of viral infections due to their ability to modulate the host immune response, enhance mucosal barrier function and exert direct antiviral effects. This review aims to provide a comprehensive overview of the therapeutic landscape of probiotics against enteric and respiratory viruses. Based on latest findings from preclinical and clinical studies, we have explored the mechanisms underlying the antiviral activity of probiotics and their potential role in mitigating viral infections. Furthermore, promising avenues for harnessing probiotics as adjunctive or standalone interventions against enteric and respiratory viral infections have been discussed here.}, }
@article {pmid40745489, year = {2025}, author = {Caminero, A and Tropini, C and Valles-Colomer, M and Shung, DL and Gibbons, SM and Surette, MG and Sokol, H and Tomeo, NJ and ,  and Tarr, PI and Verdu, EF}, title = {Credible inferences in microbiome research: ensuring rigour, reproducibility and relevance in the era of AI.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, pmid = {40745489}, issn = {1759-5053}, abstract = {The microbiome has critical roles in human health and disease. Advances in high-throughput sequencing and metabolomics have revolutionized our understanding of human gut microbial communities and identified plausible associations with a variety of disorders. However, microbiome research remains constrained by challenges in establishing causality, an over-reliance on correlative studies, and methodological and analytical limitations. Artificial intelligence (AI) has emerged as a powerful tool to address these challenges; however, the seamless integration of preclinical models and clinical trials is crucial to maximizing the translational impact of microbiome studies. This manuscript critically evaluates best methodological practices and limitations in the field, focusing on how emerging AI tools can bridge the gap between microbial insights and clinical applications. Specifically, we emphasize the necessity of rigorous, reproducible methodologies that integrate multiomics approaches, preclinical models and clinical trials in the AI-driven era. We propose a practical framework for applying AI to microbiome studies, alongside strategic recommendations for clinical trial design, regulatory pathways, and best practices for microbiome-based informed diagnostics, AI training and clinical interventions. By establishing these guidelines, we aim to accelerate the translation of microbiome research into clinical practice, enabling precision medicine approaches informed by the human microbiome.}, }
@article {pmid40742180, year = {2025}, author = {Tang, G and Carr, AV and Perez, C and Ramos Sarmiento, K and Levy, L and Lampe, JW and Diener, C and Gibbons, SM}, title = {Metagenomic estimation of absolute bacterial biomass in the mammalian gut through host-derived read normalization.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0098425}, doi = {10.1128/msystems.00984-25}, pmid = {40742180}, issn = {2379-5077}, abstract = {Absolute bacterial biomass estimation in the human gut is crucial for understanding microbiome dynamics and host-microbe interactions. Current methods for quantifying bacterial biomass in stool, such as flow cytometry, quantitative polymerase chain reaction (qPCR), or spike-ins, can be labor-intensive, costly, and confounded by factors like water content, DNA extraction efficiency, PCR inhibitors, and other technical challenges that add bias and noise. We propose a simple, cost-effective approach that circumvents some of these technical challenges: directly estimating bacterial biomass from metagenomes using bacterial-to-host (B:H) read count ratios. We compared B:H ratios to the standard methods outlined above, demonstrating that B:H ratios are useful proxies for bacterial biomass in stool and possibly in other host-associated substrates. B:H ratios in stool were correlated with bacterial-to-diet (B:D) read count ratios, but B:D ratios exhibited a substantial number of outlier points. Host read depletion methods reduced the total number of human reads in a given sample, but B:H ratios were strongly correlated before and after host read depletion, indicating that host read depletion did not reduce the utility of B:H ratios. B:H ratios showed expected variation between health and disease states and were generally stable in healthy individuals over time. Finally, we showed how B:H and B:D ratios can be used to track antibiotic treatment response and recovery. B:H ratios offer a convenient alternative to other absolute biomass quantification methods, without the need for additional measurements, experimental design considerations, or machine learning, enabling robust absolute biomass estimates directly from stool metagenomic data.IMPORTANCEIn this study, we asked whether normalization by host reads alone was sufficient to estimate absolute bacterial biomass directly from stool metagenomic data, without the need for synthetic spike-ins, additional experimental biomass measurements, or training data. The approach assumes that the contribution of host DNA to stool is more constant or stable than biologically relevant fluctuations in bacterial biomass. We find that host read normalization is an effective method for detecting variation in gut bacterial biomass. Absolute bacterial biomass is a key metric that often gets left out of gut microbiome studies, and empowering researchers to include this measure more broadly in their metagenomic analyses should serve to improve our understanding of host-microbiota interactions.}, }
@article {pmid40739603, year = {2025}, author = {Tao, R and Wang, X and Zhen, X and Xia, R and Chen, K and Zhang, H and Deng, Y and Zhang, S}, title = {Skin Microbiome alterations in heroin users revealed by full-length 16S rRNA sequencing.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {461}, pmid = {40739603}, issn = {1471-2180}, support = {2022YFC3302004//National Key Research and Development Program of China/ ; 2022YFC3302004//National Key Research and Development Program of China/ ; 82202080//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *RNA, Ribosomal, 16S/genetics ; *Skin/microbiology ; *Microbiota/genetics ; Adult ; *Bacteria/genetics/classification/isolation &amp; purification ; Male ; *Heroin Dependence/microbiology ; DNA, Bacterial/genetics ; Phylogeny ; Female ; Sequence Analysis, DNA ; Middle Aged ; Heroin ; Young Adult ; Skin Microbiome ; }, abstract = {BACKGROUND: Identifying key characteristics of unknown suspects, such as age, height, and drug use, is essential for advancing forensic investigations.<br><br>METHODS: In this study, we employed full-length 16S rRNA gene sequencing to analyze the bacterial communities of nasal skin (NaS), oral epithelial skin (OrE), and palm skin (PaS) in heroin users and healthy controls.<br><br>RESULTS: Our results revealed a significant reduction in bacterial community diversity among heroin users compared to the control group. Notably, bacterial composition differences were more pronounced in OrE and PaS than in NaS, with genus-level variations being more significant than those at the phylum level. Differential bacterial taxa were identified across all three distinct skin sites, with the most remarkable differences observed in OrE samples. In both NaS and OrE, the differential bacterial genera between the two groups were predominantly aerobic. In addition, the Random Forest model constructed based on the RFE feature selection strategy demonstrated strong potential of OrE bacteria for distinguishing heroin users from non-users, achieving an optimal classification accuracy of over 94% and AUC values exceeding 0.988.<br><br>CONCLUSION: In conclusion, this study highlights the differences in bacterial diversity between heroin users and healthy controls across different skin sites, supporting the potential use of skin bacterial features as forensic identifiers for heroin use. Future research should explore the mechanisms underlying these microbiome alterations and incorporate larger sample sizes to enhance the robustness of findings.}, }
@article {pmid40738103, year = {2025}, author = {Carter, MM and Demis, D and Perelman, D and St Onge, M and Petlura, C and Cunanan, K and Mathi, K and Maecker, HT and Chow, JM and Robinson, JL and Sabag-Daigle, A and Sonnenburg, ED and Buck, RH and Gardner, CD and Sonnenburg, JL}, title = {A human milk oligosaccharide alters the microbiome, circulating hormones, and metabolites in a randomized controlled trial of older adults.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {102256}, doi = {10.1016/j.xcrm.2025.102256}, pmid = {40738103}, issn = {2666-3791}, abstract = {Aging-related immune dysfunction is linked to cancer, atherosclerosis, and neurodegenerative diseases. This 6-week randomized controlled trial evaluated whether 2'-fucosyllactose (2'-FL), a human breast milk oligosaccharide with established benefits in infants and animal models, could improve gut microbiota and immune function in 89 healthy older adults (mean age 67.3 years). While the primary endpoint of cytokine response change was not met, 2'-FL supplementation increased gut Bifidobacterium levels and elevated serum insulin, high-density lipoprotein (HDL) cholesterol, and FGF21 hormone. Bifidobacterium "responders" experienced additional metabolic and proteomic changes and also performed better on a cognitive test of visual memory. Nonresponders were more likely to lack Bifidobacterium in their gut microbiota at the start of the intervention. Multi-omics analysis indicated a systemic response to 2'-FL, which could be detected in blood and urine, showcasing the potential of this prebiotic to provide diverse benefits for healthy aging. This trial was registered at ClinicalTrials.gov (NCT03690999).}, }
@article {pmid40735951, year = {2025}, author = {Liang, C and Zhou, Z and Li, P and Xiao, H}, title = {The role of Gram-positive cocci in cancer initiation, progression, and its application in therapy.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.70063}, pmid = {40735951}, issn = {1097-0215}, support = {81903199//National Natural Science Foundation of China/ ; 81802871//National Natural Science Foundation of China/ ; 2021JJ40373//Natural Science Foundation of Hunan Province/ ; 2023JJ30901//Natural Science Foundation of Hunan Province/ ; S202212652011//Hunan Province College Students' Research Learning and Innovative Experiment Project/ ; }, abstract = {Tumors are one of the most critical health issues and a leading cause of human mortality. Over the past two decades, research on the human microbiome and its functions has revealed microbiota-focused strategies for health and disease. Several studies have demonstrated the presence of intratumoral bacteria in many solid tumors, with distinct microbial compositions across different cancer types. Notably, recent studies have shown that the distribution of Gram-positive cocci differs between tumor patients and healthy individuals. Mechanistic investigations indicate that Gram-positive cocci and their metabolites play roles in inducing genomic instability and mutations, influencing epigenetic modifications, promoting inflammatory responses, regulating host immunity, and activating invasion and metastasis. With the deepening understanding of the mechanisms underlying Gram-positive cocci in tumors, novel anti-tumor therapies have been investigated. In this review, we summarize the distribution of Gram-positive cocci within the human body, explore their complex roles in the initiation, progression, and metastasis of tumors, and overview their potential in early cancer diagnosis, prognostic assessment, and therapeutic strategies. Finally, we discuss the prospects and limitations of targeting or harnessing Gram-positive cocci in cancer.}, }
@article {pmid40720439, year = {2025}, author = {Anholt, H}, title = {The association between Toxoplasma gondii infection and asthma in the United States: A cross-sectional survey analysis.}, journal = {PloS one}, volume = {20}, number = {7}, pages = {e0304044}, pmid = {40720439}, issn = {1932-6203}, mesh = {Humans ; *Asthma/epidemiology ; *Toxoplasmosis/epidemiology/complications ; Cross-Sectional Studies ; Middle Aged ; Adult ; United States/epidemiology ; Female ; Male ; Aged ; Adolescent ; Child ; Young Adult ; *Toxoplasma ; Aged, 80 and over ; Nutrition Surveys ; }, abstract = {The hygiene hypothesis proposes that declining exposure to microbial influences early in life is implicated in the rising trend of allergy and asthma in high-income societies. Approximately 8% of Americans have been diagnosed with asthma, representing 25 million people, and understanding how the human microbiome affects asthma could help guide exposure recommendations or microbe-based therapeutics. Toxoplasma gondii is a common gastro-intestinal microorganism that may modulate immune function. We used a cross-sectional study design to examine a public database of U.S. residents aged 6-80 years or older from the 2012-2014 survey cycles of the American National Health and Nutrition Examination Survey (NHANES) to construct an ordinal logistic regression model of the relationship between T. gondii infection and asthma. Of the 12,620 subjects tested for T. gondii infection, 89.2% were seronegative and 10.8% seropositive. No asthma was reported by 83.5% of subjects, while 16.5% reported varying degrees of asthma severity. We detected no significant association between T. gondii infection and asthma. While the unadjusted regression model suggested a small protective effect of T. gondii on asthma (OR = 0.90; 95% CI = 0.83-0.97), no effect was detected when the model was adjusted for key demographic factors (OR = 1.00, 95% CI = 0.91-1.10). While T. gondii may be a marker for the protective effect of exposure to a diversity of microbial organisms early in life, it has no apparent causal effect on asthma, or it may not be significant when considered in isolation.}, }
@article {pmid40715136, year = {2025}, author = {Qi, H and Gao, H and Li, M and Sun, T and Gu, X and Wei, L and Zhi, M and Li, Z and Fu, D and Liu, Y and Wei, Z and Dou, Y and Feng, Q}, title = {Author Correction: Parvimonas micra promotes oral squamous cell carcinoma metastasis through TmpC-CKAP4 axis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {6856}, doi = {10.1038/s41467-025-62180-4}, pmid = {40715136}, issn = {2041-1723}, }
@article {pmid40706714, year = {2025}, author = {Verma, B and Kumar, N and Ashique, S and Debnath, B and Garg, A and Mishra, N and Mojgani, N and Kaurav, M and Gupta, M and Bhowmick, M and Taghizadeh-Hesary, F}, title = {Probiotics: An adjuvant treatment strategy for chronic respiratory diseases.}, journal = {Respiratory medicine}, volume = {247}, number = {}, pages = {108268}, doi = {10.1016/j.rmed.2025.108268}, pmid = {40706714}, issn = {1532-3064}, abstract = {Chronic respiratory disease is considered by reduced airflow and heightened airway inflammation, a pattern that has progressively increased in past few decades. Currently, chronic respiratory disease is considered one of the main leading causes of death worldwide. The gut-lung axis, which connects these two organs, facilitates bidirectional communication and may be influenced by microbiome populations in the context of disease interactions. The human microbiome, particularly in the gastrointestinal tract is thought to play a pivotal role in affecting diseases and maintaining homeostasis. Dysbiosis, defined as an imbalance in the gut microbiota, is associated with an elevated risk of lung infections. Studies have shown that modifying the gut microbiota by the use of probiotics, prebiotics, and synbiotics can reduce the duration and extent of respiratory infections. Probiotics have been observed to significantly alter serum cytokine and IgE levels in allergic conditions, as well as reduce eosinophilia in individuals with asthma. However, there has been no discernible improvement in clinical symptoms, although this approach may diminish eosinophilia in chronic obstructive pulmonary disease (COPD) patients and mitigate serum cytokine and IgE levels. Several factors such as illness severity, treatment duration, patient-specific, environmental characteristics, and treatment regimen seem to influence the effectiveness of these interventions. Research indicates that direct interaction and colonization of respiratory epithelial cells by probiotic microbes can enhance the success of intranasal probiotic delivery compared to oral administration. Although allergic rhinitis is a chronic inflammatory ailment, nasal probiotics have been utilized to address acute infections and respiratory disorders, offering a promising therapeutic avenue for a range of chronic inflammatory conditions.}, }
@article {pmid40705071, year = {2025}, author = {Zhao, Y and Liu, X and Song, P and Chen, Q and Yang, X and Yu, W}, title = {Advances in the Relationship Between Skin Tumor Occurrence, Development, Prognosis, and the Human Microbiome.}, journal = {Current microbiology}, volume = {82}, number = {9}, pages = {408}, pmid = {40705071}, issn = {1432-0991}, mesh = {Humans ; *Microbiota ; *Skin Neoplasms/microbiology/pathology/therapy/diagnosis ; Prognosis ; Tumor Microenvironment ; Bacteria/classification/isolation &amp; purification/genetics ; Skin/microbiology ; }, abstract = {The human microbiome, including bacteria, fungi, and viruses, is widely distributed on the skin, in the oral cavity, in the gastrointestinal tract, and is also present in tumors. It is closely associated with the occurrence, development, and treatment of skin cancers and contributes to the formation of the tumor microenvironment. This review provides a detailed overview of the composition and origin of microorganisms in different types of skin tumors, focuses on the roles and mechanisms of microbiome in skin cancer, discusses their applications in the treatment of skin tumors, and outlines future research directions.}, }
@article {pmid40704713, year = {2025}, author = {Männistö, SA and Muotka, J and Suojanen, LU and Lappalainen, R and Pietiläinen, KH and Korpela, R}, title = {Effect of Minimal Individual or Group Enhancement in an eHealth Program on Mental Health, Health Behavior, and Work Ability in Employees With Obesity: Randomized Controlled Trial.}, journal = {JMIR mental health}, volume = {12}, number = {}, pages = {e66518}, pmid = {40704713}, issn = {2368-7959}, mesh = {Humans ; Female ; Male ; *Obesity/psychology/therapy ; Adult ; Telemedicine ; Middle Aged ; *Health Behavior ; *Mental Health ; }, abstract = {BACKGROUND: Mental health problems and adverse health behaviors are enriched in individuals with obesity and need to be considered in weight loss interventions. Regarding weight loss, hybrid interventions combining digital and in-person elements have proven superior to eHealth-only interventions. However, it remains unclear whether minimal group or individual enhancement could bring additional benefits to the mental health and health behavior domains in individuals with obesity.<br><br>OBJECTIVE: This study aimed to explore whether minimal group or individual enhancements could offer additional benefits to an eHealth intervention in relation to mental health, perceived work ability, and health behavior in a sample of occupational health patients with obesity. In addition, the study sought to examine the overall effects of the health behavior-focused intervention across these domains.<br><br>METHODS: This study was a randomized controlled trial with a 12-month intervention (March 2021-2022), with selected variables followed for another 12 months without additional support. Recruited from occupational health care, 111 working-age adults with BMI 30-40 kg/m2 were randomized to one of the 3 treatment arms, such as eHealth, eHealth+Group, or eHealth+Individual. All treatment arms received a web-administered, coach-assisted eHealth program based on acceptance and commitment therapy, and, in addition, the eHealth+Group and eHealth+Individual arms received 3 remotely facilitated group or individual meetings. The overall intervention effects were evaluated quasi-experimentally by combining the 3 treatment arms into a single eHealth arm. Participants were assessed for depression (the Beck Depression Index 21 [BDI-21]), burnout (Bergen Burnout Inventory 18 [BBI-15]), perceived work ability, eating behavior (ecSatter 2.0, Three Factor Eating Questionnaire [TFEQ], and Binge Eating Scale [BES]), and physical activity (Baecke Habitual Physical Activity Questionnaire, BHPAQ).<br><br>RESULTS: We observed inconsistent fluctuations between the treatment arms in depression and burnout scores, indicating a lack of meaningful intervention effects despite statistical significance. Therefore, none of the treatment arms showed superiority over another. Across all participants, depression showed an estimated mean decrease of 2.5 BDI-21 points, with older participants experiencing a greater reduction in depressive symptoms. Furthermore, binge eating tendency decreased by 4.9 BES points during the 12-month intervention. We also observed increases in eating competence, controlled restraint, and physical activity. However, the 24-month measurements showed an adverse effect on eating competence, especially on attitudes toward eating and food, during the follow-up period without further support.<br><br>CONCLUSIONS: Minimal enhancement through either group or individual video-conference meetings did not provide additional benefits in the mental health or eating habit domains compared with the eHealth intervention alone. Nevertheless, our results indicate that eHealth interventions for weight loss have the potential to reduce depression symptoms and binge-eating tendencies, while also improving eating competence and physical activity across the study population. Continued support may be necessary to sustain positive changes.}, }
@article {pmid40704481, year = {2025}, author = {Xiao, YY and Ma, YY and Zhang, YB and Chen, C and Meng, Y and Zhao, MY}, title = {Advances in Influencing Mechanisms and Therapeutic Effects of Bacteriophages on Cancer.}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {47}, number = {3}, pages = {470-477}, doi = {10.3881/j.issn.1000-503X.16282}, pmid = {40704481}, issn = {1000-503X}, mesh = {Humans ; *Bacteriophages ; Microbiota ; *Neoplasms/therapy ; *Phage Therapy ; }, abstract = {Cancer brings about an enormous threat to human health,making the exploration of its mechanisms and therapeutic strategies a current focal point and challenge in research.Bacteriophages are integral components of the human microbiome,and studies have shown their influences on tumor growth and metastasis and their pivotal role in cancer treatment.This article elucidates the mechanisms by which bacteriophages impact the occurrence and development of cancer from their interactions with cancer cells,effects on bacteria,and influence on the immune system.Additionally,it explores bacteriophage-based strategies in cancer treatment and their potential in this field.This article aims to bring new thoughts and insights to the research in this field.}, }
@article {pmid40701239, year = {2025}, author = {Aro, T and Häkkinen, TA and Holmberg, V and Kajova, M and Kantele, A}, title = {War on antimicrobial resistance: high carriage rates of multidrug-resistant bacteria among war-injured Ukrainian refugees.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.07.010}, pmid = {40701239}, issn = {1469-0691}, }
@article {pmid40693205, year = {2025}, author = {Sun, H and Finlay, B and Azad, MB and Cuomo, CA and Cowen, LE and Berdy, B and Livny, J and Shea, T and Aquino, EE and Godoy-Vitorino, F and Woortman, MA and Shumaker, M and Alba, C and Rodríguez, JM and Domínguez-Bello, MG}, title = {The human milk bacteriome and mycobiome and their inter-kingdom interactions viewed across geography.}, journal = {Frontiers in nutrition}, volume = {12}, number = {}, pages = {1610346}, pmid = {40693205}, issn = {2296-861X}, abstract = {BACKGROUND: The human milk microbiota is one of the biologically active components of human milk, and factors affecting it and the effect size are not well understood. Assessments of human milk microbiota have mainly been done in small cohorts and/or in single geographical locations, and most have been restricted to the bacteriome. Here we assessed the bacterial, archaeal and fungal composition of human milk and the potential inter-kingdom interactions in milk collected from women living in a wide spectrum of countries, environments, and socio-economical settings.<br><br>MATERIALS AND METHODS: About 518 human milk samples were collected in 16 countries. After DNA extraction, bacterial and fungal metataxonomic analyses were performed via amplification and sequencing of the 16S rDNA and the ITS2 genes, respectively. In parallel, the presence of methanogenic archaea was determined by qPCR.<br><br>RESULTS: Bacterial analysis revealed significant Country variations in human milk microbiota diversity and taxa distribution. Core genera such as Staphylococcus, Streptococcus, and Bifidobacterium were universally prevalent, and their abundance varied geographically. Methanogenic sequences were found in the amplicon sequences, mostly of Methanobrevibacter (11.8% of samples), while qPCR only detected 0.7% (2 out of 268) methanogens. Fungi-mostly Candida-were detected in 7% of samples, with wide country variations. Co-abundance network analysis revealed mostly positive bacterial correlations and negative inter-kingdom interactions.<br><br>CONCLUSION: This study shows substantial global variation in the human milk microbiome with bacterial-fungal interactions, highlighting the importance of global-scale studies to understand the human microbiome and its role in maternal and infant health.}, }
@article {pmid40692685, year = {2025}, author = {Mun, S and Jo, H and Heo, YM and Baek, C and Kim, HB and Lee, H and Yun, K and Jeong, J and Lee, W and Jeon, D and Kang, SM and Kang, S and Choi, YB and Han, S and Kim, G and Ahn, K and Lee, DH and Ahn, YJ and Lee, DG and Han, K}, title = {Skin microbiome-biophysical association: a first integrative approach to classifying Korean skin types and aging groups.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1561590}, pmid = {40692685}, issn = {2235-2988}, mesh = {Humans ; *Microbiota ; *Skin/microbiology ; Adult ; Female ; Middle Aged ; Republic of Korea ; Young Adult ; *Aging ; Aged ; Male ; Bacteria/classification/genetics/isolation &amp; purification ; Cluster Analysis ; Skin Microbiome ; }, abstract = {INTRODUCTION: The field of human microbiome research is rapidly expanding beyond the gut and into the facial skin care industry. However, there is still no established criterion to define the objective relationship between the microbiome and clinical trials for developing personalized skin solutions that consider individual diversity.<br><br>OBJECTIVES: In this study, we conducted an integrated analysis of skin measurements, clinical Baumann skin type indicator (BSTI) surveys, and the skin microbiome of 950 Korean subjects to examine the ideal skin microbiome-biophysical associations.<br><br>METHODS: By utilizing four skin biophysical parameters, we identified four distinct Korean Skin Cutotypes (KSCs) and categorized the subjects into three aging groups: the Young (under 34 years old), the Aging I group (35-50), and the Old group (over 51). To unravel the intricate connection between the skin's microbiome and KSC types, we conducted DivCom clustering analysis.<br><br>RESULTS: This endeavor successfully classified 726 out of 740 female skin microbiomes into three subclusters: DC1-sub1, DC1-sub2, and DC2 with 15 core genera. To further amplify our findings, we harnessed the potent capabilities of the CatBoost boosting algorithm and achieved a reliable framework for predicting skin types based on microbial composition with an impressive average accuracy of 0.96 AUC value. Our study conclusively demonstrated that these 15 core genera could serve as objective indicators, differentiating the microbial composition among the aging groups.<br><br>CONCLUSION: In conclusion, this study sheds light on the complex relationship between the skin microbiome and biophysical properties, and the findings provide a promising approach to advance the field of skincare, cosmetics, and broader microbial research.}, }
@article {pmid40682107, year = {2025}, author = {Pianka, ML and Werba, A and Zimmermann, S and Vey, JA and Kalkum, E and Tenckoff, S and Tony-Odigie, A and Michalski, CW and Pianka, F}, title = {The role of the MicroBiome in PANCreatic cancer and its precursors- the study protocol of the MiBiPanc systematic review and meta-analysis.}, journal = {Systematic reviews}, volume = {14}, number = {1}, pages = {150}, pmid = {40682107}, issn = {2046-4053}, support = {01KC2310//Bundesministerium f&#xfc;r Bildung und Forschung/ ; }, mesh = {Humans ; *Pancreatic Neoplasms/microbiology ; Systematic Reviews as Topic ; *Microbiota ; Meta-Analysis as Topic ; Pancreas/microbiology ; *Gastrointestinal Microbiome ; Pancreatitis, Chronic/microbiology ; *Precancerous Conditions/microbiology ; }, abstract = {BACKGROUND: Pancreatic cancer is the third leading cause of cancer-related death in Northern America and fourth in Europe. Emerging evidence suggests that the pancreatic microbiome may play a significant role in the development and progression of this disease. Although the human microbiota contributes to health by supporting nutritional and hormonal homeostasis, modulating inflammation, detoxifying harmful compounds, and producing beneficial metabolites, several studies have implicated its crucial modulatory role in numerous diseases, including cancer. The main objective of this review is to investigate the specific relationship between the microbiome and pancreatic carcinogenesis.<br><br>METHODS: A comprehensive literature search will identify studies examining the microbiome in human samples of saliva, pancreatic fluid, bile, pancreatic tissue, and feces of patients with chronic pancreatitis, precancerous pancreatic lesions, and pancreatic cancer. Studies differentiating bacteria to at least the genus level will be prioritized. Eligible studies include randomized controlled trials and observational studies analyzing the human microbiome in patients with chronic pancreatitis, pancreatic precursor lesions, or pancreatic cancer compared to healthy controls. Studies analyzing nonhuman samples, single bacterial strains, or lacking comparator groups will be excluded. The following databases will be searched without any restrictions to the publication date up until December 2024: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Embase, and Web of Science. Animal studies, case reports, and studies not reporting analyses of human samples are excluded. Details regarding blinding, risk of bias, and funding sources will be extracted and assessed. The main outcomes include the bacterial diversity in each sample type (stool, saliva, bile, intratumoral, and tissue) itemized for each diagnosis, identifying differentially abundant or depleted taxa, and evaluating the correlation of specific bacteria with disease prevention or progression and clinical outcomes. Data extraction will be performed independently by two reviewers. Risk-of-bias assessment will be performed using Cochrane tools appropriate for each study design. Comparisons will be analyzed by descriptive statistics, and meta-analyses will be performed when applicable. The review will be conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.<br><br>DISCUSSION: In summary, this systematic review aims to synthesize studies analyzing microbiome profiles in patients with chronic pancreatitis, precursor lesions, and pancreatic cancer, focusing on identifying bacterial diversity and specific taxa related to disease progression and development of cancer in comparison to healthy controls and will include a thorough critical appraisal of the available literature. Anticipated limitations include heterogeneity in microbiome sampling methods and potential variability in taxonomic resolution across studies.<br><br>PROSPERO CRD42023487995.}, }
@article {pmid40679396, year = {2025}, author = {Searle, T and Al-Niaimi, F and Ali, FR}, title = {Modulation of the microbiome: a paradigm shift in the treatment of acne.}, journal = {Clinical and experimental dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1093/ced/llaf328}, pmid = {40679396}, issn = {1365-2230}, abstract = {The role of the gut-skin axis and the human microbiome has become increasingly explored in various studies and as a result, the therapeutic potential of microbiome-modulatory agents has piqued interest. Probiotics have been explored as both a monotherapy for acne but also as an adjunct to reduce the side-effects of traditional established prescriptions to improve compliance. We review the evidence to support the use of topical and oral probiotics, prebiotics and synbiotics in treating acne vulgaris. There is some evidence of a correlation between increased C. acnes colonisation and acne severity, supporting treatments targeting the skin microbiome. However, most studies rely on in vitro, animal models, or are of small sample sizes, with limited robust clinical trials currently available. Research often overlooks the interplay of endogenous and external factors affecting skin microbiota. Whilst many microbiome modulatory products are available, their multiple ingredients require further scrutiny to isolate any beneficial components and their potential adverse effects. Additionally, the role of other microbial species in acne pathogenesis needs further examination.}, }
@article {pmid40679335, year = {2025}, author = {Parks, ST and Marchesani, A and Taylor, C}, title = {Scaffolding of assignments and grading to promote STEM literacy in a human microbiome course.}, journal = {Journal of microbiology &amp; biology education}, volume = {}, number = {}, pages = {e0007625}, doi = {10.1128/jmbe.00076-25}, pmid = {40679335}, issn = {1935-7877}, abstract = {A special topics course investigating the human microbiome was developed such that there were three layers of feedback and grading available to students throughout the semester. An instructor of record, a teaching assistant, and a writing-across-the-curriculum consultant overlayed feedback and formative assessment to support student learning. Individual and group assignments were developed to build upon each other, with iterative feedback, to facilitate student STEM literacy. Rubrics were used at all levels of assessment to provide detailed feedback for students, with repetitive rubric components incorporated throughout the semester. Overall, scaffolding of assignments (both individual and group), along with scaffolded support and feedback, promoted student literacy and confidence.}, }
@article {pmid40676225, year = {2025}, author = {Zhang, J and Dong, H and Liang, L and Hu, L and Chen, J and Li, W and Liu, J and Su, Y and Shi, M and Feng, Y and Naccasha, EZ and Lewis, C and Liu, H and Yang, X and Wen, C}, title = {Targeting gut microbiota and arginase boosts MEK inhibitors' enhancement of antitumour immunity via MHC-I upregulation in colorectal cancer.}, journal = {British journal of cancer}, volume = {}, number = {}, pages = {}, pmid = {40676225}, issn = {1532-1827}, support = {82172337//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {BACKGROUND: Elevating major histocompatibility complex class I (MHC-I) levels in tumour cells can boost antitumour immunity and enhance immunotherapy for colorectal cancer (CRC). Screening an FDA-approved drug library showed that MEK inhibitors (MEKis) significantly increase MHC-I expression in CRC cells, though the mechanisms and antitumour effects of MEKis, as well as their impact on gut microbiota, remain unclear.<br><br>METHODS: Dual-luciferase reporter system was employed to screen MHC-I inducers. MHC-I expression was analysed using qRT-PCR, flow cytometry, and western blot. OT-I TCR transgenic mice, subcutaneous mouse tumour models, RNA-seq, and ChIP-qPCR were used to identify the underlying mechanism. Gut microbiota was depleted using antibiotics cocktail and analysed via Shotgun sequencing, 16S rRNA sequencing and nontargeted metabolomic sequencing.<br><br>RESULTS: MEKis, particularly cobimetinib, increased MHC-I expression by inhibiting PRMT5-mediated repression of NLRC5, boosting CD8[+] T cell-mediated immunity and enhancing PD-L1 blockade efficacy. Cobimetinib also altered gut microbiota, reducing L-arginine via arginase production, which compromised antitumour immunity. Arginase inhibition or L-arginine supplementation restored immune responses.<br><br>CONCLUSIONS: This study uncovers a novel mechanism of MEKi-induced MHC-I expression and highlights the interplay between gut microbiota and antitumour immunity, providing insights for MEKi-based CRC immunotherapy.}, }
@article {pmid40675954, year = {2025}, author = {Serna, C and Matamoros, BR and Pulido-Vadillo, M and Delgado-Blas, JF and Jansen, RR and Willems, RJL and Almeida, A and Harrison, EM and Dupuy, B and Coll, F and Gonzalez-Zorn, B}, title = {Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {6360}, pmid = {40675954}, issn = {2041-1723}, mesh = {DNA Transposable Elements/genetics ; *Methyltransferases/genetics/metabolism ; *Anti-Bacterial Agents/pharmacology ; *Enterococcus faecium/genetics/drug effects ; Humans ; *Aminoglycosides/pharmacology ; Clostridioides difficile/genetics/drug effects ; Genome, Bacterial/genetics ; *Interspersed Repetitive Sequences/genetics ; *Bacterial Proteins/genetics/metabolism ; *Gram-Positive Bacteria/genetics/drug effects ; *Drug Resistance, Bacterial/genetics ; Microbial Sensitivity Tests ; }, abstract = {The npmA gene, encoding a 16S rRNA methyltransferase, confers resistance to all clinically available aminoglycosides, posing a significant threat to effective antibiotic therapy. We analyze 1,932,812 bacterial genomes to investigate the distribution and mobilization of npmA variants. npmA is not found in Gram-negative bacteria, where it was originally described, but is identified among Gram-positive bacteria, predominantly as the npmA2 variant in the globally distributed Clostridioides difficile ST11 lineage. We also detect npmA2 in two vancomycin-resistant Enterococcus faecium isolates from a Dutch hospital. Upon sequencing and phenotypic analysis, we determine that E. faecium isolates are pan-resistant to aminoglycosides. Genomic characterization links npmA2 to a composite transposon, Tn7734, which is integrated within a previously uncharacterized Integrative and Conjugative Element (ICE) Tn7740, present in both npmA2-carrying C. difficile and E. faecium clinical isolates. Tn7740-like, but not npmA2, appears across diverse taxa, including human microbiome members. Here, we show that Tn7740 likely facilitates cross-species npmA2 mobilization between these Gram-positive bacteria and emphasize the risk of mobile genetic elements transferring pan-aminoglycoside resistance between clinically important bacterial pathogens.}, }
@article {pmid40674653, year = {2025}, author = {Saarimäki, LA and Fratello, M and Del Giudice, G and Di Lieto, E and Afantitis, A and Alenius, H and Chiavazzo, E and Gulumian, M and Karisola, P and Lynch, I and Mancardi, G and Melagraki, G and Netti, P and Papadiamantis, AG and Peijnenburg, W and A Santos, H and Serchi, T and Shahbazi, MA and Stoeger, T and Valsami-Jones, E and Vivo, P and Vinković Vrček, I and Vogel, U and Wick, P and Winkler, DA and Serra, A and Greco, D}, title = {Wisdom of Crowds for Supporting the Safety Evaluation of Nanomaterials.}, journal = {Environmental science &amp; technology}, volume = {59}, number = {29}, pages = {14969-14980}, pmid = {40674653}, issn = {1520-5851}, mesh = {*Nanostructures/toxicity ; Humans ; }, abstract = {The development of new approach methodologies (NAMs) to replace current in vivo testing for the safety assessment of engineered nanomaterials (ENMs) is hindered by the scarcity of validated experimental data for many ENMs. We introduce a framework to address this challenge by harnessing the collective expertise of professionals from multiple complementary and related fields ("wisdom of crowds" or WoC). By integrating expert insights, we aim to fill data gaps and generate consensus concern scores for diverse ENMs, thereby enhancing the predictive power of nanosafety computational models. Our investigation reveals an alignment between expert opinion and experimental data, providing robust estimations of concern levels. Building upon these findings, we employ predictive machine learning models trained on the newly defined concern scores, ENM descriptors, and gene expression profiles, to quantify potential harm across various toxicity end points. These models further reveal key genes potentially involved in underlying toxicity mechanisms. Notably, genes associated with metal ion homeostasis, inflammation, and oxidative stress emerge as predictors of ENM toxicity across diverse end points. This study showcases the value of integrating expert knowledge and computational modeling to support more efficient, mechanism-informed, and scalable safety assessment of nanomaterials in the rapidly evolving landscape of nanotechnology.}, }
@article {pmid40674481, year = {2025}, author = {Whitaker, WR and Russ, ZN and Stanley Shepherd, E and Popov, LM and Louie, A and Lam, K and Zong, DM and Gill, CCC and Gehrig, JL and Rishi, HS and Tan, JA and Buness, A and Godoy, J and Banta, D and Jaidka, S and Wilson, K and Flood, J and Bukshpun, P and Yocum, R and Cook, DN and Warsi, T and McLean, L and Sonnenburg, JL and DeLoache, WC}, title = {Controlled colonization of the human gut with a genetically engineered microbial therapeutic.}, journal = {Science (New York, N.Y.)}, volume = {389}, number = {6757}, pages = {303-308}, doi = {10.1126/science.adu8000}, pmid = {40674481}, issn = {1095-9203}, mesh = {Animals ; Humans ; Mice ; *Colon/microbiology ; *Gastrointestinal Microbiome/genetics ; Genetic Engineering ; *Kidney Calculi/etiology/prevention &amp; control/therapy ; Oxalates/urine/metabolism ; Prebiotics ; Promoter Regions, Genetic ; *Bacteroidaceae ; *Hyperoxaluria/complications/therapy ; *Polysaccharides, Bacterial/metabolism ; *Sepharose/analogs &amp; derivatives/metabolism/analogs &amp; derivatives ; }, abstract = {Precision microbiome programming for therapeutic applications is limited by challenges in achieving reproducible colonic colonization. Previously, we created an exclusive niche that we used to engraft engineered bacteria into diverse microbiota in mice by using a porphyran prebiotic. Building on this approach, we have now engineered conditional attenuation into a porphyran-utilizing strain of Phocaeicola vulgatus by replacing native essential gene regulation with a porphyran-inducible promoter to allow reversible engraftment. Engineering a five-gene oxalate degradation pathway into the reversibly engrafting strain resulted in a therapeutic candidate that reduced hyperoxaluria, a cause of kidney stones, in preclinical models. Our phase 1/2a clinical trial demonstrated porphyran dose-dependent abundance and reversible engraftment in humans, reduction of oxalate in the urine, and characterized genetic stability challenges to achievinglong-term treatment.}, }
@article {pmid40669445, year = {2025}, author = {Omary, L and Canfora, EE and Puhlmann, ML and Gavriilidou, A and Rijnaarts, I and Holst, JJ and Op den Kamp-Bruls, YMH and de Vos, WM and Blaak, EE}, title = {Intrinsic chicory root fibers modulate colonic microbial butyrate-producing pathways and improve insulin sensitivity in individuals with obesity.}, journal = {Cell reports. Medicine}, volume = {6}, number = {7}, pages = {102237}, pmid = {40669445}, issn = {2666-3791}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Butyrates/metabolism ; *Cichorium intybus/chemistry ; *Colon/microbiology/metabolism ; Diabetes Mellitus, Type 2 ; *Dietary Fiber ; *Gastrointestinal Microbiome/drug effects ; *Insulin Resistance ; *Obesity/microbiology/metabolism/diet therapy ; Plant Roots/chemistry/metabolism ; Triglycerides/blood ; }, abstract = {Type 2 diabetes and obesity have become major public health concerns. Growing evidence suggests that increased dietary fiber intake, through its interaction with the gut microbiota, may help prevent these diseases. Here, we demonstrate in a 12-week randomized, placebo-controlled trial in individuals at risk for type 2 diabetes that intake of an intrinsic fiber product, consisting of entire plant cells, tended to improve peripheral insulin sensitivity (p = 0.085), increased whole-body insulin sensitivity (p = 0.032), reduced circulating triglycerides (p = 0.049), and tended to reduce intrahepatic lipid content (p = 0.063), along with an increased proportion of small adipocytes (p = 0.008). Phylogenetic and metagenomic analysis revealed that these outcomes coincided with increased levels of fiber-degrading Bifidobacterium spp. and butyrate-producing Anaerostipes spp. and a functional shift toward a distal butyrogenic trophic chain while the best responding individuals had increased levels of pectin degraders that may produce propionate. Our findings demonstrate the pivotal role of slowly fermented, intrinsic plant cell fibers in improving cardiometabolic health. This study was registered at ClinicalTrials.gov (NCT04714944).}, }
@article {pmid40666679, year = {2025}, author = {Lei, S and Wang, J and Zhang, M and Huang, J and Liu, Y and Long, Y and Xing, Y and Yu, Z}, title = {The Succession of Cervical Canal Microbiota in Endometrial Cancer and Cervical Cancer: A Clinical Metagenomics Study.}, journal = {International journal of women's health}, volume = {17}, number = {}, pages = {2039-2050}, pmid = {40666679}, issn = {1179-1411}, abstract = {OBJECTIVE: To define stage-specific cervical canal microbiota signatures across the continuum of gynecologic malignancies from benign endometrial cancer (BE)/cervical cancer precancerous lesions (CIN) to endometrial cancer (EC)/cervical cancers (CC), and to evaluate their potential as diagnostic biomarkers and therapeutic targets.<br><br>METHODS: In the observational study, metagenomic sequencing was employed to investigate the cervical canal microbiota of 45 patients, including BE, EC, CIN, and CC. Specimen collection was performed by an experienced physician. All samples were sequenced utilizing the shotgun approach. The microbial statistical analyses were conducted using R.<br><br>RESULTS: Compared to the non-cancerous group (BE and CIN), the index related to microbial community stability decreases significantly and the incidence of cervical canal dysbiosis increases in the cancerous group (EC and CC). Microbial diversity exhibited significant differences between BE and EC, CIN and CC, as well as cancerous and non-cancerous groups. At the species level, some species were significantly decreased (eg, Lactobacillus iners) and increased (eg, Staphylococcus haemolyticus, Pasteurella multocida, Pseudomonas putida, and other opportunistic pathogen) in the cancerous group.<br><br>CONCLUSION: The cervical canal represents a distinct microbial niche, with its dysbiotic progression reflecting the trajectory of oncogenic transformation. The progression from non-cancerous to cancerous states is characterized by the replacement of the vaginal microbial community, which is dominated by Lactobacillus iners, with a gradual shift towards opportunistic pathogen. Disease diagnosis and complementary therapies focused on lactobacilli and hallmark opportunistic pathogen may offer new insights for precision oncology.}, }
@article {pmid40660385, year = {2025}, author = {Ji, X and Zhi, M and Gu, X and Han, Y and Lan, X and Song, L and Sun, P and Li, J and Qi, X and Feng, Q}, title = {DnaK of Parvimonas micra extracellular vesicles interacts with the host fibroblasts BAG3-IKK-γ axis to accelerate TNF-α secretion in oral lichen planus.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {164}, pmid = {40660385}, issn = {2049-2618}, support = {ZR2023MH045//Shandong Natural Science Foundation/ ; YJRC2021002//the start-up fund for introduction of talents to Jinan Central Hospital/ ; 2022-2-7//Science and Technology Development Program of Jinan Municipal Health Commission/ ; 82270980//National Natural Science Foundation of China/ ; 2019//he National Young Scientist Support Foundation/ ; ZR2021JQ29//Excellent Young Scientist Foundation of Shandong Province/ ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; 2021GXRC021//the Periodontitis innovation team of Jinan City/ ; 2019//Taishan Young Scientist Project of Shandong Province/ ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; 2021ZDSYS18//Shandong Province Key Research and Development Program/ ; }, mesh = {Humans ; *Fibroblasts/metabolism/microbiology ; *Extracellular Vesicles/metabolism ; *Tumor Necrosis Factor-alpha/metabolism ; *Lichen Planus, Oral/microbiology/metabolism/pathology ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Mouth Mucosa/microbiology ; *I-kappa B Kinase/metabolism/genetics ; Male ; Signal Transduction ; Female ; NF-kappa B/metabolism ; Middle Aged ; *Bacterial Proteins/metabolism/genetics ; *HSP70 Heat-Shock Proteins/metabolism/genetics ; Apoptosis Regulatory Proteins ; }, abstract = {BACKGROUND: Oral lichen planus (OLP) is one of the most frequent oral mucosal diseases associated with chronic inflammation, despite a profoundly limited understanding of its underlying pathogenic mechanisms.<br><br>RESULTS: The microbiome analysis was conducted on buccal and lip mucosae, tongue dorsum, and saliva in nonerosive/erosive OLP patients and healthy individuals. Significant variations were observed in the oral microbiome of OLP patients, particularly in the buccal mucosa. Network, random forest, and NetShift analysis collectively indicated that Parvimonas micra (P. micra) emerged as a crucial bacterium in OLP. In vivo analysis further demonstrated that P. micra was abundant at the junction of epithelial and connective tissue layers in OLP lesions. Single-cell RNA sequencing data implicated fibroblasts as potential targets, characterized by upregulation of the NF-&#x3ba;B pathway linked to TNF-&#x3b1;. Co-culturing of P. micra or its extracellular vesicles (EVs) with fibroblasts showed that P. micra and EVs could activate the NF-&#x3ba;B signaling pathway and suppress autophagy in buccal mucosal fibroblasts. Among the pathogenic effectors, DnaK from P. micra EVs was identified to interact with BAG3 in fibroblasts. The interaction of DnaK with BAG3 subsequently activated the NF-&#x3ba;B pathway and decreased autophagy flux. Additionally, we identified that IKK-&#x3b3; was the key downstream protein that could bind with DnaK-BAG3, thereby inhibiting autophagy and promoting TNF-&#x3b1; secretion.<br><br>CONCLUSIONS: We initially revealed that P. micra was a crucial pathogen in the development of OLP and demonstrated that P. micra's EVs induce the inhibition of autophagy and enhanced TNF-&#x3b1; secretion in OLP fibroblasts via the DnaK-BAG3-IKK-&#x3b3; axis. This study offers novel insights into the pathogenic mechanisms underlying OLP. Video Abstract.}, }
@article {pmid40657927, year = {2025}, author = {Robinson, JM and Crino, OL and Camargo, A and Breed, MF}, title = {Does a microbial-endocrine interplay shape love-associated emotions in humans? A hypothesis.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0041525}, doi = {10.1128/msystems.00415-25}, pmid = {40657927}, issn = {2379-5077}, abstract = {Emerging evidence suggests that the human gut microbiome plays a regulatory role in the endocrine system, influencing hormone activity and potentially shaping the emotional and physiological dimensions of behaviors such as aggression and emotional states, including love. Here, we review the hypothesis that microbial-endocrine interactions shape love-associated emotions by modulating hormone levels and activity. While the division of love into discrete components such as lust, attraction, and attachment is somewhat artificial and may not fully capture the complexity of human experience, the associated emotions nevertheless correspond to well-characterized neuroendocrine processes. Psycho-endocrinological theory proposes that the complex and nonlinear interplay between testosterone, estradiol, and other hormones drives emotions associated with lust; serotonin and dopamine play a role in emotions linked to attraction; and oxytocin and vasopressin influence the modulation of attachment and social bonds. Microbial communities may influence emotions and relationship dynamics through effects on the hormonal pathways linked to love-associated emotions. While non-human animal studies suggest microbiota can impact social bonding, sexual preferences, and stress-related behaviors, direct evidence in humans remains limited. Investigating the evolutionary underpinnings of microbial-endocrine interactions could provide insights into how microbes influence emotions beyond love, including hate and aggression-with important societal implications. Indeed, understanding these mechanisms could have profound implications for human relationships, mental health, and even therapeutic interventions targeting the microbiota-gut-brain axis. Future research is needed to unravel the extent to which microbiomes contribute to the neurobiology of love (and other emotions) and whether manipulating microbial communities could modulate emotional and social behaviors.IMPORTANCELove is often considered an abstract emotion, but emerging science suggests that it may be shaped by the microscopic inhabitants of our bodies: microbes. This paper explores the intriguing hypothesis that microbes can influence the hormonal and neural systems linked to love-associated emotions-via the microbiota-gut-brain axis. Drawing on animal studies and early human microbiome and endocrine research, we highlight how microbes modulate neurohormones like oxytocin, dopamine, and testosterone, which play key roles in social bonding. By regulating these systems, microbes may also shape emotional and behavioral responses. This research opens new avenues for understanding not just the (micro)biology of love but also the potential for microbiome-targeted therapies to support relational well-being. By linking microbiome and emotion science, the article raises the important question of whether love is a phenomenon influenced by our resident symbionts, adding an intriguing and potentially impactful dimension to our understanding of human connection and behavior.}, }
@article {pmid40655157, year = {2025}, author = {Pena-Amelunxen, G and Asghari, M and Khatri, K and Glesner, J and Versteeg, SA and van Ree, R and Chapman, MD and Smith, SA and Chruszcz, M and Pomés, A and Aglas, L}, title = {Pre-clinical allergenicity assessment of IgE epitope-targeted Der p 2 mutants demonstrate potential as hypoallergenic AIT candidates.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1623920}, pmid = {40655157}, issn = {1664-3224}, mesh = {*Immunoglobulin E/immunology ; *Antigens, Dermatophagoides/immunology/genetics ; Animals ; Humans ; *Epitopes/immunology/genetics ; *Arthropod Proteins/immunology/genetics ; Rats ; Mutation ; Antibodies, Monoclonal/immunology ; *Desensitization, Immunologic/methods ; *Allergens/immunology/genetics ; Epitope Mapping ; *Hypersensitivity/immunology ; *Cysteine Endopeptidases/immunology/genetics ; Cell Line, Tumor ; }, abstract = {BACKGROUND: Advancements in hybridoma technology have enabled the production of human IgE monoclonal antibodies (hIgE mAb) for successful IgE epitope mapping of major allergens. Here, we assessed the hypoallergenicity of three IgE-epitope mutants (single 4C8 or 2F10, and double 4C8 + 2F10 epitope mutants) of house dust mite allergen (HDM) Der p 2.<br><br>METHODS: Humanized rat basophilic leukemia (huRBL) cells, passively sensitized overnight with either pairs of Der p 2 specific hIgE mAb (2F10, 4C8 or 2G1) or HDM-allergic serum (n=8), were stimulated with either wildtype (WT) Der p 2 or an epitope mutant and mediator release was measured.<br><br>RESULTS: No degranulation was induced upon stimulation with all mutants, when cells were sensitized with pairs of hIgE mAb specific for at least one mutated epitope. HIgE mAb specific for non-mutated epitopes led to mediator release comparable to WT Der p 2, indicating that epitopes recognized by the three different hIgE mAb are not overlapping and that the 3D-structure of the mutants is conserved. The double 4C8 + 2F10 epitope mutant had a significantly reduced maximal mediator release (48.3%) compared to the WT, in cells sensitized with allergic donor serum. Overall, the area-under-the-curve of mediator release curves induced by the mutants was significantly lower (31-65%) compared to WT. When comparing the EC20, the double 4C8 + 2F10 epitope mutant required a 158-fold higher antigen concentration to induce the same extent of mediator release as WT Der p 2.<br><br>CONCLUSION: Der p 2 epitope mutants display significantly reduced allergenicity. Particularly, the double 4C8 + 2F10 epitope mutant demonstrated a strong potential as a novel AIT vaccine candidate.}, }
@article {pmid40653356, year = {2025}, author = {Sarath Krishnan, MP and Goyal, B and Nampui, L and Gupta, SC}, title = {The role of microbiome in gastrointestinal cancer.}, journal = {International review of cell and molecular biology}, volume = {395}, number = {}, pages = {67-98}, doi = {10.1016/bs.ircmb.2024.12.009}, pmid = {40653356}, issn = {1937-6448}, mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/pathology/therapy ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {The human microbiome consists of the diverse microorganisms with their equally diverse functional abilities that have evolved over millions of years with humans. This microbiome creates a mutually beneficial symbiotic relationship with their host. Through their varied functions, the human gut microbiota is crucial for preserving health and homeostasis. Any imbalance in this microbial population can lead to an array of diseased states, including cancer especially of the gastrointestinal system. The focus of this chapter is to discuss the mechanisms through which the gut microbiome creates a conducive environment for initiation and progression of cancer. In addition, the effect of microbial products such as short chain fatty acids, bile acids and Trimethylamine N-oxide on the formation of gastrointestinal cancer is also discussed. The various experimental methods and new molecular techniques that have facilitated the characterization and study of microorganisms is also discussed. The developments in microbiome research have shed light on the potential role of gut microbiota for novel biomarker discovery and therapeutic interventions in gastrointestinal cancer, like fecal microbiota transplantation. The prospects of these areas for further exploration are discussed.}, }
@article {pmid40647535, year = {2025}, author = {Palkovsky, M and Modrackova, N and Neuzil-Bunesova, V and Liberko, M and Hlodakova, A and Soumarova, R}, title = {Role of Human Microbiome in Development and Management of Head and Neck Squamous Cell Carcinoma.}, journal = {Cancers}, volume = {17}, number = {13}, pages = {}, pmid = {40647535}, issn = {2072-6694}, abstract = {Despite decades of research, cancer remains a major global health problem [...].}, }
@article {pmid40643244, year = {2025}, author = {Seekatz, AM}, title = {Straining to define a healthy microbiome.}, journal = {mSphere}, volume = {10}, number = {7}, pages = {e0079724}, pmid = {40643244}, issn = {2379-5042}, support = {R35 GM150609/GM/NIGMS NIH HHS/United States ; 2025541//National Science Foundation/ ; R35GM150609/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Clostridium Infections/therapy/microbiology ; *Microbiota ; }, abstract = {In 2020, I wrote an mSphere of Influence commentary on two studies that shaped my research perspective on the human gut microbiome (McNulty et al., Sci Transl Med 3:106ra106, 2011, https://doi.org/10.1126/scitranslmed.3002701; Hamilton et al., Gut Microbes 4:125, 2013, https://doi.org/10.4161/gmic.23571). The microbiome field has continued to progress since the publication of these studies over 10 years ago, emerging as a considerable factor in almost all areas focused on disease development. My previous commentary highlighted two areas that piqued my interest early on in my career: (i) that the extant microbial community should be considered when proposing to manipulate the microbiota, such as via probiotics or fecal microbiota transplantation, and (ii) that realized (i.e., transcribed) functional changes of the microbiota may occur independent of changes in its composition. Since writing that commentary, two microbiota-based therapeutics for the treatment of Clostridioides difficile infection have been approved, highlighting the potential success of using the microbiota to treat or prevent disease. Despite these wins and ever-growing evidence of the importance of the microbiome in managing our health, translating mechanistic studies into therapeutic value has been slower. In this minireview, I expand upon two large questions that would increase our ability to translate the microbiome into therapies, highlighting both historical and recent progress.}, }
@article {pmid40642982, year = {2025}, author = {Qi, X and Zhang, M and Wei, T and Lin, J and Zhao, X and Yao, Y and Hu, Y and Zheng, Y}, title = {LorDist: a novel method for calculating the distance based on functional data analysis with application to longitudinal microbial data.}, journal = {Microbiology spectrum}, volume = {13}, number = {8}, pages = {e0154225}, pmid = {40642982}, issn = {2165-0497}, support = {2021YFA1301000//National Key Research and Development Program of China/ ; 2023YFF1205101//National Key Research and Development Program of China/ ; }, mesh = {Humans ; Longitudinal Studies ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria/classification/genetics/isolation &amp; purification ; Data Analysis ; *Computational Biology/methods ; }, abstract = {Longitudinal human microbial data offer insights into microbiome dynamics over time. Traditional methods usually overlook temporal relationships among samples from the same subject. Here, we presented the Longitudinal Microbial Data Distance (LorDist) method, which uses functional data fitting to construct a distance matrix integrating information from the same subject at different time points. Simulation data showed that LorDist handled well up to 60% sparseness and worked robustly with various sequencing depths and time points. Empirical data analysis demonstrated that LorDist excels in capturing differences across subjects with longitudinal microbiome data. LorDist presented the potential of longitudinal microbial data in addressing temporal autocorrelation and distinguishing phenotypes.IMPORTANCELongitudinal analysis of the human microbiome is critical for understanding its dynamic role in health and disease. However, current analytical approaches struggle to address key challenges, such as data sparsity and irregular sampling, inherent to time-series microbiome studies. Here, we developed longitudinal microbial data distance (LorDist), an innovative method leveraging functional data analysis to model temporal microbial dynamics with enhanced precision. Compared to existing methods, LorDist consistently outperforms in discerning biologically meaningful group differences, even in highly sparse data sets or under fluctuating sequencing depths. Our findings demonstrate LorDist's robust performance on real-world data sets involving inflammatory bowel disease and infant gut development. By explicitly preserving the temporal structure inherent in microbiome data, LorDist enables robust detection of subtle yet critical biological shifts, paving the way for improved diagnostics and personalized therapeutic strategies in microbiome science.}, }
@article {pmid40642105, year = {2025}, author = {Jasemi, SK and Faridafshar, H and Amin, MN and Babamohamadi, M and Falahati, M and Amirian, R and Izadi, Z}, title = {NO: a key player in microbiome dynamics and cancer pathogenesis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1532255}, pmid = {40642105}, issn = {2235-2988}, mesh = {Humans ; *Neoplasms/pathology/metabolism/microbiology/etiology ; *Nitric Oxide/metabolism ; *Microbiota/physiology ; Mouth/microbiology ; Nitrates/metabolism ; Animals ; Bacteria/metabolism ; }, abstract = {The human microbiome refers to the genomic content of microorganisms inhabiting the human body, including the lungs, oral cavity, intestinal tract, esophagus, and other areas. The human oral microbiota is a diverse and complex ecosystem that includes bacteria, microeukaryotes, archaea, and viruses. These communities have a highly structured biogeography resulting from the various microenvironments in the oral cavity, shaping local metabolic exchange. Dietary nitrate (NO3 [-]) is an ion naturally present in vegetables, especially leafy greens. When consumed, it leads to the production of nitric oxide (NO). This bioactive molecule benefits bodily functions like host defense and neuronal communication and improves vascular and metabolic health. Dietary NO3 [-] is reduced to NO via the nitrate-nitrite-NO pathway, facilitated by nitrate-reducing bacteria inside the oral cavity. NO has a leading role in different types of diseases, including cancer, cardiovascular disease, and diabetes. The bioavailability of NO is greatly enhanced by the activity of bacteria residing in the mouth, which reduces NO3 [-]to NO2 [-] and increases the concentration of circulating NO2 [-]. NO is the key to causing different malignancies, including gastrointestinal cancers. NO can cause cell death by inducing DNA damage and anti-apoptotic signaling pathways. Low to moderate levels of NO derived from tumors can activate angiogenesis and promote an invasive phenotype, while high levels of NO may have an anti-tumor effect in protecting against cancer. In this review, we intend to discuss the human microbiome, dietary NO3 [-]consumption, the vital role of NO in the human body, types of cancers, and treatments based on it.}, }
@article {pmid40638549, year = {2025}, author = {Dasgupta, S}, title = {Unraveling the Microbiome-Asthma Axis: Metagenomic Insights from Airway and Gut Microbial Communities.}, journal = {Omics : a journal of integrative biology}, volume = {29}, number = {8}, pages = {374-383}, doi = {10.1177/15578100251358958}, pmid = {40638549}, issn = {1557-8100}, mesh = {Humans ; *Asthma/microbiology ; *Gastrointestinal Microbiome ; *Metagenomics/methods ; Dysbiosis/microbiology ; *Microbiota ; *Respiratory System/microbiology ; }, abstract = {Asthma is a heterogeneous respiratory disease with complex pathogenesis involving immune dysregulation, environmental triggers, and increasingly recognized to have contributions from the human microbiome. Emerging evidence from longitudinal birth cohorts and multi-omics studies reveals that early-life microbial colonization patterns in both the gastrointestinal and respiratory tracts play a crucial role in shaping immune trajectories and influencing asthma susceptibility. This expert review highlights the findings from pivotal studies that associate dysbiosis in the gut and airway microbiota with asthma development and its diverse phenotypic manifestations. Reduced abundance of immunomodulatory genera such as Bifidobacterium, Faecalibacterium, and Lachnospira in the gut has been consistently associated with increased asthma risk. In the airways, increased colonization by potentially pathogenic taxa, including Moraxella, Haemophilus, and Streptococcus, correlates with viral respiratory infections and persistent wheezing. Microbiome diversity patterns also differ between asthma phenotypes: eosinophilic asthma typically features a community profile closer to healthy individuals, while neutrophilic asthma is marked by enrichment of pro-inflammatory bacterial species. Moreover, protective genera such as Dolosigranulum and Corynebacterium in the upper airways are associated with lower risk of asthma and reduced respiratory infections. Elucidating these microbiome-mediated mechanisms holds promise for the development of targeted microbiota-based strategies for asthma prevention and phenotype-specific therapeutic interventions. The present review unpacks these localized microbial patterns and their mechanistic implications for asthma development, severity, and endotypic variation. Finally, unraveling the microbiome-asthma axis from airway and gut microbial communities also has implications for new ways of thinking personalized medicine in the future.}, }
@article {pmid40638496, year = {2025}, author = {Hyvönen, S and Solasaari, T and Pokka, T and Korpela, K and de Vos, WM and Salonen, A and Ruuska-Loewald, T and Kolho, KL}, title = {Maternal Prenatal and Postnatal Stress and Infections in Infancy.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {}, number = {}, pages = {}, doi = {10.1111/apa.70228}, pmid = {40638496}, issn = {1651-2227}, support = {5044//Signe and Ane Gyllenberg Foundation/ ; 200141/WT_/Wellcome Trust/United Kingdom ; 210168//Lastentautien Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; 5851//Finnish Medical Foundation/ ; //Juho Vainio Foundation/ ; 329/31/2015//Tekes/Business Finland/ ; }, abstract = {AIM: To study maternal stress as a possible risk factor for early infections in infants in a well-characterised, prospective infant HELMi cohort.<br><br>METHODS: We measured maternal stress during the last trimester with questionnaires (4 items, scales 0-100) and breastmilk cortisol levels at 3&#x2009;months. We compared maternal stress between infants with several infections (n&#x2009;=&#x2009;125) and infants with no infections (n&#x2009;=&#x2009;122) during the first 6 months of life. The episodes and days with symptoms were recorded using an online diary. Control subjects were matched for sex, year of birth, mode of delivery, and timing of breastmilk sample. The analysis was adjusted for season of birth and number of siblings.<br><br>RESULTS: The median maternal prenatal stress, related to household during the last trimester, was higher in the infection group than in controls (37 [IQR 19.5-61] vs. 19 [7.8-42.3]; p&#x2009;=&#x2009;0.02). There was no difference in prenatal stress related to pregnancy or the relationship between the groups. The breastmilk cortisol levels did not differ between the groups (medians of 6.8&#x2009;nmol/L [IQR 4.8-8.8] and 6.2&#x2009;nmol/L [4.5-8.4], respectively; p&#x2009;=&#x2009;0.12).<br><br>CONCLUSION: Prenatal stress was linked to the occurrence of infections in infancy. Whether support for stress reduction may reduce the risk for infections warrants further study.}, }
@article {pmid40626521, year = {2025}, author = {Wan, H and Weng, J and Cai, J and Chen, Z and Li, P and Han, J and Li, Z and Wan, Z and Yuan, Z and Gan, Y and Huang, M and Li, X and Li, T and Liu, X and Wang, X and Yu, H and Liu, B and Lin, J and Luo, Y}, title = {Nodal Downstaging in Rectal Cancer Patients: Survival is Promising if YpN0 is Achieved.}, journal = {Diseases of the colon and rectum}, volume = {}, number = {}, pages = {}, doi = {10.1097/DCR.0000000000003846}, pmid = {40626521}, issn = {1530-0358}, abstract = {BACKGROUND: Locally advanced rectal cancer is a critical health concern, with neoadjuvant therapy emerging as a pivotal strategy to enhance survival rates.<br><br>OBJECTIVE: This study aims to evaluate the prognostic value of achieving ypN0 status following neoadjuvant therapy patients with locally advanced rectal cancer, comparing survival outcomes among natural N0, downstaged N0, and ypN + groups.<br><br>DESIGN: We conducted a post hoc analysis of the FOWARC trial, employing Kaplan-Meier survival analysis and Cox regression models to assess overall survival, disease-free survival, and locoregional recurrence-free survival.<br><br>SETTINGS: The multicenter, randomized phase III FOWARC trial was conducted across 15 hospitals in China, adhering to ethical standards.<br><br>PATIENTS: Our cohort included 449 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision.<br><br>INTERVENTIONS: Neoadjuvant chemoradiotherapy followed by total mesorectal excision.<br><br>MAIN OUTCOME MEASURES: The primary endpoint was 5-year overall survival, with secondary endpoints being 3-year disease-free survival and 3-year locoregional recurrence-free survival.<br><br>RESULTS: The 5-year overall survival for natural N0 and downstaged N0 groups were 88% and 89%, respectively, significantly higher than the 73% observed in the ypN+ group (p = 0.0034). The complete pathological response rate was markedly lower in the ypN+ group. Multivariable analysis showed the ypN stage as an independent prognostic factor for overall survival.<br><br>LIMITATIONS: The study's retrospective design may introduce potential biases in patient selection and preoperative staging.<br><br>CONCLUSIONS: Achieving ypN0 status via neoadjuvant chemoradiotherapy significantly improves survival in patients with locally advanced rectal cancer, regardless of ypT or cN status. This status not only serves as an independent prognostic factor, but may also help to guide hypothesis-driven, individualized postoperative-treatment strategies. See Video Abstract.ClinicalTrials.gov identifier: NCT01211210.}, }
@article {pmid40626364, year = {2025}, author = {Sequoia, JA and Haddock, NL and Gay, PM and Barkal, LJ and Narasimhan, P and Martinez, N and Winn, VD and Bollyky, PL}, title = {Identification of bacteriophage DNA in human umbilical cord blood.}, journal = {JCI insight}, volume = {10}, number = {13}, pages = {}, pmid = {40626364}, issn = {2379-3708}, support = {T32 HL129970/HL/NHLBI NIH HHS/United States ; R01 HD094513/HD/NICHD NIH HHS/United States ; R01 HL139844/HL/NHLBI NIH HHS/United States ; R01 DC019965/DC/NIDCD NIH HHS/United States ; R01 HL148184/HL/NHLBI NIH HHS/United States ; R21 GM147838/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Fetal Blood/virology ; Female ; Pregnancy ; *DNA, Viral/blood/genetics/isolation &amp; purification ; *Bacteriophages/genetics/isolation &amp; purification ; Adult ; Infant, Newborn ; Pre-Eclampsia/virology/blood ; Cell-Free Nucleic Acids/blood ; Chorioamnionitis/virology/blood ; Premature Birth/virology/blood ; }, abstract = {Bacteriophages, viruses that parasitize bacteria, are abundant in the human microbiome and may influence human health, in part, through their interactions with bacterial hosts. Whether endogenous bacteriophages or their products are vertically transmitted from mother to fetus during human pregnancy is not known. Here, we searched for bacteriophage sequences from five bacteriophage databases (474,031 total sequences) in cell-free DNA (cfDNA) of paired maternal and umbilical cord blood samples from two independent cohorts. First, we sequenced cfDNA from 10 pairs of maternal and cord blood samples, including four pairs affected by preeclampsia. We validated our findings in a previously published dataset of 62 paired maternal and cord blood samples, including 43 pairs from preterm or chorioamnionitis-affected deliveries. We identified 94 and 596 bacteriophage sequences in maternal and cord blood cfDNA samples from the first and second cohort, respectively. We identified 58 phage sequences across maternal-infant dyads and 581 phage sequences that were unique to a single sample. We did not identify any phage sequences consistently associated with preeclampsia, preterm, or chorioamnionitis-affected samples. This study demonstrated the presence of bacteriophage DNA in human cord blood at birth, providing evidence that the human fetus is exposed to bacteriophage DNA in utero.}, }
@article {pmid40623769, year = {2025}, author = {Basoya, R and Singh, B and Basi, A and Aggarwal, S}, title = {Role of microbiome in cancer progression.}, journal = {International review of cell and molecular biology}, volume = {394}, number = {}, pages = {79-106}, doi = {10.1016/bs.ircmb.2024.12.013}, pmid = {40623769}, issn = {1937-6448}, mesh = {Humans ; *Neoplasms/microbiology/pathology/therapy ; *Disease Progression ; *Microbiota ; Animals ; }, abstract = {The human microbiome plays a crucial role in maintaining health and preventing disease. Dysbiosis, or imbalance, in the microbiome, has been linked to various diseases, including cancer. This chapter explores the influence of microbiomes on different organs, immune system modulation, and cancer development. Specific microorganisms, such as Helicobacter pylori, Escherichia coli, and human papillomavirus (HPV), contribute to gastric, colorectal, and cervical cancer through mechanisms like immunomodulation and proliferative signaling pathways. Dysbiosis-induced cancer progression involves NF-κB, Wnt/β-catenin, and JAK/STAT signaling. Recent studies highlight the microbiome's potential in cancer diagnosis and immunotherapy. Fecal Microbiota Transplantation (FMT) and predictive biomarkers, such as Porphyromonas gingivalis and Escherichia-Shigella, show promise in treating colorectal cancer. The microbiome influences tumor biology and immune response, affecting immunotherapeutic efficacy. Understanding microbiome-cancer interactions offers new opportunities for improved diagnosis and personalized therapy. This chapter provides comprehensive insights into the role of microbiome in cancer progression, emphasizing the importance of microbiome research in developing effective cancer treatments.}, }
@article {pmid40621920, year = {2025}, author = {Ventin-Holmberg, R and Eriksson, J and Eberl, A and Sipponen, T and Nissilä, E and Saavalainen, P}, title = {The total gut mucosal and fecal bacterial load increases in successful treatment of inflammatory bowel disease with infliximab.}, journal = {Microbiology spectrum}, volume = {13}, number = {8}, pages = {e0189424}, pmid = {40621920}, issn = {2165-0497}, support = {//Mary och Georg C. Ehrnrooths Stiftelse/ ; //Orionin Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; //Victoriastiftelsen/ ; //Biomedicum Helsinki-s&#xe4;&#xe4;ti&#xf6;/ ; //HY | Folkh&#xe4;lsan Research Center, University of Helsinki (Folkh&#xe4;lsan Research Center)/ ; //University of Helsinki/ ; }, mesh = {Humans ; *Infliximab/therapeutic use ; *Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Female ; Male ; Adult ; Middle Aged ; *Inflammatory Bowel Diseases/drug therapy/microbiology ; *Intestinal Mucosa/microbiology/drug effects ; *Bacterial Load/drug effects ; *Bacteria/classification/genetics/isolation &amp; purification/drug effects ; RNA, Ribosomal, 16S/genetics ; Young Adult ; Aged ; }, abstract = {Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory gastrointestinal disorders linked to genetic predisposition and environmental factors. The gut microbiota, composed of various microorganisms, plays a crucial role in IBD, as reduced anaerobic bacteria and short-chain fatty acid (SCFA) producers are associated with predisposition to IBD. There is no cure for IBD, but the treatment aims for mucosal healing including conventional treatment and biological therapies such as infliximab (IFX). IFX, a tumor necrosis factor alpha (TNF-α) blocker, effectively reduces inflammation, but around 50% of patients do not achieve long-term remission. Fecal samples were collected from 70 patients with IBD (24 CD, 44 UC, and 2 IBDU), and mucosal samples were collected from both ileum and colon from 63 patients before, during, and after IFX treatment. The bacterial microbiota composition was investigated by targeting the conserved 16S region in MiSeq sequencing. Additionally, the relative sequencing data were quantified by qPCR. Responders to IFX had an increase in the total bacterial load in ileum and fecal samples during treatment, primarily driven by butyrate-producing bacteria in the Firmicutes phylum. Interestingly, this was only observed in the fecal samples in responders, but not non-responders to IFX. These results indicate that the gut bacterial microbiota of responders to IFX is changing toward a more favorable composition during successful IFX treatment.IMPORTANCEThe research described in this paper enhances our understanding of how infliximab (IFX) treatment affects the gut mucosal and fecal microbiota in patients with inflammatory bowel disease (IBD). Using 16S sequencing technique and quantification by qPCR, the study revealed that successful treatment with IFX led to an increase in the total bacterial load in both ileal and fecal samples, as well as a shift in bacterial composition toward a more favorable profile with an increase in butyrate-producing bacteria in the fecal samples in responders but not in non-responders to infliximab. This study emphasizes that the gut microbiota plays an important role in the healing process during infliximab treatment in IBD.}, }
@article {pmid40618318, year = {2025}, author = {Wu, K and Zhu, E and Chen, J and Kuang, Q and Lin, J and Zhao, S and Xu, X and Li, S and Sui, Y and Huang, M and Zhang, Y}, title = {Overexpression of GPX4 in diabetic rat kidney alleviates renal injury induced by ferroptosis.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {38}, number = {4}, pages = {1281-1297}, doi = {10.1007/s10534-025-00706-5}, pmid = {40618318}, issn = {1572-8773}, mesh = {Animals ; *Ferroptosis ; *Phospholipid Hydroperoxide Glutathione Peroxidase/genetics/metabolism ; Rats ; Male ; *Diabetes Mellitus, Experimental/metabolism/pathology ; *Diabetic Nephropathies/metabolism/pathology ; Rats, Sprague-Dawley ; *Kidney/metabolism/pathology/injuries ; Streptozocin ; }, abstract = {Ferroptosis-mediated injury in diabetic kidney (DKD) is receiving increasing attention. Glutathione Peroxidase 4 (GPX4) has long been considered a key protein to prevent ferroptosis, but its exact role in the progression of DKD, where this protein down-regulated, remains unclear. Thus, to clarify GPX4 in DKD progression, we have used adeno-associated viruses (AAVs) to overexpress it in kidneys of DKD rats. Streptozotocin (STZ)-induced DKD rats were injected once with GPX4-AAVs via tail vein. Renal function and kidney pathology were measured. Before and after treatment with GPX4-AAV, variations in kidney of ferroptosis-related indicators, such as GPX4, dihydroorotate dehydrogenase (DHODH), iron content, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), were monitored. The kidneys of STZ-treated rats showed reduced expression of GPX4, DHODH, GSH and SOD, increased expression of TFR1 and FTH, and higher levels of iron and MDA. Histopathology was consistent with renal fibrosis and thickened renal tubules. Changes were partly reversed after overexpression of GPX4, with decreased expression of FTH, together with reduced iron and MDA levels, although expression of TFR1, GSH and SOD showed no significant change. Renal function showed a lower urine protein-creatinine ratio, whereas the effect on renal fibrosis and thickened renal tubules was alleviated. Our study demonstrates that GPX4 is downregulated in DKD, and its AAV-mediated overexpression in kidney of DKD rats partly alleviates the diabetic kidney injury induced by ferroptosis.}, }
@article {pmid40616741, year = {2025}, author = {Renton, N and Pillinger, MH and Toprover, M}, title = {Gout, Hyperuricemia, and the Intestinal Microbiome.}, journal = {Inflammation}, volume = {}, number = {}, pages = {}, pmid = {40616741}, issn = {1573-2576}, abstract = {Gout is a disease of hyperuricemia (HU) leading to monosodium urate crystal deposition in the joint, resulting in inflammation and joint damage. Recently, efforts have been made to characterize the intestinal microbiome of patients who suffer from HU and gout, and pre-clinical studies have evaluated the utility of prebiotics and probiotics in alleviating gout. Herein we review recent notable studies addressing these topics. In brief, the "gouty" microbiome is characterized by reduced diversity, an elevated Bacteroides: Firmicutes ratio, and reduced presence of Akkermansia and Bifidobacterium. In anserine models, supplementation with Lactobacillus probiotic strains appears to reduce serum urate (SU) and HU-induced inflammation. Murine models suggest that the chicory-derived prebiotic inulin may reduce SU, and oral supplementation with the anti-inflammatory short-chain fatty acid butyrate may lower SU by enhancing urate excretion and alleviate HU-induced tissue inflammation. Many of these studies are limited by modest numbers of participants and/or incompletely documented experimental controls, and, in the case of animal models, questionable reproducibility in humans. Many studies have been geographically limited. There remains a need for more information regarding the features of the "gouty" microbiome in wider populations, as well as for additional well-controlled probiotic and prebiotic studies in more physiologically relevant animal models prior to clinical trials.}, }
@article {pmid40615170, year = {2025}, author = {Chowdhury, R and Maddheshiya, A and Taneja, S and Bhandari, N and Majumder, PP and Strand, TA and Pandey, RM and Kurpad, AV and Mukherjee, S}, title = {Impact of an Integrated Intervention Package During Preconception, Pregnancy, and Early Childhood on the Gut Microbiome at Six Months of Age: Findings from the Women and Infants Integrated Growth Study (WINGS) Randomized Controlled Trial.}, journal = {The Journal of nutrition}, volume = {155}, number = {7}, pages = {2355-2366}, doi = {10.1016/j.tjnut.2025.04.016}, pmid = {40615170}, issn = {1541-6100}, mesh = {Humans ; Female ; *Gastrointestinal Microbiome ; Pregnancy ; Infant ; Adult ; Young Adult ; Adolescent ; Male ; Feces/microbiology ; *Preconception Care ; }, abstract = {BACKGROUND: The infant gut microbiome is essential for healthy growth and development. However, limited research has explored how interventions targeting maternal and infant health, nutrition, and psychosocial conditions during preconception, pregnancy, and early childhood impact microbiome development. To address this research gap and better understand the potential impact of such interventions, this study was designed to evaluate their effects on the infant gut microbiome.<br><br>OBJECTIVE: The aim was to evaluate the effects of an integrated intervention package on infant gut microbiome at 6 mo of age compared with routine care.<br><br>METHODS: The study was embedded in a randomized factorial trial involving women aged 18-30 y. Participants were randomly assigned to receive either a preconception intervention package or routine care until pregnancy. Pregnant women were then randomly assigned to receive a pregnancy and early childhood intervention package or routine care. The intervention included health care for growth-related conditions, nutrition, water, sanitation, and hygiene (WASH), and psychosocial care. Stool samples from 392 infants (185 from the preconception, pregnancy, and early childhood intervention group and 207 from the routine care group) were collected at 6 mo, followed by microbiome DNA isolation and high-throughput sequencing of the V3-V4 region of 16S rRNA gene. Generalized linear models were used to estimate the mean relative abundance of core gut microbiome phyla, genera, and species between the intervention and routine care groups.<br><br>RESULTS: Infants in the group who received preconception, pregnancy, and early childhood intervention had a significantly lower mean relative abundance of Klebsiella genus under the Pseudomonadota phylum (45% lower; 95% confidence interval [CI]: 18, 63) and Klebsiella pneumoniae species (38% lower; 95% CI: 8, 59) compared with routine care group. In contrast, the relative abundance of Megasphaera (72% higher; 95% CI: 7, 175), Prevotella (72% higher; 95% CI: 3, 187), and Bifidobacterium breve (34% higher; 95% CI: 2, 79) was significantly higher in the group received preconception, pregnancy and early childhood intervention compared with routine care.<br><br>CONCLUSIONS: The findings indicate that improving maternal and infant health, nutrition, and psychosocial conditions enhances the relative abundance of beneficial gut bacteria at 6 mo of age, supporting healthy growth and development. This trial was registered at Clinical Trials Registry-India as CTRI/2020/10/028770; https://ctri.nic.in/Clinicaltrials/advsearch2.php.}, }
@article {pmid40613581, year = {2025}, author = {Dang, T and Lysenko, A and Boroevich, KA and Tsunoda, T}, title = {VBayesMM: variational Bayesian neural network to prioritize important relationships of high-dimensional microbiome multiomics data.}, journal = {Briefings in bioinformatics}, volume = {26}, number = {4}, pages = {}, pmid = {40613581}, issn = {1477-4054}, support = {JP20H03240//JSPS KAKENHI/ ; JP24K15175//JSPS KAKENHI/ ; JPMJCR2231//JST CREST/ ; }, mesh = {Bayes Theorem ; *Microbiota ; *Neural Networks, Computer ; *Metagenomics/methods ; Humans ; *Computational Biology/methods ; Algorithms ; Multiomics ; }, abstract = {The analysis of high-dimensional microbiome multiomics datasets is crucial for understanding the complex interactions between microbial communities and host physiological states across health and disease conditions. Despite their importance, current methods, such as the microbe-metabolite vectors approach, often face challenges in predicting metabolite abundances from microbial data and identifying keystone species. This arises from the vast dimensionality of metagenomics data, which complicates the inference of significant relationships, particularly the estimation of co-occurrence probabilities between microbes and metabolites. Here we propose the variational Bayesian microbiome multiomics (VBayesMM) approach, which aims to improve the prediction of metabolite abundances from microbial metagenomics data by incorporating a spike-and-slab prior within a Bayesian neural network. This allows VBayesMM to rapidly and precisely identify crucial microbial species, leading to more accurate estimations of co-occurrence probabilities between microbes and metabolites, while also robustly managing the uncertainty inherent in high-dimensional data. Moreover, we have implemented variational inference to address computational bottlenecks, enabling scalable analysis across extensive multiomics datasets. Our large-scale comparative evaluations demonstrate that VBayesMM not only outperforms existing methods in predicting metabolite abundances but also provides a scalable solution for analyzing massive datasets. VBayesMM enhances the interpretability of the Bayesian neural network by identifying a core set of influential microbial species, thus facilitating a deeper understanding of their probabilistic relationships with the host.}, }
@article {pmid40611411, year = {2025}, author = {Islam, A}, title = {Advances in Microbiome Research: Implications for Infectious Disease Management and Treatment.}, journal = {Recent advances in anti-infective drug discovery}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724344384934250624040634}, pmid = {40611411}, issn = {2772-4352}, abstract = {INTRODUCTION: The human microbiome plays a pivotal role in health and disease, with microbial imbalances (dysbiosis) increasingly linked to heightened susceptibility to infections and exacerbated disease severity. This review explores how the microbiome confers protection through mechanisms, such as colonization resistance, immune modulation, and antimicrobial metabolite production, while also examining its potential as a predictive tool for infection risk and outcomes, as exemplified in COVID-19.<br><br>METHODS: This article synthesizes current literature on microbiome dynamics, leveraging advances in high-throughput sequencing, bioinformatics, and machine learning to analyze microbial profiles and identify biomarkers. It evaluates microbiome-based therapeutic strategies, including probiotics, prebiotics, and engineered microbes, and assesses challenges in translating these approaches into clinical practice.<br><br>RESULTS: Microbiome profiles demonstrate prognostic value in predicting infection risk and severity, supported by enhanced analytical tools that enable precise biomarker discovery for diagnostics and personalized medicine. Therapeutic interventions show promise in restoring microbial balance and combating infections, though clinical adoption is hindered by variability, regulatory hurdles, and the need for standardized methodologies.<br><br>CONCLUSION: Integrating microbiome insights into clinical practice requires rigorous clinical trials, standardized protocols, and resolution of ethical and regulatory challenges. Future research should focus on elucidating microbiome-host-pathogen interactions and developing targeted interventions, and advanced computational models are critical to unlocking the full potential of microbiome-based diagnostics and therapeutics for infectious disease management.}, }
@article {pmid40607434, year = {2025}, author = {Kim, SI and Rha, MS and Kim, J and Ahn, SH and Ryu, JH and Cho, HJ and Kim, CH}, title = {Inflammation-driven periostin in ECRS has contrasting effects on tissue structural integrity and osteitis.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1596746}, pmid = {40607434}, issn = {1664-3224}, mesh = {Animals ; *Cell Adhesion Molecules/metabolism/genetics ; Humans ; Mice ; *Sinusitis/metabolism/immunology/pathology ; Mice, Knockout ; *Osteitis/metabolism/immunology/pathology/etiology ; *Rhinitis/metabolism/immunology/pathology ; Inflammation/immunology/metabolism ; Disease Models, Animal ; Male ; Chronic Disease ; Female ; Osteogenesis ; Nasal Mucosa/metabolism/pathology/immunology ; Fibroblasts/metabolism/immunology ; *Eosinophilia/immunology/metabolism/pathology ; Periostin ; }, abstract = {INTRODUCTION: Eosinophilic chronic rhinosinusitis (ECRS) is a severe form of chronic rhinosinusitis characterized by type 2 inflammation, tissue remodeling, and bone thickening, known as osteitis. Periostin, a matricellular protein involved in extracellular matrix (ECM) regulation and T helper 2 (Th2)-mediated inflammation, is markedly elevated in patients with ECRS; however, its pathophysiological role remains unclear.<br><br>METHODS: We investigated the role of periostin in inflammation and tissue remodeling in ECRS using samples from ECRS patients, human nasal epithelial cells and fibroblasts, as well as an ECRS mouse model including periostin knockout mice.<br><br>RESULTS: Periostin levels were elevated in ECRS tissues and modestly correlated with osteitis scores. Th2 cytokines increased periostin expression, particularly in nasal fibroblasts. Conditioned medium containing periostin promoted osteogenic differentiation in vitro, whereas neutralizing antibodies reduced the expression of osteogenic markers. In an ECRS mouse model, periostin deficiency led to reduced bone thickening and lower expression of osteogenic markers despite similar eosinophil infiltration. Furthermore, periostin-deficient mice exhibited greater epithelial collapse and reduced fibronectin levels, indicating compromised ECM integrity.<br><br>DISCUSSION: These findings demonstrate that periostin contributes to osteogenesis and maintenance of structural stability in the inflamed sinonasal mucosa. Periostin may be a potential therapeutic target for controlling chronic inflammation and tissue remodeling in ECRS.}, }
@article {pmid40607343, year = {2025}, author = {Xu, H and Zhang, F and Che, Y and Cui, Y and Yao, Q and Guan, Y and Chen, H and Huang, Y}, title = {Integrative multi-omics and bioinformatics analysis of the effects of BaiRui YuPingFeng Powder on intestinal health in broilers.}, journal = {Frontiers in veterinary science}, volume = {12}, number = {}, pages = {1606531}, pmid = {40607343}, issn = {2297-1769}, abstract = {INTRODUCTION: In recent years, global poultry consumption has increased rapidly, making chicken the most widely consumed meat worldwide by 2019. To increase livestock development, antibiotics are often added to animal feed as growth promoters. But overuse of antibiotics may alter the gut microbiota, make people more resistant to them, and raise the possibility that they will spread antibiotic resistance genes to the human microbiome. Therefore, identifying safe and effective alternatives to antibiotics in livestock production is crucial for maintaining and improving gut microbial balance, ultimately promoting poultry health. The aim of this study was to investigate the mechanisms behind the impacts of BaiRui YuPingFeng Powder (TCYP) on intestinal health in broilers using combined metabolomics, bioinformatics analysis, and 16S rRNA sequencing.<br><br>METHODS: In a 42-day feeding trial, 300 one-day-old broilers were randomly divided into five groups (six replicates per group; 10 broilers per replicate) fed a basal diet with or without supplements: control (CON), antibiotic (ATB), and TCYP at 500, 1000, and 1500 mg/kg. Growth performance, serum biochemical parameters, intestinal morphology, cecal microbiota composition, and metabolomic profiles were analyzed. Bioinformatics analysis was used to identify potential targets and pathways, followed by qPCR validation of key genes.<br><br>RESULTS: Compared with the CON group, TCYP administration dose-dependently reduced the feed-to-gain ratio (F/G) and average daily feed intake (ADFI) while increasing average daily gain (ADG), with the high-dose TCYP showing more pronounced effects (p < 0.05). Serum biochemical analysis revealed that TCYP treatment significantly decreased serum levels of total cholesterol (T-CHO), triglycerides (TG), lactate dehydrogenase (LDH), and alanine aminotransferase (ALT) in a dose-dependent manner, while elevating albumin (ALB) content. These beneficial effects were particularly marked in the high-dose TCYP group (p < 0.05). Histopathological examination indicated that high-dose TCYP significantly enhanced villus height and the villus-to-crypt ratio (V/C) in the duodenum, jejunum, and ileum compared to the CON group (p < 0.05). 16S rRNA sequencing analysis revealed that TCYP treatment significantly modified the &#x3b2;-diversity of cecal microbiota (p < 0.01). Compared to the CON group, ATB treatment increased the abundance of Faecalibacterium and Lachnospiraceae_unclassified but reduced Ruminococcaceae_unclassified and Firmicutes_unclassified. Notably, dietary TCYP supplementation maintained gut microbiota profiles similar to the CON group, demonstrating its stabilizing effect on microbial community structure in broilers. Metabolomic analysis identified differential metabolites primarily involved in lipid and lipid-like molecules, organic heterocyclic compounds, and organic acids and derivatives. Spearman correlation analysis revealed significant associations between Lachnospiraceae_unclassified and metabolites such as Gly-Leu, fumarate, and phenylpyruvic acid (|r| > 0.5, p < 0.05). Bioinformatics analysis suggested that TCYP may improve intestinal health by regulating key targets, including MMP9, TGFB1, and PPARG, as well as the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Quantitative PCR (qPCR) results showed that, compared to the CON group, TCYP dose-dependently significantly upregulated the mRNA expression of PPARG, PDPK1, and Bcl2 in jejunal tissues (p < 0.05), while significantly downregulating the expression of MMP1 and Bax (p < 0.05).<br><br>CONCLUSION: TCYP enhances growth performance and intestinal health in broilers through multiple mechanisms, including maintaining cecal microbial homeostasis, modulating lipid and amino acid metabolism, with potential involvement of the PPAR signaling pathway based on bioinformatics and gene expression analysis.}, }
@article {pmid40606566, year = {2025}, author = {Wang, L and Wang, L and Chen, L}, title = {NetNiche: Microbe-Metabolite Network Reconstruction and Microbial Niche Analysis.}, journal = {Phenomics (Cham, Switzerland)}, volume = {5}, number = {2}, pages = {208-211}, pmid = {40606566}, issn = {2730-5848}, abstract = {UNLABELLED: Metagenomics and metabolomics technologies have been widely used to investigate the microbe-metabolite interactions in vivo. However, the computational methods that accurately infer the microbe-metabolite interactions are lacking. We present a context-aware framework for graph representation learning, NetNiche, which predicts microbe-metabolite and microbe-microbe interactions in an accurate manner, by integrating their abundance data with prior knowledge. We applied NetNiche to datasets on gut and soil microbiome, and demonstrated that NetNiche can outperform the state-of-the-art methods, such as SParse InversE Covariance Estimation for Ecological Association Inference (SPIEC-EASI), Sparse Correlations for Compositional data (SparCC) and microbe-metabolite vectors (mmvec). NetNiche is an effective tool with wide applicability for the multi-omics study of human microbiome.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-024-00168-8.}, }
@article {pmid40604393, year = {2025}, author = {Yao, S and Yan, X and Chen, H and Lei, S and Huang, J and Guo, K and Yu, Z}, title = {Dynamic changes of gut and skin microbiota in pancreatic cancer-induced skin injury.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {392}, pmid = {40604393}, issn = {1471-2180}, support = {32170071//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Skin lesions can occur during the progression of pancreatic cancer. With growing attention on the gut-skin axis, these lesions may be linked to the microbiota. Microbiota play a crucial role in skin-related conditions, including hair loss and overall skin health. However, few studies have investigated the dynamic changes in gut and skin microbiota associated with skin lesions during cancer progression. In this study, 16S rRNA gene sequencing was used to investigate the dynamic changes of the gut microbiota in mice without non-depilation (Unepi) and depilation (Epi) after PAN02 cell injection. We also revealed the changes in skin microbiota of Unepi mice (Unepi_D) and Epi mice (Epi_D) after depilation.<br><br>RESULTS: Our study found that the alpha diversity significantly increased in Unepi_D, indicating an imbalance in gut microbiota homeostasis. In the skin microbiota, certain genera such as Staphylococcus and Devosia were up-regulated, while others like Lactobacillus were down-regulated. Similarly, in the gut microbiota, Parasutterella was enriched, whereas Blautia showed reduced abundance. In the Epi group, the trend of increasing pathogenic bacteria and decreasing probiotics suggests a disrupted microbial environment that may contribute to skin injury through the gut&#x2013;skin axis. These findings highlight potential microbial targets for diagnosis and therapeutic intervention in pancreatic cancer-associated skin complications.<br><br>CONCLUSION: Therefore, our findings provide new insights and references for the prevention and treatment of skin-related diseases in clinical practice. Specific gut and skin microbiota alterations may serve as potential biomarkers or therapeutic targets for managing skin complications in pancreatic cancer patients.<br><br>CLINICAL TRIAL NUMBER: Not applicable.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-025-04068-3.}, }
@article {pmid40604155, year = {2025}, author = {Wen, W and Yang, C and Zuo, T}, title = {Viewing MASLD through an integrative gut microbiome lens.}, journal = {Nature metabolism}, volume = {7}, number = {7}, pages = {1315-1317}, pmid = {40604155}, issn = {2522-5812}, }
@article {pmid40601380, year = {2025}, author = {Bağcı, U and Ulusan Bağcı, &#xd6;}, title = {The bibliometric analysis of documents concerning the relationship between the microbiota and urological malignancies.}, journal = {Journal of medical microbiology}, volume = {74}, number = {7}, pages = {}, pmid = {40601380}, issn = {1473-5644}, mesh = {Humans ; *Bibliometrics ; *Microbiota ; *Urologic Neoplasms/microbiology ; Male ; Prostatic Neoplasms/microbiology ; Urinary Bladder Neoplasms/microbiology ; Kidney Neoplasms/microbiology ; }, abstract = {Introduction. The microbiota, which has a major impact on both health and illness, has recently become one of the most popular research topics.Hypothesis/Gap statement. To the best of our knowledge, no research has undertaken a bibliometric analysis of publications examining the connection between microbiome and urological cancer to date. In this respect, it is thought that our study will contribute to the literature.Aim. The purpose of this study is to raise awareness of the topic by performing a bibliometric analysis of the publications examining the connection between the microbiota and the most common urological cancers, including bladder, prostate, and kidney cancers.Methodology. All publications about prostate, renal and bladder cancers and microbiota indexed in Web of Science between 2000 and 2024 were included in the study.Results. A total of 310 publications were obtained. Before 2018, there were only three or fewer publications annually; however, following 2018, the number of publications increased rapidly, reaching a peak of 77 in 2024. The USA led with 98 (31.61%) documents, followed by China (60, 19.35%) and Italy (31, 10%). With 19 publications, Hirotsugu Uemura is the most contributing author, followed by Norio Nonomura with 17. Prostate cancer accounted for 45.48% of the publications, bladder cancer for 36.77% and kidney malignancies for 17.64%.Conclusion. Despite the fact that microbiota has been known for 80 years, research on the connection between microbiota and cancer accelerated after the completion of the Human Microbiome Project. The number of studies examining the connection between urological cancer and microbiota peaked in 2024 and is probably going to rise. More research is required on this topic, since the correlation between microbiota and especially prostate and bladder malignancies raises the possibility that variations in microbiota may be utilized in diagnosis, treatment and prognosis.}, }
@article {pmid40593076, year = {2025}, author = {Krawczyk, K and Rybaczek, D and Locht, C and Pyrzanowska-Banasiak, A and Ciołek, M and Sicinska, P and Rachubik, M and Kowalewicz-Kulbat, M}, title = {Uptake of environmental halophilic archaea by human dendritic cells.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {21912}, pmid = {40593076}, issn = {2045-2322}, support = {2017/27/N/NZ6/02850//Narodowe Centrum Nauki/ ; }, mesh = {Humans ; *Dendritic Cells/microbiology/metabolism/immunology ; *Halobacteriaceae ; Apoptosis ; *Archaea ; }, abstract = {Halophilic archaea are a group distinct from Bacteria and Eukarya, which belong to extremophiles living in highly saline environments. However, they can also exist in the human microbiome. Their impact on the human immune system is poorly known. In this study we examined the interaction of Halorhabdus rudnickae WSM-64[T], isolated from the Barycz area of the Wieliczka Salt-Mine in Poland, and of Natrinema salaciae MDB25[T] from the brine of Lake Medee in Italy, with human monocyte-derived dendritic cells (Mo-DCs). We found that these halophilic archaea invade the cytoplasm and the nucleus of Mo-DCs, but, in contrast to intracellular bacterial pathogens, they do not cause cytotoxic effects on DCs, as no single- or double-stranded DNA breaks (SSB and DSB, respectively), nor chromatin aberrations were noted. Moreover, they did not induce cell cycle alterations, apoptosis or necrosis of DCs. Surprisingly, these halophiles were found to protect against genotoxic activities of Staphylococcus aureus enterotoxin B (SEB), as pre-incubation of the Mo-DCs with the halophilic archaea significantly reduced SEB-induced SSB and DSB, as well as cell cycle disturbance and apoptosis. Therefore, these halophilic archaea can be regarded as safe stimulators for the Mo-DCs to potentially be used as immunomodulators and protective agents for various disorders.}, }
@article {pmid40590527, year = {2025}, author = {Bridy, PV and Cruz, JC and Covington, JL and Islam, TI and Hadley, CE and Tran, K and Fry, R and Sheffield, BA and Serrano, M and Buck, GA and Zhao, J and Tossas, KY and Meyers, C and Morgan, IM and James, CD and Jefferson, KK}, title = {Human papillomavirus 16 mitigates Sneathia vaginalis-induced damage to cervical keratinocytes.}, journal = {mSphere}, volume = {10}, number = {7}, pages = {e0015225}, pmid = {40590527}, issn = {2379-5042}, support = {R21AI166168/NH/NIH HHS/United States ; K01 CA285946/CA/NCI NIH HHS/United States ; R25 GM102795/GM/NIGMS NIH HHS/United States ; Breakthrough Award//Virginia Commonwealth University/ ; R01 DE029471/DE/NIDCR NIH HHS/United States ; R01DE029471,R21AI178143/NH/NIH HHS/United States ; R21 AI178143/AI/NIAID NIH HHS/United States ; K01CA285946/NH/NIH HHS/United States ; P30 CA016059/CA/NCI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; R21 AI166168/AI/NIAID NIH HHS/United States ; R25GM102795/NH/NIH HHS/United States ; V2023-005//V Foundation for Cancer Research/ ; }, mesh = {Humans ; *Keratinocytes/virology/microbiology ; Female ; *Human papillomavirus 16/physiology/genetics ; Papillomavirus Infections/virology ; RNA, Ribosomal, 16S/genetics ; *Cervix Uteri/microbiology/cytology ; Microbiota ; Vagina/microbiology ; Coculture Techniques ; }, abstract = {Sneathia vaginalis is a bacterial component of the vaginal microbiome that is of clinical interest because of its association with preterm birth and other obstetric complications. It produces a cytotoxin, but little is known about the mechanism through which it kills epithelial cells or the role that cytotoxicity plays in bacterial survival. Recent microbiome studies demonstrate an association between S. vaginalis and human papillomavirus (HPV) within the female reproductive tract, suggesting that HPV and S. vaginalis could interact in some way within this shared niche. We analyzed 16S rRNA survey and HPV typing data from our Vaginal Human Microbiome Project and found, in agreement with other reports, that S. vaginalis was associated with HPV infection. To test the hypothesis that HPV promotes the growth of S. vaginalis, growth and cytotoxicity of S. vaginalis in co-culture with HPV16-positive and HPV-negative human cervical keratinocytes (HCK) were quantitatively assessed. Organotypic HCK rafts expressing HPV16 were more resistant to S. vaginalis-induced damage, as assessed by histology, and supported increased bacterial growth relative to HPV-negative HCK rafts. When S. vaginalis was co-cultured with HPV16-positive and HPV-negative HCK monolayers, cytotoxicity was observed in both HPV16-positive and HPV-negative cells, but HPV16-positive cells were more resistant to the toxic effects of the bacteria and supported bacterial growth for an extended period of time. In conclusion, HPV16 may protect cervical keratinocytes from the cytotoxic effects of S. vaginalis, preventing the eradication of colonized cells and supporting bacterial growth, and this could underlie the association between S. vaginalis and HPV in vivo.IMPORTANCESneathia vaginalis (S. vaginalis) is a bacterial species that lives in the human vagina and can cause complications during pregnancy if it invades the uterus. It is capable of killing cervical epithelial cells. Human papillomaviruses (HPV) are sexually transmitted viruses that can cause genital lesions and cervical cancer. Recently, multiple reports describe an association between S. vaginalis and HPV. This study used cultured cervical epithelial cells expressing the high-risk HPV type, HPV16, and HPV-negative cells to determine whether HPV promotes the growth of S. vaginalis. We found that HPV16 promotes the survival of cervical epithelial cells that are exposed to S. vaginalis. Survival of cervical epithelial cells may benefit the growth of S. vaginalis, which adhere to and feed off of these cells to survive in the female reproductive tract.}, }
@article {pmid40587084, year = {2025}, author = {Li, Y and He, Z and Li, C and Huang, J and Yu, Z}, title = {Mechanisms of efficacy of drug therapy in type 2 diabetes: the role of microbiomes.}, journal = {Minerva endocrinology}, volume = {}, number = {}, pages = {}, doi = {10.23736/S2724-6507.25.04306-4}, pmid = {40587084}, issn = {2724-6116}, abstract = {The gut microbiota plays a crucial role in the human body and has an impact on the physiological function of the host. In particular, changes in the gut microbiota are especially pronounced in patients with type 2 diabetes. There is ample evidence that glucose-lowering drugs exert their therapeutic effects precisely through their interactions with the gut microbiota, but there is a lack of summarization. An overall comparison of the effects of each hypoglycemic agent on the gut flora can provide new inspiration for combinations. In this paper, we selected several representative glucose-lowering drugs, such as metformin, sodium-dependent glucose transporters 2 inhibitors (dapagliflozin), glucagon-like peptide-1 receptor agonists (semaglutide, liraglutide), and the traditional Chinese medicine (berberine), and illustrated how they can affect the disease process by regulating metabolic homeostasis, immune response, and gut barrier. We found that each of these four hypoglycemic agents can have conflicting effects on the gut flora depending on the timing and mode of administration. Meanwhile, the potential impact of gut microbiota on drug safety is explored, and an outlook for the optimization of future type 2 diabetes treatment regimens is presented.}, }
@article {pmid40586597, year = {2025}, author = {Khatib, L and Song, SJ and Dilmore, AH and Sanders, JG and Brennan, C and Hernandez, AR and Myers, T and Oles, R and Farmer, S and Cowart, C and Birmingham, A and Diaz, EA and Nizet, O and Gilbert, K and Litwin, N and Das, P and Nowinski, B and Bryant, M and Tribelhorn, C and Sanders-Bodai, K and Chaumont, S and Knol, J and Roeselers, G and Laiola, M and Shetty, SA and Veiga, P and Tap, J and Derrien, M and Koutnikova, H and Cotillard, A and Lay, C and Tovar, AR and Torres, N and Arteaga, L and González, A and McDonald, D and Bartko, A and Knight, R}, title = {A three-country analysis of the gut microbiome indicates taxon associations with diet vary by taxon resolution and population.}, journal = {mSystems}, volume = {10}, number = {7}, pages = {e0054425}, pmid = {40586597}, issn = {2379-5077}, support = {//Danone Nutricia Research/ ; //Center for Microbiome Innovation/ ; //Microsetta Initative/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Diet ; Feces/microbiology ; Metagenomics/methods ; Male ; Female ; Adult ; Metagenome ; Prevotella/genetics/classification/isolation &amp; purification ; Middle Aged ; Faecalibacterium/genetics/classification/isolation &amp; purification ; }, abstract = {UNLABELLED: Emerging research suggests that diet plays a vital role in shaping the composition and function of the gut microbiota. Although substantial efforts have been made to identify general patterns linking diet to the gut microbiome, much of this research has been concentrated on a small number of countries. Additionally, both diet and the gut microbiome have highly complex and individualized configurations, and there is growing evidence that tailoring diets to individual gut microbiota profiles may optimize the path toward improving or maintaining health and preventing disease. Using fecal metagenomic data from 1,177 individuals across three countries, we examine the relationship between diet and bacterial genera, focusing on Prevotella and Faecalibacterium, which have gained significant attention for their potential roles in human health and strong associations with dietary patterns. We find that these two genera in particular show significant associations with many aspects of diet but these associations vary in scale and direction, depending on the level of metagenomic resolution (i.e., genus level by reads and strain level by metagenome-assembled genomes) and the contextual population. These results highlight the growing importance of building metagenomic data sets that are standardized, comprehensive, and representative of diverse populations to increase our ability to tease apart the complex relationship between diet and the microbiome.<br><br>IMPORTANCE: An analysis of fecal microbiome data from individuals in the United States, United Kingdom, and Mexico shows that associations with dietary components vary both by country and by level of resolution (i.e., genus and strain). Our work sheds light on why there may be conflicting reports regarding microbial associations with diet, disease, and health.}, }
@article {pmid40585799, year = {2025}, author = {Alty, JW and Barnes, CE and Nicoli, AM and Turner, BS and Beneman, EA and Dugan, AE and Brucks, SD and Kruger, AG and Schrock, RR and Ribbeck, K and Kiessling, LL}, title = {Synthetic Mucins as Glycan-Defined Prebiotics.}, journal = {ACS central science}, volume = {11}, number = {6}, pages = {918-926}, pmid = {40585799}, issn = {2374-7943}, abstract = {The human microbiome contains at least as many bacterial cells as human cells. Some bacteria offer benefits, like improving gut barrier function, suppressing pathobiont growth, and modulating immunity. These benefits have popularized probiotics, but probiotic retention is often hindered by low colonization efficiency in the mucosal layer that lines all epithelial cells. Mucins, the primary components of mucus, are essential for the organization and regulation of microbial populations. The molecular mechanisms of mucin-probiotic interactions remain understudied due, in part, to the inability to incisively manipulate native mucin sequences or their glycans. Here, we used synthetic mucins with defined glycan presentations to interrogate glycan-dependent interactions between mucus and three probiotic lactobacilli species. The nutrient conditions under which bacteria were cultured influenced glycan binding preferences, suggesting mucin-probiotic interactions change with nutrient availability. The addition of synthetic mucins to native mucin increased Limosilactobacillus fermentum adherence. Additionally, an increase in glycosidase activity indicated that native and synthetic mucins function as prebiotics, as probiotic bacteria can cleave the displayed O-glycans. Thus, synthetic mucins can cultivate target probiotic bacteria and increase adhesion as binding sites, highlighting their value as tools for elucidating native mucin functions and as promising agents for promoting human health.}, }
@article {pmid40575486, year = {2025}, author = {Nieves, L and Roach, A and Hunter, J and Smeh, S and Islas, A and Islas, A and Blattman, J and Di Palma, M}, title = {Harnessing the microbiome to improve clinical outcomes for cancer, transplant, and immunocompromised patients in the intensive care unit (ICU).}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1577108}, pmid = {40575486}, issn = {2235-2988}, mesh = {Humans ; *Intensive Care Units ; *Neoplasms/microbiology/therapy/immunology ; *Immunocompromised Host ; *Microbiota ; Dysbiosis/microbiology ; *Transplant Recipients ; Treatment Outcome ; }, abstract = {In recent decades, there has been a growing emphasis on understanding how the architecture of the human microbiome can impact typical biological processes and patient clinical outcomes. In fact, microbiome modifications and modulations have not only been associated with impacts on general health and well-being but have also been shown to yield differences in patient responsiveness to vaccines, medications, and chemotherapeutic regimens. Much of this influence likely stems from how changes in the microbiome result in differences in microbial communities and the subsequent release of microbial-derived metabolites that can alter typical immunological processes. Understanding how microbial composition can impact patient responsiveness can be particularly important in the intensive care unit (ICU), where the efficacy of medications and treatments can result in negative patient outcomes if unsuccessful. Clinical scientists have further developed the concept of the pathobiome, a disease-promoting microbiome whose development can be associated with dysbiosis. Understanding how the microbiome and its associated components can impact patient responsiveness, especially in the ICU, must be further researched and understood. Here, we analyze what causes variances in the microbiome and pathobiome in significant immunocompromised populations, including cancer patients and transplant recipients, and how variances in the microbiome can impact patient outcomes in the ICU. Further, we detail potential future applications of how our understanding of what impacts the human microbiome during the treatment of these populations may be exploited to improve patient prognosis.}, }
@article {pmid40574683, year = {2025}, author = {}, title = {Correction to: Human microbiome: Impact of newly approved treatments on C. difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {82}, number = {15}, pages = {e656}, doi = {10.1093/ajhp/zxaf137}, pmid = {40574683}, issn = {1535-2900}, }
@article {pmid40572254, year = {2025}, author = {Park, Y and Kyung, S and Mun, S and Yu, BS and Yun, K and Baek, C and Lee, DG and Kang, S and Kim, SR and Kim, JH and Lee, Y and Park, BC and Han, K}, title = {Comparative Analysis of Bacteriome in Hair Follicle Layers of Patients with Female Pattern Androgenic Alopecia.}, journal = {Microorganisms}, volume = {13}, number = {6}, pages = {}, pmid = {40572254}, issn = {2076-2607}, abstract = {Androgenetic alopecia (AGA) is the most common form of patterned hair loss, exhibiting gender-specific clinical features. Recent studies highlight the importance of the skin microbiome in maintaining skin health, but the relationship between the hair follicle microbiome and hair loss, particularly AGA, remains understudied. Hair follicle layer samples were collected directly from the crown region of female pattern hair loss (FPHL), male pattern hair loss (MPHL), and healthy adult women (control) groups. Microbial DNA was extracted and analyzed using Illumina 16S rRNA V3-V4 gene amplicon sequencing. Alpha-diversity and beta-diversity analyses and taxonomic and functional profiling were conducted through relative abundance, LEfSe, and PICRUSt2 analyses. The alpha-diversity analysis showed a significant decrease in microbial richness in the hair loss groups. Unweighted UniFrac-based beta-diversity analysis revealed significant clustering between the control group and the FPHL group. Taxonomic profiling and LEfSe analysis identified differences in microbial composition and biomarkers. PICRUSt2 analysis further revealed altered pathways related to porphyrin metabolism, fatty acid biosynthesis, and steroid hormone metabolism. Additionally, differences in microbiome composition and potential functions were found between the FPHL and MPHL groups. This study provides comprehensive insights into the hair follicle microbiome, revealing unique microbial patterns and functional alterations associated with FPHL. Understanding these microbiome characteristics may contribute to targeted approaches for addressing AGA. Further research is warranted.}, }
@article {pmid40571109, year = {2025}, author = {Chen, H and Qiu, X and Lei, S and Zhao, Y and Zhang, M and Gao, M and Guo, R and Di, H and Huang, J and Yu, Z}, title = {Gut vs. vaginal microbiome in diabetes Progression: Key microbial shifts and implications.}, journal = {Microbial pathogenesis}, volume = {206}, number = {}, pages = {107833}, doi = {10.1016/j.micpath.2025.107833}, pmid = {40571109}, issn = {1096-1208}, mesh = {Humans ; Female ; *Diabetes Mellitus, Type 2/microbiology ; *Gastrointestinal Microbiome ; *Vagina/microbiology ; Middle Aged ; Feces/microbiology ; Disease Progression ; Metagenomics ; Aged ; Blood Glucose/analysis ; Glycated Hemoglobin/analysis ; Bacteria/classification/genetics/isolation &amp; purification ; *Microbiota ; Dysbiosis/microbiology ; Adult ; }, abstract = {BACKGROUND: Dysiosis in gut and vaginal microbiome is implicated in type 2 diabetes (T2D) pathogenesis, but their contributions remain unclear. This study aims to compare their alterations and clinical relevance in diabetes development.<br><br>METHODS: Metagenomic sequencing was performed on vaginal and fecal samples from T2D patients. Differential feature selection and correlation model were used to dissect microbial contributions to diabetic markers.<br><br>RESULTS: Gut microbiota exhibited reduced diversity in T2D patients, with enrichment of Desulfovibrio desulfuricans and Adlercreutzia equolifaciens validated in public cohorts. Vaginal microbiota diversity remained unaffected. Furthermore, structural equation modeling revealed stronger gut microbiota associations with blood glucose and HbA1c. Notably, Romboutsia ilealis-derived pgm was enriched in the diabetes group, which could catalyze the production of glucose, suggesting that it may be involved in the progression of T2D.<br><br>CONCLUSION: Our findings establish the gut microbiome as the dominant driver of T2D progression, with R. ilealis emerging as a potential therapeutic target. This highlights the priority of gut-centric microbiota interventions in diabetes management.}, }
@article {pmid40569694, year = {2025}, author = {Kasmanas, JC and Magnúsdóttir, S and Zhang, J and Smalla, K and Schloter, M and Stadler, PF and de Leon Ferreira de Carvalho, ACP and Rocha, U}, title = {Integrating comparative genomics and risk classification by assessing virulence, antimicrobial resistance, and plasmid spread in microbial communities with gSpreadComp.}, journal = {GigaScience}, volume = {14}, number = {}, pages = {}, pmid = {40569694}, issn = {2047-217X}, support = {2019/03,396-9//S&#xe3;o Paulo Research Foundation/ ; 2022/03,534-5//S&#xe3;o Paulo Research Foundation/ ; //Deutsche Forschungsgemeinschaft/ ; //International Development Research Centre/ ; }, mesh = {*Plasmids/genetics ; Humans ; *Genomics/methods ; Virulence/genetics ; *Drug Resistance, Bacterial/genetics ; Gastrointestinal Microbiome/genetics ; Virulence Factors/genetics ; Computational Biology/methods ; Software ; Genome, Bacterial ; *Bacteria/genetics/pathogenicity/drug effects ; }, abstract = {BACKGROUND: Comparative genomics, genetic spread analysis, and context-aware ranking are crucial in understanding microbial dynamics' impact on public health. gSpreadComp streamlines the path from in silico analysis to hypothesis generation. By integrating comparative genomics, genome annotation, normalization, plasmid-mediated gene transfer, and microbial resistance-virulence risk-ranking into a unified workflow, gSpreadComp facilitates hypothesis generation from complex microbial datasets.<br><br>FINDINGS: The gSpreadComp workflow works through 6 modular steps: taxonomy assignment, genome quality estimation, antimicrobial resistance (AMR) gene annotation, plasmid/chromosome classification, virulence factor annotation, and downstream analysis. Our workflow calculates gene spread using normalized weighted average prevalence and ranks potential resistance-virulence risk by integrating microbial resistance, virulence, and plasmid transmissibility data and producing an HTML report. As a use case, we analyzed 3,566 metagenome-assembled genomes recovered from human gut microbiomes across diets. Our findings indicated consistent AMR across diets, with diet-specific resistance patterns, such as increased bacitracin in vegans and tetracycline in omnivores. Notably, ketogenic diets showed a slightly higher resistance-virulence rank, while vegan and vegetarian diets encompassed more plasmid-mediated gene transfer.<br><br>CONCLUSIONS: The gSpreadComp workflow aims to facilitate hypothesis generation for targeted experimental validations by the identification of concerning resistant hotspots in complex microbial datasets. Our study raises attention to a more thorough study of the critical role of diet in microbial community dynamics and the spread of AMR. This research underscores the importance of integrating genomic data into public health strategies to combat AMR. The gSpreadComp workflow is available at https://github.com/mdsufz/gSpreadComp/.}, }
@article {pmid40568731, year = {2025}, author = {Masetti, R and Barbara, G and Muratore, E and Marasco, G and Cremon, C and Marangoni, A and Brigidi, P and Putignani, L and Angelino, G and Quagliarella, F and Galaverna, F and Leardini, D and Lazzarotto, T and Gabelli, M and Savarino, E and Zecca, M and Faraci, M and Prete, A and Biffi, A and Locatelli, F and Merli, P}, title = {Fecal microbiota transplantation for decolonization from multidrug-resistant bacteria in pediatric allogeneic hematopoietic stem cell transplantation recipients: a retrospective real-word data study.}, journal = {Haematologica}, volume = {}, number = {}, pages = {}, doi = {10.3324/haematol.2025.288067}, pmid = {40568731}, issn = {1592-8721}, abstract = {Not available.}, }
@article {pmid40566568, year = {2025}, author = {Papakonstantinou, A and Moustakli, E and Potiris, A and Zikopoulos, A and Tsarna, E and Christodoulaki, C and Tsakiridis, I and Dagklis, T and Panagopoulos, P and Drakakis, P and Stavros, S}, title = {Behind-the-Scenes Actors in Fertility: A Comprehensive Review of the Female Reproductive Tract Microbiome and Its Clinical Relevance.}, journal = {Life (Basel, Switzerland)}, volume = {15}, number = {6}, pages = {}, pmid = {40566568}, issn = {2075-1729}, abstract = {The study of the microbiome has rapidly progressed over the past few decades, capturing the interest of both scientists and the general public. Nevertheless, there is still no widely agreed-upon definition for the term "microbiome" despite tremendous advances in our knowledge. The international scientific literature consistently underscores the difference between the human microbiome and human microbiota. Recent research has emphasized the importance of the female reproductive tract microbiome in fertility, impacting natural conception and assisted reproductive technologies (ARTs). This review explores the relationship between infertility and the microbiota of the female reproductive tract through a thorough evaluation of research papers and large-scale studies published up to 2024. The objective of this review is to critically assess current evidence on the role of the reproductive tract microbiome in female infertility and ART outcomes. Relevant papers were identified and analyzed through the electronic medical databases PubMed/MEDLINE and Scopus. A comprehensive synthesis of data from 36 original studies was performed, including observational, case-control, cohort, and randomized trials. By focusing on the vagina, cervix, and endometrium, this study offers a comprehensive overview of the microbiome throughout the female reproductive tract. RIF and poor reproductive outcomes are strongly linked to dysbiosis, which is characterized by a reduction in Lactobacillus species. Lactobacillus crispatus, in particular, plays a significant role in protecting against bacterial vaginosis and infertility. A thorough understanding of how the microbiome impacts fertility and the development of clinical strategies to improve reproductive outcomes requires standardized microbiome investigation techniques and larger, randomized trials that account for diverse patient characteristics.}, }
@article {pmid40562845, year = {2025}, author = {Shiner, YA and Caplan, S and Doweck, I}, title = {Actinomyces findings in tonsillectomy specimens- comparison between adults and pediatrics populations.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {}, number = {}, pages = {}, pmid = {40562845}, issn = {1434-4726}, abstract = {BACKGROUND: Tonsillectomy is a common surgical procedure primarily performed for obstructive sleep apnea (OSA) and recurrent acute tonsillitis. Actinomyces are gram-positive, anaerobic bacteria commonly found in the oral cavity and known to form part of the human microbiome, occasionally associated with localized infections. While Actinomyces bacterial colonization in tonsils has been previously studied, its correlation with surgical indications and outcomes remains unclear.<br><br>OBJECTIVES: The study aimed to investigate the relationship between Actinomyces colonization in tonsillar specimens and surgical indications, and to examine whether Actinomyces presence influences tonsillectomy outcomes, specifically post-operative hemorrhage and hospital stay.<br><br>METHODS: This retrospective cohort study analyzed electronic medical records from Lady Davis Carmel Medical Centre between 2011 and 2021. The study included 1,333 patients who underwent extra-capsular tonsillectomies. Patient demographics, surgical indications, length of hospital stay, post-surgical complications, and pathological reports were collected and analyzed using IBM SPSS Statistics 28.0.<br><br>RESULTS: The study population consisted of 760 (57%) males and 573 (43%) females, with an age range of 0.98 to 67.5&#xa0;years (mean 9.1&#xa0;years). Actinomyces was present in 13.2% of specimens from patients with infectious indications compared to 4.5% in patients with obstructive indications (p&#x2009;<&#x2009;0.001). A statistically significant age difference was observed between patients with (17.78&#xa0;years) and without (8.55&#xa0;years) Actinomyces. Multivariate analysis revealed that age was the most significant predictor of Actinomyces presence (OR 1.047, p&#x2009;<&#x2009;0.0001).<br><br>CONCLUSIONS: The study found a significant correlation between Actinomyces presence, older age, and infectious surgical indications. While Actinomyces colonization did not demonstrate a direct influence on surgical complications, the findings suggest potential clinical relevance that merits further research to elucidate the bacterium's role in tonsillar pathology.}, }
@article {pmid40560509, year = {2025}, author = {Andersen, C and Ebsen, TS and Thorup, CA and Reinholdt, KB and Kjaerulff, AMG and Udholm, N and Khalid, V and Madzak, A and Duez, C and Münch, H and Pauli, S and Danstrup, CS and Petersen, NK and Greve, T and Klug, TE}, title = {Next-generation sequencing of the tonsillar microbiome in severe acute tonsillitis: comparison with healthy controls and culture-based findings.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {40560509}, issn = {1435-4373}, abstract = {PURPOSE: Previous culture-based studies suggest three significant pathogens in acute tonsillitis (AT): Streptococcus pyogenes, Fusobacterium necrophorum, and Streptococcus dysgalactiae. Next-generation sequencing (NGS) provides further insights into the human microbiome and may pinpoint additional pathogens in bacterial infections. We aimed to investigate the tonsillar microbiome and identify pathogens associated with AT by applying NGS to tonsillar swabs from patients with severe AT, comparing the findings with both healthy controls and culture-based results.<br><br>METHODS: Full-length sequencing of the 16S rRNA gene (16S tNGS) was performed on tonsillar swabs from 64 AT patients and 55 controls, who were prospectively enrolled at two Danish Ear-Nose-Throat Departments between June 2016 and December 2019.<br><br>RESULTS: The mean number of detected bacteria was significantly higher in patients analysed with 16S tNGS (36) than with culture methods (6.5, p&#x2009;<&#x2009;0.001). The alpha diversity was lower in patients compared to controls (p&#x2009;<&#x2009;0.001) and beta diversity showed separation of the two groups (p&#x2009;=&#x2009;0.001). S. pyogenes (p&#x2009;=&#x2009;0.001) and Bifidobacteriaceae (p&#x2009;=&#x2009;0.002) were significantly more abundant in patients compared to controls. The three suggested pathogens were detected more frequently using 16S tNGS compared to culture: S. pyogenes (38% vs. 27%, p&#x2009;=&#x2009;0.26), F. necrophorum (19% vs. 11%, p&#x2009;=&#x2009;0.32), and S. dysgalactiae (14% vs. 11%, p&#x2009;=&#x2009;0.79).<br><br>CONCLUSION: The tonsillar microbiome differed significantly between AT patients and healthy controls. Our findings confirm the role of S. pyogenes in AT, but did not identify additional likely pathogens. The addition of 16S tNGS to cultures increased the collective detection rate of three previously suggested pathogens from 48 to 70%.}, }
@article {pmid40550997, year = {2025}, author = {Zhang, Y and Ke, S and Wang, XW and Sun, Y and Weiss, ST and Liu, YY}, title = {Association rule mining of the human gut microbiome.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, pmid = {40550997}, issn = {1869-1889}, abstract = {The human gut carries a vast and diverse microbial community that is essential for human health. Understanding the structure of this complex community is a crucial step toward comprehending human-microbiome interactions. Traditional co-occurrence and correlation analyses typically focus on pairwise relationships and ignore higher-order relationships. Association rule mining (ARM) is a well-developed technique in data mining and has been applied to human microbiome data to identify higher-order relationships. Yet, existing attempts suffer from small sample sizes and low taxonomic resolution. We developed an advanced ARM framework and systematically investigated the interactions between microbial species using a public large-scale uniformly processed human microbiome data from the curatedMetagenomicData (CMD) together with ARM. First, we inferred association rules in the gut microbiome samples of healthy individuals (n=2,815) in CMD. Then we compared those rules with those inferred from the individuals with different diseases: inflammatory bowel disease (IBD, n=768), colorectal cancer (CRC, n=368), impaired glucose tolerance (IGT, n=199), and type 2 diabetes (T2D, n=164). Finally, we demonstrated that ARM is an efficient feature selection tool that can improve the performance of microbiome-based disease classification. Together, this study illustrates the higher-order microbial relationships in the human gut microbiome and highlights the critical importance of incorporating association rules in microbiome-based disease classification.}, }
@article {pmid40550653, year = {2025}, author = {Lai, P and He, Z}, title = {[Probiotics empower postoperative intestinal function recovery after colorectal surgery: mechanisms and clinical progress].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {6}, pages = {619-626}, doi = {10.3760/cma.j.cn441530-20250310-00093}, pmid = {40550653}, issn = {1671-0274}, mesh = {Humans ; Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Recovery of Function ; *Colorectal Surgery ; Dysbiosis ; *Intestines/microbiology ; Postoperative Period ; Postoperative Complications/prevention &amp; control ; }, abstract = {Gastrointestinal dysfunction is a common and significant complication in colorectal surgical practice, which is associated with gut microbiota dysbiosis caused by various perioperative interventions. Currently, enhanced recovery after surgery (ERAS) protocols have been increasingly adopted in clinical practice, greatly accelerating the recovery of postoperative intestinal function. However, there are still no effective interventions in the ERAS protocols to target surgery-induced gut microbiota dysbiosis. Probiotics, as a key treatment method targeting the gut microbiota, can stimulate intestinal motility, inhibit the colonization of pathogenic bacteria, enhance intestinal barrier function, among other effects. Based on these effects of probiotics, they are expected to resolve the neglected gut microbiota dysbiosis, further accelerating the postoperative recovery of intestinal function after colorectal surgery. This article reviews the mechanisms and clinical progress in postoperative bowel functional recovery after colorectal surgery.}, }
@article {pmid40546285, year = {2025}, author = {Pei, X and Liu, M and Yu, S}, title = {How is the human microbiome linked to kidney stones?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1602413}, pmid = {40546285}, issn = {2235-2988}, mesh = {Humans ; *Kidney Calculi/microbiology ; *Microbiota ; Dysbiosis/microbiology ; Gastrointestinal Microbiome ; Bacteria/classification/metabolism/isolation &amp; purification ; }, abstract = {In recent years, the incidence of kidney stones has continued to rise worldwide, and conventional treatments have limited efficacy in treating stones associated with recurrent or metabolic abnormalities. The microbiome, as the 'second genome' of the host, is involved in the development of kidney stones through metabolic regulation, immune homeostasis and inflammatory response. Studies have shown that the urinary microbiome of healthy people is dominated by commensal bacteria such as Lactobacillus and Streptococcus, which maintain microenvironmental homeostasis, whereas patients with renal stones have a significantly reduced diversity of intestinal and urinary microbiomes, with a reduced abundance of oxalic acid-degrading bacteria (e.g., Bifidobacterium oxalicum, Bifidobacterium bifidum), and a possible concentration of pathogenic bacteria (e.g., Proteus mirabilis). The microbiome regulates stone formation through mechanisms such as metabolites (e.g., short-chain fatty acids), changes in urine physicochemical properties (e.g., elevated pH), and imbalances in the inflammatory and immune microenvironments. For example, urease-producing bacteria promote magnesium ammonium phosphate stone formation through the breakdown of urea, whereas dysbiosis of the intestinal flora increases urinary oxalic acid excretion and exacerbates the risk of calcium oxalate stones. Microbiome-based diagnostic markers (e.g., elevated abundance of Aspergillus phylum) and targeted intervention strategies (e.g., probiotic supplementation, faecal bacteria transplantation) show potential for clinical application. However, technical bottlenecks (e.g., sequencing bias in low-biomass samples), mechanistic complexity (e.g., multistrain synergism), and individual heterogeneity remain major challenges for future research. Integration of multi-omics data, development of personalised therapies and interdisciplinary research will be the core directions to decipher the relationship between microbiome and kidney stones.}, }
@article {pmid40538714, year = {2025}, author = {Guan, Z and Wang, H and Feng, Q}, title = {Establishment and improvement of genetic manipulation tools for Fusobacterium nucleatum.}, journal = {Engineering microbiology}, volume = {5}, number = {1}, pages = {100192}, pmid = {40538714}, issn = {2667-3703}, abstract = {An imbalance in oral microbial homeostasis is significantly associated with the onset and progression of several systemic diseases. Fusobacterium nucleatum, a ubiquitous periodontitis-causing bacterium in the oral cavity, is frequently detected in focal sites and contributes to the pathogenesis of many extraoral diseases, including cancers, cardiovascular diseases, and adverse pregnancy outcomes (APOs). F. nucleatum is one of the few oral anaerobes that can be cultured purely in vitro and is a 'model species' for studying the impact of oral health on systemic health. The establishment and development of genetic manipulation tools for F. nucleatum and the construction of pathogenic gene-disrupted strains are important strategies for studying the pathogenicity of F. nucleatum. Here, we review the establishment and development of the genetic manipulation systems for F. nucleatum and summarize the characteristics of various genetic manipulation tools, such as suicide plasmid-based systems for gene inactivation, replicable plasmid-based systems controlling gene expression, and transposon-based random mutagenesis systems. Notably, we summarize and analyze their applications in the study of the pathogenic mechanisms of F. nucleatum. We hope to provide reference information and ideas for future research on genetic manipulation tools and the pathogenic mechanisms of F. nucleatum and other Fusobacterium species.}, }
@article {pmid40527211, year = {2025}, author = {Ghosh, S and Nath, S and Chakraborty, A and Bhowmick, S and Majumdar, KK and Mukherjee, S and Pramanik, S}, title = {Long-term arsenic exposure perturbs gut microbial diversity, composition and predicts metabolic dysregulation.}, journal = {Journal of hazardous materials}, volume = {495}, number = {}, pages = {138836}, doi = {10.1016/j.jhazmat.2025.138836}, pmid = {40527211}, issn = {1873-3336}, abstract = {The present study documents significant alterations in human gut microbial composition in arsenic exposed populations of West Bengal, India through amplicon sequencing of human stool metagenomic DNA. A notable reduction in α-diversity underscored a reduced species richness and an altered predominance. β- diversity analysis revealed prominent inter-individual differences. Among the 26 phyla detected, significant perturbation was noted in Bacteroidetes, Actinobacteria, Proteobacteria, and Firmicutes. Species analysis identified significant increase in Bifidobacterium adolescentis, B.longum, Blautia luti, B.wexlerae, Clostridium saudiense, Romboutsia timonensis and Streptococcus salivarius whereas members of Faecalibacterium prausnitzii, Megasphaera elsdenii, Prevotella copri and P. stercorea were found to be highly diminished due to As stress. PICRUSt analysis predicted significant upregulation (pT-test< 0.05) in gene families associated with carbohydrate, amino acid, nucleotide and lipid metabolism along with fermentation and secondary metabolite/ vitamin synthesis pathways in exposed group confirmed through Linear Discriminant Analysis. B.longum, B.luti and S.salivarius were found to be associated with obesity and ulcerative colitis. Network interactions were also characterized with major disruptions in keystone species interaction. The major findings of this study shall drive future studies like community-based metagenomics, metabolomics and in-vitro microbial verifications for designing of microbial therapeutics targeting gut health to combat the harmful impact of As exposure.}, }
@article {pmid40526755, year = {2025}, author = {Zheng, Q and Zhong, Y and Lian, H and Zhuang, J and Wang, L and Chen, J and Wang, H and Wang, H and Ye, X and Huang, Z and Yang, K}, title = {Gut Microbial Signatures Associated With Clinical Remission in Inflammatory Bowel Disease Treated With Biologics: A Comprehensive Multi-Cohort Analysis.}, journal = {United European gastroenterology journal}, volume = {}, number = {}, pages = {}, doi = {10.1002/ueg2.70064}, pmid = {40526755}, issn = {2050-6414}, support = {No. 82300619//National Natural Science Foundation of China/ ; 2023A04J2245//Science and Technology Project in Guangzhou/ ; No. 20231800936102//Dongguan Science and Technology of Social Development Program/ ; No. 2022E02125//Science and Technology Aid Project of Xinjiang Uygur Autonomous Region/ ; }, abstract = {BACKGROUND AND AIMS: The relationship between gut microbiota and biological treatment response in inflammatory bowel disease (IBD) remains incompletely understood. We sought to characterize microbial signatures associated with clinical remission and develop a prediction model for clinical remission.<br><br>METHODS: We analyzed 16&#xa0;S rRNA gene sequencing data from two independent public cohorts (n&#xa0;=&#xa0;231) treated with biologics (infliximab: n&#xa0;=&#xa0;23; adalimumab: n&#xa0;=&#xa0;22; ustekinumab: n&#xa0;=&#xa0;186). Microbial diversity and taxonomic compositions were compared between the remission and non-remission groups. Random Forest algorithm was employed to construct a prediction model using differential genera and clinical features, with performance evaluated through cross-validation. The model was further validated in a local cohort (n&#xa0;=&#xa0;29).<br><br>RESULTS: Significant differences in alpha and beta diversity were observed between the remission and non-remission groups (p&#xa0;<&#xa0;0.05). MaAsLin2 analysis identified 25 differentially abundant genera (p&#xa0;<&#xa0;0.05). Among these, we selected the top 10 genera with highest importance scores (Parabacteroides_B_862066, Agathobaculum, Ruminococcus_E, Sutterella, Clostridium_R_135822, Hominilimicola, Onthenecus, Butyricimonas, Bariatricus, Hominenteromicrobium) to build the Random Forest model, notably all enriched in remission patients. The model demonstrated robust predictive performance for clinical remission (AUC: 0.895), which was further validated in the local cohort (AUC: 0.750).<br><br>CONCLUSION: There is a relationship between gut microbial signatures and biological treatment outcomes in IBD patients. A predictive model based on gut microbiota composition may help stratify patients for treatment response. Further investigation of microbiome modulation strategies may enhance therapeutic efficacy.}, }
@article {pmid40524314, year = {2025}, author = {Schumacher, J and Müller, P and Sulzer, J and Faber, F and Molitor, B and Maier, L}, title = {Proton-pump inhibitors increase C. difficile infection risk by altering pH rather than by affecting the gut microbiome based on a bioreactor model.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2519697}, pmid = {40524314}, issn = {1949-0984}, mesh = {*Proton Pump Inhibitors/adverse effects/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Humans ; Hydrogen-Ion Concentration ; *Clostridioides difficile/drug effects/growth &amp; development ; Omeprazole/pharmacology/adverse effects ; *Clostridium Infections/microbiology ; Bioreactors/microbiology ; Bacteria/drug effects/classification/genetics/growth &amp; development/isolation &amp; purification ; Feces/microbiology ; }, abstract = {Clostridioides difficile infections often occur after antibiotic use, but they have also been linked to proton-pump inhibitor (PPI) therapy. The underlying mechanism - whether infection risk is due to a direct effect of PPIs on the gut microbiome or changes in gastrointestinal pH - has remained unclear. To disentangle both possibilities, we studied the impact of the proton-pump inhibitor omeprazole and pH changes on key members of the human gut microbiome and stool-derived microbial communities from different donors in vitro. We then developed a custom multiple-bioreactor system to grow a model human microbiome community and a stool-derived community in chemostat mode and tested the effects of omeprazole exposure, pH changes, and their combination on C. difficile growth within these communities. Our findings show that changes in pH significantly affect the gut microbial community's biomass and the abundances of different bacterial taxa, leading to increased C. difficile growth within the community. However, omeprazole treatment alone did not result in such effects. These findings imply that the higher risk of C. difficile infection following proton-pump inhibitor therapy is probably because of alterations in gastrointestinal pH rather than a direct interaction between the drug and the microbiome. This understanding offers a new perspective on infection risks in proton-pump inhibitor therapy.}, }
@article {pmid40524025, year = {2025}, author = {Mallari, P and Rostami, LD and Alanko, I and Howaili, F and Ran, M and Bansal, KK and Rosenholm, JM and Salo-Ahen, OMH}, title = {The Next Frontier: Unveiling Novel Approaches for Combating Multidrug-Resistant Bacteria.}, journal = {Pharmaceutical research}, volume = {42}, number = {6}, pages = {859-889}, pmid = {40524025}, issn = {1573-904X}, support = {190913//Svenska Kulturfonden/ ; 188147//Svenska Kulturfonden/ ; }, mesh = {*Drug Resistance, Multiple, Bacterial/drug effects ; Humans ; *Anti-Bacterial Agents/pharmacology/therapeutic use/administration &amp; dosage ; *Bacterial Infections/drug therapy/microbiology ; Animals ; *Bacteria/drug effects ; Drug Delivery Systems/methods ; Drug Discovery/methods ; Drug Repositioning ; }, abstract = {BACKGROUND: The rapid occurrence of bacterial antibiotic resistance poses a significant threat to public health worldwide. Since particularly multidrug-resistant (MDR) pathogens are becoming untreatable with currently available antibiotics, new treatment modalities must be deployed.<br><br>OBJECTIVES: This review explores the recent advancements and the enduring challenges in new antibacterial&#xa0;development for drug-resistant organisms.<br><br>RESULTS: We describe how bacterial resistance to antibiotics arises and discuss why the traditional drug discovery&#xa0;routes are inefficient. The best alternative strategies to overcome these challenges might include exploring new&#xa0;bacterial pathways, utilizing compounds with antibacterial activities from the human microbiome, and repurposing&#xa0;existing drugs. Moreover, novel drug delivery mechanisms that leverage, for example, nanotechnology-based&#xa0;carriers may be breakthrough ideas that can increase antibiotic efficacy and, at the same time, reduce toxicity.&#xa0;Current clinical trials of next-generation drugs indicate that some treatments possess excellent potential to&#xa0;overcome the MDR issue.<br><br>CONCLUSION: Despite the substantial obstacles to getting bench findings to the patient, numerous scientists are still&#xa0;working towards this goal. Both the application of antibiotic stewardship principles and timely considerations through&#xa0;the regulatory pathways are needed to release the next generation of antibiotics that are suitable for the fight&#xa0;against superbugs.}, }
@article {pmid40520768, year = {2025}, author = {Feng, Z and Burgermeister, E and Philips, A and Zuo, T and Wen, W}, title = {The gut virome in association with the bacteriome in gastrointestinal diseases and beyond: roles, mechanisms, and clinical applications.}, journal = {Precision clinical medicine}, volume = {8}, number = {2}, pages = {pbaf010}, pmid = {40520768}, issn = {2516-1571}, abstract = {The gut virome, an essential component of the intestinal microbiome, constitutes ∼0.1% of the total microbial biomass but contains a far greater number of particles than bacteria, with phages making up 90%-95% of this virome. This review systematically examines the developmental patterns of the gut virome, focusing on factors influencing its composition, including diet, environment, host genetics, and immunity. Additionally, it explores the gut virome's associations with various diseases, its interactions with gut bacteria and the immune system, and its emerging clinical applications.}, }
@article {pmid40520523, year = {2025}, author = {Zaki, EA and Afifi, SM and Ammar, NM and Kadry, MO}, title = {Assembled human microbiome and metabolome in chronic kidney disease: Dysbiosis a double-edged sword interlinking Circ-YAP1, Circ-APOE &amp; Circ-SLC8A1.}, journal = {Toxicology reports}, volume = {14}, number = {}, pages = {102058}, pmid = {40520523}, issn = {2214-7500}, abstract = {Dysbiosis is an alteration in microbiota diversity previously elucidated in patients with chronic kidney disease (CKD). Relationship between dysbiosis and CKD is bidirectional; Uremic milieu disturbs the human microbiota on the other hand, gut metabolites influence CKD development. As a result, we outline the possible contribution of microbiota in the pathophysiology, diagnosis and monitoring of CKD. A growing body of research indicates that changes in circular RNAs (circ-RNAs) were observed in CKD with pathogenic implications, including modifying intracellular signaling, exaggerating oxidative stress, cellular apoptosis and inflammation. Additionally, Circ-RNAs exhibit promising role in clinical settings for monitoring, diagnosis, prognostication, and treatment of CKD. Herein blood samples were collected from 60 Egyptian patients with CKD as well as 60 healthy volunteers who served as controls. Following clinical evaluations, OPLS-DA and PCA GC-MS analysis were performed to detect metabolite perturbations. The levels of toxic uremic metabolites, such as urea, hexanedioic acid, ribonic acid, dodecanoic acid, pyrimidine, 1H-indole, 1H-indole-3-acetic acid, butanoic acid, L-cystine, and benzaldehyde linked to renal fibrosis were found to be elevated. Conversely, Reno-protective metabolites, such as short-chain fatty acids; 1H-indole were found to be negatively correlated with indole propionic acid, acetic acid, 2-propenoic acid, tryptophan, tyrosine, and glucitol (AUC 0.65) derived from the gut flora. CKD patients clarified an alteration both gene and protein expression of circRNAs (Circ-YAP1, circ-APOE, and circ-SLC8A1)/mTOR. Moreover, these biomarkers had a significant correlation with clinical investigations such as Creatinine, Glomerular filtration rate (GFR) and albumin/Creatinine (A/C) ratio. These results shed some light on the metabolic biomarkers that are associated with CKD and novel insights into metabolomics/microbiota/Circ-YAP1/circ-APOE/circ-SLC8A1/mTOR interlinked with disease prognosis/diagnosis that could be translated into clinically relevance.}, }
@article {pmid40517367, year = {2025}, author = {Xi, S and Lin, T and Haiyan, Z and Shiyue, Z and Qi, Q and Qiangqiang, X and Mingzhi, Z and Liu, L}, title = {Propionate ameliorates neural degeneration by modulating mitochondrial fission and fusion in nerve cells.}, journal = {Neurological research}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/01616412.2025.2520019}, pmid = {40517367}, issn = {1743-1328}, abstract = {BACKGROUND: Sporadic global cognitive decline is on the rise, and current drugs exhibit limited efficacy. Propionate, an SCFAs of the human microbiome, exhibits robust neuroprotective effects.<br><br>METHODS: We used CCK8 to evaluate neuronal proliferation, DCFH-DA fluorescence probe to quantify ROS production, ELISA to detect IL-1&#x3b2; and IL-6 release, MitoTracker to assess mitochondrial membrane potential, real-time quantitative PCR, and western blotting to analyze DRP1 and anti-Mfn2 protein expression. We also established an in vitro blood-brain barrier model and AD mouse model.<br><br>RESULTS: Propionate normalized the mitochondrial membrane potential in glutamate-treated HT22 cells, reversed growth suppression, ROS accumulation, and elevated IL-1 and IL-6 release. Propionate also decreases Drp1 expression and elevates Mfn2 expression via GRP41 receptor binding. In vitro blood-brain barrier models illustrated the potential of propionate to ameliorate glutamate-induced blood-brain barrier damage. In vivo, propionate notably improved the learning and memory capabilities of AD mice and mitigated AD-induced mitochondrial defects.<br><br>CONCLUSION: Supplementation with propionate provides neuroprotection against neurodegenerative diseases. Propionate supplementation may provide a novel strategy for early intervention of neurological disorders.}, }
@article {pmid40507344, year = {2025}, author = {Gomes de Sousa, R and Guerreiro, CS and Santos, I and Cravo, M}, title = {The Knowledge Gap in Gut Microbiome Characterization in Early-Onset Colorectal Cancer Patients: A Systematic Scoping Review.}, journal = {Cancers}, volume = {17}, number = {11}, pages = {}, pmid = {40507344}, issn = {2072-6694}, abstract = {BACKGROUND/OBJECTIVES: Over the past two decades, the incidence of early-onset colorectal cancer (EoCRC) has been increasing, although its underlying causes remain unclear. Gut microbiome is known to play a role in carcinogenesis of colorectal cancer. This scoping review aims to systematically map and synthetize current evidence on gut microbiome characterization in EoCRC (vs. late-onset colorectal cancer (LoCRC) and healthy individuals), describe the methodology used, and identify knowledge gaps to inform and guide future research.<br><br>METHODS: This systematic scoping review followed the Joanna Briggs Institute (JBI) methodology for scoping reviews. Searches were conducted in PubMed, Web of Science, and Scopus between January and February 2025. Two reviewers independently screened and selected the studies. One reviewer extracted the relevant information, using an adapted version of the JBI template.<br><br>RESULTS: Seven studies met eligibility criteria. Compared to healthy young adults, EoCRC patients had a predominance of lower &#x3b1; diversity, different &#x3b2; diversity, and greater abundance of Flavonifractor plautii, Akkermansia muciniphila, Bacteroides, and Fusobacteria. Comparisons with LoCRC showed that EoCRC had distinct &#x3b2; diversity and a higher abundance in Fusobacterium, Akkermansia, Bacteroides, and Actinomyces. Only three studies correlated the microbiota composition of EoCRC with clinicopathology features and suggested positive associations between Fusobacterium abundance, rectal tumors and lower survival and Akkermansia abundance with body mass index (BMI) &#x2265; 25 kg/m[2], rectal EoCRC, and better survival.<br><br>CONCLUSIONS: There is a lack of large, methodologically robust studies linking gut microbiota with clinicopathological, lifestyle, and tumor molecular features in EoCRC. Our review highlights critical knowledge gaps, the need for standardized methodologies, and key areas for future investigation.}, }
@article {pmid40505619, year = {2025}, author = {Bakkeren, E and Piskovsky, V and Foster, KR}, title = {Metabolic ecology of microbiomes: Nutrient competition, host benefits, and community engineering.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {6}, pages = {790-807}, doi = {10.1016/j.chom.2025.05.013}, pmid = {40505619}, issn = {1934-6069}, mesh = {*Microbiota/physiology ; Humans ; *Nutrients/metabolism ; Animals ; *Bacteria/metabolism/genetics ; *Host Microbial Interactions ; Plants/microbiology ; }, abstract = {Many plants and animals, including humans, host diverse communities of microbes that provide many benefits. A key challenge in understanding microbiomes is that the species composition often differs among individuals, which can thwart generalization. Here, we argue that the key to identifying general principles for microbiome science lies in microbial metabolism. In the human microbiome and in other systems, every microbial species must find ways to harvest nutrients to thrive. The available nutrients in a microbiome interact with microbial metabolism to define which species have the potential to persist in a host. The resulting nutrient competition shapes other mechanisms, including bacterial warfare and cross-feeding, to define microbiome composition and properties. We discuss impacts on ecological stability, colonization resistance, nutrient provision for the host, and evolution. A focus on the metabolic ecology of microbiomes offers a powerful way to understand and engineer microbiomes in health, agriculture, and the environment.}, }
@article {pmid40501963, year = {2025}, author = {Chouhan, D and Grossman, AS and Kerns, KA and Stocke, KS and Kim, M and Dong, PT and Kumar, A and Lei, L and Lamont, RJ and McLean, JS and He, X and Bor, B}, title = {Episymbiotic Saccharibacteria suppresses epithelial immunoactivation through Type IV pili and TLR2 dependent endocytosis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40501963}, issn = {2692-8205}, support = {R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE031274/DE/NIDCR NIH HHS/United States ; S10 OD034405/OD/NIH HHS/United States ; }, abstract = {Saccharibacteria are episymbionts that require host-bacteria to grow. They are positively associated with inflammatory diseases within the human microbiome, yet their mechanisms for interacting with the human host and contributing to diseases remain unknown. This study investigated interactions between a Saccharibacterium (Nanosynbacter lyticus), its host-bacteria (Schaalia odontolytica), and oral epithelial cells. The host-bacteria induced proinflammatory cytokines in epithelial cells, while Saccharibacteria were immune silent. Remarkably, Saccharibacteria dampened cytokine responses to host-bacteria during coinfection. This effect was driven by Saccharibacteria-induced clustering of TLR2 receptors, a process likely facilitated by type IV, ultimately leading to reduced TLR2-mediated cytokine signalling. High resolution imaging showed that Saccharibacteria were endocytosed by oral epithelial cells, and colocalized with endosome markers, eventually trafficking to lysosomes. Moreover, a subset of the Saccharibacteria survive endocytosis long-term, and retains their capability to reinfect host-bacteria, highlighting a mechanism for persistence in the oral microbiome and a vital role in mammalian immune system modulation.}, }
@article {pmid40498317, year = {2025}, author = {Viets, C and Stevens, CA}, title = {Measuring and Analyzing Bacterial Movement in Mucus.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2942}, number = {}, pages = {187-197}, pmid = {40498317}, issn = {1940-6029}, mesh = {Humans ; *Mucus/microbiology/metabolism ; Mucins/metabolism ; *Time-Lapse Imaging/methods ; *Bacteria ; Microbiota ; }, abstract = {Humans are colonized by trillions of microbes that compose the human microbiome. Much of the microbiome inhabits the mucus layers. Mucus layers, covering digestive, reproductive, ocular, and respiratory tracts, are viscous networks consisting mainly of water and mucin glycoproteins. Mucins assemble into a dense, cross-linked network that can affect bacterial swimming patterns, and studying this behavior provides valuable insights into how the body regulates interactions with both harmful and beneficial microbes. Here we present the use of time-lapse imaging to track individual bacterial cells within mucin and discuss techniques for accurately extracting cell trajectory data from these images. By integrating theoretical and experimental approaches, we also describe how to quantify bacterial movement in terms of speed, persistence, and randomness.}, }
@article {pmid40492849, year = {2025}, author = {Coccolini, F and Kirkpatrick, AW and Cremonini, C and Sartelli, M}, title = {Source control in intra-abdominal infections: What you need to know.}, journal = {The journal of trauma and acute care surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/TA.0000000000004654}, pmid = {40492849}, issn = {2163-0763}, abstract = {Providing optimal source control (SC) for intra-abdominal sepsis (IAS) is a critically important surgical principle, yet one that remains nebulous in terms of strict definitions and required conduct. The entire concept of SC has evolved in the last decades. Contemporary SC is not only surgical but also embraces minimally invasive percutaneous and medical therapies. We propose that adequate SC has evolved from the mere anatomical control of enteric leakage, cleansing of obvious contaminants and necrosis, to a more comprehensive anatomo-phyiological-biochemical model. While any breaches in the integrity of the gastrointestinal tract should be addressed urgently, SC should ultimately aim to control the generation and propagation of systemic biomediators, bacterial toxins, and toxic catabolites that perpetuate multisystem organ failure and death. Much urgently needs to be learned to understand and hopefully mitigate the dysbiotic influences of IAS on the human microbiome. Finally, the therapy offered should always be individualized, recognizing patient's unique pathophysiology, clinical condition, comorbidities, and predeclared preferences regarding invasive therapies and life-support.}, }
@article {pmid40491241, year = {2025}, author = {Stringari, A and Tlais, AZA and Tonini, S and Pinto, D and Mondadori, G and Filannino, P and Di Cagno, R and Gobbetti, M}, title = {Revitalising Brewers' Spent Grains and Enriching With Biogenic Compounds Through the Fermentation of Fructophilic Lactic Acid Bacteria and Yeasts.}, journal = {Microbial biotechnology}, volume = {18}, number = {6}, pages = {e70171}, pmid = {40491241}, issn = {1751-7915}, support = {//Open Access Publishing Fund of the Free University of Bozen-Bolzano/ ; }, mesh = {Fermentation ; *Lactobacillales/metabolism ; *Edible Grain/metabolism/microbiology ; *Saccharomycetales/metabolism ; Filaggrin Proteins ; Antioxidants/metabolism ; Lactic Acid/metabolism ; }, abstract = {The large output of spent grains from the brewing industry presents environmental concerns but also offers promising nutritional and functional potential for valorization by researchers and industrial stakeholders. In this perspective, we investigated how non-conventional starters like Fructobacillus fructosus PL22 and Wickerhamomyces anomalus GY1 can drive the fermentation of brewer's spent grain (BSG), a solid by-product of the brewing industry, to enrich its portfolio of bioactive compounds. While sugar reduction was comparable between started- and unstarted-BSG, the effect of the fermentation became evident through the release of key microbial metabolites (lactic and acetic acids and ethanol). Both starters generated the highest number of unique peptides, with only one previously identified as antioxidant peptide found in BSG fermented with F. fructosus. During fermentation, most amino acids and phenolic compounds decreased, while BSG fermented with W. anomalus distinctly enhanced the release of Ala, Cys and GABA, and health-promoting phenolic compounds, such as gallic acid, gallocatechin, quercetin, naringenin, kaempferol, and isorhamnetin. These metabolic changes were associated with the enhanced antifungal and antioxidant properties, which in turn positively reflected on skin protection as shown by the increased proliferation of human keratinocytes, over-expression of the filaggrin (FLG) gene, and wound healing. The power of fermentation to revitalise BSG, giving it a second life chance through the improvement of its nutritional value and further multifunctionality, was demonstrated.}, }
@article {pmid40488826, year = {2025}, author = {Lee, CJ and Carpenter, PA}, title = {Modern-Era Challenges in the Clinical Management of Graft-Versus-Host Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1475}, number = {}, pages = {103-128}, pmid = {40488826}, issn = {0065-2598}, mesh = {*Graft vs Host Disease/therapy/diagnosis/immunology/etiology ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Animals ; Disease Management ; }, abstract = {For several decades, graft-versus-host disease (GVHD) has been a long-standing barrier to successful allogenic hematopoietic cell transplantation and a significant cause of post-transplant morbidity and mortality. Initially described as secondary disease or wasting syndrome in transplanted mice, the pathobiology of GVHD is increasingly understood as a dynamic interplay between innate and adaptive immunity in response to initial tissue damage, leading to inflammation and end-organ damage. In parallel, more uniform symptom capture, diagnosis, and response criteria have facilitated rigorous clinical trial design and conduct; together, these advancements have facilitated the development of novel GVHD prevention and treatment strategies. While these advancements have improved the GVHD treatment paradigm, new questions arise within this complex patient population. This chapter discusses several of the most pertinent current clinical practice challenges in GVHD, including its earlier diagnosis, risk stratification, initial and more advanced stage management, as well as a renewed focus on supportive care, given our increased understanding of key roles played by the human microbiome.}, }
@article {pmid40488467, year = {2025}, author = {Liu, Y and Qiu, Q and Chen, Y and Deng, Y and Huang, W and Sun, C and Shang, X and Chen, X and Wang, C and Han, L and Chen, S and Yuan, J and Xu, F and Yang, Z and Fang, X and Huang, L}, title = {Integrated multi-omics analysis reveals the functional signature of microbes and metabolomics in pre-diabetes individuals.}, journal = {Microbiology spectrum}, volume = {13}, number = {7}, pages = {e0145924}, pmid = {40488467}, issn = {2165-0497}, support = {2024YFC3506300, 2024YFC3506303//National Key R&amp;D Program of China/ ; }, mesh = {Humans ; *Prediabetic State/microbiology/metabolism ; *Metabolomics/methods ; *Gastrointestinal Microbiome/genetics ; Male ; Diabetes Mellitus, Type 2/microbiology/metabolism ; Female ; Middle Aged ; Adult ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/metabolism/isolation &amp; purification ; Metagenome ; Blood Glucose ; Multiomics ; }, abstract = {Pre-diabetes (PD) represents a critical stage in the progression toward type 2 diabetes, with significant alterations observed in the human microbial community among pre-diabetic individuals in observational studies. However, understanding the interaction between human microbiota and the host during pre-diabetes remains limited. Therefore, this study aims to understand the alterations in the human microbial community during pre-diabetes, a critical stage toward type 2 diabetes. Using an integrated analysis of human microbiota and metabolomics data, we seek to identify the functional signature associated with PD and gain insights into potential mechanisms driving its progression to type 2 diabetes. These findings could inform the development of early intervention strategies for those at high risk. Samples were collected from pre-diabetes, diabetes, and healthy control groups. Through metagenome and 16S rRNA sequencing, we analyzed the gut microbial and tongue coating compositions, respectively. Untargeted metabolomics techniques were also applied for comprehensive plasma data. Using integrated multi-omics analysis, we aim to understand the metabolic potentials of the human microbiome, its molecular links with host targets, and their effects on pre-diabetes, thereby deepening our understanding of microbiome-host interactions in this context. The pre-diabetes group exhibited distinct clinical characteristics, particularly in blood glucose levels and a higher average level of γ-glutamyl transferase. We identified 509 intestinal bacterial species, with Megamonas funiformis and Parabacteroides merdae showing higher abundance in the PD group. In tongue coating samples, we found 1,122 bacterial genera, with the PD group showing altered levels of Corynebacterium and Johnsonella. Furthermore, we detected 795 metabolites, primarily involved in carbohydrate and lipid metabolism. Importantly, our integrated multi-omics analysis suggested Flavonifractor plautii's role in modulating blood glucose through influencing carbohydrate metabolism. Our integrated multi-omics analysis revealed significant alterations in several regulatory pathways associated with pre-diabetes, particularly emphasizing the impact of gut bacterium Flavonifractor plautii on blood glucose levels through its influence on carbohydrate metabolism. These intricate relationships among gut microbiota, metabolites, and blood glucose levels underscore the significance of personalized treatment approaches and preventive strategies for pre-diabetes. The insights gained from this research hold considerable promise for advancing our understanding and management of pre-diabetes.IMPORTANCEThis study investigates alterations in the human microbial community during PD, a critical stage leading to type 2 diabetes. Through integrated analysis of metagenomic and metabolomics data from pre-diabetes, diabetes, and healthy control groups, we identified distinct clinical characteristics in the PD group, including elevated blood glucose levels and γ-glutamyl transferase. A total of 509 intestinal bacterial species were identified, with Flavonifractor plautii playing a key role in modulating blood glucose levels via its influence on carbohydrate metabolism. Our findings underscore the complex interactions among gut microbiota, metabolites, and blood glucose levels, highlighting the potential for personalized treatment approaches and early intervention strategies for individuals at high risk of developing type 2 diabetes.}, }
@article {pmid40482318, year = {2025}, author = {Häggqvist, IM and Jernman, J and Snellman, E and Kärhä, P and Pasternack, R and Partonen, T and Karisola, P}, title = {Infrared-A (IR-A) modulates the p53 pathway and diurnal clock in human skin and subcutaneous adipose tissue in vivo.}, journal = {Journal of photochemistry and photobiology. B, Biology}, volume = {269}, number = {}, pages = {113199}, doi = {10.1016/j.jphotobiol.2025.113199}, pmid = {40482318}, issn = {1873-2682}, mesh = {Humans ; *Tumor Suppressor Protein p53/metabolism ; *Skin/metabolism/radiation effects ; *Subcutaneous Fat/metabolism/radiation effects ; *Infrared Rays ; *Circadian Clocks/radiation effects ; Adult ; Cryptochromes/metabolism ; Male ; Cyclin-Dependent Kinase Inhibitor p21/metabolism/genetics ; Female ; Apoptosis/radiation effects ; Signal Transduction/radiation effects ; Skin Temperature/radiation effects ; Circadian Rhythm/radiation effects ; }, abstract = {Infrared-A (IR-A) radiation is thought to protect the skin from damage due to ultraviolet radiation and alter its carcinogenic potential, possibly by preventing keratinocyte apoptosis via p53 pathway modulation. Solar radiation, including IR-A, is a major factor in contributing to the entrainment of circadian rhythms. We examined the impacts of IR-A on the intrinsic clock and transcriptomics in individuals with different diurnal preference to understand the mechanisms by which IR-A acts in the human skin and subcutaneous adipose tissue. IR-A caused multiple gene expressional changes, mainly as immediate stress responses in 15 min, that were reversed within 24 h. IR-A irradiation increased the skin surface temperature (mean peak temperature 42.9 °C). In skin, the zinc finger proteins ZNF490 and ZNHIT2 correlated negatively with the maximum skin surface temperature. In adipose tissue, CDKN1A, which codes p21 protein, had a negative correlation with the skin surface temperature change. In the skin immunohistochemical staining, the circadian regulators CRY1 and CRY2 increased significantly 24 h after the irradiation, CRY1 already in 15 min. According to the diurnal preferences, morning-type individuals develop mostly innate immune responses, whereas evening-type of individuals had more pronounced responses through p53 pathway modulation, apoptosis, and autophagy.}, }
@article {pmid40479572, year = {2025}, author = {Lee, PJ and Lo, YC and Chen, YY and Hu, CJ and Lin, YK and Trang Pham, QT and Sim, NK and Then, CK and Shen, SC}, title = {Short-Chain Fatty Acids Improve Hippocampal Atrophy, Ventricular Dilatation and Cognitive Function Decline in Aged Mice.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2025.0426}, pmid = {40479572}, issn = {2152-5250}, abstract = {Many countries are becoming aged or super-aged societies. This demographic shift causes substantial social, economic, and personal costs directly and indirectly attributable to cognitive decline. Recent studies have shown that dietary fiber can slow down memory decline, with short-chain fatty acids being the primary metabolites produced by gut microbiota from the fermentation of dietary fiber. Despite this, there are limited studies investigating the effect of SCFAs on age-related cognitive function and morphological changes of the brain. In this study, we used B6C3F1 male mice at the age of 3 months and treated them with water, low dose, and high dose SCFAs for 9 months. We assessed their short- and long-term cognitive functions using the Novel Object Recognition test, Morris Water Maze, and Rotarod test. Their brain structure was assessed by 7 Tetra Magnetic Resonance Imaging (7TMRI) and gut microbiota analyzed by 16S rRNA sequencing. Our results show that both short-term and long-term SCFA treatment significantly improve cognitive deficits in the Novel Objective Recognition test and Morris Water Maze tests. Additionally, the 7T MRI results show that SCFAs mitigated hippocampal atrophy compared to the control group. These improvements were accompanied by alteration of gut microbiota composition. We also found that, after treatment, the beneficial gut microbiota Alloprevotella was positively correlated with hippocampal volume. Therefore, we propose that SCFAs may be a promising therapeutic strategy to counteract age-related cognitive decline.}, }
@article {pmid40476583, year = {2025}, author = {Jang, JY and Seo, JH and Choi, JJ and Ryu, HJ and Yun, H and Ha, DM and Yang, J}, title = {Insight into microbial extracellular vesicles as key communication materials and their clinical implications for lung cancer (Review).}, journal = {International journal of molecular medicine}, volume = {56}, number = {2}, pages = {}, pmid = {40476583}, issn = {1791-244X}, mesh = {Humans ; *Extracellular Vesicles/metabolism ; *Lung Neoplasms/microbiology/metabolism/pathology/etiology ; Microbiota ; Animals ; Cell Communication ; *Bacteria/metabolism ; Dysbiosis ; Lung/microbiology ; }, abstract = {The complexity of lung cancer, driven by multifactorial causes such as genetic, environmental and lifestyle factors, underscores the necessity for tailored treatment strategies informed by recent advancements. Studies highlight a significant association between the lung microbiome and lung cancer, with dysbiosis potentially contributing to disease development via inflammation, immune response alterations and bacterial metabolite production. Furthermore, exposure to airborne bacteria may influence lung health by introducing pathogenic species or altering the human microbiome, thereby implicating certain dominant airborne bacteria in lung diseases, including the exacerbation of lung cancer. Extracellular vesicles (EVs) facilitate cell‑to‑cell communication, penetrating mucosal barriers to impact various organs, notably the lung. Epidemiological evidence suggests a strong relationship between the presence of microbial EVs (MEVs) in the air and chronic pulmonary diseases, with indications of a potential risk for lung cancer. MEVs play a significant role in pulmonary disease development by inducing airway inflammation and affecting lung function. The microbiome and MEVs offer considerable potential as novel tools in precision medicine for lung cancer. Biological data analysis and artificial intelligence technology advancements are pivotal for fully realizing their diagnostic and therapeutic capabilities. These developments can potentially shape the future landscape of lung cancer diagnostics, therapeutics and prevention strategies.}, }
@article {pmid40476157, year = {2025}, author = {Rashid, M and Pereira, HS and Alissa, A and Keraidi, S and Wipf, N and Sowa, AM and McDonnell, JM and Darwish, S and Butler, JS}, title = {Microbiome dysbiosis in spinal pathology: Mechanisms, evidence, and research limitations.}, journal = {Brain &amp; spine}, volume = {5}, number = {}, pages = {104272}, pmid = {40476157}, issn = {2772-5294}, abstract = {INTRODUCTION: The microbiome's relevance has become increasingly discussed amid the rising prevalence of chronic illnesses. Microbiome research to date focuses predominantly on its relationship with the GI tract while largely ignoring any impact on the rest of the body. This narrative review aims to lay a foundation of knowledge to fill this gap in the literature and discuss other microbiomes within the human body and their relation to spinal health.<br><br>RESEARCH QUESTION: What is the relationship between the human microbiome and spinal pathologies?<br><br>MATERIALS AND METHODS: A narrative review of all available literature (written or translated to English) was performed using PubMed, MEDLINE, and Google Scholar using relevant search terms including: "microbiome", "spine", "spinal pathology", "ankylosing spondylitis", and "seronegative arthropathies".<br><br>RESULTS: This review found that with dysbiosis, specific bacterial such as Bacteroidaceae and Rikenellaceae proliferate, altering the cytokine microenvironment and subsequently increasing gut wall permeability. This immune overactivation and improper cell function results in an increased susceptibility to autoimmunity; specifically ankylosing spondylitis and seronegative arthropathies. This review also highlights the significant gaps in the available literature.<br><br>DISCUSSION AND CONCLUSION: This review aims to equip clinicians with an understanding of how the collection of microbiomes in the human body have specific implications for spinal health. By building on the current literature and integrating this knowledge into practice, more patient-specific practices in the treatment of spinal pathologies can be implemented, ultimately improving and optimizing patient care in a field in which the microbiome is not currently at the forefront of pathology.}, }
@article {pmid40474070, year = {2025}, author = {Boodaghidizaji, M and Jungles, T and Chen, T and Zhang, B and Yao, T and Landay, A and Keshavarzian, A and Hamaker, B and Ardekani, A}, title = {Machine learning based gut microbiota pattern and response to fiber as a diagnostic tool for chronic inflammatory diseases.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {353}, pmid = {40474070}, issn = {1471-2180}, mesh = {Humans ; *Machine Learning ; *Dietary Fiber ; *Gastrointestinal Microbiome ; Crohn Disease/diagnosis/microbiology ; Feces/microbiology ; Parkinson Disease/diagnosis/microbiology ; Colitis, Ulcerative/diagnosis/microbiology ; HIV Infections/diagnosis/microbiology ; Dysbiosis/microbiology/diagnosis ; Bacteria/classification/genetics/isolation &amp; purification ; Algorithms ; Female ; Male ; *Inflammation/diagnosis/microbiology ; Chronic Disease ; }, abstract = {Gut microbiota has been implicated in the pathogenesis of multiple gastrointestinal (GI) and systemic metabolic and inflammatory disorders where disrupted gut microbiota composition and function (dysbiosis) has been found in multiple studies. Thus, human microbiome data holds significant potential as a source of information for diagnosing and characterizing diseases-such as phenotypes, disease course, and therapeutic response-associated with dysbiotic microbiota communities. However, multiple attempts to leverage gut microbiota taxonomic data for diagnostic and disease characterization have failed due to significant inter-individual variability of microbiota community and overlap of disrupted microbiota communities among multiple diseases. One potential approach is to look at the microbiota community pattern and response to microbiota modifiers like dietary fiber in different disease states. This approach has become feasible with the advent of machine learning, which can uncover hidden patterns in human microbiome data and enable disease prediction. Accordingly, the aim of our study was to test the hypothesis that machine learning algorithms can distinguish stool microbiota patterns-and their responses to fiber-across diseases with previously reported overlapping dysbiotic microbiota profiles. Here, we applied machine learning algorithms to distinguish between Parkinson's disease, Crohn's disease (CD), ulcerative colitis (UC), human immune deficiency virus (HIV), and healthy control (HC) subjects in the presence and absence of fiber treatments. We demonstrated that machine learning algorithms can classify diseases with accuracy as high as 95%. Furthermore, applying machine learning to microbiome data to distinguish UC from CD yielded a prediction accuracy of up to 90%.}, }
@article {pmid40473134, year = {2025}, author = {Sadeghi, S and Faramarzi, MA and Siroosi, M}, title = {Design of novel human microbiome-derived peptides for inhibition of OXA-48 Carbapenemase: An in-silico and in-vitro approach.}, journal = {Microbial pathogenesis}, volume = {206}, number = {}, pages = {107779}, doi = {10.1016/j.micpath.2025.107779}, pmid = {40473134}, issn = {1096-1208}, mesh = {*beta-Lactamases/metabolism/chemistry/genetics ; Humans ; Molecular Docking Simulation ; *Bacterial Proteins/antagonists &amp; inhibitors/metabolism/chemistry ; Molecular Dynamics Simulation ; Anti-Bacterial Agents/pharmacology/chemistry ; Microbial Sensitivity Tests ; Drug Design ; Computer Simulation ; *Antimicrobial Peptides/pharmacology/chemistry ; *beta-Lactamase Inhibitors/pharmacology/chemistry ; *Peptides/pharmacology/chemistry ; }, abstract = {Drug-resistant bacteria have become a global healthcare challenge, especially due to their acquisition of resistance to last-resort antibiotics. OXA-48 carbapenemase is one of the notorious enzymes that inactivates carbapenems through hydrolysis. The emergence of OXA-48 and OXA-48-like carbapenemases is a significant concern as they are responsible for many outbreaks of hospital-acquired infections in various countries, with limited treatment options available. Thus, targeting this enzyme and inhibiting its activity can be an attractive therapeutic strategy. In this study, a rational computer-aided approach was applied to design effective inhibitory peptides against OXA-48 carbapenemase. The primary library was constructed based on peptides derived from the Human Antimicrobial Peptide (HAMP) database. The binding of peptides to the enzyme was investigated through molecular docking studies using ClusPro. After each screening step, numerous targeted amino acid substitutions were performed to enhance the affinity and physicochemical properties of the selected peptides. The final selected peptides, in complex with the enzyme, were subjected to 200 ns molecular dynamics (MD) simulations using the GROMACS package, and MM/PBSA analysis was conducted to evaluate the binding free energy of the enzyme-peptide complexes. Finally, the inhibitory effects of the designed peptides were also computationally assessed on OXA-48-like carbapenemases. Homology modeling was used to generate 3D structures of the enzymes whose structures were not solved experimentally. Results indicated that the two final selected peptides effectively interacted with the important residues of OXA-48 carbapenemase and spatially blocked its active site. These peptides also demonstrated high binding affinity to the most common OXA-48-like carbapenemases in silico. In vitro studies on the efficacy of one of the designed peptides, M104, demonstrated that this peptide enhanced the activity of meropenem against a meropenem-resistant, clinical Klebsiella pneumoniae strain harboring the gene blaOXA48 by reducing its minimum inhibitory concentration (MIC) by 4-fold. In an era where effective inhibitors against OXA-48 carbapenemase are limited, present study addressed this urgent need by rationally designed novel peptides.}, }
@article {pmid40470258, year = {2025}, author = {Demirci, M and Gadhave, K}, title = {Editorial: Human microbiome and COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1613825}, pmid = {40470258}, issn = {2235-2988}, }
@article {pmid40468659, year = {2025}, author = {Hossain, MS and Seo, H and Lee, KA and Ul-Haq, A and Kim, S and Jo, S and Rahim, MA and Tajdozian, H and Ghorbanian, F and Yoon, Y and Barman, I and Shuvo, MSH and Kim, HS and Song, HY}, title = {Microbiome therapeutic PMC72 through reverse translational research in gout.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {63}, number = {5}, pages = {e2501002}, doi = {10.71150/jm.2501002}, pmid = {40468659}, issn = {1976-3794}, support = {RS-202300219563//National Research Foundation of Korea/ ; //Ministry of Science and ICT/ ; 2020R1I1A-3072680//Ministry of Education/ ; //Soonchunhyang University Research Fund/ ; }, mesh = {Animals ; *Gout/therapy/microbiology/chemically induced ; Humans ; Mice ; *Gastrointestinal Microbiome/drug effects ; Hyperuricemia/chemically induced/therapy ; Uric Acid/blood/metabolism ; Disease Models, Animal ; Translational Research, Biomedical ; Dysbiosis ; Male ; Feces/microbiology ; Febuxostat/therapeutic use ; Oxonic Acid ; Oxidative Stress ; }, abstract = {Gout is an inflammatory arthritis resulting from the deposition of monosodium urate crystals. Urate-lowering therapies for gout have limitations, including side effects and limited efficacy, highlighting the need for novel therapeutic approaches to improve patient outcomes. In this context, our research team conducted a microbiome analysis of fecal samples from healthy individuals and gout patients, identifying Bifidobacterium as a key biomarker. Subsequently, we isolated and identified this strain, B. longum PMC72, and demonstrated its efficacy in a gout mouse model. In potassium oxonate (PO)-induced hyperuricemia mice, PMC72 significantly alleviated nausea, gait disturbances, ankle inflammation, and improved renal health. These effects were associated with marked reductions in oxidative stress markers, including serum uric acid, blood urea nitrogen, hepatic xanthine oxidase, and malondialdehyde (MDA) levels in serum, liver, and joint samples, as well as the downregulation of inflammation and uric acid transport-related gene expression in kidney samples. These benefits were comparable to those treated with Febuxostat, a standard urate-lowering therapy for gout. Furthermore, gut microbiome analysis revealed that PMC72 restored dysbiosis induced by hyperuricemia, contrasting with the reduced microbial diversity observed with febuxostat alone, and showed a complete recovery to eubiosis when combined with Febuxostat. These findings position PMC72 as a promising microbial therapeutic candidate for gout management, demonstrating significant development potential and serving as a benchmark for reverse translational microbiome-based therapeutic research.}, }
@article {pmid40467859, year = {2025}, author = {Ferretti, P and Johnson, K and Priya, S and Blekhman, R}, title = {Genomics of host-microbiome interactions in humans.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, pmid = {40467859}, issn = {1471-0064}, abstract = {The human microbiome is a complex ecosystem of microorganisms that inhabit the human body and have a crucial role in human health. Microbiome composition is shaped by its interaction with many factors, including human genetics. Advances in genomic technologies are improving the ability to quantify the effect of human genetics on the microbiome through improved heritability studies and microbiome genome-wide association studies (GWAS). Complementary studies using transcriptomic analyses are providing a more comprehensive view of the bidirectional relationship between host gene expression and the microbiome. The resulting insights into the genetic mechanisms driving host-microbiome interactions will ultimately contribute to the development of personalized medicine and targeted therapies.}, }
@article {pmid40467839, year = {2025}, author = {Chen, YA and Kawashima, H and Park, J and Mohsen, A and Hosomi, K and Nakagata, T and Murakami, H and Nanri, H and Miyachi, M and Kunisawa, J and Mizuguchi, K}, title = {NIBN Japan Microbiome Database, a database for exploring the correlations between human microbiome and health.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {19640}, pmid = {40467839}, issn = {2045-2322}, support = {22AC5002//Ministry of Health, Labour and Welfare/ ; 22AC5002//Ministry of Health, Labour and Welfare/ ; 20AC5004//Ministry of Health, Labour and Welfare/ ; 20AC5004//Ministry of Health, Labour and Welfare/ ; }, mesh = {Humans ; Japan ; *Databases, Factual ; *Gastrointestinal Microbiome ; *Microbiota ; Metadata ; }, abstract = {Recent research has highlighted the substantial impact of gut microbiome on various aspects of human health, such as obesity, inflammation, infectious diseases, and cancer. As a result, gut microbiota composition is increasingly recognized as a potential health indicator and biomarker for disease. Numerous factors, including lifestyle, diet, and physical fitness, are known to shape the composition of the human microbiome. However, a significant challenge in elucidating the relationships between these factors and the gut microbiome lies in needing a comprehensive database that integrates diverse human microbiome profiles with extensive sample metadata. To address this issue, we developed an extensive human microbiome database for healthy individuals. This initiative led to the establishment of the NIBN Japan Microbiome Database (NIBN JMD), one of the largest resources of its kind, encompassing up to 1,000 metadata points and more than 2,000 microbiome samples, including data from longitudinal studies. In this article, we describe the creation and features of NIBN JMD, detailing the data collection, processing, and database implementation. NIBN JMD is publicly accessible at https://jmd.nibn.go.jp/ .}, }
@article {pmid40456421, year = {2025}, author = {Talukdar, D and Raju, YJ and Jana, P and Sharma, K and Babele, P and Kothidar, A and Ahrodia, T and Narendrakumar, L and Shyam, KR and Singh, U and Tanwar, S and Harle, S and Chaudhuri, S and Raghavan, S and Wadhwa, N and Mukherjee, S and Bhatnagar, S and Das, B and , }, title = {Genomic insights into the potency and functional roles of Lactobacillus species in term and preterm births.}, journal = {Genomics}, volume = {117}, number = {4}, pages = {111063}, doi = {10.1016/j.ygeno.2025.111063}, pmid = {40456421}, issn = {1089-8646}, mesh = {Humans ; Female ; *Lactobacillus/genetics/isolation &amp; purification/physiology/classification ; *Premature Birth/microbiology/prevention &amp; control ; Pregnancy ; *Genome, Bacterial ; Vagina/microbiology ; *Term Birth ; Bacteriocins/pharmacology ; }, abstract = {The vaginal microbiome, typically dominated by Lactobacillus species, plays a key role in reducing the risk of preterm birth (PTB) by protecting against infections. In this study, we sequenced 133 Lactobacillus genomes isolated from the reproductive tracts of pregnant Indian women. Genomic analysis identified genes linked to pathogen resistance and anti-inflammatory functions. Further proteome analysis of cell-free supernatant revealed antimicrobial properties, including lysin and bacteriocin, while antibacterial tests confirmed their ability to inhibit reproductive tract pathogens. These findings suggest that Lactobacillus strains protect against harmful microbes, potentially reducing infection risks and PTB. This Lactobacillus consortium holds promise for developing biotherapeutics aimed at improving maternal health.}, }
@article {pmid40456384, year = {2025}, author = {Nayyar, J and Bedu-Ferrari, C and Patangia, D and Hurley, E and Feeley, L and Ross, RP and Stanton, C and Brady, P}, title = {Gut and oral microbial profile associations to oral cancer.}, journal = {Journal of dentistry}, volume = {160}, number = {}, pages = {105848}, doi = {10.1016/j.jdent.2025.105848}, pmid = {40456384}, issn = {1879-176X}, mesh = {Humans ; *Mouth Neoplasms/microbiology/pathology ; Saliva/microbiology ; Male ; Female ; Middle Aged ; *Mouth/microbiology ; Aged ; *Microbiota ; *Gastrointestinal Microbiome ; Adult ; Fusobacterium nucleatum/isolation &amp; purification ; Biomarkers, Tumor/analysis ; }, abstract = {The human microbiome is widely known to be associated with health and disease. The oral microbiome has been linked with oral diseases and infections, though not many studies have explored the relation between oral and gut microbiome with oral cancer based on lesion histology METHODS: This study uniquely explores the oral and gut microbiota in 30 participants (n = 30) divided into three groups based on histology; Benign (B) (n = 15), Potentially Malignant (PM) (n = 8), and Malignant (M) (n = 7) oral lesions. Using shotgun metagenomic sequencing, we analysed microbiota profiles to determine their potential as biomarkers for oral malignancy RESULTS: Distinct gut microbial profiles were observed between Benign and Malignant groups and the association of specific microbes in oral saliva, such as Haemophilus parainfluenzae, Veillonella parvula, Fusobacterium nucleatum and Rothia mucilaginosa were strongly associated with malignancy CONCLUSION: The data from this exploratory study suggest that oral and gut microbiomes could act as possible biomarkers and aid in early detection and assessment of oral cancer risk. With regard to potentially malignant lesions, future research could study individual Oral Potentially Malignant Disorders (OPMDs) as distinct entities due to the wide variation in clinical and histological presentation. Further research is required to develop definitive biomarkers in both potentially malignant and malignant oral lesions CLINICAL SIGNIFICANCE: While smoking and alcohol are known risk factors for oral cancer, a biomarker such as the saliva/stool microbiome profile could help identify a risk indicator or a potential risk factor. Additionally such a biomarker could help identify patients with OPMDs that are likely to undergo malignant transformation.}, }
@article {pmid40455399, year = {2025}, author = {Qayyum, H and Raziq, MF and Manzoor, H and Zaidi, SSA and Ali, A and Kayani, MUR}, title = {Efficient De Novo Assembly and Recovery of Microbial Genomes from Complex Metagenomes Using a Reduced Set of k-mers.}, journal = {Interdisciplinary sciences, computational life sciences}, volume = {}, number = {}, pages = {}, pmid = {40455399}, issn = {1867-1462}, abstract = {De novo assembly and genome binning are fundamental steps for genome-resolved metagenomics analyses. However, the availability of limited computational resources and extensive processing time limit the broader application of these analyses. To address these challenges, the optimization of the parameters employed in these processes can improve the effective utilization of available metagenomics tools. Therefore, this study tested three sets of k-mers (default, reduced, and extended) for their efficiency in metagenome assembly and suitability in recovering metagenome-assembled genomes. The results demonstrate that the reduced set of k-mers outperforms the other two sets in computational efficiency and the quality of results. The assemblies from the default set are comparable with those from the reduced set; however, less complete and highly contaminated metagenome-assembled genomes are obtained at the expense of higher processing time. The extended set of k-mers yields less contiguous but computationally expensive assemblies. This set takes approximately 3-times more processing time than the reduced k-mers and recovers the lowest proportions of high and medium-quality metagenome-assembled genomes. Contrarily, the reduced set produces better assemblies, substantially improving the number and quality of the recovered metagenome-assembled genomes in significantly reduced processing time. Validation of the reduced k-mer set on previously published metagenome datasets further demonstrates its effectiveness not only for human metagenomes but also for the metagenomes of environmental origin. These findings underscore that the reduced k-mer set is optimal for efficient metagenome analyses of varying complexities and origins. This optimization of the k-mer set used in metagenome assemblers significantly reduces computational time while improving the quality of the assemblies and recovered metagenome-assembled genomes. This efficient solution will facilitate the widespread application of genome-resolved analyses, even in resource-limited settings, and help the recovery of better-quality metagenome-assembled genomes for downstream analyses.}, }
@article {pmid40454482, year = {2025}, author = {Koletic, C and Mrad, A and Martin, A and Devkota, S}, title = {Diet's impact on gut microbial assemblage in health and disease.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {11}, pages = {}, pmid = {40454482}, issn = {1558-8238}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Diet ; Animals ; Chronic Disease ; }, abstract = {The gut microbiome has been linked to everything from human behavior to athletic performance to disease pathogenesis. And yet, few universal truths have emerged regarding how the microbiome exerts its effects or responds to the host environment except for one: gut microbiota are exquisitely sensitive to human diets. What we eat from birth onward shapes our gut microbiome composition and function, and this is likely an evolutionarily conserved interaction that benefits the microbe and often the host. However, modern diets and lifestyles have created discordance between our slowly evolving human genome and rapidly adaptable microbiome, and have been implicated in the rise of chronic diseases over the past 75 years. Diet and microbiome interactions have been reviewed extensively, so here we focus on areas of microbiome research that have most illuminated natural and disruptive dietary forces over time in humans, and where we may have opportunities to restore the natural balance of host with microbes in our modern world.}, }
@article {pmid40448308, year = {2025}, author = {Gu, BH and Jung, HY and Rim, CY and Kim, TY and Lee, SJ and Choi, DY and Park, HK and Kim, M}, title = {Comparative Colonisation Ability of Human Faecal Microbiome Transplantation Strategies in Murine Models.}, journal = {Microbial biotechnology}, volume = {18}, number = {6}, pages = {e70173}, pmid = {40448308}, issn = {1751-7915}, support = {2024-ER2113-00//the Korea National Institute of Health (KNIH) research project/ ; 20019505//the Ministry of Trade, Industry &amp; Energy (MOTIE, Korea)/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; Humans ; Mice ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Disease Models, Animal ; *Bacteria/classification/growth &amp; development/isolation &amp; purification/genetics ; Dysbiosis/therapy/microbiology ; Male ; Models, Animal ; }, abstract = {The gut microbiome plays a crucial role in maintaining intestinal homeostasis and influencing immune-mediated diseases. Human faecal microbiota transplantation (FMT) is often employed in murine models to investigate the role of human microbes in disease regulation, but methods for effective colonisation require refinement. This study aimed to assess the colonisation efficiency of human microbiota in a murine model using FMT with human faeces, focusing particularly on the impact of gut microbiota depletion via polyethylene glycol (PEG) and comparing oral-gastric gavage with enema administration routes. Our findings revealed that PEG-induced depletion enhanced human microbiome colonisation in mice. Oral-gastric gavage prolonged colonisation, while enema administration facilitated quicker resolution of dysbiosis, both inducing selective human microbial colonisation in a time-dependent manner. Notably, genera such as Bacteroides, Blautia, Medicaternibacter and Bifidobacteria were successfully colonised, whereas Roseburia, Anaerostipes, Anaerobutyricum and Faecalibacterium failed to establish in the murine gut post-FMT. These findings highlight the challenges of replicating human gut microbiota in murine models and underscore the importance of selecting appropriate FMT methods based on desired outcomes. This study provides valuable insights into the colonisation dynamics of human microbiota in mice, contributing to the development of more effective FMT strategies for disease treatment.}, }
@article {pmid40441709, year = {2025}, author = {Dang, T and Fuji, Y and Kumaishi, K and Usui, E and Kobori, S and Sato, T and Narukawa, M and Toda, Y and Sakurai, K and Yamasaki, Y and Tsujimoto, H and Hirai, MY and Ichihashi, Y and Iwata, H}, title = {I-SVVS: integrative stochastic variational variable selection to explore joint patterns of multi-omics microbiome data.}, journal = {Briefings in bioinformatics}, volume = {26}, number = {3}, pages = {}, pmid = {40441709}, issn = {1477-4054}, support = {JP21J21850//JSPS KAKENHI/ ; JPMJCR1602//JST-CREST Program/ ; JPMJMI120C7//JST-Mirai Program/ ; JPMJAN23D1//JST ALCA-Next Program/ ; }, mesh = {*Microbiota ; Mice ; Animals ; Humans ; Stochastic Processes ; Bayes Theorem ; Glycine max/microbiology ; *Metabolomics/methods ; Algorithms ; *Computational Biology/methods ; Metabolome ; Cluster Analysis ; Multiomics ; }, abstract = {High-dimensional multi-omics microbiome data play an important role in elucidating microbial community interactions with their hosts and environment in critical diseases and ecological changes. Although Bayesian clustering methods have recently been used for the integrated analysis of multi-omics data, no method designed to analyze multi-omics microbiome data has been proposed. In this study, we propose a novel framework called integrative stochastic variational variable selection (I-SVVS), which is an extension of stochastic variational variable selection for high-dimensional microbiome data. The I-SVVS approach addresses a specific Bayesian mixture model for each type of omics data, such as an infinite Dirichlet multinomial mixture model for microbiome data and an infinite Gaussian mixture model for metabolomic data. This approach is expected to reduce the computational time of the clustering process and improve the accuracy of the clustering results. Additionally, I-SVVS identifies a critical set of representative variables in multi-omics microbiome data. Three datasets from soybean, mice, and humans (each set integrated microbiome and metabolome) were used to demonstrate the potential of I-SVVS. The results indicate that I-SVVS achieved improved accuracy and faster computation compared to existing methods across all test datasets. It effectively identified key microbiome species and metabolites characterizing each cluster. For instance, the computational analysis of the soybean dataset, including 377 samples with 16 943 microbiome species and 265 metabolome features, was completed in 2.18 hours using I-SVVS, compared to 2.35 days with Clusternomics and 1.12 days with iClusterPlus. The software for this analysis, written in Python, is freely available at https://github.com/tungtokyo1108/I-SVVS.}, }
@article {pmid40436194, year = {2025}, author = {Chang, VC and Purandare, V and Li, S and Andreotti, G and Hua, X and Wan, Y and Dagnall, CL and Jones, K and Hicks, BD and Hutchinson, A and Yano, Y and Dalton, KR and Lee, M and Parks, CG and London, SJ and Sandler, DP and Gail, MH and Shi, J and Hofmann, JN and Sinha, R and Abnet, CC and Vogtmann, E and Beane Freeman, LE}, title = {Animal farming and the oral microbiome in the Agricultural Health Study.}, journal = {Environmental research}, volume = {281}, number = {}, pages = {121964}, pmid = {40436194}, issn = {1096-0953}, support = {Z01 CP010119/ImNIH/Intramural NIH HHS/United States ; Z01 ES049030/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Microbiota ; Animals ; Humans ; Male ; Female ; Middle Aged ; Adult ; *Animal Husbandry ; *Mouth/microbiology ; Aged ; Cattle ; Bacteria/classification/isolation &amp; purification ; RNA, Ribosomal, 16S/analysis ; Farmers ; }, abstract = {BACKGROUND: Raising farm animals imparts various exposures that may shape the human microbiome. The oral microbiome has been increasingly implicated in disease development. Animal farming has also been associated with certain chronic diseases such as cancer; however, underlying biological mechanisms are unclear. We investigated associations between raising farm animals and the oral microbiome in the Agricultural Health Study.<br><br>METHODS: This analysis included 1,245 participants (865 farmers and 380 spouses) who provided oral wash specimens and information on types and numbers of specific animals raised on their farms within 2 years before sample collection. The oral microbiome was measured by sequencing the V4 region of the 16S ribosomal RNA gene. We evaluated associations of farm animal exposures with alpha and beta diversity metrics (within- and between-sample diversity, respectively), as well as presence and relative abundance of specific bacterial genera. All analyses adjusted for potential confounders (e.g., age, sex, smoking, alcohol consumption).<br><br>RESULTS: Overall, 63&#xa0;% of participants raised farm animals, most commonly cattle (46&#xa0;%) and hogs (20&#xa0;%). Those who raised a large number of hogs (&#x2265;2,000 vs. no hogs) had higher alpha diversity. Conversely, raising sheep/goats and raising larger numbers of poultry were associated with lower alpha diversity. Beta diversity was not significantly different between participants with and without any farm animals. Participants raising any farm animals had higher relative abundance of Porphyromonas and lower relative abundances of Prevotella and Ruminococcaceae UCG-014. Several genera were more likely to be absent with specific animal exposures (e.g., Capnocytophaga for cattle and sheep/goats; Corynebacterium, Dialister, Stomatobaculum, and Solobacterium for sheep/goats and poultry).<br><br>CONCLUSIONS: This was the largest study of farm animal exposures and the human microbiome to date. Findings suggest that raising specific farm animals may influence the oral microbiome, supporting the need to further investigate the potential role of animal farming in disease etiology.}, }
@article {pmid40434093, year = {2025}, author = {Koldaş, SS and Sezerman, OU and Timuçin, E}, title = {Exploring the role of microbiome in cystic fibrosis clinical outcomes through a mediation analysis.}, journal = {mSystems}, volume = {10}, number = {6}, pages = {e0019625}, pmid = {40434093}, issn = {2379-5077}, mesh = {*Cystic Fibrosis/microbiology/physiopathology ; Humans ; *Microbiota/genetics ; Sputum/microbiology ; Female ; Male ; RNA, Ribosomal, 16S/genetics ; Adult ; Lung/physiopathology/microbiology ; }, abstract = {UNLABELLED: Human microbiome plays a crucial role in host health and disease by mediating the impact of environmental factors on clinical outcomes. Mediation analysis is a valuable tool for dissecting these complex relationships. However, existing approaches are primarily designed for cross-sectional studies. Modern clinical research increasingly utilizes long follow-up periods, leading to complex data structures, particularly in metagenomic studies. To address this limitation, we introduce a novel mediation framework based on structural equation modeling that leverages linear mixed-effects models using penalized quasi-likelihood estimation with a debiased lasso. We applied this framework to a 16S rRNA sputum microbiome data set collected from patients with cystic fibrosis over 10 years to investigate the mediating role of the microbiome in the relationship between clinical states, disease aggressiveness phenotypes, and lung function. We identified richness as a key mediator of lung function. Specifically, Streptococcus was found to be significantly associated with mediating the decline in lung function on treatment compared to exacerbation, while Gemella was associated with the decline in lung function on recovery. This approach offers a powerful new tool for understanding the complex interplay between microbiome and clinical outcomes in longitudinal studies, facilitating targeted microbiome-based interventions.<br><br>IMPORTANCE: Understanding the mechanisms by which the microbiome influences clinical outcomes is paramount for realizing the full potential of microbiome-based medicine, including diagnostics and therapeutics. Identifying specific microbial mediators not only reveals potential targets for novel therapies and drug repurposing but also offers a more precise approach to patient stratification and personalized interventions. While traditional mediation analyses are ill-equipped to address the complexities of longitudinal metagenomic data, our framework directly addresses this gap, enabling robust investigation of these increasingly common study designs. By applying this framework to a decade-long cystic fibrosis study, we have begun to unravel the intricate relationships between the sputum microbiome and lung function decline across different clinical states, yielding insights that were previously unknown.}, }
@article {pmid40433658, year = {2025}, author = {Śmiga, M and Olczak, T}, title = {HmuY proteins of the Porphyromonas genus show diversity in heme-binding properties.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1560779}, pmid = {40433658}, issn = {2235-2988}, mesh = {*Heme/metabolism ; *Bacterial Proteins/metabolism/genetics/chemistry ; Humans ; *Porphyromonas gingivalis/metabolism/genetics ; Protein Binding ; *Porphyromonas/metabolism/genetics ; Computational Biology ; Phylogeny ; Iron/metabolism ; Protoporphyrins/metabolism ; Binding Sites ; }, abstract = {INTRODUCTION: Bacteria of the Porphyromonas genus, belonging to the Bacteroidota phylum, colonize various host niches in health and disease. As heme auxotrophs, they rely on heme uptake for iron and protoporphyrin IX. A key heme acquisition system in Porphyromonas gingivalis is the Hmu system, where the hemophore-like HmuY[Pg] protein plays a major role. HmuY[Pg] coordinates heme-iron using two histidines, whereas other known HmuY proteins produced by other Bacteroidota members prefer a pair of histidine-methionine or two methionines. Some of them bind heme via the protoporphyrin ring without heme-iron coordination, similar to the P. gingivalis HusA protein.<br><br>METHODS: This study used bioinformatics, spectroscopic, and electrophoretic methods to compare the genomic organization of the Hmu system and the structural and functional properties of HmuY proteins within the Porphyromonas genus.<br><br>RESULTS AND DISCUSSION: We revealed variations in the heme-binding properties of proteins belonging to the HmuY family and susceptibility to modifications in their heme-binding pockets. These findings suggest that HmuY proteins may have undergone evolutionary adaptations to enhance bacterial survival in the human microbiome, contributing to dysbiosis and disease development. These evolutionary changes may explain the superior heme-binding ability of P. gingivalis HmuY[Pg] compared to HmuY homologs produced by other Porphyromonas species.}, }
@article {pmid40430019, year = {2025}, author = {Kozhakhmetov, S and Kossumov, A and Zhakupova, T and Polyakova, T and Imambayeva, N and Syzdykova, B and Rakhmankulova, A and Dalibayeva, G and Kovenskiy, A and Jarmukhanov, Z and Issilbayeva, A and Vinogradova, E and Kushugulova, A}, title = {Characterization of Gut Microbiome Composition in Depression and Completed Suicide.}, journal = {International journal of molecular sciences}, volume = {26}, number = {10}, pages = {}, pmid = {40430019}, issn = {1422-0067}, support = {AP19676162//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Male ; Female ; *Depression/microbiology ; Middle Aged ; Adult ; *Suicide, Completed/psychology ; Feces/microbiology ; Dysbiosis/microbiology ; Energy Metabolism ; }, abstract = {Growing evidence supports a bidirectional relationship between the gut microbiome and mental health. This study investigated the association between gut microbiota, depression, and suicidal behavior by analyzing fecal samples from 35 individuals with varying depression levels and 36 completed suicide cases. Standardized psychometric assessments were used for depression evaluation. Analysis revealed significant taxonomic differences between groups, with increased abundance of Firmicutes, Clostridia, Lachnospiraceae, Blautia, and Dorea in suicide cases, which also positively correlated with depression severity. Metabolic pathway analysis demonstrated a notable dichotomy: suicide cases showed elevated pathways related to infection processes, inflammation, and antibiotic resistance, while the control group exhibited higher energy metabolism and vitamin synthesis pathways. The findings establish specific microbiome profiles associated with both depression symptoms and suicidal behavior, suggesting that gut dysbiosis may influence mental health through altered energy metabolism and inflammatory processes, potentially offering new perspectives for diagnostic and therapeutic approaches.}, }
@article {pmid40423870, year = {2025}, author = {Zhang, M and Zhang, H and Hong, A and Huang, J and Yang, L and Long, Y and Yu, Z}, title = {Dynamic changes of dental plaque and saliva microbiota in OSCC progression.}, journal = {Clinical oral investigations}, volume = {29}, number = {6}, pages = {314}, pmid = {40423870}, issn = {1436-3771}, support = {32170071//This work was funded by the National Natural Science Foundation of China/ ; 82273466//This work was funded by the National Natural Science Foundation of China/ ; 2023ZJ1120//Hunan Provincial Science and Technology Department/ ; 2024JJ2039//Natural Science Foundation of Hunan Province/ ; 2024JJ8117//Natural Science Foundation of Hunan Province/ ; }, mesh = {Humans ; *Saliva/microbiology ; Disease Progression ; *Dental Plaque/microbiology ; *Mouth Neoplasms/microbiology/pathology ; *Carcinoma, Squamous Cell/microbiology/pathology ; Female ; *Microbiota ; Male ; Middle Aged ; Neoplasm Staging ; Metagenomics ; }, abstract = {OBJECTIVES: To elucidate the changes in microbial composition and genomics in saliva and dental plaque during the progression of Oral Squamous Cell Carcinoma (OSCC), and to identify virulence factors and pathways associated with tumor differentiation in OSCC patients.<br><br>MATERIALS AND METHODS: Using metagenomic sequencing, 64 saliva and dental plaque samples from OSCC patients at different stages of differentiation were examined.<br><br>RESULTS: The results showed notable differences in the microbial composition and genomic profiles across ecological regions and differentiation degrees. Notably, the relative abundance of specific microbes, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Haemophilus parainfluenzae, increased in poorly differentiated OSCC. Microbial alpha diversity in dental plaque and saliva correlates with tumor T staging. Dental plaque microbiota shows higher specialization, especially in poorly differentiated tumors. Both microbiota types become more stable with advanced T staging. Genomic analysis reveals increased virulence factors in poorly differentiated stages.Subsequently, functional pathway analysis and tracing of pathogens reveal specific microbial mechanisms in oral cancer pathogenesis. Certain oral pathogens may promote tumorigenesis by secreting factors like GAPDH (glyceraldehyde-3-phosphate dehydrogenase), GspG (a gingipain precursor), and AllS (a lysine-specific gingipain precursor).<br><br>CONCLUSIONS: OSCC progression is associated with altered microbial composition, diversity, and genomic profiles in saliva and dental plaque. Poorly differentiated stages show higher abundance of pathogens and virulence factors, implicating them in tumorigenesis.<br><br>CLINICAL RELEVANCE: Understanding the microbial and genomic changes in saliva and dental plaque during OSCC progression could aid in developing new diagnostic biomarkers and targeted therapies, potentially enhancing early detection, treatment efficacy, and patient prognosis. Maintaining oral microbiota homeostasis may also help prevent oral cancer.}, }
@article {pmid40420833, year = {2025}, author = {Clasen, F and Yildirim, S and Arıkan, M and Garcia-Guevara, F and Hanoğlu, L and Yılmaz, NH and Şen, A and Celik, HK and Neslihan, AA and Demir, TK and Temel, Z and Mardinoglu, A and Moyes, DL and Uhlen, M and Shoaie, S}, title = {Microbiome signatures of virulence in the oral-gut-brain axis influence Parkinson's disease and cognitive decline pathophysiology.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2506843}, pmid = {40420833}, issn = {1949-0984}, mesh = {Humans ; *Parkinson Disease/microbiology/physiopathology ; *Cognitive Dysfunction/microbiology/physiopathology ; *Gastrointestinal Microbiome ; *Mouth/microbiology ; *Brain/physiopathology/microbiology ; Male ; Female ; Aged ; *Bacteria/genetics/classification/pathogenicity/isolation &amp; purification ; Metagenomics ; Virulence ; Virulence Factors/genetics/metabolism ; Saliva/microbiology/chemistry ; Middle Aged ; }, abstract = {The human microbiome is increasingly recognized for its crucial role in the development and progression of neurodegenerative diseases. While the gut-brain axis has been extensively studied, the contribution of the oral microbiome and gut-oral tropism in neurodegeneration has been largely overlooked. Cognitive impairment (CI) is common in neurodegenerative diseases and develops on a spectrum. In Parkinson's Disease (PD) patients, CI is one of the most common non-motor symptoms but its mechanistic development across the spectrum remains unclear, complicating early diagnosis of at-risk individuals. Here, we generated 228 shotgun metagenomics samples of the gut and oral microbiomes across PD patients with mild cognitive impairment (PD-MCI) or dementia (PDD), and a healthy cohort, to study the role of gut and oral microbiomes on CI in PD. In addition to revealing compositional and functional signatures, the role of pathobionts, and dysregulated metabolic pathways of the oral and gut microbiome in PD-MCI and PDD, we also revealed the importance of oral-gut translocation in increasing abundance of virulence factors in PD and CI. The oral-gut virulence was further integrated with saliva metaproteomics and demonstrated their potential role in dysfunction of host immunity and brain endothelial cells. Our findings highlight the significance of the oral-gut-brain axis and underscore its potential for discovering novel biomarkers for PD and CI.}, }
@article {pmid40418963, year = {2025}, author = {Tyson-Carr, J and Leng, J and Scott, M and Adams, S and Hoptroff, M and Murphy, B and Fallon, N and Paterson, S and Thomas, A and Giesbrecht, T and Roberts, C}, title = {Body-site specific associations between human skin microbiome composition and psychological wellbeing.}, journal = {The British journal of dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1093/bjd/ljaf177}, pmid = {40418963}, issn = {1365-2133}, abstract = {BACKGROUND/OBJECTIVES: There is increasing scientific interest in understanding the interplay between psychological wellbeing and the human microbiome, with a particular focus on the gut microbiome's impact on psychological health. However, the role of the skin microbiome remains underexplored. The current study addresses this gap by investigating the relationship between the human skin microbiome at various body sites (face, scalp, forearm, axilla) and psychological wellbeing. This unique multi body site investigation aims to provide an understanding of the skin microbiome's role in psychological health.<br><br>METHODS: Fifty-three participants underwent microbiome sampling via skin swabbing from four body regions (forearm, face, scalp, and axilla) and completed psychological measures of global/general wellbeing (Affect Grid, Sleep Quality, Stress NRS-11, PSS-10) and body site-related wellbeing (Hair &amp; ScalpCARE, SkinCARE, UnderarmCARE). All bacterial DNA extracts were analysed using quantitative polymerase chain reaction (qPCR) and Illumina sequencing of the V1 - V2 region of the 16S gene. Microbial diversity was computed as Shannon diversity and Faith's Phylogenetic diversity. Correlations were determined between psychological measures, microbial diversity, and genera for each body site.<br><br>RESULTS: The current study uncovered that specific bacterial genera were associated with aspects of wellbeing. Specifically, Cutibacterium showed consistent associations with psychological wellbeing across multiple body locations. Key findings showed increased Cutibacterium on the face and axilla was associated with reduced stress, increased Cutibacterium in the axilla was associated with increased mood pleasantness.<br><br>CONCLUSIONS: These findings highlight, for the first time, the nuanced relationship between skin microbiome and psychological wellbeing. Increased Cutibacterium across multiple body-sites was consistently associated with positive wellbeing outcomes. This underscores the need for further investigation into specific bacterial taxa that may be involved in a skin-brain axis, as well as the importance of specific microbial communities on the body and their potential influence on this connection.}, }
@article {pmid40417982, year = {2025}, author = {Brown, SE and He, X and Magder, L and Johnston, ED and Morgan, D and Ravel, J and Mark, K and Ghanem, KG and Brotman, RM}, title = {Bacterial vaginosis incidence following a single hyperosmolal vaginal lubricant exposure: A comparison of two observational cohorts.}, journal = {Sexually transmitted diseases}, volume = {}, number = {}, pages = {}, pmid = {40417982}, issn = {1537-4521}, support = {R01 AI119012/AI/NIAID NIH HHS/United States ; T32 AG000262/AG/NIA NIH HHS/United States ; UH2 AI083264/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Hyperosmolal lubricants may negatively affect the vaginal microenvironment, increasing the risk for bacterial vaginosis (BV). We compared the incidence of Amsel-defined BV in reproductive-age women exposed to hyperosmolal lubricant during transvaginal ultrasound to those without recent lubricant exposure.<br><br>METHODS: We analyzed two observational cohorts over 10 weeks: 58 lubricant-exposed women from the Gynecology and Lubricants Effects study and 59 lubricant-unexposed women from a University of Alabama Birmingham cohort linked to the University of Maryland Human Microbiome Project. BV was diagnosed using Amsel criteria at baseline, mid-study (lubricant-exposed: week 2, lubricant-unexposed: week 5), and final visit (week 10), and categorized by symptomatology. Risks for incident BV and Amsel criteria were assessed using modified Poisson regression with robust standard errors. An additional outcome of new-onset/newly-symptomatic BV included those with baseline asymptomatic BV. A secondary analysis focused on Black participants (N = 73) due to an observed higher BV incidence.<br><br>RESULTS: Baseline demographics and behaviors were similar between the cohorts. Among all participants, lubricant was not associated with new-onset BV (adjusted relative risk (aRR):1.32, 95% CI:0.58-3.01). 88% (23/26) of all new-onset/newly-symptomatic BV cases occurred in Black participants. Among Black participants, exposure to lubricant doubled the risk of developing new-onset BV (aRR:2.18, 95% CI:1.16-4.11) and new-onset/newly-symptomatic BV (aRR:1.91, 95% CI: 1.04-3.51), and increased the risk for new-onset clue cells (aRR:2.18, 95% CI:1.17 - 4.06) versus no lubricant exposure.<br><br>CONCLUSION: Hyperosmolal lubricants was associated with BV incidence in Black women. Factors contributing to this elevated risk require further research.}, }
@article {pmid40415928, year = {2025}, author = {Karimianghadim, R and Satokari, R and Yeo, S and Arkkila, P and Kao, D and Pakpour, S}, title = {Prolonged effect of antibiotic therapy on the gut microbiota composition, functionality, and antibiotic resistance genes' profiles in healthy stool donors.}, journal = {Frontiers in microbiology}, volume = {16}, number = {}, pages = {1589704}, pmid = {40415928}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is highly effective in preventing Clostridioides difficile recurrence by restoring gut microbiota composition and function. However, the impact of recent antibiotic use, a key exclusion criterion for stool donors, on gut microbiota recovery is poorly understood.<br><br>METHODS: We investigated microbial recovery dynamics following antibiotic use in three long-term stool donors from Canada and Finland. Using longitudinal stool sampling, metagenomic sequencing, and qPCR, we assessed changes in bacterial diversity, community composition, microbial functions, the gut phageome, and the risk of transmitting antibiotic-resistant genes (ARGs).<br><br>RESULTS: Antibiotics caused lasting disruption to bacterial communities, significantly reducing important taxa like Bifidobacterium bifidum, Blautia wexlerae, Akkermansia muciniphila, Eubacterium sp. CAG 180, and Eubacterium hallii, with effects persisting for months. Functional analyses revealed alterations in housekeeping genes critical for energy production and biosynthesis, with no direct links to key health-related pathways. Antibiotics also disrupted viral populations, decreasing diversity and increasing crAssphage abundance, reflecting disrupted host-bacteriophage dynamics. No significant increase in clinically important ARGs was detected.<br><br>DISCUSSION: These findings highlight the unpredictable and complex recovery of gut microbiota post-antibiotics. Individualized suspension periods in donor programs, guided by metagenomic analyses, are recommended to optimize FMT outcomes in various indications by considering antibiotic spectrum, duration, and host-specific factors.}, }
@article {pmid40414632, year = {2025}, author = {Srinivasan, S}, title = {Disruption in the human microbiome causing behavioural changes in bipolar disorder.}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {157-187}, doi = {10.1016/bs.irn.2025.04.001}, pmid = {40414632}, issn = {2162-5514}, mesh = {Humans ; *Bipolar Disorder/microbiology/physiopathology/psychology ; *Gastrointestinal Microbiome/physiology ; *Microbiota/physiology ; }, abstract = {This chapter explores the intriguing and complex relationship between the human microbiome and Bipolar Disorder (BD). The microbiome, notably the gut microbiota, has been increasingly recognised as a key performer in brain health and disease. This is due to its role in the gut-brain axis, a bidirectional communication between the gastrointestinal tract and the central nervous system. Disruptions in the gut microbiota due to factors such as diet, and stress, may influence this axis and potentially trigger or exacerbate psychiatric conditions. Hence, we investigate into the present interpretation of the microbiome's role in mental health, concentrating on its impact on mood regulation and cognitive function. Consequently, we also explore the possible mechanisms through which microbiome disruption may pay to the behavioural changes observed in BD. Further exploration understand the complex interplay between the microbiome and BD and translate these findings into effective therapeutic plans.}, }
@article {pmid40414631, year = {2025}, author = {Krishnan, D and Ghosh, P and Lakshman, N and Justin, A and Ramasamy, S}, title = {Oro-pharyngeal mucosal microbiome alternations causing immune system dysregulation in schizophrenia.}, journal = {International review of neurobiology}, volume = {180}, number = {}, pages = {125-156}, doi = {10.1016/bs.irn.2025.03.003}, pmid = {40414631}, issn = {2162-5514}, mesh = {Humans ; *Schizophrenia/immunology/microbiology ; *Microbiota/immunology/physiology ; *Oropharynx/microbiology/immunology ; *Mouth Mucosa/microbiology/immunology ; }, abstract = {Schizophrenia is a chronic and thoughtful psychological disorder that affects a person's thinking, feelings, and behaviours. Multi-factorial genetic, environmental, and neurological variables cause it. Recently, more research focused on the human microbiome, which alters the immune system and develops adverse health effects on the human body. The study discusses a possible relationship between the oropharyngeal microbiome and schizophrenia. According to recent studies, the oropharyngeal microbiome may alter the immune system in the human body and cause various psychiatric disorders, including schizophrenia. The oropharyngeal microbiome can cause schizophrenia either by affecting the genes, chromosomes, and immune system in the human body. Additionally, it examines the combined mechanism of how the oropharyngeal microbiome's alterations lead to genetic abnormalities and immune dysregulation in schizophrenia. By combining the various approaches, this chapter offers a comprehensive view of the oropharyngeal microbiome's role in schizophrenia and suggests that microbial alterations could serve as biomarkers or therapeutic targets for the disorder.}, }
@article {pmid40411603, year = {2025}, author = {Georgakis, N and Premetis, GE and Pantiora, P and Varotsou, C and Bodourian, CS and Labrou, NE}, title = {The impact of metagenomic analysis on the discovery of novel endolysins.}, journal = {Applied microbiology and biotechnology}, volume = {109}, number = {1}, pages = {126}, pmid = {40411603}, issn = {1432-0614}, support = {4036//HFRI/ ; }, mesh = {*Metagenomics/methods ; *Endopeptidases/genetics/isolation &amp; purification/pharmacology/metabolism ; Bacteriophages/enzymology/genetics ; Anti-Bacterial Agents/pharmacology ; Computational Biology ; Humans ; }, abstract = {Metagenomics has revolutionized enzyme discovery by enabling the study of genetic material directly from environmental samples, bypassing the need for microbial cultivation. This approach is particularly effective for identifying novel endolysins, phage-derived enzymes with antibacterial properties suited for therapeutic and industrial applications. Diverse ecosystems, such as biofilms, human microbiome, hot springs, and geothermal areas, serve as rich reservoirs for endolysins with traits like thermostability, broad-spectrum activity, specificity and resistance to harsh conditions. Functional metagenomics, complemented by bioinformatics, enables the discovery and annotation of previously uncharacterized endolysins. Examples of endolysins discovered from metagenomics analysis are discussed. Despite the challenges of analyzing complex microbial ecosystems and isolating target genes, metagenomics holds immense potential for uncovering innovative endolysins, paving the way for developing new biotechnological applications. KEY POINTS: • Endolysins offer antibacterial potential for therapeutic and industrial use. • Metagenomics enables discovery of novel endolysins from diverse ecosystems. • Advances in tools and methods have accelerated novel endolysins discovery.}, }
@article {pmid40409390, year = {2025}, author = {Mlangeni, T and Jian, C and Häkkinen, HK and de Vos, WM and Salonen, A and Kantele, A}, title = {Travel to the tropics: Impact on gut microbiota.}, journal = {Travel medicine and infectious disease}, volume = {66}, number = {}, pages = {102869}, doi = {10.1016/j.tmaid.2025.102869}, pmid = {40409390}, issn = {1873-0442}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Travel ; Female ; Male ; Feces/microbiology ; Adult ; *Diarrhea/microbiology/epidemiology ; Benin ; Tropical Climate ; RNA, Ribosomal, 16S/genetics ; Young Adult ; Middle Aged ; }, abstract = {BACKGROUND: Visitors to low- and middle-income countries (LMICs) encounter numerous new intestinal microbes, including diarrhoeal pathogens and multidrug-resistant (MDR) bacteria, such as extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE). Consequently, many develop travellers' diarrhoea (TD) and/or become colonised by ESBL-PE. We explored the impact of LMIC travel, TD, and ESBL-PE/diarrheal pathogen colonisation on gut microbiota.<br><br>METHODS: The present study included 92 participants from the clinical vaccine trial OEV123, who spent 12 days in Benin, West Africa, and provided exploratory pre- and post-travel stool microbiota samples. The samples were subjected to quantitative polymerase chain reaction (qPCR) to detect diarrhoeal pathogens and 16S rRNA gene amplicon sequencing for microbiota profiling.<br><br>RESULTS: Travel significantly altered gut microbiota, showing reduced richness, decreased &#x3b1;-diversity, and a 40-fold increase in Escherichia/Shigella. qPCR detected diarrhoeagenic Escherichia coli (DEC) in post-travel stools of 89&#xa0;% of the 92 participants. No specific microbiota signatures were linked to TD or ESBL-PE acquisition. Participants acquiring multiple DEC pathotypes had higher pre-travel levels of Ruminococcaceae and Coprococcus spp., while their post-travel microbiota was enriched with oxygen-tolerant and oral and upper gastrointestinal tract-associated taxa.<br><br>CONCLUSION: Travel to an LMIC significantly impacted intestinal microbiota. Individuals with high pre-travel proportions of Ruminococcaceae and Coprococcus spp. acquired a greater DEC pathotype diversity. However, no specific pre-travel microbiota profile was identified as protective against or predisposing to TD or acquisition of MDR bacteria.}, }
@article {pmid40409379, year = {2025}, author = {Meesters, LD and Roubroeks, JAY and Gerritsen, A and Velthuijs, N and Klijnhout, JA and Laberthonnière, C and van Vlijmen-Willems, IM and Hübenthal, M and Rodijk-Olthuis, D and Peters, RHW and Rikken, G and Szymczak, S and Fyhrquist, N and Alenius, H and Weidinger, S and Smits, JPH and Mhlanga, M and Zhou, H and Niehues, H and van den Bogaard, EH}, title = {Dissecting key contributions of TH2 and TH17 cytokines to atopic dermatitis pathophysiology.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2025.05.007}, pmid = {40409379}, issn = {1097-6825}, abstract = {BACKGROUND: In atopic dermatitis (AD), epidermal disease hallmarks are driven by a complex cutaneous inflammatory milieu that varies between patients. How these variable inflammatory signals affect cellular and molecular epidermal AD phenotypes is difficult to study in vivo.<br><br>OBJECTIVE: We aimed to unravel which AD-associated cytokines drive specific epidermal disease hallmarks.<br><br>METHODS: We utilized primary and immortalized keratinocyte-derived human epidermal equivalents stimulated with TH2, TH17, and TH22 cytokines.<br><br>RESULTS: Morphologic, functional, and transcriptomic analyses revealed that TH2 cytokines IL-4 and IL-13 were the main inducers of a proinflammatory and hyperproliferative epidermis. The presence of IL-17A or IL-22 in the TH2 milieu, and especially TH2 + IL-22, most closely resembled AD hallmarks including spongiosis, more severe keratinocyte differentiation defects, and epidermal barrier dysfunction. Single-cell spatial transcriptomics showed expansion of keratinocytes expressing high levels of proliferation genes and downregulation of differentiation genes in the upper epidermal layers. The transcriptomic comparison to in vivo AD lesional skin indicated that the TH2 + IL-22 AD model demonstrated greatest resemblance and identified AD disease marker genes altered by TH2 + IL-22 such as downregulated ACER1 and AKR1C3. Gene expression levels were restored by combinatory exposure to the aryl hydrocarbon receptor ligand tapinarof and the Janus kinase inhibitor tofacitinib. This combined therapeutic approach also completely restored epidermal barrier function and improved morphologic disease hallmarks.<br><br>CONCLUSION: Our results reveal the important role of IL-22 in the TH2-driven acute AD pathophysiology and highlight the potential of combinatory medicine in targeted treatment of AD.}, }
@article {pmid40401972, year = {2025}, author = {Pitek, AP and Daisley, BA and Chmiel, JA and Chernyshova, AM and Dhami, G and Reid, G and Thompson, GJ}, title = {Probiotic effects on ectoparasitic mite infestations in honey bees (Apis mellifera) are modulated by environmental conditions and route of administration.}, journal = {Microbiology spectrum}, volume = {13}, number = {7}, pages = {e0249824}, pmid = {40401972}, issn = {2165-0497}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; //Ontario Ministry of Agriculture, Food and Rural Affairs/ ; }, mesh = {Animals ; Bees/parasitology/microbiology ; *Probiotics/administration &amp; dosage ; *Varroidae ; *Mite Infestations/veterinary/prevention &amp; control/parasitology ; Paenibacillus larvae ; Larva/microbiology ; }, abstract = {Beneficial bacteria can improve the health of managed honey bees (Apis mellifera) via immune system support as well as direct inhibition of pathogens. However, our understanding of how environmental factors and delivery methods impact treatment outcomes is limited. Here, we evaluated how supplementation of a three-strain lactobacilli consortium (Lactiplantibacillus plantarum Lp39, Apilactobacillus kunkeei BR-1, and Lacticaseibacillus rhamnosus; LX3) affects ectoparasitic mite (Varroa destructor) and bacterial (Paenibacillus larvae) load. We measured this effect following delivery of LX3 in either edible (protein patty) or topical (spray) forms and did so across three distinct habitats (forage-rich, agricultural, and urban). Results demonstrate significant control of mite infestation levels following patty delivery, relative to untreated patty controls. Spray methods, by contrast, were ineffective. Specifically, a control group that received only an uninoculated patty carried more mites than any other group, suggesting excess protein within hives is a catalyst for mite proliferation. This effect, whereby the excess-protein group had the highest parasite load, was pronounced in the most natural (forage-rich) environment type, indicating a significant site-by-treatment interaction. No influence of LX3 on P. larvae loads was observed in the asymptomatic colonies studied, which is likely attributable to the already low levels of pathogenic spores present and challenges associated with detection limits. In summary, this multi-site field study suggests that an LX3-infusion of standard protein patties is an effective method to control Varroa destructor infestations in commercial honey bee colonies.IMPORTANCECommercial beekeeping operations typically have a narrow profit range that depends on maintaining healthy hives throughout the season. Unfortunately, parasitic Varroa mites and bacterial pathogens can contribute to colony losses. The plight of honey bees can in turn affect the price and availability of produce on the agri-food market. There is therefore a need for innovation in the beekeeping industry to help secure bee livestock from season to season. One relatively new approach to sustainable beekeeping is the use of beneficial bacterial supplements that beekeepers can feed to or otherwise apply to hives in aid of the bee's natural health and abilities as mediated through their gut-brain axis. Our multi-site field study applies this approach. We find that a pollen protein patty is an effective vehicle for delivering probiotic bacteria to commercial honey bee colonies and for helping to keep Varroa destructor infestation levels in check.}, }
@article {pmid40398637, year = {2025}, author = {Alaguthevar, R and Pawale, AV and Murugesan, B and Khan, A and Rhim, JW and Chelladurai, D}, title = {Comprehensive review of food Archaeome: Exploring the understudied microbiome and health benefits of fermented foods.}, journal = {Microbial pathogenesis}, volume = {205}, number = {}, pages = {107718}, doi = {10.1016/j.micpath.2025.107718}, pmid = {40398637}, issn = {1096-1208}, mesh = {*Archaea/genetics/pathogenicity/classification ; Humans ; *Fermented Foods/microbiology ; *Food Microbiology ; *Microbiota ; Gastrointestinal Microbiome ; }, abstract = {Extremophiles are species that thrive optimally in extreme environmental conditions, and advances in DNA-based identification methods have sparked increased interest in studying the dynamic ecosystem of archaea outside their harsh environmental niches. Most studies on the food microbiome have primarily focused on bacterial and fungal communities. In contrast, food archaea play an essential role in human-related foods, despite being largely ignored and understudied. Archaea can survive, colonize, and thrive under harsh processing conditions in food manufacturing, and they can enter the human body and modulate the human microbiome. Additionally, gut microbiomes can be influenced through vertical transmission facilitated by breast milk, organic animal products, and salty fermented foods. Early studies on foods concentrated mostly on salty and fermented items because these foods represent extreme environments. However, gut-associated archaea may be linked to disease as they produce toxic compounds and detoxify pathogen growth inhibitors. The precise mechanisms by which this pathogenicity occurs are still unknown, and further studies are necessary to illuminate potential human health implications. Despite the growing understanding of the prevalence of archaeal pathogens in extreme environments, current research on food-related archaeal communities remains limited. This review emphasizes the role of food archaeal pathogens in human health and describes new technologies for producing novel nutritious foods utilizing archaeal-derived materials in the food industry.}, }
@article {pmid40396735, year = {2025}, author = {Zhang, J and Chen, B-Y and Zhi, M-F and Lin, W-Z and Li, Y-L and Ye, H-L and Xu, S and Zhu, H and Zhou, L-J and Du, L-J and Meng, X-Q and Liu, Y and Feng, Q and Duan, S-Z}, title = {Linking oral microbiota to periodontitis and hypertension unveils that Filifactor alocis aggravates hypertension via infiltration of interferon-γ[+] T cells.}, journal = {mSystems}, volume = {10}, number = {6}, pages = {e0008425}, pmid = {40396735}, issn = {2379-5077}, support = {82330015,81991503,81991500//National Natural Science Foundation of China/ ; 2023YFA1801100,2023YFA1801104//National Key Research and Development Program of China/ ; BX20230226//China National Postdoctoral Program for Innovative Talents/ ; SHSMU-ZDCX20212500//Innovative Research Team of High-level Local University in Shanghai (Innovative Research Team of High-level Local Universities in Shanghai)/ ; }, mesh = {*Hypertension/microbiology/immunology/complications ; *Periodontitis/microbiology/complications/immunology ; Humans ; Animals ; *Interferon-gamma/metabolism ; *Microbiota ; Male ; Mice ; Female ; Middle Aged ; *Clostridiales ; *T-Lymphocytes/immunology/metabolism ; *Mouth/microbiology ; Saliva/microbiology ; Disease Models, Animal ; }, abstract = {UNLABELLED: Periodontal disease (PD), an inflammatory disease initiated by oral microbiota, may aggravate hypertension (HTN). Few studies were employed to characterize the oral microbiota in hypertensive patients with periodontitis. To investigate the interplay between oral microbiota and hypertension in individuals with periodontitis, we initiated a metagenomic sequencing study on subgingival plaque and saliva samples sourced from HTN patients and those with hypertension and periodontitis (PDHTN). Our primary objective was to characterize species serving as pivotal links (bridge species) in exacerbating hypertension induced by periodontal disease. Within subgingival plaque and saliva specimens, we pinpointed 31 and 28 bridge species, respectively. Furthermore, we noted a decrease in the abundance of nitrate-reducing bacteria, such as Actinomyces spp., Rothia spp., and Veillonella spp., in PDHTN samples. Employing network analysis, we distinguished distinct polymicrobial clusters within the two patient groups. These bridge species coalesced into polymicrobial clusters, revealing intricate symbiotic and competitive relationships. To substantiate our findings, we leveraged an angiotensin II-infused animal model of ligature-induced periodontitis (LIP), confirming the contributory role of Filifactor alocis-a selectively analyzed subgingival bridge species-in exacerbating hypertension and upregulating the frequency of renal CD4[+]IFNγ[+] and CD8[+]IFNγ[+] T cells. Our study screened a list of species linking PD and HTN. PD may aggravate HTN by decreasing the abundance of nitrate-reducing bacteria and increasing the abundance of pathogens. Using an animal model, we demonstrated that F. alocis aggravates HTN via the accumulation of IFNγ[+] T cells in the kidneys.<br><br>IMPORTANCE: Both periodontal disease and hypertension are widely prevalent all over the world. PD may aggravate the development of HTN via oral microbiota. However, few studies were employed to characterize the oral microbiota in hypertensive patients with periodontitis. Here, the present study profiled the oral microbiota in hypertensive participants with periodontitis. We found that the depleted abundance of nitrate-reducing bacteria and the enriched abundance of pathogens. Finally, we validated the role of Filifactor alocis in exacerbating HTN via infiltration of IFN&#x3b3;[+] T cells in mice kidneys. Our study improved the understanding of oral microbiota linking PD and HTN.}, }
@article {pmid40386394, year = {2025}, author = {Chiu, CJ and Chiu, E and Chang, ML}, title = {Interaction between Infection of Porphyromonas gingivalis, A Keystone Microbe of Oral Microbiome, and Serum Levels of Lutein/Zeaxanthin Is Associated with Risk for Age-related Macular Degeneration.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {40386394}, issn = {2693-5015}, support = {R01 EY021826/EY/NEI NIH HHS/United States ; R21 EY028209/EY/NEI NIH HHS/United States ; }, abstract = {UNLABELLED: Porphyromonas gingivalis (P. gingivalis) functions as a catalyst bacterium in the development of periodontitis, and the serum antibody level against P. gingivalis is considered a surrogate marker for the activity level of periodontopathic microbiome. The chronic systemic inflammation induced by P. gingivalis elevates the risk of various systemic and neurodegenerative disorders, including atherosclerosis, diabetes, and Alzheimer's disease. Although the connection between human microbiome and age-related macular degeneration (AMD) remains relatively unexplored, it is noteworthy that AMD shares risk factors and etiological mechanisms with diseases related to P. gingivalis. To investigate the potential association between periodontopathic microbiome and AMD occurrence, we conducted a candidate microbe approach case-control study. Our hypothesis was tested by examining the correlation between serum P. gingivalis immunoglobulin G (IgG) levels and AMD. Comparing the lowest IgG category (≤ 57 enzyme-linked immunosorbent assay units (EU)) with higher categories revealed escalating risks: the second higher category (58-65 EU) conferred almost a 30% increased risk (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.17 to 1.4), the third higher category (66-119 EU) conferred nearly a 60% increase (OR = 1.58, 95% CI: 1.46 to 1.72), and the highest category (> 119 EU) conveyed over a two-fold risk (OR = 2.04, 95% CI: 1.62 to 2.58) of early AMD. Aligning with the notion that the microbiome composition is significantly shaped by the host's diet, our analysis indicates that sustaining elevated serum levels of lutein/zeaxanthin (≥ 0.35 μmol/L or ≥ 20 μg/dL) might potentially mitigate the P. gingivalis-related AMD risk by as much as 35% (P for interaction < 0.0001). Although the precise mechanism requires additional exploration, these findings suggest a connection between nutrition and oral microbiome, emphasizing their collective role in maintaining eye health.<br><br>SIGNIFICANCE STATEMENT: While our oral microbiome may impact eye health, nutritional factors could play a modulatory role in mitigating the associated risk.}, }
@article {pmid40381618, year = {2025}, author = {Kim, M and Kim, J and Lee, GS and Olinares, PDB and Airan, Y and Chow, JL and Park, J and Jeong, Y and Park, J and Chait, BT and Herzon, SB and Kim, CS and Kang, JY}, title = {Structural study on human microbiome-derived polyketide synthases that assemble genotoxic colibactin.}, journal = {Structure (London, England : 1993)}, volume = {33}, number = {7}, pages = {1208-1223.e5}, doi = {10.1016/j.str.2025.04.017}, pmid = {40381618}, issn = {1878-4186}, mesh = {Humans ; *Polyketide Synthases/chemistry/metabolism ; *Peptides/metabolism/chemistry ; *Polyketides/metabolism/chemistry ; Cryoelectron Microscopy ; Binding Sites ; Peptide Synthases/metabolism/chemistry ; Protein Binding ; *Bacterial Proteins/chemistry/metabolism ; Models, Molecular ; Microbiota ; Molecular Docking Simulation ; }, abstract = {Colibactin, a human microbiome-derived genotoxin, promotes colorectal cancer by damaging the host gut epithelial genomes. While colibactin is synthesized via a hybrid non-ribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) pathway, known as pks or clb, the structural details of its biosynthetic enzymes remain limited, hindering our understanding of its biosynthesis and clinical application. In this study, we report the cryo-EM structures of two colibactin-producing PKS enzymes, ClbC and ClbI, captured in different reaction states using a substrate-mimic crosslinker. Our structural analysis revealed the binding sites of carrier protein (CP) domains of the ClbC and ClbI on their ketosynthase (KS) domains. Further, we identified a novel NRPS-PKS docking interaction between ClbI and its upstream enzyme, ClbH, mediated by the C-terminal peptide ClbH and the dimeric interface of ClbI, establishing a 1:2 stoichiometry. These findings advance our understanding of colibactin assembly line and provide broader insights into NRPS-PKS natural product biosynthesis mechanisms.}, }
@article {pmid40381485, year = {2025}, author = {Hartjes, ED and Lim, YJ and Velenosi, TJ and Al, KF and Macklaim, JM and Kucey, AS and Reid, G and Burton, JP and Gloor, GB and Urquhart, BL}, title = {The impact of progressive chronic kidney disease on hepatic drug metabolism.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {53}, number = {6}, pages = {100085}, pmid = {40381485}, issn = {1521-009X}, mesh = {Animals ; *Renal Insufficiency, Chronic/metabolism ; Rats ; Male ; *Liver/metabolism ; Gastrointestinal Microbiome/physiology ; Dysbiosis/metabolism ; Rats, Sprague-Dawley ; Disease Progression ; Cytochrome P450 Family 2/metabolism ; Steroid 16-alpha-Hydroxylase/metabolism ; Uremia/metabolism ; Uremic Toxins/metabolism ; Adenine ; Metabolome ; Cytochrome P-450 Enzyme System/metabolism ; Aryl Hydrocarbon Hydroxylases ; }, abstract = {Nonrenal clearance pathways such as drug metabolism are decreased in severe chronic kidney disease (CKD). The impact of progression of CKD on hepatic drug metabolism is unknown. We characterized the effect of progressive CKD on hepatic cytochrome P450 expression and evaluated dysbiosis and uremia as kidney function declined. Rats fed control or CKD-inducing adenine diet were studied at 5 time points over 42 days. Cytochrome P450 expression and activity were compared with alterations in the (1) plasma and liver metabolome and (2) gut bacterial microbiota. CYP3A2 and CYP2C11 were downregulated in CKD by ≥76% (P < .001) concurrently with or slightly prior to CKD onset as defined by serum creatinine. Metabolite profiles were altered prior to changes in the gut microbiota, and gut-derived uremic toxins including indoxyl sulfate, phenyl sulfate, and 4-ethylphenyl sulfate correlated with CYP3A2 or CYP2C11 expression. Bacterial genera Turicibacter and Parabacteroides were identified as being characteristic of CKD. In conclusion, CYP3A2 and CYP2C11 are downregulated before dysbiosis and uremia. SIGNIFICANCE STATEMENT: This study describes the effect of progressive kidney disease on hepatic CYP2C11 and CYP3A2 enzyme expression and activity in a rat model of CKD. Expression and activity of drug metabolizing enzymes occurs prior to uremia or dysbiosis.}, }
@article {pmid40378286, year = {2025}, author = {Fields, BD and Pascal, DG and Rando, OK and Huddleston, ME and Ingram, K and Hopton, R and Grogg, MW and Nelson, MT and Voigt, CA}, title = {Design of a Continuous GAA-Producing Probiotic as a Potential Mitigator of the Effects of Sleep Deprivation.}, journal = {ACS synthetic biology}, volume = {14}, number = {6}, pages = {1963-1976}, doi = {10.1021/acssynbio.4c00690}, pmid = {40378286}, issn = {2161-5063}, mesh = {*Probiotics/metabolism ; *Escherichia coli/genetics/metabolism ; Humans ; *Glycine/analogs &amp; derivatives/metabolism/biosynthesis ; *Sleep Deprivation ; Metabolic Engineering/methods ; Actinobacteria/enzymology/genetics ; Bacterial Proteins/genetics/metabolism ; }, abstract = {Creatine is a popular athletic supplement that has also been shown to improve cognitive performance upon sleep deprivation. However, it is rapidly cleared from the gastrointestinal tract a few hours after consumption. Toward providing a persistent creatine dose, we engineered the human probiotic Escherichia coli Nissle (EcN) to produce guanidinoacetic acid (GAA), which is converted to creatine in the liver. We find GAA-producing enzymes present in the human microbiome and compare their activities to known enzymes. Three copies of arginine:glycine amidinotransferase (AGAT) from Actinokineospora terrae are expressed from the genome, and native gcvP, argR, and argA are edited or deleted to improve substrate availability without negatively impacting cell viability. A standard EcN dose (10[12] cells) produces 41 ± 7 mg GAA per hour under laboratory conditions. This work demonstrates that a probiotic bacterium can be engineered to produce sustained GAA titers known to impact cognitive performance.}, }
@article {pmid40377870, year = {2025}, author = {Amen, RA and Hassan, YM and Essmat, RA and Ahmed, RH and Azab, MM and Shehata, NR and Elgazzar, MM and El-Sayed, WM}, title = {Harnessing the Microbiome: CRISPR-Based Gene Editing and Antimicrobial Peptides in Combating Antibiotic Resistance and Cancer.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {40377870}, issn = {1867-1314}, abstract = {The growing crisis of antibiotic resistance and the increasing incidence of cancer have prompted the exploration of innovative approaches, such as gene editing and antimicrobial peptides (AMPs). The human microbiome is integral to various aspects of health, disease, and therapeutic development, influencing metabolic pathways, immune function, and pathogen resistance. Recent advances in gene editing technologies, particularly CRISPR (clustered regularly interspaced short palindromic repeats), have opened new avenues for leveraging the microbiome to address complex medical challenges, including combating multidrug-resistant pathogens and cancer. The microbiome plays a crucial role in combating antibiotic resistance by modulating microbial communities, influencing pathogen survival and susceptibility to treatments. This review explores the microbiome's dynamic role in metabolic regulation, its contribution to cancer management, and how AMPs help maintain homeostasis and exhibit emerging anticancer properties, supported by both preclinical findings and clinical evidence. Additionally, CRISPR-based microbiome engineering offers potential to enhance host-microbiome interactions, optimizing therapeutic outcomes. The integration of microbiome metagenomics and proteomics has led to the discovery of novel AMPs with targeted anticancer effects. Innovative strategies, such as engineered probiotics and CRISPR-based microbiome engineering, present exciting prospects for next-generation therapies. Despite these advances, the translation of microbiome-based therapies into clinical settings remains challenging due to ethical, regulatory, and ecological hurdles. This review underscores the transformative potential of microbiome-based interventions, emphasizing the role of personalized medicine in maximizing therapeutic efficacy. Furthermore, we also address critical research gaps, limitations, and future directions, including optimizing AMP stability, delivery, and bioavailability, as well as overcoming the regulatory and ethical challenges in clinical translation.}, }
@article {pmid40375898, year = {2025}, author = {Xu, C and Zhao, LY and Ye, CS and Xu, KC and Xu, KY}, title = {The application of machine learning in clinical microbiology and infectious diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1545646}, pmid = {40375898}, issn = {2235-2988}, mesh = {Humans ; *Machine Learning ; *Communicable Diseases/diagnosis/microbiology ; *Microbiology ; Artificial Intelligence ; Algorithms ; }, abstract = {With the development of artificial intelligence(AI) in computer science and statistics, it has been further applied to the medical field. These applications include the management of infectious diseases, in which machine learning has created inroads in clinical microbiology, radiology, genomics, and the analysis of electronic health record data. Especially, the role of machine learning in microbiology has gradually become prominent, and it is used in etiological diagnosis, prediction of antibiotic resistance, association between human microbiome characteristics and complex host diseases, prognosis judgment, and prevention and control of infectious diseases. Machine learning in the field of microbiology mainly adopts supervised learning and unsupervised learning, involving algorithms from classification and regression to clustering and dimensionality reduction. This Review explains crucial concepts in machine learning for unfamiliar readers, describes machine learning's current applications in clinical microbiology and infectious diseases, and summarizes important approaches clinicians must be aware of when evaluating research using machine learning.}, }
@article {pmid40371892, year = {2025}, author = {Metris, A and Walker, AW and Showering, A and Doolan, A and McBain, AJ and Ampatzoglou, A and Murphy, B and O'Neill, C and Shortt, C and Darby, EM and Aldis, G and Hillebrand, GG and Brown, HL and Browne, HP and Tiesman, JP and Leng, J and Lahti, L and Jakubovics, NS and Hasselwander, O and Finn, RD and Klamert, S and Korcsmaros, T and Hall, LJ}, title = {Assessing the safety of microbiome perturbations.}, journal = {Microbial genomics}, volume = {11}, number = {5}, pages = {}, pmid = {40371892}, issn = {2057-5858}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Microbiota/genetics ; Gastrointestinal Microbiome ; Skin/microbiology ; Mouth/microbiology ; }, abstract = {Everyday actions such as eating, tooth brushing or applying cosmetics inherently modulate our microbiome. Advances in sequencing technologies now facilitate detailed microbial profiling, driving intentional microbiome-targeted product development. Inspired by an academic-industry workshop held in January 2024, this review explores the oral, skin and gut microbiomes, focussing on the potential long-term implications of perturbations. Key challenges in microbiome safety assessment include confounding factors (ecological variability, host influences and external conditions like geography and diet) and biases from experimental measurements and bioinformatics analyses. The taxonomic composition of the microbiome has been associated with both health and disease, and perturbations like regular disruption of the dental biofilm are essential for preventing caries and inflammatory gum disease. However, further research is required to understand the potential long-term impacts of microbiome disturbances, particularly in vulnerable populations including infants. We propose that emerging technologies, such as omics technologies to characterize microbiome functions rather than taxa, leveraging artificial intelligence to interpret clinical study data and in vitro models to characterize and measure host-microbiome interaction endpoints, could all enhance the risk assessments. The workshop emphasized the importance of detailed documentation, transparency and openness in computational models to reduce uncertainties. Harmonisation of methods could help bridge regulatory gaps and streamline safety assessments but should remain flexible enough to allow innovation and technological advancements. Continued scientific collaboration and public engagement are critical for long-term microbiome monitoring, which is essential to advancing safety assessments of microbiome perturbations.}, }
@article {pmid40371708, year = {2025}, author = {Attaye, I and Bird, JK and Nieuwdorp, M and Gül, S and Seegers, JFML and Morrison, S and Hofkens, S and Herrema, H and Bui, N and Puhlmann, ML and de Vos, WM}, title = {Anaerobutyricum soehngenii improves glycemic control and other markers of cardio-metabolic health in adults at risk of type 2 diabetes.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2504115}, pmid = {40371708}, issn = {1949-0984}, mesh = {Humans ; *Diabetes Mellitus, Type 2/metabolism/microbiology/prevention &amp; control ; Middle Aged ; Male ; Female ; Double-Blind Method ; *Glycemic Control ; Adult ; Glycated Hemoglobin/analysis/metabolism ; Blood Glucose/metabolism ; Aged ; Prediabetic State/therapy ; Biomarkers/blood ; Blood Pressure ; Gastrointestinal Microbiome ; Europe ; }, abstract = {Anaerobutyricum soehngenii (previously Eubacterium hallii) is a butyrate-producing next-generation beneficial microbe generally recognized as safe. Several short-term intervention trials by A. soehngenii L2-7 have shown improvement of insulin sensitivity in prediabetic subjects and type 2 diabetes patients. To determine the long-term cardiometabolic benefits and safety, we performed a 3-month double-blind, randomized placebo-controlled intervention in 98 prediabetic insulin-resistant adults in Europe and U.S. with daily administration of encapsulated cells of A. soehngenii CH-106, a tetracycline-sensitive isogenic derivative of strain L2-7. Compared to placebo, A. soehngenii-treated subjects showed significantly reduced glycemic variability (1% reduction in the coefficient of variation; p = 0.01) and improved glycemic control (6% reduction in the overall net glycemic action-1; p < 0.05), including reduced serum glycated hemoglobin (HbA1c) levels when including the 4-week washout period (1 mmol/mol reduction; p < 0.05). Moreover, diastolic blood pressure was significantly reduced in all A. soehngenii-treated subjects (3 mm Hg; p < 0.05). The study product was well-tolerated and had no effect on the global intestinal microbiota composition, including alpha and beta-diversity, besides an increased abundance of A. soehngenii in the treatment group, indicative of compliance. The U.S. participants, compared to those in Europe, responded best, notably in the oral glucose tolerance tests (15% improvement in the area-under-the curve of plasma glucose levels; p = 0.039) or coefficient of variation (reduction of 3.1%; p < 0.05). This potentially relates to a more severe prediabetic state in U.S. subjects, associated with significantly reduced (1.5-3.5-fold) relative abundance of Bifidobacterium, Coprococcus, Ruminococcus spp. and two-fold increased relative abundance of Lachnoclostridium spp. In conclusion, daily oral supplementation with A. soehngenii was safe and improved various markers of glycemic control, reduced HbA1c levels and diastolic blood pressure, indicating a novel microbiome-based approach to improve cardio-metabolic health in adults at risk for developing type 2 diabetes.Clinical trial reg. no. NCT04529473, clinicaltrials.govSocial media summary 120 characters: Anaerobutyricum soehngenii supplementation improves #cardio-metabolic health in subjects at risk for type 2 #diabetes.}, }
@article {pmid40371158, year = {2025}, author = {Liu, Y and Ning, H and Li, Y and Li, Y and Ma, J}, title = {The microbiota in breast cancer: dysbiosis, microbial metabolites, and therapeutic implications.}, journal = {American journal of cancer research}, volume = {15}, number = {4}, pages = {1384-1409}, pmid = {40371158}, issn = {2156-6976}, abstract = {The human microbiome plays a pivotal role in host health and disease, with emerging evidence underscoring its significant influence on the development and progression of breast cancer. Studies have revealed that dysbiosis in both the gut and breast tissue microbiota is strongly associated with an elevated risk of breast cancer. Distinct microbial profiles have been identified among healthy individuals, patients with benign breast conditions, and those with malignant tumors, with further variations observed across different ethnic groups and breast cancer subtypes. The complex interplay between breast cancer risk factors and microbial populations, coupled with the direct impact of microbial communities and their metabolites on inflammatory pathways and immune responses, underscores the importance of this field. Additionally, the interaction between gut microbiota and therapeutic modalities such as chemotherapy and radiotherapy is of particular interest, as these interactions can significantly influence treatment outcomes, either enhancing or diminishing efficacy. This review explores the effects of the Mediterranean diet, probiotics, prebiotics, and natural medicinal products on gut microbiota, emphasizing their potential as innovative therapeutic strategies. Notably, the use of engineered probiotics within the tumor microenvironment represents a promising frontier in breast cancer treatment. In conclusion, research on the human microbiome not only deepens our understanding of breast cancer pathogenesis but also lays the groundwork for the development of novel and targeted therapeutic interventions.}, }
@article {pmid40370098, year = {2025}, author = {Wang, N and Wu, M and Gu, W and Dai, C and Shao, Z and Subbalakshmi, KP}, title = {MSFT-transformer: a multistage fusion tabular transformer for disease prediction using metagenomic data.}, journal = {Briefings in bioinformatics}, volume = {26}, number = {3}, pages = {}, pmid = {40370098}, issn = {1477-4054}, support = {JUSRP123035//Fundamental Research Funds for the Central Universities/ ; }, mesh = {*Metagenomics/methods ; Humans ; *Metagenome ; *Computational Biology/methods ; Algorithms ; }, abstract = {More and more recent studies highlight the crucial role of the human microbiome in maintaining health, while modern advancements in metagenomic sequencing technologies have been accumulating data that are associated with human diseases. Although metagenomic data offer rich, multifaceted information, including taxonomic and functional abundance profiles, their full potential remains underutilized, as most approaches rely only on one type of information to discover and understand their related correlations with respect to disease occurrences. To address this limitation, we propose a multistage fusion tabular transformer architecture (MSFT-Transformer), aiming to effectively integrate various types of high-dimensional tabular information extracted from metagenomic data. Its multistage fusion strategy consists of three modules: a fusion-aware feature extraction module in the early stage to improve the extracted information from inputs, an alignment-enhanced fusion module in the mid stage to enforce the retainment of desired information in cross-modal learning, and an integrated feature decision layer in the late stage to incorporate desired cross-modal information. We conduct extensive experiments to evaluate the performance of MSFT-Transformer over state-of-the-art models on five standard datasets. Our results indicate that MSFT-Transformer provides stable performance gains with reduced computational costs. An ablation study illustrates the contributions of all three models compared with a reference multistage fusion transformer without these novel strategies. The result analysis implies the significant potential of the proposed model in future disease prediction with metagenomic data.}, }
@article {pmid40369669, year = {2025}, author = {Purse, C and Parker, A and James, SA and Baker, DJ and Moss, CJ and Evans, R and Durham, J and Funnell, SGP and Carding, SR}, title = {Intestinal microbiota profiles of captive-bred cynomolgus macaques reveal influence of biogeography and age.}, journal = {Animal microbiome}, volume = {7}, number = {1}, pages = {47}, pmid = {40369669}, issn = {2524-4671}, support = {BB/T008717/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1//BBSRC/ ; }, abstract = {BACKGROUND: Age-associated changes to the intestinal microbiome may be linked to inflammageing and the development of age-related chronic diseases. Cynomolgus macaques, a common animal model in biomedical research, have strong genetic physiological similarities to humans and may serve as beneficial models for the effect of age on the human microbiome. However, age-associated changes to their intestinal microbiome have previously only been investigated in faecal samples. Here, we have characterised and investigated the effects of age in the cynomolgus macaque intestinal tract in luminal samples from both the small and large intestine.<br><br>RESULTS: Whole metagenomic shotgun sequencing was used to analyse the microbial communities in intestinal content obtained from six different intestinal regions, covering the duodenum to distal colon, of 24 healthy, captive-bred cynomolgus macaques, ranging in age from 4 to 20&#xa0;years. Both reference-based and assembly-based computational profiling approaches were used to analyse changes to intestinal microbiota composition and metabolic potential associated with intestinal biogeography and age. Reference-based computational profiling revealed a significant and progressive increase in both species richness and evenness along the intestinal tract. The microbial community composition also significantly differed between the small intestine, caecum, and colon. Notably, no significant changes in the taxonomic abundance of individual taxa with age were found except when sex was included as a covariate. Additionally, using an assembly-based computational profiling approach, 156 putative novel bacterial and archaeal species were identified.<br><br>CONCLUSIONS: We observed limited effects of age on the composition of the luminal microbiota in the profiled regions of the intestinal tract except when sex was included as a covariate. The enteric microbial communities of the small and the large intestine were, however, distinct, highlighting the limitations of frequently used faecal microbial profiling as a proxy for the intestinal microbiota. The identification of a number of putative novel microbial taxa contributes to knowledge of the full diversity of the cynomolgus macaque intestinal microbiome.}, }
@article {pmid40369630, year = {2025}, author = {Dong, R and Li, M and Gu, XF and Gao, H and Wei, Z and Qi, H and Zhang, J and Feng, Q}, title = {The surface protein Gbp of Fusobacterium nucleatum inhibits osteogenic differentiation by inactivating the Wnt/β-catenin pathway via binding to Annexin A2.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {540}, pmid = {40369630}, issn = {1479-5876}, support = {82270980//National Natural Science Foundation of China/ ; 82071122//National Natural Science Foundation of China/ ; the National Clinical Key Specialty (Periodontology) Construction Project//the National Clinical Key Specialty (Periodontology) Construction Project/ ; the National Young Scientist Support Foundation (2019)//the National Young Scientist Support Foundation (2019)/ ; 2021GXRC021//Periodontitis innovation team of Jinan City/ ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; 2021ZDSYS18//Shandong Province Key Research and Development Program/ ; }, mesh = {*Osteogenesis/genetics/drug effects ; *Wnt Signaling Pathway ; Humans ; *Annexin A2/metabolism ; Animals ; *Cell Differentiation/genetics ; *Fusobacterium nucleatum/metabolism ; Osteoblasts/metabolism/pathology ; Protein Binding ; *Bacterial Proteins/metabolism ; Mice ; Male ; Periodontitis/pathology/microbiology/genetics ; Protein Interaction Maps/genetics ; Mice, Inbred C57BL ; Mesenchymal Stem Cells/metabolism ; Cell Proliferation ; beta Catenin/metabolism ; }, abstract = {BACKGROUND: Periodontitis is a chronic inflammatory disease that significantly impacts periodontal bone regeneration, yet the distinct biological features of osteoblasts in this condition remain poorly understood. This study aims to elucidate the cellular and molecular mechanisms underlying osteoblast dysfunction in periodontitis, with a focus on the role of Fusobacterium nucleatum (Fn) and its effector protein, D-galactose-binding periplasmic protein (Gbp).<br><br>METHOD: Single-cell RNA sequencing (scRNA-seq) data from human gingival tissues of periodontitis patients (PD) and healthy controls (HC) were analyzed to identify cellular heterogeneity and molecular pathways. An experimental periodontitis model in mice and primary osteoblast cultures were used to investigate the effects of Fn and Gbp on osteogenic differentiation. Transcriptomic analysis, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks were employed to explore the underlying mechanisms.<br><br>RESULTS: scRNA-seq revealed a reduction in mesenchymal stem cells (MSCs) and osteoblastic lineage cells in PD tissues, with significant downregulation of osteogenic pathways such as Wnt signaling. Fn infection induced alveolar bone destruction in vivo and inhibited osteoblast proliferation, differentiation, and mineralization in vitro. Gbp, an Fn adhesin, similarly impaired osteogenic differentiation by downregulating key osteogenic genes and pathways. Transcriptomic analysis identified shared inflammatory and osteogenic pathways affected by Fn and Gbp, with NF-&#x3ba;B signaling activated and Wnt/&#x3b2;-catenin signaling inhibited. Mechanistically, Gbp interacted with the host protein ANXA2, disrupting the ANXA2/GSK3&#x3b2; complex and inhibiting Wnt/&#x3b2;-catenin signaling, a pivotal route for osteoblast differentiation. ANXA2 knockdown mitigated the Fn/Gbp-induced suppression of osteogenic activity, emphasizing its role in Fn-induced bone loss.<br><br>CONCLUSION: This study demonstrates that Fn and its effector Gbp disrupt osteogenic differentiation by inactivating the Wnt/&#x3b2;-catenin pathway binding to ANXA2.}, }
@article {pmid40362812, year = {2025}, author = {Cominelli, G and Sulas, F and Pinto, D and Rinaldi, F and Favero, G and Rezzani, R}, title = {Neuro-Nutritional Approach to Neuropathic Pain Management: A Critical Review.}, journal = {Nutrients}, volume = {17}, number = {9}, pages = {}, pmid = {40362812}, issn = {2072-6643}, support = {Grant donation//Franchini Acciai S.p.A./ ; }, mesh = {Humans ; *Neuralgia/diet therapy/therapy ; *Melatonin/administration &amp; dosage/therapeutic use ; Antioxidants/administration &amp; dosage ; *Pain Management/methods ; Dietary Supplements ; Quality of Life ; *Diet ; Oxidative Stress ; }, abstract = {Pain is a significant global public health issue that can interfere with daily activities, sleep, and interpersonal relationships when it becomes chronic or worsens, ultimately impairing quality of life. Despite ongoing efforts, the efficacy of pain treatments in improving outcomes for patients remains limited. At present, the challenge lies in developing a personalized care and management plan that helps to maintain patient activity levels and effectively manages pain. Neuropathic pain is a chronic condition resulting from damage to the somatosensory nervous system, significantly impacting quality of life. It is partly thought to be caused by inflammation and oxidative stress, and clinical research has suggested a link between this condition and diet. However, these links are not yet well understood and require further investigation to evaluate the pathways involved in neuropathic pain. Specifically, the question remains whether supplementation with dietary antioxidants, such as melatonin, could serve as a potential adjunctive treatment for neuropathic pain modulation. Melatonin, primarily secreted by the pineal gland but also produced by other systems such as the digestive system, is known for its anti-inflammatory, antioxidant, and anti-aging properties. It is found in various fruits and vegetables, and its presence alongside other polyphenols in these foods may enhance melatonin intake and contribute to improved health. The aim of this review is to provide an overview of neuropathic pain and examine the potential role of melatonin as an adjunctive treatment in a neuro-nutritional approach to pain management.}, }
@article {pmid40362760, year = {2025}, author = {Sechi, A and Cedirian, S and Brunetti, T and Quadrelli, F and Torres, F and Tosti, A and Rinaldi, F and Pinto, D and Bolognino, R and Marzano, AV and Piraccini, BM}, title = {Safety First: A Comprehensive Review of Nutritional Supplements for Hair Loss in Breast Cancer Patients.}, journal = {Nutrients}, volume = {17}, number = {9}, pages = {}, pmid = {40362760}, issn = {2072-6643}, mesh = {Humans ; *Dietary Supplements/adverse effects ; *Breast Neoplasms/therapy/drug therapy/complications ; Female ; *Alopecia/etiology/chemically induced/drug therapy/prevention &amp; control ; Antioxidants/adverse effects/administration &amp; dosage ; Quality of Life ; Vitamin D/adverse effects/administration &amp; dosage ; }, abstract = {Among the distressing side effects of cancer treatments, hair loss is one of the most disturbing for the quality of life and adherence to therapy in breast cancer patients. Many patients take nutritional supplements to prevent hair loss or enhance regrowth. Based on their mechanism and timing of use, nutritional supplements could be divided into safe, cautious, debated, and contraindicated categories. Non-contraindicated supplements generally include safe supplements like vitamin D, which is not known to interfere with cancer treatments. Those that are contraindicated include phytoestrogens and compounds affecting estrogen pathways because of the risk of stimulating tumor growth in cancers sensitive to estrogen. Antioxidants like tocotrienols and resveratrol are given judiciously because of potential interference with cancer therapies dependent on reactive oxygen species. Supplements debated, including nicotinamide, folate, and iron, pose a risk by promoting cellular proliferation or altering the tumor microenvironment. Biotin is nontoxic but interferes with blood test results and is thus difficult in cancer monitoring. Evidence regarding nutritional supplements' safety and efficacy in this context is conflicting. Management by an oncologist is required along with more studies to clearly establish the safety parameters and efficacy guidelines.}, }
@article {pmid40359847, year = {2025}, author = {Liu, S and Ao, C and Li, Z and Chio, LH and Gu, Y and Zhan, H and Li, H and Li, H and Li, Z and Wang, Q}, title = {Development and validation of a polysomnography-based nomogram for predicting amnestic mild cognitive impairment in middle-aged and elderly people.}, journal = {Sleep medicine}, volume = {132}, number = {}, pages = {106564}, doi = {10.1016/j.sleep.2025.106564}, pmid = {40359847}, issn = {1878-5506}, mesh = {Humans ; *Cognitive Dysfunction/diagnosis ; *Nomograms ; Male ; Female ; *Polysomnography/methods ; Aged ; Middle Aged ; *Amnesia/diagnosis ; ROC Curve ; }, abstract = {BACKGROUND: Amnestic mild cognitive impairment (aMCI) is a subtype of mild cognitive impairment (MCI) that is considered an early stage of Alzheimer's disease (AD). Although early identification of aMCI is crucial for mitigating disease progression, objective and economic evaluation tools designed for aMCI prediction are lacking. Hence, we aimed to develop and validate a novel nomogram based on sleep characteristics to predict the risk of aMCI in middle-aged and elderly adults.<br><br>METHODS: This study included 817 eligible participants who underwent polysomnography (PSG), comprising 339 individuals diagnosed with aMCI. The participants were divided into a training cohort and a validation cohort using a 7:3 random split. Least absolute shrinkage and selection operator (LASSO) regression was employed to identify key predictive factors, followed by multivariable logistic regression to refine the predictors, which were subsequently used to construct a nomogram. The predictive performance of the nomogram was evaluated through receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).<br><br>RESULTS: Among the 30 potential predictors, 9 independent sleep-related predictors were incorporated into the final nomogram: total sleep time (TST), sleep efficiency (SE), the proportions of nonrapid eye movement stage 1 (N1), nonrapid eye movement stage 3 (N3), and rapid eye movement (REM) sleep, the density and amplitude of fast spindles and the density and amplitude of K-complexes (KCs). The nomogram demonstrated excellent discriminative ability, with an area under the curve (AUC) of 0.968 in the training cohort and 0.953 in the validation cohort. Calibration curves indicated strong agreement between the predicted and observed outcomes, and DCA confirmed the clinical usefulness of the nomogram by showing consistent net benefits across a wide range of threshold probabilities.<br><br>CONCLUSION: In this study, we developed and validated an innovative nomogram based on objective sleep characteristics to predict aMCI risk. By reducing the reliance on subjective or costly diagnostic tools, the nomogram offers a reliable, accessible, and practical method for the early identification of aMCI.}, }
@article {pmid40335149, year = {2025}, author = {Koskenvuo, L and Paajanen, P and Varpe, P and Seppälä, T and Mentula, P and Haapamäki, C and Carpelan-Holmström, M and Carpelan, A and Lehto, K and Satokari, R and Lepistö, A and Sallinen, V}, title = {PROtective ileoStomy versus ProtectivE colostomy in anterior Rectal resectIon: study protocol for a multicenter, open-label, randomised conTrolled studY (PROSPERITY).}, journal = {BMJ open}, volume = {15}, number = {5}, pages = {e096091}, pmid = {40335149}, issn = {2044-6055}, mesh = {Humans ; *Ileostomy/methods/adverse effects ; *Colostomy/methods/adverse effects ; *Postoperative Complications/epidemiology ; Multicenter Studies as Topic ; *Rectal Neoplasms/surgery ; Quality of Life ; Randomized Controlled Trials as Topic ; *Rectum/surgery ; Female ; Male ; }, abstract = {INTRODUCTION: Loop ileostomy and loop colostomy are both used to form a protective stoma after anterior resection. Evidence regarding which of these two procedures is superior is lacking. Furthermore, no studies comparing changes in the microbiome after loop ileostomy or loop colostomy exist.<br><br>METHODS AND ANALYSIS: This multicentre, open-label, superiority, individually randomised controlled trial will include patients who undergo anterior rectal resection with primary anastomosis with a protective stoma. The exclusion criteria are patients who already have a stoma, technical inability to create either type of stoma, aged <18 years and inadequate cooperation. Patients scheduled for anterior rectal resection will be randomised intraoperatively in a 1:1 ratio to undergo either loop ileostomy or loop colostomy. The primary outcome is cumulative stoma-related adverse events within 60 days after primary surgery, measured using the Comprehensive Complication Index (CCI). Secondary outcomes include all postoperative complications (measured using the CCI), number of hospital-free days within 30 days after primary surgery, quality of life at 2 months (measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires-Core 30 and Colorectal 29), complications within 30 days after stoma closure (measured using the CCI) and kidney function (measured using estimated glomerular filtration rate) at 1 year. Tertiary outcomes are survival, kidney function and number of stoma site hernias at 5 years. The sample size was calculated to detect a mean difference of five CCI points between groups, resulting in a final sample size of 350 patients. Microbiome samples will be collected from the faeces and mucous membrane from patients in Helsinki University Hospital.<br><br>ETHICS AND DISSEMINATION: The Ethics Committee of Helsinki University Hospital approved the study (approval number 4579/2024). The findings will be disseminated in peer-reviewed academic journals.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT06650085, registered on 20 August 2024.<br><br>PROTOCOL VERSION: Version 3.0, dated 17 April 2025.}, }
@article {pmid40333113, year = {2025}, author = {Bordea, MA and Nutz, BTG and Chiorean, AD and Samasca, G and Lupan, I and Simon, LM and Pepelea, L}, title = {Microbial Interactions in Nature: The Impact of Gram-Negative Bacilli on the Hyphal Growth of Candida albicans.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {4}, pages = {}, pmid = {40333113}, issn = {2076-0817}, mesh = {*Candida albicans/growth &amp; development/pathogenicity ; Humans ; *Microbial Interactions ; *Hyphae/growth &amp; development ; *Gram-Negative Bacteria/physiology ; Coinfection/microbiology ; *Candidiasis/microbiology ; Virulence ; Microbiota ; }, abstract = {The escalating global prevalence of fungal and bacterial co-infections underscores the significant and multifaceted impact of ubiquitous microorganisms on both environmental equilibria and human well-being. The human microbiome, a complex ecosystem of bacterial communities, harbors opportunistic pathogens capable of inducing superinfections or concurrent infections with Candida spp. The intricate interplay, exemplified by the interaction between Candida albicans and diverse bacteria, necessitates rigorous investigation to elucidate mechanisms by which this polymicrobial behavior potentiates fungal virulence, particularly in immunocompromised individuals. Our study aims to comprehensively examine the ramifications of these interactions, with a specific focus on their influence on fungal virulence and the consequent exacerbation of disease severity. Achieving a comprehensive understanding of these complex relationships is paramount for informing effective clinical management strategies for infectious diseases, and the accurate identification of fungal-bacterial co-infections holds substantial implications for optimizing clinical treatment paradigms, especially in vulnerable immunocompromised hosts.}, }
@article {pmid40330025, year = {2025}, author = {Smail, SW and Albarzinji, N and Salih, RH and Taha, KO and Hirmiz, SM and Ismael, HM and Noori, MF and Azeez, SS and Janson, C}, title = {Microbiome dysbiosis in SARS-CoV-2 infection: implication for pathophysiology and management strategies of COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {15}, number = {}, pages = {1537456}, pmid = {40330025}, issn = {2235-2988}, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *COVID-19/microbiology/physiopathology/therapy/complications ; *SARS-CoV-2 ; *Gastrointestinal Microbiome ; }, abstract = {The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), in late 2019 initiated a global health crisis marked by widespread infection, significant mortality, and long-term health implications. While SARS-CoV-2 primarily targets the respiratory system, recent findings indicate that it also significantly disrupts the human microbiome, particularly the gut microbiota, contributing to disease severity, systemic inflammation, immune dysregulation, and increased susceptibility to secondary infections and chronic conditions. Dysbiosis, or microbial imbalance, exacerbates the clinical outcomes of COVID-19 and has been linked to long-COVID, a condition affecting a significant proportion of survivors and manifesting with over 200 symptoms across multiple organ systems. Despite the growing recognition of microbiome alterations in COVID-19, the precise mechanisms by which SARS-CoV-2 interacts with the microbiome and influences disease progression remain poorly understood. This narrative review investigates the impact of SARS-CoV-2 on host-microbiota dynamics and evaluates its implications in disease severity and for developing personalized therapeutic strategies for COVID-19. Furthermore, it highlights the dual role of the microbiome in modulating disease progression, and as a promising target for advancing diagnostic, prognostic, and therapeutic approaches in managing COVID-19.}, }
@article {pmid40329426, year = {2025}, author = {Ren, L and Yang, J and Xiao, Y and Guo, L and Rao, J and Wu, C and Wang, X and Wang, Y and Zhang, L and Zhang, L and Jiang, X and Zhong, J and Zhong, J and Yang, W and Wang, C and Wang, J and Li, M}, title = {Transmission of the human respiratory microbiome and antibiotic resistance genes in healthy populations.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {115}, pmid = {40329426}, issn = {2049-2618}, support = {2020-I2M-2-013//Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)/ ; 2023-I2M-2-001//Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)/ ; 2023-I2M-2-001//Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS)/ ; 2019PT310029//Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; 2022YFA1304300//National Key R&amp;D Program of China/ ; 2022YFA1304300//National Key R&amp;D Program of China/ ; NSFC82221004//Foundation for Innovative Research Groups of the National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Microbiota/genetics ; Female ; *Bacteria/genetics/classification/isolation &amp; purification/drug effects ; Male ; Adult ; Metagenomics/methods ; *Oropharynx/microbiology ; Middle Aged ; *Drug Resistance, Microbial/genetics ; Family Characteristics ; Young Adult ; Metagenome ; }, abstract = {BACKGROUND: The human microbiome is transmissible between individuals, including pathogens and commensals with metabolic and immune-modulating effects, which could influence susceptibility, severity, and outcomes of both infection and non-infection diseases. However, limited studies of respiratory microbiome transmission within populations have been conducted. Herein, we performed species- and strain-level metagenomic analyses on oropharyngeal (OP) swabs from 1046 healthy urban dwellers across 13 districts, including 111 households with at least two cohabitants, to elucidate the transmission dynamics of the respiratory microbiome within households and communities.<br><br>RESULTS: We found that geographic districts accounted for the greatest variation in the OP microbiome, with unrelated individuals from the same district showing greater microbiome similarity and higher strain-sharing rates than those from different districts. Cohabitants, especially spouses and siblings, exhibited similar microbial abundances and shared more strains, with 16.7% (IQR 0.0-33.3%) of strains shared among cohabitants, compared to 0.0% (IQR 0.0-11.1%) in non-cohabiting pairs (p&#x2009;<&#x2009;0.05). Both respiratory commensals and opportunistic pathogens were shared among cohabitants. In contrast, no evidence of vertical transmission was detected between mother-offspring pairs. Additionally, the OP microbiome contained diverse antibiotic resistance genes (ARGs), with 15.0% linked to mobile genetic elements (MGEs) or plasmids; the flanking sequences of these ARGs were more conserved across species than those of non-MGE-associated ARGs, suggesting horizontal transfer of ARGs among respiratory microorganisms.<br><br>CONCLUSIONS: In summary, we characterized the transmissible nature of the OP microbiome and the risk of ARG dissemination among respiratory microorganisms. These findings underscore the role of respiratory microbes and ARGs exchange in shaping the microbiome of healthy populations and emphasize their relevance to public health strategies for respiratory health management. Video Abstract.}, }
@article {pmid40328944, year = {2025}, author = {Kim, Y and Worby, CJ and Acharya, S and van Dijk, LR and Alfonsetti, D and Gromko, Z and Azimzadeh, PN and Dodson, KW and Gerber, GK and Hultgren, SJ and Earl, AM and Berger, B and Gibson, TE}, title = {Longitudinal profiling of low-abundance strains in microbiomes with ChronoStrain.}, journal = {Nature microbiology}, volume = {10}, number = {5}, pages = {1184-1197}, pmid = {40328944}, issn = {2058-5276}, support = {R35 GM149270/GM/NIGMS NIH HHS/United States ; R35GM141861//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01 GM130777/GM/NIGMS NIH HHS/United States ; R01DK121822//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R21 AI154075/AI/NIAID NIH HHS/United States ; R35 GM141861/GM/NIGMS NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; R21AI154075//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; U19AI110818//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R35 GM143056/GM/NIGMS NIH HHS/United States ; R35GM149270//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01 DK121822/DK/NIDDK NIH HHS/United States ; R35GM143056//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, mesh = {Humans ; *Microbiota/genetics ; Feces/microbiology ; Female ; *Metagenomics/methods ; Bayes Theorem ; Longitudinal Studies ; Escherichia coli/genetics/isolation &amp; purification/classification ; Infant ; Algorithms ; Enterococcus faecalis/genetics/isolation &amp; purification/classification ; Adult ; *Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {The ability to detect and quantify microbiota over time from shotgun metagenomic data has a plethora of clinical, basic science and public health applications. Given these applications, and the observation that pathogens and other taxa of interest can reside at low relative abundance, there is a critical need for algorithms that accurately profile low-abundance microbial taxa with strain-level resolution. Here we present ChronoStrain: a sequence quality- and time-aware Bayesian model for profiling strains in longitudinal samples. ChronoStrain explicitly models the presence or absence of each strain and produces a probability distribution over abundance trajectories for each strain. Using synthetic and semi-synthetic data, we demonstrate how ChronoStrain outperforms existing methods in abundance estimation and presence/absence prediction. Applying ChronoStrain to two human microbiome datasets demonstrated its improved interpretability for profiling Escherichia coli strain blooms in longitudinal faecal samples from adult women with recurring urinary tract infections, and its improved accuracy for detecting Enterococcus faecalis strains in infant faecal samples. Compared with state-of-the-art methods, ChronoStrain's ability to detect low-abundance taxa is particularly stark.}, }
@article {pmid40322904, year = {2025}, author = {Hinkkanen, VI and Savinko, T and Palosuo, K and Alenius, H and Mäkelä, MJ and Karisola, P}, title = {Regular Allergen Exposure During Oral Immunotherapy Alters the Transcriptomic Innate Immune Response After Cellular Restimulation in Children With Egg Allergy.}, journal = {Journal of investigational allergology &amp; clinical immunology}, volume = {}, number = {}, pages = {0}, doi = {10.18176/jiaci.1079}, pmid = {40322904}, issn = {1018-9068}, abstract = {BACKGROUND AND OBJECTIVES: Oral immunotherapy (OIT) is a promising treatment for food allergies. However, the molecular mechanisms leading to desensitization remain unknown. To better understand the immunological mechanisms and transcriptional changes underlying desensitization to food allergens during OIT.<br><br>METHODS: Our cohort consisted of 40 Finnish children with egg allergy who underwent OIT. Peripheral blood mononuclear cells (PBMCs) were collected at 0, 3, and 8 months of therapy and stimulated with an egg allergen extract. Differentially expressed genes (DEGs) were identified based on quantile-normalized and batch-corrected microarray data using a linear model. Gene enrichment and Pearson correlation analyses were conducted.<br><br>RESULTS: After 8 months of therapy, 45% of patients were fully desensitized and 55% partially desensitized. Stimulation with egg yielded 49 DEGs at 0 months, 723 DEGs at 3 months, and 759 DEGs at 8 months in PBMCs after comparison with unstimulated controls. At 8 months of OIT, allergen stimulation led to down regulation of proinflammatory pathways, as well as IL-4 and IL-13 signaling. At baseline, the immune response in the fully desensitized group was more reactive than in the partially desensitized group.<br><br>CONCLUSIONS: During OIT, general immune activity is increased, especially the number of down-regulated genes, suggesting active immune suppression. Transcriptomic profiles differ between fully and partially desensitized patients, with a notably more reactive immune response in the fully desensitized group at baseline. Innate immunity seems to play a significant role in the development of desensitization during OIT.}, }
@article {pmid40322851, year = {2025}, author = {Zeng, Z and Li, M and Vannucci, M}, title = {Bayesian covariate-dependent graph learning with a dual group spike-and-slab prior.}, journal = {Biometrics}, volume = {81}, number = {2}, pages = {}, doi = {10.1093/biomtc/ujaf053}, pmid = {40322851}, issn = {1541-0420}, support = {2153704//DMS/NIGMS/ ; //National Science Foundation/ ; }, mesh = {Bayes Theorem ; Computer Simulation ; Humans ; *Models, Statistical ; Microbiota ; Algorithms ; }, abstract = {Covariate-dependent graph learning has gained increasing interest in the graphical modeling literature for the analysis of heterogeneous data. This task, however, poses challenges to modeling, computational efficiency, and interpretability. The parameter of interest can be naturally represented as a 3-dimensional array with elements that can be grouped according to 2 directions, corresponding to node level and covariate level, respectively. In this article, we propose a novel dual group spike-and-slab prior that enables multi-level selection at covariate-level and node-level, as well as individual (local) level sparsity. We introduce a nested strategy with specific choices to address distinct challenges posed by the various grouping directions. For posterior inference, we develop a full Gibbs sampler for all parameters, which mitigates the difficulties of parameter tuning often encountered in high-dimensional graphical models and facilitates routine implementation. Through simulation studies, we demonstrate that the proposed model outperforms existing methods in its accuracy of graph recovery. We show the practical utility of our model via an application to microbiome data where we seek to better understand the interactions among microbes as well as how these are affected by relevant covariates.}, }
@article {pmid40315414, year = {2025}, author = {Galperina, A and Lugli, GA and Milani, C and De Vos, WM and Ventura, M and Salonen, A and Hurwitz, B and Ponsero, AJ}, title = {The Aggregated Gut Viral Catalogue (AVrC): A unified resource for exploring the viral diversity of the human gut.}, journal = {PLoS computational biology}, volume = {21}, number = {5}, pages = {e1012268}, pmid = {40315414}, issn = {1553-7358}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Virome/genetics ; *Viruses/genetics/classification ; Computational Biology/methods ; Feces/virology ; Metagenome/genetics ; Infant ; Databases, Genetic ; }, abstract = {The growing interest in the role of the gut virome in human health and disease, has led to several recent large-scale viral catalogue projects mining human gut metagenomes each using varied computational tools and quality control criteria. Importantly, there has been to date no consistent comparison of these catalogues' quality, diversity, and overlap. In this project, we therefore systematically surveyed nine previously published human gut viral catalogues. While these catalogues collectively screened >40,000 human fecal metagenomes, 82% of the recovered 345,613 viral sequences were unique to one catalogue, highlighting limited redundancy between the ressources and suggesting the need for an aggregated resource bringing these viral sequences together. We further expanded these viral catalogues by mining 7,867 infant gut metagenomes from 12 large-scale infant studies collected in 9 different countries. From these datasets, we constructed the Aggregated Gut Viral Catalogue (AVrC), a unified modular resource containing 1,018,941 dereplicated viral sequences (449,859 species-level vOTUs). Using computational inference tools, annotations were obtained for each vOTU representative sequence quality, viral taxonomy, predicted viral lifestyle, and putative host. This project aims to facilitate the reuse of previously published viral catalogues by the research community and follows a modular framework to enable future expansions as novel data becomes available.}, }
@article {pmid40314735, year = {2025}, author = {Rohde, C}, title = {[Basic knowledge of phages and their therapeutic application].}, journal = {Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz}, volume = {68}, number = {6}, pages = {600-607}, pmid = {40314735}, issn = {1437-1588}, mesh = {Humans ; *Bacterial Infections/therapy/microbiology ; *Bacteriophages/physiology ; *Phage Therapy/methods/trends ; }, abstract = {Phages (bacteriophages) are viruses that specifically infect and kill bacteria. They are very abundant in nature, playing a highly relevant role in microbial ecosystems. In medicine, they are investigated as a potential alternative or supplement to antibiotics and can be used to treat wound, urinary tract and lung infections, for example. Single phages or so-called "phage cocktails" are applied.This overview article on basic knowledge of phages sheds light on well-known keywords from classical knowledge of phage biology and on state-of-the-art research focuses. Mechanisms of phage activity are presented as a basis for therapeutic application. Particularly, the phage-host interaction, lysis mechanisms, phage morphologies and specific methods for visualisation are discussed. Being part of the human microbiome, phages contribute to immune defence, especially in the mucosa. Temperate phages that are able to reside in bacterial genomes as prophages and therefore not suitable for therapy use as well as the CrAss phages (Crassvirales) and Lak megaphages discovered in recent years are also introduced. Further topics are bacterial phage defence, phage resistance and phage-antibiotic synergies. An outlook on future research is given, emphasising the importance of a coordinated collection of scientific results.Phages should not replace antibiotics, but they can even improve their efficiency. Currently, the licensing processes for phage therapy are still challenging. However, trust in phage preparations must be based on quality, which has to be guaranteed by harmonised standards.}, }
@article {pmid40314614, year = {2025}, author = {Lee, WM and Ahn, SY and Lee, GS and Park, I and Kim, J and Lee, SH and Lee, S and Kim, CS}, title = {Discovery and Biosynthesis of Indole-Functionalized Metabolites from the Human Blood Bacterium, Paracoccus sanguinis, and Their Anti-Skin Aging Activity.}, journal = {Journal of natural products}, volume = {88}, number = {5}, pages = {1120-1129}, doi = {10.1021/acs.jnatprod.4c01354}, pmid = {40314614}, issn = {1520-6025}, mesh = {Humans ; *Skin Aging/drug effects ; *Indoles/pharmacology/chemistry/metabolism ; Reactive Oxygen Species/metabolism ; Molecular Structure ; Fibroblasts/drug effects/metabolism ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Matrix Metalloproteinase 1/metabolism ; Tumor Necrosis Factor-alpha/pharmacology ; }, abstract = {The human microbiome plays a crucial role in health and disease, with microbial metabolites acting as key mediators of physiological processes. While extensive research has focused on gut-derived microbes, the metabolic contributions of blood-derived bacteria remain underexplored. Here, we investigate the facultative anaerobe Paracoccus sanguinis, a Gram-negative bacterium isolated from human blood, and its metabolome, revealing insights into its potential impacts on health and disease. Using advanced analytical methods, we characterized 12 metabolites (1-12), including six novel compounds (1-3, 9, 10, and 12). Biosynthetic studies demonstrated that these metabolites are derived through enzymatic and nonenzymatic pathways. Functional evaluations revealed significant antiaging activities for 1, 6, and 11 in TNF-α-stimulated normal human dermal fibroblasts (NHDFs), including suppression of reactive oxygen species (ROS), inhibition of matrix metalloproteinase-1 (MMP-1) secretion, and reduction of inflammatory cytokines interleukin (IL)-6 and IL-8. Among the tested compounds, 11 exhibited the highest antiaging efficacy, highlighting its potential as a candidate for therapeutic applications targeting skin aging. This study elucidates the biosynthetic pathways of P. sanguinis metabolites and their antiskin aging activity, underscoring their potential in modulating skin health and offering novel insights into the functional roles of blood-derived microbiota in human health.}, }
@article {pmid40311618, year = {2025}, author = {Andreu-Sánchez, S and Blanco-Míguez, A and Wang, D and Golzato, D and Manghi, P and Heidrich, V and Fackelmann, G and Zhernakova, DV and Kurilshikov, A and Valles-Colomer, M and Weersma, RK and Zhernakova, A and Fu, J and Segata, N}, title = {Global genetic diversity of human gut microbiome species is related to geographic location and host health.}, journal = {Cell}, volume = {188}, number = {15}, pages = {3942-3959.e9}, doi = {10.1016/j.cell.2025.04.014}, pmid = {40311618}, issn = {1097-4172}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Genetic Variation ; Phylogeny ; Metagenome/genetics ; Male ; Female ; Bile Acids and Salts/blood ; Clostridiales ; }, abstract = {The human gut harbors thousands of microbial species, each exhibiting significant inter-individual genetic variability. Although many studies have associated microbial relative abundances with human-health-related phenotypes, the substantial intraspecies genetic variability of gut microbes has not yet been comprehensively considered, limiting the potential of linking such genetic traits with host conditions. Here, we analyzed 32,152 metagenomes from 94 microbiome studies across the globe to investigate the human microbiome intraspecies genetic diversity. We reconstructed 583 species-specific phylogenies and linked them to geographic information and species' horizontal transmissibility. We identified 484 microbial-strain-level associations with 241 host phenotypes, encompassing human anthropometric factors, biochemical measurements, diseases, and lifestyle. We observed a higher prevalence of a Ruminococcus gnavus clade in nonagenarians correlated with distinct plasma bile acid profiles and a melanoma and prostate-cancer-associated Collinsella clade. Our large-scale intraspecies genetic analysis highlights the relevance of strain diversity as it relates to human health.}, }
@article {pmid40304519, year = {2025}, author = {Swayambhu, M and Gysi, M and Haas, C and Schuh, L and Walser, L and Javanmard, F and Flury, T and Ahannach, S and Lebeer, S and Hanssen, E and Snipen, L and Bokulich, NA and Kümmerli, R and Arora, N}, title = {Standardizing a microbiome pipeline for body fluid identification from complex crime scene stains.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {5}, pages = {e0187124}, pmid = {40304519}, issn = {1098-5336}, support = {//Swiss Government Excellence Scholarship/ ; //Emma Luis Kessler Funds/ ; //ERC Lact-Be Grant/ ; }, mesh = {Humans ; *Microbiota ; *Body Fluids/microbiology ; Female ; Male ; Machine Learning ; High-Throughput Nucleotide Sequencing ; Saliva/microbiology ; *Bacteria/classification/isolation &amp; purification/genetics ; }, abstract = {Recent advances in next-generation sequencing have opened up new possibilities for applying the human microbiome in various fields, including forensics. Researchers have capitalized on the site-specific microbial communities found in different parts of the body to identify body fluids from biological evidence. Despite promising results, microbiome-based methods have not been integrated into forensic practice due to the lack of standardized protocols and systematic testing of methods on forensically relevant samples. Our study addresses critical decisions in establishing these protocols, focusing on bioinformatics choices and the use of machine learning to present microbiome results in case reports for forensically relevant and challenging samples. In our study, we propose using operational taxonomic units (OTUs) for read data processing and generating heterogeneous training data sets for training a random forest classifier. We incorporated six forensically relevant classes: saliva, semen, skin from hand, penile skin, urine, and vaginal/menstrual fluid, and our classifier achieved a high weighted average F1 score of 0.89. Systematic testing on mock forensic samples, including mixed-source samples and underwear, revealed reliable detection of at least one component of the mixture and the identification of vaginal fluid from underwear substrates. Additionally, when investigating the sexually shared microbiome (sexome) of heterosexual couples, our classifier could potentially infer the nature of sexual activity. We therefore highlight the value of the sexome for assessing the nature of sexual activities in forensic investigations while delineating areas that warrant further research.IMPORTANCEMicrobiome-based analyses combined with machine learning offer potential avenues for use in forensic science and other applied fields, yet standardized protocols remain lacking. Moreover, machine learning classifiers have shown promise for predicting body sites in forensics, but they have not been systematically evaluated on complex mixed-source samples. Our study addresses key decisions for establishing standardized protocols and, to our knowledge, is the first to report classification results from uncontrolled mixed-source samples, including sexome (sexually shared microbiome) samples. In our study, we explore both the strengths and limitations of classifying the mixed-source samples while also providing options for tackling the limitations.}, }
@article {pmid40302548, year = {2025}, author = {Singh, A and Mazumder, A and Das, S and Kanda, A and Tyagi, PK and Chaitanya, MVNL}, title = {Harnessing the Power of Probiotics: Boosting Immunity and Safeguarding against Various Diseases and Infections.}, journal = {Recent advances in anti-infective drug discovery}, volume = {20}, number = {1}, pages = {5-29}, pmid = {40302548}, issn = {2772-4352}, mesh = {*Probiotics/administration &amp; dosage/therapeutic use ; Humans ; Animals ; Gastrointestinal Microbiome/immunology ; *Virus Diseases/immunology/prevention &amp; control ; }, abstract = {The human microbiome, a diverse microorganism community, crucially defends against pathogens. Probiotics, postbiotics, and paraprobiotics alone and in combination are potent in countering fungal and waterborne infections, particularly against viral threats. This review focuses on the mechanisms of the microbiome against viral infections, emphasizing probiotic interventions. Certain Lactic Acid Bacteria (LAB) strains effectively eliminate toxic aflatoxin B1 (AFB1) from microfungi-produced mycotoxins. LAB binding to AFB1 persists post-gastric digestion, and pre-incubation with mycotoxins reduces probiotic adhesion to mucus. Oral probiotic administration in animals increases mycotoxin excretion, reducing associated health risks. Bifidobacterium longum and Lactobacillus rhamnosus show exceptional efficacy in removing cyanobacterial toxin microcystin-LR from drinking water. Engineered probiotics promise advanced therapeutic applications for metabolic disorders, Alzheimer's, and type 1 diabetes, serving as diagnostic tools for detecting pathogens and inflammation markers. In antimicrobial peptide production, genetically modified probiotics producing human β-defensin 2 (HBD2) treat Crohn's disease with implemented biocontainment strategies preventing unintended environmental impacts.}, }
@article {pmid40301726, year = {2025}, author = {Yao, C and Zhang, Y and You, L and E, J and Wang, J}, title = {Comparative analysis of three experimental methods for revealing human fecal microbial diversity.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {258}, pmid = {40301726}, issn = {1471-2180}, support = {2024L154//the Fundamental Research Program of Shanxi Province/ ; 202403021212101//the Science and Technology Innovation Project of Shanxi Provincial Universities/ ; 2018ZD14//the Major Program of Natural Science Foundation of Inner Mongolia/ ; }, mesh = {Humans ; *Feces/microbiology ; *Bacteria/genetics/classification/isolation &amp; purification/growth &amp; development ; *Metagenomics/methods ; *Gastrointestinal Microbiome ; Culture Media/chemistry ; *Biodiversity ; *Bacteriological Techniques/methods ; Sequence Analysis, DNA ; DNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Due to the heterogeneity of the human gut environment, the gut microbiota is complex and diverse, and has been insufficiently explored. In this study, one fresh fecal sample was cultured using 12 commercial or modified media and incubation of culture plates anaerobically and aerobically, the conventional experienced colony picking (ECP) was first used to isolate the colonies and obtain pure culture strains. On this basis, all the colonies grown on the culture plates were collected for culture-enriched metagenomic sequencing (CEMS), and the original sample was also subjected to direct culture-independent metagenomic sequencing (CIMS), the study compared the effects of three methods for analyzing the microbiota contained in the sample. It was found that compared with CEMS, conventional ECP failed to detect a large proportion of strains grown in culture media, resulting in missed detection of culturable microorganisms in the gut. Microbes identified by CEMS and CIMS showed a low degree of overlap (18% of species), whereas species identified by CEMS and CIMS alone accounted for 36.5% and 45.5%, respectively. It suggests that both culture-dependent and culture-independent approaches are essential in revealing gut microbial diversity. Moreover, based on the CEMS results, growth rate index (GRiD) values for various strains on different media were calculated to predict the optimal medium for bacterial growth; this method can be used to design new media for intestinal microbial isolation, promote the recovery of specific microbiota, and obtain new insights into the human microbiome diversity. This is among the first studies on CEMS of the human gut microbiota.}, }
@article {pmid40299456, year = {2025}, author = {Meiirmanova, Z and Mukhanbetzhanov, N and Jarmukhanov, Z and Vinogradova, E and Kozhakhmetova, S and Morenko, M and Duisebayeva, A and Poddighe, D and Kushugulova, A and Kozhakhmetov, S}, title = {Alterations in Gut Microbiota of Infants Born to Mothers with Obesity.}, journal = {Biomedicines}, volume = {13}, number = {4}, pages = {}, pmid = {40299456}, issn = {2227-9059}, support = {Grant No. AP19575153 "Metagenomic predictors of childhood obesity, cross-talk with maternal mi-croflora", Grant No. AP23489538 and Grant No. BR21882152//Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; Grant No. 20122022CRP1602//Nazarbayev University under Collaborative Research Program/ ; }, abstract = {Background: The impact of maternal obesity on offspring health remains a major and pressing issue. We investigated its impact on the development of the infant gut microbiome during the first six months of life, examining the taxonomic composition, metabolic pathways, and antibiotic resistance genes. Methods: Twenty-four mother-infant pairs were divided into maternally obese (OB, BMI > 36) and normal weight (BM) groups. Shotgun metagenomic sequencing was performed on stool samples collected at birth and at 1, 3, and 6 months. A total of 12 maternal samples and 23 infant samples (n = 35) in the obese group and 12 maternal samples and 30 infant samples (n = 42) in the control group were sequenced. The analysis included taxonomic profiling (MetaPhlAn 4), metabolic pathway analysis (HUMAnN 3), and antibiotic resistance gene screening (CARD/ABRicate). Results: The OB group showed reduced alpha diversity in the first month (p ≤ 0.01) and an increased Firmicutes/Bacteroidetes ratio, peaking at 3 months (p ≤ 0.001). The metabolic profiling revealed enhanced carbohydrate breakdown (p ≤ 0.001) in the BM group and lipid biosynthesis (p ≤ 0.0001) in the OB group pathways. Strong correlations emerged between Lactobacillales and fatty acid biosynthesis (r = 0.7, p ≤ 0.0001) and between Firmicutes and lincosamide (r = 0.8, p ≤ 0.0001). Conclusions: The infants of obese mothers had significantly altered development of the infant gut microbiome, affecting both composition and metabolic potential. These changes may have long-term health consequences and suggest potential therapeutic targets for intervention.}, }
@article {pmid40298367, year = {2025}, author = {Zhou, Z and Ma, Y and Zhang, D and Ji, R and Wang, Y and Zhao, J and Ma, C and Zhu, H and Shen, H and Jiang, X and Niu, Y and Lu, J and Zhang, B and Tu, L and Zhang, H and Ma, X and Chen, P}, title = {Microbiome and fragmentation pattern of blood cell-free DNA and fecal metagenome enhance colorectal cancer micro-dysbiosis and diagnosis analysis: a proof-of-concept study.}, journal = {mSystems}, volume = {10}, number = {5}, pages = {e0027625}, pmid = {40298367}, issn = {2379-5077}, support = {24ZDFA001//Gansu Provincial Science and Technology Major Project/ ; 2024-8-27,2024-8-30,2024-4-2//The Lanzhou Municipal Science and Technology Program/ ; 20240260001,20240260017//The College Students' Innovation and Entrepreneurship Program of Lanzhou University, China/ ; }, mesh = {Humans ; *Colorectal Neoplasms/microbiology/diagnosis/blood ; *Feces/microbiology ; Male ; Female ; *Metagenome/genetics ; Middle Aged ; *Dysbiosis/microbiology/diagnosis/blood ; *Cell-Free Nucleic Acids/blood ; Gastrointestinal Microbiome/genetics ; Adenoma/microbiology/diagnosis/blood ; Proof of Concept Study ; Aged ; Adult ; *Microbiota/genetics ; }, abstract = {Colorectal cancer (CRC) is the third most common cancer, and it can be prevented by performing early screening. As a hallmark of cancer, the human microbiome plays important roles in the occurrence and development of CRC. Recently, the blood microbiome has been proposed as an effective diagnostic tool for various diseases, yet its performance on CRC deserves further exploration. In this study, 133 human feces and 120 blood samples are collected, including healthy individuals, adenoma patients, and CRC patients. The blood cfDNA and fecal genome are subjected to shotgun metagenome sequencing. After removing human sequences, the microbial sequences in blood are analyzed. Based on the differential microbes and functions, random forest (RF) models are constructed for adenoma and CRC diagnosis. The results show that alterations of blood microbial signatures can be captured under low coverage (even at 3×). RF diagnostic models based on blood microbial markers achieve high area under the curve (AUC) values for adenoma patients (0.8849) and CRC patients (0.9824). When the fragmentation pattern is combined with microbial and KEGG markers, higher AUC values are obtained. Furthermore, compared to the blood microbiome, the fecal microbiome shows a different community composition, whereas their changes in KEGG pathways are similar. Pathogenic bacteria Fusobacterium nucleatum (F. nucleatum) in feces increased gradually from the healthy group to the adenoma and CRC groups. Additionally, F. nucleatum in feces and blood shows a positive correlation in CRC patients. Cumulatively, the integration of blood microbiome and fragmentation pattern is promising for CRC diagnosis.IMPORTANCEThe cell-free DNA of the human microbiome can enter the blood and can be used for cancer diagnosis, whereas its diagnostic potential in colorectal cancer and association with gut microbiome has not been explored. The microbial sequences in blood account for less than 1% of the total sequences. The blood microbial composition, KEGG functions, and fragmentation pattern are different among healthy individuals, adenoma patients, and CRC patients. Machine learning models based on these differential characteristics achieve high diagnostic accuracy, especially when they are integrated with fragmentation patterns. The great difference between fecal and blood microbiomes indicates that microbial sequences in blood may originate from various organs. Therefore, this study provides new insights into the community composition and functions of the blood microbiome of CRC and proposes an effective non-invasive diagnostic tool.}, }
@article {pmid40296251, year = {2025}, author = {Zheng, H and Chen, Y and Lu, S and Liu, Z and Ma, Y and Zhang, C and Zhang, Y and Zhang, J and Liu, C and Chu, M and Pei, F and Liu, S and Duan, L}, title = {Mechanosensory Piezo2 regulated by gut microbiota participates in the development of visceral hypersensitivity and intestinal dysmotility.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2497399}, pmid = {40296251}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Animals ; Humans ; Mice ; *Irritable Bowel Syndrome/microbiology/physiopathology/metabolism/therapy ; *Ion Channels/metabolism/genetics ; Male ; Female ; Fecal Microbiota Transplantation ; *Gastrointestinal Motility ; Adult ; Middle Aged ; Colon/metabolism ; Mice, Inbred C57BL ; Feces/microbiology ; Fusobacterium/physiology ; Dysbiosis/microbiology ; Disease Models, Animal ; Ganglia, Spinal/metabolism ; Akkermansia ; }, abstract = {The gut microbiota plays a crucial role in the manifestation of intestinal dysfunction associated with irritable bowel syndrome (IBS). The mechanosensory Piezo2 has been implicated in the regulation of intestinal function. However, it remains unclear whether Piezo2 is modulated by the gut microbiota, thus contributing to the development of visceral hypersensitivity and gut dysmotility. The study enrolled patients with diarrhea-predominant IBS (IBS-D) alongside healthy controls (HC). Questionnaires, rectal barostat test, and colonoscopy with mucosal biopsy were conducted. Fecal microbiota transplantation (FMT) was performed using samples from HC or IBS-D patients, and interventions with Akkermansia muciniphila or Fusobacterium varium were carried out on colon- or dorsal root ganglion (DRG)- Piezo2 knockdown pseudo-germ-free mice. Visceral sensitivity and intestinal motility were assessed. Piezo2 levels were detected using western blot and immunofluorescence. Fecal 16S rRNA sequencing and cecum untargeted metabolomics analysis, followed by molecular docking predictions of Piezo2, were also performed. The ratio of Piezo2[+]/5-HT[+] cells was lower in IBS-D patients, positively correlated with visceral sensation and intestinal dysbiosis. The mice that received FMT from IBS-D patients exhibited colonic dysmotility and visceral hypersensitivity, along with elevated Piezo2 protein levels in the colon and DRG. Knockdown of Piezo2 in the colon or DRG ameliorated the FMT-induced colonic dysmotility and visceral hypersensitivity. Fecal 16S rRNA sequencing revealed distinct microbiota composition. Notably, Fusobacterium varium, but not Akkermansia muciniphila, induced gut dysmotility and visceral hypersensitivity, effects that could be alleviated by colon or DRG Piezo2 knockdown. Additionally, Fusobacterium varium lead to increased Piezo2 protein levels, as well as elevated levels of indole-3-acetic acid and indole-3-acrylic acid, which were predicted to bind to Piezo2, causing disturbances. Piezo2 can be regulated by gut microbiota and involved in visceral hypersensitivity and colonic dysmotility, with Fusobacterium varium playing a crucial role.}, }
@article {pmid40296128, year = {2025}, author = {Adlakha, YK and Chhabra, R}, title = {The human microbiome: redefining cancer pathogenesis and therapy.}, journal = {Cancer cell international}, volume = {25}, number = {1}, pages = {165}, pmid = {40296128}, issn = {1475-2867}, abstract = {The human microbiome has always been an important determinant of health and recently, its role has also been described in cancer. The altered microbiome could aid cancer progression, modulate chemoresistance and significantly alter drug efficacy. The broad implications of microbes in cancer have prompted researchers to investigate the microbe-cancer axis and identify whether modifying the microbiome could sensitize cancer cells for therapy and improve the survival outcome of cancer patients. The preclinical data has shown that enhancing the number of specific microbial species could restore the patients' response to cancer drugs and the microbial biomarkers may play a vital role in cancer diagnostics. The elucidation of detailed interactions of the human microbiota with cancer would not only help identify the novel drug targets but would also enhance the efficacy of existing drugs. The field exploring the emerging roles of microbiome in cancer is at a nascent stage and an in-depth scientific perspective on this topic would make it more accessible to a wider audience. In this review, we discuss the scientific evidence connecting the human microbiome to the origin and progression of cancer. We also discuss the potential mechanisms by which microbiota affects initiation of cancer, metastasis and chemoresistance. We highlight the significance of the microbiome in therapeutic outcome and evaluate the potential of microbe-based cancer therapy.}, }
@article {pmid40291991, year = {2025}, author = {Crakes, KR and Questell, L and Soni, S and Suez, J}, title = {Impacts of non-nutritive sweeteners on the human microbiome.}, journal = {Immunometabolism (Cobham, Surrey)}, volume = {7}, number = {2}, pages = {e00060}, pmid = {40291991}, issn = {2633-0407}, abstract = {Replacing sugar with non-nutritive sweeteners (NNS) is a common dietary strategy for reducing the caloric content and glycemic index of foods and beverages. However, the efficacy of this strategy in preventing and managing metabolic syndrome and its associated comorbidities remains uncertain. Human cohort studies suggest that NNS contribute to, rather than prevent, metabolic syndrome, whereas randomized controlled trials yield heterogeneous outcomes, ranging from beneficial to detrimental impacts on cardiometabolic health. The World Health Organization recently issued a conditional recommendation against using NNS, citing the need for additional evidence causally linking sweeteners to health effects. One proposed mechanism through which NNS induce metabolic derangements is through disruption of the gut microbiome, a link strongly supported by evidence in preclinical models. This review summarizes the evidence for similar effects in interventional and observational trials in humans. The limited available data highlight heterogeneity between trials, as some, but not all, find NNS consumption associated with microbiome modulation as well as metabolic effects independent of sweetener type. In other trials, the lack of microbiome changes coincides with the absence of metabolic effects. We discuss the hypothesis that the impacts of NNS on health are personalized and microbiome dependent. Thus, a precision nutrition approach may help resolve the conflicting reports regarding NNS impacts on the microbiome and health. This review also discusses additional factors contributing to study heterogeneity that should be addressed in future clinical trials to clarify the relationship between NNS, the microbiome, and health to better inform dietary guidelines and public health policies.}, }
@article {pmid40264322, year = {2025}, author = {Jain, MS and Prasanthi, S and Bommala, ND and Goudanavar, P and Naveen, NR}, title = {Harnessing the Human Microbiome for Innovative Drug Delivery Systems: Exploring Pharmacomicrobiomics and Targeted Therapies.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113816128354250250326045943}, pmid = {40264322}, issn = {1873-4286}, abstract = {The human gut microbiome has emerged as a crucial component of health and disease, presenting novel opportunities for the development of drug delivery systems based on microbiome interactions. This paper explores advanced strategies utilizing microorganisms, engineered bacteria, viruses, and bacteria-encapsulated nanoparticles as next-generation therapeutic vehicles. Focusing on analytical approaches to phage therapy and bio-hybrid bacteria for targeted drug delivery, the article highlights recent breakthroughs in colon-specific targeting for gastrointestinal disorders. The study also delves into the emerging field of pharmacomicrobiomics, with an emphasis on applications in cancer, cardiovascular, digestive, and nervous system treatments, specifically targeting key drug classes such as ACE inhibitors, proton-pump inhibitors, and NSAIDs. Challenges related to cytotoxicity and toxicity are addressed, offering proposals for safer therapeutic applications. This review underscores the transformative potential of the microbiome in personalized medicine and targeted drug delivery, with a focus on its integration with advanced technologies to optimize therapeutic outcomes.}, }
@article {pmid40261032, year = {2025}, author = {Cho, M-Y and Eom, J-H and Choi, E-M and Yang, S-J and Lee, D and Kim, YY and Kim, H-S and Hwang, I}, title = {Recent advances in therapeutic probiotics: insights from human trials.}, journal = {Clinical microbiology reviews}, volume = {38}, number = {2}, pages = {e0024024}, pmid = {40261032}, issn = {1098-6618}, support = {2024ER050700//MOHW | Korea National Institute of Health (KNIH)/ ; }, mesh = {Humans ; *Probiotics/therapeutic use ; Gastrointestinal Microbiome ; Microbiota ; Randomized Controlled Trials as Topic ; Gastrointestinal Diseases/therapy ; }, abstract = {SUMMARYRecent advances in therapeutic probiotics have shown promising results across various health conditions, reflecting a growing understanding of the human microbiome's role in health and disease. However, comprehensive reviews integrating the diverse therapeutic effects of probiotics in human subjects have been limited. By analyzing randomized controlled trials (RCTs) and meta-analyses, this review provides a comprehensive overview of key developments in probiotic interventions targeting gut, liver, skin, vaginal, mental, and oral health. Emerging evidence supports the efficacy of specific probiotic strains and combinations in treating a wide range of disorders, from gastrointestinal (GI) and liver diseases to dermatological conditions, bacterial vaginosis, mental disorders, and oral diseases. We discuss the expanding understanding of microbiome-organ connections underlying probiotic mechanisms of action. While many clinical trials demonstrate significant benefits, we acknowledge areas requiring further large-scale studies to establish definitive efficacy and optimal treatment protocols. The review addresses challenges in standardizing probiotic research methodologies and emphasizes the importance of considering individual variations in microbiome composition and host genetics. Additionally, we explore emerging concepts such as the oral-gut-brain axis and future directions, including high-resolution microbiome profiling, host-microbe interaction studies, organoid models, and artificial intelligence applications in probiotic research. Overall, this review offers a comprehensive update on the current state of therapeutic probiotics across multiple domains of human health, providing insights into future directions and the potential for probiotics to revolutionize preventive and therapeutic medicine.}, }
@article {pmid40257583, year = {2025}, author = {Hu, J and Chen, W and Zhu, R and Yang, F and Xu, J and Xiang, B and Li, Y and Wang, W and Zhu, L and Chen, G and Zhi, M}, title = {Correction: Dietary risk factors in Crohn's disease and ulcerative colitis: a cohort study with paired healthy relatives as controls.}, journal = {European journal of nutrition}, volume = {64}, number = {4}, pages = {161}, doi = {10.1007/s00394-025-03669-y}, pmid = {40257583}, issn = {1436-6215}, }
@article {pmid40253432, year = {2025}, author = {Kelliher, JM and Aljumaah, M and Bordenstein, SR and Brister, JR and Chain, PSG and Dundore-Arias, JP and Emerson, JB and Fernandes, VMC and Flores, R and Gonzalez, A and Hansen, ZA and Hatcher, EL and Jackson, SA and Kellogg, CA and Madupu, R and Miller, CML and Mirzayi, C and Moustafa, AM and Mungall, C and Oliver, A and Pariente, N and Pett-Ridge, J and Record, S and Reji, L and Reysenbach, AL and Rich, VI and Richardson, L and Schriml, LM and Shabman, RS and Sierra, MA and Sullivan, MB and Sundaramurthy, P and Thibault, KM and Thompson, LR and Tighe, S and Vereen, E and Eloe-Fadrosh, EA}, title = {Microbiome data management in action workshop: Atlanta, GA, USA, June 12-13, 2024.}, journal = {Environmental microbiome}, volume = {20}, number = {1}, pages = {40}, pmid = {40253432}, issn = {2524-6372}, support = {2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; 2422717//Directorate for Biological Sciences/ ; }, abstract = {Microbiome research is revolutionizing human and environmental health, but the value and reuse of microbiome data are significantly hampered by the limited development and adoption of data standards. While several ongoing efforts are aimed at improving microbiome data management, significant gaps still remain in terms of defining and promoting adoption of consensus standards for these datasets. The Strengthening the Organization and Reporting of Microbiome Studies (STORMS) guidelines for human microbiome research have been endorsed and successfully utilized by many research organizations, publishers, and funding agencies, and have been recognized as a consensus community standard. No equivalent effort has occurred for environmental, synthetic, and non-human host-associated microbiomes. To address this growing need within the microbiome research community, we convened the Microbiome Data Management in Action Workshop (June 12-13, 2024, in Atlanta, GA, USA), to bring together key decision makers in microbiome science including researchers, publishers, funders, and data repositories. The 50 attendees, representing the diverse and interdisciplinary nature of microbiome research, discussed recent progress and challenges, and brainstormed actionable recommendations and paths forward for coordinated environmental microbiome data management and the modifications necessary for the STORMS guidelines to be applied to environmental, non-human host, and synthetic microbiomes. The outcomes of this workshop will form the basis of a formalized data management roadmap to be implemented across the field. These best practices will drive scientific innovation now and in years to come as these data continue to be used not only in targeted reanalyses but in large-scale models and machine learning efforts.}, }
@article {pmid40251928, year = {2025}, author = {Boem, F and Lamminpää, I and Amedei, A}, title = {Updating the Discontinuity Theory to the Extended Immunity: The Symmunobiome Concept.}, journal = {European journal of immunology}, volume = {55}, number = {4}, pages = {e202451528}, pmid = {40251928}, issn = {1521-4141}, support = {PE0000006//Italian Ministry of University and Research MNESYS/ ; B55F2100//University of Florence-European Union-Next Generation EU-CUP/ ; B83C22003920001//The National Recovery and Resilience Plan, Investment 1.5 Ecosystems of Innovation, Project Tuscany Health Ecosystem (THE), CUP/ ; }, mesh = {Humans ; *Microbiota/immunology ; Animals ; *Immune System/immunology ; Symbiosis/immunology ; Homeostasis/immunology ; *Immunity ; Biological Evolution ; Immunity, Innate ; Adaptive Immunity ; }, abstract = {The immune system (IS) is commonly understood as a system composed of specific cells and tissues that have evolved to contrast pathogens and defend the host. By virtue of this capacity, it has come to be considered capable of making an essential distinction, that between self versus non-self, which would contribute to a clear identity of the organism. However, in the wake of evolution and ecology, growing evidence suggests that the so-called immune system, which also evolved from symbiotic interactions with external agents, is not just a defensive system that merely protects the organism but, on the contrary, is involved in many global regulatory and homeostatic functions. Moreover, in performing these many functions, IS is not only an ensemble of host cells and tissues but functionally is constitutively determined by the interaction with a set of associated microorganisms, that is, the human microbiome. In this scenario, it is open-and-shut that the microbiome itself is a functional part of this extended immune system. Organisms and microbiomes together, therefore, form a functional whole, which constitutes a privileged form of biological organization. In light of this evidence showing the inadequacy of traditional accounts, we propose to extend and supplement the current IS conceptualization by introducing the notion of the symmunobiome. With this term, we intend to characterize the microbiome's own and unavoidable component to overall immune functionality. Therefore, we suggest a new immune system determination, articulated in three linked pillars-adaptive immunity, innate immunity, and symmunobiome-to better grasp the diverse functionality of extended immunity.}, }
@article {pmid40246834, year = {2025}, author = {Beaudoin, CA and Norget, S and Omran, Z and Hala, S and Daqeeq, AH and Burnet, PWJ and Blundell, TL and van Tonder, AJ}, title = {Similarity of drug targets to human microbiome metaproteome promotes pharmacological promiscuity.}, journal = {The pharmacogenomics journal}, volume = {25}, number = {3}, pages = {9}, pmid = {40246834}, issn = {1473-1150}, support = {ANTSRG 01/2019//Antibiotic Research UK (ANTRUK)/ ; }, mesh = {Humans ; Female ; *Microbiota/drug effects/genetics ; *Proteome/genetics ; *Gastrointestinal Microbiome/drug effects ; Vagina/microbiology ; Proteomics/methods ; Mouth/microbiology ; Bacteria/drug effects/genetics/metabolism ; }, abstract = {Similarity between candidate drug targets and human proteins is commonly assessed to minimize the occurrence of side effects. Although numerous drugs have been found to disrupt the health of the human microbiome, no comprehensive comparison between established drug targets and the human microbiome metaproteome has yet been conducted. Therefore, herein, sequence and structure alignments between human and pathogen drug targets and representative human gut, oral, and vaginal microbiome metaproteomes were performed. Both human and pathogen drug targets were found to be similar in sequence, function, structure, and drug binding capacity to proteins in diverse pathogenic and non-pathogenic bacteria from all three microbiomes. The gut metaproteome was identified as particularly susceptible overall to off-target effects. Certain symptoms, such as infections and immune disorders, may be more common among drugs that non-selectively target host microbiota. These findings suggest that similarities between human microbiome metaproteomes and drug target candidates should be routinely checked.}, }
@article {pmid40243330, year = {2025}, author = {Walker, AR and Pham, DN and Noeparvar, P and Peterson, AM and Lipp, MK and Lemos, JA and Zeng, L}, title = {Fructose activates a stress response shared by methylglyoxal and hydrogen peroxide in Streptococcus mutans.}, journal = {mBio}, volume = {16}, number = {5}, pages = {e0048525}, pmid = {40243330}, issn = {2150-7511}, support = {R01 DE012236/DE/NIDCR NIH HHS/United States ; DE12236/DE/NIDCR NIH HHS/United States ; DE032555, DE019783/DE/NIDCR NIH HHS/United States ; R01 DE032555/DE/NIDCR NIH HHS/United States ; R01 DE019783/DE/NIDCR NIH HHS/United States ; }, mesh = {*Streptococcus mutans/genetics/drug effects/metabolism ; *Fructose/metabolism/pharmacology ; *Pyruvaldehyde/metabolism/pharmacology ; *Hydrogen Peroxide/metabolism/pharmacology ; Gene Expression Regulation, Bacterial/drug effects ; Gene Expression Profiling ; *Stress, Physiological ; Oxidative Stress ; Zinc/metabolism ; Glucose/metabolism ; }, abstract = {Fructose catabolism by Streptococcus mutans is initiated by three phosphotransferase (PTS) transporters yielding fructose-1-phosphate (F-1-P) or fructose-6-phosphate. Deletion of one such F-1-P-generating PTS, fruI, was shown to reduce the cariogenicity of S. mutans in rats fed a high-sucrose diet. Moreover, a recent study linked fructose metabolism in S. mutans to a reactive electrophile species methylglyoxal. Here, we conducted a comparative transcriptomic analysis of S. mutans treated briefly with 50 mM fructose, 50 mM glucose, 5 mM methylglyoxal, or 0.5 mM hydrogen peroxide (H2O2). The results revealed a striking overlap between the fructose and methylglyoxal transcriptomes, totaling 176 genes, 61 of which were also shared with the H2O2 transcriptome. This core of 61 genes encompassed many of the same pathways affected by exposure to low pH or zinc intoxication. Consistent with these findings, fructose negatively impacted the metal homeostasis of a mutant deficient in zinc expulsion and the growth of a mutant of the major oxidative stress regulator SpxA1. Importantly, fructose metabolism lowered culture pH at a faster pace, allowed better survival under acidic and nutrient-depleted conditions, and enhanced the competitiveness of S. mutans against Streptococcus sanguinis, although a moderated level of F-1-P might further boost some of these benefits. Conversely, several commensal streptococcal species displayed a greater sensitivity to fructose that may negatively affect their persistence and competitiveness in dental biofilm. In conclusion, fructose metabolism is integrated into the stress core of S. mutans and regulates critical functions required for survival and its ability to induce dysbiosis in the oral cavity.IMPORTANCEFructose is a common monosaccharide in the biosphere, yet its overconsumption has been linked to various health problems in humans including insulin resistance, obesity, diabetes, non-alcoholic liver diseases, and even cancer. These effects are in large part attributable to the unique biochemical characteristics and metabolic responses associated with the degradation of fructose. Yet, an understanding of the effects of fructose on the physiology of bacteria and its implications for the human microbiome is severely lacking. Here, we performed a series of analyses on the gene regulation of a dental pathogen Streptococcus mutans by exposing it to fructose and other important stress agents. Further supported by growth, persistence, and competition assays, our findings revealed the ability of fructose to activate a set of stress-related functions that may prove critical to the ability of the bacterium to persist and cause diseases both within and without the oral cavity.}, }
@article {pmid40238826, year = {2025}, author = {Lee, J and Kim, B}, title = {Zero inflated high dimensional compositional data with DeepInsight.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0320832}, pmid = {40238826}, issn = {1932-6203}, mesh = {Humans ; High-Throughput Nucleotide Sequencing/methods ; *Microbiota/genetics ; Neural Networks, Computer ; Inflammatory Bowel Diseases/microbiology ; Child ; }, abstract = {Through the Human Microbiome Project, research on human-associated microbiomes has been conducted in various fields. New sequencing techniques such as Next Generation Sequencing (NGS) and High-Throughput Sequencing (HTS) have enabled the inclusion of a wide range of features of the microbiome. These advancements have also contributed to the development of numerical proxies like Operational Taxonomic Units (OTUs) and Amplicon Sequence Variants (ASVs). Studies involving such microbiome data often encounter zero-inflated and high-dimensional problems. Based on the need to address these two issues and the recent emphasis on compositional interpretation of microbiome data, we conducted our research. To solve the zero-inflated problem in compositional microbiome data, we transformed the data onto the surface of the hypersphere using a square root transformation. Then, to solve the high-dimensional problem, we modified DeepInsight, an image-generating method using Convolutional Neural Networks (CNNs), to fit the hypersphere space. Furthermore, to resolve the common issue of distinguishing between true zero values and fake zero values in zero-inflated images, we added a small value to the true zero values. We validated our approach using pediatric inflammatory bowel disease (IBD) fecal sample data and achieved an area under the curve (AUC) value of 0.847, which is higher than the previous study's result of 0.83.}, }
@article {pmid40237489, year = {2025}, author = {Rybicka, I and Kaźmierczak, Z}, title = {The human phageome: niche-specific distribution of bacteriophages and their clinical implications.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {6}, pages = {e0178824}, pmid = {40237489}, issn = {1098-5336}, support = {UMO-2019/35/B/NZ7/01824//Narodowe Centrum Nauki/ ; UMO-2023/51/D/NZ7/02145//Narodowe Centrum Nauki/ ; }, mesh = {Humans ; *Bacteriophages/physiology/genetics/isolation &amp; purification ; *Bacteria/virology ; *Virome ; *Microbiota ; Gastrointestinal Microbiome ; }, abstract = {Bacteriophages (phages) play a crucial role in shaping the composition and diversity of the human microbiome across various body niches. Recent advancements in high-throughput sequencing technologies have enabled comprehensive analysis of the human phageome in different body sites. This review comprehensively analyzes phage populations across major human body niches, examining their distribution and dynamics through recent metagenomic discoveries. We explore how phage-bacteria interactions within different body sites contribute to homeostasis and disease development. Emerging evidence demonstrates that phageome perturbations can serve as early indicators of various disorders, particularly in the gut microbiome. Understanding these complex microbial interactions offers promising opportunities for developing novel diagnostic markers and therapeutic approaches. However, the causal relationship between phages, bacteria, and disease development remains unclear. Further research is needed to elucidate the role of phages in human health and disease and to explore their potential as diagnostic or therapeutic tools. Understanding the intricate interactions between phages, bacteria, and the human host is crucial for unraveling the complexities of the human microbiome and its impact on health and disease.}, }
@article {pmid40237447, year = {2025}, author = {Choudoir, MJ and Ishaq, SL and Beiko, RG and Silva, DS and Allen-Vercoe, E and O'Doherty, KC}, title = {The case for microbiome stewardship: what it is and how to get there.}, journal = {mSystems}, volume = {10}, number = {5}, pages = {e0006225}, pmid = {40237447}, issn = {2379-5077}, support = {//University of Guelph Institute of Environmental Research/ ; R15 DK133826/DK/NIDDK NIH HHS/United States ; 191753/CAPMC/CIHR/Canada ; //Canada Research Chairs/ ; 7004439, ME022329//U.S. Department of Agriculture's National Institute of Food and Agriculture/ ; //Natural Sciences and Engineering Research Council of Canada/ ; NIH/NIDDK 1R15DK133826-01/NH/NIH HHS/United States ; }, mesh = {Animals ; Humans ; Agriculture ; Anti-Bacterial Agents ; Ecosystem ; *Microbiota ; Public Health ; }, abstract = {Microbiomes are essential for human, animal, plant, and ecosystem health. Despite widespread recognition of the importance of microbiomes, there is little attention paid to monitoring and safeguarding microbial ecologies on policy levels. We observe that microbiomes are deteriorating owing to practices at societal levels such as pesticide use in agriculture, air and water pollution, and overuse of antibiotics. Potential policy on these issues would cross multiple domains such as public health, environmental protection, and agriculture. We propose microbiome stewardship as a foundational concept that can act across policy domains to facilitate healthy microbiomes for human and ecosystem health. We examine challenges to be addressed and steps to take toward developing meaningful microbiome stewardship.}, }
@article {pmid40236770, year = {2025}, author = {Zhang, C and Chen, Y and Duan, R and Zhang, Y and Zheng, H and Zhang, J and Zhang, T and Xu, J and Li, K and Pei, F and Duan, L}, title = {Preconception maternal gut dysbiosis affects enteric nervous system development and disease susceptibility in offspring via the GPR41-GDNF/RET/SOX10 signaling pathway.}, journal = {iMeta}, volume = {4}, number = {2}, pages = {e70012}, pmid = {40236770}, issn = {2770-596X}, abstract = {Maternal health, specifically changes in the gut microbiota, can profoundly impact offspring health; however, our understanding of how gut microbiota alterations during the preconception period influence the offspring remains limited. In this study, we investigated the impact and mechanisms of preconception maternal gut dysbiosis on the development of the enteric nervous system (ENS) in mice. We found that preconception maternal exposure to antibiotics led to the abnormal development of the ENS in offspring, increasing their susceptibility to water avoidance stress at the adult stage. Metagenomic, targeted metabolomic, and transcriptomic analyses revealed that preconception antibiotic exposure disrupted the expression of genes crucial for embryonic ENS development by altering maternal gut microbiota composition. Multi-omics analysis combined with Limosilactobacillus reuteri and propionate gestational supplementation demonstrated that the maternal gut microbiota and metabolites may influence embryonic ENS development via the GPR41-GDNF/RET/SOX10 signaling pathway. Our findings highlight the critical importance of maintaining a healthy maternal gut microbiota before conception to support normal ENS development in offspring.}, }
@article {pmid40235960, year = {2025}, author = {Basgaran, A and Lymberopoulos, E and Burchill, E and Reis-Dehabadi, M and Sharma, N}, title = {Machine learning determines the incidence of Alzheimer's disease based on population gut microbiome profile.}, journal = {Brain communications}, volume = {7}, number = {2}, pages = {fcaf059}, pmid = {40235960}, issn = {2632-1297}, abstract = {The human microbiome is a complex and dynamic community of microbes, thought to have symbiotic benefit to its host. Influences of the gut microbiome on brain microglia have been identified as a potential mechanism contributing to neurodegenerative diseases, such as Alzheimer's disease, motor neurone disease and Parkinson's disease (Boddy SL, Giovannelli I, Sassani M, et al. The gut microbiome: A key player in the complexity of amyotrophic lateral sclerosis (ALS). BMC Med. 2021;19(1):13). We hypothesize that population level differences in the gut microbiome will predict the incidence of Alzheimer's disease using machine learning methods. Cross-sectional analyses were performed in R, using two large, open-access microbiome datasets (n = 959 and n = 2012). Countries in these datasets were grouped based on Alzheimer's disease incidence and the gut microbiome profiles compared. In countries with a high incidence of Alzheimer's disease, there is a significantly lower diversity of the gut microbiome (P < 0.05). A permutational analysis of variance test (P < 0.05) revealed significant differences in the microbiome profile between countries with high versus low incidence of Alzheimer's disease with several contributing taxa identified: at a species level Escherichia coli, and at a genus level Haemophilus and Akkermansia were found to be reproducibly protective in both datasets. Additionally, using machine learning, we were able to predict the incidence of Alzheimer's disease within a country based on the microbiome profile (mean area under the curve 0.889 and 0.927). We conclude that differences in the microbiome can predict the varying incidence of Alzheimer's disease between countries. Our results support a key role of the gut microbiome in neurodegeneration at a population level.}, }
@article {pmid40235735, year = {2025}, author = {Xu, R and Yu, Y and Chen, T}, title = {Exploring the dark side of probiotics to pursue light: Intrinsic and extrinsic risks to be opportunistic pathogens.}, journal = {Current research in food science}, volume = {10}, number = {}, pages = {101044}, pmid = {40235735}, issn = {2665-9271}, abstract = {Probiotics, live microorganisms with multiple health benefits, have gained popularity for their roles in maintaining daily health and treating a variety of diseases. However, they have the potential to be opportunistic pathogens in some conditions. This review delves into the intrinsic and extrinsic risks associated with probiotics. Intrinsic risks involve the production of harmful substances, such as toxins and invasive factors, biofilm formation, bacteria emboli, antibiotic resistance with relevant genetic materials, genetic plasticity, and metabolic issues, while extrinsic risks include problems in regulatory oversight and public awareness, host health status and appropriately administration. It emphasizes the need for a balanced view of their therapeutic benefits and potential hazards, advocating for further research to understand the complex interactions between probiotics and the human microbiome, to optimize the safety and efficacy of probiotics.}, }
@article {pmid40231347, year = {2025}, author = {Hoffmanns, L and Svedberg, D and Mateus, A}, title = {Protein O-glycosylation in the Bacteroidota phylum.}, journal = {FEBS open bio}, volume = {}, number = {}, pages = {}, doi = {10.1002/2211-5463.70041}, pmid = {40231347}, issn = {2211-5463}, support = {Wallenberg Academy Fellows 2025//Knut och Alice Wallenbergs Stiftelse/ ; 2021-06602//Vetenskapsr&#xe5;det/ ; 2022-02958//Vetenskapsr&#xe5;det/ ; ProFITGut-101076015//H2020 European Research Council/ ; }, abstract = {Glycans play crucial roles in bacteria, such as providing structural integrity or enabling interactions with the ecosystem. They can be linked to lipids, peptides, or proteins. In proteins, they modify either asparagine (N-glycosylation) or serine or threonine (O-glycosylation). Species of the Bacteroidota phylum, a major component of the human microbiome and marine and soil ecosystems, have a unique type of O-glycosylation that modifies multiple noncytoplasmic proteins containing a specific amino acid sequence. Only a small number of species have currently been characterized, but within one species, generally all proteins are modified with the same glycan structure. Most species share a common inner part but differ in the sugar composition and branching of the outer part of their glycan. This suggests that the biosynthesis of the glycan occurs in two separate steps. Both the inner core and the outer glycan are likely assembled from nucleotide-activated monosaccharides on undecaprenyl phosphate on the cytoplasmic side of the inner membrane, prior to being flipped to the periplasm and transferred to the protein. A genomic locus responsible for the biosynthesis of the outer glycan has been identified, containing some conserved genes across species. Despite substantial progress in the characterization of this O-glycosylation system, its function, the overall diversity of glycan structures across the phylum, and the complete biosynthetic pathway remain mostly unknown. Due to the importance of this group of species for the human gut microbiome, elucidating these aspects can open up strategies to modulate the composition of the microbiome community toward a healthy state.}, }
@article {pmid40229539, year = {2025}, author = {Magne, F and Ruiz-Ruiz, S and Pérez-Brocal, V and Ponce, CA and Bustamante, R and Martin, VS and Gutierrez, M and Gatti, G and Vargas, SL and Moya, A}, title = {Pneumocystis jirovecii is a potential pivotal ecological driver contributing to shifts in microbial equilibrium during the early-life lower airway microbiome assembly.}, journal = {Communications biology}, volume = {8}, number = {1}, pages = {609}, pmid = {40229539}, issn = {2399-3642}, mesh = {Humans ; Infant ; *Microbiota ; *Lung/microbiology ; Female ; *Pneumocystis carinii/physiology/genetics ; Male ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics/classification ; Infant, Newborn ; }, abstract = {Early life gut microbiota is being increasingly recognized as a major contributor to short and/or long-term human health and diseases. However, little is known about these early-life events in the human microbiome of the lower respiratory tract. This study aims to investigate fungal and bacterial colonization in the lower airways over the first year of life by analyzing lung tissue from autopsied infants. The fungal and bacterial communities of lung tissue samples from 53 autopsied infants were characterized by Next-Generation Sequencing (NGS), based on universal PCR amplification of the ITS region and the 16S rRNA gene, respectively. Our study highlights a high degree of inter-individual variability in both fungal and bacterial communities inhabiting the infant lung. The lower respiratory tract microbiota is mainly composed of transient microorganisms that likely travel from the upper respiratory tract and do not establish permanent residence. However, it could also contain some genera identified as long-term inhabitants of the lung, which could potentially play a role in lung physiology or disease. At 3-4 months of age, important dynamic changes to the microbial community were observed, which might correspond to a transitional time period in the maturation of the lung microbiome. This timeframe represents a susceptibility period for the colonization of pathogens such as Pneumocystis. The asymptomatic colonization of Pneumocystis was associated with changes in the fungal and bacterial communities. These findings suggest that the period of 2-4 months of age is a "critical window" early in life. Pneumocystis jirovecii could be a potential pivotal ecological driver contributing to shifts in microbial equilibrium during the early-life lower airway microbiome assembly, and to the future health of children.}, }
@article {pmid40227812, year = {2025}, author = {Leigh, J and Skidmore, B and Wong, A and Maleki Vareki, S and Ng, TL}, title = {Exploring the Microbiome's Impact on Glioma and Brain Metastases: Insights into Development, Progression, and Treatment Response-A Scoping Review.}, journal = {Cancers}, volume = {17}, number = {7}, pages = {}, pmid = {40227812}, issn = {2072-6694}, abstract = {Background: The human microbiome plays a crucial role in health and disease. Dysbiosis, an imbalance of microorganisms, has been implicated in cancer development and treatment response, including in primary brain tumors and brain metastases, through interactions mediated by the gut-brain axis. This scoping review synthesizes current evidence on the relationship between the human microbiome and brain tumors. Methods: A systematic search of five electronic databases was conducted by an expert librarian, using controlled vocabulary and keywords. A targeted grey literature search in Google Scholar and clinical trial registries was also undertaken. Eligible studies included primary research involving human patients, or in vivo, or in vitro models of glioma or brain metastasis, with a focus on the microbiome's role in tumor development, treatment response, and outcomes. Results: Out of 584 citations screened, 40 studies met inclusion criteria, comprising 24 articles and 16 conference abstracts. These included 12 human studies, 16 using mouse models, 7 combining both, and 5 employing large datasets or next-generation sequencing of tumor samples. Thirty-one studies focused on primary brain tumors, six on brain metastases, and three on both. Of the 20 studies examining dysbiosis in tumor development, 95% (n = 19) found an association with tumor growth. Additionally, 71.4% (n = 5/7) of studies reported that microbiome alterations influenced treatment efficacy. Conclusions: Although the role of the gut-brain axis in brain tumors is still emerging and is characterized by heterogeneity across studies, existing evidence consistently supports a relationship between the gut microbiome and both brain tumor development and treatment outcomes.}, }
@article {pmid40219702, year = {2025}, author = {Xiao, Y and Yue, X and Zhang, X and Yang, Y and Zhang, Y and Sun, L}, title = {The role of bacteriophage in inflammatory bowel disease and its therapeutic potential.}, journal = {Critical reviews in microbiology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/1040841X.2025.2492154}, pmid = {40219702}, issn = {1549-7828}, abstract = {Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory disorders impacting the gastrointestinal (GI) tract. It represents a significant public health challenge due to its rising global incidence and substantial impact on patients' quality of life. Emerging research suggests a pivotal role of the human microbiome in IBD pathogenesis. Bacteriophages, integral components of the human microbiome, are indicated to influence the disease onset, progression, and therapeutic strategies. Here, we review the effect of bacteriophages on the pathogenesis of IBD and, more specifically, on the gut bacteria, the systemic immunity, and the susceptibility genes. Additionally, we explore the potential therapeutic use of the bacteriophages to modify gut microbiota and improve the health outcomes of IBD patients. This review highlights the potential of therapeutic bacteriophages in regulating gut microbiota and modulating the immune response to improve health outcomes in IBD patients. Future studies on personalized bacteriophage therapy and its integration into clinical practice could advance treatment strategies for IBD.}, }
@article {pmid40214493, year = {2025}, author = {Rahim, MA and Seo, H and Barman, I and Hossain, MS and Shuvo, MSH and Song, HY}, title = {Insights into Autophagy in Microbiome Therapeutic Approaches for Drug-Resistant Tuberculosis.}, journal = {Cells}, volume = {14}, number = {7}, pages = {}, pmid = {40214493}, issn = {2073-4409}, support = {RS-2023-00219563//National Research Foundation of Korea/ ; P248400003//Korea Institute for Advancement of Technology (KIAT)/ ; Soonchunhyang University Research Fund//Soonchunhyang University/ ; }, mesh = {Humans ; *Autophagy ; *Tuberculosis, Multidrug-Resistant/therapy/microbiology ; *Microbiota ; Mycobacterium tuberculosis/drug effects ; Animals ; Antitubercular Agents/therapeutic use/pharmacology ; }, abstract = {Tuberculosis, primarily caused by Mycobacterium tuberculosis, is an airborne lung disease and continues to pose a significant global health threat, resulting in millions of deaths annually. The current treatment for tuberculosis involves a prolonged regimen of antibiotics, which leads to complications such as recurrence, drug resistance, reinfection, and a range of side effects. This scenario underscores the urgent need for novel therapeutic strategies to combat this lethal pathogen. Over the last two decades, microbiome therapeutics have emerged as promising next-generation drug candidates, offering advantages over traditional medications. In 2022, the Food and Drug Administration approved the first microbiome therapeutic for recurrent Clostridium infections, and extensive research is underway on microbiome treatments for various challenging diseases, including metabolic disorders and cancer. Research on microbiomes concerning tuberculosis commenced roughly a decade ago, and the scope of this research has broadened considerably over the last five years, with microbiome therapeutics now viewed as viable options for managing drug-resistant tuberculosis. Nevertheless, the understanding of their mechanisms is still in its infancy. Although autophagy has been extensively studied in other diseases, research into its role in tuberculosis is just beginning, with preliminary developments in progress. Against this backdrop, this comprehensive review begins by succinctly outlining tuberculosis' characteristics and assessing existing treatments' strengths and weaknesses, followed by a detailed examination of microbiome-based therapeutic approaches for drug-resistant tuberculosis. Additionally, this review focuses on establishing a basic understanding of microbiome treatments for tuberculosis, mainly through the lens of autophagy as a mechanism of action. Ultimately, this review aims to contribute to the foundational comprehension of microbiome-based therapies for tuberculosis, thereby setting the stage for the further advancement of microbiome therapeutics for drug-resistant tuberculosis.}, }
@article {pmid40211685, year = {2025}, author = {Kim, JW and Choi, EC and Lee, KJ}, title = {Standardizing the approach to clinical-based human microbiome research: from clinical information collection to microbiome profiling and human resource utilization.}, journal = {Osong public health and research perspectives}, volume = {16}, number = {3}, pages = {300-307}, pmid = {40211685}, issn = {2210-9099}, support = {2023-NI-019-01//Korea National Institute of Health/ ; }, abstract = {BACKGROUND: This study presents the standardized protocols developed by the Clinical-Based Human Microbiome Research and Development Project (cHMP) in the Republic of Korea.<br><br>METHODS: It addresses clinical metadata collection, specimen handling, DNA extraction, sequencing methods, and quality control measures for microbiome research.<br><br>RESULTS: The cHMP involves collecting samples from healthy individuals and patients across various body sites, including the gastrointestinal tract, oral cavity, respiratory system, urogenital tract, and skin. These standardized procedures ensure consistent data quality through controlled specimen collection, storage, transportation, DNA extraction, and sequencing. Sequencing encompasses both amplicon and whole metagenome methods, followed by stringent quality checks. The protocols conform to international guidelines, ensuring that the data generated are both reliable and comparable across microbiome studies.<br><br>CONCLUSION: The cHMP underscores the importance of methodological standardization in enhancing data integrity, reproducibility, and advancing microbiome-based research with potential applications for improving human health outcomes.}, }
@article {pmid40207916, year = {2025}, author = {Lebrun-Corbin, M and Cheung, BH and Hullahalli, K and Dailey, KG and Bailey, K and Waldor, MK and Wunderink, RG and Bachta, KER and Hauser, AR}, title = {Pseudomonas aeruginosa population dynamics in a vancomycin-induced murine model of gastrointestinal carriage.}, journal = {mBio}, volume = {16}, number = {5}, pages = {e0313624}, pmid = {40207916}, issn = {2150-7511}, support = {R21 AI153953/AI/NIAID NIH HHS/United States ; U19 AI135964/AI/NIAID NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; T32 GM008152/GM/NIGMS NIH HHS/United States ; R01 AI118257/AI/NIAID NIH HHS/United States ; T32 GM144295/GM/NIGMS NIH HHS/United States ; R21 AI129167/AI/NIAID NIH HHS/United States ; K24 AI104831/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Pseudomonas aeruginosa/growth &amp; development/isolation &amp; purification/drug effects/genetics ; Mice ; *Carrier State/microbiology ; *Pseudomonas Infections/microbiology ; Disease Models, Animal ; *Vancomycin/administration &amp; dosage ; *Gastrointestinal Tract/microbiology ; *Anti-Bacterial Agents/administration &amp; dosage ; Female ; Humans ; Gastrointestinal Microbiome ; }, abstract = {UNLABELLED: Pseudomonas aeruginosa is a common nosocomial pathogen and a major cause of morbidity and mortality in hospitalized patients. Multiple reports highlight that P. aeruginosa gastrointestinal colonization may precede systemic infections by this pathogen. Gaining a deeper insight into the dynamics of P. aeruginosa gastrointestinal carriage is an essential step in managing gastrointestinal colonization and could contribute to preventing bacterial transmission and progression to systemic infection. Here, we present a clinically relevant mouse model relying on parenteral vancomycin pretreatment and a single orogastric gavage of a controlled dose of P. aeruginosa. Robust carriage was observed with multiple clinical isolates, and carriage persisted for up to 60 days. Histological and microbiological examination of mice indicated that this model indeed represented carriage and not infection. We then used a barcoded P. aeruginosa library along with the sequence tag-based analysis of microbial populations (STAMPR) analytic pipeline to quantify bacterial population dynamics and bottlenecks during the establishment of the gastrointestinal carriage. Analysis indicated that most of the P. aeruginosa population was rapidly eliminated in the stomach, but the few bacteria that moved to the small intestine and the cecum expanded rapidly. Hence, the stomach constitutes a significant barrier against gastrointestinal carriage of P. aeruginosa, which may have clinical implications for hospitalized patients.<br><br>IMPORTANCE: While Pseudomonas aeruginosa is rarely part of the normal human microbiome, carriage of the bacterium is quite frequent in hospitalized patients and residents of long-term care facilities. P. aeruginosa carriage is a precursor to infection. Options for treating infections caused by difficult-to-treat P. aeruginosa strains are dwindling, underscoring the urgency to better understand and impede pre-infection stages, such as colonization. Here, we use vancomycin-treated mice to model antibiotic-treated patients who become colonized with P. aeruginosa in their gastrointestinal tracts. We identify the stomach as a major barrier to the establishment of gastrointestinal carriage. These findings suggest that efforts to prevent gastrointestinal colonization should focus not only on judicious use of antibiotics but also on investigation into how the stomach eliminates orally ingested P. aeruginosa.}, }
@article {pmid40207286, year = {2025}, author = {Ronkainen, A and Khan, I and Satokari, R}, title = {Pathogen exclusion from intestinal mucus and antimicrobial susceptibility of Bifidobacterium spp. strains from fecal donors.}, journal = {Microbiome research reports}, volume = {4}, number = {1}, pages = {5}, pmid = {40207286}, issn = {2771-5965}, abstract = {Aim: To study the ability of bifidobacterial strains isolated from fecal donors to prevent pathogens from adhering to intestinal mucus, along with their antimicrobial susceptibility. Methods: Pathogen prevention was assessed through an in vitro adhesion assay using immobilized porcine mucus. Subsequently, bifidobacterial RNA-Seq data were analyzed to pinpoint glycoside hydrolases and glycosyltransferases possibly involved in mucus degradation affecting pathogen adhesion. The antimicrobial susceptibility of bifidobacterial strains was evaluated using in vitro susceptibility testing, followed by analysis of whole-genome sequencing data to reveal antimicrobial resistance genes. Results: Bifidobacterial strains inhibited pathogen adhesion to intestinal mucus, with most strains reducing the adhesion levels of pathogens like Escherichia coli, Listeria monocytogenes, Salmonella Typhimurium, and Staphylococcus aureus by at least 70%. None of the strains significantly affected Pseudomonas aeruginosa, but they moderately reduced the adhesion of Yersinia enterocolitica. Gene expression analysis indicated that the more effective strains expressed higher levels of glycoside hydrolases, correlating with their pathogen exclusion capabilities. Antimicrobial susceptibility testing revealed that most strains were sensitive to several antibiotics, though some exhibited resistance to tobramycin, trimethoprim, and ciprofloxacin. Notably, one strain carried the tetW gene, conferring resistance to tetracycline. Conclusion: The bifidobacterial strains characterized in this study show potential for bacteriotherapeutic applications due to their strong ability to interfere with the adhesion of pathogenic bacteria and their lack of alarming antimicrobial resistance patterns.}, }
@article {pmid40207282, year = {2025}, author = {Stuivenberg, GA and Poon, A and Burton, JP and Spence, JD}, title = {Potential effects of probiotics on atherosclerosis.}, journal = {Microbiome research reports}, volume = {4}, number = {1}, pages = {11}, pmid = {40207282}, issn = {2771-5965}, abstract = {The rising global incidence of atherosclerosis highlights the inadequacies in our understanding of the pathophysiology and treatment of the disease. Increasing evidence outlines the importance of the intestinal microbiome in atherosclerosis, wherein gut-derived uremic toxins (GDUTs) may be of concern. Plasma levels of the GDUTs trimethylamine n-oxide (TMAO), p-cresyl sulfate, and indoxyl sulfate are associated with accelerated renal function decline and increased cardiovascular risk. Thus, reducing the amount of GDUTs in circulation is expected to benefit patients with atherosclerosis. Because some beneficial bacteria can clear GDUTs in vitro and in vivo, orally administered probiotics targeting the intestinal tract represent a promising way to bring about these changes. Atherosclerosis such, this perspective reviews the potential use of probiotics to treat atherosclerosis, particularly in patients with non-traditional risk factors and/or impaired renal function.}, }
@article {pmid40207275, year = {2025}, author = {Horwell, E and Bearn, P and Cutting, SM}, title = {A microbial symphony: a literature review of the factors that orchestrate the colonization dynamics of the human colonic microbiome during infancy and implications for future health.}, journal = {Microbiome research reports}, volume = {4}, number = {1}, pages = {1}, pmid = {40207275}, issn = {2771-5965}, abstract = {Since the advent of new sequencing and bioinformatic technologies, our understanding of the human microbiome has expanded rapidly over recent years. Numerous studies have indicated causal links between alterations to the microbiome and a range of pathological conditions. Furthermore, a large body of epidemiological data is starting to suggest that exposure, or lack thereof, to specific microbial species during the first five years of life has key implications for long-term health outcomes. These include chronic inflammatory and metabolic conditions such as diabetes, asthma, inflammatory bowel disease (IBD), and obesity, with the effects lasting into adulthood. Human microbial colonisation during these first five years of life is a highly dynamic process, with multiple environmental exposures recently being characterised to have influence before the microbiome stabilises and resembles that of an adult at 3-5 years. This short period of time, known as the window of opportunity, appears to "prime" immunoregulation for later life. Understanding and appreciating this aspect of human physiology is therefore crucial for clinicians, scientists, and public health officials. This review outlines the most recent evidence for the pre- and post-natal environments that order the development of the microbiome, how these influences metabolic and immunoregulatory pathways, and their associated health outcomes. It also discusses the limitations of the current knowledge base, and describes the potential microbiome-mediated interventions and public health measures that may have therapeutic potential in the future.}, }
@article {pmid40207273, year = {2025}, author = {van Beek, N and Katavisto, I and Lehto, M and Kolho, KL and de Vos, WM and Salonen, A and Korpela, K}, title = {Host-microbiota interactions in the infant gut revealed by daily faecal sample time series.}, journal = {Microbiome research reports}, volume = {4}, number = {1}, pages = {13}, pmid = {40207273}, issn = {2771-5965}, abstract = {Aim: This study aims to explore the interplay between host immune factors and gut microbiota in human infants in vivo using time-series daily stool samples and identify biomarkers of host-microbe interactions. Methods: 216 faecal samples collected from infants aged 5-6 or 11-12 months were analysed for gut microbiota composition, total bacterial load, and biomarkers of immune function. Results: We identified indications of microbial stimulation of eosinophil cationic protein (ECP), IgA, calprotectin (Cal), intestinal alkaline phosphatase (IAP), and Bactericidal/permeability-increasing protein (BPI) at 6 and 12 months, as well as stimulation of lipocalin 2 (LCN2), lactoferrin (LTF), and alpha-defensin-5 only at 6 months. The associations between biomarker concentrations and bacterial population growth were primarily positive at 6 months and mostly negative at 12 months, suggesting increasing host regulation of the microbiota with age. The exceptions were IAP, which was predictive of declining bacterial populations at both time points, and Cal, whose associations changed from negative at 6 months to positive at 12 months. Conclusion: There is an age-associated development in the correlation pattern between bacterial population growth and the biomarker concentrations, suggesting that host-microbe interactions change during early development. Albumin appeared as a potential marker of gut permeability, while LCN2 seemed to correlate with gut transit time. Mucin degradation appeared to decrease with age. Mucin2 and IAP emerged as potentially important regulators of the bacterial populations in the infant gut. The study demonstrates the utility of biomarker and bacteria profiling from daily stool samples for analysing in vivo associations between the immune system and the gut microbiota and provides evidence of host regulation of the microbiota in infants.}, }
@article {pmid40195307, year = {2025}, author = {Zhang, J and Yang, J and Luo, J and Wu, W and Luo, H and Wei, W and Lyu, H and Wang, Y and Yi, H and Zhang, Y and Fan, Z and Lyu, H and Kanakaveti, VP and Qin, B and Yuan, P and Yang, R and Zhang, H and Zuo, T and Felsher, DW and Lee, MH and Li, K}, title = {Lactobacillus acidophilus potentiates oncolytic virotherapy through modulating gut microbiota homeostasis in hepatocellular carcinoma.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3315}, pmid = {40195307}, issn = {2041-1723}, support = {R35 CA253180/CA/NCI NIH HHS/United States ; 82373139//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82204411//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2023A1515010737//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; 2023A1515030245//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; 82473321//National Natural Science Foundation of China (National Science Foundation of China)/ ; U01 CA288433/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Lactobacillus acidophilus/metabolism/physiology ; *Carcinoma, Hepatocellular/therapy/microbiology ; *Liver Neoplasms/therapy/microbiology ; *Oncolytic Virotherapy/methods ; Mice ; Female ; Homeostasis ; Humans ; Oncolytic Viruses/genetics ; Mice, Inbred C57BL ; Dysbiosis/microbiology ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; }, abstract = {Oncolytic viruses (OVs) hold promise for cancer treatment. However, the antitumor efficacy is limited. Microbiota plays a pivotal role in cancer treatment and its impact on oncolytic virotherapy is unknown. Here, we show that VSVΔ51 has higher antitumor efficacy for hepatocellular carcinoma in the absence of microbiota in female mouse models. VSVΔ51 infection causes microbiota dysbiosis, increasing most of the gut bacteria abundance, while decreasing the commensal Lactobacillus. VSVΔ51 reduced intestinal expression of SLC20A1 that binds to Lactobacillus acidophilus (L. acidophilus) CdpA cell wall protein through IL6-JAK-STAT3 signaling, thereby attenuating attachment and colonization of L. acidophilus. L. acidophilus supplementation confers sensitivity to VSVΔ51 through restoring gut barrier integrity and microbiota homeostasis destroyed by VSVΔ51. In this work, we show that targeting microbiota homostasis holds substantial potential in improving therapeutic outcomes of oncolytic virotherapy.}, }
@article {pmid40193328, year = {2025}, author = {Jagadesan, S and Guda, C}, title = {MetaDAVis: An R shiny application for metagenomic data analysis and visualization.}, journal = {PloS one}, volume = {20}, number = {4}, pages = {e0319949}, pmid = {40193328}, issn = {1932-6203}, mesh = {*Metagenomics/methods ; Humans ; RNA, Ribosomal, 16S/genetics ; *Software ; *Metagenome ; Microbiota/genetics ; High-Throughput Nucleotide Sequencing ; }, abstract = {The human microbiome exerts tremendous influence on maintaining a balance between human health and disease. High-throughput sequencing has enabled the study of microbial communities at an unprecedented resolution. Generation of massive amounts of sequencing data has also presented novel challenges to analyzing and visualizing data to make biologically relevant interpretations. We have developed an interactive Metagenome Data Analysis and Visualization (MetaDAVis) tool for 16S rRNA as well as the whole genome sequencing data analysis and visualization to address these challenges using an R Shiny application. MetaDAVis can perform six different types of analyses that include: i) Taxonomic abundance distribution; ii) Alpha and beta diversity analyses; iii) Dimension reduction tasks using PCA, t-SNE, and UMAP; iv) Correlation analysis using taxa- or sample-based data; v) Heatmap generation; and vi) Differential abundance analysis. MetaDAVis creates interactive and dynamic figures and tables from multiple methods enabling users to easily understand their data using different variables. Our program is user-friendly and easily customizable allowing those without any programming background to perform comprehensive data analyses using a standalone or web-based interface.}, }
@article {pmid40192037, year = {2025}, author = {Verma, M and Randhawa, S and Bathla, M and Teji, N and Acharya, A}, title = {Strategic use of nanomaterials as double-edged therapeutics to control carcinogenesis via regulation of dysbiosis and bacterial infection: current status and future prospects.}, journal = {Journal of materials chemistry. B}, volume = {13}, number = {16}, pages = {4770-4790}, doi = {10.1039/d4tb02409e}, pmid = {40192037}, issn = {2050-7518}, mesh = {Humans ; *Dysbiosis/drug therapy ; *Bacterial Infections/drug therapy ; *Carcinogenesis/drug effects ; *Nanostructures/chemistry/therapeutic use ; *Neoplasms/drug therapy ; Animals ; *Antineoplastic Agents/pharmacology/chemistry ; Anti-Bacterial Agents/pharmacology/chemistry ; }, abstract = {The human microbiome plays a crucial role in modulating health and disease susceptibility through a complex network of interactions with the host. When the delicate balance of this microbial ecosystem is disrupted, it often correlates with the onset of systemic diseases. An over-abundance of pathogenic microorganisms within the microbiome has been implicated as a driving factor in the development of disease conditions such as diabetes, obesity, and chronic infections. It has been observed that microbiome dysbiosis perturbs metabolic, inflammatory, and immunological pathways, potentially facilitating carcinogenesis. Furthermore, the metabolites associated with microbial dysbiosis exert multifaceted effects, including metabolic interference, host DNA damage, and tumor promotion, further underscoring the microbiome's significance in several of the cancers. This new exploration of microbiome involvement in carcinogenesis needs additional patient sample analysis, which could provide new insights into cancer diagnosis and treatment. However, treating these diseases using drugs, traditional methods, etc. has resulted in multi-drug resistance, and this has eventually made the situation worrisome. This review highlights the importance of nanotechnology, which may tackle these pathogenic conditions simultaneously by targeting common receptors present in bacteria and cancer. Herein, we have explained how nanotechnology may come to the forefront for these treatments. It explores the potential of non-antibiotic disinfectants, i.e., nanoparticles (NPs) with dual targeting capabilities against microbes and cancer cells, using mechanisms such as ROS generation and DNA damage while minimizing the chances of drug resistance.}, }
@article {pmid40191210, year = {2025}, author = {Karisola, P and Kanerva, M and Vuokko, A and Liira, H and Wang, S and Kvarnström, K and Varonen, M and Suojalehto, H and Alenius, H}, title = {Patients with post-COVID-19 condition show minor blood transcriptomic changes, with altered erythrocyte gene expression in a male subgroup.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1500997}, pmid = {40191210}, issn = {1664-3224}, mesh = {Humans ; *COVID-19/genetics/blood/immunology/complications ; Male ; Middle Aged ; *Transcriptome ; *SARS-CoV-2 ; Aged ; *Erythrocytes/metabolism ; Female ; Adult ; Gene Expression Profiling ; Leukocytes, Mononuclear/metabolism ; Quality of Life ; }, abstract = {BACKGROUND: The mechanisms underlying persistent symptoms after non-severe COVID-19 remain unclear. This study aimed to investigate transcriptomic changes in peripheral blood cells of patients with post-COVID-19 condition (PCC) and assess if distinct clinical subtypes with specific gene signatures could be identified.<br><br>METHODS: The cohort included 111 PCC patients from the SARS-CoV-2 Omicron variant era, with 57 recovered (Recov) and 54 having prolonged symptoms indicative of PCC. The results were compared to 63 healthy controls (Ctrl) without known SARS-CoV-2 infection. Clinical data included patient assessments, laboratory results, comorbidities, and questionnaires on quality of life and functioning. Transcriptomic analysis and cellular deconvolution methods were used on total RNA from peripheral blood mononuclear cells (PBMCs).<br><br>RESULTS: PCC patients had more comorbidities (mean 1.3) and more frequently (59%) at least one comorbidity than recovered patients (31%) and controls (24%). Overall, past COVID-19 illness or current PCC symptoms caused minimal changes in the blood cell transcriptome, with only 3-6 differentially expressed genes (DEGs) identified across comparisons. However, a subset of male PCC patients exhibited an increased fraction of deconvoluted erythroblasts and significant genome-wide gene expression changes, with 399 DEGs compared to recovered and control males. These genes were enriched in pathways related to heme metabolism and gas exchange in erythrocytes.<br><br>CONCLUSIONS: Persistent symptoms in PCC are multifactorial and not directly linked to peripheral blood cell gene expression changes. However, a subgroup of male PCC patients shows distinct erythrocyte responses that may contribute to long-term symptoms.}, }
@article {pmid40190580, year = {2025}, author = {Delicati, A and Marcante, B and Catelan, D and Biggeri, A and Caenazzo, L and Tozzo, P}, title = {Hand-to-surface bacterial transfer and healthcare-associated infections prevention: a pilot study on skin microbiome in a molecular biology laboratory.}, journal = {Frontiers in medicine}, volume = {12}, number = {}, pages = {1546298}, pmid = {40190580}, issn = {2296-858X}, abstract = {BACKGROUND: Healthcare-associated infections (HAIs) are a major global public health problem, contributing significantly to patient morbidity and mortality. This study analyses differences in type and amounts of bacteria transferred from volunteers' dominant palm to two healthcare-relevant surfaces (glass and laminate table), both before and after hand washing with water and antibacterial soap. The aim was to understand hand-to-surface microbial contamination and support the development of HAI prevention strategies.<br><br>METHODS: Microbial DNA was extracted and sequenced to identify bacteria species. Taxonomic and statistical analyses were performed to evaluate bacterial diversity and abundance across the experimental groups.<br><br>RESULTS: The results confirmed greater bacteria abundance and species richness on palm compared to surfaces, with a significant reduction after hand washing, especially on glass. Taxa analysis highlighted the increased persistence of Gram-negative HAIs-related bacteria on laminate surface, while Gram-positive opportunistic bacteria were more abundant on palms and glass surface. Beta diversity confirmed significant differences in microbial composition between the groups, highlighting the importance of bacteria-surface characteristics in designing preventive measures.<br><br>CONCLUSION: Despite some limitations, our study emphasizes the importance of microbiological surveillance for all opportunistic bacteria with pathogenic potential. These findings can contribute to more effective guidelines for surface disinfection and hand washing, key elements in preventing HAIs.}, }
@article {pmid40188410, year = {2025}, author = {Oyovwi, MO and Ben-Azu, B and Babawale, KH}, title = {Therapeutic potential of microbiome modulation in reproductive cancers.}, journal = {Medical oncology (Northwood, London, England)}, volume = {42}, number = {5}, pages = {152}, pmid = {40188410}, issn = {1559-131X}, mesh = {Humans ; *Microbiota ; Probiotics/therapeutic use ; Female ; Dysbiosis/microbiology/therapy ; *Genital Neoplasms, Female/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Animals ; Gastrointestinal Microbiome ; }, abstract = {The human microbiome, a complex ecosystem of microbial communities, plays a crucial role in physiological processes, and emerging research indicates a potential link between it and reproductive cancers. This connection highlights the significance of understanding the microbiome's influence on cancer development and treatment. A comprehensive review of current literature was conducted, focusing on studies that investigate the relationship between microbiome composition, reproductive cancer progression, and potential therapeutic approaches to modulate the microbiome. Evidence suggests that imbalances in the microbiome, known as dysbiosis, may contribute to the development and progression of reproductive cancers. Specific microbial populations have been associated with inflammatory responses, immune modulation, and even resistance to conventional therapies. Interventions such as probiotics, dietary modifications, and fecal microbiota transplantation have shown promise in restoring healthy microbiome function and improving cancer outcomes in pre-clinical models, with pilot studies in humans indicating potential benefits. This review explores the therapeutic potential of microbiome modulation in the management of reproductive cancers, discussing the mechanisms involved and the evidence supporting microbiome-targeted therapies. Future research is warranted to unravel the complex interactions between the microbiome and reproductive cancer pathophysiology, paving the way for innovative approaches.}, }
@article {pmid40177558, year = {2025}, author = {Xia, S and Jiang, D and Zhou, Q and Lyu, H and Voigt, AY and Zhou, X and Zhou, Z and Huang, Y}, title = {Unlocking the healthy human microbiome: Redefining core microbial signatures.}, journal = {Acta pharmaceutica Sinica. B}, volume = {15}, number = {2}, pages = {1189-1192}, pmid = {40177558}, issn = {2211-3835}, }
@article {pmid40174574, year = {2025}, author = {Zeng, S and Almeida, A and Mu, D and Wang, S}, title = {Embracing the unknown: Proteomic insights into the human microbiome.}, journal = {Cell metabolism}, volume = {37}, number = {4}, pages = {799-801}, doi = {10.1016/j.cmet.2025.02.003}, pmid = {40174574}, issn = {1932-7420}, mesh = {Humans ; *Proteomics/methods ; *Microbiota ; Animals ; *Gastrointestinal Microbiome ; Mice ; Inflammatory Bowel Diseases/microbiology/metabolism ; Metagenome ; *Proteome ; }, abstract = {Protein-level investigations into the human microbiome provide insights into active microbial functions. Recently, Valdés-Mas et al.[1] introduced a metagenome-informed metaproteomics approach to functionally explore species-level microbiome-host interactions and quantify the dietary exposome. Its potential has been implemented in mice and humans to uncover proteomic signatures of health and inflammatory bowel disease.}, }
@article {pmid40170399, year = {2025}, author = {Schütz, B and Krause, FF and Taudte, RV and Zaiss, MM and Luu, M and Visekruna, A}, title = {Modulation of Host Immunity by Microbiome-Derived Indole-3-Propionic Acid and Other Bacterial Metabolites.}, journal = {European journal of immunology}, volume = {55}, number = {4}, pages = {e202451594}, pmid = {40170399}, issn = {1521-4141}, support = {VI562/7-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Indoles/metabolism/immunology ; Animals ; Immunity, Mucosal ; *Bacteria/metabolism/immunology ; Dysbiosis/immunology ; Intestinal Mucosa/immunology ; }, abstract = {In recent years, we have witnessed a rapidly growing interest in the intricate communications between intestinal microorganisms and the host immune system. Research on the human microbiome is evolving from merely descriptive and correlative studies to a deeper mechanistic understanding of the bidirectional interactions between gut microbiota and the mucosal immune system. Despite numerous challenges, it has become increasingly evident that an imbalance in gut microbiota composition, known as dysbiosis, is associated with the development and progression of various metabolic, immune, cancer, and neurodegenerative disorders. A growing body of evidence highlights the importance of small molecules produced by intestinal commensal bacteria, collectively referred to as gut microbial metabolites. These metabolites serve as crucial diffusible messengers, translating the microbial language to host cells. This review aims to explore the complex and not yet fully understood molecular mechanisms through which microbiota-derived metabolites influence the activity of the immune cells and shape immune reactions in the gut and other organs. Specifically, we will discuss recent research that reveals the close relationship between microbial indole-3-propionic acid (IPA) and mucosal immunity. Furthermore, we will emphasize the beneficial effects of IPA on intestinal inflammation and discuss its potential clinical implications.}, }
@article {pmid40166311, year = {2025}, author = {Inglis, LK and Grigson, SR and Roach, MJ and Edwards, RA}, title = {Prophages as a source of antimicrobial resistance genes in the human microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40166311}, issn = {2692-8205}, support = {RC2 DK116713/DK/NIDDK NIH HHS/United States ; }, abstract = {Prophages-viruses that integrate into bacterial genomes-are ubiquitous in the microbial realm. Prophages contribute significantly to horizontal gene transfer, including the potential spread of antimicrobial resistance (AMR) genes, because they can collect host genes. Understanding their role in the human microbiome is essential for fully understanding AMR dynamics and possible clinical implications. We analysed almost 15,000 bacterial genomes for prophages and AMR genes. The bacteria were isolated from diverse human body sites and geographical regions, and their genomes were retrieved from GenBank. AMR genes were detected in 6.6% of bacterial genomes, with a higher prevalence in people with symptomatic diseases. We found a wide variety of AMR genes combating multiple drug classes. We discovered AMR genes previously associated with plasmids, such as blaOXA-23 in Acinetobacter baumannii prophages or genes found in prophages in species they had not been previously described in, such as mefA-msrD in Gardnerella prophages, suggesting prophage-mediated gene transfer of AMR genes. Prophages encoding AMR genes were found at varying frequencies across body sites and geographical regions, with Asia showing the highest diversity of AMR genes.}, }
@article {pmid40162761, year = {2025}, author = {Jung, M and Boutin, S and Simon, MM and Frese, C}, title = {Comparative analysis of oral microbiome in molar-incisor-hypomineralization vs healthy age-matched controls.}, journal = {Microbiology spectrum}, volume = {13}, number = {5}, pages = {e0289724}, pmid = {40162761}, issn = {2165-0497}, abstract = {UNLABELLED: Molar-incisor-hypomineralization (MIH) is one of the most challenging dental diseases in children. While the association of oral microbiomes with caries and periodontitis has been studied thoroughly, limited data on the microbial composition in MIH and its clinical significance exist. This cross-sectional study aimed to compare the supragingival plaque microbiome between children and adolescents affected by MIH and a healthy age-matched control group. Ninety-five patients aged 7-17 years were recruited at the Department of Conservative Dentistry, Heidelberg University Hospital. The final sample included 29 participants with a confirmed diagnosis of MIH, treated preventively and restoratively, and 35 orally healthy controls. Clinical data were obtained, and supragingival plaque samples were collected using OMNIgene ORAL OMR-110 (DNA Genotek Inc.), followed by 16S rRNA amplicon sequencing. The microbiome composition was analyzed using α-diversity (Shannon index) and evenness (Pielou index), with group differences assessed using permutational multivariate analysis of variance (PERMANOVA) and MaAsLin2. The overall microbiome composition showed mostly similarities between both groups (PERMANOVA: R[2] = 0.019, P-value = 0.287), indicating no major dysbiosis. However, a significant decrease in α-diversity and evenness was observed with an increasing number of MIH-affected teeth. Pronounced positive correlations were found between ASV0055 (Streptococcus spp.), caries experience, and MIH severity. ASV0100 (Mannheimia sp.) increased significantly with the increasing number of MIH-affected teeth, whereas ASV0053 (Bergeyella sp.) decreased with higher caries experience. In summary, the oral microbiome of children and adolescents with MIH exhibits no significant differences from healthy children and adolescents of the same age group. Depending on MIH severity, the presence of early plaque-forming species and cariogenic biofilm may increase, requiring intensive, tailored preventive care and appropriate restorative treatment to achieve microbial homeostasis.<br><br>IMPORTANCE: Molar-incisor-hypomineralization (MIH) represents a significant burden for affected children and adolescents, playing an increasingly important role in pediatric dentistry worldwide. Despite its high global prevalence, data on the microbiome of MIH patients remains limited. This study is the first to compare the oral microbiome composition of MIH patients with a healthy control group, making a significant contribution to pediatric dentistry and microbiology. Our results indicate that the oral microbiome of children with MIH is similar to that of healthy children of the same age. Although this structural anomaly predisposes patients to caries, effective preventive and restorative treatments can help maintain microbial homeostasis. However, MIH-affected children remain high-risk patients, as the disease severity may reduce microbial diversity. Furthermore, the increased abundance of Streptococcus spp. in MIH patients indicates a higher caries susceptibility, emphasizing the need for targeted dental care focusing on plaque control and topical fluoride use.}, }
@article {pmid40161742, year = {2025}, author = {Wong, MK and Armstrong, E and Heirali, AA and Schneeberger, PHH and Chen, H and Cochrane, K and Sherriff, K and Allen-Vercoe, E and Siu, LL and Spreafico, A and Coburn, B}, title = {Assessment of ecological fidelity of human microbiome-associated mice in observational studies and an interventional trial.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {40161742}, issn = {2692-8205}, support = {UM1 CA186644/CA/NCI NIH HHS/United States ; }, abstract = {Composition and function of the gut microbiome is associated with diverse health conditions and treatment responses. Human microbiota-associated (HMA) mouse models are used to establish causal links for these associations but have important limitations. We assessed the fidelity of HMA mouse models to recapitulate ecological responses to a microbial consortium using stools collected from a human clinical trial. HMA mice were generated using different routes of consortium exposure and their ecological features were compared to human donors by metagenomic sequencing. HMA mice were more similar in gut composition to other mice than their respective human donors, with taxa including Akkermansia muciniphila and Bacteroides species enriched in mouse recipients. A limited repertoire of microbes was able to engraft into HMA mice regardless of route of consortium exposure. In publicly available HMA mouse datasets from four distinct health conditions, we confirmed our observation that a taxonomically restricted set of microbes reproducibly engrafts in HMA mice and observed that stool microbiome composition of HMA mice were more like other mice than their human donor. Our data suggest that HMA mice are limited models to assess the ecological impact of microbial consortia, with ecological effects in HMA mice being more strongly associated with host species than donor stool ecology or ecological responses to treatment in humans. Comparisons to published studies suggest this may be due to comparatively large host-species effects that overwhelm ecological effects of treatment in humans that HMA models aim to recapitulate.}, }
@article {pmid40158322, year = {2025}, author = {Hamza, M and Wang, S and Liu, Y and Li, K and Zhu, M and Chen, L}, title = {Unraveling the potential of bioengineered microbiome-based strategies to enhance cancer immunotherapy.}, journal = {Microbiological research}, volume = {296}, number = {}, pages = {128156}, doi = {10.1016/j.micres.2025.128156}, pmid = {40158322}, issn = {1618-0623}, mesh = {Humans ; *Immunotherapy/methods ; *Neoplasms/therapy/immunology/microbiology ; Tumor Microenvironment/immunology ; *Bioengineering/methods ; Animals ; *Microbiota/immunology ; Gastrointestinal Microbiome/immunology ; }, abstract = {The human microbiome plays a pivotal role in the field of cancer immunotherapy. The microbial communities that inhabit the gastrointestinal tract, as well as the bacterial populations within tumors, have been identified as key modulators of therapeutic outcomes, affecting immune responses and reprogramming the tumor microenvironment. Advances in synthetic biology have made it possible to reprogram and engineer these microorganisms to improve antitumor activity, enhance T-cell function, and enable targeted delivery of therapies to neoplasms. This review discusses the role of the microbiome in modulating both innate and adaptive immune mechanisms-ranging from the initiation of cytokine production and antigen presentation to the regulation of immune checkpoints-and discusses how these mechanisms improve the efficacy of immune checkpoint inhibitors. We highlight significant advances with bioengineered strains like Escherichia coli Nissle 1917, Lactococcus lactis, Bifidobacterium, and Bacteroides, which have shown promising antitumor efficacy in preclinical models. These engineered microorganisms not only efficiently colonize tumor tissues but also help overcome resistance to standard therapies by reprogramming the local immune environment. Nevertheless, several challenges remain, such as the requirement for genetic stability, effective tumor colonization, and the control of potential safety issues. In the future, the ongoing development of genetic engineering tools and the optimization of bacterial delivery systems are crucial for the translation of microbiome-based therapies into the clinic. This review highlights the potential of bioengineered microbiota as an innovative, personalized approach in cancer immunotherapy, bringing hope for more effective and personalized treatment options for patients with advanced malignancies.}, }
@article {pmid40158141, year = {2025}, author = {Jiang, Y and Aton, M and Zhu, Q and Lu, YY}, title = {Modeling microbiome-trait associations with taxonomy-adaptive neural networks.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {87}, pmid = {40158141}, issn = {2049-2618}, support = {RGPIN-03270-2023//Canadian NSERC Discovery Grant/ ; }, mesh = {Humans ; *Neural Networks, Computer ; *Microbiota ; Metagenomics/methods ; *Bacteria/classification/genetics/isolation &amp; purification ; Computer Simulation ; }, abstract = {The human microbiome, a complex ecosystem of microorganisms inhabiting the body, plays a critical role in human health. Investigating its association with host traits is essential for understanding its impact on various diseases. Although shotgun metagenomic sequencing technologies have produced vast amounts of microbiome data, analyzing such data is highly challenging due to its sparsity, noisiness, and high feature dimensionality. Here, we develop MIOSTONE, an accurate and interpretable neural network model for microbiome-disease association that simulates a real taxonomy by encoding the relationships among microbial features. The taxonomy-encoding architecture provides a natural bridge from variations in microbial taxa abundance to variations in traits, encompassing increasingly coarse scales from species to domains. MIOSTONE has the ability to determine whether taxa within the corresponding taxonomic group provide a better explanation in a data-driven manner. MIOSTONE serves as an effective predictive model, as it not only accurately predicts microbiome-trait associations across extensive simulated and real datasets but also offers interpretability for scientific discovery. Both attributes are crucial for facilitating in silico investigations into the biological mechanisms underlying such associations among microbial taxa. Video Abstract.}, }
@article {pmid40156096, year = {2025}, author = {Patjas, A and Kantele, A}, title = {Travel to low- and middle-income countries and travellers' diarrhoea increase risk of mismatching antimicrobial therapy for urinary tract infection.}, journal = {Journal of travel medicine}, volume = {32}, number = {4}, pages = {}, pmid = {40156096}, issn = {1708-8305}, support = {1726//Sigrid Juselius Foundation/ ; TYH2021314//Finnish Governmental Funding for Health Science Research/ ; //The University of Helsinki Doctoral School/ ; //Finnish Multidisciplinary Centre of Excellence in Antimicrobial Resistance Research/ ; 346127//Academy of Finland/ ; }, mesh = {Humans ; *Urinary Tract Infections/drug therapy/microbiology ; Male ; Female ; Adult ; Middle Aged ; *Travel ; *Diarrhea ; *Anti-Bacterial Agents/therapeutic use ; Aged ; Risk Factors ; Developing Countries ; Adolescent ; Young Adult ; *Enterobacteriaceae Infections/drug therapy ; Enterobacteriaceae/isolation &amp; purification/drug effects ; }, abstract = {BACKGROUND: Travel to low- and middle-income countries (LMICs) increases the risk of urinary tract infections (UTIs), including those caused by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Focusing on international travel, we explored resistance profiles of urinary ESBL-PE and non-ESBL-PE isolates in a low antimicrobial resistance prevalence country and factors associated with UTI treatment failure.<br><br>METHODS: During 2015-19, we recruited 18-65-year-old individuals with recent ESBL-PE UTI and a respective cohort of those with non-ESBL-PE UTI to complete questionnaires on symptoms, antibiotic therapies and treatment failure risk factors. We compared uropathogens' resistance profiles amongst patients with or without LMIC travel history and conducted multivariable analyses to identify factors contributing to mismatching antimicrobial treatment (uropathogen resistant to the initial antimicrobial used) and clinical failure.<br><br>RESULTS: Amongst non-ESBL-PE UTI patients (n&#x2009;=&#x2009;187), trimethoprim resistance was more common in isolates from individuals with recent LMIC travel (8/19, 42.1%) compared to those without (30/167, 18.0%) [odds ratio (OR) 3.3, compatibility interval (CI) 95% 1.2-9.0]. ESBL-PE isolates (n&#x2009;=&#x2009;130) showed no differences in resistance profiles with respect to LMIC travel history.In the group non-ESBL-PE UTI, risk factors included microbiological mismatching recent LMIC travel [adjusted odds ratio (AOR) 3.6, CI 95% 1.0-12.7] and travellers' diarrhoea (AOR 7.1, CI 95% 1.1-45.6); no factors were significantly associated with mismatching in the group ESBL-PE UTI. As risk factors for clinical failure, in the group non-ESBL-PE UTI, we identified microbiological mismatching (AOR 15.2, CI 95% 4.0-57.9), and renal/bladder disease (AOR 5.2, CI 95% 1.1-23.2), and in the group ESBL-PE UTI, microbiological mismatching (AOR 8.1, CI 95% 2.6-24.7).<br><br>CONCLUSIONS: LMIC travel increases the risk of nonmatching empiric antimicrobials, concurring with increased trimethoprim resistance rates amongst the non-ESBL-PE isolates. Our data suggest that UTI patients with recent LMIC travel should not be empirically treated with trimethoprim and, when possible, urinary culturing is warranted.}, }
@article {pmid40155374, year = {2025}, author = {Zhang, J and Zhang, D and Xu, Y and Zhang, J and Liu, R and Gao, Y and Shi, Y and Cai, P and Zhong, Z and He, B and Li, X and Zhou, H and Chen, M and Li, YX}, title = {Large-scale biosynthetic analysis of human microbiomes reveals diverse protective ribosomal peptides.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {3054}, pmid = {40155374}, issn = {2041-1723}, support = {C7014-24GF//Research Grants Council, University Grants Committee (RGC, UGC)/ ; }, mesh = {Humans ; Animals ; Mice ; *Peptides/metabolism/pharmacology ; *Gastrointestinal Microbiome/genetics ; *Microbiota/genetics ; Biofilms/drug effects/growth &amp; development ; *Ribosomes/metabolism ; Inflammatory Bowel Diseases/microbiology ; Protein Processing, Post-Translational ; Bacteria/metabolism/genetics ; *Ribosomal Proteins/metabolism/biosynthesis/genetics ; Biological Products/metabolism ; }, abstract = {The human microbiome produces diverse metabolites that influence host health, yet the chemical landscape of ribosomally synthesized and post-translationally modified peptides (RiPPs)-a versatile class of bioactive compounds-remains underexplored. Here, we conduct a large-scale biosynthetic analysis of 306,481 microbial genomes from human-associated microbiomes, uncovering a broad array of yet-to-be-discovered RiPPs. These RiPPs are distributed across various body sites but show a specific enrichment in the gut and oral microbiome. Big data omics analysis reveals that numerous RiPP families are inversely related to various diseases, suggesting their potential protective effects on health. For a proof of principle study, we apply the synthetic-bioinformatic natural product (syn-BNP) approach to RiPPs and chemically synthesize nine autoinducing peptides (AIPs) for in vitro and ex vivo assay. Our findings reveal that five AIPs effectively inhibit the biofilm formation of disease-associated pathogens. Furthermore, when ex vivo testing gut microbiota from mice with inflammatory bowel disease, we observe that two AIPs can regulate the microbial community and reduce harmful species. These findings highlight the vast potential of human microbial RiPPs in regulating microbial communities and maintaining human health, emphasizing their potential for therapeutic development.}, }
@article {pmid40144639, year = {2025}, author = {Sabu, P and Pathak, HB and Nissen, E and Chalise, P and Koestler, DC and Godwin, AK and Umar, S and Spoozak, L and Jewell, A and Mahoney, DE}, title = {Translational Implications of The Gut Microbiome in Women with A Benign or Malignant Pelvic Mass.}, journal = {Annals of obstetrics and gynecology}, volume = {8}, number = {1}, pages = {}, pmid = {40144639}, issn = {2641-6522}, support = {P20 GM103418/GM/NIGMS NIH HHS/United States ; P20 GM130423/GM/NIGMS NIH HHS/United States ; P30 CA168524/CA/NCI NIH HHS/United States ; R01 CA260132/CA/NCI NIH HHS/United States ; }, abstract = {OBJECTIVE: The role of the gut microbiome in non-gastrointestinal cancers has generated growing interest in the field of gynecologic oncology. Our objective was to characterize the gut microbiome in women with a pelvic mass suspicious for ovarian cancer. We hypothesized that (1) women with a pelvic mass would have reduced gut microbiota bacterial diversity compared to healthy controls and (2) gut microbial diversity would differ between benign disease compared to ovarian cancer.<br><br>METHODS: In this case-control observational study, patients who presented with a suspicious pelvic mass were recruited from university affiliated gynecologic oncology clinics for fecal biospecimen donation. Fecal samples that were obtained from patients underwent 16S rRNA gene sequencing for microbial evaluation and statistical analysis. We used the Human Microbiome Project (HMP) Data Portal to compare gut microbiota profiles for our study to that of healthy female controls.<br><br>RESULTS: Fifteen patients with a pelvic mass were included ages 24-75 years. When comparing the gut microbiomes of these patients to 82 healthy females from the HMP Dataset, those with a pelvic mass had a significantly lower microbiota gut bacterial diversity. On the final pathology, 8 of the 15 patients with a suspicious pelvic mass had ovarian cancer and 7 had benign disease. Although not statistically significant, the alpha diversity was marginally reduced in patients with ovarian cancer compared to those with benign disease.<br><br>CONCLUSION: These findings underscore the necessity for validation in larger patient cohorts for clinical translation as a potential tool for disease diagnostics and disease prediction in diverse populations.}, }
@article {pmid40142442, year = {2025}, author = {Fan, X and Lv, N and Quan, Z}, title = {Culturable Human Microorganisms and the Impact of Transportation Conditions on Cultivability.}, journal = {Microorganisms}, volume = {13}, number = {3}, pages = {}, pmid = {40142442}, issn = {2076-2607}, support = {2021YFA1301000//the National Key Research and Development Program of China/ ; 2017SHZDZX01//Shanghai Municipal Science and Technology Major Project/ ; 32470099//the National Natural Foundation of China/ ; }, abstract = {The composition of the human microbiome is a critical health indicator, and culture-independent methodologies have substantially advanced our understanding of human-associated microorganisms. However, precise identification and characterization of microbial strains require culture-based techniques. Recently, the resurgence of culturomics, combined with high-throughput sequencing technology, has reduced the high labor demand of pure culture methods, facilitating a more efficient and comprehensive acquisition of culturable microbial strains. This study employed an integrated approach combining culturomic and high-throughput sequencing to identify culturable microorganisms on the human scalp and in human saliva and feces. Several Staphylococcus strains were identified from the scalp, whereas anaerobic microorganisms were dominant in the saliva and fecal samples. Additionally, the study highlighted the beneficial effects of transportation conditions (liquid nitrogen treatment, dry ice transport, and dimethyl sulfoxide [DMSO] buffer) in preserving culturable microorganisms. A robust methodology was developed for the large-scale acquisition of culturable microorganisms with optimized transport conditions that enhance the potential for isolating a greater diversity of culturable strains.}, }
@article {pmid40140901, year = {2025}, author = {Wu, Y and Cheng, R and Lin, H and Li, L and Jia, Y and Philips, A and Zuo, T and Zhang, H}, title = {Gut virome and its implications in the pathogenesis and therapeutics of inflammatory bowel disease.}, journal = {BMC medicine}, volume = {23}, number = {1}, pages = {183}, pmid = {40140901}, issn = {1741-7015}, support = {2023YFS0279//Sichuan Science and Technology Program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Virome ; *Inflammatory Bowel Diseases/virology/therapy/microbiology ; }, abstract = {Inflammatory bowel disease (IBD) refers to chronic, recurrent inflammatory intestinal disorders, primarily including Crohn's disease (CD) and Ulcerative colitis (UC). Numerous studies have elucidated the importance of the gut microbiome in IBD. Recently, numerous studies have focused on the gut virome, an intriguing and enigmatic aspect of the gut microbiome. Alterations in the composition of phages, eukaryotic viruses, and human endogenous retroviruses that occur in IBD suggest potential involvement of the gut virome in IBD. Nevertheless, the mechanisms by which it maintains intestinal homeostasis and interacts with diseases are only beginning to be understood. Here, we thoroughly reviewed the composition of the gut virome in both healthy individuals and IBD patients, emphasizing the key viruses implicated in the onset and progression of IBD. Furthermore, the complex connections between the gut virome and the intestinal barrier, immunity, and gut microbiome were dissected to advance the interpretation of IBD pathogenesis. The updated discussion of the evidence regarding the gut virome will advance our knowledge in gut virome and chronic gastrointestinal diseases. Targeting the gut virome is a promising avenue for IBD treatment in future.}, }
@article {pmid40140341, year = {2025}, author = {Rodolfi, S and Selmi, C}, title = {Environmental factors and rheumatic diseases.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {39}, number = {2}, pages = {102053}, doi = {10.1016/j.berh.2025.102053}, pmid = {40140341}, issn = {1532-1770}, mesh = {Humans ; *Rheumatic Diseases/etiology/immunology/epidemiology ; Risk Factors ; *Environmental Exposure/adverse effects ; Lupus Erythematosus, Systemic/etiology/immunology ; Alcohol Drinking/adverse effects ; Autoimmunity ; Cigarette Smoking/adverse effects ; }, abstract = {The pathogenesis and pathophysiology of rheumatic diseases is complex and relies on the interaction of different factors. The common view is that the pathological autoimmunity develops in genetically predisposed individuals upon exposure to an environmental trigger. This highlights the importance of recognizing and deconstructing the effects of environmental agents in rheumatic diseases. Several factors have been identified in the last decades, with detrimental or protective effects, impacting not only on disease onset, but also on its natural history. Cigarette smoking has been identified as one of the strongest environmental risk factors, being associated with disease development and severity for several rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and spondyloarthropathies. Moreover, other airborne pollutants, such as silica, solvents, asbestos and metals are recognized risk factors for rheumatic diseases. The effect of some other agents is however not straightforward, of which a remarkable example is alcohol consumption. Alcohol has been associated with both pro- and anti-inflammatory effects, exerting a variable effect on rheumatic diseases depending on quantity and frequency of consumption, as well as sex and ethnicity. Similarly, ultraviolet light exposure has been associated with a higher risk of SLE but lower risk of RA. The relationship between microbial exposure and autoimmunity is also complex: while some infectious agents increase the risk of rheumatic diseases, it is widely accepted that less exposure to microbial agents, particularly during immune system development, increases the risk of autoimmunity. Furthermore, in recent years the spotlight has switched to the human microbiome, as alterations in organ-specific microbiome composition are anticipated to be early participants in the onset of immune-mediated illnesses. The aim of this review is to highlight the most relevant environmental factors and their role in Rheumatology, with a specific focus on proposed pathophysiological effect and correlation with clinical outcomes.}, }
@article {pmid40137778, year = {2025}, author = {Papamentzelopoulou, M and Pitiriga, VC}, title = {Unlocking the Interactions Between the Whole-Body Microbiome and HPV Infection: A Literature Review.}, journal = {Pathogens (Basel, Switzerland)}, volume = {14}, number = {3}, pages = {}, pmid = {40137778}, issn = {2076-0817}, mesh = {Humans ; *Papillomavirus Infections/microbiology/immunology/virology ; *Microbiota ; Female ; Uterine Cervical Neoplasms/microbiology/virology ; *Papillomaviridae ; *Host-Pathogen Interactions ; Dysbiosis ; }, abstract = {The human microbiome plays a vital role in maintaining human homeostasis, acting as a key regulator of host immunity and defense mechanisms. However, dysbiotic microbial communities may cause disruption of the symbiotic relationship between the host and the local microbiota, leading to the pathogenesis of various diseases, including viral infections and cancers. One of the most common infectious agents causing cancer is the human papilloma virus (HPV), which accounts for more than 90% of cervical cancers. In most cases, the host immune system is activated and clears HPV, whereas in some cases, the infection persists and can lead to precancerous lesions. Over the last two decades, the advent of next-generation sequencing (NGS) technology and bioinformatics has allowed a thorough and in-depth analysis of the microbial composition in various anatomical niches, allowing researchers to unveil the interactions and the underlying mechanisms through which the human microbiota could affect HPV infection establishment, persistence, and progression. Accordingly, the present narrative review aims to shed light on our understanding of the role of the human microbiome in the context of HPV infection and its progression, mainly to cervical cancer. Furthermore, we explore the mechanisms by which the composition and balance of microbial communities exert potential pathogenic or protective effects, leading to either HPV persistence and disease outcomes or clearance. Special interest is given to how the microbiome can modulate host immunity to HPV infection. Lastly, we summarize the latest findings on the therapeutic efficacy of probiotics and prebiotics in preventing and/or treating HPV infections and the potential of vaginal microbiota transplantation while highlighting the significance of personalized medicine approaches emerging from NGS-based microbiome profiling and artificial intelligence (AI) for the optimal management of HPV-related diseases.}, }
@article {pmid40137432, year = {2025}, author = {Ziogou, A and Giannakodimos, I and Giannakodimos, A and Mitakidi, E and Charalampakis, N and Ioannou, P}, title = {Primary Actinomycosis of the Stomach: A Review of the Literature for A Rare Entity.}, journal = {Journal of personalized medicine}, volume = {15}, number = {3}, pages = {}, pmid = {40137432}, issn = {2075-4426}, abstract = {Background/Objectives: Primary gastric actinomycosis is extremely rare and only a limited number of cases are published in the literature. Actinomycosis is caused by anaerobic Gram-positive bacteria; these microorganisms are members of the normal human microbiome and occasionally lead to infection, especially in immunocompromised patients or patients subjected to abdominal surgery. Advances in personalized medicine, including tailored antimicrobial therapy based on individual patient profiles, may enhance treatment efficacy and reduce unnecessary interventions. Methods: A review was performed through a literature search of the PubMed/MedLine and Scopus databases. Results: A total of 27 patients were included, 15 males (55.56%) and 12 (44.44%) females, with a mean age of 55.11 ± 17.48 years. Among the included patients, 25.93% had a history of abdominal surgery. Abdominal pain (73.08%), weight loss (40.74%), nausea or vomiting (30.77%) and fever (19.23%) constitute the most commonly reported clinical manifestations. Endoscopy (59.26%), computed tomography (48.15%), ultrasonography (22.22%) and magnetic resonance imaging (11.11%) assisted in indicating the primary lesion. Diagnosis was achieved preoperatively in 66.66% of patients, via endoscopy and biopsy (51.85%) or via cultures (14.81%), while nine cases (33.33%) were diagnosed postoperatively. The therapeutic approaches included antimicrobial administration (32%), surgery (24%) or both (44%). The most widely used antimicrobial was penicillin (77.78%) and the mean duration of antimicrobial treatment was 5.85 months. The protocol for this review was registered in Prospero (ID:CRD42025649532). Conclusions: Due to the divergent clinical presentation of primary gastric actinomycosis, clinicians should be aware of this rare entity in order to establish diagnosis in a timely manner and provide prompt and effective treatment.}, }
@article {pmid40128848, year = {2025}, author = {Byrne, SR and DeMott, MS and Yuan, Y and Ghanegolmohammadi, F and Kaiser, S and Fox, JG and Alm, EJ and Dedon, PC}, title = {Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {81}, pmid = {40128848}, issn = {2049-2618}, support = {P30-ES002109//NIEHS Core Center Grant/ ; R01-OD028099-01//NIH Transformative Award/ ; R01 CA281732/CA/NCI NIH HHS/United States ; T32-ES007020//NIEHS Training Grant in Environmental Toxicology/ ; T32 ES007020/ES/NIEHS NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Metagenomics/methods ; Feces/microbiology ; Mice ; Animals ; *Bacteria/genetics/classification/isolation &amp; purification/metabolism ; *Epigenesis, Genetic ; *Epigenome ; *Phosphates/metabolism ; Metagenome ; Female ; Male ; Mass Spectrometry ; }, abstract = {BACKGROUND: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by dnd and ssp gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications.<br><br>RESULTS: Exploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5-10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m[6]dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor's Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Bacillota (formerly Firmicutes), Actinomycetota (formerly Actinobacteria), and Pseudomonadota (formerly Proteobacteria), which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies. Video Abstract CONCLUSIONS: The results of our studies provide a benchmark for understanding the behavior of an abundant and chemically reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.}, }
@article {pmid40122597, year = {2025}, author = {Su, R and Wen, W and Jin, Y and Cao, Z and Feng, Z and Chen, J and Lu, Y and Zhou, G and Dong, C and Gao, S and Li, X and Zhang, H and Chao, K and Lan, P and Wu, X and Philips, A and Li, K and Gao, X and Zhang, F and Zuo, T}, title = {Dietary whey protein protects against Crohn's disease by orchestrating cross-kingdom interaction between the gut phageome and bacteriome.}, journal = {Gut}, volume = {74}, number = {8}, pages = {1246-1260}, doi = {10.1136/gutjnl-2024-334516}, pmid = {40122597}, issn = {1468-3288}, mesh = {*Crohn Disease/microbiology/prevention &amp; control ; *Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Animals ; Mice ; *Whey Proteins/pharmacology/administration &amp; dosage ; Female ; Male ; Adult ; *Bacteriophages ; *Diet ; Disease Models, Animal ; Middle Aged ; Intestinal Mucosa/microbiology ; }, abstract = {BACKGROUND: The gut microbiome and diet are important factors in the pathogenesis and management of Crohn's disease (CD). However, the role of the gut phageome under dietary influences is unknown.<br><br>OBJECTIVE: We aim to explore the effect of diet on the gut phageome-bacteriome interaction linking to CD protection.<br><br>DESIGN: We recruited CD patients and healthy subjects (n=140) and conducted a multiomics investigation, including paired ileal mucosa phageome and bacteriome profiling, dietary survey and phenome interrogation. We screened for the effect of diet on the gut phageome and bacteriome, as well as its epidemiological association with CD risks. The underlying mechanisms were explored in target phage-bacteria monocultures and cocultures in vitro and in two mouse models in vivo.<br><br>RESULTS: On dietary screening in humans, whey protein (WP) consumption was found to profoundly impact the gut phageome and bacteriome (more pronounced on the phageome) and was associated with a lower CD risk. Indeed, the WP reshaped gut phageome can causally attenuate intestinal inflammation, as shown by faecal phageome versus bacteriome transplantation from WP-consuming versus WP-non-consuming mice to recipient mice. Mechanistically, WP induced phage (a newly isolated phage AkkZT003P herein) lysis of the mucin-foraging bacterium Akkermansia muciniphila, which unleashed the symbiotic bacterium Streptococcus thermophilus to counteract intestinal inflammation.<br><br>CONCLUSION: Our study charted the importance of cross-kingdom interaction between gut phage and bacteria in mediating the dietary effect on CD protection. Importantly, we uncovered a beneficial dietary WP, a keystone phage AkkZT003P, and a probiotic S. thermophilus that can be used in CD management in the future.}, }
@article {pmid40120775, year = {2025}, author = {Onali, T and Slabá, H and Jian, C and Koivumäki, T and Päivärinta, E and Marttinen, M and Määttänen, M and Salonen, A and Pajari, AM}, title = {Berry supplementation in healthy volunteers modulates gut microbiota, increases fecal polyphenol metabolites and reduces viability of colon cancer cells exposed to fecal water- a randomized controlled trial.}, journal = {The Journal of nutritional biochemistry}, volume = {141}, number = {}, pages = {109906}, doi = {10.1016/j.jnutbio.2025.109906}, pmid = {40120775}, issn = {1873-4847}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Polyphenols/metabolism/analysis ; *Feces/chemistry/microbiology ; *Fruit/chemistry ; Male ; Female ; Adult ; *Colonic Neoplasms/pathology/prevention &amp; control ; Middle Aged ; *Dietary Supplements ; Caco-2 Cells ; Healthy Volunteers ; Cell Survival/drug effects ; }, abstract = {Diets high in red and processed meat and low in plant-based foods are associated with an increased risk of colorectal cancer. We investigated whether berry supplementation can impact gut metabolism to counteract the presumably cancer promoting luminal environment sustained by high red and processed meat consumption. Altogether 43 healthy adults were randomized either into Meat group (150 g/d red and processed pork meat) or Meat &amp; Berries group (150 g/d red and processed meat and 200 g/d of mixed berries). Fecal samples and 3-d food records were collected at baseline and at the end of the four-week intervention. Intakes of vitamin C, vitamin E, manganese, insoluble fiber, and the polyphenols available in the database were significantly higher in the Meat &amp; Berries than Meat group. While between-group comparisons found no significant differences in the gut microbiota, the within-group analyses showed that the relative abundances of beneficial Roseburia and Faecalibacterium were decreased and an unclassified group of Peptostreptococcaceae increased significantly in the Meat group. In comparison to the Meat group, berry consumption resulted in higher fecal concentrations of p-coumaric and protocatechuic acids and lower viability of fecal water (FW) -treated CV1-P fibroblastoma and human colon adenocarcinoma HCA-7 and Caco-2 cells (P<.05 with 30% FW). Berry consumption provided protective nutrients and mitigated potentially unfavourable gut microbiota changes seen in the Meat group, increased fecal polyphenol metabolites, and reduced viability of FW-treated colon adenocarcinoma cells, collectively suggesting that berries may protect against colorectal cancer development.}, }
@article {pmid40120687, year = {2025}, author = {Caffrey, EB and Perelman, D and Ward, CP and Sonnenburg, ED and Gardner, CD and Sonnenburg, JL}, title = {Unpacking Food Fermentation: Clinically Relevant Tools for Fermented Food Identification and Consumption.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {16}, number = {5}, pages = {100412}, pmid = {40120687}, issn = {2156-5376}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Fermented Foods ; Gastrointestinal Microbiome ; Food Safety ; *Food Microbiology ; Fermentation ; *Diet ; }, abstract = {Fermented foods have been consumed for millennia, valued for their extended shelf life, distinctive sensory properties, and potential health benefits. Emerging research suggests that fermented food consumption may contribute to gut microbiome diversity, immune modulation, and metabolic regulation; however, mechanistic insights and clinical validation remain limited. This review synthesizes current scientific evidence on the microbial and metabolite composition of fermented foods, their proposed health effects, and safety considerations for vulnerable populations. Additionally, we highlight the need for standardized definitions, serving sizes, and regulatory frameworks to enhance consumer transparency and research reproducibility. By providing a structured overview of existing data and knowledge gaps, this review establishes a foundation for integrating fermented foods into dietary recommendations and guiding future research directions.}, }
@article {pmid40119445, year = {2025}, author = {Niaz, H and Skurnik, M and Adnan, F}, title = {Genomic and proteomic characterization of four novel Schitoviridae family phages targeting uropathogenic Escherichia coli strain.}, journal = {Virology journal}, volume = {22}, number = {1}, pages = {83}, pmid = {40119445}, issn = {1743-422X}, mesh = {*Uropathogenic Escherichia coli/virology ; Humans ; *Genome, Viral ; Host Specificity ; Proteomics ; Phylogeny ; Genomics ; Escherichia coli Infections/microbiology/therapy ; Urinary Tract Infections/microbiology/therapy ; Proteome/analysis ; Wastewater/virology ; *Coliphages/genetics/classification/isolation &amp; purification/ultrastructure ; *Bacteriophages/genetics/classification/isolation &amp; purification/ultrastructure ; Viral Proteins/genetics ; }, abstract = {BACKGROUND: Escherichia coli-associated urinary tract infections (UTIs) are among the most prevalent bacterial infections in humans. Typically, antibiotic medication is used to treat UTIs, but over the time, growth of multidrug resistance among these bacteria has created a global public health issue that necessitates other treatment modalities, such as phage therapy.<br><br>METHODS: The UPEC strain PSU-5266 (UE-17) was isolated from human urine samples, while phages were obtained from wastewater. These phages were characterized through host range analysis, stability studies, adsorption assays, and electron microscopy. Additionally, genomic, phylogenetic, and proteomic analyses were conducted to provide further insights.<br><br>RESULTS: The current study describes the isolation and characterization of four Escherichia coli phages designated as UE-S5a, UE-S5b, UE-M3 and UE-M6. Bactericidal assays depicted that all bacteriophages exhibited a strong lytic ability against uropathogenic E. coli (UPEC) strain PSU-5266 (UE-17). The phages displayed a broad host range (31-41%) among 104 tested isolates and adsorption rate of 15-20&#xa0;min. They were stable within pH range of 5-11 and temperature range of 4 to 55&#xa0;&#xb0;C. Electron microscopy showed that all phages have icosahedral heads (70-74&#xa0;nm) and short non-contractile tails, thus exhibiting a podovirus morphology. Sequencing results showed that they have linear double stranded DNA, genome of 73 to 76&#xa0;kb in length, with GC content of 42% and short direct terminal repeats. Their genomes contain 84-88 predicted genes with putative functions predicted to 42-48% of gene products. The phylogenetic and comparative genomic analysis results depicted that these phages, sharing&#x2009;>&#x2009;98% sequence similarity, are new members of genus Gamaleyavirus of subfamily Enquatrovirinae, in the Schitoviridae family. Mass spectrometric analysis of purified phage particles identified 44-56 phage particle-associated proteins (PPAPs) belonging to various functional groups such as lysis proteins, structural proteins, DNA packaging related proteins, and proteins involved in replication, metabolism and regulation. In addition, no genes encoding virulence factors, antibiotic resistance or lysogeny factors were identified.<br><br>CONCLUSION: The overall findings suggest that these bacteriophages are potential candidates for phage therapy in treating UTIs caused by UPEC strains.}, }
@article {pmid40116497, year = {2025}, author = {Moreland, RB and Choi, BI and Fontes Noronha, M and Baker, J and Kaindl, J and Wolfe, AJ}, title = {Complete genome sequence of Trueperella bernardiae strain UMB8254, isolated from the bladder of a female with metabolic syndrome and nephrolithiasis.}, journal = {Microbiology resource announcements}, volume = {14}, number = {4}, pages = {e0126524}, pmid = {40116497}, issn = {2576-098X}, support = {NA//Pathnostics/ ; }, abstract = {Trueperella bernardiae is infrequently isolated, usually in polymicrobial communities, from human hosts with a wide variety of symptoms and diseases. Here, we report a complete genome sequence of Trueperella bernardiae (UMB8254), isolated from the bladder of a human female with metabolic syndrome and nephrolithiasis.}, }
@article {pmid40111686, year = {2025}, author = {Colombo, APV and Lourenço, TGB and de Oliveira, AM and da Costa, ALA}, title = {Link Between Oral and Gut Microbiomes: The Oral-Gut Axis.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {71-87}, pmid = {40111686}, issn = {0065-2598}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Mouth/microbiology ; Animals ; Dysbiosis/microbiology ; *Gastrointestinal Tract/microbiology ; }, abstract = {In the last decades, groundbreaking research on the human microbiome has changed our reductionist conception of the etiology and pathogenesis of several chronic diseases. As a result, we have come to appreciate the significance of a balanced microbiome in maintaining human health. In this context, the upper and lower gastrointestinal tracts (GITs) comprise the most abundant and diverse microbiotas of the human body. In addition to its diversity, functional redundancy, and temporal stability, a healthy GIT microbiome is characterized by its body site specificity. In fact, current evidence has indicated that the translocation of oral species to the gut environment through the oral-gut axis is increased in an array of illnesses, including chronic inflammatory and metabolic diseases, neurological disorders, and cancer. Oral pathogens have also been shown to promote gut dysbiosis and systemic inflammation in animal models. Yet, some level of overlapping between oral and gut microbiomes may occur without disruption of these microbial communities and loss of site specificity. The uniqueness of each host-microbiome entity may hinder our ability to define a "universal" normal GIT microbiome. Despite that, this chapter summarizes the predominant health-related taxa along the human GIT, as well as their role in the physiology and immunity of the digestive system. Some mechanisms that may lead to disturbances and relevant shifts in the oral and gut microbiomes of major inflammatory chronic diseases are also pointed out. Lastly, oral-fecal microbial signatures are presented as potential biomarkers for several oral and systemic disorders. The recognition of such symbiotic/dysbiotic microbial profiles may provide insights into the development of more accurate early diagnosis and therapeutic ecological approaches to restore the balance of the GIT microbiome.}, }
@article {pmid40111682, year = {2025}, author = {Dame-Teixeira, N and Do, T and Deng, D}, title = {The Oral Microbiome and Us.}, journal = {Advances in experimental medicine and biology}, volume = {1472}, number = {}, pages = {3-9}, pmid = {40111682}, issn = {0065-2598}, mesh = {Humans ; *Mouth/microbiology ; *Microbiota/physiology ; Dysbiosis/microbiology ; Periodontitis/microbiology ; }, abstract = {Oral and systemic human health depend on the symbiotic relationship between the human host and its microbiome. As the second most diverse site of the human microbiome, the oral cavity is instrumental in symbiotic relationships, transforming nutrients and acting as the human body's initial barrier against pathogens. However, under certain conditions, the typically beneficial oral microbiome can become harmful. Systemic inflammatory diseases can send signals through the oral-gut axis, such as cytokines and host defensins, altering gene expression and, consequently, the composition of the oral microbiome. These changes can be responsible for causing oral diseases, such as periodontitis and candidiasis. Evidence of metabolic syndrome, including obesity, hypertension, hyperglycemia, and dyslipidemia, exacerbates oral microbiome dysbiosis. On the other hand, the oral microbiota can also influence systemic health. Inflammatory processes in the gingival structures caused by a dysbiotic oral microbiome are linked to worsen glycemic levels in diabetics, premature birth, and rheumatoid arthritis, among others. The idea for this book emerged from the need to explore the multifaceted nature of this relationship in its various dimensions. We discuss multispecies characteristics from an ecological perspective, focusing on how the host affects the microbiome and vice versa. Understanding how the oral microbiome influences human health will guide tailored strategies for disease prevention and treatment, which is discussed in the last section of the book. Looking ahead, predictive health and disease models will enable personalized therapies centered on restoring the healthy human microbiome.}, }
@article {pmid40111647, year = {2025}, author = {Choi, Y and Jeong, J and Kim, M and Cha, S and Han, K}, title = {Backtracking identification techniques for predicting unclear bacterial taxonomy at species level: molecular diagnosis-based bacterial classification.}, journal = {Genes &amp; genomics}, volume = {47}, number = {5}, pages = {503-508}, pmid = {40111647}, issn = {2092-9293}, support = {RS-2024-00355393//National Institute for International Education/ ; }, mesh = {*Bacteria/genetics/classification ; RNA, Ribosomal, 16S/genetics ; Humans ; Microbiota/genetics ; High-Throughput Nucleotide Sequencing/methods ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {Bacterial 16S rRNA genes are widely used to classify bacterial communities within interesting environments (e.g., plants, water, human body) because they contain nine hyper-variable regions (V1-V9) reflecting a large number of sequence variation sites between species. Short-read sequencing platform (targeting partial region of 16S rRNA gene; approximately 150-500 bp) commonly used in the 16S-based microbiome study is favored by many researchers because it is economical and can generate highthroughput sequencing data faster than long-read sequencing platforms. However, this sequencing platform has technical limitations in that it cannot clarify bacterial classification at the species level compared to long-read sequencing technology, which can cover the unclassification issue due to sequence similarity between species by targeting the 16S full-length region. In recent microbiome research-related industries, species-level high-resolution microbial classification is considered a key challenge to secure microbial resources among institutions in the field. However, the long-read sequencing platforms currently offered are still under price adjustment (demanding higher cost than short-read sequencing platforms) and have the disadvantage of low base-calling accuracy compared to short-read sequencing platforms. Therefore, this brief communication introduces the'Molecular diagnosis-based bacterial classification' technology to predict candidate species by backtracking for unclassified bacterial taxonomy at the species level in the NGS-based 16S microbiome study.}, }
@article {pmid40110560, year = {2025}, author = {Adachi, A and Zhang, F and Kanaya, S and Ono, N}, title = {Quantifying uncertainty in microbiome-based prediction using Gaussian processes with microbial community dissimilarities.}, journal = {Bioinformatics advances}, volume = {5}, number = {1}, pages = {vbaf045}, pmid = {40110560}, issn = {2635-0041}, abstract = {SUMMARY: The human microbiome is closely associated with the health and disease of the human host. Machine learning models have recently utilized the human microbiome to predict health conditions and disease status. Quantifying predictive uncertainty is essential for the reliable application of these microbiome-based prediction models in clinical settings. However, uncertainty quantification in such prediction models remains unexplored. In this study, we have developed a probabilistic prediction model using a Gaussian process (GP) with a kernel function that incorporates microbial community dissimilarities. We evaluated the performance of probabilistic prediction across three regression tasks: chronological age, body mass index, and disease severity, using publicly available human gut microbiome datasets. The results demonstrated that our model outperformed existing methods in terms of probabilistic prediction accuracy. Furthermore, we found that the confidence levels closely matched the empirical coverage and that data points predicted with lower uncertainty corresponded to lower prediction errors. These findings suggest that GP regression models incorporating community dissimilarities effectively capture the characteristics of phylogenetic, high-dimensional, and sparse microbial abundance data. Our study provides a more reliable framework for microbiome-based prediction, potentially advancing the application of microbiome data in health monitoring and disease diagnosis in clinical settings.<br><br>The code is available at https://github.com/asahiadachi/gp4microbiome.}, }
@article {pmid40102379, year = {2025}, author = {Deng, L and Taelman, S and Olm, MR and Toe, LC and Balini, E and Ouédraogo, LO and Bastos-Moreira, Y and Argaw, A and Tesfamariam, K and Sonnenburg, ED and Hanley-Cook, GT and Ouédraogo, M and Ganaba, R and Van Criekinge, W and Huybregts, L and Stock, M and Kolsteren, P and Sonnenburg, JL and Lachat, C and Dailey-Chwalibóg, T}, title = {Maternal balanced energy-protein supplementation reshapes the maternal gut microbiome and enhances carbohydrate metabolism in infants: a randomized controlled trial.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2683}, pmid = {40102379}, issn = {2041-1723}, support = {OPP1175213//Bill and Melinda Gates Foundation (Bill &amp; Melinda Gates Foundation)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; Female ; *Dietary Supplements ; Infant ; *Carbohydrate Metabolism/drug effects ; Pregnancy ; Adult ; Burkina Faso ; Male ; Infant, Newborn ; *Dietary Proteins/administration &amp; dosage ; Lactation ; Feces/microbiology ; Maternal Nutritional Physiological Phenomena ; }, abstract = {Balanced energy-protein (BEP) supplementation during pregnancy and lactation can improve birth outcomes and infant growth, with the gut microbiome as a potential mediator. The MISAME-III randomized controlled trial (ClinicalTrial.gov: NCT03533712) assessed the effect of BEP supplementation, provided during pregnancy and the first six months of lactation, on small-for-gestational age prevalence and length-for-age Z-scores at six months in rural Burkina Faso. Nested within MISAME-III, this sub-study examines the impact of BEP supplementation on maternal and infant gut microbiomes and their mediating role in birth outcomes and infant growth. A total of 152 mother-infant dyads (n = 71 intervention, n = 81 control) were included for metagenomic sequencing, with stool samples collected at the second and third trimesters, and at 1-2 and 5-6 months postpartum. BEP supplementation significantly altered maternal gut microbiome diversity, composition, and function, particularly those with immune-modulatory properties. Pathways linked to lipopolysaccharide biosynthesis were depleted and the species Bacteroides fragilis was enriched in BEP-supplemented mothers. Maternal BEP supplementation also accelerated infant microbiome changes and enhanced carbohydrate metabolism. Causal mediation analyses identified specific taxa mediating the effect of BEP on birth outcomes and infant growth. These findings suggest that maternal supplementation modulates gut microbiome composition and influences early-life development in resource-limited settings.}, }
@article {pmid40099907, year = {2025}, author = {Reetz, L and Schulze, L and Kronenberger, T and Selim, KA and Schaefle, T and Dema, T and Zipperer, A and Mößner, J and Poso, A and Grond, S and Peschel, A and Krismer, B}, title = {The human microbiome-derived antimicrobial lugdunin self-regulates its biosynthesis by a feed-forward mechanism.}, journal = {mBio}, volume = {16}, number = {4}, pages = {e0357124}, pmid = {40099907}, issn = {2150-7511}, support = {TRR261, GRK1708, Cluster of Excellence EXC2124, TRR156//Deutsche Forschungsgemeinschaft (DFG)/ ; TRR261, GRK1708, Cluster of Excellence EXC2124//Deutsche Forschungsgemeinschaft (DFG)/ ; Cluster of Excellence EXC2124//Deutsche Forschungsgemeinschaft (DFG)/ ; Cluster of Excellence EXC2124//Deutsche Forschungsgemeinschaft (DFG)/ ; //Deutsches Zentrum f&#xfc;r Infektionsforschung (DZIF)/ ; //Deutsches Zentrum f&#xfc;r Infektionsforschung (DZIF)/ ; Culture Challenge//Bundesministerium f&#xfc;r Bildung und Forschung (BMBF)/ ; }, mesh = {Humans ; *Gene Expression Regulation, Bacterial ; Multigene Family ; *Microbiota ; Staphylococcus aureus/drug effects ; *Staphylococcus lugdunensis/genetics/metabolism ; Promoter Regions, Genetic ; *Anti-Bacterial Agents/biosynthesis ; Bacterial Proteins/genetics/metabolism ; Operon ; }, abstract = {Many human microbiome members inhibit bacterial competitors by production of antimicrobial compounds whose expression needs to be tightly controlled to balance the costs and benefits of compound biosynthesis. The nasal commensal Staphylococcus lugdunensis outcompetes Staphylococcus aureus using the antimicrobial lugdunin. The lugdunin biosynthetic gene cluster (BGC) encodes two potential regulators whose roles have remained unknown. Deletion of the regulator genes lugR or lugJ led to increased lugdunin production and/or immunity. While LugR was found to repress the transcription of the biosynthetic lugRABCTDZ operon, LugJ repressed the lugIEFGH export and immunity genes. Both regulators bound to different inverted repeats in the controlled promoter regions. Notably, both repressors were released from cognate promoters to allow transcription upon addition of exogenous lugdunin. Even minor structural changes disabled lugdunin derivatives to induce expression of its BGC, which is consistent with inferior binding to the predicted LugR and LugJ binding pockets. Thus, lugdunin controls its own biosynthesis through a feed-forward mechanism probably to avoid futile production.IMPORTANCEBiosynthetic gene clusters (BGCs) are usually tightly controlled to avoid production of costly goods at inappropriate time points or unfavorable conditions. However, in most cases, the regulatory signals of these clusters have remained unknown. Frequently, quorum sensing or two-component regulatory systems are involved in BGC expression control. This study elucidates the sophisticated regulation of lugdunin biosynthesis and secretion via two independent regulators, LugR and LugJ. Although belonging to different families of repressors, both directly interact with the antimicrobial lugdunin and thereby enhance biosynthesis and secretion in a feed forward-like mechanism.}, }
@article {pmid40086654, year = {2025}, author = {Pietilä, JP and Häkkinen, TA and Ollgren, J and Kantele, A}, title = {Modelling international travel as risk of acquiring Dientamoeba fragilis: Comparison to Giardia duodenalis data.}, journal = {Travel medicine and infectious disease}, volume = {65}, number = {}, pages = {102836}, doi = {10.1016/j.tmaid.2025.102836}, pmid = {40086654}, issn = {1873-0442}, mesh = {Humans ; *Travel ; *Dientamoeba/isolation &amp; purification ; Finland/epidemiology ; *Dientamoebiasis/epidemiology/transmission/parasitology ; *Giardia lamblia/isolation &amp; purification ; *Giardiasis/epidemiology/parasitology/transmission ; Male ; Female ; Middle Aged ; Adult ; Risk Factors ; Animals ; Aged ; }, abstract = {BACKGROUND: The intestinal parasite Dientamoeba fragilis (DF) is spread worldwide and can cause prolonged gastrointestinal symptoms, yet its link to international travel has been scarcely studied. To explore this connection, we examined the association between DF cases and international travel history by destination, comparing the findings to data on Giardia duodenalis (GD), a common travel-acquired intestinal parasite.<br><br>METHODS: We analysed clinical data from patients with DF or GD infection in the Helsinki Metropolitan Area, categorizing the patients as travellers and non-travellers on the basis of their travel history. To assess acquisition risk by destination, we devised a DF/GD risk score (RS) relating case numbers to travel volumes as denominators in each destination, with travel data retrieved from the Official Statistics of Finland (OSF).<br><br>RESULTS: Travel history was reported less frequently by patients with DF (30&#xa0;%) than GD (60&#xa0;%). DF had the highest RSs for Africa (41.3), followed by Asia and Oceania (17.9) and the Americas (11.5). The respective GD RSs were 32.8, 25.4, and 11.9. The lowest RSs for both parasites were recorded for Eastern and Western Europe, Russia and the Baltic countries, and Scandinavia. For Asia and Oceania, the GD RS exceeded that of DF; for the other sites, DF had higher RSs than GD.<br><br>CONCLUSIONS: Dientamoeba fragilis appears to be transmitted both domestically and internationally. Although the overall acquisition risk appears low, for both Dientamoeba fragilis and Giardia duodenalis, the highest RSs are linked to visits to (sub)tropical regions, with subregional differences between the two parasites.}, }
@article {pmid40084887, year = {2025}, author = {Sun, Y-Y and Liu, N-N}, title = {Mycobiome: an underexplored kingdom in cancer.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {89}, number = {2}, pages = {e0026124}, pmid = {40084887}, issn = {1098-5557}, support = {32422004, 32270202//National Natural Science Foundation of China/ ; 23XD1422300//Program of Shanghai Academic Research Leader/ ; }, mesh = {Humans ; *Neoplasms/microbiology ; *Mycobiome/physiology ; *Fungi/pathogenicity/metabolism/genetics ; Dysbiosis/microbiology ; Bacteria ; Microbiota ; Animals ; }, abstract = {SUMMARYThe human microbiome, including bacteria, fungi, archaea, and viruses, is intimately linked to both health and disease. The relationship between bacteria and disease has received much attention and intensive investigation, while that of the fungal microbiome, also known as mycobiome, has lagged far behind bacteria. There is growing evidence showing mycobiome dysbiosis in cancer patients, and certain cancer-specific fungi may contribute to cancer progression by interacting with both host and bacteria. It was also demonstrated that the role of fungi-derived products in cancer should also not be underestimated. Therefore, investigating how fungal pathogenesis contributes to the onset and spread of cancer would yield crucial information for cancer diagnosis, prevention, and anti-cancer therapy.}, }
@article {pmid40077792, year = {2025}, author = {Costa, CJ and Prescott, S and Fourie, NH and Abey, SK and Sherwin, LB and Rahim-Williams, B and Joseph, PV and Posada-Quintero, H and Hoffman, RK and Henderson, WA}, title = {Host Transcriptome and Microbial Variation in Relation to Visceral Hyperalgesia.}, journal = {Nutrients}, volume = {17}, number = {5}, pages = {}, pmid = {40077792}, issn = {2072-6643}, support = {K22 MD006143/MD/NIMHD NIH HHS/United States ; 1ZIANR000018-01-09; K22MD006143-01/GF/NIH HHS/United States ; ZIA NR000018/ImNIH/Intramural NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; *Transcriptome ; Female ; *Visceral Pain/microbiology/genetics ; *Hyperalgesia/microbiology/genetics ; Adult ; Middle Aged ; RNA, Messenger/blood/genetics ; *Microbiota ; Mouth/microbiology ; *Gastrointestinal Microbiome ; }, abstract = {BACKGROUND: Chronic visceral hypersensitivity is associated with an overstressed pain response to noxious stimuli (hyperalgesia). Microbiota are active modulators of host biology and are implicated in the etiology of visceral hypersensitivity.<br><br>OBJECTIVES: we studied the association between the circulating mRNA transcriptome, the intensity of induced visceral pain (IVP), and variation in the oral microbiome among participants with and without baseline visceral hypersensitivity.<br><br>METHODS: Transcriptomic profiles and microbial abundance were correlated with IVP intensity. Host mRNA and microbes associated with IVP were explored, linking variation in the microbiome to host RNA biology.<br><br>RESULTS: 259 OTUs were found to be associated with IVP through correlation to differential expression of 471 genes in molecular pathways related to inflammation and neural mechanisms, including Rho and PI3K/AKT pathways. The bacterial families Lachnospiraceae, Prevotellaceae, and Veillonellaceae showed the highest degree of association. Oral microbial profiles with reduced diversity were characteristic of participants with visceral hypersensitivity.<br><br>CONCLUSIONS: Our results suggest that the oral microbiome may be involved in systemic immune and inflammatory effects and play a role in nervous system and stem cell pathways. The interactions between visceral hypersensitivity, differentially expressed molecular pathways, and microbiota described here provide a framework for further work exploring the relationship between host and microbiome.}, }
@article {pmid40076446, year = {2025}, author = {Li, Y and Zhang, ZJ and Saarela, O and Sharma, D and Xu, W}, title = {Mediation CNN (Med-CNN) Model for High-Dimensional Mediation Data.}, journal = {International journal of molecular sciences}, volume = {26}, number = {5}, pages = {}, pmid = {40076446}, issn = {1422-0067}, support = {RGPIN-2024-06081//Natural Sciences and Engineering Research Council/ ; }, mesh = {Humans ; *Neural Networks, Computer ; Algorithms ; *Microbiota ; Computer Simulation ; }, abstract = {Complex biological features such as the human microbiome and gene expressions play a crucial role in human health by mediating various biomedical processes that influence disease progression, such as immune responses and metabolic processes. Understanding these mediation roles is essential for gaining insights into disease pathogenesis and improving treatment outcomes. However, analyzing such high-dimensional mediation features presents challenges due to their inherent structural and correlations, such as the hierarchical taxonomic structures in microbial operational taxonomic units (OTUs), gene-pathway relationships, and the high dimensionality of the datasets, which complicates mediation analysis. We propose the Med-CNN model, an iterative approach using Convolutional Neural Networks (CNNs) to incorporate the complex biological network of the mediation features. The output values from network-specific CNN models are condensed into an integrative mediation metric (IMM), which captures essential biological information for estimating mediation effects. Our approach is designed to handle high-dimensional data and accommodate their unique structures and non-linear interactive mediation effects. Through comprehensive simulation studies, we evaluated the performance of our algorithm across different scenarios, including various mediation effects, effect sizes, and sample sizes, and we compared it to conventional methods. Our simulations demonstrated consistently lower biases in mediation effect estimates, with values ranging from 0.17 to 0.56, which were lower than other established methods ranging from 0.24 to 13.27. In a real data application, our method identified a mediation effect of 0.06 between ethnicity and vaginal pH levels.}, }
@article {pmid40072660, year = {2025}, author = {Hu, J and Chen, W and Zhu, R and Yang, F and Xu, J and Xiang, B and Li, Y and Wang, W and Zhu, L and Chen, G and Zhi, M}, title = {Dietary risk factors in Crohn's disease and ulcerative colitis: a cohort study with paired healthy relatives as controls.}, journal = {European journal of nutrition}, volume = {64}, number = {3}, pages = {123}, pmid = {40072660}, issn = {1436-6215}, support = {2014008//Sun Yat-sen University Clinical Research 5010 Program/ ; 82170542//National Natural Science Foundation of China/ ; 92251307//National Natural Science Foundation of China/ ; 82270544//National Natural Science Foundation of China/ ; 2019ZT08Y464//Guangdong Province "Pearl River Talent Plan" Innovation and Entrepreneurship Team Project/ ; 2021YFF0703702//National Key Research and Development Program of China/ ; 2023YFF1104404//National Key Research and Development Program of China/ ; 2023AFD124//Hubei Provincial Natural Science Foundation of China/ ; }, mesh = {Humans ; *Colitis, Ulcerative/etiology/epidemiology ; *Crohn Disease/etiology/epidemiology ; Female ; Male ; Risk Factors ; *Diet/methods/adverse effects ; Adult ; Middle Aged ; Cohort Studies ; Case-Control Studies ; Family ; }, abstract = {PURPOSE: Conflicting results have been reported on dietary factors in inflammatory bowel diseases (IBDs). Here, we compared the dietary intakes of IBD patients with those of paired healthy relatives (HRs), aiming to minimize the impact of genetic and environmental confounders.<br><br>METHODS: Patients with Crohn's disease (CD, N&#x2009;=&#x2009;45) and ulcerative colitis (UC, N&#x2009;=&#x2009;20), their paired HRs (NCD-HR = 45, NUC-HR = 20) and healthy non-relative (HNR, NCD-HNR = 25, NUC-HNR = 55) controls were recruited. Participants have kept dietary habits since the onset of IBDs and report no other recent digestive diseases or surgeries. Pre-illness dietary factors were assessed through 24-hour recall interviews. Statistical analyses included Analysis of Variance, Fisher's exact tests, Wilcoxon rank sum tests, logistic regressions, Area Under the Receiver-Operator Curve (AUROC) analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) regression.<br><br>RESULTS: Dietary features identified in IBD patients using the HR controls differed from those identified using the HNR controls. For CD, lower intakes of vitamin C, dietary fiber, calcium, vegetables, decanoic acid (10:0), milk, dairy foods, and &#x3b2;-carotene were identified as risk factors when compared to HRs. LASSO regression highlighted milk, vegetables, and vitamin C as the most significant risk factors for CD. In UC patients, lower intakes of phosphorus, docosapentaenoic acid (DPA, 22:5, n-3), vitamins B-2 and B-12, and choline, along with a higher intake of &#x3b1;-carotene, were identified as risk factors compared to HRs. LASSO regression emphasized DPA, vitamins B-2 and B-12, and &#x3b1;-carotene as the most significant risk factors for UC.<br><br>CONCLUSION: Monitoring dietary intake patterns is crucial for the prevention and personalized treatment of CD and UC.}, }
@article {pmid40069468, year = {2025}, author = {Yang, Y and Meng, Y and Xu, Z and Zhang, Q and Li, M and Kong, F and Zhang, S and Li, X and Zhu, Y}, title = {Leveraging microbiome signatures to predict tumor immune microenvironment and prognosis of patients with endometrial carcinoma.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {299}, pmid = {40069468}, issn = {2730-6011}, support = {20214Y0226//Shanghai Municipal Health Commission/ ; 2024CRTS045//Sunshine Clinical Research Incubator Program/ ; 2024CRTS017//Sunshine Clinical Research Incubator Program/ ; 2024CRTS015//Sunshine Clinical Research Incubator Program/ ; }, abstract = {Recent studies suggest that the human microbiome influence tumor development. Endometrial carcinoma (EC) is the sixth most common malignancy in women. Recent research has demonstrated the microbes play a critical role in the development and metastasis of EC. However, it remains unclear whether intratumoral microbes are associated with tumor microenvironment (TME) and prognosis of EC. In this study, we collected the EC microbiome data from cBioPortal and constructed a prognostic model based on Resident Microbiome of Endometrium (RME). We then examined the relationship between the RME score, immune cell infiltration, immunotherapy-related signature, and prognosis. The findings demonstrated the independent prognostic value of the RME score for EC. The group with low RME scores had higher enrichment of immune cells. Drug sensitivity analysis revealed that the RME score may serve as a potential predictor of chemotherapy efficacy. In conclusion, our research offers new perspectives on the relationships between tumor immunity and microbes.}, }
@article {pmid40069378, year = {2025}, author = {Gulyaeva, K and Nadinskaia, M and Maslennikov, R and Aleshina, Y and Goptar, I and Lukashev, A and Poluektova, E and Ivashkin, V}, title = {Gut microbiota analysis in cirrhosis and non-cirrhotic portal hypertension suggests that portal hypertension can be main factor of cirrhosis-specific dysbiosis.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {8394}, pmid = {40069378}, issn = {2045-2322}, support = {123021000156-7//Ministry of Health/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hypertension, Portal/microbiology/complications ; *Dysbiosis/microbiology/etiology ; Male ; Female ; Middle Aged ; *Liver Cirrhosis/microbiology/complications ; Cross-Sectional Studies ; RNA, Ribosomal, 16S/genetics ; Adult ; Aged ; Bacteria/genetics/classification ; Feces/microbiology ; Case-Control Studies ; }, abstract = {Gut dysbiosis plays an important role in cirrhosis, but the mechanism of its development was not established. The aim of the study was to test the hypothesis that portal hypertension can be the main factor in the development of gut dysbiosis in cirrhosis. This cross-sectional study included 25 patients with chronic non-cirrhotic portal hypertension due to extrahepatic portal vein obstruction after portal vein thrombosis (PVT) (NCPVT group), 29 cirrhotic patients without PVT (CirNoPVT), 15 cirrhotic patients with chronic PVT (CPVT), and 22 healthy controls. The fecal microbiota was assessed using 16S rRNA gene sequencing. The CirNoPVT and CPVT groups had largely similar differences in gut microbiota composition from the control group. Patients with NCPVT, as well as patients with cirrhosis, had a higher abundance of Streptococcus, Escherichia, Enterococcus, Enterobacteriaceae, Enterococcaceae, Streptococcaceae, Bacilli, Gammaproteobacteria, Proteobacteria, and a lower abundance of Roseburia, Faecalibacterium, Methanobrevibacter, Ruminococcaceae, Methanobacteriaceae, Clostridia, Methanobacteria, and Euryarchaeota as they were compared with healthy individuals. Patients with NCPVT had a higher abundance of Bifidobacterium, Bifidobacteriaceae, Actinobacteria, and a lower abundance of Gemmiger and Catenibacterium compared to healthy individuals, which was not observed in the cirrhosis groups. The abundance of Porphyromonadaceae with the genus Parabacteroides was reduced in both groups with PVT, but not in CirNoPVT. There were no significant differences in gut microbiota beta-diversity among the CirNoPVT, CPVT and NCPVT groups. All these groups had significant differences in beta-diversity from the control group. Portal hypertension seems be the main factor in the development of gut dysbiosis in cirrhosis.}, }
@article {pmid40059472, year = {2025}, author = {Elahi, Z and Mokhtaryan, M and Mahmoodi, S and Shahroodian, S and Darbandi, T and Ghasemi, F and Ghanavati, R and Darbandi, A}, title = {All Properties of Infertility Microbiome in a Review Article.}, journal = {Journal of clinical laboratory analysis}, volume = {39}, number = {6}, pages = {e25158}, pmid = {40059472}, issn = {1098-2825}, support = {4150//Behbahan Faculty of Medical Sciences/ ; }, mesh = {Humans ; *Microbiota/physiology ; Female ; *Infertility/microbiology ; Dysbiosis/microbiology ; }, abstract = {BACKGROUND: The microbiome is crucial for many physiological processes, including immunity, metabolism, and reproduction.<br><br>AIMS: This review aims to contribute to a detailed understanding of the microbiome of the genital tract, which can lead to better management of dysbiosis and reproductive disorders.<br><br>METHODS: Data from the four international information databases Medline, Scopus, Embase, and Google Scholar. The search strategy was based on the combination of the following terms: "microbiota," "microbiome," "microfilm," "microflora," "fertility," or "infertility."<br><br>RESULT: The advent of next-generation sequencing-based technologies during the last decade has revealed the presence of microbial communities in nearly every part of the human body, including the reproductive system. Several studies have shown significant differences between the microbiota of the vagina and endometrium, as well as other parts of the upper genital tract.<br><br>DISCUSSION: The human microbiome plays a critical role in determining a person's health state, and the microbiome of the genital tract may impact fertility potential before and after assisted reproductive treatments (ARTs).<br><br>CONCLUSION: To completely understand the role of the microbiome, future research should focus not only on the description of microbiota but also on the interaction between bacteria, the production of biofilms, and the interaction of microorganisms with human cells.}, }
@article {pmid40055343, year = {2025}, author = {Qi, H and Gao, H and Li, M and Sun, T and Gu, X and Wei, L and Zhi, M and Li, Z and Fu, D and Liu, Y and Wei, Z and Dou, Y and Feng, Q}, title = {Parvimonas micra promotes oral squamous cell carcinoma metastasis through TmpC-CKAP4 axis.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {2305}, pmid = {40055343}, issn = {2041-1723}, support = {82270980//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; *Mouth Neoplasms/microbiology/pathology/metabolism ; Animals ; Cell Line, Tumor ; *Carcinoma, Squamous Cell/microbiology/pathology/metabolism ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Male ; Female ; Neoplasm Metastasis ; *Membrane Proteins/metabolism/genetics ; Autophagy ; Mice, Nude ; }, abstract = {Parvimonas micra (P. micra), an opportunistic oral pathogen associated with multiple cancers, has limited research on its role in oral squamous cell carcinoma (OSCC). This study shows that P. micra is enriched in OSCC tissues and positively correlated with tumor metastasis and stages. P. micra infection promotes OSCC metastasis by inducing hypoxia/HIF-1α, glycolysis, and autophagy. Mechanistically, P. micra surface protein TmpC binds to CKAP4, a receptor overexpressed in OSCC, facilitating bacterial attachment and invasion. This interaction activates HIF-1α and autophagy via CKAP4-RanBP2 and CKAP4-NBR1 pathways, driving metastasis. Targeting CKAP4 with masitinib or antibodies impairs P. micra attachment and abolishes P. micra-promoted OSCC metastasis in vitro and in vivo. Together, our findings identify P. micra as a pathogen that promotes OSCC metastasis and highlight that TmpC-CKAP4 interaction could be a potential therapeutic target for OSCC.}, }
@article {pmid40054744, year = {2025}, author = {Fyhrquist, N and Yang, Y and Karisola, P and Alenius, H}, title = {Endotypes of atopic dermatitis.}, journal = {The Journal of allergy and clinical immunology}, volume = {156}, number = {1}, pages = {24-40.e4}, doi = {10.1016/j.jaci.2025.02.029}, pmid = {40054744}, issn = {1097-6825}, mesh = {Humans ; *Dermatitis, Atopic/immunology/classification/genetics/therapy ; Animals ; }, abstract = {Atopic dermatitis (AD) is a chronic, heterogeneous skin condition driven by a combination of genetic, immune, and environmental factors. The original classification into extrinsic and intrinsic endotypes has proven to be too simplistic. Recent research into the varied immune profiles and molecular signatures of AD has revealed distinct endotypes-that is, subtypes defined by specific biological processes rather than visible symptoms alone. These endotypes encompass classifications that are based on immune pathways, including TH2 dominant, TH1, TH17/TH22-driven responses, genetic factors, and microbial interactions. Recognizing these endotypes has become essential for advancing personalized treatments because each subtype responds differently to immune-modulating therapies. Current treatment options, such as moisturizers, immunosuppressants, and biologics, show varied efficacy across AD endotypes, underscoring the need for more precise, endotype-specific approaches. Emerging molecular profiling technologies offer promising avenues to identify distinct biomarkers, refining AD classification and paving the way for more targeted treatments and improved patient outcomes.}, }
@article {pmid40051624, year = {2025}, author = {De Martinis, ECP and Alves, VF and Pereira, MG and Andrade, LN and Abichabki, N and Abramova, A and Dannborg, M and Bengtsson-Palme, J}, title = {Applying 3D cultures and high-throughput technologies to study host-pathogen interactions.}, journal = {Frontiers in immunology}, volume = {16}, number = {}, pages = {1488699}, pmid = {40051624}, issn = {1664-3224}, mesh = {Humans ; *Host-Pathogen Interactions ; *Cell Culture Techniques, Three Dimensional/methods ; Animals ; *High-Throughput Screening Assays/methods ; }, abstract = {Recent advances in cell culturing and DNA sequencing have dramatically altered the field of human microbiome research. Three-dimensional (3D) cell culture is an important tool in cell biology, in cancer research, and for studying host-microbe interactions, as it mimics the in vivo characteristics of the host environment in an in vitro system, providing reliable and reproducible models. This work provides an overview of the main 3D culture techniques applied to study interactions between host cells and pathogenic microorganisms, how these systems can be integrated with high-throughput molecular methods, and how multi-species model systems may pave the way forward to pinpoint interactions among host, beneficial microbes and pathogens.}, }
@article {pmid40048849, year = {2025}, author = {Bargheet, A and Noordzij, HT and Ponsero, AJ and Jian, C and Korpela, K and Valles-Colomer, M and Debelius, J and Kurilshikov, A and Pettersen, VK}, title = {Dynamics of gut resistome and mobilome in early life: a meta-analysis.}, journal = {EBioMedicine}, volume = {114}, number = {}, pages = {105630}, pmid = {40048849}, issn = {2352-3964}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Infant ; Metagenomics/methods ; Infant, Newborn ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Metagenome ; Female ; Interspersed Repetitive Sequences ; *Drug Resistance, Bacterial/genetics ; Computational Biology/methods ; }, abstract = {BACKGROUND: The gut microbiota of infants harbours a higher proportion of antibiotic resistance genes (ARGs) compared to adults, even in infants never exposed to antibiotics. Our study aims to elucidate this phenomenon by analysing how different perinatal factors influence the presence of ARGs, mobile genetic elements (MGEs), and their bacterial hosts in the infant gut.<br><br>METHODS: We searched MEDLINE and Embase up to April 3rd, 2023, for studies reporting infant cohorts with shotgun metagenomic sequencing of stool samples. The systematic search identified 14 longitudinal infant cohorts from 10 countries across three continents, featuring publicly available sequencing data with corresponding metadata. For subsequent integrative bioinformatic analyses, we used 3981 high-quality metagenomic samples from 1270 infants and 415 mothers.<br><br>FINDINGS: We identified distinct trajectories of the resistome and mobilome associated with birth mode, gestational age, antibiotic use, and geographical location. Geographical variation was exemplified by differences between cohorts from Europe, Southern Africa, and Northern America, which showed variation in both diversity and abundance of ARGs. On the other hand, we did not detect a significant impact of breastfeeding on the infants' gut resistome. More than half of detected ARGs co-localised with plasmids in key bacterial hosts, such as Escherichia coli and Enterococcus faecalis. These ARG-associated plasmids were gradually lost during infancy. We also demonstrate that E.&#xa0;coli role as a primary modulator of the infant gut resistome and mobilome is facilitated by its increased abundance and strain diversity compared to adults.<br><br>INTERPRETATION: Birth mode, gestational age, antibiotic exposure, and geographical location significantly influence the development of the infant gut resistome and mobilome. A reduction in E. coli relative abundance over time appears as a key factor driving the decrease in both resistome and plasmid relative abundance as infants grow.<br><br>FUNDING: Centre for Advanced Study in Oslo, Norway. Centre for New Antibacterial Strategies through the Troms&#xf8; Research Foundation, Norway.}, }
@article {pmid40040485, year = {2025}, author = {Wang, Y and Li, B and Jian, C and Gagaoua, M and Estévez, M and Puolanne, E and Ertbjerg, P}, title = {Oxidative stress-induced changes in wooden breast and mitigation strategies: A review.}, journal = {Comprehensive reviews in food science and food safety}, volume = {24}, number = {2}, pages = {e70148}, doi = {10.1111/1541-4337.70148}, pmid = {40040485}, issn = {1541-4337}, support = {348385//Research Council of Finland/ ; }, mesh = {*Oxidative Stress ; Animals ; *Muscular Diseases/veterinary/prevention &amp; control ; *Poultry Diseases/prevention &amp; control ; Meat/analysis ; Muscle, Skeletal/metabolism ; Humans ; }, abstract = {Wooden breast (WB) is a multifactorial muscular abnormality resulting from the interplay between genetic predispositions for rapid growth, physiological stress, and anatomical impairments. This myopathy has been a persistent challenge in the poultry industry since its initial identification a decade ago. WB negatively impacts meat quality, leading to increased toughness and reduced nutritional value. Building on foundational research utilizing multiomics technologies, hypoxia-induced oxidative stress has been identified as a key early event driving the pathological processes of WB. This review provides a comprehensive overview and the state-of-the-art evidence on the pivotal role of oxidative stress in WB myopathy. It begins by examining the generation of reactive intermediates that induce oxidative damage and the host's defense mechanisms aimed at mitigating these threats. The discussion then focuses on the consequences of oxidative damage for mitochondria, protein and lipid oxidation, connective tissue remodeling, and inflammation-pathological hallmarks of WB-affected muscles. Additionally, the review highlights how oxidative stress influences satellite cell behavior, impairing the repair and regeneration of muscle tissues, a process implicated in WB. Finally, efforts to prevent or mitigate WB myopathy are summarized, with particular attention to potential intervention strategies targeting oxidative stress. These include innovative feed formulations and gut microbiota modulation, which show promise in alleviating the severity of the condition.}, }
@article {pmid40033410, year = {2025}, author = {Ranta, K and Skurnik, M and Kiljunen, S}, title = {Isolation and characterization of fMGyn-Pae01, a phiKZ-like jumbo phage infecting Pseudomonas aeruginosa.}, journal = {Virology journal}, volume = {22}, number = {1}, pages = {55}, pmid = {40033410}, issn = {1743-422X}, mesh = {*Pseudomonas aeruginosa/virology/physiology ; Genome, Viral ; *Pseudomonas Phages/isolation &amp; purification/genetics/ultrastructure/physiology/classification ; Host Specificity ; Biofilms/growth &amp; development ; Whole Genome Sequencing ; Phage Therapy ; Microscopy, Electron, Transmission ; }, abstract = {BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide variety of infections, and belongs to the group of ESKAPE pathogens that are the leading cause of healthcare-associated infections and have high level of antibiotic resistance. The treatment of infections caused by antibiotic-resistant P. aeruginosa is challenging, which makes it a common target for phage therapy. The successful utilization of phage therapy requires a collection of well characterized phages.<br><br>METHODS: Phage fMGyn-Pae01 was isolated from a commercial phage therapy cocktail. The phage morphology was studied by transmission electron microscopy and the host range was analyzed with a liquid culture method. The phage genome was sequenced and characterized, and the genome was compared to closest phage genomes. Phage resistant bacterial mutants were isolated and whole genome sequencing and motility, phage adsorption and biofilm formation assays were performed to the mutants and host bacterium.<br><br>RESULTS: The genomic analysis revealed that fMGyn-Pae01 is a lytic, phiKZ-like jumbo phage with genome size of 277.8&#xa0;kb. No genes associated with lysogeny, bacterial virulence, or antibiotic resistance were identified. Phage fMGyn-Pae01 did not reduce biofilm formation of P. aeruginosa, suggesting that it may not be an optimal phage to be used in monophage therapy in conditions where biofilm formation is expected. Host range screening revealed that fMGyn-Pae01 has a wide host range among P. aeruginosa strains and its infection was not dependent on O-serotype. Whole genome sequencing of the host bacterium and phage resistant mutants revealed that the mutations had inactivated either a flagellar or rpoN gene, thereby preventing the biosynthesis of a functional flagellum. The lack of functional flagella was confirmed in motility assays. Additionally, fMGyn-Pae01 failed to adsorb on non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor.<br><br>CONCLUSION: fMGyn-Pae01 is a phiKZ-like jumbo phage infecting P. aeruginosa. fMGyn-Pae01 uses the flagellum as its phage-binding receptor, supporting earlier suggestions that flagellum might be utilized by phiKZ but differs from some other previous findings showing that phiKZ-like phages use the type-IV pili as the phage-binding receptor.}, }
@article {pmid40033063, year = {2025}, author = {Metwaly, A and Kriaa, A and Hassani, Z and Carraturo, F and Druart, C and ,  and Arnauts, K and Wilmes, P and Walter, J and Rosshart, S and Desai, MS and Dore, J and Fasano, A and Blottiere, HM and Maguin, E and Haller, D}, title = {A Consensus Statement on establishing causality, therapeutic applications and the use of preclinical models in microbiome research.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {22}, number = {5}, pages = {343-356}, pmid = {40033063}, issn = {1759-5053}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Animals ; Consensus ; Delphi Technique ; Disease Models, Animal ; Dysbiosis ; }, abstract = {The gut microbiome comprises trillions of microorganisms and profoundly influences human health by modulating metabolism, immune responses and neuronal functions. Disruption in gut microbiome composition is implicated in various inflammatory conditions, metabolic disorders and neurodegenerative diseases. However, determining the underlying mechanisms and establishing cause and effect is extremely difficult. Preclinical models offer crucial insights into the role of the gut microbiome in diseases and help identify potential therapeutic interventions. The Human Microbiome Action Consortium initiated a Delphi survey to assess the utility of preclinical models, including animal and cell-based models, in elucidating the causal role of the gut microbiome in these diseases. The Delphi survey aimed to address the complexity of selecting appropriate preclinical models to investigate disease causality and to study host-microbiome interactions effectively. We adopted a structured approach encompassing a literature review, expert workshops and the Delphi questionnaire to gather insights from a diverse range of stakeholders. Experts were requested to evaluate the strengths, limitations, and suitability of these models in addressing the causal relationship between the gut microbiome and disease pathogenesis. The resulting consensus statements and recommendations provide valuable insights for selecting preclinical models in future studies of gut microbiome-related diseases.}, }
@article {pmid40030005, year = {2025}, author = {Darwin, A and Xie, J and Smith, M}, title = {Antibiotic use: impact on the microbiome and cellular therapy outcomes.}, journal = {Blood advances}, volume = {9}, number = {13}, pages = {3356-3367}, pmid = {40030005}, issn = {2473-9537}, mesh = {Humans ; *Anti-Bacterial Agents/adverse effects/therapeutic use/pharmacology ; *Gastrointestinal Microbiome/drug effects ; *Cell- and Tissue-Based Therapy/methods/adverse effects ; *Microbiota/drug effects ; Hematopoietic Stem Cell Transplantation/adverse effects ; Treatment Outcome ; }, abstract = {Antibiotics disrupt the delicate balance of bacteria, fungi, and viruses in the human microbiome. Growing evidence indicates a significant relationship between the intestinal microbiome and cellular therapy, which aligns with the established influence of the microbiome on immune responses. When examining the link between cellular therapy and the microbiome, it is essential to understand how disruptions in the microbiome, especially those caused by antibiotics, affect these therapies. Here, we discuss the impact of antibiotics on the intestinal microbiome, cellular therapy outcomes, and associated toxicities, particularly in the context of hematopoietic cell transplantation and chimeric antigen receptor T-cell therapy. Furthermore, we examine the mechanisms through which antibiotics affect cellular therapy, the future implications of this knowledge, and the areas that warrant further investigation.}, }
@article {pmid40026151, year = {2025}, author = {Jena, PK and Wakita, D and Gomez, AC and Carvalho, TT and Atici, AE and Aubuchon, E and Narayanan, M and Lee, Y and Fishbein, MC and Takasato, Y and Kurashima, Y and Kiyono, H and Cani, PD and de Vos, WM and Underhill, DM and Devkota, S and Chen, S and Shimada, K and Crother, TR and Arditi, M and Noval Rivas, M}, title = {Intestinal Microbiota Contributes to the Development of Cardiovascular Inflammation and Vasculitis in Mice.}, journal = {Circulation research}, volume = {136}, number = {8}, pages = {e53-e72}, pmid = {40026151}, issn = {1524-4571}, support = {R01 HL139766/HL/NHLBI NIH HHS/United States ; R01 HL159297/HL/NHLBI NIH HHS/United States ; R01 HL149972/HL/NHLBI NIH HHS/United States ; R01 AI157274/AI/NIAID NIH HHS/United States ; R01 HL170580/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; Lacticaseibacillus casei ; Disease Models, Animal ; *Mucocutaneous Lymph Node Syndrome/microbiology/pathology ; Mice, Inbred C57BL ; *Vasculitis/microbiology/pathology ; Male ; Toll-Like Receptor 2/metabolism ; Inflammation/microbiology ; Akkermansia ; }, abstract = {BACKGROUND: Alterations in the intestinal microbiota contribute to the pathogenesis of various cardiovascular disorders, but how they affect the development of Kawasaki disease (KD) an acute pediatric vasculitis, remains unclear.<br><br>METHODS: We used the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to assess the contribution of the intestinal microbiota to the development of vascular inflammation. We evaluated the severity of vasculitis in microbiota-depleted mice. 16S rRNA gene sequencing was used to characterize the fecal microbiome composition of LCWE-injected mice. Some groups of mice were orally treated with selected live or pasteurized bacteria, short-chain fatty acids, or Amuc_1100, the Toll-like receptor 2 signaling outer membrane protein from Akkermansia muciniphila, and their impact on vasculitis development was assessed.<br><br>RESULTS: We report that depleting the gut microbiota reduces the development of cardiovascular inflammation in a murine model mimicking KD vasculitis. The development of cardiovascular lesions was associated with alterations in the intestinal microbiota composition and, notably, a decreased abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Oral supplementation with either of these live or pasteurized individual bacteria or with short-chain fatty acids produced by them attenuated cardiovascular inflammation, as reflected by decreased local immune cell infiltrations. Treatment with Amuc_1100 also reduced the severity of vascular inflammation.<br><br>CONCLUSIONS: This study reveals an underappreciated gut microbiota-cardiovascular inflammation axis in KD vasculitis pathogenesis and identifies specific intestinal commensals that regulate vasculitis in mice by producing metabolites or via extracellular proteins capable of enhancing and supporting gut barrier function.}, }
@article {pmid40023841, year = {2025}, author = {Pérez Escriva, P and Correia Tavares Bernardino, C and Letellier, E}, title = {De-coding the complex role of microbial metabolites in cancer.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115358}, doi = {10.1016/j.celrep.2025.115358}, pmid = {40023841}, issn = {2211-1247}, mesh = {Humans ; *Neoplasms/microbiology/metabolism/pathology ; *Microbiota ; Animals ; }, abstract = {The human microbiome, an intricate ecosystem of trillions of microbes residing across various body sites, significantly influences cancer, a leading cause of morbidity and mortality worldwide. Recent studies have illuminated the microbiome's pivotal role in cancer development, either through direct cellular interactions or by secreting bioactive compounds such as metabolites. Microbial metabolites contribute to cancer initiation through mechanisms such as DNA damage, epithelial barrier dysfunction, and chronic inflammation. Furthermore, microbial metabolites exert dual roles on cancer progression and response to therapy by modulating cellular metabolism, gene expression, and signaling pathways. Understanding these complex interactions is vital for devising new therapeutic strategies. This review highlights microbial metabolites as promising targets for cancer prevention and treatment, emphasizing their impact on therapy responses and underscoring the need for further research into their roles in metastasis and therapy resistance.}, }
@article {pmid40023356, year = {2025}, author = {Das, M and Kiruthiga, C and Shafreen, RB and Nachammai, K and Selvaraj, C and Langeswaran, K}, title = {Harnessing the human microbiome and its impact on immuno-oncology and nanotechnology for next-generation cancer therapies.}, journal = {European journal of pharmacology}, volume = {996}, number = {}, pages = {177436}, doi = {10.1016/j.ejphar.2025.177436}, pmid = {40023356}, issn = {1879-0712}, mesh = {Humans ; *Neoplasms/immunology/therapy/microbiology/drug therapy ; *Microbiota/immunology/drug effects ; *Immunotherapy/methods ; *Nanotechnology ; *Immune Checkpoint Inhibitors/therapeutic use/administration &amp; dosage ; Animals ; Drug Delivery Systems ; }, abstract = {The integration of microbiome research and nanotechnology represents a significant advancement in immuno-oncology, potentially improving the effectiveness of cancer immunotherapies. Recent studies highlight the influential role of the human microbiome in modulating immune responses, presenting new opportunities to enhance immune checkpoint inhibitors (ICIs) and other cancer therapies. Nanotechnology offers precise drug delivery and immune modulation capabilities, minimizing off-target effects while maximizing therapeutic outcomes. This review consolidates current knowledge on the interactions between the microbiome and the immune system, emphasizing the microbiome's impact on ICIs, and explores the incorporation of nanotechnology in cancer treatment strategies. Additionally, it provides a forward-looking perspective on the synergistic potential of microbiome modulation and nanotechnology to overcome existing challenges in immuno-oncology. This integrated approach may enhance the personalization and effectiveness of next-generation cancer treatments, paving the way for transformative patient care.}, }
@article {pmid40019912, year = {2025}, author = {Ryan, N and O'Mahony, S and Leahy-Warren, P and Philpott, L and Mulcahy, H}, title = {The impact of perinatal maternal stress on the maternal and infant gut and human milk microbiomes: A scoping review.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0318237}, pmid = {40019912}, issn = {1932-6203}, mesh = {Humans ; Female ; *Milk, Human/microbiology ; Pregnancy ; *Gastrointestinal Microbiome/physiology ; *Stress, Psychological/microbiology ; Infant, Newborn ; Infant ; Stress, Physiological ; }, abstract = {BACKGROUND: Perinatal maternal stress, which includes both psychological and physiological stress experienced by healthy women during pregnancy and the postpartum period, is becoming increasingly prevalent. Infant early exposure to adverse environments such as perinatal stress has been shown to increase the long-term risk to metabolic, immunologic and neurobehavioral disorders. Evidence suggests that the human microbiome facilitates the transmission of maternal factors to infants via the vaginal, gut, and human milk microbiomes. The colonization of aberrant microorganisms in the mother's microbiome, influenced by the microbiome-brain-gut axis, may be transferred to infants during a critical early developmental period. This transfer may predispose infants to a more inflammatory-prone microbiome which is associated with dysregulated metabolic process leading to adverse health outcomes. Given the prevalence and potential impact of perinatal stress on maternal and infant health, with no systematic mapping or review of the data to date, the aim of this scoping review is to gather evidence on the relationship between perinatal maternal stress, and the human milk, maternal, and infant gut microbiomes.<br><br>METHODS: This is an exploratory mapping scoping review, guided by the Joanna Briggs Institute's methodology along with use of the Prisma Scr reporting guideline. A comprehensive search was conducted using the following databases, CINAHL Complete; MEDLINE; PsycINFO, Web of Science and Scopus with a protocol registered with Open Science Framework DOI 10.17605/OSF.IO/5SRMV.<br><br>RESULTS: After screening 1145 papers there were 7 paper that met the inclusion criteria. Statistically significant associations were found in five of the studies which identify higher abundance of potentially pathogenic bacteria such as Erwinia, Serratia, T mayombie, Bacteroides with higher maternal stress, and lower levels of stress linked to potentially beneficial bacteria such Lactococcus, Lactobacillus, Akkermansia. However, one study presents conflicting results where it was reported that higher maternal stress was linked to the prevalence of more beneficial bacteria.<br><br>CONCLUSION: This review suggests that maternal stress does have an impact on the alteration of abundance and diversity of influential bacteria in the gut microbiome, however, it can affect colonisation in different ways. These bacterial changes have the capacity to influence long term health and disease. The review analyses data collection tools and methods, offers potential reasons for these findings as well as suggestions for future research.}, }
@article {pmid40016751, year = {2025}, author = {Gan, Y and Yuan, Z and Weng, J and Huang, M and Li, T and Wu, Y and Lin, K and Han, J and Li, X and Liu, H and Wan, Z and Li, Z and Chen, Z and Cui, J and Luo, Y and Huang, M and Yu, H and Lin, J}, title = {Transcriptomic profile of RNA pseudouridine modification as a biomarker for cellular senescence associated with survival outcomes in colorectal cancer.}, journal = {BMC biology}, volume = {23}, number = {1}, pages = {61}, pmid = {40016751}, issn = {1741-7007}, mesh = {Humans ; *Colorectal Neoplasms/genetics/mortality ; *Cellular Senescence/genetics ; *Transcriptome ; *Pseudouridine/metabolism/genetics ; *Biomarkers, Tumor/genetics/metabolism ; Cell Line, Tumor ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) is considered as an age-related disease, and cellular senescence (CS) plays a crucial role in cancer development and progression. Previous studies have shown the role of epigenetic changes in aging and cancer development, but the role of RNA pseudouridine (Ψ) modification in aging and cancer remains to be explored.<br><br>RESULTS: Using bulk RNA sequencing, CRC cells with low &#x3a8; writers expression levels have higher CS levels. We developed the Psi Score for assessing the transcriptomic profile of RNA &#x3a8; modification regulation and found that the Psi Score correlates with CS. Furthermore, Psi-related senescence may be mediated by mTOR, TGF-&#x3b2;, TNF-&#x3b1;, and inflammatory response signaling pathways. Meanwhile, Psi Score could predict the anti-cancer treatment outcomes of anti-aging interventions and could be used to predict the response to immunotherapy.<br><br>CONCLUSIONS: Overall, these findings reveal that RNA &#x3a8; modification connected aging and cancer and provided novel insights into biomarker-guided cancer regimens.}, }
@article {pmid40016656, year = {2025}, author = {Koslovsky, MD}, title = {Analyzing microbiome data with taxonomic misclassification using a zero-inflated Dirichlet-multinomial model.}, journal = {BMC bioinformatics}, volume = {26}, number = {1}, pages = {69}, pmid = {40016656}, issn = {1471-2105}, support = {DMS-2245492//National Science Foundation/ ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Obesity/microbiology ; Child ; Algorithms ; }, abstract = {The human microbiome is the collection of microorganisms living on and inside of our bodies. A major aim of microbiome research is understanding the role microbial communities play in human health with the goal of designing personalized interventions that modulate the microbiome to treat or prevent disease. Microbiome data are challenging to analyze due to their high-dimensionality, overdispersion, and zero-inflation. Analysis is further complicated by the steps taken to collect and process microbiome samples. For example, sequencing instruments have a fixed capacity for the total number of reads delivered. It is therefore essential to treat microbial samples as compositional. Another complicating factor of modeling microbiome data is that taxa counts are subject to measurement error introduced at various stages of the measurement protocol. Advances in sequencing technology and preprocessing pipelines coupled with our growing knowledge of the human microbiome have reduced, but not eliminated, measurement error. Ignoring measurement error during analysis, though common in practice, can then lead to biased inference and curb reproducibility. We propose a Dirichlet-multinomial modeling framework for microbiome data with excess zeros and potential taxonomic misclassification. We demonstrate how accommodating taxonomic misclassification improves estimation performance and investigate differences in gut microbial composition between healthy and obese children.}, }
@article {pmid40009328, year = {2025}, author = {Mivehchi, H and Eskandari-Yaghbastlo, A and Pour Bahrami, P and Elhami, A and Faghihinia, F and Nejati, ST and Kazemi, KS and Nabi Afjadi, M}, title = {Exploring the role of oral bacteria in oral cancer: a narrative review.}, journal = {Discover oncology}, volume = {16}, number = {1}, pages = {242}, pmid = {40009328}, issn = {2730-6011}, abstract = {A growing body of research indicates that a wide range of cancer types may correlate with human microbiome components. On the other hand, little is known about the potential contribution of the oral microbiota to oral cancer. However, some oral microbiome components can stimulate different tumorigenic processes associated with the development of cancer. In this line, two prevalent oral infections, Porphyromonas gingivalis, and Fusobacterium nucleatum can increase tumor growth. The microbiome can impact the course of the illness through direct interactions with the human body and major modifications to the toxicity and responsiveness to different kinds of cancer therapy. Recent research has demonstrated a relationship between specific phylogenetic groupings and the results of immunotherapy treatment for particular tumor types. Conversely, there has been a recent upsurge in interest in the possibility of using microbes to treat cancer. At the moment, some species, such as Salmonella typhimurium and Clostridium spp., are being explored as possible cancer treatment vectors. Thus, understanding these microbial interactions highlights the importance of maintaining a healthy oral microbiome in preventing oral cancers. From this perspective, this review will discuss the role of the microbiome on oral cancers and their possible application in oral cancer treatment/improvement.}, }
@article {pmid40005682, year = {2025}, author = {Ece, G and Aktaş, A and Caner, A and Sağlık, &#x130; and Kula Atik, T and Ulusan Bağcı, &#xd6; and Bayındır Bilman, F and Demirbakan, H and Güdül Havuz, S and Kaya, E and Koyuncu Özyurt, &#xd6; and Yetkin, G and Zorbozan, O}, title = {The Urogenital System Microbiota: Is It a New Gamechanger in Urogenital Cancers?.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005682}, issn = {2076-2607}, abstract = {The human microbiome, which encompasses microbial communities and their genetic material, significantly influences health and disease, including cancer. The urogenital microbiota, naturally present in the urinary and genital tracts, interact with factors such as age, lifestyle, and health conditions to affect homeostasis and carcinogenesis. Studies suggest that alterations in this microbiota contribute to the development and progression of genitourinary cancers, emphasizing the concept of oncobiome, which refers to microbial genetic contributions to cancer. Similarly, gut microbiota can influence hormone levels and systemic inflammation, impacting cancers such as cervical and prostate cancer. Advanced studies indicate that microbial communities in genitourinary cancers have distinct profiles that may serve as diagnostic biomarkers or therapeutic targets. Dysbiosis of the urinary microbiota correlates with bladder and kidney cancer. Additionally, gut microbiota influence the effectiveness of cancer treatments. However, further research is necessary to clarify causality, the role of microbial metabolites, and hormonal regulation. The aim of this review is to understand that these dynamics present opportunities for innovative cancer diagnostics and therapies, highlighting the need for integration of microbiology, oncology, and genomics to explore the role of microbiota in genitourinary cancers. For this, a comprehensive search of relevant databases was conducted, applying specific inclusion and exclusion criteria to identify studies examining the association between microbiota and urogenital cancers. Research into the mechanisms by which microbiota influence urogenital cancers may pave the way for new diagnostic and therapeutic approaches, ultimately improving patient outcomes.}, }
@article {pmid40005646, year = {2025}, author = {Choi, Y and Jeong, J and Han, Y and Han, M and Yu, B and Han, K}, title = {Exploring Competitive Relationship Between Haemophilus parainfluenzae and Mitis Streptococci via Co-Culture-Based Molecular Diagnosis and Metabolomic Assay.}, journal = {Microorganisms}, volume = {13}, number = {2}, pages = {}, pmid = {40005646}, issn = {2076-2607}, support = {RS-2024-00355393//the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea/ ; }, abstract = {Various bacterial strains with nitrate-reducing capacity (NRC), such as Haemophilus, Actinomyces, and Neisseria, are known to promote NH3 production, control pH in the oral cavity, and inhibit the growth of aciduric bacteria. However, experimental evidence on various estimated bacterial networks within the salivary microbiome is insufficient. This study aims to explore potential bacterial compositional competition observed within saliva samples from dental caries patients through a co-culture assay of mitis Streptococci, which is a primary colonizer in the salivary microbiome, and nitrate-reducing bacteria Haemophilus parainfluenzae. We investigated bacterial growth efficiency change by co-culture time using the qRT-PCR method. In addition, we applied LC/Q-TOF-based metabolites screening to confirm metabolic interactions between oral bacterial species and their association with dental caries from a metabolomics perspective. As a result, we first found that the nitrate reduction ability of H. parainfluenzae is maintained even in a co-culture environment with the mitis Streptococci group through a nitrate reduction test. However, nitrate reduction efficiency was hindered when compared with monoculture-based nitrate reduction test results. Next, we designed species-specific primers, and we confirmed by qRT-PCR that there is an obvious competitive relationship in growth efficiency between H. parainfluenzae and two mitis Streptococci (S. australis and S. sanguinis). Furthermore, although direct effects of nitrate reduction on competition have not been identified, we have potentially confirmed through LC/Q-TOF-based metabolite screening analysis that the interaction of various metabolic compounds synthesized from mitis Streptococci is driving inter-strain competition. In particular, we constructed a basic reference core-metabolites list to understand the metabolic network between each target bacterial species (H. parainfluenzae and mitis Streptococci) within the salivary microbiome, which still lacks accumulated research data. Ultimately, we suggest that our data have potential value to be referenced in further metagenomics and metabolomics-based studies related to oral health care.}, }
@article {pmid39999339, year = {2025}, author = {Hohmann, M and Iliasov, D and Larralde, M and Johannes, W and Janßen, KP and Zeller, G and Mascher, T and Gulder, TAM}, title = {Heterologous Expression of a Cryptic BGC from Bilophila sp. Provides Access to a Novel Family of Antibacterial Thiazoles.}, journal = {ACS synthetic biology}, volume = {14}, number = {3}, pages = {967-978}, pmid = {39999339}, issn = {2161-5063}, mesh = {*Thiazoles/pharmacology/metabolism/chemistry ; *Anti-Bacterial Agents/pharmacology/metabolism/chemistry ; Humans ; Gastrointestinal Microbiome ; *Bacteroidetes/genetics/metabolism ; }, abstract = {Human health is greatly influenced by the gut microbiota and microbiota imbalance can lead to the development of diseases. It is widely acknowledged that the interaction of bacteria within competitive ecosystems is influenced by their specialized metabolites, which act, e.g., as antibacterials or siderophores. However, our understanding of the occurrence and impact of such natural products in the human gut microbiome remains very limited. As arylthiazole siderophores are an emerging family of growth-promoting molecules in pathogenic bacteria, we analyzed a metagenomic data set from the human microbiome and thereby identified the bil-BGC, which originates from an uncultured Bilophila strain. Through gene synthesis and BGC assembly, heterologous expression and mutasynthetic experiments, we discovered the arylthiazole natural products bilothiazoles A-F. While established activities of related molecules indicate their involvement in metal-binding and -uptake, which could promote the growth of pathogenic strains, we also found antibiotic activity for some bilothiazoles. This is supported by biosensor-experiments, where bilothiazoles C and E show PrecA-suppressing activity, while bilothiazole F induces PblaZ, a biosensor characteristic for β-lactam antibiotics. These findings serve as a starting point for investigating the role of bilothiazoles in the pathogenicity of Bilophila species in the gut.}, }
@article {pmid39998261, year = {2025}, author = {Woh, PY and Chen, Y and Kumpitsch, C and Mohammadzadeh, R and Schmidt, L and Moissl-Eichinger, C}, title = {Reevaluation of the gastrointestinal methanogenic archaeome in multiple sclerosis and its association with treatment.}, journal = {Microbiology spectrum}, volume = {13}, number = {4}, pages = {e0218324}, pmid = {39998261}, issn = {2165-0497}, support = {F83, P32697, COE7//Austrian Science Fund (FWF)/ ; }, mesh = {Humans ; *Multiple Sclerosis/microbiology/drug therapy ; Female ; Middle Aged ; *Gastrointestinal Microbiome ; Adult ; Male ; Aged ; *Archaea/classification/genetics/metabolism/isolation &amp; purification ; Methanobrevibacter/genetics/isolation &amp; purification/metabolism/classification ; Metagenomics ; Methane/metabolism ; }, abstract = {The role of the gut archaeal microbiome (archaeome) in health and disease remains poorly understood. Methanogenic archaea have been linked to multiple sclerosis (MS), but prior studies were limited by small cohorts and inconsistent methodologies. To address this, we re-evaluated the association between methanogenic archaea and MS using metagenomic data from the International Multiple Sclerosis Microbiome Study. We analyzed gut microbiome profiles from 115 MS patients and 115 healthy household controls across Buenos Aires (27.8%), Edinburgh (33.9%), New York (10.4%), and San Francisco (27.8%). Metagenomic sequences were taxonomically classified using kraken2/bracken and a curated profiling database to detect archaea, specifically Methanobrevibacter species. Most MS patients were female (80/115), aged 25-72 years (median: 44.5), and 70% were undergoing treatment, including dimethyl fumarate (n = 21), fingolimod (n = 20), glatiramer acetate (n = 14), interferon (n = 18), natalizumab (n = 6), or ocrelizumab/rituximab (n = 1). We found no significant differences in overall archaeome profiles between MS patients and controls. However, treated MS patients exhibited higher abundances of Methanobrevibacter smithii and M. sp900766745 compared to untreated patients. Notably, M. sp900766745 abundance correlated with lower disease severity scores in treated patients. Our results suggest that gut methanogens are not directly associated with MS onset or progression but may reflect microbiome health during treatment. These findings highlight potential roles for M. smithii and M. sp900766745 in modulating treatment outcomes, warranting further investigation into their relevance to gut microbiome function and MS management.IMPORTANCEMultiple sclerosis (MS) is a chronic neuroinflammatory disease affecting the central nervous system, with approximately 2.8 million people diagnosed worldwide, mainly young adults aged 20-30 years. While recent studies have focused on bacterial changes in the MS microbiome, the role of gut archaea has been less explored. Previous research suggested a potential link between methanogenic archaea and MS disease status, but these findings remained inconclusive. Our study addresses this gap by investigating the gut archaeal composition in MS patients and examining how it changes in response to treatment. By focusing on methanogens, we aim to uncover novel insights into their role in MS, potentially revealing new biomarkers or therapeutic targets. This research is crucial for enhancing our understanding of the gut microbiome's impact on MS and improving patient management.}, }
@article {pmid39998226, year = {2025}, author = {Martino, C and Kellman, BP and Sandoval, DR and Clausen, TM and Cooper, R and Benjdia, A and Soualmia, F and Clark, AE and Garretson, AF and Marotz, CA and Song, SJ and Wandro, S and Zaramela, LS and Salido, RA and Zhu, Q and Armingol, E and Vázquez-Baeza, Y and McDonald, D and Sorrentino, JT and Taylor, B and Belda-Ferre, P and Das, P and Ali, F and Liang, C and Zhang, Y and Schifanella, L and Covizzi, A and Lai, A and Riva, A and Basting, C and Broedlow, CA and Havulinna, AS and Jousilahti, P and Estaki, M and Kosciolek, T and Kuplicki, R and Victor, TA and Paulus, MP and Savage, KE and Benbow, JL and Spielfogel, ES and Anderson, CAM and Martinez, ME and Lacey, JV and Huang, S and Haiminen, N and Parida, L and Kim, H-C and Gilbert, JA and Sweeney, DA and Allard, SM and Swafford, AD and Cheng, S and Inouye, M and Niiranen, T and Jain, M and Salomaa, V and Zengler, K and Klatt, NR and Hasty, J and Berteau, O and Carlin, AF and Esko, JD and Lewis, NE and Knight, R}, title = {SARS-CoV-2 infectivity can be modulated through bacterial grooming of the glycocalyx.}, journal = {mBio}, volume = {16}, number = {4}, pages = {e0401524}, pmid = {39998226}, issn = {2150-7511}, support = {R01 GM069811/GM/NIGMS NIH HHS/United States ; NNF20SA0066621//Novo Nordisk Foundation/ ; R01 ES027595/ES/NIEHS NIH HHS/United States ; 1P30DK120515//HHS | National Institutes of Health (NIH)/ ; U19 AI116497/AI/NIAID NIH HHS/United States ; R00RG2503//UC | University of California, San Diego (UCSD)/ ; 2031989//National Science Foundation (NSF)/ ; ANR-17-CE11-0014//French National Research Agency/ ; 335525//Academy of Finland/ ; 3022//Emerald Foundation/ ; 1DP1AT010885//HHS | National Institutes of Health (NIH)/ ; U01 CA199277/CA/NCI NIH HHS/United States ; R01-CA077398//HHS | National Institutes of Health (NIH)/ ; R01ES027595//HHS | National Institutes of Health (NIH)/ ; UM1 CA164917/CA/NCI NIH HHS/United States ; R01GM069811//HHS | National Institutes of Health (NIH)/ ; RG/18/13/33946//British Heart Foundation (BHF)/ ; 2018-72190270//ANID Becas Chile Doctorado/ ; //Emil Aaltosen S&#xe4;&#xe4;ti&#xf6; (Emil Aaltonen Foundation)/ ; UH2AI153029//HHS | National Institutes of Health (NIH)/ ; //Health Data Research UK (HDR UK)/ ; AI Horizons Network//IBM | IBM Research/ ; P30-CA023100//HHS | National Institutes of Health (NIH)/ ; P30-CA033572//HHS | National Institutes of Health (NIH)/ ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; //NIHR | NIHR Cambridge Biomedical Research Centre (NIHR Cambridge BRC)/ ; //Syd&#xe4;ntutkimuss&#xe4;&#xe4;ti&#xf6; (Finnish Foundation for Cardiovascular Research)/ ; UH2 AI153029/AI/NIAID NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; 101046041//Union's Horizon Europe Research and Innovation 459 Actions/ ; //Munz Chair of Cardiovascular Prediction and Prevention/ ; 321351 and 354447//Academy of Finland/ ; R35GM119850//HHS | National Institutes of Health (NIH)/ ; UM1-CA164917//HHS | National Institutes of Health (NIH)/ ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 CA077398/CA/NCI NIH HHS/United States ; BRC-1215-20014//NIHR | NIHR Cambridge Biomedical Research Centre (NIHR Cambridge BRC)/ ; R35 GM119850/GM/NIGMS NIH HHS/United States ; RG/13/13/30194//British Heart Foundation (BHF)/ ; P30 CA033572/CA/NCI NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; 2038509//National Science Foundation (NSF)/ ; N/A//UC San Diego Center for Microbiome Innovation/ ; P01 HL131474/HL/NHLBI NIH HHS/United States ; U01-CA199277//HHS | National Institutes of Health (NIH)/ ; 321356//Academy of Finland/ ; //Alfred Benzon Foundation (The Alfred Benzon Foundation)/ ; ANR-20-CE44-0005//French National Research Agency/ ; }, mesh = {Humans ; *COVID-19/virology/microbiology/metabolism ; *Glycocalyx/metabolism/virology ; *SARS-CoV-2/pathogenicity/physiology ; *Gastrointestinal Microbiome/physiology ; Male ; Female ; Heparan Sulfate Proteoglycans/metabolism ; Middle Aged ; Gastrointestinal Tract/microbiology ; Adult ; *Bacteria/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; }, abstract = {The gastrointestinal (GI) tract is a site of replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and GI symptoms are often reported by patients. SARS-CoV-2 cell entry depends upon heparan sulfate (HS) proteoglycans, which commensal bacteria that bathe the human mucosa are known to modify. To explore human gut HS-modifying bacterial abundances and how their presence may impact SARS-CoV-2 infection, we developed a task-based analysis of proteoglycan degradation on large-scale shotgun metagenomic data. We observed that gut bacteria with high predicted catabolic capacity for HS differ by age and sex, factors associated with coronavirus disease 2019 (COVID-19) severity, and directly by disease severity during/after infection, but do not vary between subjects with COVID-19 comorbidities or by diet. Gut commensal bacterial HS-modifying enzymes reduce spike protein binding and infection of authentic SARS-CoV-2, suggesting that bacterial grooming of the GI mucosa may impact viral susceptibility.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019, can infect the gastrointestinal (GI) tract, and individuals who exhibit GI symptoms often have more severe disease. The GI tract's glycocalyx, a component of the mucosa covering the large intestine, plays a key role in viral entry by binding SARS-CoV-2's spike protein via heparan sulfate (HS). Here, using metabolic task analysis of multiple large microbiome sequencing data sets of the human gut microbiome, we identify a key commensal human intestinal bacteria capable of grooming glycocalyx HS and modulating SARS-CoV-2 infectivity in vitro. Moreover, we engineered the common probiotic Escherichia coli Nissle 1917 (EcN) to effectively block SARS-CoV-2 binding and infection of human cell cultures. Understanding these microbial interactions could lead to better risk assessments and novel therapies targeting viral entry mechanisms.}, }
@article {pmid39994360, year = {2025}, author = {Kurt, KC and Kurt, H and Tokuç, E and Özbey, D and Arabacı, DN and Aydın, S and Gönüllü, N and Skurnik, M and Tokman, HB}, title = {Isolation and characterization of new lytic bacteriophage PSA-KC1 against Pseudomonas aeruginosa isolates from cystic fibrosis patients.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6551}, pmid = {39994360}, issn = {2045-2322}, support = {IUC-BAP 34517//Istanbul University-Cerrahpasa, BAP/ ; }, mesh = {*Pseudomonas aeruginosa/virology/isolation &amp; purification ; *Cystic Fibrosis/microbiology ; Humans ; Genome, Viral ; *Pseudomonas Phages/isolation &amp; purification/genetics/physiology ; *Pseudomonas Infections/microbiology/therapy ; *Bacteriophages/isolation &amp; purification/genetics/physiology ; Drug Resistance, Multiple, Bacterial ; }, abstract = {A novel lytic bacteriophage, PSA-KC1, was isolated from wastewater. In this study, the whole genome of the bacteriophage PSA-KC1 was analyzed, and its lytic properties were assessed. PSA-KC1 has a linear double-stranded DNA genome with a total length of 43,237 base pairs and a GC content of 53.6%. In total, 65 genes were predicted, 46 of which were assigned functions as structural proteins involved in genome replication, packaging or phage lysis. PSA-KC1 belongs to the genus Septimatrevirus under the Caudoviricetes class. The aim of this study was to investigate the efficacy of the lytic bacteriophage PSA-KC1 and compare it with that of the Pyophage phage cocktail on 25 multi drug resistant (MDR) Pseudomonas aeruginosa strains isolated from sputum samples of cystic fibrosis patients. Seventeen of these strains were susceptible (68%) to the PSA-KC1 lytic phage we isolated, whereas eight clinical strains were resistant. However, 22 (88%) of the P. aeruginosa strains were susceptible to the Pyophage cocktail, and three (12%) were resistant to the Phage cocktail. At the end of our study, a new lytic phage active against multidrug-resistant P. aeruginosa strains from CF patients was isolated, and its genome was characterized. Since the PSA-KC1 phage does not contain virulence factors, toxins or integrase genes, it can be expected to be a therapeutic candidate with the potential to be used safely in phage therapy.}, }
@article {pmid39994329, year = {2025}, author = {Abdelqader, EM and Mahmoud, WS and Gebreel, HM and Kamel, MM and Abu-Elghait, M}, title = {Correlation between gut microbiota dysbiosis, metabolic syndrome and breast cancer.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6652}, pmid = {39994329}, issn = {2045-2322}, mesh = {Humans ; Female ; *Breast Neoplasms/microbiology/epidemiology/complications ; *Metabolic Syndrome/microbiology/complications/epidemiology ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology/complications ; Middle Aged ; Adult ; Bifidobacterium/genetics/isolation &amp; purification ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Lactobacillus/genetics/isolation &amp; purification ; Case-Control Studies ; Risk Factors ; Aged ; }, abstract = {Breast cancer is a widespread cancer with a high death rate globally. The incidence of breast cancer is expected to increase, particularly in low and middle-income countries due to environmental factors and lifestyle changes. Several risk factors, such as age, family history, hormonal and reproductive factors, have been identified to influence breast cancer development. Metabolic syndrome, is a metabolic disorder that has also been linked to breast cancer risk. The gut microbiome has been suggested as one of the environmental factors leading to breast cancer. The human microbiome is mainly colonized in the intestine by various bacterial species, including Lactobacillus, Bifidobacterium, and Streptococcus and protect the host against pathogenic microorganisms and regulate the immune system. This study included 50 female breast cancer patients and 50 healthy controls with matched ages. Stool fresh samples were taken from test and control groups and stored at - 20 °C until further investigations. DNA of the bacteria in stool samples was extracted using reverse transcription-quantitative polymerase chain reaction to check for the bacterial 16s rRNA gene. The exclusion criteria included other malignancies, recent intestinal surgery, infectious diarrhea, prolonged use of antibiotics, substance addiction, and pregnancy or lactation. Our findings exhibited that breast cancer patients had a higher incidence of metabolic syndrome (60%) compared to cancer-free controls (40%). Furthermore, breast cancer patients had significantly lower Bifidobacterium and Lactobacillus counts than the controls. No significant difference was found in Streptococcus counts between groups. These findings support the relationship between breast cancer and metabolic syndrome and suggest the potential involvement of Lactobacillus and Bifidobacterium in breast cancer pathophysiology. Our study supports the relation between breast cancer and disorder of metabolic syndrome and suggests the potential involvement of Lactobacillus and Bifidobacterium in breast cancer pathophysiology. Further research is necessary to investigate the complex interactions between genes, the environment, and the gut microbiome in breast cancer development. Understanding these interactions could lead to the progress of novel strategies for breast cancer prevention and treatment.}, }
@article {pmid39992142, year = {2025}, author = {Sun, L and Wang, Q and Huang, J and Wang, H and Yu, Z}, title = {Disrupting the balance: how acne duration impacts skin microbiota assembly processes.}, journal = {Microbiology spectrum}, volume = {13}, number = {4}, pages = {e0260324}, pmid = {39992142}, issn = {2165-0497}, support = {32000054, 32170071//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Humans ; *Acne Vulgaris/microbiology ; *Skin/microbiology ; *Microbiota/genetics ; *Bacteria/classification/genetics/isolation &amp; purification ; Female ; Male ; Adult ; Young Adult ; Skin Microbiome ; }, abstract = {Growing interest in the impact of microbial balance on health has driven studies on the ecological processes shaping the skin microbiota. Skin diseases, which alter the skin's local environment, can disrupt the microbial structure and interact with the disease itself. However, research on microbial assembly in diseased skin remains limited. In this study, we applied ecological models to characterize the processes shaping the skin microbiota in acne patients, considering the impact of disease duration on both skin pores and surfaces using bacterial amplicon sequencing. Our results revealed a significant shift in microbial diversity on the skin surface of patients with long-term acne. Further microbial community analyses showed a transition in ecological processes from healthy to diseased skin. Microbial communities on the skin surfaces of healthy controls and individuals with short-duration acne were primarily driven by heterogeneous selection, whereas microbial drift dominated the assembly process in the long-duration groups. Using the Sloan neutral model, we classified amplicon sequence variants (ASVs) into high-effect and low-effect groups based on relative abundance and sample occurrence. High-effect ASVs, likely exerting a greater ecological influence, were predominantly represented by Cutibacterium across all acne-affected skin groups, while Staphylococcus became enriched among high-effect ASVs in patients with long-term acne. Functional profiling further demonstrated that high-effect ASVs were significantly enriched in motility-related pathways. Additionally, we observed a reduction in microbial network complexity on skin surfaces as disease duration increased. Overall, the ecological dynamics of skin microbial communities may offer valuable insights into the mechanisms underlying disease onset and persistence.IMPORTANCEThe skin microbiota plays a critical role in acne development, yet the processes governing microbial assembly during acne progression remain poorly understood. Previous studies predominantly focused on factors such as acne severity, location, and duration in relation to skin microbial structure, with little attention given to the ecological mechanisms shaping the communities. In this study, we applied ecological models to investigate the processes influencing microbial assembly of skin microbiota in acne patients with varying disease durations and examined functions of ecologically important non-neutral amplicon sequence variants (ASVs). Our findings reveal a transition in ecological processes from deterministic to neutral processes as acne duration increased, with non-neutral ASVs potentially contributing to acne pathogenicity and persistence. These insights contribute to a deeper understanding of the ecological dynamics underlying acne and indicate that targeting these non-neutral ASVs or their associated functions may serve as the basis for future therapeutic strategies.}, }
@article {pmid39990405, year = {2025}, author = {Thinnes, CC and Waschkowitz, R and Courtney, E and Culligan, E and Fahy, K and Ferrazza, RAM and Ferris, C and Lagali, A and Lane, R and Maye, C and Murphy, O and Noone, D and Ryan, S and Bet, M and Corr, MC and Cummins, H and Hackett, D and Healy, E and Kulczycka, N and Lang, N and Madden, L and McHugh, L and Pyne, I and Varley, C and Harkin, N and Meade, R and O'Donnell, G and Nap, B and Martinelli, F and Heinken, A and Thiele, I}, title = {The MicroMap is a network visualisation resource for microbiome metabolism.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39990405}, issn = {2692-8205}, support = {RF1 AG058942/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; }, abstract = {The human microbiome plays a crucial role in metabolism and thereby influences health and disease. Constraint-based reconstruction and analysis (COBRA) has proven an attractive framework to generate mechanism-derived hypotheses along the nutrition-host-microbiome-disease axis within the computational systems biology community. Unlike for human, no large-scale visualisation resource for microbiome metabolism has been available to date. To address this gap, we created the MicroMap, a manually curated microbiome metabolic network visualisation, which captures the metabolic content of over a quarter million microbial genome-scale metabolic reconstructions. The MicroMap contains 5,064 unique reactions and 3,499 unique metabolites, including for 98 drugs. The MicroMap allows users to intuitively explore microbiome metabolism, inspect microbial metabolic capabilities, and visualise computational modelling results. Further, the MicroMap shall serve as an educational tool to make microbiome metabolism accessible to broader audiences beyond computational modellers. For example, we utilised the MicroMap to generate a comprehensive collection of 257,429 visualisations, corresponding to the entire scope of our current microbiome reconstruction resources, to enable users to visually compare and contrast the metabolic capabilities for diaerent microbes. The MicroMap seamlessly integrates with the Virtual Metabolic Human (VMH, www.vmh.life) and the COBRA Toolbox (opencobra.github.io), and is freely accessible at the MicroMap dataverse (https://dataverse.harvard.edu/dataverse/micromap), in addition to all the generated reconstruction visualisations.}, }
@article {pmid39983320, year = {2025}, author = {Yu, D and Wang, T and Zhang, L and Gao, N and Huang, Y and Zhang, J and Yan, J}, title = {Identification of body fluid sources based on microbiome antibiotic resistance genes using high-throughput qPCR.}, journal = {Forensic science international. Genetics}, volume = {77}, number = {}, pages = {103241}, doi = {10.1016/j.fsigen.2025.103241}, pmid = {39983320}, issn = {1878-0326}, mesh = {Humans ; *Microbiota/genetics ; Female ; High-Throughput Nucleotide Sequencing ; Real-Time Polymerase Chain Reaction ; Saliva/chemistry/microbiology ; Male ; Semen/chemistry/microbiology ; Feces/microbiology/chemistry ; *Drug Resistance, Microbial/genetics ; Cervix Mucus/chemistry ; Forensic Genetics ; *Genes, Bacterial ; Vagina/microbiology ; *Body Fluids ; }, abstract = {Identifying the origin of body fluids is a critical step in forensic investigation. Recently, the development of high-throughput sequencing technology has led to the use of microbiomes for body fluid identification in forensic studies. However, high-throughput sequencing data are difficult to analyze, the sequencing protocol is complicated. An increasing number of studies have focused on antibiotic resistance genes (ARGs) in the human microbiome. The abundance and diversity of ARGs in different parts of the human body can be detected using quantitative polymerase chain reaction (qPCR). To date, no studies have inferred the sources of body fluids based on ARGs. Therefore, we attempted to use ARGs as a tool to infer the origin of body fluids. We assessed the abundance and diversity of 64 ARGs in blood, semen, saliva, vaginal secretions (VS), nasal secretions (NS), and fecal samples using high-throughput qPCR. The results showed that ARGs were more diverse in fecal samples, which was significantly higher than those of other sample types (P < 0.05). Principal coordinate analysis (PCoA) showed that the samples clustered mainly according to their type. We constructed a random forest classification model based on 64 ARGs with a prediction accuracy of 92.68 %. Next, we evaluated the importance of the features in the random forest model (mean decrease accuracy, MDA). Subsequently, we constructed prediction models for the top 40 and 20 ARGs after sorting genes with the highest MDA, and their prediction accuracies were both 92.68 %. The accuracy of the top 10 ARGs was 87.80 %. Notably, when only the top 10 characterized ARGs were used to construct models for saliva, semen, and VS samples, the prediction accuracy reached was 95.24 %. This shows that blood, semen, saliva, NS, VS, and fecal samples can be accurately identified using ARGs. Our results suggest that ARGs are promising markers for forensic body fluid identification.}, }
@article {pmid39980568, year = {2025}, author = {Davis, T and Decker, KT and Hosseini, D and Jameson, G and Borazanci, E}, title = {Skin microbiome differences in pancreatic adenocarcinoma, other cancers, and healthy controls: a pilot study.}, journal = {Frontiers in oncology}, volume = {15}, number = {}, pages = {1495500}, pmid = {39980568}, issn = {2234-943X}, abstract = {INTRODUCTION: Many studies have reported the importance of the human microbiome in relationship to the overall health of its host. While recent studies have explored the microbiome's role in various types of cancer compared to healthy patients, this pilot study is the first to investigate differences in the skin microbiome composition among pancreatic adenocarcinoma patients, individuals with other cancers, and cancer-free controls.<br><br>METHODS: The study characterizes the skin microbiome's potential associations with cancer status by analyzing skin swabs from the forehead and cheek of 58 participants using Next Generation Sequencing (NGS), differential abundance analysis, and machine learning techniques.<br><br>RESULTS: The study results indicated that the cancer group displayed a significantly higher mean alpha diversity compared to the control group. Additionally, a machine learning classification model achieved a mean F1 Score of 0.943 in predicting cancer status, indicating measurable differentiation in the skin microbiome between the study groups. This differentiation is supported by differential abundance methods, including ANCOM-BC and MaAsLin2.<br><br>DISCUSSION: This pilot study suggests that skin microbiome profiling could serve as a non-invasive biomarker for cancer detection and monitoring, which warrants a larger, longitudinal study to validate these results.}, }
@article {pmid39979818, year = {2025}, author = {Li, W and Yang, J}, title = {Investigating the Anna Karenina principle of the breast microbiome.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {81}, pmid = {39979818}, issn = {1471-2180}, support = {202203021222244//Basic Research Program of Shanxi Province/ ; TYSGJ202201//Critical Talent Workstation Project/ ; 202105AC160030//Top Experts training Project for the Academy and Technology in Yunnan province/ ; XDYC-MY-2022-0005//Famous doctor project of Xingdian talent plan in Yunnan province/ ; 202201AY070001-232//The Scientific Research Fund of Yunnan province of China, Kunming Medical University Joint Research Project/ ; 2024EKKFKT-03//Neonatal Key Specialty of Yunnan province/ ; L-2024015//Yunnan health training project of high level talents/ ; }, mesh = {Humans ; Female ; *Microbiota ; *Milk, Human/microbiology ; *Breast/microbiology ; *Mastitis/microbiology ; *Bacteria/classification/genetics/isolation &amp; purification ; Breast Neoplasms/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The relationship between the microbiome and disease has long been a central focus of research in human microbiome. Inspired by Leo Tolstoy's dictum, the Anna Karenina Principle (AKP) offers a framework for understanding the complex dynamics of microbial communities in response to perturbations, suggesting that dysbiotic individuals exhibit greater variability/heterogeneity in their microbiome compared to healthy counterparts. While some studies have proved the alignment of microbiome responses to disease with the AKP effect, it remains uncertain whether the human breast microbiome responds similarly to breast disease. This study used beta-diversity and similarity in Hill numbers, along with shared species analysis (SSA), to explore this issue. We observed that during mastitis, changes in both the taxa richness and composition in the breast milk microbiome align with the AKP effect, while alterations in abundant taxa exhibit an anti-AKP effect. The response of breast tissue microbiome to breast cancer differs from that of milk microbiome to mastitis. Breast cancer induce anti-AKP effects in taxa richness, and non-AKP effects in common taxa and taxa composition. Overall, our findings identified different responses to breast diseases across taxa abundance in the breast microbiome. Mastitis primarily involves increasing the heterogeneity of rare taxa in the breast milk microbiome, while breast cancer associates with decreased dispersion of rare taxa in the tissue microbiome.}, }
@article {pmid39977268, year = {2025}, author = {Zhang, Q and Cui, K and Kong, Y and Yu, J and Luo, Z and Yang, X and Gong, L and Xie, Y and Lin, J and Liu, C and Zhang, Z and Liu, Y and Liu, B and Liang, D and Zeng, W and He, Z and Lan, P}, title = {Targeting both the enzymatic and non-enzymatic functions of DHODH as a therapeutic vulnerability in c-Myc-driven cancer.}, journal = {Cell reports}, volume = {44}, number = {3}, pages = {115327}, doi = {10.1016/j.celrep.2025.115327}, pmid = {39977268}, issn = {2211-1247}, mesh = {Dihydroorotate Dehydrogenase ; Humans ; *Proto-Oncogene Proteins c-myc/metabolism/genetics ; *Oxidoreductases Acting on CH-CH Group Donors/metabolism/antagonists &amp; inhibitors/genetics ; Animals ; Mice ; Cell Line, Tumor ; *Colorectal Neoplasms/drug therapy/pathology/genetics/metabolism ; Pyrimidines ; *Neoplasms/drug therapy ; }, abstract = {c-Myc (Myc)-driven cancers exhibit aggressive phenotypes and therapeutic resistance. Here, integrating CRISPR-Cas9 screening, we identify dihydroorotate dehydrogenase (DHODH) as a promising target in Myc-driven cancer. Mechanistically, DHODH interacts with Myc to stabilize it independently of its enzymatic activity, thereby antagonizing SKP2-mediated polyubiquitination and proteasomal degradation. EN4, a Myc transcriptional activity inhibitor, disrupts DHODH-Myc interaction, promoting Myc degradation via SKP2. Additionally, Myc transcriptionally activates DHODH, enhancing pyrimidine biosynthesis and ferroptosis defense, processes dependent on DHODH enzymatic activity. Clinically, DHODH positively correlates with Myc, activating pyrimidine metabolism and ferroptosis defense in Myc-driven cancers. Hyperactivation of the DHODH-Myc axis is linked to colorectal cancer progression and poor prognosis. Therapeutically, combining EN4 with a DHODH enzymatic inhibitor demonstrates potent antitumor efficacy in Myc-driven colorectal cancer. Overall, our findings elucidate the metabolic and non-metabolic roles of DHODH in Myc-driven cancer, underscoring its dual potential as a therapeutic target addressing both enzymatic and non-enzymatic functions.}, }
@article {pmid39972069, year = {2025}, author = {Höyhtyä, M and Haaramo, A and Nikkonen, A and Ventin-Holmberg, R and Agrawal, N and Ritari, J and Hickman, B and Partanen, J and Alapulli, H and Tuokkola, J and Salonen, A and de Vos, WM and Kolho, KL}, title = {Fecal microbiota and genetics in pediatric-onset orofacial granulomatosis and Crohn´s disease.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {6020}, pmid = {39972069}, issn = {2045-2322}, support = {TYH2016224//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; }, mesh = {Humans ; *Crohn Disease/genetics/microbiology ; Female ; *Feces/microbiology ; Male ; *Granulomatosis, Orofacial/genetics/microbiology ; Child ; Adolescent ; Nod2 Signaling Adaptor Protein/genetics ; Case-Control Studies ; Saliva/microbiology ; *Gastrointestinal Microbiome ; Leukocyte L1 Antigen Complex ; Microbiota ; }, abstract = {Orofacial granulomatosis (OFG) is a rare chronic inflammatory condition. It is under debate, whether it is a condition of its own or merely a subtype of Crohn's disease (CD). We aimed to search for markers characteristic of patients with pediatric-onset OFG compared to patients with pediatric-onset CD. We recruited young patients with OFG (with or without CD, n = 29), CD (n = 24), and healthy controls (n = 20). All participants provided a fecal sample for microbiota and calprotectin analyses and saliva for DNA analysis of genes associated with OFG and kept a 3-day food diary. Oral disease activity was evaluated using The Oral Disease Activity Score by an otorhinolaryngologist and a dentist. We observed decreased relative abundance in class Clostridia and increased relative abundances of classes Actinobacteria and Bacilli in the feces of patients with OFG when compared to patients with CD and healthy controls. The relative abundances of Bifidobacterium adolescentis increased and Faecalibacterium prausnitzii decreased along with the increase in the Oral Disease Activity Score. We found the NOD2 gene rs8057341 allele A to be enriched in patients with OFG compared to patients with CD. These findings support the theory that OFG is a distinct disease phenotype.}, }
@article {pmid39971547, year = {2025}, author = {Lan, P and He, XS and Zhang, ZJ and Zhang, B}, title = {[Critical issues in surgical treatment for colorectal cancer].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {28}, number = {1}, pages = {21-27}, doi = {10.3760/cma.j.cn441530-20250106-00010}, pmid = {39971547}, issn = {1671-0274}, support = {2022YFA1304000//National Key R&amp;D Program of China/ ; U21A20344//National Natural Science Foundation of China/ ; }, mesh = {Humans ; China ; *Colorectal Neoplasms/surgery ; }, abstract = {Clinical research on colorectal cancer in China has developed rapidly in recent years. Based on evidence-based medicine, the Chinese Colorectal Cancer Diagnosis and Treatment Standards and the CSCO Guidelines for Colorectal Cancer are continuously updated, which have been instrumental in optimizing the full-process management of colorectal cancer and improving cancer outcomes. While significant progress has been made, we must remain aware that there are still many urgent and key issues to be solved in the field of surgical treatment e.g. sphincter-preserving strategies, surgical approaches, management of T1 stage tumors, and surgical treatment for metastatic colorectal cancer. In the future, more high-quality, original research from China will be needed to address these challenges, standardize surgical approaches, and improve treatment effect.}, }
@article {pmid39971202, year = {2025}, author = {Li, T and Wu, X and Li, X and Chen, M}, title = {Cancer-associated fungi: An emerging powerful player in cancer immunotherapy.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1880}, number = {2}, pages = {189287}, doi = {10.1016/j.bbcan.2025.189287}, pmid = {39971202}, issn = {1879-2561}, mesh = {Humans ; *Neoplasms/immunology/microbiology/therapy ; *Immunotherapy/methods ; *Fungi/immunology/pathogenicity ; Tumor Microenvironment/immunology ; Animals ; }, abstract = {The role of the human microbiome in cancer has been extensively studied, focusing mainly on bacteria-host interactions and their impact on tumor development and treatment response. However, fungi, an immune-active component of the human microbiome, have received less attention regarding their roles in cancer. Recent studies have identified the widespread and specific colonization and distribution of fungi in multiple sites in patients across various cancer types. Importantly, host-fungal immune interactions significantly influence immune regulation within the tumor microenvironment. The rapid advancement of immune-checkpoint blockade (ICB)-based cancer immunotherapy creates an urgent need for effective biomarkers and synergistic therapeutic targets. Cancer-associated fungi and their associated antifungal immunity demonstrate significant potential and efficacy in enhancing cancer immunotherapy. This review summarizes and discusses the growing evidence of the functions and mechanisms of commensal and pathogenic cancer-associated fungi in cancer immunotherapy. Additionally, we emphasize the potential of fungi as predictive biomarkers and therapeutic targets in cancer immunotherapy.}, }
@article {pmid39966419, year = {2025}, author = {Heidrich, V and Fackelmann, G and Malesevic, M and Armanini, F and Dey, H and Mengoni, C and Stanisavljevic, N and Vukotic, G and Segata, N}, title = {Newly identified species from the dog dental plaque microbiome highlight little overlap with humans.}, journal = {NPJ biofilms and microbiomes}, volume = {11}, number = {1}, pages = {30}, pmid = {39966419}, issn = {2055-5008}, mesh = {Dogs/microbiology ; Animals ; *Dental Plaque/microbiology ; Humans ; *Microbiota ; *Bacteria/classification/genetics/isolation &amp; purification ; Metagenomics ; Metagenome ; Sequence Analysis, DNA ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Understudied pet-associated microbiomes represent a rich source for the discovery of microbial taxa important for pet and human health. From a cohort of 23 dogs, we sampled and metagenomically sequenced 64 dental plaque microbiomes, generating 1945 metagenome-assembled genomes spanning 347 microbial species, including 277 undercharacterized species without cultivated representatives. Integration with human microbiome data revealed the dog plaque microbiome is more diverse than - and shows little overlap (5.9% species in common) with - the human plaque microbiome, even though some shared periodontal pathobionts arise as a potential concern.}, }
@article {pmid39966341, year = {2025}, author = {Qin, L and Sun, T and Li, X and Zhao, S and Liu, Z and Zhang, C and Jin, C and Xu, Y and Gao, X and Cao, Y and Wang, J and Han, T and Yan, L and Song, J and Zhang, F and Liu, F and Zhang, Y and Huang, Y and Song, Y and Liu, Y and Zhang, J and Zhang, X and Yao, Z and Chen, H and Zhang, Z and Zhao, S and Feng, Y and Zhang, YN and Yu, Q and Cao, F and Zhao, L and Xie, L and Geng, L and Feng, Q and Zhao, H and Chen, ZJ}, title = {Population-level analyses identify host and environmental variables influencing the vaginal microbiome.}, journal = {Signal transduction and targeted therapy}, volume = {10}, number = {1}, pages = {64}, pmid = {39966341}, issn = {2059-3635}, mesh = {Female ; Humans ; *Vagina/microbiology ; *Microbiota/genetics ; Adult ; *Vaginosis, Bacterial/microbiology/genetics/epidemiology ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; Lactobacillus/genetics/isolation &amp; purification ; }, abstract = {The vaginal microbiome is critical for the reproductive health of women, yet the differential impacts exerted by the host and by ambient environmental variables on the vaginal microbiome remain largely unknown. Here, we conducted a comprehensive cross-sectional study of the relationships between the vaginal microbiome and 81 matched host and environmental variables across 6755 Chinese women. By 16S rRNA sequencing, we identified four core vaginal microbiota with a prevalence of over 90% and a total median abundance of 98.8%. Twenty-four variables, including physiology, lifestyle behaviors, gynecologic history, social and environmental information, were found associated with the microbiome composition, of which bacterial vaginosis (BV) showed the largest effect size. Age was among the strongest explanatory variables and the vaginal microbiome dynamically succeeded with increasing age, especially with a composition turning point at the age of 45. Our mediation analyses indicated that the effects of age on the microbiome could be mediated by variables such as parity number and lifestyles. We further classified the vaginal microbiomes of the population into 13 "Vagitypes". Women with Lactobacillus iners- and Lactobacillus jensenii-dominated Vagitypes had significantly higher live birth rate than those with Vagitype dominated by Fannyhessea vaginae (53.40%, 59.09% vs 21.43%; OR [95% CI]: 3.62 [1.12-14.87], 5.39 [1.27-27.36]; P = 0.031, P = 0.021). This study provides a comprehensive overview of the associations between identified variables and the vaginal microbiome, representing an important step toward understanding of environment-microbe-host interactions.}, }
@article {pmid39956340, year = {2025}, author = {Sharma, M and Pudlo, N and Järvå, MA and Kaur, A and John, A and Burchill, L and Lingford, JP and Epa, R and Abayakoon, P and Scott, NE and Turkenburg, JP and Davies, GJ and Martens, EC and Goddard-Borger, ED and Williams, SJ}, title = {Sulfoglycolysis sustains Eubacterium rectale in low-fiber diets.}, journal = {The Journal of biological chemistry}, volume = {301}, number = {3}, pages = {108320}, pmid = {39956340}, issn = {1083-351X}, mesh = {*Dietary Fiber/metabolism ; *Eubacterium/metabolism/growth &amp; development/enzymology ; Humans ; Animals ; Gastrointestinal Microbiome ; Mice ; Bacterial Proteins/metabolism/chemistry/genetics ; }, abstract = {The production of short-chain fatty acids (SCFAs) by Firmicutes (Bacillota) within the human gastrointestinal tract is recognized as critical for gut health and the progression of a range of disease states. Firmicutes are the most diverse phylum of human gut bacteria, are highly studied, and are often specialized to degrade just a few polysaccharide substrates. Members of the Firmicutes include key bacteria that produce butyrate, an SCFA that is generally not produced by members of the other major phyla. Recently, it was shown that Eubacterium rectale, a widespread member of the Firmicutes belonging to the Clostridiales cluster XIVa, can grow on the unusual but ubiquitous plant-derived sugar SQ using a sulfoglycolytic sulfofructose transaldolase pathway. Here, we show that in addition to SQ, E. rectale can also grow on the SQ glycoside sulfoquinovosyl glycerol (SQGro). The 3D structure of the E. rectale sulfoquinovosidase (SftG) shares strong structural conservation with other carbohydrate-active enzyme family GH31 SQases. Using sequence-similarity networks, we provide new biological context to a conserved domain of unknown function protein SftX belonging to DUF4867, which is conserved in the sulfoglycolytic sulfofructose transaldolase pathway, and determine its 3D structure. Finally, with the aid of a synthetic mini-human microbiome reconstituted in germ-free mice, we show that an SQ dietary supplement can rescue E. rectale from population crashes that occur upon switching from a high-fiber to a low-fiber, high-fat diet. This suggests that SQ or SQGro has the potential as a prebiotic for promoting the maintenance of this important butyrate-producing bacterium within the colonic microbiota.}, }
@article {pmid39956335, year = {2025}, author = {Abreu, MT and Devkota, S and Issokson, K}, title = {A Mediterranean Diet for Crohn's Disease: Embracing Colorful Diversity to Improve the Microbiome.}, journal = {Gastroenterology}, volume = {168}, number = {5}, pages = {872-874}, doi = {10.1053/j.gastro.2025.02.003}, pmid = {39956335}, issn = {1528-0012}, }
@article {pmid39955481, year = {2025}, author = {Wan, Y and Pike, R and Harley, A and Mumin, Z and Potterill, I and Meunier, D and Ganner, M and Getino, M and Coelho, J and Jauneikaite, E and Moganeradj, K and Brown, CS and Holmes, AH and Demirjian, A and Hopkins, KL and Pichon, B}, title = {Complete genome assemblies and antibiograms of 22 Staphylococcus capitis isolates.}, journal = {BMC genomic data}, volume = {26}, number = {1}, pages = {12}, pmid = {39955481}, issn = {2730-6844}, support = {/WT_/Wellcome Trust/United Kingdom ; NIHR200876//National Institute for Health and Care Research/ ; PSN109/WT_/Wellcome Trust/United Kingdom ; UGG10057//Price David Evans endowment/ ; }, mesh = {Humans ; Microbial Sensitivity Tests ; *Anti-Bacterial Agents/pharmacology ; *Staphylococcus capitis/genetics/drug effects/isolation &amp; purification ; *Genome, Bacterial ; Whole Genome Sequencing ; Staphylococcal Infections/microbiology ; Drug Resistance, Multiple, Bacterial/genetics ; }, abstract = {OBJECTIVE: Staphylococcus capitis is part of the human microbiome and an opportunistic pathogen known to cause catheter-associated bacteraemia, prosthetic joint infections, skin and wound infections, among others. Detection of S. capitis in normally sterile body sites saw an increase over the last decade in England, where a multidrug-resistant clone, NRCS-A, was widely identified in blood samples from infants in neonatal intensive care units. To address a lack of complete genomes and antibiograms of S. capitis in public databases, we performed long- and short-read whole-genome sequencing, hybrid genome assembly, and antimicrobial susceptibility testing of 22 diverse isolates.<br><br>DATA DESCRIPTION: We present complete genome assemblies of two S. capitis type strains (subspecies capitis: DSM 20326; subspecies urealyticus: DSM 6717) and 20 clinical isolates (NRCS-A: 10) from England. Each genome is accompanied by minimum inhibitory concentrations of 13 antimicrobials including vancomycin, teicoplanin, daptomycin, linezolid, and clindamycin. These 22 genomes were 2.4-2.7 Mbp in length and had a GC content of 33%. Plasmids were identified in 20 isolates. Resistance to teicoplanin, daptomycin, gentamicin, fusidic acid, rifampicin, ciprofloxacin, clindamycin, and erythromycin was seen in 1-10 isolates. Our data are a resource for future studies on genomics, evolution, and antimicrobial resistance of S. capitis.}, }
@article {pmid39952625, year = {2025}, author = {Javanshir, N and Ebrahimi, V and Mazhary, Z and Saadaie Jahromi, B and Zuo, T and Fard, NA}, title = {The antiviral effects and underlying mechanisms of probiotics on viral infections.}, journal = {Microbial pathogenesis}, volume = {200}, number = {}, pages = {107377}, doi = {10.1016/j.micpath.2025.107377}, pmid = {39952625}, issn = {1096-1208}, mesh = {*Probiotics/therapeutic use/pharmacology ; Humans ; *Virus Diseases/immunology/virology/therapy/drug therapy ; *Antiviral Agents/therapeutic use/pharmacology ; COVID-19/immunology/virology ; *Respiratory Tract Infections/virology/immunology ; SARS-CoV-2 ; Influenza, Human/immunology ; Immunity, Innate/drug effects ; Adaptive Immunity ; }, abstract = {In public health emergencies, viral diseases like influenza and COVID-19 have become a major concern. One of the proposed responses to this concern is the use of probiotics. Probiotics have a potent role in arming our bodies to combat viral infections. They affect the innate and adaptive immune systems in various ways. Accumulating studies has shown that probiotics can reduce the possibility of infection or the duration of respiratory symptoms by modulating the functions of the immune system. This review aims to summarize the impacts of probiotics on respiratory viral infections and their potential antiviral mechanisms. Therefore, we herein discussed probiotics in relation to lung immunity, distinct types of respiratory viral infections (VRIs), including influenza, rhinoviruses, respiratory syncytial virus, and upper respiratory viral infections, and lastly, probiotics and their effects on COVID-19. However, more studies are needed to explore the antiviral mechanisms of probiotics.}, }
@article {pmid39949350, year = {2024}, author = {Lee, DB and Hwang, IS}, title = {Macronutrient balance determines the human gut microbiome eubiosis: insights from in vitro gastrointestinal digestion and fermentation of eight pulse species.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1512217}, pmid = {39949350}, issn = {1664-302X}, abstract = {The interactions between macronutrients, the human gut microbiome, and their metabolites (short-chain fatty acids) were comprehensively investigated via an in vitro digestion and fermentation model subjected to eight pulse species. 16S rRNA sequencing and taxonomic analysis of pulse digesta fermented for up to 24 h revealed an increase in the relative abundance of gut health-detrimental genera represented by Escherichia-Shigella in kidney bean, soybean, cowpea, chickpea, and black bean samples. In contrast, the relative abundance of health-positive genera, including Bacteroides, Eubacterium, and Akkermansia, was elevated in red bean, mung bean, and Heunguseul. At the same time, the proportion of the pathogenic Escherichia-Shigella decreased. Concurrently, these three species exhibited an increase in microbial diversity as evidenced by the calculation of α-diversity (Shannon index) and β-diversity (Bray-Curtis distance). Despite the lower nutrient contents in the three pulses, represented by carbohydrates, amino acids, and fatty acids, network analysis revealed that the nutrient contents in the pulse digesta possess complex positive or negative correlations with a variety of bacteria, as well as their metabolites. These correlations were more pronounced in red bean, mung bean, and Heunguseul than in the other pulses. It was postulated that the overall potential to nourish gut environments in these species was due to the balance of their nutritional components. The linear regression analysis demonstrated that there was a negative association between carbohydrate and amino acid contents and the increase in Shannon indices. Furthermore, the ratio of carbohydrates to fatty acids and amino acids to fatty acids displayed negative correlations with the diversity increase. The ratio of carbohydrates to amino acids showed a weak positive correlation. It is noteworthy that a diet comprising foods with a balanced nutritional profile supports the growth of beneficial gut microbes, thereby promoting microbial eubiosis. Consistent work on different ingredients is essential for precise insight into the interplay between food and the human microbiome in complex dietary patterns.}, }
@article {pmid39947133, year = {2025}, author = {Elmassry, MM and Sugihara, K and Chankhamjon, P and Kim, Y and Camacho, FR and Wang, S and Sugimoto, Y and Chatterjee, S and Chen, LA and Kamada, N and Donia, MS}, title = {A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules.}, journal = {Cell host &amp; microbe}, volume = {33}, number = {2}, pages = {218-234.e12}, pmid = {39947133}, issn = {1934-6069}, support = {DP2 AI124441/AI/NIAID NIH HHS/United States ; K23 DK119544/DK/NIDDK NIH HHS/United States ; R01 AI172144/AI/NIAID NIH HHS/United States ; R01 DK108901/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; Animals ; Mice ; *Inflammatory Bowel Diseases/microbiology ; Feces/microbiology/chemistry ; Crohn Disease/microbiology ; Disease Models, Animal ; Multigene Family ; Fatty Acids/metabolism/chemistry ; Metagenomics ; Clostridium/genetics/metabolism ; }, abstract = {Gut microbiome changes have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a meta-analysis of small molecule biosynthetic gene clusters (BGCs) in metagenomic samples of the gut microbiome from inflammatory bowel disease (IBD) patients and matched healthy subjects and identified two Clostridia-derived BGCs that are significantly associated with Crohn's disease (CD), a main IBD type. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the CD-enriched BGCs, which we subsequently detected in fecal samples from IBD patients. Finally, we show that the discovered molecules disrupt gut permeability and exacerbate disease in chemically or genetically susceptible mouse models of colitis. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of disease-relevant microbiome-host interactions.}, }
@article {pmid39947073, year = {2025}, author = {Cotugno, N and Sanna, M and Amodio, D and Morrocchi, E and Pighi, C and Medri, C and Pascucci, GR and Santilli, V and Manno, EC and Zangari, P and Rossetti, C and Colantoni, N and Olivieri, G and Emili, E and Neri, A and Rotili, A and Rossi, P and Levy, O and Putignani, L and Palma, P and , }, title = {Pre-vaccination immune markers predict response to BNT162b2 mRNA vaccine in vulnerable groups - The CONVERS project, report from a pediatric tertiary hospital.}, journal = {Vaccine}, volume = {49}, number = {}, pages = {126778}, doi = {10.1016/j.vaccine.2025.126778}, pmid = {39947073}, issn = {1873-2518}, mesh = {Humans ; *BNT162 Vaccine/immunology ; Female ; Male ; *COVID-19/prevention &amp; control/immunology ; *SARS-CoV-2/immunology ; Antibodies, Viral/blood/immunology ; Child ; Adolescent ; *COVID-19 Vaccines/immunology/administration &amp; dosage ; Tertiary Care Centers ; Vaccination ; Adult ; Immunogenicity, Vaccine ; Young Adult ; B-Lymphocytes/immunology ; Biomarkers ; CD4-Positive T-Lymphocytes/immunology ; Child, Preschool ; }, abstract = {BACKGROUND: Whereas several studies have demonstrated the long-term immunogenicity of BNT162b2 vaccine in healthy adults, little evidence was provided in vulnerable populations (VPs) with generally low ability to respond to immunizations. We aimed to identify pre-vaccination immune phenotype and transcriptional signatures in B and T-cell subsets associated with immune response and long-term maintenance upon SARS-CoV-2 vaccination in VPs.<br><br>METHODS: A cohort of VPs (N&#xa0;=&#xa0;169) including solid organ transplant recipients (SOT; N&#xa0;=&#xa0;35), Inflammatory Bowel Disease (N&#xa0;=&#xa0;31), Down Syndrome (N&#xa0;=&#xa0;42), people living with HIV (N&#xa0;=&#xa0;36), primary immune deficiencies (N&#xa0;=&#xa0;25) and healthy controls (N&#xa0;=&#xa0;37) were enrolled in the CONVERS Study. SARS-CoV-2 Vaccine responsiveness was evaluated by SARS-CoV-2-specific Ab and SARS-CoV-2-specific CD4+ T cells in VPs naive to infection or vaccination. Based on the humoral response at T28, individuals were classified as Protected (P: anti-spike antibody [anti-S] titer &#x2265;0.8) and Not-Protected (NP: anti-S titer <0.8). Peripheral blood mononuclear cells, after SARS-CoV-2 Prot-S peptides stimulation were sort-purified in four cell subsets and analyzed by multiplexed RT-PCR (Fluidigm, Biomark).<br><br>RESULTS: SOT presented a significantly lower serological immunogenicity with 31&#xa0;% of individuals being NP at T28 whereas only 1 out of the remaining 119 resulted Ab negative at T28. At T0, NP individuals showed a lower increase of Ag specific CD40L+ T cells and lower switched memory B cells compared to P patients. Gene-expression analysis revealed distinct signatures at baseline between P and NP individuals with 63 and 49 DEGs identified in two experimental conditions, respectively unstimulated and stimulated.<br><br>CONCLUSIONS: Pre-vaccination B and T-cell characteristics at both phenotypic and gene- expression level correlate with short- and long- term memory maintenance in VPs with lower immunogenicity upon BNT162b2 vaccine. Such signatures need to be validated in larger cohorts and may provide a predictive score to inform personalized and more effective vaccine interventions.}, }
@article {pmid39940948, year = {2025}, author = {Rastegari, F and Driscoll, M and Riordan, JD and Nadeau, JH and Johnson, JS and Weinstock, GM}, title = {Comparison of Lysis and Amplification Methodologies for Optimal 16S rRNA Gene Profiling for Human and Mouse Microbiome Studies.}, journal = {International journal of molecular sciences}, volume = {26}, number = {3}, pages = {}, pmid = {39940948}, issn = {1422-0067}, support = {R01 HG012444/HG/NHGRI NIH HHS/United States ; HG01244/GF/NIH HHS/United States ; }, mesh = {*RNA, Ribosomal, 16S/genetics ; Animals ; Mice ; Humans ; *Microbiota/genetics ; Feces/microbiology ; *Bacteria/genetics/classification ; Polymerase Chain Reaction/methods ; DNA, Bacterial/genetics/isolation &amp; purification ; }, abstract = {When conducting sequence-based analysis of microbiome samples, it is important to accurately represent the bacterial communities present. The aim of this study was to compare two commercially available DNA isolation and PCR amplification approaches to determine their impact on the taxonomic composition of microbiome samples following 16S rRNA gene sequencing. A well-established 16S rRNA gene profiling approach, which was widely used in the Human Microbiome Project (HMP), was compared with a novel alkaline degenerative technique that utilizes alkaline cell lysis in combination with a degenerate pool of primers for nucleic acid extraction and PCR amplification. When comparing these different approaches for the microbiome profiling of human and mouse fecal samples, we found that the alkaline-based method was able to detect greater taxonomic diversity. An in silico analysis of predicted primer binding against a curated 16S rRNA gene reference database further suggested that this novel approach had the potential to reduce population bias found with traditional methods, thereby offering opportunities for improved microbial community profiling.}, }
@article {pmid39939954, year = {2025}, author = {Swarup, S and Gupta, A and Chung, M and Radhakrishnan, V and Davis, V and Lynch, MDJ and Charles, TC and Cheng, J and Mendoza, G}, title = {Rapid shift of gut microbiome and enrichment of beneficial microbes during arhatic yoga meditation retreat in a single-arm pilot study.}, journal = {BMC complementary medicine and therapies}, volume = {25}, number = {1}, pages = {51}, pmid = {39939954}, issn = {2662-7671}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Diet, Vegetarian ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; *Meditation ; Mouth/microbiology ; Pilot Projects ; RNA, Ribosomal, 16S ; *Yoga ; }, abstract = {BACKGROUND: The human microbiome plays a vital role in human health, mediated by the gut-brain axis, with a large diversity of functions and physiological benefits. The dynamics and mechanisms of meditations on oral and gut microbiome modulations are not well understood. This study investigates the short-term modulations of the gut and oral microbiome during an Arhatic Yoga meditation retreat as well as on the role of microbiome in improving well-being through a possible gut-brain axis.<br><br>METHODS: A single-arm pilot clinical trial was conducted in a controlled environment during a 9-day intensive retreat of Arhatic Yoga meditation practices with vegetarian diet. Oral and fecal samples of 24 practitioners were collected at the start (Day0: T1), middle (Day3: T2), and end (Day9:T3) of the retreat. Targeted 16S rRNA gene amplicon sequencing was performed for both oral and gut samples. Functional pathway predictions was identified using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). DESeq2 was used to identify the differential abundant taxa. Various statistical analyses were performed to assess the significant changes in the data.<br><br>RESULTS: Our findings revealed that Arhatic Yoga meditation together with a vegetarian diet led to changes in the oral and gut microbiome profiles within the 9-day retreat. Oral microbiome profile showed a significant (p&#x2009;<&#x2009;0.05) difference in the species richness and evenness at the end of study, while non-metric multidimensional scaling (NMDS) confirmed the shift in the gut microbiome profile of the practitioners by T2 timepoint, which was further supported by PERMANOVA analysis (p&#x2009;<&#x2009;0.05). Health-benefiting microbes known to improve the gastrointestinal and gut-barrier functions, immune modulation, and gut-brain axis were enriched. Gut microbiome of both beginner and advanced Arhatic Yoga practitioners showed similar trends of convergence by the end of study. This implies a strong selection pressure by Arhatic Yoga meditation together with a vegetarian diet on the beneficial gut microbiome.<br><br>CONCLUSION: This pilot study demonstrates that Arhatic Yoga meditation practices combined with a vegetarian diet during a short intensive retreat resulted in enrichment of known health-promoting microbes. Such microbial consortia may be developed for potential health benefits and used as probiotics to improve the gastrointestinal and immune systems, as well as functions mediated by the gut-brain axis.<br><br>TRIAL REGISTRATION: Study was submitted in https://clinicaltrials.gov/on28-02-2024 . Retrospective registered.}, }
@article {pmid39932857, year = {2025}, author = {Lopetuso, LR and Deleu, S and Puca, P and Abreu, MT and Armuzzi, A and Barbara, G and Caprioli, F and Chieng, S and Costello, SP and Damiani, A and Danese, S and Del Chierico, F and D'Haens, G and Dotan, I and Facciotti, F and Falony, G and Fantini, MC and Fiorino, G and Gionchetti, P and Godny, L and Hart, A and Kupčinskas, J and Iqbal, T and Laterza, L and Lombardini, L and Maharshak, N and Marasco, G and Masucci, L and Papa, A and Paramsothy, S and Petito, V and Piovani, D and Pugliese, D and Putignani, L and Raes, J and Ribaldone, DG and Sanguinetti, M and Savarino, EV and Sokol, H and Vetrano, S and Ianiro, G and Cammarota, G and Cominelli, F and Pizarro, TT and Tilg, H and Gasbarrini, A and Vermeire, S and Scaldaferri, F}, title = {Guidance for Fecal Microbiota Transplantation Trials in Ulcerative Colitis: The Second ROME Consensus Conference.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaf013}, pmid = {39932857}, issn = {1536-4844}, support = {//European Crohn's and Colitis Organization/ ; //Crohn's &amp; Colitis Foundation: Clinical Research Investigator Initiated Award (CRIA)/ ; 882725//Senior Research Award (SRA)/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is emerging as a potential treatment modality for individuals living with inflammatory bowel disease (IBD). Despite its promise, the effectiveness of FMT for treating IBD, particularly for ulcerative colitis (UC), still requires thorough clinical investigation. Notwithstanding differences in methodologies, current studies demonstrate its potential for inducing remission in UC patients. Therefore, standardized and robust randomized clinical trials (RCTs) are needed to further support its efficacy for managing UC. The aim of the second Rome Consensus Conference was to address gaps and uncertainties identified in previous research regarding FMT and to offer a robust framework for future studies applied to the treatment of UC.<br><br>METHODS: Global experts in the field of clinical IBD, mucosal immunology, and microbiology (N&#x2005;=&#x2005;48) gathered to address the need for standardized clinical trials in FMT investigation. The group focused on key issues, such as stool donation, donor selection, characterization of fecal biomass, potential administration routes, as well as the process of induction, maintenance, and endpoint readouts.<br><br>RESULTS AND CONCLUSIONS: The consensus achieved during this conference established standardization of methods and protocols to enhance the current quality of research, with the aim of eventual implementation of FMT in managing UC and the ultimate goal of improving patient outcomes.}, }
@article {pmid39930028, year = {2025}, author = {Rook, O and Zwart, H}, title = {Awareness of human microbiome may promote healthier lifestyle and more positive environmental attitudes.}, journal = {Communications medicine}, volume = {5}, number = {1}, pages = {39}, pmid = {39930028}, issn = {2730-664X}, support = {No 964590//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; No 964590//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; }, abstract = {BACKGROUND: The human microbiome is an essential factor of physical and mental health, yet the general population has little knowledge about it. This survey explores public familiarity with the human microbiome and (potential) public preferences related to monitoring and improving one's microbiome health. The study also examines whether recognizing the importance of one's microbiome may promote a more ecosystem-aware perspective towards microorganisms.<br><br>METHODS: We conducted an online survey with nationally representative samples from France, Germany, South Korea, and Taiwan (N&#x2009;=&#x2009;2860). The results were interpreted using descriptive statistics and network analysis. We also performed a t-test to compare perceptions of microorganisms before and after a short reflection on the role of human microbiome for one's body and health.<br><br>RESULTS: In our data, most respondents express willingness to monitor the health of their microbiome (especially, in the European countries) and to adjust their lifestyle such as diet and exercise to improve it. A paired samples t-test shows a slight positive shift in perceptions of microorganisms and the microbial world after the reflection exercise compared to baseline.<br><br>CONCLUSIONS: The study shows that the public recognize the essential role of the human microbiome in health and are willing to take care of it, which may have implications for public health policy. Our findings also suggest that stronger awareness of the human microbiome may promote lifestyle change and a more encompassing environmental outlook.}, }
@article {pmid39927868, year = {2025}, author = {Zouiouich, S and Wan, Y and Vogtmann, E and Porras, C and Abnet, CC and Shi, J and Sinha, R}, title = {Sample Size Estimations Based on Human Microbiome Temporal Stability Over 6 Months: A Shallow Shotgun Metagenome Sequencing Analysis.}, journal = {Cancer epidemiology, biomarkers &amp; prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {34}, number = {4}, pages = {588-597}, doi = {10.1158/1055-9965.EPI-24-0839}, pmid = {39927868}, issn = {1538-7755}, support = {//Division of Intramural Research (DIR)/ ; }, mesh = {Humans ; *Metagenome/genetics ; *Feces/microbiology ; Case-Control Studies ; Sample Size ; *Microbiota/genetics ; Female ; Male ; *Gastrointestinal Microbiome/genetics ; }, abstract = {BACKGROUND: Biological factors affect the human microbiome, highlighting the need for reasonably estimating sample sizes in future population studies.<br><br>METHODS: We assessed the temporal stability of fecal microbiome diversity, species composition, and genes and functional pathways through shallow shotgun metagenome sequencing. Using intraclass correlation coefficients (ICC), we measured biological variability over 6 months. We estimated case numbers for 1:1 or 1:3 matched case-control studies, considering significance levels of 0.05 and 0.001 with 80% power, based on the collected fecal specimens per participant.<br><br>RESULTS: The fecal microbiome's temporal stability over 6 months varied (ICC < 0.6) for most alpha and beta diversity metrics. Heterogeneity was seen in species, genes, and pathways stability (ICC, 0.0-0.9). Detecting an OR of 1.5 per SD required 1,000 to 5,000 cases (0.05 significance for alpha and beta; 0.001 for species, genes, and pathways) with equal cases and controls. Low-prevalence species needed 15,102 cases, and high-prevalence species required 3,527. Similar needs applied to genes and pathways. In a 1:3 matched case-control study with one fecal specimen, 10,068 cases were needed for low-prevalence species and 2,351 for high-prevalence species. For ORs of 1.5 with multiple specimens, cases needed for low-prevalence species were 15,102 (one specimen), 8,267 (two specimens), and 5,989 (three specimens).<br><br>CONCLUSIONS: Detecting disease associations requires a large number of cases. Repeating prediagnostic samples and matching cases to more controls could decrease the needed number of cases for such detections.<br><br>IMPACT: Our results will help future epidemiologic study designs and implement well-powered microbiome studies.}, }
@article {pmid39927761, year = {2025}, author = {Frame, LA}, title = {Fiber, microbiomes, and SCFAs: insights from companion animal models to inform personalized nutrition.}, journal = {mSystems}, volume = {10}, number = {3}, pages = {e0145424}, pmid = {39927761}, issn = {2379-5077}, mesh = {*Dietary Fiber/metabolism ; Animals ; *Gastrointestinal Microbiome/physiology ; *Fatty Acids, Volatile/metabolism ; *Pets/microbiology ; Humans ; Precision Medicine ; Models, Animal ; }, abstract = {A recent study by A. Bhosle, M. I. Jackson, A. M. Walsh, E. A. Franzosa, et al. (mSystems 10:e00452-24, 2024, https://doi.org/10.1128/msystems.00452-24) enhances our understanding of dietary fiber's impact on the gut microbiome and metabolome in companion animals, uncovering individual variations in microbial and metabolic responses. By examining short-chain fatty acid (SCFA) profiles in response to fiber, the authors reveal potential therapeutic benefits of tailored dietary interventions, such as enhanced gut and immune health. These findings resonate with human microbiome research, where dietary fiber has shown health benefits through microbial diversity and SCFA production. The study emphasizes the potential for breed-specific responses to fiber, given the variation in microbiome composition and physiology across breeds. Such insights align with emerging concepts of personalized nutrition, offering an opportunity to develop precision dietary strategies that address specific health needs in both veterinary and human contexts. This foundational research positions dietary fiber as a valuable tool in preventive health, providing a roadmap for future studies to refine individualized approaches for gut microbiome modulation.}, }
@article {pmid39923780, year = {2025}, author = {Huang, Z and Liu, Y and Philips, A and Zhang, F and Zuo, T}, title = {Varied prevalence and asymptomatic carriage of Cryptococcus gattii in the gut of Chinese populations.}, journal = {The Lancet. Microbe}, volume = {6}, number = {7}, pages = {101086}, doi = {10.1016/j.lanmic.2025.101086}, pmid = {39923780}, issn = {2666-5247}, }
@article {pmid39920776, year = {2025}, author = {Han, Y and Teng, TM and Han, J and Kim, HS}, title = {Antibiotic-associated changes in Akkermansia muciniphila alter its effects on host metabolic health.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {48}, pmid = {39920776}, issn = {2049-2618}, support = {NRF-2018M3A9F3055923 and NRF-2015M3C9A4053393//The national research foundation of the Republic of Korea/ ; }, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Mice ; Humans ; *Akkermansia/drug effects/genetics ; Obesity/microbiology ; *Verrucomicrobia/drug effects/genetics ; Mutation ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Altered gut microbiota has emerged as a major contributing factor to the etiology of chronic conditions in humans. Antibiotic exposure, historically dating back to the mass production of penicillin in the early 1940s, has been proposed as a primary contributor to the cumulative alteration of microbiota over generations. However, the mechanistic link between the antibiotics-altered microbiota and chronic conditions remains unclear.<br><br>RESULTS: In this study, we discovered that variants of the key beneficial gut microbe, Akkermansia muciniphila, were selected upon exposure to penicillin. These variants had mutations in the promoter of a TEM-type &#x3b2;-lactamase gene or pur genes encoding the de novo purine biosynthesis pathway, and they exhibited compromised abilities to mitigate host obesity in a murine model. Notably, variants of A. muciniphila are prevalent in the human microbiome worldwide.<br><br>CONCLUSIONS: These findings highlight a previously unknown mechanism through which antibiotics influence host health by affecting the beneficial capacities of the key gut microbes. Furthermore, the global prevalence of A. muciniphila variants raises the possibility that these variants contribute to global epidemics of chronic conditions, warranting further investigations in human populations. Video Abstract.}, }
@article {pmid39916516, year = {2025}, author = {Nunez, H and Nieto, PA and Mars, RA and Ghavami, M and Sew Hoy, C and Sukhum, K}, title = {Early life gut microbiome and its impact on childhood health and chronic conditions.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2463567}, pmid = {39916516}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; Chronic Disease ; Animals ; Infant ; Child ; Bacteria/classification/genetics/isolation &amp; purification ; Child, Preschool ; Feces/microbiology ; *Child Health ; }, abstract = {The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.}, }
@article {pmid39913324, year = {2025}, author = {Huang, H and Mani, J and Vetter, TR and Gan, TJ}, title = {Examining the Impact of the Human Microbiome in the Perioperative Setting.}, journal = {Anesthesia and analgesia}, volume = {140}, number = {4}, pages = {906-912}, pmid = {39913324}, issn = {1526-7598}, }
@article {pmid39912642, year = {2025}, author = {Masarweh, C and Maldonado-Gomez, M and Paviani, B and Bhattacharya, M and Weng, C-Y and Suarez, C and Ehlers-Cheang, S and Stacy, A and Castillo, J and Krishnakumar, N and Kalanetra, KA and Barile, D and German, JB and Lebrilla, CB and Mills, DA}, title = {Generation of novel prebiotic oligosaccharide pools from fiber drives biological insight in bacterial glycan metabolism.}, journal = {Applied and environmental microbiology}, volume = {91}, number = {3}, pages = {e0207724}, pmid = {39912642}, issn = {1098-5336}, support = {R01 DK124193/DK/NIDDK NIH HHS/United States ; //Bill and Melinda Gates Foundation (GF)/ ; R01DK1124193//HHS | National Institutes of Health (NIH)/ ; }, mesh = {*Prebiotics/analysis ; *Oligosaccharides/metabolism/chemistry ; *Dietary Fiber/metabolism ; *Gastrointestinal Microbiome ; *Beta vulgaris/chemistry/metabolism ; *Polysaccharides/metabolism ; Humans ; Feces/microbiology ; *Bacteria/metabolism/genetics ; Fermentation ; }, abstract = {Prebiotic oligosaccharides are dietary supplements that modulate the intestinal gut microbiome by selectively nourishing subsets of the microbial community with a goal to enhance host health. To date, the diversity of polysaccharide compositions in the fiber consumed by humans is not well represented by the limited scope of oligosaccharide compositions present in current commercial prebiotics. Recently, our UC Davis group developed a novel method to generate oligosaccharides from any polysaccharide fiber, termed Fenton's Initiation Toward Defined Oligosaccharide Groups (FITDOG). Using this method, sugar beet pulp (SBP) was transformed into sugar beet oligosaccharides (SBOs) composed of arabinose- and galactose-containing oligosaccharides. Fecal fermentations of SBO and SBP produced similar shifts in donor-specific bacterial communities and acid metabolite profiles with a general enrichment of Bacteroides and Bifidobacterium. However, in vitro tests revealed more Bifidobacterium strains could consume SBO than sugar beet arabinan, and specific strains showed differential consumption of arabinofuranooligosaccharides or galactooligosaccharide (GOS) portions of the SBO pool. Genomic and glycomic comparisons suggest that previously characterized, arabinan-specific, extracellular arabinofuranosidases from Bifidobacterium are not necessary to metabolize the arabino-oligosaccharides within SBO. Synbiotic application of SBO with an SBO-consuming strain Bifidobacterium longum subsp. longum SC596 in serial fecal enrichments resulted in enhanced persistence among 9 of 10 donor feces. This work demonstrates a novel workflow whereby FITDOG creates novel oligosaccharide pools that can provide insight into how compositional differences in fiber drive differential gut fermentation behaviors as well as their downstream health impacts. Moreover, these oligosaccharides may be useful in new prebiotic and synbiotic applications.IMPORTANCEPrebiotics seek to selectively alter the host microbiome composition or function, resulting in a concurrent health benefit to the host. However, commercial prebiotics represent a small fraction of the diversity of food polysaccharide compositions. In this work a novel method, Fenton's Initiation Toward Defined Oligosaccharide Groups (FITDOG) was used to generate an oligosaccharide pool from sugar beet pulp (SBP). Sugar beet oligosaccharides (SBOs) resulted in similar changes to SBP in fecal enrichments; however, SBO could be consumed by more beneficial bifidobacterial strains than the cognate polysaccharide. These results demonstrate how the details of glycan structure have a profound influence on how gut bacteria metabolize food carbohydrates. The implications of this work are relevant to understanding how different dietary sources influence the human microbiome and extend to developing novel oligosaccharide pools for prebiotic applications.}, }
@article {pmid39906620, year = {2025}, author = {Wawrety, W and Kedziora, A}, title = {Role of bacteria in cancers and their therapeutic potential: Review of current knowledge.}, journal = {Iranian journal of basic medical sciences}, volume = {28}, number = {3}, pages = {273-282}, pmid = {39906620}, issn = {2008-3866}, abstract = {Cancers are extremely dynamic diseases that can actively cause refractorines to be gained from applied therapies, which is why they are at the forefront of deaths worldwide. In this literature review, we covered the most recent and important discoveries regarding the influence of human microbiota, including tumor bacteriome, on the development and treatment of cancer. Advances in research on microbial communities have enabled us to discover the role of the human microbiome in the development and course of this disease, helping us understand neoplasms better and design new potential therapies. As we show through our findings, by immunomodulation and the secretion of certain chemical substances, the correct bacteriome of the intestinal tract, respiratory system, or skin can protect humans against cancer development and help during the treatment process. Bacteria also reside inside tumors, forming part of the tumor microenvironment (TME), where they interact with immunological and cancer cells in many complex ways. Some bacteria, such as Pseudomonas aeruginosa or Akkermansia muciniphila, can stimulate anticancer cell-mediated immune responses or even directly lead to cancer cell death. We also present the clinical possibilities of using some live, usually modified bacteria to develop bacteriotherapies. Modifying the gut microbiome to stimulate standard treatment is also important. Research on the microbiome and cancer remains a challenging topic in microbiology, having a great potential for advancements in cancer therapy in the future, and is continuously becoming a more and more popular field of research, as shown by our statistical analysis of PubMed data.}, }
@article {pmid39895074, year = {2025}, author = {Lee, KA and Ul-Haq, A and Seo, H and Jo, S and Kim, S and Song, HY and Kim, HS}, title = {Characteristics of skin microbiome associated with disease severity in systemic sclerosis.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {63}, number = {1}, pages = {e.2409018}, doi = {10.71150/jm.2409018}, pmid = {39895074}, issn = {1976-3794}, support = {//Korea Health Industry Development Institute/ ; HI21C1888//Ministry of Health and Welfare/ ; //National Research Foundation of Korea/ ; RS-2023-00219563//Ministry of Science and ICT/ ; //Soonchunhyang University Research Fund/ ; }, mesh = {Humans ; *Scleroderma, Systemic/microbiology/pathology ; *Skin/microbiology/pathology ; Female ; Male ; Middle Aged ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/genetics/isolation &amp; purification ; Adult ; Severity of Illness Index ; Aged ; Metagenomics ; Biomarkers ; DNA, Bacterial/genetics ; Case-Control Studies ; Skin Microbiome ; }, abstract = {Systemic sclerosis (SSc) is a chronic autoimmune disorder characterised by skin fibrosis and internal organ involvement. Disruptions in the microbial communities on the skin may contribute to the onset of autoimmune diseases that affect the skin. However, current research on the skin microbiome in SSc is lacking. This study aimed to investigate skin microbiome associated with disease severity in SSc. Skin swabs were collected from the upper limbs of 46 healthy controls (HCs) and 36 patients with SSc. Metagenomic analysis based on the 16S rRNA gene was conducted and stratified by cutaneous subtype and modified Rodnan skin score (mRSS) severity. Significant differences in skin bacterial communities were observed between the HCs and patients with SSc, with further significant variations based on subtype and mRSS severity. The identified biomarkers were Bacteroides and Faecalibacterium for patients with diffuse cutaneous SSc with high mRSS (≥ 10) and Mycobacterium and Parabacteroides for those with low mRSS (< 10). Gardnerella, Abies, Lactobacillus, and Roseburia were the biomarkers in patients with limited cutaneous SSc (lcSS) and high mRSS, whereas Coprococcus predominated in patients with lcSS and low mRSS. Cutaneous subtype analysis identified Pediococcus as a biomarker in the HCs, whereas mRSS analysis revealed the presence of Pseudomonas in conjunction with Pediococcus. In conclusion, patients with SSc exhibit distinct skin microbiota compared with healthy controls. Bacterial composition varies by systemic sclerosis cutaneous subtype and skin thickness.}, }
@article {pmid39892949, year = {2025}, author = {McGann, C and Phyu, R and Bittinger, K and Mukhopadhyay, S}, title = {Role of the Microbiome in Neonatal Infection: Pathogenesis and Implications for Management.}, journal = {Clinics in perinatology}, volume = {52}, number = {1}, pages = {147-166}, doi = {10.1016/j.clp.2024.10.010}, pmid = {39892949}, issn = {1557-9840}, mesh = {Humans ; Infant, Newborn ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; *Neonatal Sepsis/microbiology/therapy ; Anti-Bacterial Agents/therapeutic use ; *Microbiota ; }, abstract = {The human microbiome refers to the collective genome of microorganisms, including bacteria, fungi, and viruses residing on human body surfaces that are in contact with the environment. Together these communities protect against invasive infections. Conversely, when disrupted, the microbiome can be the source of pathogens causing invasive infection. Interventions to manipulate it via probiotics, antibiotics, and fecal transplantation are available. The risk benefit of these interventions remains unclear. In this review, the authors discuss evidence linking the gut microbiome to neonatal sepsis and also discuss the challenges for translating this knowledge into better clinical care.}, }
@article {pmid39891027, year = {2025}, author = {Nissilä, E and Starck, L and Aho, E and Venerandi, E and Jalkanen, P and Leskinen, K and Uvarov, P and Saavalainen, P and Julkunen, I and Kotimaa, J and Haapasalo, K and Meri, S}, title = {The COVID-19 vaccine ChAdOx1 is opsonized by anti-vector antibodies that activate complement and promote viral vector phagocytosis.}, journal = {Scandinavian journal of immunology}, volume = {101}, number = {2}, pages = {e70000}, doi = {10.1111/sji.70000}, pmid = {39891027}, issn = {1365-3083}, support = {4708373//Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; TYH2023322//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; 336411//Academy of Finland/ ; 336410//Academy of Finland/ ; }, mesh = {Humans ; *Phagocytosis/immunology ; *SARS-CoV-2/immunology ; *COVID-19/immunology/prevention &amp; control ; ChAdOx1 nCoV-19/immunology ; *COVID-19 Vaccines/immunology ; *Antibodies, Viral/immunology/blood ; *Complement Activation/immunology ; Immunoglobulin G/immunology/blood ; Neutrophils/immunology ; Opsonization/immunology ; Genetic Vectors/immunology ; Male ; Female ; Adult ; Middle Aged ; }, abstract = {The ChAdOx1 nCoV-19 vaccine has been in large-scale use during the COVID-19 pandemic. Limited efficacy compared to mRNA vaccines and certain potential side effects raise the question of whether anti-adenoviral vector antibodies influence immune responses against the vaccine. Complement activation by ChAdOx1 and leukocyte phagocytosis of ChAdOx1 in vitro were studied. Plasma IgG levels against ChAdOx1 and human adenovirus 2 (hAdV2) hexon protein were determined (n = 20) and IgGs from high- and low-titre plasmas were isolated (n = 3). Complement activation was measured as cleavage of C3 by immunoblotting and generation of C3a and sC5b-9 by ELISA. pHrodo-labelled ChAdOx1 was opsonized with complement and IgG, and phagocytosis by isolated blood PMNs in vitro was studied by flow cytometry. The transcriptomic profile of PMN cells exposed to ChAdOx1 was analysed by RNA-seq. ChAdOx1 activated the classical complement pathway in an anti-adenovirus antibody-dependent manner. Generation of the terminal complement complex sC5b-9 in individual sera correlated with anti-hAdV2 hexon and anti-ChAdOx1 IgG levels. Phagocytosis of ChAdOx1 also correlated significantly with anti-hAdV2 hexon IgG, anti-ChAdOx1 IgG and serum sC5b-9 levels. High-titre anti-hAdv2 hexon IgG increased phagocytosis in the presence of normal serum. Anti-vector antibodies induced rapid complement activation and promoted phagocytosis of the ChAdOx1 vaccine by neutrophils. Moreover, transcriptomic analysis revealed upregulation of complement-related genes induced by the ChAdOx1 vaccine in vitro. Anti-adenovirus vector antibodies and complement activation may thus influence the efficacy of the ChAdOx1 vaccine against SARS-CoV-2 and be also involved in vaccine-related side effects.}, }
@article {pmid39886886, year = {2025}, author = {Pitkänen, HH and Helin, T and Khawaja, T and Pietilä, JP and Kajova, M and Välimaa, H and Vahlberg, T and Ihalainen, J and Vierikko, A and Vapalahti, O and Kantele, A and Lassila, R}, title = {Coagulation Profile of Convalescent Plasma Donors and Recipients.}, journal = {Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis}, volume = {31}, number = {}, pages = {10760296251317522}, pmid = {39886886}, issn = {1938-2723}, mesh = {Humans ; Male ; Female ; Middle Aged ; *COVID-19/therapy/blood ; Double-Blind Method ; *Blood Coagulation ; Adult ; COVID-19 Serotherapy ; *Blood Donors ; *SARS-CoV-2 ; Immunization, Passive ; Aged ; Thrombin ; }, abstract = {Convalescent plasma (CP) therapy for COVID-19 infection may have favorable safety but varying efficacy, with concerns about its procoagulant impact. We investigated whether administration of CP to hospitalized patients affects their coagulation profile. Fifty-four patients randomized in a double-blinded fashion received either placebo, low-titer CP (LCP) or high-titer CP (HCP). Donor blood samples were obtained at the time of the plasmapheresis, while recipient blood samples were collected before infusion, one day post-infusion and between two and six days after infusion. Routine laboratory follow-up, coagulation biomarkers, antiphospholipid antibodies, and thrombin generation (TG) were assessed. CP donors had normal blood cell counts and coagulation profiles, without differences between LCP and HCP donors at the baseline. All CP recipients were on low-molecular-weight heparin thromboprophylaxis at the time of the infusion. Despite randomization, the HCP group had lower baseline (p = 0.004) and Day 1 platelet counts (p = 0.019) than the LCP group. Von Willebrand antigen (VWF:Ag) levels clearly exceeded normal without differences at baseline. At Day 1, LCP recipients had higher VWF:Ag (mean ± SD 224 ± 15%) than HCP recipients (210 ± 8%) (p = 0.012). In all groups, overall 80% lupus anticoagulant was positive. Baseline TG variables were comparable, but again LCP recipients exhibited higher endogenous thrombin potential (ETP) (1313 ± 535 nM.min) (p = 0.038) and peak TG (184 ± 106 nM) (p = 0.037) than the HCP group (870 ± 425 nM.min and 86 ± 54 nM). Our findings show that LCP increases VWF:Ag levels and enhances TG despite the thromboprophylaxis. These results suggest that HCP induces less hypercoagulability than LCP, which may contribute to the variability in CP efficacy.}, }
@article {pmid39885552, year = {2025}, author = {Koh, H and Kim, J and Jang, H}, title = {MiCML: a causal machine learning cloud platform for the analysis of treatment effects using microbiome profiles.}, journal = {BioData mining}, volume = {18}, number = {1}, pages = {10}, pmid = {39885552}, issn = {1756-0381}, support = {2021R1C1C1013861//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: The treatment effects are heterogenous across patients due to the differences in their microbiomes, which in turn implies that we can enhance the treatment effect by manipulating the patient's microbiome profile. Then, the coadministration of microbiome-based dietary supplements/therapeutics along with the primary treatment has been the subject of intensive investigation. However, for this, we first need to comprehend which microbes help (or prevent) the treatment to cure the patient's disease.<br><br>RESULTS: In this paper, we introduce a cloud platform, named microbiome causal machine learning (MiCML), for the analysis of treatment effects using microbiome profiles on user-friendly web environments. MiCML is in particular unique with the up-to-date features of (i) batch effect correction to mitigate systematic variation in collective large-scale microbiome data due to the differences in their underlying batches, and (ii) causal machine learning to estimate treatment effects with consistency and then discern microbial taxa that enhance (or lower) the efficacy of the primary treatment. We also stress that MiCML can handle the data from either randomized controlled trials or observational studies.<br><br>CONCLUSION: We describe MiCML as a useful analytic tool for microbiome-based personalized medicine. MiCML is freely available on our web server (http://micml.micloud.kr). MiCML can also be implemented locally on the user's computer through our GitHub repository (https://github.com/hk1785/micml).}, }
@article {pmid39880761, year = {2024}, author = {Nandwana, D and Zhang, Y and Feng, N}, title = {Contribution of the Microbiome to Interstitial Cystitis/Bladder Pain Syndrome: A Mini Review.}, journal = {European urology focus}, volume = {10}, number = {6}, pages = {893-897}, doi = {10.1016/j.euf.2025.01.008}, pmid = {39880761}, issn = {2405-4569}, mesh = {Humans ; *Cystitis, Interstitial/microbiology/physiopathology ; *Microbiota/physiology ; Dysbiosis/microbiology/complications ; Female ; Vagina/microbiology ; Pelvic Pain/microbiology ; }, abstract = {Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by pelvic pain and urinary urgency and frequency with an unclear etiology. Emerging evidence implicates microbiome dysbiosis-disruptions in the microbial communities inhabiting the body-in IC/BPS pathophysiology. This review synthesizes the literature on microbial alterations in IC/BPS, including urinary, vaginal, and gastrointestinal microbiota, and their interactions with host inflammatory and metabolic pathways. PATIENT SUMMARY: We reviewed studies from the past 10 years on microbial communities in the body for patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Studies have revealed significant changes in microbial species for these patients, especially in urine. However, research on whether IC/BPS can be treated with interventions to modify microbial communities in the body is still needed.}, }
@article {pmid39877362, year = {2024}, author = {Slater, AS and Hickey, RM and Davey, GP}, title = {Interactions of human milk oligosaccharides with the immune system.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1523829}, pmid = {39877362}, issn = {1664-3224}, mesh = {Humans ; *Milk, Human/immunology/chemistry ; *Oligosaccharides/immunology/metabolism/chemistry ; *Immune System/immunology/metabolism ; Gastrointestinal Microbiome/immunology ; Immunomodulation ; Infant, Newborn ; }, abstract = {Human milk oligosaccharides (HMOs) are abundant, diverse and complex sugars present in human breast milk. HMOs are well-characterized barriers to microbial infection and by modulating the human microbiome they are also thought to be nutritionally beneficial to the infant. The structural variety of over 200 HMOs, including neutral, fucosylated and sialylated forms, allows them to interact with the immune system in various ways. Clinically, HMOs impact allergic diseases, reducing autoimmune and inflammatory responses, and offer beneficial support to the preterm infant immune health. This review examines the HMO composition and associated immunomodulatory effects, including interactions with immune cell receptors and gut-associated immune responses. These immunomodulatory properties highlight the potential for HMO use in early stage immune development and for use as novel immunotherapeutics. HMO research is rapidly evolving and promises innovative treatments for immune-related conditions and improved health outcomes.}, }
@article {pmid39877080, year = {2025}, author = {Fehringer, M and Vogl, T}, title = {Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases.}, journal = {Journal of translational autoimmunity}, volume = {10}, number = {}, pages = {100269}, pmid = {39877080}, issn = {2589-9090}, abstract = {Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of conditions characterized by excessive and misdirected immune responses against the body's own musculoskeletal tissues. Their exact aetiology remains unclear, with genetic, demographic, behavioural and environmental factors implicated in disease onset. One prominent hypothesis for the initial breach of immune tolerance (leading to autoimmunity) is molecular mimicry, which describes structural or sequence similarities between human and microbial proteins (mimotopes). This similarity can lead to cross-reactive antibodies and T-cell receptors, resulting in an immune response against autoantigens. Both commensal microbes in the human microbiome and pathogens can trigger molecular mimicry, thereby potentially contributing to the onset of ARDs. In this review, we focus on the role of molecular mimicry in the onset of rheumatoid arthritis and systemic lupus erythematosus. Moreover, implications of molecular mimicry are also briefly discussed for ankylosing spondylitis, systemic sclerosis and myositis.}, }
@article {pmid39875781, year = {2025}, author = {Tiwari, S and Paramanik, V}, title = {Role of Probiotics in Depression: Connecting Dots of Gut-Brain-Axis Through Hypothalamic-Pituitary Adrenal Axis and Tryptophan/Kynurenic Pathway involving Indoleamine-2,3-dioxygenase.}, journal = {Molecular neurobiology}, volume = {62}, number = {6}, pages = {7230-7241}, pmid = {39875781}, issn = {1559-1182}, mesh = {Humans ; *Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; *Tryptophan/metabolism ; *Probiotics/therapeutic use/pharmacology ; *Hypothalamo-Hypophyseal System/metabolism/drug effects ; *Kynurenine/metabolism ; *Depression/metabolism/drug therapy ; Animals ; *Pituitary-Adrenal System/metabolism/drug effects ; Gastrointestinal Microbiome/physiology/drug effects ; *Brain-Gut Axis/drug effects ; *Brain/metabolism ; }, abstract = {Depression is one of the most disabling mental disorders worldwide and characterized by symptoms including worthlessness, anhedonia, sleep, and appetite disturbances. Recently, studies have suggested that tryptophan (Trp) metabolism plays a key role in depressed mood through serotonin and kynurenine pathway involving enzyme tryptophan 5-monooxygenase (TPH) and indoleamine-2,3-dioxygenase (IDO) respectively. Moreover, during neuroinflammation, IDO is activated by proinflammatory cytokines and affects neurogenesis, cognition, disturbed hypothalamic-pituitary-adrenal (HPA) axis, and gut homeostasis by altering the gut bacteria and its metabolites like Trp derivatives. Furthermore, over the decades, researchers have focused on understanding communication between the human microbiome, especially gut microbiota, and mental health, called gut-brain-axis (GBA), particularly through Trp metabolism. Supplementation of probiotics in depression has gained attention from researchers and clinicians. However, there is limited information about probiotics supplementation on depression involving enzyme IDO and kynurenine pathway metabolites. This review discussed the potential role of probiotics in depression through the tryptophan/kynurenine pathway.}, }
@article {pmid39868147, year = {2025}, author = {Britton, GJ and Mogno, I and Chen-Liaw, A and Plitt, T and Helmus, D and Bongers, G and Brough, I and Colmenero, P and Lam, LH and Bullers, SJ and Penkava, F and Reyes-Mercedes, P and Braun, J and Jacobs, JP and Desch, AN and Gevers, D and Simmons, S and Filer, A and Taylor, PC and Bowness, P and Huttenhower, C and Littman, D and Dubinsky, MC and Raza, K and Tankou, SK and Faith, JJ}, title = {Inflammatory disease microbiomes share a functional pathogenicity predicted by C-reactive protein.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39868147}, issn = {2692-8205}, support = {F30 DK131862/DK/NIDDK NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; IK2 CX001717/CX/CSRD VA/United States ; }, abstract = {We examine disease-specific and cross-disease functions of the human gut microbiome by colonizing germ-free mice, at risk for inflammatory arthritis, colitis, or neuroinflammation, with over 100 human fecal microbiomes from subjects with rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, ulcerative colitis, Crohn's disease, or colorectal cancer. We find common inflammatory phenotypes driven by microbiomes from individuals with intestinal inflammation or inflammatory arthritis, as well as distinct functions specific to microbiomes from multiple sclerosis patients. Inflammatory disease in mice colonized with human microbiomes correlated with systemic inflammation, measured by C-reactive protein, in the human donors. These cross-disease patterns of human microbiome pathogenicity mirror features of the inflammatory diseases, including therapeutic targets and the presence or absence of systemic inflammation, suggesting shared and disease-specific mechanisms by which the microbiome is shaped and drives pathogenic inflammatory responses.}, }
@article {pmid39866415, year = {2025}, author = {Freibauer, A and Pai, N and RamachandranNair, R}, title = {Characterizing the fecal microbiome in patients on the ketogenic diet for drug resistant epilepsy.}, journal = {Heliyon}, volume = {11}, number = {1}, pages = {e41631}, pmid = {39866415}, issn = {2405-8440}, abstract = {BACKGROUND: The ketogenic diet is a dietary therapy with anti-seizure effects. The efficacy of the diet is variable, with initial animal studies suggesting the intestinal microbiome may have a modulating effect. Initial research on the role of the human microbiome in pediatric epilepsy management has been inconclusive.<br><br>METHODS: In this single-center prospective cohort study, stool samples were collected from 4 patients with drug resistant epilepsy on the ketogenic diet and 9 with drug resistant epilepsy as controls. The samples were analyzed by 16S RNA sequencing.<br><br>RESULTS: A trend towards increased alpha diversity was noted among patients on the ketogenic diet compared to the control group. Patients on the ketogenic diet also trended towards a higher relative abundance of Bacteroidaceae, Ruminococcaceae, and Prevotellaceae species. A subset of the control group had a high relative abundance of Bifidobacterium, which may make them a candidate for a trial of the ketogenic diet as a therapeutic option.<br><br>CONCLUSION: These findings add to the growing field of research of how the ketogenic diet modulates the intestinal microbiome in pediatric epilepsy patients. Future emphasis on multi-centre trials, consistent stool collection practices and the establishment of standardized stool biobanking protocols are needed further to validate these novel findings in a pediatric population.}, }
@article {pmid39866243, year = {2025}, author = {Hao, T and Li, Y and Ren, Q and Zeng, Y and Gao, L and Zhu, W and Liang, J and Lin, Y and Hu, J and Yan, G and Sun, S and Cai, J}, title = {circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer.}, journal = {Molecular therapy. Oncology}, volume = {33}, number = {1}, pages = {200919}, pmid = {39866243}, issn = {2950-3299}, abstract = {Pancreatic cancer is among the most challenging tumors to treat, and due to its immune tolerance characteristics, existing immunotherapy methods are not effective in alleviating the disease. Oncolytic virus therapy, a potential new strategy for treating pancreatic cancer, also faces the limitation of being ineffective when used alone. Elucidating the key host endogenous circular RNAs (circRNAs) involved in M1 virus-mediated killing of pancreatic ductal adenocarcinoma (PDAC) cells may help overcome this limitation. Here, we report that the oncolytic virus M1, a nonpathogenic alphavirus, exhibits different cell viability-inhibitory effects on different pancreatic cancer cells in the clinical stage. Through high-throughput circRNA sequencing, we found that circRNA expression varies among these cells. Further gain-of-function and loss-of-function experiments have shown that circ-1584 can selectively enhance the anti-pancreatic cancer effects of the M1 virus in vitro and in vivo. Additionally, circ-1584 may negatively regulate miR-578 to modulate the anti-pancreatic cancer effects of the M1 virus. Our findings lay the foundation for using circRNA as an adjuvant to enhance the M1 virus efficacy against pancreatic cancer.}, }
@article {pmid39864562, year = {2025}, author = {Hong, X and Chen, T and Liu, Y and Li, J and Huang, D and Ye, K and Liao, W and Wang, Y and Liu, M and Luan, P}, title = {Design, current states, and challenges of nanomaterials in anti-neuroinflammation: A perspective on Alzheimer's disease.}, journal = {Ageing research reviews}, volume = {105}, number = {}, pages = {102669}, doi = {10.1016/j.arr.2025.102669}, pmid = {39864562}, issn = {1872-9649}, mesh = {*Alzheimer Disease/drug therapy/metabolism/pathology ; Humans ; *Nanostructures/therapeutic use ; Animals ; *Neuroinflammatory Diseases/drug therapy/metabolism ; Amyloid beta-Peptides/metabolism ; }, abstract = {Alzheimer's disease (AD), an age-related neurodegenerative disease, brings huge damage to the society, to the whole family and even to the patient himself. However, until now, the etiological factor of AD is still unknown and there is no effective treatment for it. Massive deposition of amyloid-beta peptide(Aβ) and hyperphosphorylation of Tau proteins are acknowledged pathological features of AD. Recent studies have revealed that neuroinflammation plays a pivotal role in the pathology of AD. With the rise of nanomaterials in the biomedical field, researchers are exploring how the unique properties of these materials can be leveraged to develop effective treatments for AD. This article has summarized the influence of neuroinflammation in AD, the design of nanoplatforms, and the current research status and inadequacy of nanomaterials in improving neuroinflammation in AD.}, }
@article {pmid39863780, year = {2025}, author = {Toivonen, E and Sikkinen, J and Salonen, A and Kärkkäinen, O and Koistinen, V and Klåvus, A and Meuronen, T and Heini, T and Maltseva, A and Niku, M and Jääskeläinen, T and Laivuori, H}, title = {Metabolic profiles of meconium in preeclamptic and normotensive pregnancies.}, journal = {Metabolomics : Official journal of the Metabolomic Society}, volume = {21}, number = {1}, pages = {21}, pmid = {39863780}, issn = {1573-3890}, mesh = {Humans ; Female ; Pregnancy ; *Meconium/metabolism ; *Pre-Eclampsia/metabolism ; Adult ; *Metabolome ; Infant, Newborn ; Metabolomics/methods ; Chromatography, Liquid ; }, abstract = {INTRODUCTION: Preeclampsia (PE) is a common vascular pregnancy disorder affecting maternal and fetal metabolism with severe immediate and long-term consequences in mothers and infants. During pregnancy, metabolites in the maternal circulation pass through the placenta to the fetus. Meconium, a first stool of the neonate, offers a view to maternal and fetoplacental unit metabolism and could add to knowledge on the effects of PE on the fetus and newborn.<br><br>OBJECTIVES: To compare meconium metabolome of infants from PE and normotensive pregnancies.<br><br>METHODS: A cohort of preeclamptic parturients and normotensive controls were recruited in Tampere University Hospital during 2019-2022. Meconium was sampled and its metabolome analyzed using liquid chromatography- mass spectrometry in 48 subjects in each group.<br><br>RESULTS: Differences in abundances of 1263 compounds, of which 19 could be annotated, were detected between the two groups. Several acylcarnitines, androsterone sulfate, three bile acids, amino acid derivatives (phenylacetylglutamine, epsilon-(gamma-glutamyl)lysine and N-(phenylacetyl)glutamic acid), as well as caffeine and paraxanthine were lower in the PE group compared to the control group. Urea and progesterone were higher in the PE group.<br><br>CONCLUSION: PE is associated with alterations in the meconium metabolome of infants. The differing abundances of several metabolites show alterations in the interaction between the fetoplacental unit and mother in PE, but whether they are a cause or an effect of the disorder remains to be further investigated.}, }
@article {pmid39862468, year = {2025}, author = {Amir, S and Kumar, M and Kumar, V and Mohanty, D}, title = {HgutMgene-Miner: In silico genome mining tool for deciphering the drug-metabolizing potential of human gut microbiome.}, journal = {Computers in biology and medicine}, volume = {186}, number = {}, pages = {109679}, doi = {10.1016/j.compbiomed.2025.109679}, pmid = {39862468}, issn = {1879-0534}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Data Mining/methods ; *Xenobiotics/metabolism ; *Genome, Bacterial ; *Bacteria/genetics/enzymology ; *Software ; Databases, Genetic ; Computational Biology/methods ; }, abstract = {The biotransformation of drugs by enzymes from the human microbiome can produce active or inactive products, impacting the bioactivity and function of these drugs inside the human host. However, understanding the biotransformation reactions of drug molecules catalyzed by bacterial enzymes in human microbiota is still limited. Hence, to characterize drug utilization capabilities across all the microbial phyla inside the human gut, we have used a knowledge-based approach to develop HgutMgene-Miner software which predicts xenobiotic metabolizing enzymes (XMEs) through genome mining. HgutMgene-Miner derives its predictive power from the MicrobiomeMetDB database, which systematically catalogs all known biotransformation reactions of xenobiotics and primary metabolites mediated by host-associated microbial enzymes. Over 10,000 isolate genomes from 830 different bacterial species found in the Unified Human Gastrointestinal Genome (UHGG) collection have been analyzed by HgutMgene-Miner. This led to the identification of 89,377 xenobiotic metabolizing enzymes (XMEs) across 13 phyla, with the greatest diversity in Bacteroidota, Firmicutes_A, Firmicutes, and Proteobacteria. Bacteroides, Clostridium, and Alitsipes were found to be the richest genera, while Actinomyces were found to encode the fewest XMEs, primarily metabolizing Diclofenac, a nonsteroidal anti-inflammatory drug. Overall, we discovered XMEs in 220 genera, exceeding the number experimentally reported in fewer than 10 genera. Notably, Eggerthella lenta's cgr2 involved in Digoxin inactivation was identified in very distant Holdemania genera, likewise Clostridium leptum's nitroreductase, involved in Nitrazepam metabolism, was found in Fusobacterium. These findings highlight the extensive and diverse distribution of XMEs across microbial taxa.}, }
@article {pmid39858487, year = {2025}, author = {Tahmasebi, H and Arjmand, N and Monemi, M and Babaeizad, A and Alibabaei, F and Alibabaei, N and Bahar, A and Oksenych, V and Eslami, M}, title = {From Cure to Crisis: Understanding the Evolution of Antibiotic-Resistant Bacteria in Human Microbiota.}, journal = {Biomolecules}, volume = {15}, number = {1}, pages = {}, pmid = {39858487}, issn = {2218-273X}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; *Microbiota/drug effects/genetics ; Methicillin-Resistant Staphylococcus aureus/drug effects/genetics ; *Bacteria/drug effects/genetics ; *Drug Resistance, Multiple, Bacterial/genetics ; *Drug Resistance, Bacterial/genetics ; }, abstract = {The growing prevalence of antibiotic-resistant bacteria within the human microbiome has become a pressing global health crisis. While antibiotics have revolutionized medicine by significantly reducing mortality and enabling advanced medical interventions, their misuse and overuse have led to the emergence of resistant bacterial strains. Key resistance mechanisms include genetic mutations, horizontal gene transfer, and biofilm formation, with the human microbiota acting as a reservoir for antibiotic resistance genes (ARGs). Industrialization and environmental factors have exacerbated this issue, contributing to a rise in infections with multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae. These resistant pathogens compromise the effectiveness of essential treatments like surgical prophylaxis and chemotherapy, increase healthcare costs, and prolong hospital stays. This crisis highlights the need for a global One-Health approach, particularly in regions with weak regulatory frameworks. Innovative strategies, including next-generation sequencing (NGS) technologies, offer promising avenues for mitigating resistance. Addressing this challenge requires coordinated efforts, encompassing research, policymaking, public education, and antibiotic stewardship, to safeguard current antibiotics and foster the development of new therapeutic solutions. An integrated, multidimensional strategy is essential to tackle this escalating problem and ensure the sustainability of effective antimicrobial treatments.}, }
@article {pmid39858007, year = {2025}, author = {Al-Matouq, J and Al-Ghafli, H and Alibrahim, NN and Alsaffar, N and Radwan, Z and Ali, MD}, title = {Unveiling the Interplay Between the Human Microbiome and Gastric Cancer: A Review of the Complex Relationships and Therapeutic Avenues.}, journal = {Cancers}, volume = {17}, number = {2}, pages = {}, pmid = {39858007}, issn = {2072-6694}, abstract = {The human microbiota plays a crucial role in maintaining overall health and well-being. The gut microbiota has been implicated in developing and progressing various diseases, including cancer. This review highlights the related mechanisms and the compositions that influence cancer pathogenesis with a highlight on gastric cancer. We provide a comprehensive overview of the mechanisms by which the microbiome influences cancer development, progression, and response to treatment, with a focus on identifying potential biomarkers for early detection, prevention strategies, and novel therapeutic interventions that leverage microbiome modulation. This comprehensive review can guide future research and clinical practices in understanding and harnessing the microbiome to optimize gastric cancer therapies.}, }
@article {pmid39857728, year = {2025}, author = {Jaimez-Alvarado, S and López-Tenorio, II and Barragán-De Los Santos, J and Bello-Vega, DC and Gómez, FJR and Amedei, A and Berrios-Bárcenas, EA and Aguirre-García, MM}, title = {Gut-Heart Axis: Microbiome Involvement in Restrictive Cardiomyopathies.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857728}, issn = {2227-9059}, support = {IN212422//Universidad Nacional Aut&#xf3;noma de M&#xe9;xico/ ; CBF2023-2024-734//Consejo Nacional de Humanidades, Ciencias y Tecnolog&#xed;as/ ; }, abstract = {An intriguing aspect of restrictive cardiomyopathies (RCM) is the microbiome role in the natural history of the disease. These cardiomyopathies are often difficult to diagnose and so result in significant morbidity and mortality. The human microbiome, composed of billions of microorganisms, influences various physiological and pathological processes, including cardiovascular health. Studies have shown that gut dysbiosis, an imbalance in the composition of intestinal bacteria, can contribute to systemic inflammation, a key factor in many cardiovascular conditions. An increase in gut permeability, frequently caused by dysbiosis, allows bacterial endotoxins to enter the bloodstream, activating inflammatory pathways that exacerbate cardiac dysfunction. Recent reports highlight the potential role of microbiome in amyloidogenesis, as certain bacteria produce proteins that accelerate the formation of amyloid fibrils. Concurrently, advancements in amyloidosis treatments have sparked renewed hopes, marking a promising era for managing these kinds of diseases. These findings suggest that the gut-heart axis may be a potential factor in the development and progression of cardiovascular disease like RCM, opening new paths for therapeutic intervention. The aim of this review is to provide a detailed overview of the gut-heart axis, focusing on RCM.}, }
@article {pmid39856391, year = {2025}, author = {Tisza, MJ and Lloyd, RE and Hoffman, K and Smith, DP and Rewers, M and Javornik Cregeen, SJ and Petrosino, JF}, title = {Longitudinal phage-bacteria dynamics in the early life gut microbiome.}, journal = {Nature microbiology}, volume = {10}, number = {2}, pages = {420-430}, pmid = {39856391}, issn = {2058-5276}, support = {U01 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK063863/DK/NIDDK NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; U01 DK063790/DK/NIDDK NIH HHS/United States ; UL1 TR000064/TR/NCATS NIH HHS/United States ; HHSN267200700014C/LM/NLM NIH HHS/United States ; U01 DK063836/DK/NIDDK NIH HHS/United States ; U01 DK063829/DK/NIDDK NIH HHS/United States ; U01 DK063865/DK/NIDDK NIH HHS/United States ; UC4 DK095300/DK/NIDDK NIH HHS/United States ; U01 DK63865//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; UC4 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK063829/DK/NIDDK NIH HHS/United States ; UC4 DK063821/DK/NIDDK NIH HHS/United States ; U01 DK63821//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; UC4 DK117483/DK/NIDDK NIH HHS/United States ; UC4 DK063836/DK/NIDDK NIH HHS/United States ; UC4 DK112243/DK/NIDDK NIH HHS/United States ; U01 DK124166/DK/NIDDK NIH HHS/United States ; U01 DK063861/DK/NIDDK NIH HHS/United States ; P30 ES030285/ES/NIEHS NIH HHS/United States ; U01 DK63829//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; U01 DK128847/DK/NIDDK NIH HHS/United States ; UC4 DK063865/DK/NIDDK NIH HHS/United States ; U01 DK063863/DK/NIDDK NIH HHS/United States ; UC4 DK106955/DK/NIDDK NIH HHS/United States ; UC4 DK100238/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Bacteriophages/genetics/classification/isolation &amp; purification ; Infant ; *Bacteria/genetics/virology/classification/isolation &amp; purification ; Child, Preschool ; Longitudinal Studies ; Metagenome ; Diabetes Mellitus, Type 1/microbiology ; Female ; Male ; Infant, Newborn ; Feces/microbiology ; Machine Learning ; }, abstract = {Microbial colonization of the human gut occurs soon after birth, proceeds through well-studied phases and is affected by lifestyle and other factors. Less is known about phage community dynamics during infant gut colonization due to small study sizes, an inability to leverage large databases and a lack of appropriate bioinformatics tools. Here we reanalysed whole microbial community shotgun sequencing data of 12,262 longitudinal samples from 887 children from four countries across four years of life as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We developed an extensive metagenome-assembled genome catalogue using the Marker-MAGu pipeline, which comprised 49,111 phage taxa from existing human microbiome datasets. This was used to identify phage marker genes and their integration into the MetaPhlAn 4 bacterial marker gene database enabled simultaneous assessment of phage and bacterial dynamics. We found that individual children are colonized by hundreds of different phages, which are more transitory than bacteria, accumulating a more diverse phage community over time. Type 1 diabetes correlated with a decreased rate of change in bacterial and viral communities in children aged one and two. The addition of phage data improved the ability of machine learning models to discriminate samples by country. Finally, although phage populations were specific to individuals, we observed trends of phage ecological succession that correlated well with putative host bacteria. This resource improves our understanding of phage-bacteria interactions in the developing early life microbiome.}, }
@article {pmid39855612, year = {2025}, author = {Sutanto, H and Elisa, E and Rachma, B and Fetarayani, D}, title = {Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation.}, journal = {The American journal of medicine}, volume = {138}, number = {5}, pages = {769-777.e3}, doi = {10.1016/j.amjmed.2025.01.005}, pmid = {39855612}, issn = {1555-7162}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; *Hypersensitivity/therapy/microbiology/immunology ; Dysbiosis/therapy/immunology ; }, abstract = {The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.}, }
@article {pmid39854218, year = {2025}, author = {Zeng, T and Sun, K and Mai, L and Hong, X and He, X and Lin, W and Chen, S and Yan, L}, title = {Extracellular Vesicle-Associated miR-ERIA Exerts the Antiangiogenic Effect of Macrophages in Diabetic Wound Healing.}, journal = {Diabetes}, volume = {74}, number = {4}, pages = {596-610}, pmid = {39854218}, issn = {1939-327X}, support = {82222014//The National Natural Science Foundation of China Excellent Young Scientists Fund/ ; 2023A03J0706//Ministry of Education, China; Guangzhou Science and Technology Program/ ; 2020B1111170009//Guangdong Clinical Research Center for Metabolic Diseases/ ; 202102100004//Guangzhou Key Laboratory for Metabolic Diseases/ ; 32271185//The National Natural Science Foundation of China/ ; Sun Yat-sen University//Key Laboratory of Human Microbiome and Chronic Diseases/ ; 82200902//National Natural Science Foundation of China/ ; }, mesh = {*Extracellular Vesicles/metabolism ; *Wound Healing/physiology/drug effects ; *MicroRNAs/metabolism/genetics ; *Macrophages/metabolism ; Animals ; Glycation End Products, Advanced/metabolism/pharmacology ; Mice ; Humans ; Cell Movement ; }, abstract = {An understanding of cell interactions is needed to identify therapeutic targets for diabetic cutaneous ulcers. We explored extracellular vesicles after treatment with advanced glycation end products (AGEs-EVs) derived from macrophages that can suppress diabetic cutaneous wound healing. We found that a novel miRNA enriched in AGEs-EVs (miR-ERIA) suppresses the migration and tube formation of vascular endothelial cells by targeting helicase with zinc finger 2. miR-ERIA offers a potential therapeutic target for diabetic cutaneous ulcers.}, }
@article {pmid39849586, year = {2025}, author = {Li, L and Geng, Y and Chen, T and Lin, K and Xie, C and Qi, J and Wei, H and Wang, J and Wang, D and Yuan, Z and Wan, Z and Li, T and Luo, Y and Niu, D and Li, J and Yu, H}, title = {Deep learning model targeting cancer surrounding tissues for accurate cancer diagnosis based on histopathological images.}, journal = {Journal of translational medicine}, volume = {23}, number = {1}, pages = {110}, pmid = {39849586}, issn = {1479-5876}, support = {No. 82272965//the National Natural Science Foundation of China/ ; No. 81902877//the National Natural Science Foundation of China/ ; No. 82173067//the National Natural Science Foundation of China/ ; No. 81972245//the National Natural Science Foundation of China/ ; No. 31900505//the National Natural Science Foundation of China/ ; No. 2020J01453//the Natural Science Foundation of Xiamen Municipality/ ; No. 2022A1515012656//Science Fund for Distinguished Young Scholars of Guangdong Province/ ; No. 2021A1515010639//Science Fund for Distinguished Young Scholars of Guangdong Province/ ; No. 2021A1515010134//Science Fund for Distinguished Young Scholars of Guangdong Province/ ; No. 202201011004//Instituto Nacional de Ci&#xea;ncia e Tecnologia Centro de Estudos das Adapta&#xe7;&#xf5;es da Biota Aqu&#xe1;tica da Amaz&#xf4;nia/ ; No. R2021217202512965//the Excellent Talent Training Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; No. 2022JBGS07//Chongqing Xinqiao Hospital, Second Affiliated Hospital of Army Medical University/ ; No. 23ykbj007//the Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; }, mesh = {*Deep Learning ; Humans ; *Stomach Neoplasms/pathology/diagnosis/diagnostic imaging ; *Neoplasms/pathology/diagnosis/diagnostic imaging ; *Image Processing, Computer-Assisted ; Reproducibility of Results ; Tumor Microenvironment ; }, abstract = {Accurate and fast histological diagnosis of cancers is crucial for successful treatment. The deep learning-based approaches have assisted pathologists in efficient cancer diagnosis. The remodeled microenvironment and field cancerization may enable the cancer-specific features in the image of non-cancer regions surrounding cancer, which may provide additional information not available in the cancer region to improve cancer diagnosis. Here, we proposed a deep learning framework with fine-tuning target proportion towards cancer surrounding tissues in histological images for gastric cancer diagnosis. Through employing six deep learning-based models targeting region-of-interest (ROI) with different proportions of no-cancer and cancer regions, we uncovered the diagnostic value of non-cancer ROI, and the model performance for cancer diagnosis depended on the proportion. Then, we constructed a model based on MobileNetV2 with the optimized weights targeting non-cancer and cancer ROI to diagnose gastric cancer (DeepNCCNet). In the external validation, the optimized DeepNCCNet demonstrated excellent generalization abilities with an accuracy of 93.96%. In conclusion, we discovered a non-cancer ROI weight-dependent model performance, indicating the diagnostic value of non-cancer regions with potential remodeled microenvironment and field cancerization, which provides a promising image resource for cancer diagnosis. The DeepNCCNet could be readily applied to clinical diagnosis for gastric cancer, which is useful for some clinical settings such as the absence or minimum amount of tumor tissues in the insufficient biopsy.}, }
@article {pmid39848248, year = {2025}, author = {Abdill, RJ and Graham, SP and Rubinetti, V and Ahmadian, M and Hicks, P and Chetty, A and McDonald, D and Ferretti, P and Gibbons, E and Rossi, M and Krishnan, A and Albert, FW and Greene, CS and Davis, S and Blekhman, R}, title = {Integration of 168,000 samples reveals global patterns of the human gut microbiome.}, journal = {Cell}, volume = {188}, number = {4}, pages = {1100-1118.e17}, pmid = {39848248}, issn = {1097-4172}, support = {R01 LM013863/LM/NLM NIH HHS/United States ; R35 GM128716/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics/classification ; Europe ; Sequence Analysis, DNA ; }, abstract = {The factors shaping human microbiome variation are a major focus of biomedical research. While other fields have used large sequencing compendia to extract insights requiring otherwise impractical sample sizes, the microbiome field has lacked a comparably sized resource for the 16S rRNA gene amplicon sequencing commonly used to quantify microbiome composition. To address this gap, we processed 168,464 publicly available human gut microbiome samples with a uniform pipeline. We use this compendium to evaluate geographic and technical effects on microbiome variation. We find that regions such as Central and Southern Asia differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America and that composition alone can be used to predict a sample's region of origin. We also find strong associations between microbiome variation and technical factors such as primers and DNA extraction. We anticipate this growing work, the Human Microbiome Compendium, will enable advanced applied and methodological research.}, }
@article {pmid39844296, year = {2025}, author = {Liu, B and Xie, Y and Zhang, Y and Tang, G and Lin, J and Yuan, Z and Liu, X and Wang, X and Huang, M and Luo, Y and Yu, H}, title = {Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity.}, journal = {Cell &amp; bioscience}, volume = {15}, number = {1}, pages = {7}, pmid = {39844296}, issn = {2045-3701}, support = {81902877//National Natural Science Foundation of China/ ; 82272965//National Natural Science Foundation of China/ ; 82372715//National Natural Science Foundation of China/ ; 82173067//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure and drug resistance. However, the lack of a quick and convenient approach to determine the intratumoral epigenetic heterogeneity (eITH) limit the application of eITH in clinical settings. Here, we aimed to develop a tool that can evaluate the eITH using the DNA methylation profiles from bulk tumors.<br><br>METHODS: Genomic DNA of three laser micro-dissected tumor regions, including digestive tract surface, central bulk, and invasive front, was extracted from formalin-fixed paraffin-embedded sections of colorectal cancer patients. The genome-wide methylation profiles were generated with methylation array. The most variable methylated probes were selected to construct a DNA methylation-based heterogeneity (MeHEG) estimation tool that can deconvolve the proportion of each reference tumor region with the support vector machine model-based method. A PCR-based assay for quantitative analysis of DNA methylation (QASM) was developed to specifically determine the methylation status of each CpG in MeHEG assay at single-base resolution to realize fast evaluation of epigenetic heterogeneity.<br><br>RESULTS: In the discovery set with 79 patients, the differentially methylated CpGs among the three tumor regions were found. The 7 most representative CpGs were identified and subsequently selected to develop the MeHEG algorithm. We validated its performance of deconvolution of tumor regions in an independent cohort. In addition, we showed the significant association of MeHEG-based epigenetic heterogeneity with the genomic heterogeneity in mutation and copy number variation in our in-house and TCGA cohorts. Besides, we found that the patients with higher MeHEG score had worse disease-free and overall survival outcomes. Finally, we found dynamic change of epigenetic heterogeneity based on MeHEG score in cancer cells under the treatment of therapeutic drugs.<br><br>CONCLUSION: By developing a 7-loci panel using a machine learning approach combined with the QASM assay for PCR-based application, we present a valuable method for evaluating intratumoral heterogeneity. The MeHEG algorithm offers novel insights into tumor heterogeneity from an epigenetic perspective, potentially enriching current knowledge of tumor complexity and providing a new tool for clinical and research applications in cancer biology.}, }
@article {pmid39843757, year = {2025}, author = {Pitashny, M and Kesten, I and Shlon, D and Hur, DB and Bar-Yoseph, H}, title = {The Future of Microbiome Therapeutics.}, journal = {Drugs}, volume = {85}, number = {2}, pages = {117-125}, pmid = {39843757}, issn = {1179-1950}, mesh = {Humans ; *Microbiota/drug effects ; Fecal Microbiota Transplantation/methods ; Phage Therapy/methods ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; Synthetic Biology/methods ; Animals ; }, abstract = {The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.}, }
@article {pmid39840991, year = {2025}, author = {Dufresne, K and Al, KF and Craig, HC and Coleman, CEM and Kasper, KJ and Burton, JP and McCormick, JK}, title = {TSST-1 promotes colonization of Staphylococcus aureus within the vaginal tract by activation of CD8[+] T cells.}, journal = {Infection and immunity}, volume = {93}, number = {2}, pages = {e0043924}, pmid = {39840991}, issn = {1098-5522}, support = {PJT-166050//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; WFF//Weston Family Foundation (WFF)/ ; AUA//American Urological Association (AUA)/ ; }, mesh = {Female ; *Superantigens/immunology/metabolism ; Animals ; *Staphylococcus aureus/immunology ; *Vagina/microbiology/immunology ; *Bacterial Toxins/immunology/metabolism ; *Enterotoxins/immunology/metabolism ; *CD8-Positive T-Lymphocytes/immunology ; Mice ; *Staphylococcal Infections/immunology/microbiology ; *Lymphocyte Activation/immunology ; Mice, Inbred C57BL ; Microbiota ; }, abstract = {Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced by Staphylococcus aureus and is the determinant of menstrual toxic shock syndrome (mTSS); however, the impact of TSST-1 on the vaginal environment beyond mTSS is not understood. Herein, we assessed how TSST-1 affects vaginal colonization by S. aureus, host inflammatory responses, and changes in microbial communities within the murine vagina. We demonstrated that TSST-1 induced a CD8[+] T-cell-dependent inflammatory response in 24 h that correlated with S. aureus persistence within the vaginal tract. This increase was due to superantigen-dependent T-cell activation that triggered a change in microbial composition within the vaginal tract. Altogether, this study demonstrates that within the vaginal tract, TSST-1 modulates the vaginal microbiota to favor the survival of S. aureus in the absence of mTSS.IMPORTANCEToxic shock syndrome toxin-1 (TSST-1) is a superantigen toxin produced from Staphylococcus aureus that causes the menstrual form of toxic shock syndrome. This research demonstrates that TSST-1 also has a wider function within the vaginal tract than previously expected. We show that TSST-1, by activating CD8[+] T cells, induces an inflammatory environment that modifies the vaginal microbiota to favor colonization by S. aureus. These are important findings as S. aureus can colonize the human vaginal tract efficiently and subsequently trigger dysbiosis within the microbial communities leading to several adverse outcomes such as decreased fertility, increased risks for sexually transmitted diseases, and issues related to pregnancy and birth.}, }
@article {pmid39839711, year = {2025}, author = {Griffin, EF and Owens, MG}, title = {Dopaminergic neurodegeneration in C. elegans cultivated with Porphorymonas gingivalis.}, journal = {microPublication biology}, volume = {2025}, number = {}, pages = {}, pmid = {39839711}, issn = {2578-9430}, abstract = {Disruption of the human microbiome has emerged as a major contributing factor in the etiology of neurodegenerative disease. Previous work suggests a positive correlation between periodontal inflammation and Parkinson's disease. Here, we show that feeding C. elegans animals Porphorymonas gingivalis causes neurodegeneration that is not additive with neurodegeneration induced by the Parkinson's-associated protein, α-synuclein. In contrast, α-synuclein-expressing animals fed P. gingivalis show additional disruption in basal slowing, suggesting that P. gingivalis induces neurodegeneration while altering neuronal function of extant neurons. Though the mechanism is unclear, these results suggest a relationship between P. gingivalis and neurodegeneration that warrants further investigation.}, }
@article {pmid39839678, year = {2025}, author = {Modha, S and Hughes, J and Orton, RJ and Lytras, S}, title = {Expanding the genomic diversity of human anelloviruses.}, journal = {Virus evolution}, volume = {11}, number = {1}, pages = {veaf002}, pmid = {39839678}, issn = {2057-1577}, abstract = {Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across mammalian hosts. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus genera: Alphatorquevirus, Betatorquevirus, and Gammatorquevirus, while we also present new genomes of the under-sampled Hetorquevirus, Memtorquevirus, and Samektorquevirus genera. We performed recombination analysis and show evidence of extensive recombination across all human anelloviruses. Interestingly, more than 95% of the detected events are between members of the same genus and only 15 inter-genus recombination events were detected. The breakpoints of recombination cluster in hotspots at the ends and outside of the ORF1 gene, while a recombination coldspot was detected within the gene. Our analysis suggests that anellovirus evolution is governed by homologous recombination; however, events between distant viruses or ones producing chimaeric ORF1s likely lead to nonviable recombinants. The large number of genomes further allowed us to examine how essential genomic features vary across anelloviruses. These include functional domains in the ORF1 protein and the nucleotide motif of the replication loop region, required for the viruses' rolling-circle replication. A subset of the genomes assembled in both this and previous studies are completely lacking these essential elements, opening up the possibility that anellovirus intracellular populations contain nonstandard viral genomes. However, low-read depth of the metagenomically assembled contigs may partly explain the lack of some features. Overall, our study highlights key features of anellovirus genomics and evolution, a largely understudied group of viruses whose potential in virus-based therapeutics is recently being explored.}, }
@article {pmid39836666, year = {2025}, author = {Gill, B and Wessels, JM and Hayes, CL and Ratcliffe, J and Wokuri, J and Ball, E and Reid, G and Kaul, R and Rana, J and Alkhaifi, M and Tharao, W and Smaill, F and Kaushic, C}, title = {Feasibility, safety and tolerability of estrogen and/or probiotics for improving vaginal health in Canadian African, Caribbean, and Black women: A pilot phase 1 clinical trial.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0315576}, pmid = {39836666}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Female ; Humans ; Middle Aged ; Young Adult ; Administration, Intravaginal ; Black People ; Canada ; *Estrogens/administration &amp; dosage/adverse effects/therapeutic use ; Feasibility Studies ; HIV Infections/prevention &amp; control ; Pilot Projects ; *Probiotics/administration &amp; dosage/adverse effects/therapeutic use ; *Vagina/microbiology/drug effects ; *Vaginosis, Bacterial/drug therapy/microbiology ; Caribbean People ; }, abstract = {BACKGROUND: A dysbiotic vaginal microbiome (VMB) is associated with clinical conditions such as bacterial vaginosis (BV) and an increased risk of human immunodeficiency virus (HIV-1) infection. Considering the high prevalence of BV among African, Caribbean and Black (ACB) women, we conducted a prospective, randomized, open-label phase 1 clinical trial to determine the feasibility, safety and tolerability of administering low-dose estrogen, probiotics or both in combination to improve vaginal health and decrease HIV-1 susceptibility.<br><br>METHODS: ACB women aged 18-49 from the Greater Toronto Area (GTA) were randomized to one of four study arms: intravaginal estradiol (Estring&#xa9;; 7.5mg/day); a vaginal probiotic (RepHresh&#x2122; Pro-B&#x2122;) administered twice daily; a combination of Estring&#xa9; and vaginal RepHresh&#x2122; Pro-B&#x2122; (twice daily); or the Estring&#xa9; and oral RepHresh&#x2122; Pro-B&#x2122; (twice daily), for a duration of 30 days. Feasibility was evaluated through enrolment, retention, and adherence rates, while safety and tolerability were determined by a pre- and post-treatment blood panel and reported adverse events (AEs).<br><br>RESULTS: Overall, 63 ACB women were screened, 50 were enrolled and received the intervention while 41 completed the study, resulting in 80% enrollment and 82% retention rates. Overall adherence to the study protocol was high at 93%, with an adherence of 92% for RepHresh&#x2122; Pro-B&#x2122; and 97% for Estring&#xa9;. A total of 88 AEs were reported by 29 participants which were mild (66/88; 75%) and largely resolved (82/88;93%) by the end of the study, with no serious AEs (SAEs) noted. In addition, a panel of safety blood markers measured pre- and post-intervention confirmed no clinically significant changes in blood chemistry or blood cell count.<br><br>CONCLUSION: Overall, the administration of intravaginal estrogen and/or probiotics in pre-menopausal ACB women is feasible, safe, and well tolerated.<br><br>TRIAL REGISTRATION: The trial was registered with Clinicaltrials.gov (NCT03837015) and CIHR HIV Clinical Trials (CTN308).}, }
@article {pmid39830242, year = {2025}, author = {Carter, MM and Zeng, X and Ward, CP and Landry, M and Perelman, D and Hennings, T and Meng, X and Weakley, AM and Cabrera, AV and Robinson, JL and Nguyen, T and Higginbottom, S and Maecker, HT and Sonnenburg, ED and Fischbach, MA and Gardner, CD and Sonnenburg, JL}, title = {A gut pathobiont regulates circulating glycine and host metabolism in a twin study comparing vegan and omnivorous diets.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {39830242}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 HL161270/HL/NHLBI NIH HHS/United States ; }, abstract = {Metabolic diseases including type 2 diabetes and obesity pose a significant global health burden. Plant-based diets, including vegan diets, are linked to favorable metabolic outcomes, yet the underlying mechanisms remain unclear. In a randomized trial involving 21 pairs of identical twins, we investigated the effects of vegan and omnivorous diets on the host metabolome, immune system, and gut microbiome. Vegan diets induced significant shifts in serum and stool metabolomes, cytokine profiles, and gut microbial composition. Despite lower dietary glycine intake, vegan diet subjects exhibited elevated serum glycine levels linked to reduced abundance of the gut pathobiont Bilophila wadsworthia. Functional studies demonstrated that B. wadsworthia metabolizes glycine via the glycine reductase pathway and modulates host glycine availability. Removing B. wadsworthia from a complex microbiota in mice elevated glycine levels and improved metabolic markers. These findings reveal a previously underappreciated mechanism by which diet regulates host metabolic status via the gut microbiota.}, }
@article {pmid39829898, year = {2025}, author = {Ni, M and Fan, Y and Liu, Y and Li, Y and Qiao, W and Davey, LE and Zhang, XS and Ksiezarek, M and Mead, EA and Tourancheau, A and Jiang, W and Blaser, MJ and Valdivia, RH and Fang, G}, title = {Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39829898}, issn = {2692-8205}, support = {R35 GM139655/GM/NIGMS NIH HHS/United States ; }, abstract = {The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A strategy for bacterial genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePVs have been characterized in human pathogens' antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting those associated with antibiotics or fecal microbiota transplantation. Second, we analyzed a collection of public short-read metagenomic sequencing datasets, uncovering a great prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variation associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of an Akkermansia muciniphila isolate from an infant, highlighting that ePVs can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common strategy used by gut bacteria to adapt to the fluctuating environment.}, }
@article {pmid39824829, year = {2025}, author = {Jeyaram, K and Lahti, L and Tims, S and Heilig, HGHJ and van Gelder, AH and de Vos, WM and Smidt, H and Zoetendal, EG}, title = {Fermented foods affect the seasonal stability of gut bacteria in an Indian rural population.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {771}, pmid = {39824829}, issn = {2041-1723}, support = {BT/IN/CREST-Awards/44/KJ/2010-11//Department of Biotechnology, Ministry of Science and Technology (DBT)/ ; 295741, 330887//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Seasons ; Rural Population ; India ; Male ; Adult ; Female ; Feces/microbiology ; *Fermented Foods/microbiology ; Bacteria/classification/genetics/isolation &amp; purification ; Young Adult ; Middle Aged ; }, abstract = {The effect of fermented foods on healthy human gut microbiota structure and function, particularly its seasonal preference and frequent long-term consumption, has been largely uncharacterised. Here, we assess the gut microbiota and metabolite composition of 78 healthy Indian agrarian individuals who differ in the intake of fermented milk and soybean products by seasonal sampling during hot-humid summer, autumn and dry winter. Here we show that, seasonal shifts between the Prevotella- and Bifidobacterium/Ruminococcus-driven community types, or ecological states, and associated fatty acid derivatives, with a bimodal change in Bacteroidota community structure during summer, particularly in fermented milk consumers. Our results associate long-term fermented food consumption with reduced gut microbiota diversity and bacterial load. We identify taxonomic groups that drive the seasonal fluctuation and associated shifts between the two ecological states in gut microbiota. This understanding may pave the way towards developing strategies to sustain a healthy and resilient gut microbiota through dietary interventions.}, }
@article {pmid39824739, year = {2025}, author = {Sfanos, KS}, title = {Clinical translation of the interconnected role of the microbiome and diet in genitourinary malignancies.}, journal = {Urologic oncology}, volume = {43}, number = {4}, pages = {197-198}, doi = {10.1016/j.urolonc.2024.12.269}, pmid = {39824739}, issn = {1873-2496}, mesh = {Humans ; *Microbiota ; *Urogenital Neoplasms/microbiology ; *Diet ; Male ; }, abstract = {A complex and often under-appreciated relationship exists between the human microbiome, diet, and the development or progression of cancer. There is likewise an emerging appreciation for the role that the human-associated microbiota play in mediating cancer treatment response. This seminar series covers our current understanding of the interplay between the microbiome and cancer in genitourinary malignancies inclusive of bladder, kidney, and prostate cancers.}, }
@article {pmid39817749, year = {2025}, author = {Amari, Y and Hosonuma, M and Mizukami, T and Isobe, J and Azetsu, Y and Funayama, E and Maruyama, Y and Tsurui, T and Tajima, K and Sasaki, A and Yamazaki, Y and Nakano, R and Sano, Y and Ishida, A and Nakanishi, T and Mochizuki, S and Yoshizawa, Y and Kumagai, S and Yasuhara, S and Ryu, K and Oguchi, T and Kuramasu, A and Yoshimura, K and Sambe, T and Kobayashi, S and Uchida, N}, title = {Association between the ABCC11 gene polymorphism-determined earwax properties and external auditory canal microbiota in healthy adults.}, journal = {Microbiology spectrum}, volume = {13}, number = {2}, pages = {e0169824}, pmid = {39817749}, issn = {2165-0497}, support = {//Showa University/ ; }, mesh = {Humans ; *Ear Canal/microbiology ; *ATP-Binding Cassette Transporters/genetics ; Adult ; Male ; Female ; *Polymorphism, Single Nucleotide ; *Microbiota/genetics ; *Cerumen ; Middle Aged ; Bacteria/classification/genetics/isolation &amp; purification ; Corynebacterium/isolation &amp; purification/genetics ; Healthy Volunteers ; Young Adult ; }, abstract = {UNLABELLED: The concept of genome-microbiome interactions, in which the microenvironment determined by host genetic polymorphisms regulates the local microbiota, is important in the pathogenesis of human disease. In otolaryngology, the resident bacterial microbiota is reportedly altered in non-infectious ear diseases, such as otitis media pearls and exudative otitis media. We hypothesized that a single-nucleotide polymorphism in the ATP-binding cassette sub-family C member 11 (ABCC11) gene, which determines earwax properties, regulates the ear canal microbiota. We analyzed ABCC11 gene polymorphisms and ear canal microbiota in healthy individuals to understand the relationship between genome-microbiome interactions in the ear canal. The study included 21 subjects who were divided into two groups: 538GA (9) and 538AA (12). Staphylococcus auricularis and Corynebacterium spp. were observed in the 538GA group, whereas Methylocella spp. was observed in the 538AA group. PICRUSt analysis revealed significant enrichment of certain pathways, such as superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation, chlorosalicylate degradation, mycothiol biosynthesis, and enterobactin biosynthesis in the GA group, whereas allantoin degradation IV (anaerobic), nitrifier denitrification, starch degradation III, L-valine degradation I, and nicotinate degradation I were significantly enriched in the AA group. The ABCC11 gene polymorphism regulates the composition of the ear canal microbiota and its metabolic pathways. This study revealed a genome-microbiome interaction within the resident microbiota of the external auditory canal that may help to elucidate the pathogenesis of ear diseases and develop novel therapies.<br><br>IMPORTANCE: The ABCC11 gene polymorphism, which determines earwax characteristics, regulates the composition of the ear canal microbiota and its metabolic pathways. We determined the presence of genome-microbiome interactions in the resident microbiota of the ear canal. Future studies should focus on ABCC11 gene polymorphisms to elucidate the pathogenesis of ear diseases and develop therapeutic methods.}, }
@article {pmid39817732, year = {2025}, author = {Bao, Z and Zhang, B and Yao, J and Li, MD}, title = {MultiTax-human: an extensive and high-resolution human-related full-length 16S rRNA reference database and taxonomy.}, journal = {Microbiology spectrum}, volume = {13}, number = {2}, pages = {e0131224}, pmid = {39817732}, issn = {2165-0497}, support = {No. 2021JC06//Research Project of Joint Institue of Tobacco and Health/ ; }, mesh = {Humans ; *RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Bacteria/classification/genetics/isolation &amp; purification ; *Databases, Genetic ; Phylogeny ; *Databases, Nucleic Acid ; }, abstract = {Considering that the human microbiota plays a critical role in health and disease, an accurate and high-resolution taxonomic classification is thus essential for meaningful microbiome analysis. In this study, we developed an automatic system, named MultiTax pipeline, for generating de novo taxonomy from full-length 16S rRNA sequences using the Genome Taxonomy Database and other existing reference databases. We first constructed the MultiTax-human database, a high-resolution resource specifically designed for human microbiome research and clinical applications. The database includes 842,649 high-quality full-length 16S rRNA sequences, extracted from multiple public repositories and human-related studies, offering a comprehensive and accurate portrayal of the human microbiome. To validate the MultiTax-human database, we profiled the human microbiome across various body sites, identified core microbial taxa, and tested its performance using an independent data set. Additionally, the database is equipped with a user-friendly web interface for easy querying and data exploration. The MultiTax-human database is poised to serve as a valuable tool for researchers, enhancing the precision of human microbiome studies and advancing our understanding of its impact on human health and diseases.IMPORTANCEUnderstanding the human microbiome, the collection of microorganisms in and on our bodies, is essential for advancing health research. Current methods often lack precision and consistency, hindering our ability to study these microorganisms effectively. Our study presents the MultiTax-human database, a high-resolution reference tool specifically designed for human microbiome research. By integrating data from multiple sources and employing advanced classification techniques, this database offers an accurate and detailed map of the human microbiome. This resource enhances the ability of researchers and clinicians to explore the roles of microorganisms in health and disease, potentially leading to improved diagnostics, treatments, and insights into various medical conditions.}, }
@article {pmid39809670, year = {2025}, author = {Galeota-Sprung, B and Bhatt, AS and de la Fuente-Nunez, C}, title = {Microproteins: emerging roles as antibiotics.}, journal = {Trends in genetics : TIG}, volume = {41}, number = {2}, pages = {104-106}, doi = {10.1016/j.tig.2024.12.004}, pmid = {39809670}, issn = {0168-9525}, mesh = {*Anti-Bacterial Agents/pharmacology ; Humans ; Microbiota/genetics ; *Bacterial Proteins/genetics ; Micropeptides ; }, abstract = {Recent advances in computational prediction and experimental techniques have detected previously unknown microproteins, particularly in the human microbiome. These small proteins, produced by diverse microbial species, are emerging as promising candidates for new antibiotics.}, }
@article {pmid39809651, year = {2025}, author = {Liu, X and Meng, L and Song, W and Zhi, M and Wang, P and Liu, B and Du, M and Feng, Q}, title = {Efficacy of Toothpaste Containing Polylysine and Funme Peptide on Oral Microbiome and Oral Health.}, journal = {International dental journal}, volume = {75}, number = {2}, pages = {1068-1080}, pmid = {39809651}, issn = {1875-595X}, mesh = {Humans ; *Toothpastes/pharmacology/chemistry ; *Microbiota/drug effects ; *Polylysine/pharmacology ; Male ; *Oral Health ; Female ; Adult ; Gingivitis/microbiology/drug therapy ; Dental Plaque Index ; *Mouth/microbiology ; Middle Aged ; Dental Plaque ; Periodontal Index ; *Antimicrobial Peptides/pharmacology ; }, abstract = {OBJECTIVE: To evaluate the effect of the toothpaste containing ε-poly-L-lysine (ε-PL) and funme peptide (FP) as key components on oral microbial composition and oral health.<br><br>METHODS: An oral microbiome study was initially carried out to analyze the variation in the oral microbiota before and after use of antimicrobial peptide (AMP) toothpaste. Subsequently, a clinical trial was independently performed to assess the efficacy of AMP toothpaste by measuring the dental plaque index (PLI), volatile sulfur compounds (VSCs) levels, modified bleeding index (mBI), and bleeding on probing rate (BOP%).<br><br>RESULTS: The application of AMP toothpaste increased the &#x3b1; diversity and modified &#x3b2; diversity of oral microbiome across 3 oral niches. AMP toothpaste increased the relative abundance of the commensal oral microbes, and attenuated the abundance of pathogenic bacteria in gingivitis patients to normal levels. The clinical trial showed 44.33% and 12.29% reductions of PLI scores in the test and control groups, respectively, and the test group exhibited a more pronounced decrease in VSC levels. The test group recorded significant reductions in mBI and BOP% by 39.09% and 24.59%, respectively, exceeding the control group's reductions of 4.63% and -0.97% (P < .05).<br><br>CONCLUSION: The formulation of toothpaste with &#x3b5;-PL and FP recalibrated the oral microbiome's diversity and abundance, and mitigated common oral health issues such as plaque, halitosis, and gingivitis while maintaining well safety.<br><br>CLINICAL RELEVANCE: Oral care products containing &#x3b5;-PL and FP can be used as a new treatment for improving oral microbiota and oral diseases.}, }
@article {pmid39804694, year = {2025}, author = {Puller, V and Plaza Oñate, F and Prifti, E and de Lahondès, R}, title = {Impact of simulation and reference catalogues on the evaluation of taxonomic profiling pipelines.}, journal = {Microbial genomics}, volume = {11}, number = {1}, pages = {}, pmid = {39804694}, issn = {2057-5858}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Computer Simulation ; *Metagenomics/methods ; Microbiota/genetics ; *Bacteria/classification/genetics ; Computational Biology/methods ; Benchmarking ; }, abstract = {Microbiome profiling tools rely on reference catalogues, which significantly affect their performance. Comparing them is, however, challenging, mainly due to differences in their native catalogues. In this study, we present a novel standardized benchmarking framework that makes such comparisons more accurate. We decided not to customize databases but to translate results to a common reference to use the tools with their native environment. Specifically, we conducted two realistic simulations of gut microbiome samples, each based on a specific taxonomic profiler, and used two different taxonomic references to project their results, namely the Genome Taxonomy Database and the Unified Human Gastrointestinal Genome. To demonstrate the importance of using such a framework, we evaluated four established profilers as well as the impact of the simulations and that of the common taxonomic references on the perceived performance of these profilers. Finally, we provide guidelines to enhance future profiler comparisons for human microbiome ecosystems: (i) use or create realistic simulations tailored to your biological context (BC), (ii) identify a common feature space suited to your BC and independent of the catalogues used by the profilers and (iii) apply a comprehensive set of metrics covering accuracy (sensitivity/precision), overall representativity (richness/Shannon) and quantification (UniFrac and/or Aitchison distance).}, }
@article {pmid39802902, year = {2024}, author = {Li, D and Wu, R and Yu, Q and Tuo, Z and Wang, J and Yoo, KH and Wei, W and Yang, Y and Ye, L and Guo, Y and Chaipanichkul, P and Okoli, UA and Poolman, TM and Burton, JP and Cho, WC and Heavey, S and Feng, D}, title = {Microbiota and urinary tumor immunity: Mechanisms, therapeutic implications, and future perspectives.}, journal = {Chinese journal of cancer research = Chung-kuo yen cheng yen chiu}, volume = {36}, number = {6}, pages = {596-615}, pmid = {39802902}, issn = {1000-9604}, }
@article {pmid39800869, year = {2025}, author = {Zhang, H and Chen, A and Li, S and Chen, K and You, X and Bian, Y and Li, C and Liu, S and Huang, J and Zhang, S}, title = {Spatio-Temporal Change of Skin and Oral Microbiota: A Longitudinal Study of Microbial Diversity and Stability.}, journal = {Electrophoresis}, volume = {46}, number = {1-2}, pages = {92-103}, doi = {10.1002/elps.202400160}, pmid = {39800869}, issn = {1522-2683}, support = {82371896//National Natural Science Foundation of China/ ; 82260335//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Skin/microbiology ; *Microbiota/genetics ; *Mouth/microbiology ; Longitudinal Studies ; Male ; Bacteria/genetics/classification/isolation &amp; purification ; Female ; Adult ; Saliva/microbiology ; COVID-19/microbiology ; Spatio-Temporal Analysis ; SARS-CoV-2 ; Young Adult ; Middle Aged ; }, abstract = {The human skin and oral cavity harbor complex microbial communities, which exist in dynamic equilibrium with the host's physiological state and the external environment. This study investigates the microbial atlas of human skin and oral cavities using samples collected over a 10-month period, aiming to assess how both internal and external factors influence the human microbiome. We examined bacterial community diversity and stability across various body sites, including palm and nasal skin, saliva, and oral epithelial cells, during environmental changes and a COVID-19 pandemic. The skin microbiome was confirmed to display spatial and temporal stability compared to the oral microbiome, particularly the oral epithelium, which was susceptible to changes in the host's physiological state and immune response. Moreover, significant differences in the microbial community structure among the 4 sample types were observed, and 87 distinct bacteria biomarkers were identified. The random forest prediction model achieved an overall prediction accuracy of 95.24% across the four types of samples studied. Additionally, nasal skin samples showed significant promise for individual identification through profiling the skin microbiota. These findings highlight the potential of skin and oral microbiota as forensic markers for inferring body sites and identifying individuals. In summary, despite facing limitations such as a small cohort size and the need for broader validation, this research provides an overall perspective and initial insights for refining experimental designs and conducting in-depth research in various microbial research fields.}, }
@article {pmid39798621, year = {2025}, author = {Heckmann, ND and Culler, MW and Mont, MA and Lieberman, JR and Parvizi, J}, title = {Emerging Concepts in Periprosthetic Joint Infection Research: The Human Microbiome.}, journal = {The Journal of arthroplasty}, volume = {40}, number = {7}, pages = {1821-1826}, doi = {10.1016/j.arth.2025.01.001}, pmid = {39798621}, issn = {1532-8406}, mesh = {Humans ; *Prosthesis-Related Infections/microbiology ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology/complications ; *Osteoarthritis/microbiology ; *Microbiota ; }, abstract = {Microorganisms, including bacteria, fungi, and viruses, that reside on and within the human body are collectively known as the human microbiome. Dysbiosis, or disruption in the microbiome, has been implicated in several disease processes, including asthma, obesity, autoimmune diseases, and numerous other conditions. While the Human Microbiome Project and the generation of descriptive studies it inspired established correlations between characteristic patterns in the composition of the microbiome and specific disease phenotypes, current research has begun to focus on elucidating the causal role of the microbiome in disease pathogenesis. Within the field of orthopaedic surgery, researchers have proposed the concept of a "gut-joint axis," whereby the intestinal microbiome influences joint health and the development of diseases, such as osteoarthritis and periprosthetic joint infection (PJI). It is theorized that intestinal dysbiosis increases gut permeability, leading to the translocation of bacteria and their metabolic products into the systemic circulation and the stimulation of proinflammatory response cascades throughout the body, including within the joints. While correlative studies have identified patterns of dysbiotic derangement associated with osteoarthritis and PJI, translational research is needed to clarify the precise mechanisms by which these changes influence disease processes. Additionally, an emerging body of literature has challenged the previously held belief that certain body sites are sterile and do not possess a microbiome, with studies identifying distinct microbial genomic signatures and a core microbiome that varies between anatomic sites. A more thorough characterization of the joint microbiome may have profound implications for our understanding of PJI pathogenesis and our ability to stratify patients based on risk. The purpose of this review was to outline our current understanding of the human microbiome to describe the gut-joint axis and its role in specific pathologies, including PJI, and to highlight the potential of microbiome-based therapeutic interventions in the field of orthopaedics.}, }
@article {pmid39797472, year = {2025}, author = {Chong-Nguyen, C and Yilmaz, B and Coles, B and Sokol, H and MacPherson, A and Siepe, M and Reineke, D and Mosbahi, S and Tomii, D and Nakase, M and Atighetchi, S and Ferro, C and Wingert, C and Gräni, C and Pilgrim, T and Windecker, S and Blasco, H and Dupuy, C and Emond, P and Banz, Y and Losmanovà, T and Döring, Y and Siontis, GCM}, title = {A scoping review evaluating the current state of gut microbiota and its metabolites in valvular heart disease physiopathology.}, journal = {European journal of clinical investigation}, volume = {55}, number = {6}, pages = {e14381}, doi = {10.1111/eci.14381}, pmid = {39797472}, issn = {1365-2362}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Animals ; Methylamines/metabolism ; *Heart Valve Diseases/microbiology/physiopathology/metabolism ; *Aortic Valve Stenosis/microbiology/metabolism/physiopathology ; *Calcinosis/microbiology/metabolism/physiopathology ; Aortic Valve/pathology ; Fibrosis ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.<br><br>METHODS: Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes.<br><br>RESULTS: Thirteen studies were included in the review: five human, three animal and five in&#xa0;vitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. In&#xa0;vivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E.&#x2009;coli.<br><br>CONCLUSIONS: TMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.}, }
@article {pmid39796469, year = {2024}, author = {Wu, F and Guo, Y and Wang, Y and Sui, X and Wang, H and Zhang, H and Xin, B and Yang, C and Zhang, C and Jiang, S and Qu, L and Feng, Q and Dai, Z and Shi, C and Li, Y}, title = {Effects of Long-Term Fasting on Gut Microbiota, Serum Metabolome, and Their Association in Male Adults.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796469}, issn = {2072-6643}, support = {2022SY54B0506, BJH22WS1J002, 18035020103//the Advanced Space Medico-Engineering Research Project of China/ ; SMFA22Q03, SMFA22B04//The State Key Laboratory of Space Medicine, China Astronaut Research and Training Center/ ; HYZHXM01002//the Space Medical Experiment Project of China Manned Space Program/ ; JCYJ20200109110630285//he Shenzhen Science and Technology Innovation Commission 2020 Basic Research Project/ ; 2022YFA1604504//National Key R&amp;D Program of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Male ; *Fasting/blood/physiology ; Pilot Projects ; *Metabolome ; Adult ; Middle Aged ; Animals ; Probiotics ; }, abstract = {BACKGROUND: Long-term fasting demonstrates greater therapeutic potential and broader application prospects in extreme environments than intermittent fasting.<br><br>METHOD: This pilot study of 10-day complete fasting (CF), with a small sample size of 13 volunteers, aimed to investigate the time-series impacts on gut microbiome, serum metabolome, and their interrelationships with biochemical indices.<br><br>RESULTS: The results show CF significantly affected gut microbiota diversity, composition, and interspecies interactions, characterized by an expansion of the Proteobacteria phylum (about six-fold) and a decrease in Bacteroidetes (about 50%) and Firmicutes (about 34%) populations. Notably, certain bacteria taxa exhibited complex interactions and strong correlations with serum metabolites implicated in energy and amino acid metabolism, with a particular focus on fatty acylcarnitines and tryptophan derivatives. A key focus of our study was the effect of Ruthenibacterium lactatiformans, which was highly increased during CF and exhibited a strong correlation with fat metabolic indicators. This bacterium was found to mitigate high-fat diet-induced obesity, glucose intolerance, dyslipidemia, and intestinal barrier dysfunction in animal experiments. These effects suggest its potential as a probiotic candidate for the amelioration of dyslipidemia and for mediating the benefits of fasting on fat metabolism.<br><br>CONCLUSIONS: Our pilot study suggests that alterations in gut microbiota during CF contribute to the shift of energy metabolic substrate and the establishment of a novel homeostatic state during prolonged fasting.}, }
@article {pmid39796301, year = {2024}, author = {Galazka, S and Vigl, V and Kuffner, M and Dielacher, I and Spettel, K and Kriz, R and Kreuzinger, N and Vierheilig, J and Woegerbauer, M}, title = {Prevalence of Antibiotic Resistance Genes in Differently Processed Smoothies and Fresh Produce from Austria.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39796301}, issn = {2304-8158}, support = {BMASGK-74602/0005-IX/B/15/2019//Austrian Federal Ministry of Social Affairs, Health, Care and Consumer Protection (BMASGK)/ ; }, abstract = {Plant-derived foods are potential vehicles for microbial antibiotic resistance genes (ARGs), which can be transferred to the human microbiome if consumed raw or minimally processed. The aim of this study was to determine the prevalence and the amount of clinically relevant ARGs and mobile genetic elements (MGEs) in differently processed smoothies (freshly prepared, cold-pressed, pasteurized and high-pressure processed) and fresh produce samples (organically and conventionally cultivated) to assess potential health hazards associated with their consumption. The MGE ISPps and the class 1 integron-integrase gene intI1 were detected by probe-based qPCR in concentrations up to 10[4] copies/mL in all smoothies, lettuce, carrots and a single tomato sample. The highest total (2.2 × 10[5] copies/mL) and the most diverse ARG and MGE loads (16/26 targets) were observed in freshly prepared and the lowest prevalences (5/26) and concentrations (4.1 × 10[3] copies/mL) in high-pressure-processed (HPP) smoothies. BlaCTX-M-1-15 (1.2 × 10[5] c/mL) and strB (6.3 × 10[4] c/mL) were the most abundant, and qacEΔ1 (95%), blaTEM1 (85%), ermB and sul1 (75%, each) were the most prevalent ARGs. QnrS, vanA, sat-4, blaKPC, blaNDM-1 and blaOXA-10 were never detected. HPP treatment reduced the microbial loads by ca. 5 logs, also destroying extracellular DNA potentially encoding ARGs that could otherwise be transferred by bacterial transformation. The bacterial microbiome, potential pathogens, bacterial ARG carriers and competent bacteria able to take up ARGs were identified by Illumina 16S rRNA gene sequencing. To reduce the risk of AMR spread from smoothies, our data endorse the application of DNA-disintegrating processing techniques such as HPP.}, }
@article {pmid39794144, year = {2025}, author = {Lan, P and Zhang, ZJ and He, Z}, title = {[Progress in the study of the surgical management of Crohn disease based on the mesenteric concept].}, journal = {Zhonghua wai ke za zhi [Chinese journal of surgery]}, volume = {63}, number = {2}, pages = {107-113}, doi = {10.3760/cma.j.cn112139-20240331-00155}, pmid = {39794144}, issn = {0529-5815}, support = {2022YFA1304000//National Key R&amp;D Program of China/ ; U21A20344//Key Joint Project of National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Crohn Disease/surgery ; *Mesentery/surgery ; Anastomosis, Surgical ; }, abstract = {In recent years, with the deepening of mesentery research, it is found that its blood vessels, nerves, lymphoid tissue, adipose tissue and other structures play an important role in the occurrence and development of Crohn disease, and the degree of lesion is related with the disease process, surgical difficulty, the occurrence of intraoperative complications and postoperative recurrence. The optimal surgical strategy of Crohn disease based on mesenteric involvement has received great attention. Multiple retrospective studies found that extended mesenteric resection and Kono-S anastomosis potentially could reduce the rate of postoperative recurrence. However, the latest prospective randomized controlled studies did not achieve the expected results, and the evidence for the surgical strategy based on mesentery is still weak. This review summarises the findings of basic and clinical investigations of the mesentery in Crohn disease so far and explores its role in surgical treatment optimization, and provides new thinking and insights for the further research and surgical options for Crohn disease.}, }
@article {pmid39793044, year = {2025}, author = {Putumbaka, S and Schut, GJ and Thorgersen, MP and Poole, FL and Shao, N and Rodionov, DA and Adams, MWW}, title = {Tungsten is utilized for lactate consumption and SCFA production by a dominant human gut microbe Eubacterium limosum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {122}, number = {1}, pages = {e2411809121}, pmid = {39793044}, issn = {1091-6490}, support = {R01 GM136885/GM/NIGMS NIH HHS/United States ; }, mesh = {*Eubacterium/metabolism/genetics ; Humans ; *Gastrointestinal Microbiome/physiology ; *Lactic Acid/metabolism ; *Tungsten/metabolism ; *Fatty Acids, Volatile/metabolism ; Bacterial Proteins/metabolism/genetics ; Gene Expression Regulation, Bacterial ; }, abstract = {Eubacterium limosum is a dominant member of the human gut microbiome and produces short-chain fatty acids (SCFAs). These promote immune system function and inhibit inflammation, making this microbe important for human health. Lactate is a primary source of gut SCFAs but its utilization by E. limosum has not been explored. We show that E. limosum growing on lactate takes up added tungstate rather than molybdate and produces the SCFAs acetate and butyrate, but not propionate. The genes encoding an electron bifurcating, tungsten-containing oxidoreductase (WOR1) and a tungsten-containing formate dehydrogenase (FDH), along with an electron bifurcating lactate dehydrogenase (LCT), lactate permease, and enzymes of the propanediol pathway, are all up-regulated on lactate compared to growth on glucose. Lactate metabolism is controlled by a GntR-family repressor (LctR) and two global regulators, Rex and CcpA, where Rex in part controls W storage and tungstopyranopterin (Tuco) biosynthesis. Tuco-dependent riboswitches, along with CcpA, also control two iron transporters, consistent with the increased iron demand for many iron-containing enzymes, including WOR1 and FDH, involved in SCFA production. From intracellular aldehyde concentrations and the substrate specificity of WOR1, we propose that WOR1 is involved in detoxifying acetaldehyde produced during lactate degradation. Lactate to SCFA conversion by E. limosum is clearly highly tungstocentric and tungsten might be an overlooked micronutrient in the human microbiome and in overall human health.}, }
@article {pmid39792309, year = {2025}, author = {Wang, P and Xia, P and Gao, S and Shi, W and Zhang, X}, title = {Critical Structures of Bisphenol Analogues on Embryonic Toxicity Identified by a Computational Approach.}, journal = {Environmental science &amp; technology}, volume = {59}, number = {3}, pages = {1553-1564}, doi = {10.1021/acs.est.4c10012}, pmid = {39792309}, issn = {1520-5851}, mesh = {Animals ; Zebrafish ; *Phenols/toxicity ; *Benzhydryl Compounds/toxicity ; Embryo, Nonmammalian/drug effects ; Bisphenol A Compounds ; }, abstract = {Safer chemical alternatives to bisphenol (BP) have been a major pursuit of modern green chemistry and toxicology. Using a chemical similarity-based approach, it is difficult to identify minor structural differences that contribute to the significant changes of toxicity. Here, we used omics and computational toxicology to identify chemical features associated with BP analogue-induced embryonic toxicity, offering valuable insights to inform the design of safer chemical alternatives. The zebrafish embryonic acute toxicity, behavioral effects, and concentration-dependent transcriptome analysis of 17 BP analogues were tested, and the chemical structure characteristics and key biological activities-induced embryonic toxicity were explored. BPE, BPF, BPP, BPBP, and BPS induced lower embryonic lethality than BPA. And, 8 BP analogues triggered hyperactive behavior at environmentally and human relevant concentrations. BP analogues with phenol rings linked via hydrophobic segments ("chain:alkaneBranch_neopentyl_C5") disturbed stress response, leading to embryonic lethality, and introducing hydrophobic groups on the meta position of bisphenol structure augmented their embryonic lethality effects. "3DACorr_TotChg_3" of BP analogues is a key physicochemical feature for behavioral disorders, and BP analogues with 3DACorr_TotChg_3 value < 0.11 could induce hyperactive behavior by perturbing neurodevelopment relevant biological pathways. This study provides an integrated strategy, combining data-driven profiling and mechanism-based analysis for safer chemical alternatives.}, }
@article {pmid39791890, year = {2025}, author = {Soborowski, AL and Hackley, RK and Hwang, S and Zhou, G and Dulmage, KA and Schönheit, P and Daniels, C and Bisson-Filho, AW and Marchfelder, A and Maupin-Furlow, JA and Allers, T and Schmid, AK}, title = {Genomic re-sequencing reveals mutational divergence across genetically engineered strains of model archaea.}, journal = {mSystems}, volume = {10}, number = {2}, pages = {e0108424}, pmid = {39791890}, issn = {2379-5077}, support = {1651117//National Science Foundation (NSF)/ ; 1936024//National Science Foundation (NSF)/ ; //Pew Charitable Trusts (PCT)/ ; }, mesh = {*Genome, Archaeal ; *Mutation ; *Haloferax volcanii/genetics ; *Halobacterium salinarum/genetics ; Genomics/methods ; Whole Genome Sequencing ; Genetic Engineering ; Archaea/genetics ; Genetic Variation ; }, abstract = {UNLABELLED: Archaeal molecular biology has been a topic of intense research in recent decades as their role in global ecosystems, nutrient cycles, and eukaryotic evolution comes to light. The hypersaline-adapted archaeal species Halobacterium salinarum and Haloferax volcanii serve as important model organisms for understanding archaeal genomics, genetics, and biochemistry, in part because efficient tools enable genetic manipulation. As a result, the number of strains in circulation among the haloarchaeal research community has increased in recent decades. However, the degree of genetic divergence and effects on genetic integrity resulting from the creation and inter-lab transfer of novel lab stock strains remain unclear. To address this, we performed whole-genome re-sequencing on a cross-section of wild-type, parental, and knockout strains in both model species. Integrating these data with existing repositories of re-sequencing data, we identify mutations that have arisen in a collection of 60 strains, sampled from two species across eight different labs. Independent of sequencing, we construct strain lineages, identifying branch points and significant genetic events in strain history. Combining this with our sequencing data, we identify small clusters of mutations that definitively separate lab strains. Additionally, an analysis of gene knockout strains suggests that roughly one in three strains currently in use harbors second-site mutations of potential phenotypic impact. Overall, we find that divergence among lab strains is thus far minimal, though as the archaeal research community continues to grow, careful strain provenance and genomic re-sequencing are required to keep inter-lab divergence to a minimum, prevent the compounding of mutations into fully independent lineages, and maintain the current high degree of reproducible research between lab groups.<br><br>IMPORTANCE: Archaea are a domain of microbial life whose member species play a critical role in the global carbon cycle, climate regulation, the human microbiome, and persistence in extreme habitats. In particular, hypersaline-adapted archaea are important, genetically tractable model organisms for studying archaeal genetics, genomics, and biochemistry. As the archaeal research community grows, keeping track of the genetic integrity of strains of interest is necessary. In particular, routine genetic manipulations and the common practice of sharing strains between labs allow mutations to arise in lab stocks. If these mutations affect cellular processes, they may jeopardize the reproducibility of work between research groups and confound the results of future studies. In this work, we examine DNA sequences from 60 strains across two species of archaea. We identify shared and unique mutations occurring between and within strains. Independently, we trace the lineage of each strain, identifying which genetic manipulations lead to observed off-target mutations. While overall divergence across labs is minimal so far, our work highlights the need for labs to continue proper strain husbandry.}, }
@article {pmid39789171, year = {2025}, author = {Barman, I and Seo, H and Kim, S and Rahim, MA and Yoon, Y and Hossain, MS and Shuvo, MSH and Song, HY}, title = {Isolation of New Strains of Lactic Acid Bacteria from the Vaginal Microbiome of Postmenopausal Women and their Probiotic Characteristics.}, journal = {Current microbiology}, volume = {82}, number = {2}, pages = {76}, pmid = {39789171}, issn = {1432-0991}, support = {20018499//Ministry of Trade, Industry and Energy/ ; RS-2023-00219563//Ministry of Science and ICT, South Korea/ ; Soon Chun Hyang University Research Fund//Soon Chun Hyang University/ ; }, mesh = {Female ; *Probiotics ; Humans ; *Vagina/microbiology ; *Lactobacillales/genetics/isolation &amp; purification/classification/metabolism ; *Postmenopause ; Bacterial Adhesion ; Microbial Sensitivity Tests ; Microbiota ; Anti-Bacterial Agents/pharmacology ; Cytokines/metabolism ; Macrophages/microbiology ; }, abstract = {Lactic acid bacteria (LAB), traditionally consumed as fermented foods, are now being applied to the medical field beyond health-functional food as probiotics. Therefore, it is necessary to continuously discover and evaluate new strains with suitable probiotic characteristics, mainly focusing on safety. In this study, we isolated eight new strains from postmenopausal vaginal fluid using culturomics approaches, an emerging area of interest. Data showed that most strains possessed significant cell surface hydrophobicity (≥ 76%), auto-aggregation capacity (17 to 61%), strong adhesion activity (8 to 34%), and excellent resistance to gastric acid, bile salt, and digestive enzyme, enhancing their survival in the gastrointestinal tract. Moreover, the strains exhibited functional characteristics, including substantial antibacterial activity with a minimal inhibitory concentration (MIC) ranging from 12.5 to 50%. They also harbored bacteriocins genes, produced short-chain fatty acids (acetate and propionate), exhibited significant phagocytic activity, possessed high antioxidative properties, rapidly depleted sodium nitrite, and exhibited proteolysis and β-glucosidase activity. In addition, heat-killed LAB strains significantly reduced the gene expressions of proinflammatory cytokines such as IL-β, IL-6, and iNOS in macrophages. Safety assessment revealed no cytotoxicity in macrophage cell lines. All strains tested negative for biogenic amine or H2O2 production, displayed no gelatinase or hemolytic activity, lacked virulence genes or detrimental enzymes, and displayed antibiotic susceptibility. In summary, these newly isolated strains demonstrate excellent probiotic functionality with a strong focus on safety, making them promising candidates for future drug development in the relevant fields.}, }
@article {pmid39788169, year = {2025}, author = {Xu, B and Luo, Z and Niu, X and Li, Z and Lu, Y and Li, J}, title = {Fungi, immunosenescence and cancer.}, journal = {Seminars in cancer biology}, volume = {109}, number = {}, pages = {67-82}, doi = {10.1016/j.semcancer.2025.01.002}, pmid = {39788169}, issn = {1096-3650}, mesh = {Humans ; *Neoplasms/immunology/microbiology/pathology/therapy/etiology ; *Immunosenescence/immunology ; Tumor Microenvironment/immunology ; *Fungi/immunology/pathogenicity ; Animals ; Microbiota/immunology ; }, abstract = {Fungal microbes are a small but immunoreactive component of the human microbiome, which may influence cancer development, progression and therapeutic response. Immunosenescence is a process of immune dysfunction that occurs with aging, including lymphoid organ remodeling, contributing to alterations in the immune system in the elderly, which plays a critical role in many aspects of cancer. There is evidence for the interactions between fungi and immunosenescence in potentially regulating cancer progression and remodeling the tumor microenvironment (TME). In this review, we summarize potential roles of commensal and pathogenic fungi in modulating cancer-associated processes and provide more-detailed discussions on the mechanisms of which fungi affect tumor biology, including local and distant regulation of the TME, modulating antitumor immune responses and interactions with neighboring bacterial commensals. We also delineate the features of immunosenescence and its influence on cancer development and treatment, and highlight the interactions between fungi and immunosenescence in cancer. We discuss the prospects and challenges for harnessing fungi and immunosenescence in cancer diagnosis and/or treatment. Considering the limited understanding and techniques in conducting such research, we also provide our view on how to overcome challenges faced by the exploration of fungi, immunosenescence and their interactions on tumor biology.}, }
@article {pmid39788158, year = {2025}, author = {Theodosiou, AA and Fady, PE and Bennett, N and Read, RC and Bogaert, D and Jones, CE}, title = {Microbiotoxicity: A call to arms for cross-sector protection of the human microbiome.}, journal = {The Journal of infection}, volume = {90}, number = {2}, pages = {106408}, doi = {10.1016/j.jinf.2025.106408}, pmid = {39788158}, issn = {1532-2742}, }
@article {pmid39775305, year = {2025}, author = {Xu, Y and Wang, Z and Li, C and Tian, S and Du, W}, title = {Droplet microfluidics: unveiling the hidden complexity of the human microbiome.}, journal = {Lab on a chip}, volume = {25}, number = {5}, pages = {1128-1148}, doi = {10.1039/d4lc00877d}, pmid = {39775305}, issn = {1473-0189}, mesh = {Humans ; *Microbiota ; *Microfluidic Analytical Techniques/instrumentation ; *Microfluidics ; *Lab-On-A-Chip Devices ; Single-Cell Analysis ; }, abstract = {The human body harbors diverse microbial communities essential for maintaining health and influencing disease processes. Droplet microfluidics, a precise and high-throughput platform for manipulating microscale droplets, has become vital in advancing microbiome research. This review introduces the foundational principles of droplet microfluidics, its operational capabilities, and wide-ranging applications. We emphasize its role in enhancing single-cell sequencing technologies, particularly genome and RNA sequencing, transforming our understanding of microbial diversity, gene expression, and community dynamics. We explore its critical function in isolating and cultivating traditionally unculturable microbes and investigating microbial activity and interactions, facilitating deeper insight into community behavior and metabolic functions. Lastly, we highlight its broader applications in microbial analysis and its potential to revolutionize human health research by driving innovations in diagnostics, therapeutic development, and personalized medicine. This review provides a comprehensive overview of droplet microfluidics' impact on microbiome research, underscoring its potential to transform our understanding of microbial dynamics and their relevance to health and disease.}, }
@article {pmid39770796, year = {2024}, author = {Enderlin, D and Bieri, U and Gadient, J and Morsy, Y and Scharl, M and Rüschoff, JH and Hefermehl, LJ and Nikitin, A and Langenauer, J and Engeler, DS and Förster, B and Obrecht, F and Surber, J and Scherer, TP and Eberli, D and Poyet, C}, title = {Towards Reliable Methodology: Microbiome Analysis of Fresh Frozen vs. Formalin-Fixed Paraffin-Embedded Bladder Tissue Samples: A Feasibility Study.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, pmid = {39770796}, issn = {2076-2607}, support = {KFS-5308-02-2021-R//the Swiss Cancer Research foundation/ ; }, abstract = {Studies have shown that the human microbiome influences the response to systemic immunotherapy. However, only scarce data exist on the impact of the urinary microbiome on the response rates of bladder cancer (BC) to local Bacillus Calmette-Guérin instillation therapy. We launched the prospective SILENT-EMPIRE study in 2022 to address this question. We report the results of the pilot study of SILENT-EMPIRE, which aimed to compare the microbiome between fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) samples in the cancerous tissue and adjacent healthy tissue of BC patients. Our results show that alpha diversity is increased in FF samples compared to FFPE (coverage index p = 0.041, core abundance index p = 0.008). No significant differences concerning alpha diversity could be detected between cancerous and non-cancerous tissue in the same BC patients. This study demonstrates that microbiome analysis from both FF and FFPE samples is feasible. Implementing this finding could aid in the translation of research findings into clinical practice.}, }
@article {pmid39770627, year = {2024}, author = {Ricchezze, G and Buratti, E and De Micco, F and Cingolani, M and Scendoni, R}, title = {Medico-Legal Applications of the Human Microbiome and Critical Issues Due to Environmental Transfer: A Review.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, pmid = {39770627}, issn = {2076-2607}, support = {ECS00000041 - VITALITY - CUP n&#xb0; D83C22000710005//European Union - NextGenerationEU under the Italian Ministry of University and Research (MUR) National Innovation Ecosystem/ ; }, abstract = {Microbiome has recently seen an increase in its forensic applications. It could be employed to identify a suspect when DNA is not available; it can be used to establish postmortem interval (PMI). Furthermore, it could prove to be fundamental in cases of sexual assault. One of the most interesting aspects to study is how microbiomes are transferred. The aim of this review is to analyze the existing literature focusing on the potential transfer of microbiome from humans to environment. Searches on PubMed, Scopus, and Web of Science identified a total of 348 articles. Furthermore, from the bibliographies of the included articles, an additional publication was selected, in accordance with the established inclusion and exclusion criteria. This study has shown the potential of utilizing microbiomes as trace evidence, particularly in connecting individuals to specific environments or objects. However, the variability and dynamics of microbial transfer and persistence need to be carefully addressed.}, }
@article {pmid39763928, year = {2024}, author = {Glowacki, RWP and Engelhart, MJ and Till, JM and Kadam, A and Nemet, I and Sangwan, N and Ahern, PP}, title = {Identification of strain-specific cues that regulate biofilm formation in Bacteroides thetaiotaomicron.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.12.20.629428}, pmid = {39763928}, issn = {2692-8205}, abstract = {UNLABELLED: Members of the gut microbiome encounter a barrage of host- and microbe-derived microbiocidal factors that must be overcome to maintain fitness in the intestine. The long-term stability of many gut microbiome strains within the microbiome suggests the existence of strain-specific strategies that have evolved to foster resilience to such insults. Despite this, little is known about the mechanisms that mediate this resistance. Biofilm formation represents one commonly employed defense strategy against stressors like those found in the intestine. Here, we demonstrate strain-level variation in the capacity of the gut symbiont Bacteroides thetaiotaomicron to form biofilms. Despite the potent induction of biofilm formation by purified bile in most strains, we show that the specific bile acid species driving biofilm formation differ among strains, and uncover that a secondary bile-acid, lithocholic acid, and its conjugated forms, potently induce biofilm formation in a strain-specific manner. Additionally, we found that the short-chain fatty acid, acetic acid, could suppress biofilm formation. Thus, our data defines the molecular components of bile that promote biofilm formation in B. thetaiotaomicron and reveals that distinct molecular cues trigger the induction or inhibition of this process. Moreover, we uncover strain-level variation in these responses, thus identifying that both shared and strain-specific determinants govern biofilm formation in this species.<br><br>IMPORTANCE: In order to thrive within the intestine, it is imperative that gut microbes resist the multitude of insults derived from the host immune system and other microbiome members. As such, they have evolved strategies that ensure their survival within the intestine. We investigated one such strategy, biofilm formation, in Bacteroides thetaiotaomicron , a common member of the human microbiome. We uncovered significant variation in natural biofilm formation in the absence of an overt stimulus among different Bacteroides thetaiotaomicron strains, and revealed that different strains adopted a biofilm lifestyle in response to distinct molecular stimuli. Thus our studies provide novel insights into factors mediating gut symbiont resiliency, revealing strain-specific and shared strategies in these responses. Collectively, our findings underscore the prevalence of strain-level differences that should be factored into our understanding of gut microbiome functions.}, }
@article {pmid39757039, year = {2025}, author = {Cruz-Lebrón, A and Faiez, TS and Hess, MM and Sfanos, KS}, title = {Diet and the microbiome as mediators of prostate cancer risk, progression, and therapy response.}, journal = {Urologic oncology}, volume = {43}, number = {4}, pages = {209-220}, doi = {10.1016/j.urolonc.2024.12.001}, pmid = {39757039}, issn = {1873-2496}, mesh = {Humans ; Male ; *Prostatic Neoplasms/microbiology/therapy/etiology/pathology ; Disease Progression ; *Diet ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Complex relationships between the human microbiome and cancer are increasingly recognized for cancer sites that harbor commensal microbial communities such as the gut, genitourinary tract, and skin. For organ sites that likely do not contain commensal microbiota, there is still a substantial capacity for the human-associated microbiota to influence disease etiology across the cancer spectrum. We propose such a relationship for prostate cancer, the most commonly diagnosed cancer in males in the United States. This review explores the current evidence for a role for the urinary and gut microbiota in prostate cancer risk, via both direct interactions (prostate infections) and long-distance interactions such as via the metabolism of procarcinogenic or anticarcinogenic dietary metabolites. We further explore a newly recognized role of the gut microbiota in mediating cancer treatment response or resistance either via production of androgens and/or procarcinogenic metabolites or via direct metabolism of anticancer drugs that are used to treat advanced disease. Overall, we present the current state of knowledge relating to how the human microbiome mediates prostate cancer risk, progression, and therapy response, as well as suggest future research directions for the field.}, }
@article {pmid39754316, year = {2025}, author = {Peng, S and Wu, M and Yan, Q and Xu, G and Xie, Y and Tang, G and Lin, J and Yuan, Z and Liang, X and Yuan, Z and Weng, J and Bai, L and Wang, X and Yu, H and Huang, M and Luo, Y and Liu, X}, title = {Disrupting EDEM3-induced M2-like macrophage trafficking by glucose restriction overcomes resistance to PD-1/PD-L1 blockade.}, journal = {Clinical and translational medicine}, volume = {15}, number = {1}, pages = {e70161}, pmid = {39754316}, issn = {2001-1326}, support = {82372715//National Natural Science Foundation of China/ ; 82173067//National Natural Science Foundation of China/ ; 82272965//National Natural Science Foundation of China/ ; 2024A1515030054//Natural Science Foundation of Guangdong Province/ ; 2022A1515012656//Natural Science Foundation of Guangdong Province/ ; 2018026//Project 5010 of Clinical Medical Research of Sun Yat-sen University-5010 Cultivation Foundation/ ; 2025A04J4447//Science and Technology Program of Guangzhou/ ; 202201011004//Science and Technology Program of Guangzhou/ ; 2022JBGS07//Scientific Research Project of the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; P20150227202010251//Talent Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; R2021217202512965//Excellent Talent Training Project of the Sixth Affiliated Hospital of Sun Yat-sen University/ ; 1010CG(2022)-02//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research-'1010' Program/ ; 1010CG(2022)-03//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research-'1010' Program/ ; 1010PY(2022)-10)//Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research-'1010' Program/ ; 23ykbj007//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; //Program of Introducing Talents of Discipline to Universities/ ; //National Key Clinical Discipline/ ; }, mesh = {Humans ; Mice ; *Glucose/metabolism ; Animals ; Macrophages/metabolism/immunology/drug effects ; B7-H1 Antigen/metabolism/antagonists &amp; inhibitors ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Colorectal Neoplasms/drug therapy/immunology/metabolism ; Drug Resistance, Neoplasm/drug effects ; Membrane Proteins/metabolism ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/metabolism/immunology ; }, abstract = {BACKGROUND: Immunotherapy is beneficial for some colorectal cancer (CRC) patients, but immunosuppressive networks limit its effectiveness. Cancer-associatedfibroblasts (CAFs) are significant in immune escape and resistance toimmunotherapy, emphasizing the urgent need for new treatment strategies.<br><br>METHODS: Flow cytometric, Western blotting, proteomics analysis, analysis of public database data, genetically modified cell line models, T cell coculture, crystal violetstaining, ELISA, metabonomic and clinical tumour samples were conducted to assess the role of EDEM3 in immune escape and itsmolecular mechanisms. We evaluated theeffects of FMD plus 2-DG on antitumour immunity using multipleximmunofluorescence, flow cytometry, cytokine profiling, TUNEL assays, xenografttumours, and in vivo studies.<br><br>RESULTS: We show thatCAFs upregulate PD-L1 glycosylation and contribute to immune evasion byglycosyltransferase EDEM3. Additionally, EDEM3 plays a role in tumour immunityduring tumour progression. However, the EDEM3-mediated upregulation of PD-L1 expression underpins PD-1/PD-L1 blockade resistance in vivo. This finding contradictsthe previous trend that positive PD-L1 expression indicates a strong responseto PD-1/PD-L1 blockade. Mechanistically, high-EDEM3 expression facilitates M2-like This finding contradictsthe previous trend that positive PD-L1 expression indicates a strong responseto PD-1/PD-L1 blockade.Mechanistically, polarizationand chemotactic migration of macrophages, which are enriched in theperipheral region of tumours compared to thecore region, precluding access of CD8+ T cells to tumourfoci. Furthermore, we EDEM3 predominantly activates the recruited M2-like macrophagesvia a glucose metabolism-dependent mechanism. Manipulationof glucose utilization by a fasting-mimicking diet(FMD) plus 2-DG treatmentsynergistically with PD-1 antibody elicits potent antitumour activity byeffectively decreasing tumour glycosylated PD-L1 expression, augmenting the CD8+effector T cell infiltration and activation while concurrently reducing the infiltration.TheCAFs-EDEM3-M2-like macrophage axis plays a critical role in promotingimmunotherapy resistance. infiltration.TheCAFs-EDEM3-M2-like macrophage axis plays a critical role in promotingimmunotherapy resistance.<br><br>CONCLUSIONS: Our study suggests that blocking EDEM3-induced M2-like macro phage trafficking by FMD plus 2-DG is a promising and effective strategy to overcomeresistance to checkpoint blockade therapy offeringhope for improved treatment outcomes.<br><br>KEY POINTS: Cancer-associated fibroblasts (CAFs) can enhance PD-L1 glycosylation through the glycosyltransferase EDEM3, contributing to immune evasion during tumour progression. EDEM3 predominantly activates the recruit M2-like macrophages via a glucose metabolism-dependent mechanism. Blocking glucose utilization antagonizes recruiting and polarizing M2-like macrophages synergistically with PD-1 antibody to improve anticancer immunity.}, }
@article {pmid39747869, year = {2025}, author = {Wu, W and Zhao, Y and Cheng, X and Xie, X and Zeng, Y and Tao, Q and Yang, Y and Xiao, C and Zhang, Z and Pang, J and Jin, J and He, H and Lin, Y and Li, B and Ma, J and Ye, X and Lin, WJ}, title = {Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer's disease.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {63}, pmid = {39747869}, issn = {2041-1723}, support = {81972967//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82172526//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82272586//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32271068//National Natural Science Foundation of China (National Science Foundation of China)/ ; 202007030001//Guangzhou Science and Technology Program key projects/ ; 202007030001//Guangzhou Science and Technology Program key projects/ ; 202007030001//Guangzhou Science and Technology Program key projects/ ; }, mesh = {Animals ; *Alzheimer Disease/therapy/metabolism ; *Disease Models, Animal ; Mice ; *Mice, Transgenic ; *Aquaporin 4/metabolism/genetics ; *Memory Disorders/therapy/metabolism ; *Amyloid beta-Peptides/metabolism ; *Glymphatic System/metabolism ; Apathy ; Hippocampus/metabolism ; Male ; Light ; Humans ; }, abstract = {Alzheimer's disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer's disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy.}, }
@article {pmid39747694, year = {2025}, author = {Hsu, TY and Nzabarushimana, E and Wong, D and Luo, C and Beiko, RG and Langille, M and Huttenhower, C and Nguyen, LH and Franzosa, EA}, title = {Profiling lateral gene transfer events in the human microbiome using WAAFLE.}, journal = {Nature microbiology}, volume = {10}, number = {1}, pages = {94-111}, pmid = {39747694}, issn = {2058-5276}, support = {R24DK110499//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; K23DK125838//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; T32CA009001//U.S. Department of Health &amp; Human Services | NIH | National Cancer Institute (NCI)/ ; Career Development Award//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; U54DE023798//U.S. Department of Health &amp; Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; Research Scholars Award//American Gastroenterological Association (AGA)/ ; }, mesh = {Humans ; *Gene Transfer, Horizontal ; *Microbiota/genetics ; Phylogeny ; Metagenome/genetics ; Algorithms ; *Bacteria/genetics/classification ; Metagenomics/methods ; *Computational Biology/methods ; }, abstract = {Lateral gene transfer (LGT), also known as horizontal gene transfer, facilitates genomic diversification in microbial populations. While previous work has surveyed LGT in human-associated microbial isolate genomes, the landscape of LGT arising in personal microbiomes is not well understood, as there are no widely adopted methods to characterize LGT from complex communities. Here we developed, benchmarked and validated a computational algorithm (WAAFLE or Workflow to Annotate Assemblies and Find LGT Events) to profile LGT from assembled metagenomes. WAAFLE prioritizes specificity while maintaining high sensitivity for intergenus LGT. Applying WAAFLE to >2,000 human metagenomes from diverse body sites, we identified >100,000 high-confidence previously uncharacterized LGT (~2 per microbial genome-equivalent). These were enriched for mobile elements, as well as restriction-modification functions associated with the destruction of foreign DNA. LGT frequency was influenced by biogeography, phylogenetic similarity of involved pairs (for example, Fusobacterium periodonticum and F. nucleatum) and donor abundance. These forces manifest as networks in which hub taxa donate unequally with phylogenetic neighbours. Our findings suggest that human microbiome LGT may be more ubiquitous than previously described.}, }
@article {pmid39747692, year = {2025}, author = {Olm, MR and Spencer, SP and Takeuchi, T and Silva, EL and Sonnenburg, JL}, title = {Metagenomic immunoglobulin sequencing reveals IgA coating of microbial strains in the healthy human gut.}, journal = {Nature microbiology}, volume = {10}, number = {1}, pages = {112-125}, pmid = {39747692}, issn = {2058-5276}, support = {K08DK134856//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; K08 DK134856/DK/NIDDK NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; S10 OD026831/OD/NIH HHS/United States ; F32 DK128865/DK/NIDDK NIH HHS/United States ; DP1AT009892//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; T32DK007056//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; DP1 AT009892/AT/NCCIH NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; F32DK128865//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, mesh = {Humans ; *Immunoglobulin A/genetics/immunology/metabolism ; *Gastrointestinal Microbiome/immunology/genetics ; Feces/microbiology ; *Metagenomics/methods ; *Bacteria/genetics/immunology/classification/isolation &amp; purification ; Healthy Volunteers ; Metagenome ; }, abstract = {IgA, the primary human antibody secreted from the gut mucosa, shapes the intestinal microbiota. Methodological limitations have hindered defining which microbial strains are targeted by IgA and the implications of binding. Here we develop a technique, metagenomic immunoglobulin sequencing (MIg-seq), that provides strain-level resolution of microbes coated by IgA and use it to determine IgA coating levels for 3,520 gut microbiome strains in healthy human faeces. We find that both health and disease-associated bacteria are targeted by IgA. Microbial genes are highly predictive of IgA binding levels; in particular, mucus degradation genes are correlated with high binding, and replication rates are significantly reduced for microbes bound by IgA. We demonstrate that IgA binding is more correlated with host immune status than traditional relative abundance measures of microbial community composition. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host-microbe interactions.}, }
@article {pmid39746827, year = {2025}, author = {Goldhawk, DE and Al, KF and Donnelly, SC and Varela-Mattatall, GE and Dassanayake, P and Gelman, N and Prato, FS and Burton, JP}, title = {Assessing microbiota in vivo: debugging with medical imaging.}, journal = {Trends in microbiology}, volume = {33}, number = {4}, pages = {408-420}, doi = {10.1016/j.tim.2024.12.001}, pmid = {39746827}, issn = {1878-4380}, mesh = {Humans ; *Microbiota/physiology ; Magnetic Resonance Imaging/methods ; *Molecular Imaging/methods ; Tomography, X-Ray Computed/methods ; Animals ; Positron-Emission Tomography/methods ; Host Microbial Interactions ; }, abstract = {The microbiota is integral to human health and has been mostly characterized through various ex vivo 'omic'-based approaches. To better understand the real-time function and impact of the microbiota, in vivo molecular imaging is required. With technologies such as positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT), insight into microbiological processes may be coupled to in vivo information. Noninvasive imaging enables longitudinal tracking of microbes and their components in real time; mapping of microbiota biodistribution, persistence and migration; and simultaneous monitoring of host physiological responses. The development of molecular imaging for clinical translation is an interdisciplinary science, with broad implications for deeper understanding of host-microbe interactions and the role(s) of the microbiome in health and disease.}, }
@article {pmid39740900, year = {2025}, author = {Palkovsky, M and Modrackova, N and Neuzil-Bunesova, V and Liberko, M and Soumarova, R}, title = {The Bidirectional Impact of Cancer Radiotherapy and Human Microbiome: Microbiome as Potential Anti-tumor Treatment Efficacy and Toxicity Modulator.}, journal = {In vivo (Athens, Greece)}, volume = {39}, number = {1}, pages = {37-54}, pmid = {39740900}, issn = {1791-7549}, mesh = {Humans ; *Neoplasms/radiotherapy/microbiology ; *Gastrointestinal Microbiome/radiation effects/drug effects ; *Microbiota/radiation effects ; Radiotherapy/adverse effects/methods ; Treatment Outcome ; }, abstract = {Microbiome and radiotherapy represent bidirectionally interacting entities. The human microbiome has emerged as a pivotal modulator of the efficacy and toxicity of radiotherapy; however, a reciprocal effect of radiotherapy on microbiome composition alterations has also been observed. This review explores the relationship between the microbiome and extracranial solid tumors, particularly focusing on the bidirectional impact of radiotherapy on organ-specific microbiome. This article aims to provide a systematic review on the radiotherapy-induced microbial alteration in-field as well as in distant microbiomes. In this review, particular focus is directed to the oral and gut microbiome, its role in the development and progression of cancer, and how it is altered throughout radiotherapy. This review concludes with recommendations for future research, such as exploring microbiome modification to optimize radiotherapy-induced toxicities or enhance its anti-cancer effects.}, }
@article {pmid39738315, year = {2024}, author = {Ecklu-Mensah, G and Miller, R and Maseng, MG and Hawes, V and Hinz, D and Kim, C and Gilbert, JA}, title = {Modulating the human gut microbiome and health markers through kombucha consumption: a controlled clinical study.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31647}, pmid = {39738315}, issn = {2045-2322}, support = {S10 OD026929/OD/NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Biomarkers ; Diet, Western/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome ; Probiotics/administration &amp; dosage ; Kombucha Tea ; Cholesterol, HDL/blood ; Insulin Resistance ; Inflammation ; }, abstract = {Fermented foods are becoming more popular due to their purported links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a four-week kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n = 16) or control (n = 8) group. We collected longitudinal stool and blood samples to profile the human microbiome and inflammation markers. We did not observe significant changes in either biochemical parameters or levels of circulating markers of inflammation across the entire cohort. However, paired analysis between baseline and end of intervention time points within kombucha or control groups revealed increases in fasting insulin and in HOMA-IR in the kombucha group whereas reductions in HDL cholesterol were associated with the control group. Shotgun metagenomic analysis revealed the relative abundance of Weizmannia, a kombucha-enriched probiotic and several SCFA producing taxa to be overrepresented in consumers at the end of the intervention. Collectively, in our healthy cohort consuming a Western diet, a short-term kombucha intervention induced modest impacts on human gut microbiome composition and biochemical parameters, which may be attributed to relatively small number of participants and the extensive inter-participant variability.}, }
@article {pmid39735577, year = {2025}, author = {Monshizadeh, M and Hong, Y and Ye, Y}, title = {Multitask knowledge-primed neural network for predicting missing metadata and host phenotype based on human microbiome.}, journal = {Bioinformatics advances}, volume = {5}, number = {1}, pages = {vbae203}, pmid = {39735577}, issn = {2635-0041}, support = {R01 AI143254/AI/NIAID NIH HHS/United States ; }, abstract = {MOTIVATION: Microbial signatures in the human microbiome are closely associated with various human diseases, driving the development of machine learning models for microbiome-based disease prediction. Despite progress, challenges remain in enhancing prediction accuracy, generalizability, and interpretability. Confounding factors, such as host's gender, age, and body mass index, significantly influence the human microbiome, complicating microbiome-based predictions.<br><br>RESULTS: To address these challenges, we developed MicroKPNN-MT, a unified model for predicting human phenotype based on microbiome data, as well as additional metadata like age and gender. This model builds on our earlier MicroKPNN framework, which incorporates prior knowledge of microbial species into neural networks to enhance prediction accuracy and interpretability. In MicroKPNN-MT, metadata, when available, serves as additional input features for prediction. Otherwise, the model predicts metadata from microbiome data using additional decoders. We applied MicroKPNN-MT to microbiome data collected in mBodyMap, covering healthy individuals and 25 different diseases, and demonstrated its potential as a predictive tool for multiple diseases, which at the same time provided predictions for the missing metadata. Our results showed that incorporating real or predicted metadata helped improve the accuracy of disease predictions, and more importantly, helped improve the generalizability of the predictive models.<br><br>https://github.com/mgtools/MicroKPNN-MT.}, }
@article {pmid39732609, year = {2025}, author = {Tegegne, HA and Savidge, TC}, title = {Leveraging human microbiomes for disease prediction and treatment.}, journal = {Trends in pharmacological sciences}, volume = {46}, number = {1}, pages = {32-44}, pmid = {39732609}, issn = {1873-3735}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; T32 AI141349/AI/NIAID NIH HHS/United States ; R01 NR013497/NR/NINR NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 DK130517/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Computational Biology ; Metagenomics ; *Microbiota ; Precision Medicine/methods ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome consists of diverse microorganisms that inhabit various body sites. As these microbes are increasingly recognized as key determinants of health, there is significant interest in leveraging individual microbiome profiles for early disease detection, prevention, and drug efficacy prediction. However, the complexity of microbiome data, coupled with conflicting study outcomes, has hindered its integration into clinical practice. This challenge is partially due to demographic and technological biases that impede the development of reliable disease classifiers. Here, we examine recent advances in 16S rRNA and shotgun-metagenomics sequencing, along with bioinformatics tools designed to enhance microbiome data integration for precision diagnostics and personalized treatments. We also highlight progress in microbiome-based therapies and address the challenges of establishing causality to ensure robust diagnostics and effective treatments for complex diseases.}, }
@article {pmid39731160, year = {2024}, author = {Virtanen, S and Saqib, S and Kanerva, T and Ventin-Holmberg, R and Nieminen, P and Holster, T and Kalliala, I and Salonen, A}, title = {Metagenome-validated combined amplicon sequencing and text mining-based annotations for simultaneous profiling of bacteria and fungi: vaginal microbiota and mycobiota in healthy women.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {273}, pmid = {39731160}, issn = {2049-2618}, mesh = {Humans ; *Vagina/microbiology ; Female ; *RNA, Ribosomal, 16S/genetics ; *Fungi/genetics/classification/isolation &amp; purification ; *Bacteria/genetics/classification/isolation &amp; purification ; *Microbiota/genetics ; *Metagenome ; *Data Mining ; Metagenomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, DNA/methods ; Mycobiome ; Healthy Volunteers ; DNA, Bacterial/genetics ; }, abstract = {BACKGROUND: Amplicon sequencing of kingdom-specific tags such as 16S rRNA gene for bacteria and internal transcribed spacer (ITS) region for fungi are widely used for investigating microbial communities. So far most human studies have focused on bacteria while studies on host-associated fungi in health and disease have only recently started to accumulate. To enable cost-effective parallel analysis of bacterial and fungal communities in human and environmental samples, we developed a method where 16S rRNA gene and ITS1 amplicons were pooled together for a single Illumina MiSeq or HiSeq run and analysed after primer-based segregation. Taxonomic assignments were performed with Blast in combination with an iterative text-extraction-based filtration approach, which uses extensive literature records from public databases to select the most probable hits that were further validated by shotgun metagenomic sequencing.<br><br>RESULTS: Using 50 vaginal samples, we show that the combined run provides comparable results on bacterial composition and diversity to conventional 16S rRNA gene amplicon sequencing. The text-extraction-based taxonomic assignment-guided tool provided ecosystem-specific bacterial annotations that were confirmed by shotgun metagenomic sequencing (VIRGO, MetaPhlAn, Kraken2). Fungi were identified in 39/50 samples with ITS sequencing while in the metagenome data fungi largely remained undetected due to their low abundance and database issues. Co-abundance analysis of bacteria and fungi did not show strong between-kingdom correlations within the vaginal ecosystem of healthy women.<br><br>CONCLUSION: Combined amplicon sequencing for bacteria and fungi provides a simple and cost-effective method for simultaneous analysis of microbiota and mycobiota within the same samples. Conventional metagenomic sequencing does not provide sufficient fungal genome coverage for their reliable detection in vaginal samples. Text extraction-based annotation tool facilitates ecosystem-specific characterization and interpretation of microbial communities by coupling sequence homology to microbe metadata readily available through public databases. Video Abstract.}, }
@article {pmid39724786, year = {2025}, author = {Ma, X and Zhang, J and Jiang, Q and Li, YX and Yang, G}, title = {Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicry.}, journal = {EBioMedicine}, volume = {111}, number = {}, pages = {105516}, pmid = {39724786}, issn = {2352-3964}, mesh = {*Encephalomyelitis, Autoimmune, Experimental/immunology/etiology/metabolism/pathology ; Humans ; Animals ; *Molecular Mimicry ; Mice ; Myelin-Oligodendrocyte Glycoprotein/immunology/chemistry ; *Gastrointestinal Microbiome ; *Peptides/chemistry/immunology ; *Peptide Fragments/immunology/chemistry ; Disease Models, Animal ; Receptors, Antigen, T-Cell/metabolism ; Computational Biology/methods ; Histocompatibility Antigens Class II/metabolism ; Protein Binding ; *Microbiota ; CD4-Positive T-Lymphocytes/immunology/metabolism ; Multiple Sclerosis ; Dendritic Cells/immunology/metabolism ; Female ; }, abstract = {BACKGROUND: Gut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction.<br><br>METHODS: We employed bioinformatics methodologies to identify human microbial-derived peptides by analyzing their similarity to the MHC II-TCR binding patterns of self-antigens. Subsequently, we conducted a range of in&#xa0;vitro and in&#xa0;vivo assays to assess the encephalitogenic potential of these microbial-derived peptides.<br><br>FINDINGS: We analyzed 304,246 human microbiome genomes and 103 metagenomes collected from the MS cohort and identified 731 nonredundant analogs of myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Of note, half of these analogs could bind to MHC II and interact with TCR through structural modeling of the interaction using fine-tuned AlphaFold. Among the 8 selected peptides, the peptide (P3) shows the ability to activate MOG35-55-specific CD4[+] T cells in&#xa0;vitro. Furthermore, P3 shows encephalitogenic capacity and has the potential to induce EAE in some animals. Notably, mice immunized with a combination of P3 and MOG35-55 develop severe EAE. Additionally, dendritic cells could process and present P3 to MOG35-55-specific CD4[+] T cells and activate these cells.<br><br>INTERPRETATION: Our data suggests the potential involvement of a MOG35-55-mimic peptide derived from the gut microbiota as a molecular trigger of EAE pathogenesis. Our findings offer direct evidence of how microbes can initiate the development of EAE, suggesting a potential explanation for the correlation between certain gut microorganisms and MS prevalence.<br><br>FUNDING: National Natural Science Foundation of China (82371350 to GY).}, }
@article {pmid39723602, year = {2025}, author = {Ma, J and Palmer, DJ and Geddes, D and Lai, CT and Rea, A and Prescott, SL and D'Vaz, N and Stinson, LF}, title = {Maternal Allergic Disease Phenotype and Infant Birth Season Influence the Human Milk Microbiome.}, journal = {Allergy}, volume = {80}, number = {7}, pages = {1967-1981}, doi = {10.1111/all.16442}, pmid = {39723602}, issn = {1398-9995}, support = {//Medela/ ; //National Health and Medical Research Council/ ; //University of Western Australia/ ; //Telethon Kids Institute Ascend Fellowship/ ; }, mesh = {Adult ; Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; *Hypersensitivity/microbiology ; *Microbiota ; *Milk, Human/microbiology ; Phenotype ; RNA, Ribosomal, 16S/genetics ; *Seasons ; }, abstract = {Early infancy is a critical period for immune development. In addition to being the primary food source during early infancy, human milk also provides multiple bioactive components that shape the infant gut microbiome and immune system and provides a constant source of exposure to maternal microbiota. Given the potential interplay between allergic diseases and the human microbiome, this study aimed to characterise the milk microbiome of allergic mothers. Full-length 16S rRNA gene sequencing was performed on milk samples collected at 3 and 6 months postpartum from 196 women with allergic disease. Multivariate linear mixed models were constructed to identify the maternal, infant, and environmental determinants of the milk microbiome. Human milk microbiome composition and beta diversity varied over time (PERMANOVA R[2] = 0.011, p = 0.011). The season of infant birth emerged as the strongest determinant of the microbiome community structure (PERMANOVA R[2] = 0.014, p = 0.011) with impacts on five of the most abundant taxa. The milk microbiome also varied according to the type of maternal allergic disease (allergic rhinitis, asthma, atopic dermatitis, and food allergy). Additionally, infant formula exposure reduced the relative abundance of several typical oral taxa in milk. In conclusion, the milk microbiome of allergic mothers was strongly shaped by the season of infant birth, maternal allergic disease phenotype, and infant feeding mode. Maternal allergic disease history and infant season of birth should therefore be considered in future studies of infant and maternal microbiota. Trial Registration: ClinicalTrials.gov identifier: ACTRN12606000281594.}, }
@article {pmid39720963, year = {2024}, author = {Guha, SK and Niyogi, S}, title = {Microbial Dynamics in COVID-19: Unraveling the Impact of Human Microbiome on Disease Susceptibility and Therapeutic Strategies.}, journal = {Current microbiology}, volume = {82}, number = {1}, pages = {59}, pmid = {39720963}, issn = {1432-0991}, mesh = {Humans ; *COVID-19/microbiology/virology ; *SARS-CoV-2 ; *Microbiota ; *Dysbiosis/microbiology ; Disease Susceptibility ; Probiotics/therapeutic use ; Gastrointestinal Microbiome ; }, abstract = {This review explores the bidirectional relationship between the human microbiome and SARS-CoV-2 infection, elucidating its implications for COVID-19 susceptibility, severity, and therapeutic strategies. Metagenomic analyses reveal notable alterations in microbiome composition associated with SARS-CoV-2 infection, impacting disease severity and clinical outcomes. Dysbiosis within the respiratory, gastrointestinal, oral, and skin microbiomes exacerbates COVID-19 pathology through immune dysregulation and inflammatory pathways. Understanding these microbial shifts is pivotal for devising targeted therapeutic interventions. Notably, co-infection of oral pathogens with SARS-CoV-2 worsens lung pathology, while gut microbiome dysbiosis influences viral susceptibility and severity. Potential therapeutic approaches targeting the microbiome include probiotics, antimicrobial agents, and immunomodulatory strategies. This review underscores the importance of elucidating host-microbiota interactions to advance precision medicine and public health initiatives in combating COVID-19 and other infectious diseases.}, }
@article {pmid39717276, year = {2024}, author = {Zhou, Y and Jiang, M and Li, X and Shen, K and Zong, H and Lv, Q and Shen, B}, title = {Bibliometric and visual analysis of human microbiome-breast cancer interactions: current insights and future directions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1490007}, pmid = {39717276}, issn = {1664-302X}, abstract = {The composition of the gut microbiome differs from that of healthy individuals and is closely linked to the progression and development of breast cancer. Recent studies have increasingly examined the relationship between microbial communities and breast cancer. This study analyzed the research landscape of microbiome and breast cancer, focusing on 736 qualified publications from the Web of Science Core Collection (WoSCC). Publications in this field are on the rise, with the United States leading in contributions, followed by China and Italy. Despite this strong output, the centrality value of China in this field is comparatively low at ninth, highlighting a gap between the quantity of research and its global impact. This pattern is repetitively observed in institutional contributions, with a predominance of Western institutes among the top contributors, underscoring a potential research quality gap in China. Keyword analysis reveals that research hotspots are focused on the effect of microbiome on breast cancer pathogenesis and tumor metabolism, with risk factors and metabolic pathways being the most interesting areas. Publications point to a shift toward anti-tumor therapies and personalized medicine, with clusters such as "anti-tumor" and "potential regulatory agent" gaining prominence. Additionally, intratumor bacteria studies have emerged as a new area of significant interest, reflecting a new direction in research. The University of Helsinki and Adlercreutz H are influential institutions and researchers in this field. Current trends in microbiome and breast cancer research indicate a significant shift toward therapeutic applications and personalized medicine. Strengthening international collaborations and focusing on research quality is crucial for advancing microbiome and breast cancer research.}, }
@article {pmid39717208, year = {2025}, author = {Fallah, A and Sedighian, H and Kachuei, R and Fooladi, AAI}, title = {Human microbiome in post-acute COVID-19 syndrome (PACS).}, journal = {Current research in microbial sciences}, volume = {8}, number = {}, pages = {100324}, pmid = {39717208}, issn = {2666-5174}, abstract = {The global COVID-19 pandemic, which began in 2019, is still ongoing. SARS-CoV-2, also known as the severe acute respiratory syndrome coronavirus 2, is the causative agent. Diarrhea, nausea, and vomiting are common GI symptoms observed in a significant number of COVID-19 patients. Additionally, the respiratory and GI tracts express high level of transmembrane protease serine 2 (TMPRSS2) and angiotensin-converting enzyme-2 (ACE2), making them primary sites for human microbiota and targets for SARS-CoV-2 infection. A growing body of research indicates that individuals with COVID-19 and post-acute COVID-19 syndrome (PACS) exhibit considerable alterations in their microbiome. In various human disorders, including diabetes, obesity, cancer, ulcerative colitis, Crohn's disease, and several viral infections, the microbiota play a significant immunomodulatory role. In this review, we investigate the potential therapeutic implications of the interactions between host microbiota and COVID-19. Microbiota-derived metabolites and components serve as primary mediators of microbiota-host interactions, influencing host immunity. We discuss the various mechanisms through which these metabolites or components produced by the microbiota impact the host's immune response to SARS-CoV-2 infection. Additionally, we address confounding factors in microbiome studies. Finally, we examine and discuss about a range of potential microbiota-based prophylactic measures and treatments for COVID-19 and PACS, as well as their effects on clinical outcomes and disease severity.}, }
@article {pmid39714161, year = {2025}, author = {Neumann, CJ and Mohammadzadeh, R and Woh, PY and Kobal, T and Pausan, M-R and Shinde, T and Haid, V and Mertelj, P and Weiss, E-C and Kolovetsiou-Kreiner, V and Mahnert, A and Kumpitsch, C and Jantscher-Krenn, E and Moissl-Eichinger, C}, title = {First-year dynamics of the anaerobic microbiome and archaeome in infants' oral and gastrointestinal systems.}, journal = {mSystems}, volume = {10}, number = {1}, pages = {e0107124}, pmid = {39714161}, issn = {2379-5077}, support = {10.55776/KLI784 and 10.55776/DOC31//Austrian Science Fund (FWF)/ ; }, mesh = {Humans ; Infant ; *Mouth/microbiology ; *Gastrointestinal Microbiome ; *Archaea/classification/genetics/isolation &amp; purification ; Breast Feeding ; Female ; Male ; *Gastrointestinal Tract/microbiology ; Anaerobiosis ; *Microbiota ; Longitudinal Studies ; }, abstract = {UNLABELLED: Recent research provides new insights into the early establishment of the infant gut microbiome, emphasizing the influence of breastfeeding on the development of gastrointestinal microbiomes. In our study, we longitudinally examined the taxonomic and functional dynamics of the oral and gastrointestinal tract (GIT) microbiomes of healthy infants (n = 30) in their first year, focusing on the often-over-looked aspects, the development of archaeal and anaerobic microbiomes. Breastfed (BF) infants exhibit a more defined transitional phase in their oral microbiome compared to non-breastfed (NBF) infants, marked by a decrease in Streptococcus and the emergence of anaerobic genera such as Granulicatella. This phase, characterized by increased alpha-diversity and significant changes in beta-diversity, occurs earlier in NBF infants (months 1-3) than in BF infants (months 4-6), suggesting that breastfeeding supports later, more defined microbiome maturation. We demonstrated the presence of archaea in the infant oral cavity and GIT microbiome from early infancy, with Methanobrevibacter being the predominant genus. Still, transient patterns show that no stable archaeome is formed. The GIT microbiome exhibited gradual development, with BF infants showing increased diversity and complexity between the third and eighth months, marked by anaerobic microbial networks. NBF infants showed complex microbial co-occurrence patterns from the start. These strong differences between BF and NBF infants' GIT microbiomes are less pronounced on functional levels than on taxonomic levels. Overall, the infant microbiome differentiates and stabilizes over the first year, with breastfeeding playing a crucial role in shaping anaerobic microbial networks and overall microbiome maturation.<br><br>IMPORTANCE: The first year of life is a crucial period for establishing a healthy human microbiome. Our study analyses the role of archaea and obligate anaerobes in the development of the human oral and gut microbiome, with a specific focus on the impact of breastfeeding in this process. Our findings demonstrated that the oral and gut microbiomes of breastfed infants undergo distinct phases of increased dynamics within the first year of life. In contrast, the microbiomes of non-breastfed infants are more mature from the first month, leading to a steadier development without distinct transitional phases in the first year. Additionally, we found that archaeal signatures are present in infants under 1 year of age, but they do not form a stable archaeome. In contrast to this, we could track specific bacterial strains transitioning from oral to gut or persisting in the gut over time.}, }
@article {pmid39702789, year = {2025}, author = {Kaur, S and Patel, BCK and Collen, A and Malhotra, R}, title = {The microbiome and the eye: a new era in ophthalmology.}, journal = {Eye (London, England)}, volume = {39}, number = {3}, pages = {436-448}, pmid = {39702789}, issn = {1476-5454}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Eye Diseases/microbiology/therapy ; *Ophthalmology/trends ; *Eye/microbiology ; *Microbiota/physiology ; Fecal Microbiota Transplantation ; }, abstract = {The human microbiome has progressively been recognised for its role in various disease processes. In ophthalmology, complex interactions between the gut and distinct ocular microbiota within each structure and microenvironment of the eye has advanced our knowledge on the multi-directional relationships of these ecosystems. Increasingly, studies have shown that modulation of the microbiome can be achieved through faecal microbiota transplantation and synbiotics producing favourable outcomes for ophthalmic diseases. As ophthalmologists, we are obliged to educate our patients on measures to cultivate a healthy gut microbiome through a range of holistic measures. Further integrative studies combining microbial metagenomics, metatranscriptomics and metabolomics are necessary to fully characterise the human microbiome and enable targeted therapeutic interventions.}, }
@article {pmid39701818, year = {2025}, author = {Evans, SE and Valentine, ME and Gallimore, F and Meka, Y and Koehler, SI and Yu, HD and Valentovic, MA and Long, TE}, title = {Perturbations in the gut microbiome of C57BL/6 mice by the sobriety aid Antabuse® (disulfiram).}, journal = {Journal of applied microbiology}, volume = {136}, number = {1}, pages = {}, pmid = {39701818}, issn = {1365-2672}, support = {P20 GM103434/GM/NIGMS NIH HHS/United States ; R15 AI151970/AI/NIAID NIH HHS/United States ; AI151970//National Institute of Allergy and Infectious Diseases/ ; P20GM103434/NH/NIH HHS/United States ; }, mesh = {Animals ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; Mice ; Female ; *Feces/microbiology ; *Disulfiram/pharmacology ; Male ; *RNA, Ribosomal, 16S/genetics ; Microbial Sensitivity Tests ; Ileum/microbiology ; Cecum/microbiology ; Anti-Bacterial Agents/pharmacology ; Peptostreptococcus/drug effects/isolation &amp; purification ; Alcohol Deterrents/pharmacology ; Humans ; Bacteria, Anaerobic/drug effects/isolation &amp; purification ; Porphyromonas/drug effects/isolation &amp; purification ; Clostridium/drug effects/isolation &amp; purification ; Bacteroides/drug effects/isolation &amp; purification ; }, abstract = {AIMS: Disulfiram (Antabuse®) is an oral alcohol sobriety medication that exhibits antimicrobial activity against Gram-positive facultative anaerobes. The aims of this study were to measure the antimicrobial activity against anaerobic bacteria of the gut human microbiome and establish the extent that disulfiram alters the microbial composition of the ileum, cecum, and feces using C57BL/6 mice.<br><br>METHODS AND RESULTS: Antimicrobial susceptibility testing by the microdilution method revealed that disulfiram inhibits the in vitro growth of gut anaerobic species of Bacteroides, Clostridium, Peptostreptococcus, and Porphyromonas. Differential sequencing of 16S rRNA isolated from the ileum, cecum, and feces contents of treated vs. untreated mice showed that disulfiram enriches the Gram-negative enteric population. In female mice, the enrichment was greatest in the ileum, whereas the feces composition in male mice was the most heavily altered.<br><br>CONCLUSIONS: Daily administration of oral disulfiram depletes the enteric Gram-positive anaerobe population as predicted by the minimum inhibitory concentration data for isolates from the human gut microbiota.}, }
@article {pmid39699186, year = {2025}, author = {Lei, Y and Li, M and Zhang, H and Deng, Y and Dong, X and Chen, P and Li, Y and Zhang, S and Li, C and Wang, S and Tao, R}, title = {Comparative analysis of the human microbiome from four different regions of China and machine learning-based geographical inference.}, journal = {mSphere}, volume = {10}, number = {1}, pages = {e0067224}, pmid = {39699186}, issn = {2379-5042}, support = {2022YFC3302004//MOST | National Key Research and Development Program of China (NKPs)/ ; 2022D01C443//| Natural Science Foundation of Xinjiang Uygur Autonomous Region (Xinjiang Natural Science Foundation)/ ; //Visiting Research Fund for Teachers of Ordinary Undergraduate Universities in Shandong Province/ ; }, mesh = {Humans ; China ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; *Machine Learning ; *Bacteria/classification/genetics/isolation &amp; purification ; Nasal Cavity/microbiology ; Mouth/microbiology ; Skin/microbiology ; Female ; Male ; DNA, Bacterial/genetics/chemistry ; Adult ; Phylogeny ; Sequence Analysis, DNA ; Middle Aged ; Young Adult ; Hand/microbiology ; }, abstract = {The human microbiome, the community of microorganisms that reside on and inside the human body, is critically important for health and disease. However, it is influenced by various factors and may vary among individuals residing in distinct geographic regions. In this study, 220 samples, consisting of sterile swabs from palmar skin and oral and nasal cavities were collected from Chinese Han individuals living in Shanghai, Chifeng, Kunming, and Urumqi, representing the geographic regions of east, northeast, southwest, and northwest China. The full-length 16S rRNA gene of the microbiota in each sample was sequenced using the PacBio single-molecule real-time sequencing platform, followed by clustering the sequences into operational taxonomic units (OTUs). The analysis revealed significant differences in microbial communities among the four regions. Cutibacterium was the most abundant bacterium in palmar samples from Shanghai and Kunming, Psychrobacter in Chifeng samples, and Psychrobacillus in Urumqi samples. Additionally, Streptococcus and Staphylococcus were the dominant bacteria in the oral and nasal cavities. Individuals from the four regions could be distinguished and predicted based on a model constructed using the random forest algorithm, with the predictive effect of palmar microbiota being better than that of oral and nasal cavities. The prediction accuracy using hypervariable regions (V3-V4 and V4-V5) was comparable with that of using the entire 16S rRNA. Overall, our study highlights the distinctiveness of the human microbiome in individuals living in these four regions. Furthermore, the microbiome can serve as a biomarker for geographic origin inference, which has immense application value in forensic science.IMPORTANCEMicrobial communities in human hosts play a significant role in health and disease, varying in species, quantity, and composition due to factors such as gender, ethnicity, health status, lifestyle, and living environment. The characteristics of microbial composition at various body sites of individuals from different regions remain largely unexplored. This study utilized single-molecule real-time sequencing technology to detect the entire 16S rRNA gene of bacteria residing in the palmar skin, oral, and nasal cavities of Han individuals from four regions in China. The composition and structure of the bacteria at these three body sites were well characterized and found to differ regionally. The results elucidate the differences in bacterial communities colonizing these body sites across different regions and reveal the influence of geographical factors on human bacteria. These findings not only contribute to a deeper understanding of the diversity and geographical distribution of human bacteria but also enrich the microbiome data of the Asian population for further studies.}, }
@article {pmid39697649, year = {2024}, author = {Aluthge, N and Adams, S and Davila, CA and Gocchi Carrasco, NR and Chiou, KS and Abadie, R and Bennett, SJ and Dombrowski, K and Major, AM and Valentín-Acevedo, A and West, JT and Wood, C and Fernando, SC}, title = {Gut microbiota profiling in injection drug users with and without HIV-1 infection in Puerto Rico.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1470037}, pmid = {39697649}, issn = {1664-302X}, support = {R01 DA047823/DA/NIDA NIH HHS/United States ; }, abstract = {INTRODUCTION: The full extent of interactions between human immunodeficiency virus (HIV) infection, injection drug use, and the human microbiome is unclear. In this study, we examined the microbiomes of HIV-positive and HIV-negative individuals, both drug-injecting and non-injecting, to identify bacterial community changes in response to HIV and drug use. We utilized a well-established cohort of people who inject drugs in Puerto Rico, a region with historically high levels of injection drug use and an HIV incidence rate disproportionately associated with drug use.<br><br>METHODS: Using amplicon-based 16S rDNA sequencing, we identified amplicon sequence variants (ASVs) that demonstrated significant variations in the composition of microbial communities based on HIV status and drug use.<br><br>RESULTS AND DISCUSSION: Our findings indicate that the HIV-positive group exhibited a higher abundance of ASVs belonging to the genera Prevotella, Alloprevotella, Sutterella, Megasphaera, Fusobacterium, and Mitsuokella. However, Bifidobacteria and Lactobacillus ASVs were more abundant in injectors than in non-injectors. We examined the effect of drug use on the gut microbiome in both HIV-infected and non-infected patients, and found that multiple drug use significantly affected the microbial community composition. Analysis of differential of bacterial taxa revealed an enrichment of Bifidobacterium spp., Faecalibacterium spp., and Lactobacillus spp. in the multiple drug-injecting group. However, in the non-injecting group, Parabacteroides spp., Prevotella spp., Paraprevotella spp., Sutterella spp., and Lachnoclostridium spp. The presence of multiple drug-injecting groups was observed to be more prevalent. Our findings provide detailed insight into ASV-level changes in the microbiome in response to HIV and drug use, suggesting that the effect of HIV status and drug injection may have different effects on microbiome composition and in modulating gut bacterial populations.}, }
@article {pmid39695869, year = {2024}, author = {Rodriguez, J and Cordaillat-Simmons, M and Badalato, N and Berger, B and Breton, H and de Lahondès, R and Deschasaux-Tanguy, M and Desvignes, C and D'Humières, C and Kampshoff, S and Lavelle, A and Metwaly, A and Quijada, NM and Seegers, JFML and Udocor, A and Zwart, H and ,  and Maguin, E and Doré, J and Druart, C}, title = {Microbiome testing in Europe: navigating analytical, ethical and regulatory challenges.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {258}, pmid = {39695869}, issn = {2049-2618}, mesh = {Humans ; Europe ; *Feces/microbiology ; Microbiota ; Reproducibility of Results ; }, abstract = {BACKGROUND: In recent years, human microbiome research has flourished and has drawn attention from both healthcare professionals and general consumers as the human microbiome is now recognized as having a significant influence on human health. This has led to the emergence of companies offering microbiome testing services. Some of these services are sold directly to the consumer via companies' websites or via medical laboratory websites.<br><br>METHODOLOGY: In order to provide an overview of the consumer experience proposed by these microbiome testing services, one single faecal sample was sent to six different companies (five based in Europe and one based in the USA). Two out of the six testing kits were commercialized by medical laboratories, but without any requirement for a medical prescription. The analyses and reports received were discussed with a panel of experts (21 experts from 8 countries) during an online workshop.<br><br>RESULTS: This workshop led to the identification of several limitations and challenges related to these kits, including over-promising messages from the companies, a lack of transparency in the methodology used for the analysis and a lack of reliability of the results. The experts considered the interpretations and recommendations provided in the different reports to be premature due to the lack of robust scientific evidence and the analyses associated with the reports to be of limited clinical utility. The experts also discussed the grey areas surrounding the regulatory status of these test kits, including their positioning in the European market. The experts recommended a distinction between regulatory requirements based on the intended use or purpose of the kit: on the one hand, test kits developed to satisfy consumer curiosity, with a clear mention of this objective, and no mention of any disease or risk of disease, and on the other hand, in vitro&#xa0;diagnostic (IVD) CE-marked test kits, which could go deeper into the analysis and interpretation of samples, as such a report would be intended for trained healthcare professionals.<br><br>CONCLUSIONS: Recommendations or actions, specific to the context of use of microbiome testing kits, are listed to improve the quality and the robustness of these test kits to meet expectations of end users (consumers, patients and healthcare professionals). The need for standardization, robust scientific evidence, qualification of microbiome-based biomarkers and a clear regulatory status in Europe are the main issues that will require attention in the near future to align laboratory development with societal needs and thus foster translation into daily health practice.}, }
@article {pmid39695352, year = {2025}, author = {Moore, M and Whittington, HD and Knickmeyer, R and Azcarate-Peril, MA and Bruno-Bárcena, JM}, title = {Non-stochastic reassembly of a metabolically cohesive gut consortium shaped by N-acetyl-lactosamine-enriched fibers.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2440120}, pmid = {39695352}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; Infant ; *Bacteria/metabolism/classification/isolation &amp; purification/genetics ; Feces/microbiology ; Lactose/metabolism ; Dietary Fiber/metabolism ; Oligosaccharides/metabolism ; Amino Sugars ; }, abstract = {Diet is one of the main factors shaping the human microbiome, yet our understanding of how specific dietary components influence microbial consortia assembly and subsequent stability in response to press disturbances - such as increasing resource availability (feeding rate) - is still incomplete. This study explores the reproducible re-assembly, metabolic interplay, and compositional stability within microbial consortia derived from pooled stool samples of three healthy infants. Using a single-step packed-bed reactor (PBR) system, we assessed the reassembly and metabolic output of consortia exposed to lactose, glucose, galacto-oligosaccharides (GOS), and humanized GOS (hGOS). Our findings reveal that complex carbohydrates, especially those containing low inclusion (~1.25 gL[-1]) components present in human milk, such as N-acetyl-lactosamine (LacNAc), promote taxonomic, and metabolic stability under varying feeding rates, as shown by diversity metrics and network analysis. Targeted metabolomics highlighted distinct metabolic responses to different carbohydrates: GOS was linked to increased lactate, lactose to propionate, sucrose to butyrate, and CO2, and the introduction of bile salts with GOS or hGOS resulted in butyrate reduction and increased hydrogen production. This study validates the use of single-step PBRs for reliably studying microbial consortium stability and functionality in response to nutritional press disturbances, offering insights into the dietary modulation of microbial consortia and their ecological dynamics.}, }
@article {pmid39690351, year = {2024}, author = {Ullah, H and Hassan, SHA and Yang, Q and Salama, ES and Liu, P and Li, X}, title = {Dynamic interaction of antibiotic resistance between plant microbiome and organic fertilizers: sources, dissemination, and health risks.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {41}, number = {1}, pages = {4}, pmid = {39690351}, issn = {1573-0972}, support = {lzujbky-2024-ey12//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Animals ; Humans ; Agriculture/methods ; *Anti-Bacterial Agents/pharmacology ; *Bacteria/drug effects/genetics/classification ; Drug Resistance, Bacterial/drug effects/genetics ; *Fertilizers/analysis ; Gene Transfer, Horizontal ; *Manure/microbiology ; *Microbiota/drug effects ; *Plants/microbiology ; Sewage/microbiology ; Soil/chemistry ; *Soil Microbiology ; Wastewater/chemistry/microbiology ; }, abstract = {Antibiotic resistance is a global health problem driven by the irrational use of antibiotics in different areas (such as agriculture, animal farming, and human healthcare). Sub-lethal concentrations of antibiotic residues impose selective pressure on environmental, plant-associated, and human microbiome leading to the emergence of antibiotic-resistant bacteria (ARB). This review summarizes all sources of antibiotic resistance in agricultural soils (including manure, sewage sludge, wastewater, hospitals/pharmaceutical industry, and bioinoculants). The factors (such as the physicochemical properties of soil, root exudates, concentration of antibiotic exposure, and heavy metals) that facilitate the transmission of resistance in plant microbiomes are discussed. Potential solutions for effective measures and control of antibiotic resistance in the environment are also hypothesized. Manure exhibits the highest antibiotics load, followed by hospital and municipal WW. Chlortetracycline, tetracycline, and sulfadiazine have the highest concentrations in the manure. Antibiotic resistance from organic fertilizers is transmitted to the plant microbiome via horizontal gene transfer (HGT). Plant microbiomes serve as transmission routes of ARB and ARGS to humans. The ingestion of ARB leads to human health risks (such as ineffectiveness of medication, increased morbidity, and mortality).}, }
@article {pmid39690257, year = {2024}, author = {Tsuchida, S and Umemura, H and Iizuka, K and Yamamoto, H and Shimazaki, I and Shikata, E and Nakayama, T}, title = {Recent findings on metabolomics and the microbiome of oral bacteria involved in dental caries and periodontal disease.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {41}, number = {1}, pages = {11}, pmid = {39690257}, issn = {1573-0972}, mesh = {Animals ; Humans ; *Bacteria/classification/metabolism/genetics/isolation &amp; purification ; Biofilms/growth &amp; development ; *Dental Caries/microbiology ; Metabolomics/methods ; *Microbiota ; *Mouth/microbiology ; *Periodontal Diseases/microbiology ; }, abstract = {Periodontal disease is characterized by bacterial toxins within the oral biofilm surrounding the teeth, leading to gingivitis and the gradual dissolution of the alveolar bone, which supports the teeth. Notably, symptoms in the early stages of the disease are often absent. Similarly, dental caries occurs when oral bacteria metabolize dietary sugars, producing acids that dissolve tooth enamel and dentin. These bacteria are commonly present in the oral cavity of most individuals. Metabolomics, a relatively recent addition to the "omics" research landscape, involves the comprehensive analysis of metabolites in vivo to elucidate pathological mechanisms and accelerate drug discovery. Meanwhile, the term "microbiome" refers to the collection of microorganisms within a specific environmental niche or their collective genomes. The human microbiome plays a critical role in health and disease, influencing a wide array of physiological and pathological processes. Recent advances in microbiome research have identified numerous bacteria implicated in dental caries and periodontal disease. Additionally, studies have uncovered various pathogenic factors associated with these microorganisms. This review focuses on recent findings in metabolomics and the microbiome, specifically targeting oral bacteria linked to dental caries and periodontal disease. We acknowledge the limitation of relying exclusively on the MEDLINE database via PubMed, while excluding other sources such as gray literature, conference proceedings, and clinical practice guidelines.}, }
@article {pmid39689342, year = {2025}, author = {Chircop, O and Jaggers, C and Spiteri, M and Schembri, A and Padovese, V}, title = {DOXY do, or DOXY Don't? Syphilis and doxycycline post-exposure prophylaxis: A case report.}, journal = {International journal of STD &amp; AIDS}, volume = {36}, number = {4}, pages = {324-326}, doi = {10.1177/09564624241308026}, pmid = {39689342}, issn = {1758-1052}, mesh = {Humans ; Male ; *Anti-Bacterial Agents/therapeutic use ; *Doxycycline/therapeutic use/administration &amp; dosage ; Homosexuality, Male ; *Neurosyphilis/diagnosis/drug therapy ; *Post-Exposure Prophylaxis ; *Syphilis/diagnosis/drug therapy ; Treatment Outcome ; Treponema pallidum/isolation &amp; purification ; }, abstract = {The resurgence of syphilis across Europe has led to a growing number of atypical cases, often characterised by varied symptoms that can delay diagnosis. We report the case of a young man who has sex with men (MSM), presenting with persistent headaches and swelling of the forehead suggestive of giant cell arteritis (GCA). Despite a recent negative syphilis test, further investigations confirmed the diagnosis of neurosyphilis. The patient had been using doxycycline post-exposure prophylaxis (DoxyPEP), which is suspected to have delayed the diagnosis by masking the typical antibody response. This case highlights concerns about DoxyPEP's impact on syphilis detection and disease progression. Further research is warranted to explore its effects on antimicrobial resistance, the human microbiome, and clinical outcomes.}, }
@article {pmid39688588, year = {2025}, author = {Jiang, H and Miao, X and Thairu, MW and Beebe, M and Grupe, DW and Davidson, RJ and Handelsman, J and Sankaran, K}, title = {Multimedia: multimodal mediation analysis of microbiome data.}, journal = {Microbiology spectrum}, volume = {13}, number = {2}, pages = {e0113124}, pmid = {39688588}, issn = {2165-0497}, support = {R01 GM152744/GM/NIGMS NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; R01GM152744//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Humans ; *Software ; *Microbiota ; *Mediation Analysis ; Inflammatory Bowel Diseases/microbiology ; *Multimedia ; Metabolome ; }, abstract = {UNLABELLED: Mediation analysis has emerged as a versatile tool for answering mechanistic questions in microbiome research because it provides a statistical framework for attributing treatment effects to alternative causal pathways. Using a series of linked regressions, this analysis quantifies how complementary data relate to one another and respond to treatments. Despite these advances, existing software's rigid assumptions often result in users viewing mediation analysis as a black box. We designed the multimedia R package to make advanced mediation analysis techniques accessible, ensuring that statistical components are interpretable and adaptable. The package provides a uniform interface to direct and indirect effect estimation, synthetic null hypothesis testing, bootstrap confidence interval construction, and sensitivity analysis, enabling experimentation with various mediator and outcome models while maintaining a simple overall workflow. The software includes modules for regularized linear, compositional, random forest, hierarchical, and hurdle modeling, making it well-suited to microbiome data. We illustrate the package through two case studies. The first re-analyzes a study of the microbiome and metabolome of Inflammatory Bowel Disease patients, uncovering potential mechanistic interactions between the microbiome and disease-associated metabolites, not found in the original study. The second analyzes new data about the influence of mindfulness practice on the microbiome. The mediation analysis highlights shifts in taxa previously associated with depression that cannot be explained indirectly by diet or sleep behaviors alone. A gallery of examples and further documentation can be found at https://go.wisc.edu/830110.<br><br>IMPORTANCE: Microbiome studies routinely gather complementary data to capture different aspects of a microbiome's response to a change, such as the introduction of a therapeutic. Mediation analysis clarifies the extent to which responses occur sequentially via mediators, thereby supporting causal, rather than purely descriptive, interpretation. Multimedia is a modular R package with close ties to the wider microbiome software ecosystem that makes statistically rigorous, flexible mediation analysis easily accessible, setting the stage for precise and causally informed microbiome engineering.}, }
@article {pmid39684937, year = {2024}, author = {Balla, B and Illés, A and Tobiás, B and Pikó, H and Beke, A and Sipos, M and Lakatos, P and Kósa, JP}, title = {The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684937}, issn = {1422-0067}, support = {2020-4.1.1.-TKP2020-MOLORKIV//Hungarian Ministry of Innovation and Technology/ ; }, mesh = {Humans ; Female ; *Vagina/microbiology ; Pregnancy ; *Microbiota ; *Endometrium/microbiology/metabolism ; *Pregnancy Outcome ; Dysbiosis/microbiology ; Infertility, Female/microbiology ; Infertility/microbiology ; }, abstract = {The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with Lactobacillus spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A Lactobacillus-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced Lactobacilli as well as an increased diversity and abundance of pathogenic species (e.g., Gardnerella vaginalis or Prevotella spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes.}, }
@article {pmid39684310, year = {2024}, author = {Cominelli, G and Lonati, C and Pinto, D and Rinaldi, F and Franco, C and Favero, G and Rezzani, R}, title = {Melatonin Attenuates Ferritinophagy/Ferroptosis by Acting on Autophagy in the Liver of an Autistic Mouse Model BTBR T[+]Itpr3[tf]/J.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684310}, issn = {1422-0067}, support = {grants ex 60%//University of Brescia - Italy/ ; grant donation//FLAMMA S.p.A.- Italy/ ; }, mesh = {Animals ; *Melatonin/pharmacology ; Mice ; *Disease Models, Animal ; *Liver/metabolism/drug effects/pathology ; *Autophagy/drug effects ; *Ferroptosis/drug effects ; *Ferritins/metabolism ; Male ; Nuclear Receptor Coactivators/metabolism/genetics ; Microtubule-Associated Proteins/metabolism/genetics ; Autistic Disorder/metabolism/drug therapy/pathology ; Autism Spectrum Disorder/metabolism/drug therapy ; }, abstract = {Autism spectrum disorders (ASDs) are a pool of neurodevelopment disorders in which social impairment is the main symptom. Presently, there are no definitive medications to cure the symptoms but the therapeutic strategies that are taken ameliorate them. The purpose of this study was to investigate the effects of melatonin (MLT) in treating ASDs using an autistic mouse model BTBR T[+]Itpr3[tf]/J (BTBR). We evaluated the hepatic cytoarchitecture and some markers of autophagy, ferritinophagy/ferroptosis, in BTBR mice treated and not-treated with MLT. The hepatic morphology and the autophagy and ferritinophagy/ferroptosis pathways were analyzed by histological, immunohistochemical, and Western blotting techniques. We studied p62 and microtubule-associated protein 1 light chain 3 B (LC3B) for evaluating the autophagy; nuclear receptor co-activator 4 (NCOA4) and long-chain-coenzyme synthase (ACSL4) for monitoring ferritinophagy/ferroptosis. The liver of BTBR mice revealed that the hepatocytes showed many cytoplasmic inclusions recognized as Mallory-Denk bodies (MDBs); the expression and levels of p62 and LC3B were downregulated, whereas ACSL4 and NCOA4 were upregulated, as compared to control animals. MLT administration to BTBR mice ameliorated liver damage and reduced the impairment of autophagy and ferritinophagy/ferroptosis. In conclusion, we observed that MLT alleviates liver damage in BTBR mice by improving the degradation of intracellular MDBs, promoting autophagy, and suppressing ferritinophagy/ferroptosis.}, }
@article {pmid39683635, year = {2024}, author = {Ouédraogo, LO and Deng, L and Ouattara, CA and Compaoré, A and Ouédraogo, M and Argaw, A and Lachat, C and Houpt, ER and Saidi, Q and Haerynck, F and Sonnenburg, J and Azad, MB and Tavernier, SJ and Bastos-Moreira, Y and Toe, LC and Dailey-Chwalibóg, T}, title = {Describing Biological Vulnerability in Small, Vulnerable Newborns in Urban Burkina Faso (DenBalo): Gut Microbiota, Immune System, and Breastmilk Assembly.}, journal = {Nutrients}, volume = {16}, number = {23}, pages = {}, pmid = {39683635}, issn = {2072-6643}, support = {INV-035474/GATES/Gates Foundation/United States ; INV-036154/GATES/Gates Foundation/United States ; INV-035474 &amp; INV-036154/GATES/Gates Foundation/United States ; }, mesh = {Humans ; Burkina Faso ; Female ; Infant, Newborn ; *Gastrointestinal Microbiome ; *Milk, Human/immunology ; Prospective Studies ; *Vagina/microbiology/immunology ; *Immune System ; Pregnancy ; Breast Feeding ; Infant, Small for Gestational Age ; Adult ; }, abstract = {Background: Small vulnerable newborns (SVNs), including those born preterm, small for gestational age, or with low birth weight, are at higher risk of neonatal mortality and long-term health complications. Early exposure to maternal vaginal microbiota and breastfeeding plays a critical role in the development of the neonatal microbiota and immune system, especially in low-resource settings like Burkina Faso, where neonatal mortality rates remain high. Objectives: The DenBalo study aims to investigate the role of maternal and neonatal factors, such as vaginal and gut microbiota, immune development, and early nutrition, in shaping health outcomes in SVNs and healthy infants. Methods: This prospective cohort observational study will recruit 141 mother-infant pairs (70 SVNs and 71 healthy controls) from four health centers in Bobo-Dioulasso, Burkina Faso. The mother-infant pairs will be followed for six months with anthropometric measurements and biospecimen collections, including blood, breast milk, saliva, stool, vaginal swabs, and placental biopsies. Multi-omics approaches, encompassing metagenomics, metabolomics, proteomics, and immune profiling, will be used to assess vaginal and gut microbiota composition and functionality, immune cell maturation, and cytokine levels at critical developmental stages. Conclusions: This study will generate comprehensive data on how microbiota, metabolomic, and proteomic profiles, along with immune system development, differ between SVNs and healthy infants. These findings will guide targeted interventions to improve neonatal health outcomes and reduce mortality, particularly in vulnerable populations.}, }
@article {pmid39682776, year = {2024}, author = {Kim, S and Rahim, MA and Tajdozian, H and Barman, I and Park, HA and Yoon, Y and Jo, S and Lee, S and Shuvo, MSH and Bae, SH and Lee, H and Ju, S and Park, CE and Kim, HK and Han, JH and Kim, JW and Yoon, SG and Kim, JH and Choi, YG and Lee, S and Seo, H and Song, HY}, title = {Clinical Potential of Novel Microbial Therapeutic LP51 Based on Xerosis-Microbiome Index.}, journal = {Cells}, volume = {13}, number = {23}, pages = {}, pmid = {39682776}, issn = {2073-4409}, support = {RS-2023-00219563//National Research Foundation of Korea/ ; P248400003//Korea Institute for Advancement of Technology/ ; }, mesh = {Humans ; Female ; *Microbiota/drug effects ; Double-Blind Method ; Adult ; Skin/microbiology/pathology ; Middle Aged ; }, abstract = {Xerosis, characterized by dry, rough skin, causes discomfort and aesthetic concerns, necessitating effective treatment. Traditional treatments often show limited efficacy, prompting the need for innovative therapies. This study highlights the efficacy of microbiome therapeutic LP51, derived from a healthy vaginal microbiome, in improving xerosis. A double-blind clinical trial involving 43 subjects with dry inner arm skin compared the effects of a 2.9% LP51 extract formulation to a placebo over 4 weeks. The LP51 group exhibited a significant increase in stratum corneum hydration (10.0 A.U.) compared to the placebo group (4.8 A.U.) and a 21.4% decrease in transepidermal water loss (TEWL), whereas the placebo group showed no significant change. LP51 also demonstrated benefits in enhancing skin hydration, improving the skin barrier, and exhibited anti-atopic, anti-inflammatory, and antioxidant properties. Safety was confirmed through in vitro cytotoxicity tests. These effects are attributed to the microbiome-safe component in LP51 and its role in improving xerosis, reflected by an increase in the xerosis-microbiome index, defined by the Firmicutes/Actinobacteria ratio. These findings position microbiome therapeutic LP51 as a promising novel treatment for xerosis.}, }
@article {pmid39682751, year = {2024}, author = {Seo, H and Kim, S and Beck, S and Song, HY}, title = {Perspectives on Microbiome Therapeutics in Infectious Diseases: A Comprehensive Approach Beyond Immunology and Microbiology.}, journal = {Cells}, volume = {13}, number = {23}, pages = {}, pmid = {39682751}, issn = {2073-4409}, support = {RS-2023-00219563//Ministry of Science and ICT/ ; P248400003//Korea Institute for Advancement of Technology/ ; Soonchunhyang University Research Fund//Soonchunhyang University Research Fund/ ; }, mesh = {Humans ; *Microbiota/immunology ; *Probiotics/therapeutic use ; *COVID-19/immunology/virology/therapy ; Communicable Diseases/microbiology/therapy/immunology ; SARS-CoV-2/immunology ; }, abstract = {Although global life expectancy has increased over the past 20 years due to advancements in managing infectious diseases, one-fifth of people still die from infections. In response to this ongoing threat, significant efforts are underway to develop vaccines and antimicrobial agents. However, pathogens evolve resistance mechanisms, complicating their control. The COVID-19 pandemic has underscored the limitations of focusing solely on the pathogen-killing strategies of immunology and microbiology to address complex, multisystemic infectious diseases. This highlights the urgent need for practical advancements, such as microbiome therapeutics, that address these limitations while complementing traditional approaches. Our review emphasizes key outcomes in the field, including evidence of probiotics reducing disease severity and insights into host-microbiome crosstalk that have informed novel therapeutic strategies. These findings underscore the potential of microbiome-based interventions to promote physiological function alongside existing strategies aimed at enhancing host immune responses and pathogen destruction. This narrative review explores microbiome therapeutics as next-generation treatments for infectious diseases, focusing on the application of probiotics and their role in host-microbiome interactions. While offering a novel perspective grounded in a cooperative defense system, this review also addresses the practical challenges and limitations in translating these advancements into clinical settings.}, }
@article {pmid39682542, year = {2024}, author = {Morales, C and Ballestero, L and Del Río, P and Barbero-Herranz, R and Olavarrieta, L and Gómez-Artíguez, L and Galeano, J and Avendaño-Ortiz, J and Basterra, J and Del Campo, R}, title = {Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {23}, pages = {}, pmid = {39682542}, issn = {2075-4418}, support = {XX//Mikrobiomik/ ; }, abstract = {BACKGROUND/OBJECTIVES: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors.<br><br>METHODS: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated.<br><br>RESULTS: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.}, }
@article {pmid39681696, year = {2025}, author = {Joos, R and Boucher, K and Lavelle, A and Arumugam, M and Blaser, MJ and Claesson, MJ and Clarke, G and Cotter, PD and De Sordi, L and Dominguez-Bello, MG and Dutilh, BE and Ehrlich, SD and Ghosh, TS and Hill, C and Junot, C and Lahti, L and Lawley, TD and Licht, TR and Maguin, E and Makhalanyane, TP and Marchesi, JR and Matthijnssens, J and Raes, J and Ravel, J and Salonen, A and Scanlan, PD and Shkoporov, A and Stanton, C and Thiele, I and Tolstoy, I and Walter, J and Yang, B and Yutin, N and Zhernakova, A and Zwart, H and ,  and Doré, J and Ross, RP}, title = {Author Correction: Examining the healthy human microbiome concept.}, journal = {Nature reviews. Microbiology}, volume = {23}, number = {3}, pages = {206}, doi = {10.1038/s41579-024-01145-8}, pmid = {39681696}, issn = {1740-1534}, }
@article {pmid39676876, year = {2024}, author = {Bhatnagar, K and Jha, K and Dalal, N and Patki, N and Gupta, G and Kumar, A and Kumar, A and Chaudhary, S}, title = {Exploring micronutrients and microbiome synergy: pioneering new paths in cancer therapy.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1442788}, pmid = {39676876}, issn = {1664-3224}, mesh = {Humans ; *Micronutrients/therapeutic use ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/immunology/therapy/microbiology ; Animals ; Probiotics/therapeutic use ; Prebiotics/administration &amp; dosage ; Dysbiosis/therapy ; }, abstract = {The human microbiome is the complex ecosystem consisting of trillions of microorganisms that play a key role in developing the immune system and nutrient metabolism. Alterations in the gut microbiome have been linked to cancer initiation, progression, metastasis, and response to treatment. Accumulating evidence suggests that levels of vitamins and minerals influence the gut environment and may have implications for cancer risk and progression. Bifidobacterium has been reported to reduce the colorectal cancer risk by binding to free iron. Additionally, zinc ions have been shown to activate the immune cells and enhance the effectiveness of immunotherapy. Higher selenium levels have been associated with a reduced risk of several cancers, including colorectal cancer. In contrast, enhanced copper uptake has been implicated in promoting cancer progression, including colon cancer. The interaction between cancer and gut bacteria, as well as dysbiosis impact has been studied in animal models. The interplay between prebiotics, probiotics, synbiotics, postbiotics and gut bacteria in cancer offers the diverse physiological benefits. We also explored the particular probiotic formulations like VSL#3, Prohep, Lactobacillus rhamnosus GG (LGG), etc., for their ability to modulate immune responses and reduce tumor burden in preclinical models. Targeting the gut microbiome through antibiotics, bacteriophage, microbiome transplantation-based therapies will offer a new perspective in cancer research. Hence, to understand this interplay, we outline the importance of micronutrients with an emphasis on the immunomodulatory function of the microbiome and highlight the microbiome's potential as a target for precision medicine in cancer treatment.}, }
@article {pmid39675162, year = {2025}, author = {Skurnik, M}, title = {Scholarly discussion on the classification and electron microscopy analysis of lytic phage EC BD.}, journal = {International journal of food microbiology}, volume = {429}, number = {}, pages = {111012}, doi = {10.1016/j.ijfoodmicro.2024.111012}, pmid = {39675162}, issn = {1879-3460}, }
@article {pmid39662756, year = {2025}, author = {Hodgkiss, R and Acharjee, A}, title = {Unravelling metabolite-microbiome interactions in inflammatory bowel disease through AI and interaction-based modelling.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1871}, number = {3}, pages = {167618}, doi = {10.1016/j.bbadis.2024.167618}, pmid = {39662756}, issn = {1879-260X}, support = {HDRUK/CFC/01/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/metabolism ; *Gastrointestinal Microbiome ; *Metabolome ; Feces/microbiology ; Dysbiosis/microbiology/metabolism ; *Artificial Intelligence ; }, abstract = {Inflammatory Bowel Diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract and colon affecting approximately 7 million individuals worldwide. The knowledge of specific pathology and aetiological mechanisms leading to IBD is limited, however a reduced immune system, antibiotic use and reserved diet may initiate symptoms. Dysbiosis of the gut microbiome, and consequently a varied composition of the metabolome, has been extensively linked to these risk factors and IBD. Metagenomic sequencing and liquid-chromatography mass spectrometry (LC-MS) of N = 220 fecal samples by Fransoza et al., provided abundance data on microbial genera and metabolites for use in this study. Identification of differentially abundant microbes and metabolites was performed using a Wilcoxon test, followed by feature selection of random forest (RF), gradient-boosting (XGBoost) and least absolute shrinkage operator (LASSO) models. The performance of these features was then validated using RF models on the Human Microbiome Project 2 (HMP2) dataset and a microbial community (MICOM) model was utilised to predict and interpret the interactions between key microbes and metabolites. The Flavronifractor genus and microbes of the families Lachnospiraceae and Oscillospiraceae were found differential by all models. Metabolic pathways commonly influenced by such microbes in IBD were CoA biosynthesis, bile acid metabolism and amino acid production and degradation. This study highlights distinct interactive microbiome and metabolome profiles within IBD and the highly potential pathways causing disease pathology. It therefore paves way for future investigation into new therapeutic targets and non-invasive diagnostic tools for IBD.}, }
@article {pmid39657723, year = {2025}, author = {Sinkko, H and Olah, P and Yang, Y and Maia, G and Barrientos-Somarribas, M and Rádai, Z and Mäenpää, K and Soratto, T and Salava, A and Lauerma, A and Barker, J and Ranki, A and Homey, B and Andersson, B and Fyhrquist, N and Alenius, H and , }, title = {Taxonomic and functional profiling of skin microbiome in psoriasis.}, journal = {The British journal of dermatology}, volume = {192}, number = {5}, pages = {931-933}, doi = {10.1093/bjd/ljae471}, pmid = {39657723}, issn = {1365-2133}, support = {261366//MAARS/ ; 821511//Innovative Medicines Initiative 2 Joint Undertaking/ ; //European Union's Horizon 2020 research and innovation programme and EFPIA/ ; //Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; //Brazilian Government Agency/ ; }, }
@article {pmid39657633, year = {2025}, author = {Yang, W and Wu, K and Chen, H and Huang, J and Yu, Z}, title = {Emerging role of rare earth elements in biomolecular functions.}, journal = {The ISME journal}, volume = {19}, number = {1}, pages = {}, pmid = {39657633}, issn = {1751-7370}, support = {32&#x2009;170&#x2009;071//National Natural Science Foundation of China/ ; 2023JJ30651//Natural Science Foundation of Hunan Province/ ; 2023CXQD059//Innovation-Driven Research Programme of Central South University/ ; }, mesh = {*Metals, Rare Earth/metabolism ; *Proteins/metabolism ; }, abstract = {The importance of rare earth elements is increasingly recognized due to the increased demand for their mining and separation. This demand is driving research on the biology of rare earth elements. Biomolecules associated with rare earth elements include rare earth element-dependent enzymes (methanol dehydrogenase XoxF, ethanol dehydrogenase ExaF/PedH), rare earth element-binding proteins, and the relevant metallophores. Traditional (chemical) separation methods for rare earth elements harvesting and separation are typically inefficient, while causing environmental problems, whereas bioharvesting, potentially, offers more efficient, more green platforms. Here, we review the current state of research on the biological functions of rare earth element-dependent biomolecules, and the characteristics of the relevant proteins, including the specific amino acids involved in rare earth metal binding. We also provide an outlook at strategies for further understanding of biological processes and the potential applications of rare earth element-dependent enzymes and other biomolecules.}, }
@article {pmid39654676, year = {2024}, author = {Han, H and Choi, YH and Kim, SY and Park, JH and Chung, J and Na, HS}, title = {Optimizing microbiome reference databases with PacBio full-length 16S rRNA sequencing for enhanced taxonomic classification and biomarker discovery.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1485073}, pmid = {39654676}, issn = {1664-302X}, abstract = {BACKGROUND: The study of the human microbiome is crucial for understanding disease mechanisms, identifying biomarkers, and guiding preventive measures. Advances in sequencing platforms, particularly 16S rRNA sequencing, have revolutionized microbiome research. Despite the benefits, large microbiome reference databases (DBs) pose challenges, including computational demands and potential inaccuracies. This study aimed to determine if full-length 16S rRNA sequencing data produced by PacBio could be used to optimize reference DBs and be applied to Illumina V3-V4 targeted sequencing data for microbial study.<br><br>METHODS: Oral and gut microbiome data (PRJNA1049979) were retrieved from NCBI. DADA2 was applied to full-length 16S rRNA PacBio data to obtain amplicon sequencing variants (ASVs). The RDP reference DB was used to assign the ASVs, which were then used as a reference DB to train the classifier. QIIME2 was used for V3-V4 targeted Illumina data analysis. BLAST was used to analyze alignment statistics. Linear discriminant analysis Effect Size (LEfSe) was employed for discriminant analysis.<br><br>RESULTS: ASVs produced by PacBio showed coverage of the oral microbiome similar to the Human Oral Microbiome Database. A phylogenetic tree was trimmed at various thresholds to obtain an optimized reference DB. This established method was then applied to gut microbiome data, and the optimized gut microbiome reference DB provided improved taxa classification and biomarker discovery efficiency.<br><br>CONCLUSION: Full-length 16S rRNA sequencing data produced by PacBio can be used to construct a microbiome reference DB. Utilizing an optimized reference DB can increase the accuracy of microbiome classification and enhance biomarker discovery.}, }
@article {pmid39651993, year = {2024}, author = {Poncet, R and Gargominy, O}, title = {In the Shadow of Medicine: The Glaring Absence of Occurrence Records of Human-Hosted Biodiversity.}, journal = {Online journal of public health informatics}, volume = {16}, number = {}, pages = {e60140}, pmid = {39651993}, issn = {1947-2579}, abstract = {Microbial diversity is vast, with bacteria playing a crucial role in human health. However, occurrence records (location, date, observer, and host interaction of human-associated bacteria) remain scarce. This lack of information hinders our understanding of human-microbe relationships and disease prevention. In this study, we show that existing solutions such as France's Système d'Information sur le Patrimoine Naturel framework, can be used to efficiently collect and manage occurrence data on human-associated bacteria. This user-friendly system allows medical personnel to easily share and access data on bacterial pathogens. By adopting similar national infrastructures and treating human-associated bacteria as biodiversity data, we can significantly improve public health management and research, and our understanding of the One Health concept, which emphasizes the interconnectedness of human, animal, and environmental health.}, }
@article {pmid39648582, year = {2024}, author = {Burton, JP and Kofoed, RH and Rust, R}, title = {Science around the world.}, journal = {Trends in molecular medicine}, volume = {30}, number = {3}, pages = {197-199}, doi = {10.1016/j.molmed.2024.01.008}, pmid = {39648582}, issn = {1471-499X}, }
@article {pmid39647502, year = {2025}, author = {Porcari, S and Mullish, BH and Asnicar, F and Ng, SC and Zhao, L and Hansen, R and O'Toole, PW and Raes, J and Hold, G and Putignani, L and Hvas, CL and Zeller, G and Koren, O and Tun, H and Valles-Colomer, M and Collado, MC and Fischer, M and Allegretti, J and Iqbal, T and Chassaing, B and Keller, J and Baunwall, SM and Abreu, M and Barbara, G and Zhang, F and Ponziani, FR and Costello, SP and Paramsothy, S and Kao, D and Kelly, C and Kupcinskas, J and Youngster, I and Franceschi, F and Khanna, S and Vehreschild, M and Link, A and De Maio, F and Pasolli, E and Miguez, AB and Brigidi, P and Posteraro, B and Scaldaferri, F and Stojanovic, MR and Megraud, F and Malfertheiner, P and Masucci, L and Arumugam, M and Kaakoush, N and Segal, E and Bajaj, J and Leong, R and Cryan, J and Weersma, RK and Knight, R and Guarner, F and Shanahan, F and Cani, PD and Elinav, E and Sanguinetti, M and de Vos, WM and El-Omar, E and Dorè, J and Marchesi, J and Tilg, H and Sokol, H and Segata, N and Cammarota, G and Gasbarrini, A and Ianiro, G}, title = {International consensus statement on microbiome testing in clinical practice.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {10}, number = {2}, pages = {154-167}, pmid = {39647502}, issn = {2468-1253}, support = {R01 HL160862/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Consensus ; *Gastrointestinal Microbiome ; Microbiota ; }, abstract = {There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.}, }
@article {pmid39639265, year = {2024}, author = {Ma, ZS}, title = {Revisiting microgenderome: detecting and cataloguing sexually unique and enriched species in human microbiomes.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {284}, pmid = {39639265}, issn = {1741-7007}, mesh = {Humans ; Female ; Male ; *Microbiota ; *Sex Characteristics ; Species Specificity ; }, abstract = {BACKGROUND: Microgenderome or arguably more accurately microsexome refers to studies on sexual dimorphism of human microbiomes aimed at investigating bidirectional interactions between human microbiomes, sex hormones, and immune systems. It is important because of its implications to disease susceptibility and therapy, in which men and women demonstrate divergence in many diseases especially autoimmune diseases. In a previous report [1], we presented analyses of several key ecological aspects of microgenderome by leveraging the large datasets of the HMP (human microbiome project) but failed to offer species-level composition differences such as sexually unique species (US) and enriched species (ES). Existing approaches, for such tasks, including differential species relative abundance analysis and differential network analysis, possess certain limitations given that virtually all rely on species abundance alone or are univariate, while ignoring species distribution information across samples. Obviously, it is both species abundance and distribution that shape/drive the structure and dynamics of human microbiomes, and both should be equally responsible for the universal heterogeneity of microbiomes including the sexual dimorphism.<br><br>RESULTS: Here, we fill the gap by taking advantages of a recently developed computational algorithm, species specificity, and specificity diversity (SSD) framework (refer to the companion article) to reanalyze the HMP and complementary seminovaginal microbiome datasets. The SSD framework can randomly search and catalogue the sexually specific unique/enriched species with statistical rigor, guided by species specificity (a synthetic metric of abundance and distribution) and specificity diversity (SD). The SSD framework reveals that men seem to have more unique species than women in their gut and reproductive system microbiomes, but women seem to have more unique species than men in the airway, oral, and skin microbiomes, which is likely due to sexual dimorphism in the hormone and immune systems. We further investigate co-dependency and heterogeneity of those sexually unique/enriched species across 15 body sites, with core/periphery network analyses.<br><br>CONCLUSIONS: This study not only produced sexually unique/enriched species in the human microbiomes and analyzed their codependency and heterogeneity but also further validated the robustness of the SSD framework presented in the companion article, by performing all negative control tests based on the HMP gut microbiome samples.}, }
@article {pmid39626677, year = {2024}, author = {He, Z and Yu, J and Gong, J and Wu, J and Zong, X and Luo, Z and He, X and Cheng, WM and Liu, Y and Liu, C and Zhang, Q and Dai, L and Ding, T and Gao, B and Gharaibeh, RZ and Huang, J and Jobin, C and Lan, P}, title = {Campylobacter jejuni-derived cytolethal distending toxin promotes colorectal cancer metastasis.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {12}, pages = {2080-2091.e6}, doi = {10.1016/j.chom.2024.11.006}, pmid = {39626677}, issn = {1934-6069}, mesh = {Animals ; *Bacterial Toxins/metabolism/genetics ; *Colorectal Neoplasms/pathology/microbiology ; *Campylobacter jejuni/genetics/metabolism ; Humans ; Mice ; *STAT3 Transcription Factor/metabolism ; *Neoplasm Metastasis ; Campylobacter Infections/microbiology ; Janus Kinase 2/metabolism/genetics ; Matrix Metalloproteinase 9/metabolism ; Cell Line, Tumor ; Signal Transduction ; Disease Models, Animal ; Female ; }, abstract = {Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni-derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni-infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB (ΔcdtB) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni's pro-metastatic property. In C.-jejuni-colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.}, }
@article {pmid39624165, year = {2024}, author = {Zhang, Y and Schluter, J and Zhang, L and Cao, X and Jenq, RR and Feng, H and Haines, J and Zhang, L}, title = {Review and revamp of compositional data transformation: A new framework combining proportion conversion and contrast transformation.}, journal = {Computational and structural biotechnology journal}, volume = {23}, number = {}, pages = {4088-4107}, pmid = {39624165}, issn = {2001-0370}, support = {DP2 AI164318/AI/NIAID NIH HHS/United States ; }, abstract = {Due to the development of next-generation sequencing technology and an increased appreciation of their role in modulating host immunity and their potential as therapeutic agents, the human microbiome has emerged as a key area of interest in various biological investigations of human health and disease. However, microbiome data present a number of statistical challenges not addressed by existing methods, such as the varying sequencing depth, the compositionality, and zero inflation. Solutions like scaling and transformation methods help to mitigate heterogeneity and release constraints, but often introduce biases and yield inconsistent results on the same data. To address these issues, we conduct a systematic review of compositional data transformation, with a particular focus on the connection and distinction of existing techniques. Additionally, we create a new framework that enables the development of new transformations by combining proportion conversion with contrast transformations. This framework includes well-known methods such as Additive Log Ratio (ALR) and Centered Log Ratio (CLR) as special cases. Using this framework, we develop two novel transformations-Centered Arcsine Contrast (CAC) and Additive Arcsine Contrast (AAC)-which show enhanced performance in scenarios with high zero-inflation. Moreover, our findings suggest that ALR and CLR transformations are more effective when zero values are less prevalent. This comprehensive review and the innovative framework provide microbiome researchers with a significant direction to enhance data transformation procedures and improve analytical outcomes.}, }
@article {pmid39621633, year = {2024}, author = {Martins, FP and Andrade-Silva, J and Teixeira, BL and Ferrari, A and Christoff, AP and Cruz, GNF and Paladino, FV and de Oliveira, LFV and Hernandes, C}, title = {Oral microbiome test as an alternative diagnostic tool for gastric alterations: A prospective, bicentric cross-sectional study.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0314660}, pmid = {39621633}, issn = {1932-6203}, mesh = {Humans ; Cross-Sectional Studies ; Female ; Male ; Middle Aged ; *Mouth/microbiology ; Prospective Studies ; Adult ; *Microbiota ; Brazil ; Aged ; Stomach/microbiology ; Bacteria/genetics/isolation &amp; purification/classification ; Stomach Diseases/microbiology/diagnosis ; }, abstract = {The human microbiome plays a pivotal role in influencing various physiological processes and maintaining overall well-being, including the gastric system. Current diagnostic tests for gastric diseases often involve invasive procedures, sampling limitations, and medication effects, leading to potential diagnostic errors and discomfort to patients. Considering the connection between oral and gastric microbiomes, this cross-sectional study aimed to assess the diagnostic potential of the oral bacterial profile in patients undergoing upper digestive endoscopy. Oral samples from 266 participants across two Brazilian sites (Belterra and Sao Paulo) were sequenced and subjected to bioinformatic analysis to identify microbiome composition across endoscopy outcome groups, exploring alpha and beta-diversity, richness, and differential abundance and prevalence. Prevotella, Haemophilus, Fusobacterium, Neisseria, and Streptococcus were the most abundant genera observed. No significant associations were found between alpha diversity profiles and endoscopy outcomes; beta diversity analyses similarly showed no correlations. Overall, the study did not establish the oral microbiome as a reliable marker for gastric health, underscoring the necessity for broader studies in the development of non-invasive diagnostic tests.}, }
@article {pmid39619727, year = {2024}, author = {Sawan, HM and Shroukh, W and Abutaima, R and Al Omari, SM and Abdel-Qader, DH and Binsuwaidan, R}, title = {Impact of Jordanian Pharmacists' Knowledge of the Human Microbiome: Has the Practice of Antibiotics and Probiotics Dispensing Been Affected? A Cross-Sectional Study.}, journal = {Infection and drug resistance}, volume = {17}, number = {}, pages = {5203-5214}, pmid = {39619727}, issn = {1178-6973}, abstract = {OBJECTIVE: This study aimed to assess Jordanian pharmacists' knowledge of the human microbiome and the impact of their knowledge on their attitudes and practices toward antibiotics and probiotics.<br><br>METHODS: A self-administered survey was designed after reviewing the literature. Participants' demographics were collected, and questions to evaluate pharmacists' knowledge, attitudes, and practices toward antibiotic and probiotic dispensing were asked. The data were analyzed using the Statistical Package for the Social Sciences V.26. Pearson correlations and one-way ANOVA were employed to calculate the significance of knowledge, attitudes, and practices. Statistical significance was considered at p < 0.05.<br><br>RESULTS: Of the 333 respondents, around 75% (n=250) had a high level of general knowledge regarding the human gut microbiome. Almost equal proportions of participants had either intermediate or high levels of knowledge about the role of gut bacteria in health (n=164, 49.2%) (n=166, 49.8%), respectively, while almost two-thirds had an intermediate level of knowledge of the role of gut bacteria in disease (n=197, 59.2%). More than half of the participants had a positive attitude toward antibiotics, probiotics, and the human microbiome (n=179, 53.8%), and the majority (n=239, 71.8%) had an intermediate level of practice with them. There was a significant positive correlation between pharmacists' general knowledge of the human microbiome and their positive attitudes (r=0.306, p < 0.01) and practices (r=0.331, p < 0.01) toward antibiotics and probiotics.<br><br>CONCLUSION: Study results raise the importance of interventional educational measures to promote healthcare professionals' knowledge of the human microbiome and their potential beneficence on pharmacists' attitudes and practices regarding antibiotics and probiotics dispensing. The results also denote the urgent need for probiotics' clinical guidelines to ensure practice uniformity.}, }
@article {pmid39614246, year = {2024}, author = {Marín-Sánchez, N and Paredes, R and Borgognone, A}, title = {Exploring potential associations between the human microbiota and reservoir of latent HIV.}, journal = {Retrovirology}, volume = {21}, number = {1}, pages = {21}, pmid = {39614246}, issn = {1742-4690}, support = {847943//European Union's Horizon 2020 Research and Innovation/ ; }, mesh = {Humans ; *HIV Infections/virology/microbiology/immunology ; *Virus Latency ; *HIV-1/physiology ; *Microbiota ; *Gastrointestinal Microbiome ; Virus Replication ; Disease Reservoirs/virology/microbiology ; }, abstract = {BACKGROUND: The rapid establishment and persistence of latent HIV-1 reservoirs is one of the main obstacles towards an HIV cure. While antiretroviral therapy supresses viral replication, it does not eradicate the latent reservoir of HIV-1-infected cells. Recent evidence suggests that the human microbiome, particularly the gut microbiome, may have the potential to modulate the HIV-1 reservoir. However, literature is limited and the exact mechanisms underlying the role of the microbiome in HIV immunity and potential regulation of the viral reservoir remain poorly understood.<br><br>RESULTS: Here, we review updated knowledge on the associations between the human microbiome and HIV reservoir across different anatomical sites, including the gut, the lungs and blood. We provide an overview of the predominant taxa associated with prominent microbiome changes in the context of HIV infection. Based on the current evidence, we summarize the main study findings, with specific focus on consistent bacterial and related byproduct associations. Specifically, we address the contribution of immune activation and inflammatory signatures on HIV-1 persistence. Furthermore, we discuss possible scenarios by which bacterial-associated inflammatory mediators, related metabolites and host immune signatures may modulate the HIV reservoir size. Finally, we speculate on potential implications of microbiome-based therapeutics for future HIV-1 cure strategies, highlighting challenges and limitations inherent in this research field.<br><br>CONCLUSIONS: Despite recent advances, this review underscores the need for further research to deepen the understanding of the complex interplay between the human microbiome and HIV reservoir. Further integrative multi-omics assessments and functional studies are crucial to test the outlined hypothesis and to identify potential therapeutic targets ultimately able to achieve an effective cure for HIV.}, }
@article {pmid39614169, year = {2024}, author = {Tang, H and Du, S and Niu, Z and Zhang, D and Tang, Z and Chen, H and Chen, Z and Zhang, M and Xu, Y and Sun, Y and Fu, X and Norback, D and Shao, J and Zhao, Z}, title = {Nasal, dermal, oral and indoor dust microbe and their interrelationship in children with allergic rhinitis.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {505}, pmid = {39614169}, issn = {1471-2180}, mesh = {Humans ; *Dust/analysis ; Male ; Child ; Female ; *Rhinitis, Allergic/microbiology ; Case-Control Studies ; *RNA, Ribosomal, 16S/genetics ; *Bacteria/classification/isolation &amp; purification/genetics ; *Skin/microbiology ; *Mouth/microbiology ; *Microbiota ; Nasal Cavity/microbiology ; Air Pollution, Indoor/analysis ; Child, Preschool ; Metagenomics/methods ; Nose/microbiology ; }, abstract = {BACKGROUND: Allergic rhinitis (AR) subjects might have their microenvironment changed due to pathogenesis and living environment. Whether the nasal microbe in AR children differs from healthy subjects and how it interplays with dermal, oral and indoor dust microbe needs to be elucidated.<br><br>METHODS: In this case-control study, we analyzed and compared the bacterial characterization and associations in nasal, dermal, oral swab samples and dust samples in 62 children with physician-diagnosed AR(cases) and 51 age- and gender-matched healthy ones with no history of allergic diseases(controls). Full-length 16S rRNA sequencing(swabs) and shotgun metagenomics(dust) were applied. Bacterial diversity, composition, abundance difference characteristics and fast expectation-maximization for microbial source tracking(FEAST) analysis were performed and compared between cases and controls.<br><br>RESULTS: The &#x3b1;-diversity of dust microorganisms in AR was lower than that in control group (P&#x2009;=&#x2009;0.034), and the &#x3b2;-diversity indices of microorganisms in nasal cavity (P&#x2009;=&#x2009;0.020), skin (P&#x2009;=&#x2009;0.001) and dust (P&#x2009;=&#x2009;0.004) were significantly different from those in control group. At species levels, a total of 10, 15, 12, and 15 bacterial species were differentially enriched in either cases or controls in nasal, dermal, oral, and dust samples, respectively(Linear Discriminant Analysis(LDA) score&#x2009;>&#x2009;2, P&#x2009;<&#x2009;0.05). Staphylococcus epidermidis was the single species simultaneously more abundant in nasal, dermal and dust samples in AR children. By FEAST analysis, 8.85% and 10.11% of S. epidermidis in AR dermal and dust samples came from nasal cavity. These proportions were significantly higher than those in controls (2.70% and 3.86%) (P&#x2009;<&#x2009;0.05). The same significantly higher transfer proportions(P&#x2009;<&#x2009;0.05) were observed for Staphylococcus aureus enriched in the nasal cavity in AR children. Classification models by random forest regression at species levels showed, bacterial species enriched in indoor dust, nasal and dermal samples had substantial power in distinguishing AR children from healthy ones, with the highest power in the dust samples (AUC&#x2009;=&#x2009;0.88) followed by nasal(AUC&#x2009;=&#x2009;0.81) and dermal ones(AUC&#x2009;=&#x2009;0.80).<br><br>CONCLUSIONS: Our study presented the microbial enrichment characteristics in AR children both in the living environment(dust) and body sites exposed to environment through inhalation(nasal cavity), contact(skin) and ingestion(oral cavity) pathways, respectively. Nasal S.epidermidis and S.aureus had dominant influences on dust and other body sites in AR children.}, }
@article {pmid39607341, year = {2024}, author = {Merk, LN and Shur, AS and Jena, S and Munoz, J and Brubaker, DK and Murray, RM and Green, LN}, title = {Diagnostic and Therapeutic Microbial Circuit with Application to Intestinal Inflammation.}, journal = {ACS synthetic biology}, volume = {13}, number = {12}, pages = {3885-3896}, doi = {10.1021/acssynbio.3c00668}, pmid = {39607341}, issn = {2161-5063}, mesh = {*Escherichia coli ; Humans ; *Probiotics/therapeutic use ; *Interleukin-22 ; Interleukins/metabolism/genetics ; Tetrathionic Acid/metabolism ; Inflammation/metabolism ; Gastrointestinal Microbiome/drug effects ; Inflammatory Bowel Diseases/therapy/metabolism ; Hemolysin Proteins/metabolism/genetics ; Tetracyclines ; }, abstract = {Bacteria genetically engineered to execute defined therapeutic and diagnostic functions in physiological settings can be applied to colonize the human microbiome, providing in situ surveillance and conditional disease modulation. However, many engineered microbes can only respond to single-input environmental factors, limiting their tunability, precision, and effectiveness as living diagnostic and therapeutic systems. For engineering microbes to improve complex chronic disorders such as inflammatory bowel disease, the bacteria must respond to combinations of stimuli in the proper context and time. This work implements a previously characterized split activator AND logic gate in the probiotic Escherichia coli strain Nissle 1917 (EcN). Our system can respond to two input signals: the inflammatory biomarker tetrathionate and a second input signal, anhydrotetracycline (aTc), for manual control. We report 4-6 fold induction with a minimal leak when the two chemical signals are present. We model the AND gate dynamics using chemical reaction networks and tune parameters in silico to identify critical perturbations that affect our circuit's selectivity. Finally, we engineer the optimized AND gate to secrete a therapeutic anti-inflammatory cytokine IL-22 using the hemolysin secretion pathway in the probiotic E. coli strain. We used a germ-free transwell model of the human gut epithelium to show that our engineering bacteria produce similar host cytokine responses compared to recombinant cytokine. Our study presents a scalable workflow to engineer cytokine-secreting microbes driven by logical signal processing. It demonstrates the feasibility of IL-22 derived from probiotic EcN with minimal off-target effects in a gut epithelial context.}, }
@article {pmid39602306, year = {2024}, author = {Pasolli, E and Mauriello, IE and Avagliano, M and Cavaliere, S and De Filippis, F and Ercolini, D}, title = {Bifidobacteriaceae diversity in the human microbiome from a large-scale genome-wide analysis.}, journal = {Cell reports}, volume = {43}, number = {12}, pages = {115027}, doi = {10.1016/j.celrep.2024.115027}, pmid = {39602306}, issn = {2211-1247}, mesh = {Humans ; *Phylogeny ; *Microbiota/genetics ; Metagenome ; Genome, Bacterial ; Genome-Wide Association Study ; Probiotics ; }, abstract = {We performed a large-scale genome-wide analysis aiming to investigate the prevalence and strain-level diversity of Bifidobacteriaceae species in the human microbiome. We considered 9,528 publicly available human metagenomes and integrated them with 1,192 isolate genomes from different sources. The prevalence and abundance of Bifidobacteriaceae species in humans was linked to multiple host characteristics: they were reduced in older people and enriched in populations characterized by Westernized lifestyles with geography-specific patterns. Phylogenetic analysis highlighted 110 Bifidobacteriaceae species-level genome bins (SGBs), with 32 found in humans and 8 in food and probiotic sources. Functional annotation revealed a great diversity in carbohydrate-active enzyme families across these SGBs. We found potential subspecies for most of the SGBs prevalent in humans and identified patterns driven by age and geography. We provided evidence that strains used in probiotics were rarely identified in humans, with the only exception represented by Bifidobacterium animalis. We finally evaluated that the abundance of Bifidobacteriaceae species exhibited moderate and variable capabilities to predict health status in case-control studies.}, }
@article {pmid39600874, year = {2024}, author = {Patjas, A and Jokiranta, TS and Kantele, A}, title = {Urinary tract infections: a retrospective cohort study of (mis)matching antimicrobial therapy and clinical outcome among Finnish adults.}, journal = {JAC-antimicrobial resistance}, volume = {6}, number = {6}, pages = {dlae188}, pmid = {39600874}, issn = {2632-1823}, abstract = {OBJECTIVES: With the global spread of antimicrobial resistance, treating urinary tract infections (UTIs) is becoming more challenging. Clinical data on UTI outcomes are scarce in cases with antimicrobial treatment mismatching the uropathogens' in vitro susceptibility profiles. We explored the association of (mis)matching antimicrobial treatment and clinical outcomes among patients with either ESBL-producing Enterobacterales (ESBL-PE) or non-ESBL-PE identified in urine samples.<br><br>PATIENTS AND METHODS: In 2015-2019, we recruited 18-65-year-old patients with laboratory-confirmed, community-acquired ESBL-PE (n&#x200a;=&#x200a;130) or non-ESBL-PE (n&#x200a;=&#x200a;187) UTI. Our study involved collecting data on in vitro susceptibility profiles, antimicrobial therapy (microbiological match/mismatch) and clinical outcomes, and a follow-up of relapses/reinfections.<br><br>RESULTS: Non-beta-lactam co-resistance was found more frequent among ESBL-PE than non-ESBL-PE isolates. The initial antimicrobial matched the in vitro susceptibility for 91.6% (164/179) of those with non-ESBL-PE and 46.9% (38/81) with ESBL-PE UTI (P&#x200a;<&#x200a;0.001). The clinical cure rates in the non-ESBL-PE and ESBL-PE UTI groups were 82.6% (142/172) and 62.2% (74/119) (P&#x200a;<&#x200a;0.001) for all, 87.3% (131/150) and 83.3% (30/36) for those treated with matching antimicrobials, and 33.3% (5/15) and 41.9% (18/43) for those given mismatching antimicrobials, respectively. Mismatching antimicrobial therapy was not associated with relapse/reinfection over the 3-month follow-up (P&#x200a;=&#x200a;0.943).<br><br>CONCLUSIONS: In our data, (mis)matching microbiological susceptibility is only partially associated with the clinical outcome of UTI: microbiological matching appears to predict clinical cure better than mismatching predicts clinical failure.}, }
@article {pmid39600755, year = {2024}, author = {Castro-Vidal, ZA and Mathew, F and Ibrahim, AA and Shubhangi, F and Cherian, RR and Choi, HK and Begum, A and Ravula, HK and Giri, H}, title = {The Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Various Neurocognitive Disorders.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72451}, pmid = {39600755}, issn = {2168-8184}, abstract = {This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.}, }
@article {pmid39596404, year = {2024}, author = {Wang, Z and Kaplan, RC and Burk, RD and Qi, Q}, title = {The Oral Microbiota, Microbial Metabolites, and Immuno-Inflammatory Mechanisms in Cardiovascular Disease.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596404}, issn = {1422-0067}, support = {K01 HL169019/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Cardiovascular Diseases/microbiology/immunology/metabolism ; *Mouth/microbiology ; Inflammation/microbiology/metabolism/immunology ; Gastrointestinal Microbiome ; Microbiota ; Animals ; }, abstract = {Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality. Recent advancements in high-throughput omics techniques have enhanced our understanding of the human microbiome's role in the development of CVDs. Although the relationship between the gut microbiome and CVDs has attracted considerable research attention and has been rapidly evolving in recent years, the role of the oral microbiome remains less understood, with most prior studies focusing on periodontitis-related pathogens. In this review, we summarized previously reported associations between the oral microbiome and CVD, highlighting known CVD-associated taxa such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We also discussed the interactions between the oral and gut microbes. The potential mechanisms by which the oral microbiota can influence CVD development include oral and systemic inflammation, immune responses, cytokine release, translocation of oral bacteria into the bloodstream, and the impact of microbial-related products such as microbial metabolites (e.g., short-chain fatty acids [SCFAs], trimethylamine oxide [TMAO], hydrogen sulfide [H2S], nitric oxide [NO]) and specific toxins (e.g., lipopolysaccharide [LPS], leukotoxin [LtxA]). The processes driven by these mechanisms may contribute to atherosclerosis, endothelial dysfunction, and other cardiovascular pathologies. Integrated multi-omics methodologies, along with large-scale longitudinal population studies and intervention studies, will facilitate a deeper understanding of the metabolic and functional roles of the oral microbiome in cardiovascular health. This fundamental knowledge will support the development of targeted interventions and effective therapies to prevent or reduce the progression from cardiovascular risk to clinical CVD events.}, }
@article {pmid39595814, year = {2024}, author = {Belnap, N and Ramsey, K and Carvalho, ST and Nearman, L and Haas, H and Huentelman, M and Lee, K}, title = {Exploring the Frontier: The Human Microbiome's Role in Rare Childhood Neurological Diseases and Epilepsy.}, journal = {Brain sciences}, volume = {14}, number = {11}, pages = {}, pmid = {39595814}, issn = {2076-3425}, abstract = {Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut-brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this disease and other rare neurological diseases.}, }
@article {pmid39595625, year = {2024}, author = {Reshetova, M and Markin, P and Appolonova, S and Yunusov, I and Zolnikova, O and Bueverova, E and Dzhakhaya, N and Zharkova, M and Poluektova, E and Maslennikov, R and Ivashkin, V}, title = {Tryptophan Metabolites in the Progression of Liver Diseases.}, journal = {Biomolecules}, volume = {14}, number = {11}, pages = {}, pmid = {39595625}, issn = {2218-273X}, mesh = {Humans ; *Tryptophan/metabolism/blood ; Male ; Female ; Middle Aged ; Adult ; Kynurenine/analogs &amp; derivatives/metabolism/blood ; Disease Progression ; Liver Diseases, Alcoholic/metabolism/blood ; Serotonin/metabolism/blood ; Aged ; Fatty Liver/metabolism/blood ; Liver Cirrhosis/metabolism/blood ; }, abstract = {The aim of this study was to investigate the levels of various tryptophan metabolites in patients with alcoholic liver disease (ALD) and metabolic-associated fatty liver disease (MAFLD) at different stages of the disease. The present study included 44 patients diagnosed with MAFLD, 40 patients diagnosed with ALD, and 14 healthy individuals in the control group. The levels of tryptophan and its 16 metabolites (3-OH anthranilic acid, 5-hydroxytryptophan, 5-methoxytryptamine, 6-hydroxymelatonin, indole-3-acetic acid, indole-3-butyric, indole-3-carboxaldehyde, indole-3-lactic acid, indole-3-propionic acid, kynurenic acid, kynurenine, melatonin, quinolinic acid, serotonin, tryptamine, and xanthurenic acid) in the serum were determined via high-performance liquid chromatography and tandem mass spectrometry. In patients with cirrhosis resulting from MAFLD and ALD, there are significant divergent changes in the serotonin and kynurenine pathways of tryptophan catabolism as the disease progresses. All patients with cirrhosis showed a decrease in serotonin levels ([MAFLD]p = 0.038; [ALD]p < 0.001) and an increase in kynurenine levels ([MAFLD]p = 0.032; [ALD]p = 0.010). A negative correlation has been established between serotonin levels and the FIB-4 index (p < 0.001). The decrease in serotonin pathway metabolites was associated with manifestations of portal hypertension (p = 0.026), the development of hepatocellular insufficiency (p = 0.008) (hypoalbuminemia; hypocoagulation), and jaundice (p < 0.001), while changes in the kynurenine pathway metabolite xanthurenic acid were associated with the development of hepatic encephalopathy (p = 0.044). Depending on the etiological factors of cirrhosis, disturbances in the metabolic profile may be involved in various pathogenetic pathways.}, }
@article {pmid39589128, year = {2025}, author = {Agnew, A and Humm, E and Zhou, K and Gunsalus, RP and Zhou, ZH}, title = {Structure and identification of the native PLP synthase complex from Methanosarcina acetivorans lysate.}, journal = {mBio}, volume = {16}, number = {1}, pages = {e0309024}, pmid = {39589128}, issn = {2150-7511}, support = {T32 GM145388/GM/NIGMS NIH HHS/United States ; 1911781//National Science Foundation (NSF)/ ; S10 OD018111/OD/NIH HHS/United States ; R01 GM071940/GM/NIGMS NIH HHS/United States ; T90 DE030860/DE/NIDCR NIH HHS/United States ; R01GM071940, T32GM145388//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; T90DE030860//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; DE-FC-02-372 02ER63421//U.S. Department of Energy (DOE)/ ; }, mesh = {*Methanosarcina/enzymology/genetics/chemistry ; *Cryoelectron Microscopy ; *Archaeal Proteins/chemistry/metabolism/genetics ; Models, Molecular ; Protein Conformation ; Pyridoxal Phosphate/metabolism ; Proteomics ; }, abstract = {Many protein-protein interactions behave differently in biochemically purified forms as compared to their in vivo states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here, we apply the bottom-up structural proteomics method, cryoID, toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through the cryoID approach, we successfully reconstructed and identified the native Methanosarcina acetivorans pyridoxal 5'-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryo-EM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryo-EM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37-amino-acid insertion present in these prior cases. This study demonstrates the potential of applying the cryoID workflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.IMPORTANCEArchaea are one of the three domains of life, classified as a phylogenetically distinct lineage. There is a paucity of known enzyme structures from organisms of this domain, and this is often exacerbated by characteristically difficult growth conditions and a lack of readily available molecular biology toolkits to study proteins in archaeal cells. As a result, there is a gap in knowledge concerning the mechanisms governing archaeal protein behavior and their impacts on both the environment and human health; case in point, the synthesis of the widely utilized cofactor pyridoxal 5'-phosphate (PLP; a vitamer of vitamin B6, which humans cannot produce). By leveraging the power of single-particle cryo-EM and map-to-primary sequence identification, we determine the native structure of PLP synthase from cellular lysate. Our workflow allows the (i) rapid examination of new or less characterized systems with minimal sample requirements and (ii) discovery of structural states inaccessible by recombinant expression.}, }
@article {pmid39584055, year = {2024}, author = {Kajova, M and Khawaja, T and Levonen, I and Pietilä, JP and Virtanen, J and Pakkanen, SH and Välimaa, H and Nousiainen, A and Hepojoki, J and Sironen, T and Vierikko, A and Ihalainen, J and Vapalahti, O and Kantele, A}, title = {Convalescent plasma therapy for COVID-19 - Donor selection strategies and establishment of a plasma bank.}, journal = {New microbes and new infections}, volume = {62}, number = {}, pages = {101525}, pmid = {39584055}, issn = {2052-2975}, abstract = {BACKGROUND: Early in the COVID-19 pandemic, convalescent plasma (CP) emerged as a potentially effective treatment neutralising SARS-CoV-2. Early CP therapy with high neutralising antibody (NAb) titre may benefit COVID-19 outpatients and, in sufficient quantities even some hospitalised patients. This study details the process of setting up a CP bank, containing high- and low-titre CP for a clinical trial.<br><br>STUDY DESIGN AND METHODS: We identified 18-65-year-old convalescents with SARS-CoV-2 NAb titres of &#x2265;1:40 in microneutralisation test (MNT). Following eligibility pre-screening, the Finnish Red Cross Blood Service (FRCBS) determined suitability as CP donors.<br><br>RESULTS: Of the 6466 COVID-19 convalescents contacted, 1481 provided serum, with 851 (57.5&#xa0;%) exhibiting NAb titres &#x2265;1:40. Participation barriers included reluctance, advanced age and, for women, insufficient body size. Of the volunteers, 125 were evaluated at FRCBS, with major exclusions for HLA antibodies (42 women), interferon antibodies (five men), and NAb titres waning below 1:20 (16 participants). Finally, 70 underwent plasmapheresis, resulting in 50 suitable CP donors (0.8&#xa0;% of initial contacts and 3.4&#xa0;% of those tested for NAb).<br><br>DISCUSSION: The process of setting up a CP bank proved challenging. Excessive laboratory workloads during a pandemic hamper their ability to conduct MNT, underscoring the need for rapid screening tests. Only a small proportion of our convalescents exhibited high-titre CP, this fraction declining over time because of waning immunity. Strict plasmapheresis criteria further constrained donor eligibility. Establishing a plasma bank requires meticulous planning to maximize efficiency. Detailed insights from current experiences may prove critical in future pandemics before other remedies and vaccines become available.}, }
@article {pmid39582897, year = {2024}, author = {Wang, Z and Wu, X and Wang, Y and Wen, Q and Cui, B and Zhang, F}, title = {Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241301574}, pmid = {39582897}, issn = {1756-283X}, abstract = {The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.}, }
@article {pmid39581825, year = {2025}, author = {Isali, I and Almassi, N and Nizam, A and Campbell, R and Weight, C and Gupta, S and Pooja, G and Fulmes, A and Mishra, K and Abbosh, P and Bukavina, L}, title = {State of the Art: The Microbiome in Bladder Cancer.}, journal = {Urologic oncology}, volume = {43}, number = {4}, pages = {199-208}, doi = {10.1016/j.urolonc.2024.11.008}, pmid = {39581825}, issn = {1873-2496}, mesh = {Humans ; *Urinary Bladder Neoplasms/microbiology ; *Microbiota ; Tumor Microenvironment ; }, abstract = {This review assesses the current understanding of the relationship between the human microbiome and BCa. Recognizing how the microbiome affects the tumor microenvironment provides valuable insights into cancer biology, potentially uncovering interactions that could be leveraged to develop innovative therapeutic approaches. By clarifying these intricate microbial-tumor dynamics, novel targets for microbiome-based interventions can be identified, ultimately improving treatment effectiveness and patient outcomes. Current literature lacks comprehensive insights into the effects of BCa treatment on the microbiome and the prevalence of immunotherapy-related toxicities. Further research into the microbiome's role in BCa development could bridge the gap between fundamental research and therapeutic applications. Implementing microbiome surveillance, metagenomic sequencing, and metabolomics in clinical trials could deepen our understanding of BCa and its treatment. This review explores the existing understanding of the urine, tissue, and gut microbiomes and their connections to BCa. Enhanced knowledge of these relationships can pave the way for future research to identify reliable disease predictors, prognostic markers, and novel therapeutic targets.}, }
@article {pmid39575247, year = {2024}, author = {Zhu, Y and Liang, X and Zhi, M and Li, L and Zhang, G and Chen, C and Wang, L and Wang, P and Zhong, N and Feng, Q and Li, Z}, title = {Succession of the multi-site microbiome along pancreatic ductal adenocarcinoma tumorigenesis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1487242}, pmid = {39575247}, issn = {1664-3224}, mesh = {Humans ; *Carcinoma, Pancreatic Ductal/microbiology/pathology ; *Pancreatic Neoplasms/microbiology/pathology ; Male ; Female ; Microbiota ; Middle Aged ; Saliva/microbiology ; Aged ; Carcinogenesis ; Bacteria/classification/genetics ; Pancreatitis, Chronic/microbiology ; RNA, Ribosomal, 16S/genetics ; Adult ; }, abstract = {BACKGROUND: To investigate microbial characteristics across multibody sites from chronic pancreatitis (CP), through pancreatic benign tumors, to pancreatic ductal adenocarcinoma (PDAC) at different stages.<br><br>METHODS: 16S ribosomal RNA (rRNA) amplicon sequencing was conducted on saliva, duodenal fluid, and pancreatic tissue obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of patients with CP, pancreatic benign tumors, PDAC in stage I/II, III, and IV. The neutral community model (NCM) assessed the microbial assembly contribution and MaAslin2 identified the differential microbes.<br><br>RESULTS: From CP to stage IV PDAC patients, there was a marked surge in influence of salivary and duodenal microbiota on constitution of pancreatic microbial communities. Our observations revealed a successive alteration in microbial species across various bodily sites during PDAC tumorigenesis. Notably, Porphyromonas gingivalis, Treponema denticola, Peptoanaerobacter stomatis, Propionibacterium acidifaciens, Porphyromonas endodontalis, Filifactor alocis, etc., sequentially increased along PDAC progression in pancreatic tissue, whereas bacteria commonly used as probiotics Bifidobacterium breve, Lactiplantibacillus plantarum, etc., declined. Furthermore, the sequentially escalating trends of Peptoanaerobacter stomatis and Propionibacterium acidifaciens during PDAC tumorigenesis were mirrored in duodenal fluid and saliva. Porphyromonas gingivalis, Porphyromonas endodontalis, and Filifactor alocis, which intensified from CP to stage IV PDAC in pancreatic tissue, were also found to be enriched in saliva of patients with short-term survival (STS) compared with those with long-term survival (LTS).<br><br>CONCLUSIONS: Salivary and duodenal microorganisms were prominent factors in shaping pancreatic microbial landscape in PDAC context. Further exploration of these microbial entities is imperative to unravel their specific roles in PDAC pathogenesis, potentially yielding insights for future therapeutic strategies.}, }
@article {pmid39575165, year = {2024}, author = {Teng, Z and Li, Q and Shen, XF}, title = {Correlations of Nasal Microbiome with Allergic Rhinitis and Its Symptoms Severity in Children Progression.}, journal = {Journal of asthma and allergy}, volume = {17}, number = {}, pages = {1187-1196}, pmid = {39575165}, issn = {1178-6965}, abstract = {OBJECTIVE: Human microbiome is involved in the pathogenesis of allergic diseases, but the impact of nasal microbiota on allergic rhinitis (AR) symptoms severity has not been evaluated. This study aimed to characterize nasal microbiome in AR children and its correlations with AR symptoms.<br><br>METHODS: According to diagnostic guidelines for AR, 45 AR children and 40&#xa0;healthy subjects were recruited from July to August in 2023. Based on the total score of nasal symptoms (TNSS), the 45 AR patients were divided into a mild AR group (MAR) (n = 16) and a moderate or severe AR group (MSAR) (n = 29). Nasal swabs were collected for microbiome analysis using 16S-rDNA sequencing.<br><br>RESULTS: The Simpson and Shannon indices were significantly higher in the AR group compared to the health control group, indicating an increase of nasal microbiota at the species evenness level in AR children. Moreover, the species evenness was significantly increased in the MSAR group compared to the MAR group. Staphylococcus (member of the Firmicutes phylum) was significantly dominant in the AR group, but Moraxella (member of the Proteobacteria phylum) was significantly dominant in the CG group. The LEfSe analysis showed that the mean relative abundances of Ralstonia in the MSAR group was higher than that in the MAR group. Meanwhile, the abundance divided by Ralstonia of Spearman correlation coefficients was positively correlated with the TNSS of AR symptoms (r = 0.4, P = 0.009).<br><br>CONCLUSION: The elevation of species evenness in nasal microbiome was likely related to the aggravation of AR symptoms. The Ralstonia may play a pro-inflammatory role in AR.}, }
@article {pmid39574598, year = {2024}, author = {Nguyen, UT and Salamzade, R and Sandstrom, S and Swaney, MH and Townsend, L and Wu, SY and Cheong, JZA and Sardina, JA and Ludwikoski, I and Rybolt, M and Wan, H and Carlson, C and Zarnowski, R and Andes, D and Currie, C and Kalan, L}, title = {Large-scale investigation for antimicrobial activity reveals novel defensive species across the healthy skin microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39574598}, issn = {2692-8205}, support = {R35 GM137828/GM/NIGMS NIH HHS/United States ; T32 GM135066/GM/NIGMS NIH HHS/United States ; U19 AI142720/AI/NIAID NIH HHS/United States ; }, abstract = {The human skin microbiome constitutes a dynamic barrier that can impede pathogen invasion by producing antimicrobial natural products. Gene clusters encoding for production of secondary metabolites, biosynthetic gene clusters (BGCs), that are enriched in the human skin microbiome relative to other ecological settings, position this niche as a promising source for new natural product mining. Here, we introduce a new human microbiome isolate collection, the EPithelial Isolate Collection (EPIC). It includes a large phylogenetically diverse set of human skin-derived bacterial strains from eight body sites. This skin collection, consisting of 980 strains is larger and more diverse than existing resources, includes hundreds of rare and low-abundance strains, and hundreds of unique BGCs. Using a large-scale co-culture screen to assess 8,756 pairwise interactions between skin-associated bacteria and potential pathogens, we reveal broad antifungal activity by skin microbiome members. Integrating 287 whole isolate genomes and 268 metagenomes from sampling sites demonstrates that while the distribution of BGC types is stable across body sites, specific gene cluster families (GCFs), each predicted to encode for a distinct secondary metabolite, can substantially vary. Sites that are dry or rarely moist harbor the greatest potential for discovery of novel bioactive metabolites. Among our discoveries are four novel bacterial species, three of which exert significant and broad-spectrum antifungal activity. This comprehensive isolate collection advances our understanding of the skin microbiomes biosynthetic capabilities and pathogen-fighting mechanisms, opening new avenues towards antimicrobial drug discovery and microbiome engineering.}, }
@article {pmid39571733, year = {2024}, author = {Yu, J and Feng, L and Luo, Z and Yang, J and Zhang, Q and Liu, C and Liang, D and Xie, Y and Li, H and Gong, J and He, Z and Lan, P}, title = {Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.11.024}, pmid = {39571733}, issn = {2090-1224}, abstract = {INTRODUCTION: The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.<br><br>METHODS: The impact of Il10 deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of Parabacteroides distasonis (P. distasonis) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in P. distasonis inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both in vivo and in vitro. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.<br><br>RESULTS: We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, Il10-deficiency (Il10[-/-]) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, Il10[-/-] mice reshaped gut microbiota composition, notably enriching P. distasonis. The enriched P. distasonis produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of VEGFA, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both in vitro and in vivo lung metastasis mouse models.<br><br>CONCLUSIONS: These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-VEGFA axis mediated by gut P. distasonis, suggesting that P. distasonis or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.}, }
@article {pmid39569373, year = {2024}, author = {Talukdar, D and Sarkar, M and Ahrodia, T and Kumar, S and De, D and Nath, S and Jana, P and Verma, J and Mehta, O and Kothidar, A and Yodhaanjali, JR and Sharma, K and Bakshi, S and Singh, U and Kshetrapal, P and Wadhwa, N and Thiruvengadam, R and ,  and Nair, GB and Bhatnagar, S and Mukherjee, S and Das, B}, title = {Previse preterm birth in early pregnancy through vaginal microbiome signatures using metagenomics and dipstick assays.}, journal = {iScience}, volume = {27}, number = {11}, pages = {111238}, pmid = {39569373}, issn = {2589-0042}, abstract = {Annually, in India, 13% of all newborns are preterm, accounting for 23.4% of preterm birth (PTB) globally. The composition and diversity of the vaginal microbiome have a notable degree of ethnic inequality. For understanding differences in vaginal microbiome composition and functions between adverse and normal pregnancy, we have collected, processed and sequenced 600 high vaginal swab (HVS) samples across the three trimesters of pregnancy from 140 women who delivered at term and 60 women who delivered PTB, adopting a targeted metagenomics approach. The microbial signatures in HVS samples showed Lactobacillus genera to be highly abundant in term birth (TB), while in early pregnancy the abundances of Gardnerella, Atopobium, and Sneathia were found to be high in PTB. We further extended our analysis, identified specific microbial genomic signatures, and developed a dipstick assay for rapid identification of PTB-associated microbiota in HVS samples in low-resource settings.}, }
@article {pmid39565565, year = {2024}, author = {Pino, A and Hiippala, K and Ronkainen, A and Vaccalluzzo, A and Caggia, C and Satokari, R and Randazzo, CL}, title = {Adhesion Properties and Pathogen Inhibition of Vaginal-Derived Lactobacilli.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39565565}, issn = {1867-1314}, abstract = {In the present study, twenty-seven (27) lactobacilli strains, isolated from the vagina of healthy Italian women of reproductive age, were screened for probiotic properties. The strains were evaluated for antagonistic activity against pathogens, adhesion abilities, and potential to displace and/or inhibit the adhesion of previously adhered pathogens as a primary strain selection criterion. Overall, all the tested lactobacilli inhibited at least three pathogens, and the majority of them exhibited antimicrobial activity against Enterobacter cloacae DSM 30054, Pseudomonas aeruginosa DSM 3227, and Pseudomonas aeruginosa DSM 1117. The complete neutralization of antimicrobial activity after cell-free supernatant (CFS) neutralization suggested a pivotal role for lactic acid or other organic acids secreted by the lactobacilli. The strains showed variability in their adhesion levels, but all tested strains adhered to both human colonic epithelial cells (HT-29) and vaginal cells (VK2/E6E7) with adhesion percentages exceeding 1%. The ability to displace or inhibit pathogens was dependent on the pathogen and the lactobacilli strain; the pathogen displacement levels ranged from 9 to 82%, while pathogen exclusion levels varied from 1 to 99%. In conclusion, this study demonstrates the protective effect of vaginal lactobacilli against pathogens and confirms the suitability of the vaginal microbiota as a source of potential probiotic strains. The selected lactobacilli hold promise for the formulation of supplements to enhance genitourinary tract health.}, }
@article {pmid39565308, year = {2024}, author = {Dong, PT and Shi, W and He, X and Borisy, GG}, title = {Adhesive interactions within microbial consortia can be differentiated at the single-cell level through expansion microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {48}, pages = {e2411617121}, pmid = {39565308}, issn = {1091-6490}, support = {R01 DE023810/DE/NIDCR NIH HHS/United States ; DE023810//HHS | NIH (NIH)/ ; DE022586//HHS | NIH (NIH)/ ; DE030943//HHS | NIH (NIH)/ ; R01 DE022586/DE/NIDCR NIH HHS/United States ; K99 DE033794/DE/NIDCR NIH HHS/United States ; K99DE033794//HHS | NIH (NIH)/ ; R01 DE030943/DE/NIDCR NIH HHS/United States ; }, mesh = {*Biofilms/growth &amp; development ; *Microbial Consortia/physiology ; *Bacterial Adhesion/physiology ; Single-Cell Analysis/methods ; Microscopy/methods ; Streptococcus/physiology ; Streptococcus mutans/physiology ; Fusobacterium nucleatum/physiology ; }, abstract = {Investigating microbe-microbe interactions at the single-cell level is critical to unraveling the ecology and dynamics of microbial communities. In many situations, microbes assemble themselves into densely packed multispecies biofilms. The density and complexity pose acute difficulties for visualizing individual cells and analyzing their interactions. Here, we address this problem through an unconventional application of expansion microscopy, which allows for the "decrowding" of individual bacterial cells within a multispecies community. Expansion microscopy generally has been carried out under isotropic expansion conditions and used as a resolution-enhancing method. In our variation of expansion microscopy, we carry out expansion under heterotropic conditions; that is, we expand the space between bacterial cells but not the space within individual cells. The separation of individual bacterial cells from each other reflects the competition between the expansion force pulling them apart and the adhesion force holding them together. We employed heterotropic expansion microscopy to study the relative strength of adhesion in model biofilm communities. These included mono- and dual-species Streptococcus biofilms and a three-species synthetic community (Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sanguinis) under conditions that facilitated interspecies coaggregation. Using adhesion mutants, we investigated the interplay between F. nucleatum outer membrane protein RadD and different Streptococcus species. We also examined the Schaalia-TM7 epibiont association. Quantitative proximity analysis was used to evaluate the separation of individual microbial members. Our study demonstrates that heterotropic expansion microscopy can "decrowd" dense biofilm communities, improve visualization of individual bacterial members, and enable analysis of microbe-microbe adhesive interactions at the single-cell level.}, }
@article {pmid39563467, year = {2024}, author = {Liu, R and Wang, Y and Cheng, D}, title = {Micro-DeMix: a mixture beta-multinomial model for investigating the heterogeneity of the stool microbiome compositions.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {12}, pages = {}, pmid = {39563467}, issn = {1367-4811}, support = {DMS-2220523//National Institute of Health/ ; 854127//Simons Foundation Collaboration/ ; }, mesh = {Humans ; *Feces/microbiology ; *Gastrointestinal Microbiome ; *Software ; Inflammatory Bowel Diseases/microbiology ; }, abstract = {MOTIVATION: Extensive research has uncovered the critical role of the human gut microbiome in various aspects of health, including metabolism, nutrition, physiology, and immune function. Fecal microbiota is often used as a proxy for understanding the gut microbiome, but it represents an aggregate view, overlooking spatial variations across different gastrointestinal (GI) locations. Emerging studies with spatial microbiome data collected from specific GI regions offer a unique opportunity to better understand the spatial composition of the stool microbiome.<br><br>RESULTS: We introduce Micro-DeMix, a mixture beta-multinomial model that deconvolutes the fecal microbiome at the compositional level by integrating stool samples with spatial microbiome data. Micro-DeMix facilitates the comparison of microbial compositions across different GI regions within the stool microbiome through a hypothesis-testing framework. We demonstrate the effectiveness and efficiency of Micro-DeMix using multiple simulated datasets and the inflammatory bowel disease data from the NIH Integrative Human Microbiome Project.<br><br>The R package is available at https://github.com/liuruoqian/MicroDemix.}, }
@article {pmid39562050, year = {2025}, author = {Li, N and Li, Y and Huang, Z and Cao, Z and Cao, C and Gao, X and Zuo, T}, title = {Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice.}, journal = {Gut}, volume = {74}, number = {5}, pages = {868-870}, doi = {10.1136/gutjnl-2024-333598}, pmid = {39562050}, issn = {1468-3288}, }
@article {pmid39561848, year = {2024}, author = {Yang, J and Sun, S and Sun, N and Lu, L and Zhang, C and Shi, W and Zhao, Y and Jia, S}, title = {HMMER-Extractor: an auxiliary toolkit for identifying genomic macromolecular metabolites based on Hidden Markov Models.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 2}, pages = {137666}, doi = {10.1016/j.ijbiomac.2024.137666}, pmid = {39561848}, issn = {1879-0003}, mesh = {*Markov Chains ; *Software ; Humans ; Genome, Bacterial ; Genomics/methods ; Macromolecular Substances/chemistry ; Computational Biology/methods ; Microbiota/genetics ; }, abstract = {Human microbiome contains various microbial macromolecules with important biological functions. The Hidden Markov Models (HMMs) can overcome the problem of low similarity sequences with distant relationships and are widely implemented within various sequence alignment softwares. However, the HMM-based sequence alignments can generate a large number of results, how to quickly screen and batch extract target homologs from microbiomes is the major sticking points. It is necessary to develop an integrated gene filter and extraction pipeline to quickly and accurately screen homologs. Here, we introduced the HMMER-Extractor for amino acids or nucleotide sequences extraction, which was a supporting toolkit through provided filtering scores and an iterative keyword matching (IKM) logic. To make it more user-friendly and accessible, we further presented a visualized web server platform. An interactive HTML output provided a user-friendly way to browse homologous annotations and sequence extraction. The web server provided the community with a streamlined and user-friendly interface to analyze microbiomes. Through the HMMER-Extractor, we constructed a cardiovascular disease related gene dataset of the macromolecular metabolite trimethylamine (TMA) and lipopolysaccharide (LPS) based on 46,699 bacterial genomes from human gut. Approximately 21,014 and 1961 bacterial strains were identified to contain the cnt or cut operon of TMA, and the waa gene cluster of LPS, respectively. The Escherichia coli occupied the largest proportion among all the bacterial species, which belonged to the phyla Firmicutes. The HMMER-Extractor toolkit is an integrated pipeline and has been proven to be accurate and fast in extracting target macromolecular encoding genes from microbial genomes.}, }
@article {pmid39556491, year = {2025}, author = {Shete, O and Ghosh, TS}, title = {Normal Gut Microbiomes in Diverse Populations: Clinical Implications.}, journal = {Annual review of medicine}, volume = {76}, number = {1}, pages = {95-114}, doi = {10.1146/annurev-med-051223-031809}, pmid = {39556491}, issn = {1545-326X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; }, abstract = {The human microbiome is a sensor and modulator of physiology and homeostasis. Remarkable tractability underpins the promise of therapeutic manipulation of the microbiome. However, the definition of a normal or healthy microbiome has been elusive. This is in part due to the underrepresentation of minority groups and major global regions in microbiome studies to date. We review studies of the microbiome in different populations and highlight a commonality among health-associated microbiome signatures along with major drivers of variation. We also provide an overview of microbiome-associated therapeutic interventions for some widespread, widely studied diseases. We discuss sources of bias and the challenges associated with defining population-specific microbiome reference bases. We propose a roadmap for defining normal microbiome references that can be used for population-customized microbiome therapeutics and diagnostics.}, }
@article {pmid39555415, year = {2024}, author = {Chen, XY and Liu, Y and Zhu, WB and Li, SH and Wei, S and Cai, J and Lin, Y and Liang, JK and Yan, GM and Guo, L and Hu, C}, title = {Arming oncolytic M1 virus with gasdermin E enhances antitumor efficacy in breast cancer.}, journal = {iScience}, volume = {27}, number = {11}, pages = {111148}, pmid = {39555415}, issn = {2589-0042}, abstract = {Pyroptosis, driven by the N-terminal domain of gasdermin proteins (GSDM), promotes antitumor immunity by attracting lymphocytes to the tumor microenvironment (TME). However, current pyroptosis-inducing therapies like drug injections and phototherapy are limited to localized treatments, making them unsuitable for widespread or microscopic metastatic lesions. This study engineered oncolytic M1 viruses (rM1-mGSDME_FL and rM1-mGSDME_NT) to selectively deliver GSDME to tumor cells. These modified viruses enhanced tumor cell death in breast cancer models, suppressed tumor growth, extended survival in mice, and boosted immune cell infiltration, demonstrating significant anticancer potential through pyroptosis induction.}, }
@article {pmid39547283, year = {2025}, author = {Zelasko, S and Swaney, MH and Sandstrom, S and Lee, KE and Dixon, J and Riley, C and Watson, L and Godfrey, JJ and Ledrowski, N and Rey, F and Safdar, N and Seroogy, CM and Gern, JE and Kalan, L and Currie, C}, title = {Early-life upper airway microbiota are associated with decreased lower respiratory tract infections.}, journal = {The Journal of allergy and clinical immunology}, volume = {155}, number = {2}, pages = {436-450}, doi = {10.1016/j.jaci.2024.11.008}, pmid = {39547283}, issn = {1097-6825}, support = {U19 AI104317/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Respiratory Tract Infections/microbiology/immunology ; Infant ; Female ; Male ; Mouth/microbiology ; Child, Preschool ; *Respiratory System/microbiology ; }, abstract = {BACKGROUND: Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied.<br><br>OBJECTIVES: Our aim was to gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics within the upper respiratory tract during infancy.<br><br>METHODS: We performed shotgun metagenomic sequencing of nasal (n&#xa0;= 229) and oral (n&#xa0;= 210) microbiomes from our Wisconsin Infant Study Cohort at age 24 months and examined the influence of participant demographics and exposure history on microbiome composition. Detection of viral and bacterial respiratory pathogens by RT-PCR and culture-based studies with antibiotic susceptibility testing, respectively, to assess pathogen carriage was performed. Functional bioassays were used to evaluate pathogen inhibition by respiratory tract commensals.<br><br>RESULTS: Participants with early-life lower respiratory tract infection were more likely to be formula fed, attend day care, and experience wheezing. Composition of the nasal, but not oral, microbiome associated with prior lower respiratory tract infection, namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M catarrhalis.<br><br>CONCLUSIONS: These results suggest interbacterial competition affects nasal pathogen colonization. This work advances understanding of protective host-microbe interactions occurring in airway microbiomes that alter infection susceptibility in early life.}, }
@article {pmid39545965, year = {2024}, author = {Pawlik, MT and Rinneberg, G and Koch, A and Meyringer, H and Loew, TH and Kjellberg, A}, title = {Is there a rationale for hyperbaric oxygen therapy in the patients with Post COVID syndrome? : A critical review.}, journal = {European archives of psychiatry and clinical neuroscience}, volume = {274}, number = {8}, pages = {1797-1817}, pmid = {39545965}, issn = {1433-8491}, mesh = {Humans ; *Hyperbaric Oxygenation/methods ; *COVID-19/therapy/complications ; Post-Acute COVID-19 Syndrome ; SARS-CoV-2 ; }, abstract = {The SARS-CoV-2 pandemic has resulted in 762 million infections worldwide from 2020 to date, of which approximately ten percent are suffering from the effects after infection in 2019 (COVID-19) [1, 40]. In Germany, it is now assumed that at least one million people suffer from post-COVID condition with long-term consequences. These have been previously reported in diseases like Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS). Symptoms show a changing variability and recent surveys in the COVID context indicate that 10-30 % of outpatients, 50 to 70% of hospitalised patients suffer from sequelae. Recent data suggest that only 13% of all ill people were completely free of symptoms after recovery [3, 9]. Current hypotheses consider chronic inflammation, mitochondrial dysfunction, latent viral persistence, autoimmunity, changes of the human microbiome or multilocular sequelae in various organ system after infection. Hyperbaric oxygen therapy (HBOT) is applied since 1957 for heart surgery, scuba dive accidents, CO intoxication, air embolisms and infections with anaerobic pathogens. Under hyperbaric pressure, oxygen is physically dissolved in the blood in higher concentrations and reaches levels four times higher than under normobaric oxygen application. Moreover, the alternation of hyperoxia and normoxia induces a variety of processes at the cellular level, which improves oxygen supply in areas of locoregional hypoxia. Numerous target gene effects on new vessel formation, anti-inflammatory and anti-oedematous effects have been demonstrated [74]. The provision of intermittently high, local oxygen concentrations increases repair and regeneration processes and normalises the predominance of hyperinflammation. At present time only one prospective, randomized and placebo-controlled study exists with positive effects on global cognitive function, attention and executive function, psychiatric symptoms and pain interference. In conclusion, up to this date HBO is the only scientifically proven treatment in a prospective randomized controlled trial to be effective for cognitive improvement, regeneration of brain network and improvement of cardiac function. HBOT may have not only theoretical but also potential impact on targets of current pathophysiology of Post COVID condition, which warrants further scientific studies in patients.}, }
@article {pmid39545326, year = {2025}, author = {Shah, AB and Shim, SH}, title = {Human microbiota peptides: important roles in human health.}, journal = {Natural product reports}, volume = {42}, number = {1}, pages = {151-194}, doi = {10.1039/d4np00042k}, pmid = {39545326}, issn = {1460-4752}, mesh = {Humans ; *Microbiota/physiology ; *Peptides/chemistry/metabolism/pharmacology ; Anti-Bacterial Agents/pharmacology ; Bacteria/metabolism ; }, abstract = {Covering: 1974 to 2024Human microbiota consist of a diverse array of microorganisms, such as bacteria, Eukarya, archaea, and viruses, which populate various parts of the human body and live in a cooperatively beneficial relationship with the host. They play a crucial role in supporting the functional balance of the microbiome. The coevolutionary progression has led to the development of specialized metabolites that have the potential to substitute traditional antibiotics in combating global health challenges. Although there has been a lot of research on the human microbiota, there is a considerable lack of understanding regarding the wide range of peptides that these microbial populations produce. Particularly noteworthy are the antibiotics that are uniquely produced by the human microbiome, especially by bacteria, to protect against invasive infections. This review seeks to fill this knowledge gap by providing a thorough understanding of various peptides, along with their in-depth biological importance in terms of human disorders. Advancements in genomics and the understanding of molecular mechanisms that control the interactions between microbiota and hosts have made it easier to find peptides that come from the human microbiome. We hope that this review will serve as a basis for developing new therapeutic approaches and personalized healthcare strategies. Additionally, it emphasizes the significance of these microbiota in the field of natural product discovery and development.}, }
@article {pmid39543873, year = {2025}, author = {Saraswat, I and Goel, A}, title = {Therapeutic Modulation of the Microbiome in Oncology: Current Trends and Future Directions.}, journal = {Current pharmaceutical biotechnology}, volume = {26}, number = {5}, pages = {680-699}, pmid = {39543873}, issn = {1873-4316}, mesh = {Humans ; *Neoplasms/microbiology/therapy/immunology ; Probiotics/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Animals ; *Microbiota/drug effects ; }, abstract = {Cancer is a predominant cause of mortality worldwide, necessitating the development of innovative therapeutic techniques. The human microbiome, particularly the gut microbiota, has become a significant element in cancer research owing to its essential role in sustaining health and influencing disease progression. This review examines the microbiome's makeup and essential functions, including immunological modulation and metabolic regulation, which may be evaluated using sophisticated methodologies such as metagenomics and 16S rRNA sequencing. The microbiome influences cancer development by promoting inflammation, modulating the immune system, and producing carcinogenic compounds. Dysbiosis, or microbial imbalance, can undermine the epithelial barrier and facilitate cancer. The microbiome influences chemotherapy and radiation results by modifying drug metabolism, either enhancing or reducing therapeutic efficacy and contributing to side effects and toxicity. Comprehending these intricate relationships emphasises the microbiome's significance in oncology and accentuates the possibility for microbiome-targeted therapeutics. Contemporary therapeutic approaches encompass the utilisation of probiotics and dietary components to regulate the microbiome, enhance treatment efficacy, and minimise unwanted effects. Advancements in research indicate that personalised microbiome-based interventions, have the potential to transform cancer therapy, by providing more effective and customised treatment alternatives. This study aims to provide a comprehensive analysis of the microbiome's influence on the onset and treatment of cancer, while emphasising current trends and future possibilities for therapeutic intervention.}, }
@article {pmid39541945, year = {2024}, author = {Wu, J and Zeng, W and Xie, H and Cao, M and Yang, J and Xie, Y and Luo, Z and Zhang, Z and Xu, H and Huang, W and Zhou, T and Tan, J and Wu, X and Yang, Z and Zhu, S and Mao, R and He, Z and Lan, P}, title = {Microbiota-induced alteration of kynurenine metabolism in macrophages drives formation of creeping fat in Crohn's disease.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {11}, pages = {1927-1943.e9}, doi = {10.1016/j.chom.2024.10.008}, pmid = {39541945}, issn = {1934-6069}, mesh = {Animals ; Mice ; *Macrophages/microbiology/metabolism ; *Kynurenine/metabolism ; *Crohn Disease/microbiology/metabolism ; *Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; *Adipogenesis ; *Mice, Knockout ; *Disease Models, Animal ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/physiology ; Receptors, Aryl Hydrocarbon/metabolism ; Humans ; Adipocytes/metabolism ; Male ; Mesentery ; Microbiota ; }, abstract = {Hyperplasia of mesenteric tissues in Crohn's disease, called creeping fat (CrF), is associated with surgical recurrence. Although microbiota translocation and colonization have been found in CrF, convincing mouse phenotypes and the underlying mechanisms of CrF formation remain unclear. Utilizing single-nucleus RNA (snRNA) sequencing of CrF and different mouse models, we demonstrate that the commensal Achromobacter pulmonis induces mesenteric adipogenesis through macrophage alteration. Targeted metabolome analysis reveals that L-kynurenine is the most enriched metabolite in CrF. Upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) enhances kynurenine metabolism and drives mesenteric adipogenesis. Leveraging single-cell RNA (scRNA) sequencing of mouse mesenteric tissues and macrophage-specific IDO1 knockout mice, we verify the role of macrophage-sourced L-kynurenine in mesenteric adipogenesis. Mechanistically, L-kynurenine-induced adipogenesis is mediated by the aryl hydrocarbon receptors in adipocytes. Administration of an IDO1 inhibitor or bacteria engineered to degrade L-kynurenine alleviates mesenteric adipogenesis in mice. Collectively, our study demonstrates that microbiota-induced modulation of macrophage metabolism potentiates CrF formation.}, }
@article {pmid39541940, year = {2024}, author = {Monzel, E and Desai, MS}, title = {Bacterial small RNA makes a big impact for gut colonization.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {11}, pages = {1875-1877}, doi = {10.1016/j.chom.2024.10.010}, pmid = {39541940}, issn = {1934-6069}, mesh = {Humans ; *RNA, Bacterial/genetics/metabolism ; *Gastrointestinal Microbiome/genetics ; RNA, Small Untranslated/genetics/metabolism ; Gastrointestinal Tract/microbiology ; Animals ; Dietary Carbohydrates/metabolism ; Gene Expression Regulation, Bacterial ; }, abstract = {The functions of non-coding small RNAs (sRNAs) within the human microbiome remain largely unexplored. In this Cell Host &amp; Microbe issue, El Mouali et al. identify Segatella RNA colonization factor (SrcF), a sRNA from a prevalent gut bacterium Segatella copri. SrcF promotes colonization of S. copri by regulating bacterial degradation of complex dietary carbohydrates.}, }
@article {pmid39540274, year = {2024}, author = {Arcimowicz, M}, title = {Rational treatment of acute rhinosinusitis in the context of increasing antibiotic resistance.}, journal = {Otolaryngologia polska = The Polish otolaryngology}, volume = {78}, number = {6}, pages = {1-11}, doi = {10.5604/01.3001.0054.7506}, pmid = {39540274}, issn = {2300-8423}, mesh = {Humans ; *Sinusitis/drug therapy/microbiology ; *Rhinitis/drug therapy/microbiology ; *Anti-Bacterial Agents/therapeutic use ; Acute Disease ; Drug Resistance, Microbial ; Adult ; COVID-19 ; Drug Resistance, Bacterial ; Rhinosinusitis ; }, abstract = {Acute rhinosinusitis is one of the most common diseases in the population, both in primary and specialist otolaryngological care. It is also responsible for a disturbingly high percentage of prescribed antibiotic therapy, regardless of the etiology of the disease. Despite the fact that acute viral and acute postviral rhinosinusitis dominate among the phenotypes of acute rhinosinusitis, and the development of acute bacterial rhinosinusitis occurs in only 0.5-2% of all cases in adults and 5-10% in children, antibiotics still remain an important element of treatment, despite alarming data on the growing antibiotic resistance and the adverse effect of antibiotics on the human microbiome, leading to dysbiosis. The discovery of antibiotics was one of the greatest achievements of modern medicine, but their inappropriate use leads to the gradual increase in the phenomenon of antibiotic resistance, considered one of the most serious public health problems, recognized by the WHO as one of the 10 greatest threats to human health in the 21[st] century. The unjustified use of antibiotics in outpatient care is the key to the growth of this problem, in parallel with the lack of patient compliance. The COVID pandemic has intensified this unfavourable trend. That is why the knowledge of antibiotic stewardship is so important. According to the guidelines, in the therapy of acute rhinosinusitis, symptomatic and anti-inflammatory treatment dominates, and antibiotic therapy has very strictly defined and limited indications. The latest guidelines also recommend herbal medicines, including BNO 1016, in the treatment of acute viral and postviral rhinosinusitis. Available studies indicate that it has a beneficial effect not only on shortening the duration of the disease and reducing symptoms, but also reduces the need for antibiotic treatment in acute rhinosinusitis. Complications of acute rhinosinusitis are relatively rare and are not related to taking antibiotics.}, }
@article {pmid39539377, year = {2024}, author = {Efremova, I and Alieva, A and Maslennikov, R and Poluektova, E and Zharkova, M and Kudryavtseva, A and Krasnov, G and Zharikov, Y and Nerestyuk, Y and Karchevskaya, A and Ivashkin, V}, title = {Akkermansia muciniphila is associated with normal muscle mass and Eggerthella is related with sarcopenia in cirrhosis.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1438897}, pmid = {39539377}, issn = {2296-861X}, abstract = {BACKGROUND: Sarcopenia and gut dysbiosis are common in cirrhosis. The aim is to study the correlations between the gut microbiota taxa and muscle mass level in cirrhosis.<br><br>METHODS: The study included 40 cirrhosis patients including 18 patients with sarcopenia. The gut microbiota composition was assessed using amplicon sequencing of the hypervariable V3-V4 regions of the 16S rRNA gene. The skeletal muscle mass, subcutaneous and visceral fat levels were assessed with abdominal computed tomography as skeletal muscle, subcutaneous and visceral fat indices (SMI, SFI and VFI).<br><br>RESULTS: Patients with sarcopenia had more relative abundance (RA) of Agathobacter, Anaerostipes, Butyricicoccus, Dorea, Eggerthella, Microbacteriaceae, Veillonella and less RA of Akkermansiaceae, Akkermansia muciniphila, Verrucomicrobiae and Bilophila compared to patients with normal muscle mass. SMI directly correlated with RA of Akkermansia, Alistipes indistinctus, Anaerotruncus, Atopobiaceae, Bacteroides clarus, Bacteroides salyersiae, Barnesiellaceae, Bilophila wadsworthia, Pseudomonadota, Olsenella, and Parabacteroides distasonis, and negatively correlated with RA of Anaerostipes and Eggerthella. Sarcopenia was detected in 20.0% patients whose gut microbiota had Akkermansia but not Eggerthella, and in all the patients, whose gut microbiota had Eggerthella but not Akkermansia. The Akkermansia and Eggerthella abundances were independent determinants of SMI. RA of Akkermansia, Akkermansia muciniphila, Akkermansiaceae, Bacteroides salyersiae, Barnesiella, Bilophila, Desulfobacterota, Verrucomicrobiota and other taxa correlated positively and RA of Anaerovoracaceae, Elusimicrobiaceae, Elusimicrobium, Kiritimatiellae, Spirochaetota, and other taxa correlated negatively with the SFI. RA of Alistripes, Romboutsia, Succinivibrio, and Succinivibrionaceae correlated positively and RA of Bacteroides thetaiotaomicron correlated negatively with VFI.<br><br>CONCLUSION: The muscle mass level in cirrhosis correlates with the abundance of several gut microbiota taxa, of which Akkermansia and Eggerthella seems to be the most important.}, }
@article {pmid39534501, year = {2024}, author = {Koh, H}, title = {A general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects: Applications to human microbiome studies.}, journal = {NAR genomics and bioinformatics}, volume = {6}, number = {4}, pages = {lqae148}, pmid = {39534501}, issn = {2631-9268}, abstract = {The effect of a treatment on a health or disease response can be modified by genetic or microbial variants. It is the matter of interaction effects between genetic or microbial variants and a treatment. To powerfully discover genetic or microbial biomarkers, it is crucial to incorporate such interaction effects in addition to the main effects. However, in the context of kernel machine regression analysis of its kind, existing methods cannot be utilized in a situation, where a kernel is available but its underlying real variants are unknown. To address such limitations, I introduce a general kernel machine regression framework using principal component analysis for jointly testing main and interaction effects. It begins with extracting principal components from an input kernel through the singular value decomposition. Then, it employs the principal components as surrogate variants to construct three endogenous kernels for the main effects, interaction effects, and both of them, respectively. Hence, it works with a kernel as an input without knowing its underlying real variants, and also detects either the main effects, interaction effects, or both of them robustly. I also introduce its omnibus testing extension to multiple input kernels, named OmniK. I demonstrate its use for human microbiome studies.}, }
@article {pmid39526038, year = {2024}, author = {Feng, C and Jia, H and Wang, H and Wang, J and Lin, M and Hu, X and Yu, C and Song, H and Wang, L}, title = {MicroNet-MIMRF: a microbial network inference approach based on mutual information and Markov random fields.}, journal = {Bioinformatics advances}, volume = {4}, number = {1}, pages = {vbae167}, pmid = {39526038}, issn = {2635-0041}, abstract = {MOTIVATION: The human microbiome, comprises complex associations and communication networks among microbial communities, which are crucial for maintaining health. The construction of microbial networks is vital for elucidating these associations. However, existing microbial networks inference methods cannot solve the issues of zero-inflation and non-linear associations. Therefore, necessitating novel methods to improve the accuracy of microbial networks inference.<br><br>RESULTS: In this study, we introduce the Microbial Network based on Mutual Information and Markov Random Fields (MicroNet-MIMRF) as a novel approach for inferring microbial networks. Abundance data of microbes are modeled through the zero-inflated Poisson distribution, and the discrete matrix is estimated for further calculation. Markov random fields based on mutual information are used to construct accurate microbial networks. MicroNet-MIMRF excels at estimating pairwise associations between microbes, effectively addressing zero-inflation and non-linear associations in microbial abundance data. It outperforms commonly used techniques in simulation experiments, achieving area under the curve values exceeding 0.75 for all parameters. A case study on inflammatory bowel disease data further demonstrates the method's ability to identify insightful associations. Conclusively, MicroNet-MIMRF is a powerful tool for microbial network inference that handles the biases caused by zero-inflation and overestimation of associations.<br><br>The MicroNet-MIMRF is provided at https://github.com/Fionabiostats/MicroNet-MIMRF.}, }
@article {pmid39531852, year = {2025}, author = {Simbirtseva, KY and O'Toole, PW}, title = {Healthy and Unhealthy Aging and the Human Microbiome.}, journal = {Annual review of medicine}, volume = {76}, number = {1}, pages = {115-127}, doi = {10.1146/annurev-med-042423-042542}, pmid = {39531852}, issn = {1545-326X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Aging/physiology/immunology ; Dysbiosis ; *Healthy Aging/physiology ; }, abstract = {An altered gut microbiome is a feature of many multifactorial diseases, and microbiome effects on host metabolism, immune function, and possibly neurological function are implicated. Increased biological age is accompanied by a change in the gut microbiome. However, age-related health loss does not occur uniformly across all subjects but rather depends on differential loss of gut commensals and gain of pathobionts. In this article, we summarize the known and possible effects of the gut microbiome on the hallmarks of aging and describe the most plausible mechanisms. Understanding and targeting these factors could lead to prolonging health span by rationally maintaining the gut microbiome.}, }
@article {pmid39529240, year = {2024}, author = {Liu, S and Zhang, Z and Wang, X and Ma, Y and Ruan, H and Wu, X and Li, B and Mou, X and Chen, T and Lu, Z and Zhao, W}, title = {Biosynthetic potential of the gut microbiome in longevous populations.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2426623}, pmid = {39529240}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Feces/microbiology ; Aged ; *Metagenomics ; Multigene Family ; Aged, 80 and over ; Terpenes/metabolism ; Longevity ; Akkermansia/metabolism ; Adult ; Male ; Female ; Middle Aged ; Cohort Studies ; Biological Products/metabolism ; Metagenome ; Young Adult ; }, abstract = {Gut microbiome plays a pivotal role in combating diseases and facilitating healthy aging, and natural products derived from biosynthetic gene clusters (BGCs) of the human microbiome exhibit significant biological activities. However, the natural products of the gut microbiome in long-lived populations remain poorly understood. Here, we integrated six cohorts of long-lived populations, encompassing a total of 1029 fecal metagenomic samples, and employed the metagenomic single sample assembled BGCs (MSSA-BGCs) analysis pipeline to investigate the natural products and their associated species. Our findings reveal that the BGC composition of the extremely long-lived group differed significantly from that of younger elderly and young individuals across five cohorts. Terpene and Type I PKS BGCs were enriched in the extremely long-lived, whereas cyclic-lactone-autoinducer BGCs were more prevalent in the young. Association analysis indicated that terpene BGCs were strongly associated with the abundance of Akkermansia muciniphila, which was also more abundant in the long-lived elderly across at least three cohorts. We assembled 18 A. muciniphila draft genomes using metagenomic data from the extremely long-lived group across six cohorts and discovered that they all harbor two classes of terpene BGCs, which aligns with the 97 complete genomes of A. muciniphila strains retrieved from the NCBI database. The core domains of these two BGC classes are squalene/phytoene synthases involved in the biosynthesis of tri- and tetraterpenes. Furthermore, the abundance of fecal A. muciniphila was significantly associated with eight types of triterpenoids. Targeted terpenoid metabolomic analysis revealed that two triterpenoids, Holstinone C and colubrinic acid, were enriched in the A. muciniphila culture solution compared to the medium, thereby confirming the production of triterpenoids by A. muciniphila. The natural products derived from the gut of long-lived populations provide intriguing indications of their potential beneficial roles in regulating health.}, }
@article {pmid39512939, year = {2024}, author = {Costa, CFFA and Correia-de-Sá, T and Araujo, R and Barbosa, F and Burnet, PWJ and Ferreira-Gomes, J and Sampaio-Maia, B}, title = {The oral-gut microbiota relationship in healthy humans: identifying shared bacteria between environments and age groups.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1475159}, pmid = {39512939}, issn = {1664-302X}, abstract = {INTRODUCTION: Although the oral cavity and the gut are anatomically continuous regions of the gastrointestinal tract, research on the relationship between oral and gut microbiota remains sparse. Oral-gut bacterial translocation is mostly studied in pathological contexts, thus evidence of translocation in healthy conditions is still scarce. Studying the oral-gut microbiota relationship in humans in different life stages is necessary in order to understand how these microbial communities might relate throughout life.<br><br>METHODS: In this study, saliva and fecal samples were collected from healthy participants (39 children, 97 adults). Microbiota analysis was carried out by sequencing the V4 region of the 16S ribosomal RNA gene, followed by amplicon sequence variant (ASV) analysis.<br><br>RESULTS AND DISCUSSION: Although the oral and gut microbiota are vastly different, a subset of 61 ASVs were present in both the oral cavity and gut of the same individual, and represented 1.6% of all ASVs detected. From these, 26 ASVs (classified into 18 genera: Actinomyces, Rothia, Bacteroides, Porphyromonas, Prevotella, Alistipes, Fusobacterium, Neisseria, Haemophilus, Akkermansia, Solobacterium, Granulicatella, Streptococcus, Gemella, Mogibacterium, Dialister, Veillonella, Christensenellaceae R-7 group) were present in both children and adults, suggesting the possibility of persistent colonization of both habitats by these microorganisms, initiating in childhood. Additionally, 62% of shared ASVs were more abundant in the oral cavity, indicating that oral-to-gut translocation may be the main route of translocation between environments, and highlighting that this phenomenon might be more common than previously thought in healthy individuals of all ages.}, }
@article {pmid39507669, year = {2024}, author = {Buytaers, FE and Berger, N and Van der Heyden, J and Roosens, NHC and De Keersmaecker, SCJ}, title = {The potential of including the microbiome as biomarker in population-based health studies: methods and benefits.}, journal = {Frontiers in public health}, volume = {12}, number = {}, pages = {1467121}, pmid = {39507669}, issn = {2296-2565}, mesh = {Humans ; *Biomarkers/analysis ; *Microbiota ; Population Health ; Health Status ; Public Health ; }, abstract = {The key role of our microbiome in influencing our health status, and its relationship with our environment and lifestyle or health behaviors, have been shown in the last decades. Therefore, the human microbiome has the potential to act as a biomarker or indicator of health or exposure to health risks in the general population, if information on the microbiome can be collected in population-based health surveys or cohorts. It could then be associated with epidemiological participant data such as demographic, clinical or exposure profiles. However, to our knowledge, microbiome sampling has not yet been included as biological evidence of health or exposure to health risks in large population-based studies representative of the general population. In this mini-review, we first highlight some practical considerations for microbiome sampling and analysis that need to be considered in the context of a population study. We then present some examples of topics where the microbiome could be included as biological evidence in population-based health studies for the benefit of public health, and how this could be developed in the future. In doing so, we aim to highlight the benefits of having microbiome data available at the level of the general population, combined with epidemiological data from health surveys, and hence how microbiological data could be used in the future to assess human health. We also stress the challenges that remain to be overcome to allow the use of this microbiome data in order to improve proactive public health policies.}, }
@article {pmid39506745, year = {2024}, author = {Liechty, ZS and Agans, RT and Barbato, RA and Colston, SM and Christian, MR and Hammamieh, R and Kardish, MR and Karl, JP and Leary, DH and Mauzy, CA and de Goodfellow, IP and Racicot, K and Soares, JW and Stamps, BW and Sweet, CR and Tuck, SM and Whitman, JA and Goodson, MS}, title = {Meeting report of the seventh annual Tri-Service Microbiome Consortium Symposium.}, journal = {BMC proceedings}, volume = {18}, number = {Suppl 20}, pages = {25}, pmid = {39506745}, issn = {1753-6561}, abstract = {The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing among consortium members, which includes collaborators in academia and industry. The 2023 annual symposium was a hybrid meeting held in Washington DC on 26-27 September 2023 concurrent with the virtual attendance, with oral and poster presentations and discussions centered on microbiome-related topics within five broad thematic areas: 1) Environmental Microbiome Characterization; 2) Microbiome Analysis; 3) Human Microbiome Characterization; 4) Microbiome Engineering; and 5) In Vitro and In Vivo Microbiome Models. Collectively, the symposium provided an update on the scope of current DoD and DoD-affiliated microbiome research efforts and fostered collaborative opportunities. This report summarizes the presentations and outcomes of the 7th annual TSMC symposium.}, }
@article {pmid39505797, year = {2025}, author = {Ji, Y and Sun, H and Wang, Y and Li, Y and Piao, R and Bu, L and Xu, H}, title = {Characterizing the oral and gastrointestinal microbiome associated with healthy aging: insights from long-lived populations in Northeastern China.}, journal = {GeroScience}, volume = {47}, number = {2}, pages = {2275-2292}, pmid = {39505797}, issn = {2509-2723}, support = {2022JH2/101300031//Natural Science Foundation of Liaoning Province/ ; 2020YFA0907800//Ministry of Science and Technology of the People's Republic of China/ ; 22-322-3-05//Natural Science Foundation of Shenyang Municipality/ ; }, mesh = {Humans ; China ; *Gastrointestinal Microbiome/genetics/physiology ; Middle Aged ; Aged ; Male ; Female ; *Mouth/microbiology ; Aged, 80 and over ; *Healthy Aging/physiology ; RNA, Ribosomal, 16S/genetics ; Longevity ; }, abstract = {The oral and gastrointestinal (GI) tract microbiota in humans is susceptible to geographical influences and represents vital factors impacting healthy aging. The northeastern region of China, characterized by distinct dietary and climatic conditions, significantly influences the human microbiome composition. However, the microbial structure of the entire long-lived population in this area has not been evaluated. This study recruited a cohort of 142 individuals aged 55-102 residing in Northeast China, and their oral and gut microbiota were evaluated using full-length 16S rRNA gene amplicon sequencing. The results indicate that the oral and GI tract microbiota of long-lived individuals showed reduced microbial taxonomic richness and evenness compared to sub-longevity individuals. With aging, the core species experience a gradual decline in abundance, while subordinate species show an increase. The long-lived population exhibited a heightened ability to enrich beneficial bacteria including Akkermansia, Alistipes, Parabacteroides, and Eubacterium coprostanoligenes in the GI tract, which are associated with host metabolism and have the potential to act as probiotics, reducing the risks of unhealthy aging in the northeast population. Bifidobacterium sp. and Lactobacillus salivarius have been found to coexist in both the oral cavity and the GI tract of long-lived individuals. We hypothesize that beneficial bacterial taxa from the oral cavity colonize the GI tract more extensively in long-lived individuals compared to those with a shorter lifespan. These findings pave the way for identifying probiotic strains that can promote healthy aging in Northeast China.}, }
@article {pmid39505118, year = {2024}, author = {Ferrara, F and Valacchi, G}, title = {Role of microbiota in the GUT-SKIN AXIS responses to outdoor stressors.}, journal = {Free radical biology &amp; medicine}, volume = {225}, number = {}, pages = {894-909}, doi = {10.1016/j.freeradbiomed.2024.11.003}, pmid = {39505118}, issn = {1873-4596}, mesh = {Humans ; *Skin/microbiology/immunology ; *Gastrointestinal Microbiome ; *Oxidative Stress ; Dysbiosis/microbiology/immunology ; Air Pollutants/adverse effects ; Microbiota ; Animals ; }, abstract = {Beside the respiratory tract, the skin and the gut represent the first defensive lines of our body against the external insults displaying many important biochemical features able to maintain the epithelial barrier integrity and to regulate the tissue immune responses. The human microbiome is essential in maintaining the tissue homeostasis and its dysregulation may lead to tissue conditions including inflammatory pathologies. Among all external insults, air pollutants have been shown to cause oxidative stress damage within the target tissues via an OxInflammatory response. Dysregulation of the gut microbiome (dysbiosis) by outdoor stressors, including air pollutants, may promote the exacerbation of the skin tissue damage via the interplay between the gut-skin axis. The intent of this review is to highlight the ability of exogenous stressors to modulate the human gut-skin axis via a redox regulated mechanism affecting the microbiome and therefore contributing to the development and aggravation of gut and skin conditions.}, }
@article {pmid39504483, year = {2024}, author = {Chen, H and Chen, K}, title = {Predicting disease-associated microbes based on similarity fusion and deep learning.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {6}, pages = {}, pmid = {39504483}, issn = {1477-4054}, support = {20242BAB25083//Jiangxi Provincial Natural Science Foundation, China/ ; }, mesh = {*Deep Learning ; Humans ; *Computational Biology/methods ; *Microbiota/genetics ; Algorithms ; }, abstract = {Increasing studies have revealed the critical roles of human microbiome in a wide variety of disorders. Identification of disease-associated microbes might improve our knowledge and understanding of disease pathogenesis and treatment. Computational prediction of microbe-disease associations would provide helpful guidance for further biomedical screening, which has received lots of research interest in bioinformatics. In this study, a deep learning-based computational approach entitled SGJMDA is presented for predicting microbe-disease associations. Specifically, SGJMDA first fuses multiple similarities of microbes and diseases using a nonlinear strategy, and extracts feature information from homogeneous networks composed of the fused similarities via a graph convolution network. Second, a heterogeneous microbe-disease network is built to further capture the structural information of microbes and diseases by employing multi-neighborhood graph convolution network and jumping knowledge network. Finally, potential microbe-disease associations are inferred through computing the linear correlation coefficients of their embeddings. Results from cross-validation experiments show that SGJMDA outperforms 6 state-of-the-art computational methods. Furthermore, we carry out case studies on three important diseases using SGJMDA, in which 19, 20, and 11 predictions out of their top 20 results are successfully checked by the latest databases, respectively. The excellent performance of SGJMDA suggests that it could be a valuable and promising tool for inferring disease-associated microbes.}, }
@article {pmid39484071, year = {2024}, author = {Nurkolis, F and Utami, TW and Alatas, AI and Wicaksono, D and Kurniawan, R and Ratmandhika, SR and Sukarno, KT and Pahu, YGP and Kim, B and Tallei, TE and Tjandrawinata, RR and Alhasyimi, AA and Surya, R and Helen, H and Halim, P and Muhar, AM and Syahputra, RA}, title = {Can salivary and skin microbiome become a biodetector for aging-associated diseases? Current insights and future perspectives.}, journal = {Frontiers in aging}, volume = {5}, number = {}, pages = {1462569}, pmid = {39484071}, issn = {2673-6217}, abstract = {Growth and aging are fundamental elements of human development. Aging is defined by a decrease in physiological activities and higher illness vulnerability. Affected by lifestyle, environmental, and hereditary elements, aging results in disorders including cardiovascular, musculoskeletal, and neurological diseases, which accounted for 16.1 million worldwide deaths in 2019. Stress-induced cellular senescence, caused by DNA damage, can reduce tissue regeneration and repair, promoting aging. The root cause of many age-related disorders is inflammation, encouraged by the senescence-associated secretory phenotype (SASP). Aging's metabolic changes and declining immune systems raise illness risk via promoting microbiome diversity. Stable, individual-specific skin and oral microbiomes are essential for both health and disease since dysbiosis is linked with periodontitis and eczema. Present from birth to death, the human microbiome, under the influence of diet and lifestyle, interacts symbiotically with the body. Poor dental health has been linked to Alzheimer's and Parkinson's diseases since oral microorganisms and systemic diseases have important interactions. Emphasizing the importance of microbiome health across the lifetime, this study reviews the understanding of the microbiome's role in aging-related diseases that can direct novel diagnosis and treatment approaches.}, }
@article {pmid39483755, year = {2024}, author = {Pita, S and Myers, PN and Johansen, J and Russel, J and Nielsen, MC and Eklund, AC and Nielsen, HB}, title = {CHAMP delivers accurate taxonomic profiles of the prokaryotes, eukaryotes, and bacteriophages in the human microbiome.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1425489}, pmid = {39483755}, issn = {1664-302X}, abstract = {INTRODUCTION: Accurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites.<br><br>METHODS: CHAMP uses a reference database derived from 30,382 human microbiome samples, covering 6,567 prokaryotic and 244 eukaryotic species, as well as 64,003 viruses. We benchmarked CHAMP against established profiling tools (MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta) using a diverse set of in silico metagenomes and DNA mock communities.<br><br>RESULTS: CHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. The false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than other tools at low sequencing depths, highlighting its application for low biomass samples.<br><br>DISCUSSION: Taken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. CHAMP profiling is offered as a service by Clinical Microbiomics A/S and is available for a fee at https://cosmosidhub.com.}, }
@article {pmid39486524, year = {2024}, author = {Kapoor, B and Biswas, P and Gulati, M and Rani, P and Gupta, R}, title = {Gut microbiome and Alzheimer's disease: What we know and what remains to be explored.}, journal = {Ageing research reviews}, volume = {102}, number = {}, pages = {102570}, doi = {10.1016/j.arr.2024.102570}, pmid = {39486524}, issn = {1872-9649}, mesh = {Animals ; Humans ; *Alzheimer Disease/metabolism/microbiology/physiopathology ; Brain/metabolism/physiopathology ; *Brain-Gut Axis/physiology ; *Dysbiosis/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; }, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.}, }
@article {pmid39481381, year = {2024}, author = {Zheludev, IN and Edgar, RC and Lopez-Galiano, MJ and de la Peña, M and Babaian, A and Bhatt, AS and Fire, AZ}, title = {Viroid-like colonists of human microbiomes.}, journal = {Cell}, volume = {187}, number = {23}, pages = {6521-6536.e18}, pmid = {39481381}, issn = {1097-4172}, support = {R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; R35 GM130366/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/genetics ; *Phylogeny ; Feces/microbiology ; RNA, Circular/genetics/metabolism ; Open Reading Frames/genetics ; RNA, Catalytic/metabolism/genetics ; Gastrointestinal Microbiome/genetics ; }, abstract = {Here, we describe "obelisks," a class of heritable RNA elements sharing several properties: (1) apparently circular RNA ∼1 kb genome assemblies, (2) predicted rod-like genome-wide secondary structures, and (3) open reading frames encoding a novel "Oblin" protein superfamily. A subset of obelisks includes a variant hammerhead self-cleaving ribozyme. Obelisks form their own phylogenetic group without detectable similarity to known biological agents. Surveying globally, we identified 29,959 distinct obelisks (clustered at 90% sequence identity) from diverse ecological niches. Obelisks are prevalent in human microbiomes, with detection in ∼7% (29/440) and ∼50% (17/32) of queried stool and oral metatranscriptomes, respectively. We establish Streptococcus sanguinis as a cellular host of a specific obelisk and find that this obelisk's maintenance is not essential for bacterial growth. Our observations identify obelisks as a class of diverse RNAs of yet-to-be-determined impact that have colonized and gone unnoticed in human and global microbiomes.}, }
@article {pmid39479472, year = {2024}, author = {Mousa, WK and Shaikh, AY and Ghemrawi, R and Aldulaimi, M and Al Ali, A and Sammani, N and Khair, M and Helal, MI and Al-Marzooq, F and Oueis, E}, title = {Human microbiome derived synthetic antimicrobial peptides with activity against Gram-negative, Gram-positive, and antibiotic resistant bacteria.}, journal = {RSC medicinal chemistry}, volume = {16}, number = {1}, pages = {312-323}, pmid = {39479472}, issn = {2632-8682}, abstract = {The prevalence of antibacterial resistance has become one of the major health threats of modern times, requiring the development of novel antibacterials. Antimicrobial peptides are a promising source of antibiotic candidates, mostly requiring further optimization to enhance druggability. In this study, a series of new antimicrobial peptides derived from lactomodulin, a human microbiome natural peptide, was designed, synthesized, and biologically evaluated. Within the most active region of the parent peptide, linear peptide LM6 with the sequence LSKISGGIGPLVIPV-NH2 and its cyclic derivatives LM13a and LM13b showed strong antibacterial activity against Gram-positive bacteria, including resistant strains, and Gram-negative bacteria. The peptides were found to have a rapid onset of bactericidal activity and transmission electron microscopy clearly shows the disintegration of the cell membrane, suggesting a membrane-targeting mode of action.}, }
@article {pmid39478225, year = {2024}, author = {Lu, Z and Mo, S and Xie, D and Zhai, X and Deng, S and Zhou, K and Wang, K and Kang, X and Zhang, H and Tong, J and Hou, L and Hu, H and Li, X and Zhou, D and Lee, LTO and Liu, L and Zhu, Y and Yu, J and Lan, P and Wang, J and He, Z and He, X and Hu, Z}, title = {Polyclonal-to-monoclonal transition in colorectal precancerous evolution.}, journal = {Nature}, volume = {636}, number = {8041}, pages = {233-240}, pmid = {39478225}, issn = {1476-4687}, mesh = {Animals ; Humans ; Male ; Mice ; Carcinogenesis/genetics/pathology ; *Cell Lineage ; Cell Transformation, Neoplastic/genetics/pathology ; *Clonal Evolution ; *Clone Cells/metabolism ; Colonic Polyps/pathology/genetics ; *Colorectal Neoplasms/genetics/pathology ; Disease Models, Animal ; DNA Barcoding, Taxonomic ; Exome Sequencing ; Genes, APC ; Inflammation/pathology/genetics ; *Precancerous Conditions/genetics/pathology ; *Single-Cell Analysis ; Single-Cell Gene Expression Analysis ; Whole Genome Sequencing ; Intestines/cytology/pathology ; }, abstract = {Unravelling the origin and evolution of precancerous lesions is crucial for effectively preventing malignant transformation, yet our current knowledge remains limited[1-3]. Here we used a base editor-enabled DNA barcoding system[4] to comprehensively map single-cell phylogenies in mouse models of intestinal tumorigenesis induced by inflammation or loss of the Apc gene. Through quantitative analysis of high-resolution phylogenies including 260,922 single cells from normal, inflamed and neoplastic intestinal tissues, we identified tens of independent cell lineages undergoing parallel clonal expansions within each lesion. We also found polyclonal origins of human sporadic colorectal polyps through bulk whole-exome sequencing and single-gland whole-genome sequencing. Genomic and clinical data support a model of polyclonal-to-monoclonal transition, with monoclonal lesions representing a more advanced stage. Single-cell RNA sequencing revealed extensive intercellular interactions in early polyclonal lesions, but there was significant loss of interactions during monoclonal transition. Therefore, our data suggest that colorectal precancer is often founded by many different lineages and highlight their cooperative interactions in the earliest stages of cancer formation. These findings provide insights into opportunities for earlier intervention in colorectal cancer.}, }
@article {pmid39478172, year = {2024}, author = {Collado, MC and Devkota, S and Ghosh, TS}, title = {Gut microbiome: a biomedical revolution.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {21}, number = {12}, pages = {830-833}, pmid = {39478172}, issn = {1759-5053}, }
@article {pmid39474048, year = {2023}, author = {Wu, J and Zhang, S and Chen, Y and Zhao, J and Prosun, T and O'Brien, JW and Mueller, JF and Tscharke, BJ and Coin, LJM and Luby, SP and Hai, FI and Buchanan, T and Jiang, G}, title = {Associations between Wastewater Microbiome and Population Smoking Rate Identified Using Wastewater-Based Epidemiology.}, journal = {Environment &amp; health (Washington, D.C.)}, volume = {1}, number = {6}, pages = {394-404}, pmid = {39474048}, issn = {2833-8278}, abstract = {Tobacco use is known to cause health damage, partly by changing the mouth, respiratory tract, and gut-related microbiomes. This study aims to identify the associations between the human microbiome detected in domestic wastewater and the population smoking rate. Metagenomic sequencing and a biomarker discovery algorithm were employed to identify microorganisms as potential microbial biomarkers of smoking through wastewater-based epidemiology. Wastewater samples were collected from selected catchments with low and high smoking rates, i.e., 11.2 ± 1.5% and 17.0 ± 1.6%, respectively. Using the linear discriminant analysis effect size (LEfSe) method, Neisseria, Desulfovibrio, Megamonas, Blautia, Fusicatenibacter, Granulicatella and Enterococcus were suggested as potential biomarker microorganisms. A higher abundance of pathogens, including Neisseria, Eikenella and Haemophilus, was associated with the high smoking rate, likely because of their colonization in smoking-disturbed human guts. The identified potential microbial biomarkers reflect the change of the human gut microbiome due to the long-term smoking behavior. The metagenomic analysis also indicates that smoking upregulates microbial gene expression of genetic information processing, environmental information processing, and cell wall peptidoglycan cleavage, while it downregulates amino acid, lipid, and galactose metabolisms. The findings demonstrate the potential of microbial biomarkers for the surveillance of smoking through a wastewater-based epidemiology approach.}, }
@article {pmid39472801, year = {2024}, author = {Valiei, A and Dickson, AM and Aminian-Dehkordi, J and Mofrad, MRK}, title = {Bacterial community dynamics as a result of growth-yield trade-off and multispecies metabolic interactions toward understanding the gut biofilm niche.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {441}, pmid = {39472801}, issn = {1471-2180}, mesh = {*Bacteria/metabolism/classification/growth &amp; development/genetics ; *Biofilms/growth &amp; development ; Humans ; *Gastrointestinal Microbiome ; Microbial Interactions ; Bacterial Physiological Phenomena ; Models, Biological ; Kinetics ; Symbiosis ; Ecosystem ; Nutrients/metabolism ; }, abstract = {Bacterial communities are ubiquitous, found in natural ecosystems, such as soil, and within living organisms, like the human microbiome. The dynamics of these communities in diverse environments depend on factors such as spatial features of the microbial niche, biochemical kinetics, and interactions among bacteria. Moreover, in many systems, bacterial communities are influenced by multiple physical mechanisms, such as mass transport and detachment forces. One example is gut mucosal communities, where dense, closely packed communities develop under the concurrent influence of nutrient transport from the lumen and fluid-mediated detachment of bacteria. In this study, we model a mucosal niche through a coupled agent-based and finite-volume modeling approach. This methodology enables us to model bacterial interactions affected by nutrient release from various sources while adjusting individual bacterial kinetics. We explored how the dispersion and abundance of bacteria are influenced by biochemical kinetics in different types of metabolic interactions, with a particular focus on the trade-off between growth rate and yield. Our findings demonstrate that in competitive scenarios, higher growth rates result in a larger share of the niche space. In contrast, growth yield plays a critical role in neutralism, commensalism, and mutualism interactions. When bacteria are introduced sequentially, they cause distinct spatiotemporal effects, such as deeper niche colonization in commensalism and mutualism scenarios driven by species intermixing effects, which are enhanced by high growth yields. Moreover, sub-ecosystem interactions dictate the dynamics of three-species communities, sometimes yielding unexpected outcomes. Competitive, fast-growing bacteria demonstrate robust colonization abilities, yet they face challenges in displacing established mutualistic systems. Bacteria that develop a cooperative relationship with existing species typically obtain niche residence, regardless of their growth rates, although higher growth yields significantly enhance their abundance. Our results underscore the importance of bacterial niche dynamics in shaping community properties and succession, highlighting a new approach to manipulating microbial systems.}, }
@article {pmid39470277, year = {2024}, author = {Xie, J and Zhang, X and Cheng, L and Deng, Y and Ren, H and Mu, M and Zhao, L and Mu, C and Chen, J and Liu, K and Ma, R}, title = {Integrated multi-omics analysis of the microbial profile characteristics associated with pulmonary arterial hypertension in congenital heart disease.}, journal = {Microbiology spectrum}, volume = {12}, number = {12}, pages = {e0180824}, pmid = {39470277}, issn = {2165-0497}, abstract = {Dysregulation of immune and inflammatory cells around blood vessels and metabolic dysfunction are key mechanisms in the development of pulmonary arterial hypertension (PAH). The homeostasis of the human microbiome plays a crucial role in regulating immune responses and the progression of diseases. For pulmonary arterial hypertension associated with congenital heart disease involving body-lung shunt (PAH-CHD), the potential impact of the microbiome on the "gut-lung axis" remains underexplored. This study recruited 15 healthy individuals and 15 patients with pulmonary arterial hypertension due to congenital heart disease from Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, and Kunming Children's Hospital. We performed differential analyses of metabolites and microbiota from both the gut and lower respiratory tract for these two groups. The goal was to investigate the "gut-lung axis" microbiome and metabolome profiles in children with PAH-CHD and to analyze the interrelationships between these profiles. Ultimately, we aim to propose the potential value of these profiles in aiding diagnosis. The results indicated that the gut and pulmonary microbiota of children with PAH-CHD are characterized by an increased abundance of beneficial symbionts, which are closely linked to changes in the metabolome. Metabolite functional enrichment analysis revealed energy metabolism reprogramming in the PAH-CHD group, with active metabolic pathways associated with bile acid secretion and carnitine homeostasis. Moreover, the differential expression of metabolites was correlated with right heart function and growth development.IMPORTANCEPrevious studies have primarily focused on the relationship between the gut microbiome and PAH. However, the impact of microbial homeostasis on the progression of PAH-CHD from the perspective of the gut-lung axis has not been adequately elucidated. Our study utilizes an integrated multi-omics approach to report on the differential characteristics of gut and lung microbiota between children with PAH-CHD and reference subjects. We found that microbiota influence the pathological changes and disease manifestations of PAH-CHD through their metabolic activity. Additionally, alterations in metabolites impact the microbial ecological structure. Our findings suggest that modulating the microbiome composition may have positive implications for maintaining and regulating the immune environment and pathological progression of PAH-CHD.}, }
@article {pmid39470241, year = {2024}, author = {Bouchier, C and Touak, G and Rei, D and Clermont, D}, title = {Complete genome sequence of two Christensenella minuta strains CIP 112228 and CIP 112229, isolated from human fecal samples.}, journal = {Microbiology resource announcements}, volume = {13}, number = {12}, pages = {e0076624}, pmid = {39470241}, issn = {2576-098X}, abstract = {Christensenella minuta is one of the representative bacterial species of the human gut microbiome. We report the complete genome sequence of two strains, Christensenella minuta CIP 112228 and CIP 112229, isolated from two healthy volunteers.}, }
@article {pmid39470240, year = {2024}, author = {Dumann, G and Rohland, O and Abdel-Glil, MY and Allen, RJ and Bauer, M and Busch, A}, title = {Draft genomes of the bile duct microbiome strains Klebsiella pneumoniae and Enterococcus lactis isolated from bilioenteric drainages with biofilm-forming abilities.}, journal = {Microbiology resource announcements}, volume = {13}, number = {12}, pages = {e0020224}, pmid = {39470240}, issn = {2576-098X}, support = {EXC 2051 - Project-ID 390713860//Deutsche Forschungsgemeinschaft (DFG)/ ; }, abstract = {We describe the genetic properties of two strains isolated from the elusive bile duct microbiome from solid organ transplant patients. Bacterial strains Enterococcus lactis (MS-STENT-08-E-001) and Klebsiella pneumoniae (MS-STENT-01-M-001) were isolated from the biofilms of bile duct catheters.}, }
@article {pmid39470190, year = {2024}, author = {Toyomane, K and Kimura, Y and Fukagawa, T and Yamagishi, T and Watanabe, K and Akutsu, T and Asahi, A and Kubota, S and Sekiguchi, K}, title = {Metagenomic sequencing of CRISPRs as a new marker to aid in personal identification with low-biomass samples.}, journal = {mSystems}, volume = {9}, number = {11}, pages = {e0103824}, pmid = {39470190}, issn = {2379-5077}, support = {20K18991,24K20264//MEXT | Japan Society for the Promotion of Science (JSPS)/ ; }, mesh = {Humans ; *Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; *Metagenomics/methods ; *Skin/microbiology ; Microbiota/genetics ; Sequence Analysis, DNA/methods ; Metagenome/genetics ; Genetic Markers/genetics ; }, abstract = {The high specificity of the human skin microbiome is expected to provide a new marker for personal identification. Metagenomic sequencing of clustered regularly interspaced short palindromic repeats (CRISPRs), which we call metaCRISPR typing, was shown to achieve personal identification accurately. However, the intra-individual variability observed in previous studies, which may be due to poor DNA yields from skin samples, has resulted in non-reproducible results. Furthermore, whether metaCRISPR typing can assist in the forensic human DNA analysis of low-biomass samples, from which the information obtained is insufficient, is unknown. In the present study, we sequenced serially diluted control streptococcal CRISPRs cloned into plasmids to determine the minimum copy number required to obtain reproducible results from metaCRISPR typing. We found that at least 10[2] copies of CRISPRs are necessary to obtain reproducible results. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA typing. When the DNA extracted from the skin swabs was diluted, no information was obtained from six out of eight samples by human DNA typing. On the other hand, beta diversity indices of spacer sequences compared with reference samples were below 0.8 for three out of six samples, for which no information was obtained from human DNA analysis, indicating that the spacers observed in these samples were similar to those in the references. These results indicate that metaCRISPR typing may contribute to the identification of individuals from whom the samples were obtained, even in cases where human DNA yields are insufficient to perform human DNA analysis.IMPORTANCEPrevious studies have developed new personal identification methods utilizing personal differences in the skin microbiome. However, intra-individual diversity of skin microbiome may preclude the application of microbiome-based personal identification. Moreover, no study has compared microbiome-based personal identification and practical human DNA analysis. Here, we revealed that the results of metaCRISPR typing, a previously developed microbiome-based personal identification method, are stable if the copy number of the marker gene is sufficient. We then analyzed the skin swab samples using both metaCRISPR typing and human DNA analysis. Our results indicate that metaCRISPR typing may provide additional information for personal identification using low-biomass samples that cannot be used for conventional human DNA analysis.}, }
@article {pmid39466852, year = {2024}, author = {Chen, H and Huang, S and Yao, S and Wang, J and Huang, J and Yu, Z}, title = {Multi-omics analyses of Bacillus amyloliquefaciens treated mice infected with Schistosoma japonicum reveal dynamics change of intestinal microbiome and its associations with host metabolism.}, journal = {PLoS neglected tropical diseases}, volume = {18}, number = {10}, pages = {e0012583}, pmid = {39466852}, issn = {1935-2735}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; *Bacillus amyloliquefaciens/metabolism/genetics ; *Schistosoma japonicum/metabolism ; *Schistosomiasis japonica ; *Probiotics/administration &amp; dosage ; Female ; Multiomics ; }, abstract = {BACKGROUND: Schistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown.<br><br>PRINCIPAL FINDINGS: This study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated.<br><br>CONCLUSIONS: The recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.}, }
@article {pmid39465215, year = {2024}, author = {Lam, MI and Gleason, K and Repp, AB and Yeo, S and Vojnits, K and MacNaughton, P and Pakpour, S}, title = {The spatial and temporal effect of electrochromic windows on indoor and human microbiome in an inpatient hospital.}, journal = {Antimicrobial stewardship &amp; healthcare epidemiology : ASHE}, volume = {4}, number = {1}, pages = {e188}, pmid = {39465215}, issn = {2732-494X}, abstract = {OBJECTIVE: Improving the hospital environment and developing novel disinfection strategies are critical for infection control in healthcare settings. In this study, we explored the effects of electrochromic (EC) windows on indoor and patient microbiome in an inpatient hospital.<br><br>PATIENT AND SETTING: Hematology-Oncology patients at the University of Vermont Medical Center.<br><br>METHODS: We conducted a prospective study in ten occupied patient rooms. Five of the patient rooms had active EC windows that tint dynamically to control for heat and glare, and the other five rooms had deactivated EC windows that simulated traditional windows and blinds. Samples were collected one day before patient admission as baseline and on the 1st, 3rd, and 5th day of the patient stay. Total bacterial abundance and bacterial community structure were determined through quantitative PCR and 16s rRNA Illumina MiSeq sequencing, respectively.<br><br>RESULTS: Patient rooms with active EC windows had significantly lower light intensity and temperature than traditional patient rooms with blinds. The absolute bacterial abundance and diversities on windows were significantly lower in rooms with EC windows and the bacterial composition changed after one day EC window activation. Compared to baseline, relative abundance of the Staphylococcus genus was significantly lower on EC window surface during the five-day experiment. In contrast, the air microbiome was more diverse in rooms with EC windows.<br><br>CONCLUSION: Active electrochromic (EC) windows in patient rooms result in lower light intensity and temperature, reduced bacterial abundance and diversities on window surfaces, and a more diverse air microbiome, informing future healthcare design.}, }
@article {pmid39458569, year = {2024}, author = {Toivio, L and Launonen, H and Lindén, J and Lehto, M and Vapaatalo, H and Salmenkari, H and Korpela, R}, title = {Correction: Toivio et al. Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice. Nutrients 2024, 16, 18.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458569}, issn = {2072-6643}, abstract = {Text Correction [...].}, }
@article {pmid39458350, year = {2024}, author = {Marangelo, C and Vernocchi, P and Del Chierico, F and Scanu, M and Marsiglia, R and Petrolo, E and Fucà, E and Guerrera, S and Valeri, G and Vicari, S and Putignani, L}, title = {Stratification of Gut Microbiota Profiling Based on Autism Neuropsychological Assessments.}, journal = {Microorganisms}, volume = {12}, number = {10}, pages = {}, pmid = {39458350}, issn = {2076-2607}, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Investigations of gut microbiota (GM) play an important role in deciphering disease severity and symptoms. Overall, we stratified 70 ASD patients by neuropsychological assessment, based on Calibrated Severity Scores (CSSs) of the Autism Diagnostic Observation Schedule-Second edition (ADOS-2), Child Behavior Checklist (CBCL) and intelligent quotient/developmental quotient (IQ/DQ) parameters. Hence, metataxonomy and PICRUSt-based KEGG predictions of fecal GM were assessed for each clinical subset. Here, 60% of ASD patients showed mild to moderate autism, while the remaining 40% showed severe symptoms; 23% showed no clinical symptoms, 21% had a risk of behavior problems and 56% had clinical symptoms based on the CBCL, which assesses internalizing problems; further, 52% had no clinical symptoms, 21% showed risk, and 26% had clinical symptoms classified by CBCL externalizing problems. Considering the total CBCL index, 34% showed no clinical symptoms, 13% showed risk, and 52% had clinical symptoms. Here, 70% of ASD patients showed cognitive impairment/developmental delay (CI/DD). The GM of ASDs with severe autism was characterized by an increase in Veillonella, a decrease in Monoglobus pectinilyticus and a higher microbial dysbiosis index (MDI) when compared to mild-moderate ASDs. Patients at risk for behavior problems and showing clinical symptoms were characterized by a GM with an increase of Clostridium, Eggerthella, Blautia, Intestinibacter, Coprococcus, Ruminococcus, Onthenecus and Bariatricus, respectively. Peptidoglycan biosynthesis and biofilm formation KEGGs characterized patients with clinical symptoms, while potential microbiota-activated PPAR-γ-signaling was seen in CI/DD patients. This evidence derived from GM profiling may be used to further improve ASD understanding, leasing to a better comprehension of the neurological phenotype.}, }
@article {pmid39458307, year = {2024}, author = {Krause, JL and Engelmann, B and Lallinger, DJD and Rolle-Kampczyk, U and von Bergen, M and Chang, HD}, title = {Multi-Omics Analysis Unravels the Impact of Stool Sample Logistics on Metabolites and Microbial Composition.}, journal = {Microorganisms}, volume = {12}, number = {10}, pages = {}, pmid = {39458307}, issn = {2076-2607}, support = {NNF21OC0066551//Novo Nordisk Foundation/ ; //Dr. Rolf M. Schwiete Stiftung/ ; 375876048//Deutsche Forschungsgemeinschaft/ ; 831434//Innovative Medicines Initiative/ ; }, abstract = {Human health and the human microbiome are inevitably intertwined, increasing their relevance in clinical research. However, the collection, transportation and storage of faecal samples may introduce bias due to methodological differences, especially since postal shipping is a common practise in large-scale clinical cohort studies. Using four different Omics layer, we determined the structural (16S rRNA sequencing, cytometric microbiota profiling) and functional integrity (SCFAs, global metabolome) of the microbiota in relation to different easy-to-handle conditions. These conditions were storage at -20 °C, -20 °C as glycerol stock, 4 °C and room temperature with and without oxygen exposure for a maximum of one week. Storage time affected the microbiota on all Omics levels. However, the magnitude was donor-dependent, highlighting the need for purpose-optimized sample collection in clinical multi-donor studies. The effects of oxygen exposure were negligible for all analyses. At ambient temperature, SCFA and compositional profiles were stable for 24 h and 48 h, respectively, while at 4 °C, SCFA profiles were maintained for 48 h. The global metabolome was highly susceptible, already changing at 24 h in non-frozen conditions. Thus, faecal microbiota was best preserved on all levels when transported as a native sample frozen within 24 h, leading to the least biased outcomes in the analysis. We conclude that the immediate freezing of native stool samples for transportation to the lab is best suited for planned multi-Omics analyses that include metabolomics to extend standard sequencing approaches.}, }
@article {pmid39455951, year = {2024}, author = {Rastegar, S and Skurnik, M and Tadjrobehkar, O and Samareh, A and Samare-Najaf, M and Lotfian, Z and Khajedadian, M and Hosseini-Nave, H and Sabouri, S}, title = {Synergistic effects of bacteriophage cocktail and antibiotics combinations against extensively drug-resistant Acinetobacter baumannii.}, journal = {BMC infectious diseases}, volume = {24}, number = {1}, pages = {1208}, pmid = {39455951}, issn = {1471-2334}, support = {402000840//Hossein Hosseini-Nave/ ; }, mesh = {*Acinetobacter baumannii/virology/drug effects ; *Biofilms/drug effects/growth &amp; development ; *Anti-Bacterial Agents/pharmacology ; *Bacteriophages/physiology ; *Acinetobacter Infections/microbiology/therapy ; Humans ; *Drug Resistance, Multiple, Bacterial ; Phage Therapy/methods ; Microbial Sensitivity Tests ; }, abstract = {BACKGROUND: The extensively drug-resistant (XDR) strains of Acinetobacter baumannii have become a major cause of nosocomial infections, increasing morbidity and mortality worldwide. Many different treatments, including phage therapy, are attractive ways to overcome the challenges of antibiotic resistance.<br><br>METHODS: This study investigates the biofilm formation ability of 30 XDR A. baumannii isolates and the efficacy of a cocktail of four tempetate bacteriophages (SA1, Eve, Ftm, and Gln) and different antibiotics (ampicillin/sulbactam, meropenem, and colistin) in inhibiting and degrading the biofilms of these strains.<br><br>RESULTS: The majority (83.3%) of the strains exhibited strong biofilm formation. The bacteriophage cocktail showed varying degrees of effectiveness against A. baumannii biofilms, with higher concentrations generally leading to more significant inhibition and degradation rates. The antibiotics-bacteriophage cocktail combinations also enhanced the inhibition and degradation of biofilms.<br><br>CONCLUSION: The findings suggested that the bacteriophage cocktail is an effective tool in combating A. baumannii biofilms, with its efficacy depending on the concentration. Combining antibiotics with the bacteriophage cocktail improved the inhibition and removal of biofilms, indicating a promising strategy for managing A. baumannii infections. These results contribute to our understanding of biofilm dynamics and the potential of bacteriophage cocktails as a novel therapeutic approach to combat antibiotic-resistant bacteria.}, }
@article {pmid39452183, year = {2024}, author = {Otava, UE and Tervo, L and Havela, R and Vuotari, L and Ylänne, M and Asplund, A and Patpatia, S and Kiljunen, S}, title = {Phage-Antibiotic Combination Therapy against Recurrent Pseudomonas Septicaemia in a Patient with an Arterial Stent.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {39452183}, issn = {2079-6382}, support = {336519//Research Council of Finland/ ; PROFI7//Research Council of Finland/ ; n.a.//Jane and Aatos Erkko Foundation/ ; }, abstract = {Background: Intravascular stent infections are often associated with high risks of morbidity and mortality. We report here a case of a patient with an arterial stent and recurrent Pseudomonas septicaemias successfully treated with phage-meropenem combination therapy. Methods: A 75-year-old female with arteriosclerosis and comorbidities went through a femoropopliteal bypass with prosthesis in the right inguinal area. After the bypass, she developed a recurring Pseudomonas aeruginosa infection and also neutropenia during different antibiotics. A rapidly growing pseudoaneurysm in the right inguinal area led to an emergency intra-arterial stent placement during blood stream infection, later suspected to host a P. aeruginosa biofilm. Removing the stent was deemed precarious, and phage therapy was considered as a compassionate treatment option. A three-phage cocktail infecting the P. aeruginosa strain was prepared and administered intravenously together with meropenem for two weeks, after which, a ten-month follow-up was carried out. Results: No adverse reactions occurred during the phage therapy treatment, while infection markers were normalized. In addition, recovery was seen in a PET-CT scan. During the 10-month follow-up, no further P. aeruginosa septicaemias occurred. Conclusions: Phage-meropenem combination therapy was thus found safe and effective in the treatment of recurrent Pseudomonas septicaemia in a patient with an arterial stent.}, }
@article {pmid39450961, year = {2024}, author = {Sansonetti, PJ and Doré, J}, title = {[The human microbiome proofed by the Anthropocene: from correlation to causality and intervention].}, journal = {Medecine sciences : M/S}, volume = {40}, number = {10}, pages = {757-765}, doi = {10.1051/medsci/2024121}, pmid = {39450961}, issn = {1958-5381}, mesh = {Humans ; *Microbiota/physiology ; Animals ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Biodiversity ; Causality ; Climate Change ; }, abstract = {The deleterious effects of human activities on biodiversity in the vegetal and animal world, and on climate changes are now well-established facts. However, little is yet known on the impact of human activities on microbial diversity on the planet and more specifically on the human microbiota Large implementation of metagenomics allows exaustive microbial cataloguing with broad spatio-temporal resolution of human microbiota. A reduction in bacterial richness and diversity in the human microbiota, particularly in the intestinal tract, is now established and particularly obvious in the most industrialized regions of the planet. Massive, uncontrolled use of antibiotics, drastic changes in traditional food habits and some elements of the "global exposome" that remain to identify are usually considered as stressors accounting for this situation of "missing microbes". As a consequence, a dysbiotic situation develops, a "dysbiosis" being characterized by the erosion of the central core of shared bacterial species across individuals and the development of opportunistic "pathobionts" in response to a weaker barrier capacity of these impoverished microbiota. The current challenge is to establish a causality link between the extension of these dysbiotic situations and the steady emergence of epidemic, non-communicable diseases such as asthma, allergy, obesity, diabetes, autoimmune diseases and some cancers. Experimental animal models combined with controlled, prospective clinical interventions are in demand to consolidate causality links, with the understanding that in the deciphering of the mechanisms of alteration of the human-microbiome symbiosis resides a novel exciting chapter of medicine: "microbial medicine".}, }
@article {pmid39447121, year = {2024}, author = {Jia, B and Baek, JH and Lee, JK and Sun, Y and Kim, KH and Jung, JY and Jeon, CO}, title = {Expanding the β-Lactamase Family in the Human Microbiome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {46}, pages = {e2403563}, pmid = {39447121}, issn = {2198-3844}, support = {2024SSY0104//Pioneer"and"Leading Goose"R&amp;DProgram of Zhejiang/ ; 2023C4S01002//Xianghu Laboratory/ ; 2018R1A5A1025077//Xianghu Laboratory/ ; 2018R1A5A1025077//Ministry of Science and ICT of the Ministry of Science and ICT, Republic of Korea/ ; 2021003420003//Korea Environment Industry &amp; Technology Institute (KEITI) through the Project to make multi-ministerial national biological research resources more advanced, funded by Korea Ministry of Environment (MOE), Republic of Korea/ ; }, mesh = {Humans ; *beta-Lactamases/metabolism/genetics ; Female ; Microbiota/genetics ; Gastrointestinal Microbiome/genetics/physiology/drug effects ; Male ; Adult ; Anti-Bacterial Agents/pharmacology ; beta-Lactams/pharmacology ; Middle Aged ; }, abstract = {β-lactams, the most common antibiotics globally, have resistance primarily determined by β-lactamases. Human microbiota and β-lactams influence mutually; however, β-lactamase variety and abundance in the human microbiome remain partially understood. This study aimed to elucidate the diversity, abundance, and substrate spectrum of β-lactamases. 1369 characterized β-lactamases and 16 204 putative sequences are collected from protein databases. Upon clustering analysis and biochemical assays, nine proteins exhibiting less than 35% identity to those previously characterized are confirmed as β-lactamases. These newly identified β-lactamases originated from eight distinct clusters comprising 1163 β-lactamases. Quantifying healthy participants (n = 2394) across 19 countries using functionally confirmed clusters revealed that Japan have the highest gut β-lactamase abundance (log2[reads per million (RPM)] = 6.52) and Fiji have the lowest (log2[RPM] = 2.31). The β-lactamase abundance is correlated with β-lactam consumption (R = 0.50, p = 0.029) and income (R = 0.51, p = 0.024). Comparing individuals with ailments with healthy participants, β-lactamase abundance in the gut is increased significantly in patients with colorectal cancer, cardiovascular diseases, breast cancer, and epilepsy. These outcomes provide insights into investigating antibiotic resistance, antibiotic stewardship, and gut microbiome-antibiotic interactions.}, }
@article {pmid39443987, year = {2024}, author = {Levi Mortera, S and Marzano, V and Rapisarda, F and Marangelo, C and Pirona, I and Vernocchi, P and Di Michele, M and Del Chierico, F and Quintero, MA and Fernandez, I and Hazime, H and Killian, RM and Solis, N and Ortega, M and Damas, OM and Proksell, S and Kerman, DH and Deshpande, AR and Garces, L and Scaldaferri, F and Gasbarrini, A and Abreu, MT and Putignani, L}, title = {Metaproteomics reveals diet-induced changes in gut microbiome function according to Crohn's disease location.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {217}, pmid = {39443987}, issn = {2049-2618}, mesh = {Humans ; *Crohn Disease/microbiology ; *Gastrointestinal Microbiome ; Male ; Female ; *Feces/microbiology ; Adult ; *Proteomics ; Middle Aged ; Diet ; Dietary Fiber/administration &amp; dosage ; Bacteria/classification/isolation &amp; purification/genetics ; Colon/microbiology ; Young Adult ; Faecalibacterium/isolation &amp; purification ; }, abstract = {BACKGROUND: Crohn's disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry.<br><br>RESULTS: At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs.<br><br>CONCLUSIONS: The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. Video Abstract.}, }
@article {pmid39443812, year = {2025}, author = {Joos, R and Boucher, K and Lavelle, A and Arumugam, M and Blaser, MJ and Claesson, MJ and Clarke, G and Cotter, PD and De Sordi, L and Dominguez-Bello, MG and Dutilh, BE and Ehrlich, SD and Ghosh, TS and Hill, C and Junot, C and Lahti, L and Lawley, TD and Licht, TR and Maguin, E and Makhalanyane, TP and Marchesi, JR and Matthijnssens, J and Raes, J and Ravel, J and Salonen, A and Scanlan, PD and Shkoporov, A and Stanton, C and Thiele, I and Tolstoy, I and Walter, J and Yang, B and Yutin, N and Zhernakova, A and Zwart, H and ,  and Doré, J and Ross, RP}, title = {Examining the healthy human microbiome concept.}, journal = {Nature reviews. Microbiology}, volume = {23}, number = {3}, pages = {192-205}, pmid = {39443812}, issn = {1740-1534}, mesh = {Humans ; *Microbiota/physiology ; }, abstract = {Human microbiomes are essential to health throughout the lifespan and are increasingly recognized and studied for their roles in metabolic, immunological and neurological processes. Although the full complexity of these microbial communities is not fully understood, their clinical and industrial exploitation is well advanced and expanding, needing greater oversight guided by a consensus from the research community. One of the most controversial issues in microbiome research is the definition of a 'healthy' human microbiome. This concept is complicated by the microbial variability over different spatial and temporal scales along with the challenge of applying a unified definition to the spectrum of healthy microbiome configurations. In this Perspective, we examine the progress made and the key gaps that remain to be addressed to fully harness the benefits of the human microbiome. We propose a road map to expand our knowledge of the microbiome-health relationship, incorporating epidemiological approaches informed by the unique ecological characteristics of these communities.}, }
@article {pmid39440978, year = {2024}, author = {Soto Ocaña, J and Friedman, ES and Keenan, O and Bayard, NU and Ford, E and Tanes, C and Munneke, MJ and Beavers, WN and Skaar, EP and Bittinger, K and Zemel, BS and Wu, GD and Zackular, JP}, title = {Metal availability shapes early life microbial ecology and community succession.}, journal = {mBio}, volume = {15}, number = {11}, pages = {e0153424}, pmid = {39440978}, issn = {2150-7511}, support = {R01DK107565, P30DK050306//HHS | National Institutes of Health (NIH)/ ; R35GM138369//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; UL1 TR001878/TR/NCATS NIH HHS/United States ; R01DK107565//HHS | National Institutes of Health (NIH)/ ; P30 DK050306/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; R01 DK107565/DK/NIDDK NIH HHS/United States ; R35 GM138369/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Infant ; *Metals/metabolism ; *Leukocyte L1 Antigen Complex/metabolism/analysis ; Bacteria/metabolism/classification/genetics ; Breast Feeding ; Feces/microbiology ; Gastrointestinal Tract/microbiology ; Infant, Newborn ; Microbiota ; Infant Formula ; }, abstract = {The gut microbiota plays a critical role in human health and disease. Microbial community assembly and succession early in life are influenced by numerous factors. In turn, assembly of this microbial community is known to influence the host, including immune system development, and has been linked to outcomes later in life. To date, the role of host-mediated nutritional immunity and metal availability in shaping microbial community assembly and succession early in life has not been explored in depth. Using a human infant cohort, we show that the metal-chelating protein calprotectin is highly abundant in infants. Taxa previously shown to be successful early colonizers of the infant gut, such as Enterococcus, Enterobacteriaceae, and Bacteroides, are highly resistant to experimental metal starvation in culture. Lactobacillus, meanwhile, is highly susceptible to metal restriction, pointing to a possible mechanism by which host-mediated metal limitation shapes the fitness of early colonizing taxa in the infant gut. We further demonstrate that formula-fed infants harbor markedly higher levels of metals in their gastrointestinal tract compared to breastfed infants. Formula-fed infants with high levels of metals harbor distinct microbial communities compared to breastfed infants, with higher levels of Enterococcus, Enterobacter, and Klebsiella, taxa which show increased resistance to the toxic effects of high metal concentrations. These data highlight a new paradigm in microbial community assembly and suggest an unappreciated role for nutritional immunity and dietary metals in shaping the earliest colonization events of the microbiota.IMPORTANCEEarly life represents a critical window for microbial colonization of the human gastrointestinal tract. Surprisingly, we still know little about the rules that govern the successful colonization of infants and the factors that shape the success of early life microbial colonizers. In this study, we report that metal availability is an important factor in the assembly and succession of the early life microbiota. We show that the host-derived metal-chelating protein, calprotectin, is highly abundant in infants and successful early life colonizers can overcome metal restriction. We further demonstrate that feeding modality (breastmilk vs formula) markedly impacts metal levels in the gut, potentially influencing microbial community succession. Our work suggests that metals, a previously unexplored aspect of early life ecology, may play a critical role in shaping the early events of microbiota assembly in infants.}, }
@article {pmid39439268, year = {2024}, author = {Weinkove, D}, title = {Folates, bacteria and ageing: insights from the model organism C. elegans in the study of nutrition and ageing.}, journal = {The Proceedings of the Nutrition Society}, volume = {}, number = {}, pages = {1-5}, pmid = {39439268}, issn = {1475-2719}, support = {BB/H01974X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The relationship between nutrition and ageing is complex. The metabolism and synthesis of micronutrients within the gut microbiome can influence human health but is challenging to study. Furthermore, studying ageing in humans is time-consuming and difficult to control for environmental factors. Studies in model organisms can guide research efforts in this area. This review describes how the nematode Caenorhabditis elegans can be used to study how bacteria and diet influence ageing and inform follow-on studies in humans. It is known that certain bacteria accelerate ageing in C. elegans. This age-accelerating effect is prevented by inhibiting folate synthesis within the bacteria, and we propose that in the human microbiome, certain bacteria also accelerate ageing in a way that can be modulated by interfering with bacterial folate synthesis. Bacterial-derived folates do not promote ageing themselves; rather, ageing is accelerated by bacteria in some way, either through secondary metabolites or other bacterial activity, which is dependent on bacterial folate synthesis. In humans, it may be possible to inhibit bacterial folate synthesis in the human gut while maintaining healthy folate status in the body via food and supplementation. The supplement form of folic acid has a common breakdown product that can be used by bacteria to increase folate synthesis. Thus, supplementation with folic acid may not be good for health in certain circumstances such as in older people or those with an excess of proteobacteria in their microbiome. For these groups, alternative supplement strategies may be a safer way to ensure adequate folate levels.}, }
@article {pmid39435653, year = {2024}, author = {Rastegar, S and Sabouri, S and Tadjrobehkar, O and Samareh, A and Niaz, H and Sanjari, N and Hosseini-Nave, H and Skurnik, M}, title = {Characterization of bacteriophage vB_AbaS_SA1 and its synergistic effects with antibiotics against clinical multidrug-resistant Acinetobacter baumannii isolates.}, journal = {Pathogens and disease}, volume = {82}, number = {}, pages = {}, pmid = {39435653}, issn = {2049-632X}, support = {//University of Helsinki/ ; KMU.AC.IR.400000652//Kerman University of Medical Sciences/ ; }, mesh = {*Acinetobacter baumannii/virology/drug effects ; *Anti-Bacterial Agents/pharmacology ; *Drug Resistance, Multiple, Bacterial ; *Bacteriophages/genetics/isolation &amp; purification/physiology/classification ; *Acinetobacter Infections/microbiology ; Humans ; *Genome, Viral ; *Host Specificity ; Microbial Sensitivity Tests ; Sewage/virology/microbiology ; Phage Therapy ; DNA, Viral/genetics ; Viral Plaque Assay ; }, abstract = {Acinetobacter baumannii is a major cause of nosocomial infections globally. The increasing prevalence of multidrug-resistant (MDR) A. baumannii has become an important public health concern. To combat drug resistance, alternative methods such as phage therapy have been suggested. In total, 30 MDR A. baumannii strains were isolated from clinical specimens, and their antibiotic susceptibilities were determined. The Acinetobacter phage vB_AbaS_SA1, isolated from hospital sewage, was characterized. In addition to its plaque size, particle morphology, and host range, its genome sequence was determined and annotated. Finally, the antibacterial effects of phage alone, antibiotics alone, and phage/antibiotic combinations were assessed against the A. baumannii strains. Phage vB_AbaS_SA1 had siphovirus morphology, showed a latent period of 20 min, and a 250 PFU/cell (plaque forming unit/cell) burst size. When combined with antibiotics, vB_AbaS_SA1 (SA1) showed a significant phage-antibiotic synergy effect and reduced the overall effective concentration of antibiotics in time-kill assessments. The genome of SA1 is a linear double-stranded DNA of 50 108 bp in size with a guanine-cytosine (GC) content of 39.15%. Despite the potent antibacterial effect of SA1, it is necessary to perform additional research to completely elucidate the mechanisms of action and potential constraints associated with utilizing this bacteriophage.}, }
@article {pmid39429878, year = {2024}, author = {Chen, J and Luo, J and Pouwels, S and Li, B and Wu, B and Abdelbaki, TN and Arcot, J and Yang, W}, title = {Dietary therapies interlinking with gut microbes toward human health: Past, present, and future.}, journal = {iMeta}, volume = {3}, number = {5}, pages = {e230}, pmid = {39429878}, issn = {2770-596X}, abstract = {Overview of personalized dietary therapies. This flow chart exhibits the future prospect for integrating human microbiome and bio-medical research to revolutionize the precise personalized dietary therapies. With the development of artificial intelligence (AI), incorporating database may achieve personalized dietary therapies with high precision.}, }
@article {pmid39425798, year = {2024}, author = {Goladze, S and Patpatia, S and Tuomala, H and Ylänne, M and Gachechiladze, N and de Oliveira Patricio, D and Skurnik, M and Sundberg, LR}, title = {Isolation and characterization of Yersinia phage fMtkYen3-01.}, journal = {Archives of virology}, volume = {169}, number = {11}, pages = {226}, pmid = {39425798}, issn = {1432-8798}, support = {PHDF-21-2176//Shota Rustaveli National Science Foundation/ ; #346772//Research Council of Finland/ ; }, mesh = {*Yersinia enterocolitica/virology/genetics ; *Genome, Viral/genetics ; *Bacteriophages/genetics/classification/isolation &amp; purification/physiology ; Yersinia Infections/microbiology/therapy/virology ; Base Composition ; Humans ; Phage Therapy/methods ; }, abstract = {Yersinia enterocolitica causes yersiniosis, the third most common gastrointestinal infection in humans throughout Europe. The emergence of multidrug resistance and the lack of effective new antibiotics have drawn attention to phage therapy as a treatment option. Here, we report the complete genome sequence of phage fMtkYen3-01, which infects Y. enterocolitica serotype O:3 strains. This phage has a genome 40,415 bp in length with 45.1% GC content and 49 predicted genes. fMtkYen3-01 infected 9.5% of the 42 Y. enterocolitica strains tested and showed stability at 25-40 °C, as well as pH 5.0-10.0. These results suggest the therapeutic potential of this phage.}, }
@article {pmid39421627, year = {2024}, author = {Beschastnov, VV and Shirokova, IY and Belyanina, NA and Pogodin, IE and Tulupov, AA and Tochilina, AG and Belova, IV and Tyumenkov, YO and Kovalishena, OV and Soloveva, IV}, title = {Evaluation of the Feasibility of Using Commercial Wound Coatings as a Carrier Matrix for Bacteriophages.}, journal = {Sovremennye tekhnologii v meditsine}, volume = {16}, number = {1}, pages = {45-52}, pmid = {39421627}, issn = {2309-995X}, mesh = {Humans ; *Bacteriophages ; *Wound Infection/therapy ; Staphylococcus aureus/virology/drug effects ; Wound Healing ; Phage Therapy ; Bandages ; Feasibility Studies ; }, abstract = {UNLABELLED: The aim of the investigation is to study the possibility of applying commercial wound coatings for treating infected wounds as a carrier matrix for bacteriophages.<br><br>MATERIALS AND METHODS: Twelve varieties of commercial wound coverings based on biopolymers of natural and synthetic origin, a biological preparation Staphylophag produced by scientific-industrial association Microgen (Russia), registration certificate P N001973/01, and the S. aureus 3196 test strain (GenBank JARQZO000000000) isolated from a patient with a burn wound have been used in our work. The ability of commercial biological wound coatings to absorb solutions was examined by immersing them in a physiological solution (pH 7.0-7.2) followed by weighing. The lytic activity of three bacteriophage series against the test strain was studied using the Appelman method and a spot test. The lytic activity of the bacteriophage in the wound samples was studied within 7 days after its absorption by the wound coatings.<br><br>RESULTS: The greatest volume of fluid was absorbed by the LycoSorb, NEOFIX FibroSorb Ag, Biatravm, and Chitocol-S wound coatings. All bacteriophage series have been found to have a high lytic activity against the test strain. It has also been shown that Chitocol-S, Collachit-FA, Algipran, and Aquacel Ag Extra possessed their own inherent antibacterial activity under in vitro conditions stable for 7 days; moreover, the lysis zones of the test strain increased after their saturation with bacteriophage. On day 0, a high level of bacteriophage lytic activity with the maximum size of the test strain lysis zones from 49 to 59 mm have been found to remain in all samples of the wound coverings. The bacteriophage activity persisted for 1 day in the samples of Hydrofilm, Polypran, and NEOFIX FibroCold Ag coatings, up to 4 days in Algipran, Nano-Aseptica, and Biatravm coatings; and for 7 days in the Chitocol-S, Collachit-FA, Opsite Post-Op Visible, NEOFIX FibroSorb Ag, Aquacel Ag Extra, and LycoSorb samples.<br><br>CONCLUSION: Modern commercial wound dressings based on chitosan-collagen complex (Chitocol-S, Collachit-FA), polyurethane (Opsite Post-Op Visible, LycoSorb, NEOFIX FibroSorb Ag), and Hydrofiber (Aquacel Ag Extra) have a sufficient level of bacteriophage solution absorption, provide a stable preservation of the bacteriophage lytic activity under in vitro conditions up to 7 days. Thus, the in vitro studies prove the possibility of their use as a carrier matrix for bacteriophages.}, }
@article {pmid39421255, year = {2024}, author = {Geerlings, SY and van der Ark, K and Nijsse, B and Boeren, S and van Loosdrecht, M and Belzer, C and de Vos, WM}, title = {Omics-based analysis of Akkermansia muciniphila cultivation in food-grade media.}, journal = {Microbiome research reports}, volume = {3}, number = {3}, pages = {36}, pmid = {39421255}, issn = {2771-5965}, abstract = {Background and Aim: Over the past years, the gut microbiota and its correlation to health and disease has been studied extensively. In terms of beneficial microbes, an increased interest in Akkermansia muciniphila (A. muciniphila) has been observed since its discovery. Direct evidence for the role of A. muciniphila in host health has been provided in both mice and human studies. However, for human interventions with A. muciniphila cells, industrial-scale fermentations are needed, and hence, the used cultivation media should be free of animal-derived components, food-grade, non-allergenic and allow for efficient growth to high densities to provide cost-effective production platforms. In this study, we assessed the growth and performance of A. muciniphila in batch bioreactors using newly developed plant-based media. Methods: The bioreactors were supplemented with varying carbon sources, including different ratios of N-acetylglucosamine (GlcNAc) and glucose. We monitored the growth of A. muciniphila in the plant-based medium using optical density (OD600) measurements and microscopy. In addition, we used a combination of biochemical analysis as well as transcriptional and proteomics analysis to gain detailed insight into the physiology. Results: Comparisons between growth on these media and that on mucin revealed differences at both transcriptome and proteome levels, including differences in the expression of glycosyltransferases, signaling proteins, and stress response. Furthermore, elongated cells and higher OD600 values were observed using the plant-based media as compared to cultivation media containing mucin. Conclusion: These differences do not hamper growth, and therefore, our data suggest that the food-grade medium composition described here could be used to produce A. muciniphila with high yields for therapeutic purposes.}, }
@article {pmid39421250, year = {2024}, author = {Puhlmann, ML and van de Rakt, E and Kerezoudi, EN and Rangel, I and Brummer, RJ and Smidt, H and Kaper, FS and de Vos, WM}, title = {Analysis of the fermentation kinetics and gut microbiota modulatory effect of dried chicory root reveals the impact of the plant-cell matrix rationalizing its conversion in the distal colon.}, journal = {Microbiome research reports}, volume = {3}, number = {3}, pages = {28}, pmid = {39421250}, issn = {2771-5965}, abstract = {Aim: The cell matrix of plant foods has received little attention in prebiotic fiber research. We aimed to understand the impact of the plant cell matrix in dried chicory root on its breakdown in the human gut to explain its reported beneficial effects on gut and metabolic health. Methods: We applied in vitro digestion and fermentation models together with an ex vivo gut barrier integrity model. Plant cell matrix intactness in the upper gastrointestinal tract was investigated by scanning electron microscopy. Colonic breakdown of inulin, and chicory root cubes and powder was assessed by gut microbiota analysis using 16S rRNA gene amplicon sequencing and determining the kinetics of changes in pH, gas, and short-chain fatty acid (SCFA) production. Finally, effects on gut barrier integrity were explored by exposing colonic biopsies to fermentation supernatants in an Ussing chamber model. Results: The plant cell matrix of dried chicory root cubes remained intact throughout upper gastrointestinal transit. Dried chicory root fermentation resulted in higher final relative abundances of pectin-degrading Monoglobus and butyrate-producing Roseburia spp. compared to inulin and a seven-fold increase in Bifidobacterium spp. in donors where these species were present. Dried chicory root cubes yielded similar total SCFAs but higher final butyrate levels than chicory root powder or isolated inulin with less gas produced. No uniform but donor-specific effects of fermentation supernatants on the maintenance of gut barrier integrity were detected. Conclusion: The intact plant cell matrix of dried chicory root affected its colonic breakdown kinetics and microbiota, underpinning its beneficial effect in vivo.}, }
@article {pmid39419193, year = {2024}, author = {Chen, H and Zeng, M and Batool, SS and Zhao, Y and Yu, Z and Zhou, J and Liu, K and Huang, J}, title = {Metagenomic analysis reveals effects of gut microbiome in response to neoadjuvant chemoradiotherapy in advanced rectal cancer.}, journal = {Genomics}, volume = {116}, number = {6}, pages = {110951}, doi = {10.1016/j.ygeno.2024.110951}, pmid = {39419193}, issn = {1089-8646}, mesh = {Humans ; *Rectal Neoplasms/therapy/microbiology/genetics/metabolism ; *Gastrointestinal Microbiome ; *Neoadjuvant Therapy ; Chemoradiotherapy ; Female ; Male ; Middle Aged ; Metagenomics ; Aged ; Metagenome ; Feces/microbiology ; Bacteria/genetics/classification/metabolism ; }, abstract = {Neoadjuvant chemoradiotherapy can enhance survival rate of patients with advanced rectal cancer, but its effectiveness varies considerably. Previous studies have indicated that gut microbes may serve as biomarkers for predicting treatment efficacy. However, the specific roles of the gut microbiome in patients who have good response to nCRT remains unclear. In this study, shotgun metagenomic sequencing technology was used to analyze the fecal microbiome of patients with varying responses to nCRT. Our findings revealed that beneficial intestinal bacteria and genes from different metabolic pathways (carbohydrate metabolism, amino acid metabolism, and sulfur metabolism) were significantly enriched in patients with good response. Additionally, causal relationship in which microbial-derived GDP-D-rhamnose and butyrate could influence the response to nCRT was clarified. Our results offered new insights into the different response to nCRT, and provided valuable reference points for improving the effectiveness of nCRT in patients with advanced colorectal cancer.}, }
@article {pmid39415150, year = {2024}, author = {Ma, J and Wang, F and Zhu, Y and Tian, Y and Du, C and Yan, L and Ding, C and Wang, D}, title = {Oral microbiome dysbiosis may be associated with intra cranial aneurysms.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {1235}, pmid = {39415150}, issn = {1472-6831}, support = {2021J01217//Fujian Provincial Nature Foundation/ ; 2021Y2001//Technology Platform Construction Project of Fujian Province/ ; }, mesh = {Humans ; *Intracranial Aneurysm/microbiology ; Female ; Male ; Middle Aged ; *Dysbiosis/microbiology ; *Microbiota ; Case-Control Studies ; *Saliva/microbiology ; Mouth/microbiology ; RNA, Ribosomal, 16S/analysis ; Adult ; Aged ; High-Throughput Nucleotide Sequencing ; }, abstract = {BACKGROUND: Although the etiology of aneurysms remains elusive, recent advances in high-throughput sequencing technology and ongoing human microbiome investigations suggest a potential link between microbiome composition and the onset of various human diseases.<br><br>OBJECTIVE: This study aimed to utilize high-throughput 16&#xa0;S rRNA gene sequencing to analyze the oral flora bacterial profiles of individuals, comparing patients with intracranial aneurysms to a healthy control group. Importantly, we sought to identify differences in the oral microbiota and offer novel insights and methods for early diagnosis and identification of intracranial aneurysms.<br><br>METHOD: Saliva samples were collected from 60 patients with cerebral aneurysms (case group) and 130 healthy individuals (control group). The V3-V4 region of the bacterial 16&#xa0;S rRNA gene was amplified and sequenced using the HiSeq high-throughput sequencing platform to establish the bacterial profile. Sequencing data were analyzed using QIIME2 and Metastats software to compare composition differences and relative abundance at the phylum and genus levels in the oral microbiota of the two groups.<br><br>RESULTS: Significant differences in oral microbiota composition were observed between patients in the case and control groups (P&#x2009;<&#x2009;0.05). Genus-level identification highlighted key positions occupied by Eubacterium, Saccharimonadaceae, Rothia, Gemella, Streptococcus, Lactobacillales, Phocaeicola, Bacteroides, Saccharimonadales, and Abiotrophia.<br><br>CONCLUSION: This study revealed noteworthy distinctions in the composition, abundance, and diversity of oral microbiota between intracranial aneurysm patients and healthy controls. These disparities suggest a potential correlation between oral microbiota and the development of intracranial aneurysms, offering new avenues for early diagnosis and intervention. However, limitations such as a small sample size, lack of prospective design, and absence of causal inference warrant further validation and exploration.}, }
@article {pmid39408199, year = {2024}, author = {Iannotti, L and Rueda García, AM and Palma, G and Fontaine, F and Scherf, B and Neufeld, LM and Zimmerman, R and Fracassi, P}, title = {Terrestrial Animal Source Foods and Health Outcomes for Those with Special Nutrient Needs in the Life Course.}, journal = {Nutrients}, volume = {16}, number = {19}, pages = {}, pmid = {39408199}, issn = {2072-6643}, support = {P30 DK056341/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Animals ; Child ; Female ; Humans ; Pregnancy ; *Dairy Products ; *Diet ; *Eggs ; Food Hypersensitivity/epidemiology/prevention &amp; control ; *Meat ; Milk ; Nutrients/analysis ; }, abstract = {Background. Animal source foods are under scrutiny for their role in human health, yet some nutritionally vulnerable populations are largely absent from consideration. Methods. Applying a Population Intervention/Exposure Comparator Outcome (PICO/PECO) framework and prioritizing systematic review and meta-analyses, we reviewed the literature on terrestrial animal source foods (TASFs) and human health, by life course phase. Results. There were consistent findings for milk and dairy products on positive health outcomes during pregnancy and lactation, childhood, and among older adults. Eggs were found to promote early childhood growth, depending on context. Unprocessed meat consumption was associated with a reduced risk for anemia during pregnancy, improved cognition among school-age children, and muscle health in older adults. Milk and eggs represent a risk for food sensitivities/allergies, though prevalence is low, and individuals tend to outgrow the allergies. TASFs affect the human microbiome and associated metabolites with both positive and negative health repercussions, varying by type and quantity. Conclusions. There were substantial gaps in the evidence base for studies limiting our review, specifically for studies in populations outside high-income countries and for several TASF types (pig, poultry, less common livestock species, wild animals, and insects). Nonetheless, sufficient evidence supports an important role for TASFs in health during certain periods of the life course.}, }
@article {pmid39406893, year = {2025}, author = {Ioannou, A and Berkhout, MD and Geerlings, SY and Belzer, C}, title = {Akkermansia muciniphila: biology, microbial ecology, host interactions and therapeutic potential.}, journal = {Nature reviews. Microbiology}, volume = {23}, number = {3}, pages = {162-177}, pmid = {39406893}, issn = {1740-1534}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Akkermansia/physiology/genetics/classification ; Probiotics/therapeutic use ; *Host Microbial Interactions ; *Verrucomicrobia/physiology/genetics/classification ; Animals ; Intestinal Mucosa/microbiology ; Phylogeny ; Mucins/metabolism ; }, abstract = {Akkermansia muciniphila is a gut bacterium that colonizes the gut mucosa, has a role in maintaining gut health and shows promise for potential therapeutic applications. The discovery of A. muciniphila as an important member of our gut microbiome, occupying an extraordinary niche in the human gut, has led to new hypotheses on gut health, beneficial microorganisms and host-microbiota interactions. This microorganism has established a unique position in human microbiome research, similar to its role in the gut ecosystem. Its unique traits in using mucin sugars and mechanisms of action that can modify host health have made A. muciniphila a subject of enormous attention from multiple research fields. A. muciniphila is becoming a model organism studied for its ability to modulate human health and gut microbiome structure, leading to commercial products, a genetic model and possible probiotic formulations. This Review provides an overview of A. muciniphila and Akkermansia genus phylogeny, ecophysiology and diversity. Furthermore, the Review discusses perspectives on ecology, strategies for harnessing beneficial effects of A. muciniphila for human mucosal metabolic and gut health, and its potential as a biomarker for diagnostics and prognostics.}, }
@article {pmid39403892, year = {2024}, author = {Wang, B and Shen, Y and Fang, J and Su, X and Xu, ZZ}, title = {DeepPhylo: Phylogeny-Aware Microbial Embeddings Enhanced Predictive Accuracy in Human Microbiome Data Analysis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {45}, pages = {e2404277}, pmid = {39403892}, issn = {2198-3844}, support = {2022YFA1304200//National Key RD Program of China/ ; }, mesh = {Humans ; *Microbiota/genetics ; *Phylogeny ; Data Analysis ; Inflammatory Bowel Diseases/microbiology ; Female ; Male ; }, abstract = {Microbial data analysis poses significant challenges due to its high dimensionality, sparsity, and compositionality. Recent advances have shown that integrating abundance and phylogenetic information is an effective strategy for uncovering robust patterns and enhancing the predictive performance in microbiome studies. However, existing methods primarily focus on the hierarchical structure of phylogenetic trees, overlooking the evolutionary distances embedded within them. This study introduces DeepPhylo, a novel method that employs phylogeny-aware amplicon embeddings to effectively integrate abundance and phylogenetic information. DeepPhylo improves both the unsupervised discriminatory power and supervised predictive accuracy of microbiome data analysis. Compared to the existing methods, DeepPhylo demonstrates superiority in informing biologically relevant insights across five real-world microbiome use cases, including clustering of skin microbiomes, prediction of host chronological age and gender, diagnosis of inflammatory bowel disease (IBD) across 15 studies, and multilabel disease classification.}, }
@article {pmid39401296, year = {2024}, author = {Wang, S and Ilves, M and Mäenpää, K and Zhao, L and El-Nezami, H and Karisola, P and Alenius, H}, title = {ZnO Nanoparticles as Potent Inducers of Dermal Immunosuppression in Contact Hypersensitivity in Mice.}, journal = {ACS nano}, volume = {18}, number = {43}, pages = {29479-29491}, pmid = {39401296}, issn = {1936-086X}, mesh = {Animals ; *Zinc Oxide/chemistry/pharmacology ; Mice ; *Dermatitis, Contact/immunology/pathology ; Humans ; Female ; Skin/drug effects/immunology/pathology ; Nanoparticles/chemistry ; Oxazolone ; Mice, Inbred BALB C ; THP-1 Cells ; Disease Models, Animal ; Metal Nanoparticles/chemistry ; }, abstract = {Nanosized zinc oxide (nZnO) metal particles are used in skin creams and sunscreens to enhance their texture and optical properties as UV filters. Despite their common use, little is known about the molecular mechanisms of nZnO exposure on damaged skin. We studied the effects of topically applied nZnO particles on allergic skin inflammation in an oxazolone (OXA)-induced contact hypersensitivity (CHS) mouse model. We investigated whether exposure to nZnO during the sensitization or challenge phase would induce immunological changes and modulate transcriptional responses. We followed skin thickness, cellular infiltration, and changes in the local transcriptome up to 28 days after the challenge. The responses peaked at 24 h and were fully resolved by 28 days. Co-exposure to nZnO and hapten did not interfere with the formation of the sensitization process. Conversely, during the hapten challenge, the application of nZnO fully suppressed the development of the CHS response by the inhibition of pro-inflammatory pathways, secretion of pro-inflammatory cytokines, and proliferation of immune cells. In differentiated and stimulated THP-1 cells and the CHS mouse model, we found that nZnO particles and Zn ions contributed to anti-inflammatory responses. The immunosuppressive properties of nZnO in inflamed skin are mediated by impaired IL-1R-, CXCR2-, and LTB4-mediated pathways. nZnO-induced dermal immunosuppression may be beneficial for individuals with contact allergies who use nZnO-containing cosmetic products. Our findings also provide a deeper understanding of the mechanisms of nZnO, which could be considered when developing nanoparticle-containing skin products.}, }
@article {pmid39396734, year = {2025}, author = {Kajova, M and Khawaja, T and Kainulainen, K and Kantele, A}, title = {Carbapenemase-producing Enterobacterales emerging in Finland's capital region over 2010-2023: increasing proportion of CPE cases first detected in clinical samples.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {31}, number = {2}, pages = {296-297}, doi = {10.1016/j.cmi.2024.10.005}, pmid = {39396734}, issn = {1469-0691}, }
@article {pmid39387683, year = {2024}, author = {Li, Z and Wang, Q and Huang, X and Wu, Y and Shan, D}, title = {Microbiome's role in musculoskeletal health through the gut-bone axis insights.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2410478}, pmid = {39387683}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Bone and Bones/microbiology ; *Musculoskeletal Diseases/microbiology/physiopathology ; Animals ; Osteoarthritis/microbiology/therapy ; Osteoporosis/microbiology ; Bone Density ; Musculoskeletal System/microbiology ; }, abstract = {The interplay between the human microbiome and the musculoskeletal system represents a burgeoning field of research with profound implications for understanding and treating musculoskeletal disorders. This review articulates the pivotal role of the microbiome in modulating bone health, highlighting the gut-bone axis as a critical nexus for potential therapeutic intervention. Through a meticulous analysis of recent clinical research, we underscore the microbiome's influence on osteoporosis, sarcopenia, osteoarthritis, and rheumatoid arthritis, delineating both the direct and indirect mechanisms by which microbiota could impact musculoskeletal integrity and function. Our investigation reveals novel insights into the microbiota's contribution to bone density regulation, hormone production, immune modulation, and nutrient absorption, laying the groundwork for innovative microbiome-based strategies in musculoskeletal disease management. Significantly, we identify the challenges hindering the translation of research into clinical practice, including the limitations of current microbial sequencing techniques and the need for standardized methodologies in microbiome studies. Furthermore, we highlight promising directions for future research, particularly in the realm of personalized medicine, where the microbiome's variability offers unique opportunities for tailored treatment approaches. This review sets a new agenda for leveraging gut microbiota in the diagnosis, prevention, and treatment of musculoskeletal conditions, marking a pivotal step toward integrating microbiome science into clinical musculoskeletal care.}, }
@article {pmid39394961, year = {2024}, author = {Branck, T and Hu, Z and Nickols, WA and Walsh, AM and Bhosle, A and Short, MI and Nearing, JT and Asnicar, F and McIver, LJ and Maharjan, S and Rahnavard, A and Louyakis, AS and Badri, DV and Brockel, C and Thompson, KN and Huttenhower, C}, title = {Comprehensive profile of the companion animal gut microbiome integrating reference-based and reference-free methods.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {39394961}, issn = {1751-7370}, mesh = {Animals ; *Gastrointestinal Microbiome/genetics ; Dogs/microbiology ; Cats ; *Pets/microbiology ; *Feces/microbiology ; *Phylogeny ; *Metagenome ; Humans ; *Metagenomics ; Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {The gut microbiome of companion animals is relatively underexplored, despite its relevance to animal health, pet owner health, and basic microbial community biology. Here, we provide the most comprehensive analysis of the canine and feline gut microbiomes to date, incorporating 2639 stool shotgun metagenomes (2272 dog and 367 cat) spanning 14 publicly available datasets (n = 730) and 8 new study populations (n = 1909). These are compared with 238 and 112 baseline human gut metagenomes from the Human Microbiome Project 1-II and a traditionally living Malagasy cohort, respectively, processed in a manner identical to the animal metagenomes. All microbiomes were characterized using reference-based taxonomic and functional profiling, as well as de novo assembly yielding metagenomic assembled genomes clustered into species-level genome bins. Companion animals shared 184 species-level genome bins not found in humans, whereas 198 were found in all three hosts. We applied novel methodology to distinguish strains of these shared organisms either transferred or unique to host species, with phylogenetic patterns suggesting host-specific adaptation of microbial lineages. This corresponded with functional divergence of these lineages by host (e.g. differences in metabolic and antibiotic resistance genes) likely important to companion animal health. This study provides the largest resource to date of companion animal gut metagenomes and greatly contributes to our understanding of the "One Health" concept of a shared microbial environment among humans and companion animals, affecting infectious diseases, immune response, and specific genetic elements.}, }
@article {pmid39392836, year = {2024}, author = {Daisley, BA and Allen-Vercoe, E}, title = {Microbes as medicine.}, journal = {Annals of the New York Academy of Sciences}, volume = {1541}, number = {1}, pages = {63-82}, pmid = {39392836}, issn = {1749-6632}, support = {950-232131//Canada Research Chairs/ ; PDF-402947//Natural Sciences and Engineering Research Council of Canada/ ; //Natural Sciences and Engineering Research Council of Canada/ ; 2023//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Humans ; *Probiotics/therapeutic use ; *Microbiota/drug effects/physiology ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Precision Medicine/methods ; Animals ; }, abstract = {Over the last two decades, advancements in sequencing technologies have significantly deepened our understanding of the human microbiome's complexity, leading to increased concerns about the detrimental effects of antibiotics on these intricate microbial ecosystems. Concurrently, the rise in antimicrobial resistance has intensified the focus on how beneficial microbes can be harnessed to treat diseases and improve health and offer potentially promising alternatives to traditional antibiotic treatments. Here, we provide a comprehensive overview of both established and emerging microbe-centric therapies, from probiotics to advanced microbial ecosystem therapeutics, examine the sophisticated ways in which microbes are used medicinally, and consider their impacts on microbiome homeostasis and health outcomes through a microbial ecology lens. In addition, we explore the concept of rewilding the human microbiome by reintroducing "missing microbes" from nonindustrialized societies and personalizing microbiome modulation to fit individual microbial profiles-highlighting several promising directions for future research. Ultimately, the advancements in sequencing technologies combined with innovative microbial therapies and personalized approaches herald a new era in medicine poised to address antibiotic resistance and improve health outcomes through targeted microbiome management.}, }
@article {pmid39386965, year = {2024}, author = {Muhi, S and Marshall, JL and O'Brien, DP and Johnson, PDR and Ross, G and Ramakrishnan, A and Mackay, LK and Doerflinger, M and McCarthy, JS and Jamrozik, E and Osowicki, J and Stinear, TP}, title = {A human model of Buruli ulcer: Provisional protocol for a Mycobacterium ulcerans controlled human infection study.}, journal = {Wellcome open research}, volume = {9}, number = {}, pages = {488}, pmid = {39386965}, issn = {2398-502X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Critical knowledge gaps have impeded progress towards reducing the global burden of disease due to Mycobacterium ulcerans, the cause of the neglected tropical disease Buruli ulcer (BU). Development of a controlled human infection model of BU has been proposed as an experimental platform to explore host-pathogen interactions and evaluate tools for prevention, diagnosis, and treatment. We have previously introduced the use case for a new human model and identified M. ulcerans JKD8049 as a suitable challenge strain. Here, we present a provisional protocol for an initial study, for transparent peer review during the earliest stages of protocol development. Following simultaneous scientific peer review and community/stakeholder consultation of this provisional protocol, we aim to present a refined protocol for institutional review board (IRB) evaluation.}, }
@article {pmid39383990, year = {2024}, author = {Wang, C and Song, Y and Liang, J and Wang, Y and Zhang, D and Zhao, Z}, title = {Antibiotic resistance genes are transferred from manure-contaminated water bodies to the gut microbiota of animals through the food chain.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {363}, number = {Pt 1}, pages = {125087}, doi = {10.1016/j.envpol.2024.125087}, pmid = {39383990}, issn = {1873-6424}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Food Chain ; *Drug Resistance, Microbial/genetics ; *Manure/microbiology ; Daphnia/genetics ; Feces/microbiology ; Genes, Bacterial ; Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Water Pollutants, Chemical ; }, abstract = {Fecal-contaminated water may enter the food chain and become an important route for the transmission of antibiotic resistance genes (ARGs) to the human microbiome. However, little is known about the spread of ARGs from fecal contamination in water bodies along the aquatic food chain. In this study, laboratory-raised Daphnia magna and Aristichthys nobilis were used to investigate the effects of the addition of manure on target ARGs in water and their intestinal contents to determine the potential transmission route of ARGs in the aquatic food chain system. The abundance of target ARGs in water as well as D. magna and A. nobilis intestinal contents significantly increased when fecal contamination was present. ARGs bioaccumulated along the food chain, with four ARGs (tetM-01, tetX, qnrS, and sul2) detected regularly. Mn and Cr were key environmental factors that promoted the transfer of ARGs along the food chain. Fecal addition significantly changed the structure of microbial communities in water, D. magna gut, and A. nobilis gut. The ARG spectrum was significantly correlated with the composition and structure of the bacterial community. Proteobacteria, Bacteroidetes, and Firmicutes were identified as the main host bacteria and were likely to act as carriers of ARGs to promote the spread of antibiotic resistance in the food chain. The composition and structure of bacterial communities, along with mobile genetic elements, were two key drivers of ARG transfer. These findings provide new insights into the distribution and spread of ARGs along the freshwater food chain.}, }
@article {pmid39378356, year = {2025}, author = {Yang, I and Alford, T and Brewster, G and Geurs, N and Wharton, W and Yeager, K and Houser, M}, title = {Oral Microbiome and Cognition Among Black Cancer Caregivers.}, journal = {Nursing research}, volume = {74}, number = {1}, pages = {47-55}, pmid = {39378356}, issn = {1538-9847}, support = {P30 NR018090/NR/NINR NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; *Black or African American/psychology ; *Caregivers/psychology ; Cognition/physiology ; Georgia ; *Microbiota ; Mouth/microbiology ; *Neoplasms/psychology/microbiology ; Oral Health/statistics &amp; numerical data ; Saliva/microbiology ; }, abstract = {BACKGROUND: Despite known links between oral health and dementia and the growing understanding of the role of the human microbiome in health, few studies have explored the relationship between the oral microbiome and cognition. Additionally, there is a notable absence of research on how the oral microbiome is associated with cognitive function in Black adult caregivers of cancer patients despite their elevated risk for both oral disease and cognitive impairment.<br><br>OBJECTIVES: This study aimed to characterize the oral microbiome of Black caregivers of people living with cancer and explore the association of the oral microbiome with cognitive performance.<br><br>METHODS: Thirty-one self-identified Black or African American caregivers of cancer patients in the greater metropolitan Atlanta area participated in the study. They provided oral microbiome samples. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA), depressive symptoms with the Center for Epidemiological Studies-Depression Scale, and individual race-related stress with the Index of Race-Related Stress-Brief. Salivary microbiome diversity was analyzed using alpha and beta diversity metrics, and taxa associated with cognition were identified through differential abundance testing, adjusting for potential confounders.<br><br>RESULTS: The mean age of participants was 54.8 years. MoCA scores ranged from 18 to 30, with a mean of 25. Participants were categorized into normal cognition (MoCA &#x2265; 26, n = 12) and low cognition (MoCA < 26, n = 16) groups. Education level and individual race-related stress were associated with cognition group and were controlled for in the oral microbiome analysis. Alpha and beta diversity analyses showed no significant overall differences between cognition groups. Differential abundance testing suggested 48 taxa were associated with cognition status, many of which are known to be associated with periodontal disease and cognition.<br><br>DISCUSSION: This study revealed associations between cognition status and specific oral bacteria, many of which are known to be associated with periodontal disease and cognitive impairment. These findings underscore the complex relationship between oral health and cognitive function, suggesting a need for further research to develop oral microbiome profiles capable of identifying individuals at risk for cognitive decline and guiding targeted interventions for promoting overall well-being and cognitive health.}, }
@article {pmid39377779, year = {2024}, author = {Porreca, A and Ibrahimi, E and Maturo, F and Marcos Zambrano, LJ and Meto, M and Lopes, MB}, title = {Robust prediction of colorectal cancer via gut microbiome 16S rRNA sequencing data.}, journal = {Journal of medical microbiology}, volume = {73}, number = {10}, pages = {}, doi = {10.1099/jmm.0.001903}, pmid = {39377779}, issn = {1473-5644}, mesh = {*RNA, Ribosomal, 16S/genetics ; *Colorectal Neoplasms/microbiology ; Humans ; *Gastrointestinal Microbiome/genetics ; *Machine Learning ; *Feces/microbiology ; Bacteria/genetics/classification/isolation &amp; purification ; }, abstract = {Introduction. The study addresses the challenge of utilizing human gut microbiome data for the early detection of colorectal cancer (CRC). The research emphasizes the potential of using machine learning techniques to analyze complex microbiome datasets, providing a non-invasive approach to identifying CRC-related microbial markers.Hypothesis/Gap Statement. The primary hypothesis is that a robust machine learning-based analysis of 16S rRNA microbiome data can identify specific microbial features that serve as effective biomarkers for CRC detection, overcoming the limitations of classical statistical models in high-dimensional settings.Aim. The primary objective of this study is to explore and validate the potential of the human microbiome, specifically in the colon, as a valuable source of biomarkers for colorectal cancer (CRC) detection and progression. The focus is on developing a classifier that effectively predicts the presence of CRC and normal samples based on the analysis of three previously published faecal 16S rRNA sequencing datasets.Methodology. To achieve the aim, various machine learning techniques are employed, including random forest (RF), recursive feature elimination (RFE) and a robust correlation-based technique known as the fuzzy forest (FF). The study utilizes these methods to analyse the three datasets, comparing their performance in predicting CRC and normal samples. The emphasis is on identifying the most relevant microbial features (taxa) associated with CRC development via partial dependence plots, i.e. a machine learning tool focused on explainability, visualizing how a feature influences the predicted outcome.Results. The analysis of the three faecal 16S rRNA sequencing datasets reveals the consistent and superior predictive performance of the FF compared to the RF and RFE. Notably, FF proves effective in addressing the correlation problem when assessing the importance of microbial taxa in explaining the development of CRC. The results highlight the potential of the human microbiome as a non-invasive means to detect CRC and underscore the significance of employing FF for improved predictive accuracy.Conclusion. In conclusion, this study underscores the limitations of classical statistical techniques in handling high-dimensional information such as human microbiome data. The research demonstrates the potential of the human microbiome, specifically in the colon, as a valuable source of biomarkers for CRC detection. Applying machine learning techniques, particularly the FF, is a promising approach for building a classifier to predict CRC and normal samples. The findings advocate for integrating FF to overcome the challenges associated with correlation when identifying crucial microbial features linked to CRC development.}, }
@article {pmid39375475, year = {2025}, author = {Turocy, T and Crawford, JM}, title = {Bacterial small molecule metabolites implicated in gastrointestinal cancer development.}, journal = {Nature reviews. Microbiology}, volume = {23}, number = {2}, pages = {106-121}, pmid = {39375475}, issn = {1740-1534}, mesh = {Humans ; *Gastrointestinal Neoplasms/microbiology/metabolism ; *Gastrointestinal Microbiome/physiology ; *Bacteria/metabolism ; Animals ; Host Microbial Interactions ; }, abstract = {Numerous associations have been identified between cancer and the composition and function of the human microbiome. As cancer remains the second leading global cause of mortality, investigating the carcinogenic contributions of microbiome members could advance our understanding of cancer risk and support potential therapeutic interventions. Although fluctuations in bacterial species have been associated with cancer progression, studying their small molecule metabolites offers one avenue to establish support for causal relationships and the molecular mechanisms governing host-microorganism interactions. In this Review, we explore the expanding repertoire of small molecule metabolites and their mechanisms implicated in the risk of developing gastrointestinal cancers.}, }
@article {pmid39368472, year = {2024}, author = {El Mouali, Y and Tawk, C and Huang, KD and Amend, L and Lesker, TR and Ponath, F and Vogel, J and Strowig, T}, title = {The RNA landscape of the human commensal Segatella copri reveals a small RNA essential for gut colonization.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {11}, pages = {1910-1926.e6}, doi = {10.1016/j.chom.2024.09.008}, pmid = {39368472}, issn = {1934-6069}, mesh = {Humans ; Animals ; *Gastrointestinal Microbiome/genetics ; Mice ; *Symbiosis ; *RNA, Bacterial/genetics ; *Germ-Free Life ; Gene Expression Regulation, Bacterial ; Fructans/metabolism ; Mice, Inbred C57BL ; Gastrointestinal Tract/microbiology ; Transcriptome ; }, abstract = {The bacterium Segatella copri is a prevalent member of the human gut microbiota associated with health and disease states. However, the intrinsic factors that determine its ability to colonize the gut effectively remain largely unknown. By extensive transcriptome mapping of S. copri and examining human-derived samples, we discover a small RNA, which we name Segatella RNA colonization factor (SrcF), and show that SrcF is essential for S. copri gut colonization in gnotobiotic mice. SrcF regulates genes involved in nutrient acquisition, and complex carbohydrates, particularly fructans, control its expression. Furthermore, SrcF expression is strongly influenced by human microbiome composition and by the breakdown of fructans by cohabitating commensals, suggesting that the breakdown of complex carbohydrates mediates interspecies signaling among commensals beyond its established function in generating energy. Together, this study highlights the contribution of a small RNA as a critical regulator in gut colonization.}, }
@article {pmid39365053, year = {2024}, author = {Silk, ET and Bayer, SB and Foster, M and Roy, NC and Taylor, MW and Vatanen, T and Gearry, RB}, title = {Advancing microbiome research in Māori populations: insights from recent literature exploring the gut microbiomes of underrepresented and Indigenous peoples.}, journal = {mSystems}, volume = {9}, number = {11}, pages = {e0090924}, pmid = {39365053}, issn = {2379-5077}, support = {Doctoral Scholarship//University of Otago (Te Whare W&#x101;nanga o Ot&#x101;go)/ ; HRC 23/314//Manatu Hauora | Health Research Council of New Zealand (HRC)/ ; UOAX1421,UOAX1902//High Value Nutrition (New Zealand)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Indigenous Peoples ; Maori People ; }, abstract = {The gut microbiome plays vital roles in human health, including mediating metabolism, immunity, and the gut-brain axis. Many ethnicities remain underrepresented in gut microbiome research, with significant variation between Indigenous and non-Indigenous peoples due to dietary, socioeconomic, health, and urbanization differences. Although research regarding the microbiomes of Indigenous peoples is increasing, Māori microbiome literature is lacking despite widespread inequities that Māori populations face. These inequities likely contribute to gut microbiome differences that exacerbate negative health outcomes. Characterizing the gut microbiomes of underrepresented populations is necessary to inform efforts to address health inequities. However, for microbiome research to be culturally responsible and meaningful, study design must improve to better protect the rights and interests of Indigenous peoples. Here, we discuss barriers to Indigenous participation in research and the role disparities may play in shaping the gut microbiomes of Indigenous peoples, with a particular focus on implications for Māori and areas for improvement.}, }
@article {pmid39362115, year = {2024}, author = {Tian, H and Tang, R}, title = {Prediction of Crohn's disease based on deep feature recognition.}, journal = {Computational biology and chemistry}, volume = {113}, number = {}, pages = {108231}, doi = {10.1016/j.compbiolchem.2024.108231}, pmid = {39362115}, issn = {1476-928X}, mesh = {*Crohn Disease/genetics ; Humans ; *Deep Learning ; Support Vector Machine ; }, abstract = {BACKGROUND: Crohn's disease is a complex genetic disease that involves chronic gastrointestinal inflammation and results from a complex set of genetic, environmental, and immunological factors. By analyzing data from the human microbiome, genetic information can be used to predict Crohn's disease. Recent advances in deep learning have demonstrated its effectiveness in feature extraction and the use of deep learning to decode genetic information for disease prediction.<br><br>METHODS: In this paper, we present a deep learning-based model that utilizes a sequential convolutional attention network (SCAN) for feature extraction, incorporates adaptive additive interval losses to enhance these features, and employs support vector machines (SVM) for classification. To address the challenge of unbalanced Crohn's disease samples, we propose a random noise one-hot encoding data augmentation method.<br><br>RESULTS: Data augmentation with random noise accelerates training convergence, while SCAN-SVM effectively extracts features with adaptive additive interval loss enhancing differentiation. Our approach outperforms benchmark methods, achieving an average accuracy of 0.80 and a kappa value of 0.76, and we validate the effectiveness of feature enhancement.<br><br>CONCLUSIONS: In summary, we use deep feature recognition to effectively analyze the potential information in genes, which has a good application potential for gene analysis and prediction of Crohn's disease.}, }
@article {pmid39359681, year = {2024}, author = {Tian, S and Ding, T and Li, H}, title = {Oral microbiome in human health and diseases.}, journal = {mLife}, volume = {3}, number = {3}, pages = {367-383}, pmid = {39359681}, issn = {2770-100X}, abstract = {The oral cavity contains the second-largest microbiota in the human body. The cavity's anatomically and physiologically diverse niches facilitate a wide range of symbiotic bacteria living at distinct oral sites. Consequently, the oral microbiota exhibits site specificity, with diverse species, compositions, and structures influenced by specific aspects of their placement. Variations in oral microbiota structure caused by changes in these influencing factors can impact overall health and lead to the development of diseases-not only in the oral cavity but also in organs distal to the mouth-such as cancer, cardiovascular disease, and respiratory disease. Conversely, diseases can exacerbate the imbalance of the oral microbiota, creating a vicious cycle. Understanding the heterogeneity of both the oral microbiome and individual humans is important for investigating the causal links between the oral microbiome and diseases. Additionally, understanding the intricacies of the oral microbiome's composition and regulatory factors will help identify the potential causes of related diseases and develop interventions to prevent and treat illnesses in this domain. Therefore, turning to the extant research in this field, we systematically review the relationship between oral microbiome dynamics and human diseases.}, }
@article {pmid39358771, year = {2024}, author = {Kawano-Sugaya, T and Arikawa, K and Saeki, T and Endoh, T and Kamata, K and Matsuhashi, A and Hosokawa, M}, title = {A single amplified genome catalog reveals the dynamics of mobilome and resistome in the human microbiome.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {188}, pmid = {39358771}, issn = {2049-2618}, mesh = {Humans ; *Bacteria/genetics/classification ; *Gastrointestinal Microbiome/genetics ; *Metagenome ; *Mouth/microbiology ; *Genome, Bacterial ; Interspersed Repetitive Sequences/genetics ; Microbiota/genetics ; Drug Resistance, Bacterial/genetics ; Metagenomics/methods ; Phylogeny ; }, abstract = {BACKGROUND: The increase in metagenome-assembled genomes (MAGs) has advanced our understanding of the functional characterization and taxonomic assignment within the human microbiome. However, MAGs, as population consensus genomes, often aggregate heterogeneity among species and strains, thereby obfuscating the precise relationships between microbial hosts and mobile genetic elements (MGEs). In contrast, single amplified genomes (SAGs) derived via single-cell genome sequencing can capture individual genomic content, including MGEs.<br><br>RESULTS: We introduce the first substantial SAG dataset (bbsag20) from the human oral and gut microbiome, comprising 17,202 SAGs above medium-quality without co-assembly. This collection unveils a diversity of bacterial lineages across 312 oral and 647 gut species, demonstrating different taxonomic compositions from MAGs. Moreover, the SAGs showed cellular-level evidence of the translocation of oral bacteria to the gut. We also identified broad-host-range MGEs harboring antibiotic resistance genes (ARGs), which were not detected in the MAGs.<br><br>CONCLUSIONS: The difference in taxonomic composition between SAGs and MAGs indicates that combining both methods would be effective in expanding the genome catalog. By connecting mobilomes and resistomes in individual samples, SAGs could meticulously chart a dynamic network of ARGs on MGEs, pinpointing potential ARG reservoirs and their spreading patterns in the microbial community. Video Abstract.}, }
@article {pmid39358005, year = {2025}, author = {Manning, S and Sinha, R and Rees, CJ}, title = {Need for standardised approaches to human microbiome research using the example of colorectal neoplasia research.}, journal = {Gut}, volume = {74}, number = {6}, pages = {875-877}, doi = {10.1136/gutjnl-2024-333765}, pmid = {39358005}, issn = {1468-3288}, }
@article {pmid39352141, year = {2024}, author = {Coclet, C and Camargo, AP and Roux, S}, title = {MVP: a modular viromics pipeline to identify, filter, cluster, annotate, and bin viruses from metagenomes.}, journal = {mSystems}, volume = {9}, number = {10}, pages = {e0088824}, pmid = {39352141}, issn = {2379-5077}, mesh = {*Metagenome/genetics ; *Genome, Viral/genetics ; *Metagenomics/methods ; *Viruses/genetics/classification/isolation &amp; purification ; Software ; Virome/genetics ; Computational Biology/methods ; Molecular Sequence Annotation ; }, abstract = {While numerous computational frameworks and workflows are available for recovering prokaryote and eukaryote genomes from metagenome data, only a limited number of pipelines are designed specifically for viromics analysis. With many viromics tools developed in the last few years alone, it can be challenging for scientists with limited bioinformatics experience to easily recover, evaluate quality, annotate genes, dereplicate, assign taxonomy, and calculate relative abundance and coverage of viral genomes using state-of-the-art methods and standards. Here, we describe Modular Viromics Pipeline (MVP) v.1.0, a user-friendly pipeline written in Python and providing a simple framework to perform standard viromics analyses. MVP combines multiple tools to enable viral genome identification, characterization of genome quality, filtering, clustering, taxonomic and functional annotation, genome binning, and comprehensive summaries of results that can be used for downstream ecological analyses. Overall, MVP provides a standardized and reproducible pipeline for both extensive and robust characterization of viruses from large-scale sequencing data including metagenomes, metatranscriptomes, viromes, and isolate genomes. As a typical use case, we show how the entire MVP pipeline can be applied to a set of 20 metagenomes from wetland sediments using only 10 modules executed via command lines, leading to the identification of 11,656 viral contigs and 8,145 viral operational taxonomic units (vOTUs) displaying a clear beta-diversity pattern. Further, acting as a dynamic wrapper, MVP is designed to continuously incorporate updates and integrate new tools, ensuring its ongoing relevance in the rapidly evolving field of viromics. MVP is available at https://gitlab.com/ccoclet/mvp and as versioned packages in PyPi and Conda.IMPORTANCEThe significance of our work lies in the development of Modular Viromics Pipeline (MVP), an integrated and user-friendly pipeline tailored exclusively for viromics analyses. MVP stands out due to its modular design, which ensures easy installation, execution, and integration of new tools and databases. By combining state-of-the-art tools such as geNomad and CheckV, MVP provides high-quality viral genome recovery and taxonomy and host assignment, and functional annotation, addressing the limitations of existing pipelines. MVP's ability to handle diverse sample types, including environmental, human microbiome, and plant-associated samples, makes it a versatile tool for the broader microbiome research community. By standardizing the analysis process and providing easily interpretable results, MVP enables researchers to perform comprehensive studies of viral communities, significantly advancing our understanding of viral ecology and its impact on various ecosystems.}, }
@article {pmid39351241, year = {2024}, author = {Lu, S and Wang, C and Ma, J and Wang, Y}, title = {Metabolic mediators: microbial-derived metabolites as key regulators of anti-tumor immunity, immunotherapy, and chemotherapy.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1456030}, pmid = {39351241}, issn = {1664-3224}, mesh = {Humans ; *Neoplasms/immunology/therapy/metabolism/drug therapy ; *Immunotherapy/methods ; *Gastrointestinal Microbiome/immunology ; *Tumor Microenvironment/immunology ; Animals ; *Fatty Acids, Volatile/metabolism ; *Tryptophan/metabolism ; Methylamines/metabolism/immunology ; Antineoplastic Agents/therapeutic use ; }, abstract = {The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs' remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.}, }
@article {pmid39349378, year = {2024}, author = {Palmer, D and Henze, L and Murua Escobar, H and Walter, U and Kowald, A and Fuellen, G}, title = {Multicohort study testing the generalisability of the SASKit-ML stroke and PDAC prognostic model pipeline to other chronic diseases.}, journal = {BMJ open}, volume = {14}, number = {9}, pages = {e088181}, pmid = {39349378}, issn = {2044-6055}, mesh = {Humans ; *Diabetes Mellitus, Type 2/complications ; Prognosis ; Female ; Male ; *Pancreatic Neoplasms ; *Stroke ; Middle Aged ; Arthritis, Rheumatoid ; Machine Learning ; Inflammatory Bowel Diseases ; Aged ; Longitudinal Studies ; Chronic Disease ; Prospective Studies ; Biomarkers/blood ; Cohort Studies ; }, abstract = {OBJECTIVES: To validate and test the generalisability of the SASKit-ML pipeline, a prepublished feature selection and machine learning pipeline for the prediction of health deterioration after a stroke or pancreatic adenocarcinoma event, by using it to identify biomarkers of health deterioration in chronic disease.<br><br>DESIGN: This is a validation study using a predefined protocol applied to multiple publicly available datasets, including longitudinal data from cohorts with type 2 diabetes (T2D), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and various cancers. The datasets were chosen to mimic as closely as possible the SASKit cohort, a prospective, longitudinal cohort study.<br><br>DATA SOURCES: Public data were used from the T2D (77 patients with potential pre-diabetes and 18 controls) and IBD (49 patients with IBD and 12 controls) branches of the Human Microbiome Project (HMP), RA Map (RA-MAP, 92 patients with RA, 22 controls) and The Cancer Genome Atlas (TCGA, 16 cancers).<br><br>METHODS: Data integration steps were performed in accordance with the prepublished study protocol, generating features to predict disease outcomes using 10-fold cross-validated random survival forests.<br><br>OUTCOME MEASURES: Health deterioration was assessed using disease-specific clinical markers and endpoints across different cohorts. In the HMP-T2D cohort, the worsening of glycated haemoglobin (HbA1c) levels (5.7% or more HbA1c in the blood), fasting plasma glucose (at least 100&#x2009;mg/dL) and oral glucose tolerance test (at least 140) results were considered. For the HMP-IBD cohort, a worsening by at least 3 points of a disease-specific severity measure, the "Simple Clinical Colitis Activity Index" or "Harvey-Bradshaw Index" indicated an event. For the RA-MAP cohort, the outcome was defined as the worsening of the "Disease Activity Score 28" or "Simple Disease Activity Index" by at least five points, or the worsening of the "Health Assessment Questionnaire" score or an increase in the number of swollen/tender joints were evaluated. Finally, the outcome for all TCGA datasets was the progression-free interval.<br><br>RESULTS: Models for the prediction of health deterioration in T2D, IBD, RA and 16 cancers were produced. The T2D (C-index of 0.633 and Integrated Brier Score (IBS) of 0.107) and the RA (C-index of 0.654 and IBS of 0.150) models were modestly predictive. The IBD model was uninformative. TCGA models tended towards modest predictive power.<br><br>CONCLUSIONS: The SASKit-ML pipeline produces informative and useful features with the power to predict health deterioration in a variety of diseases and cancers; however, this performance is disease-dependent.}, }
@article {pmid39345212, year = {2024}, author = {Basting, CM and Langat, R and Broedlow, CA and Guerrero, CR and Bold, TD and Bailey, M and Velez, A and Schroeder, T and Short-Miller, J and Cromarty, R and Mayer, ZJ and Southern, PJ and Schacker, TW and Safo, SE and Bramante, CT and Tignanelli, CJ and Schifanella, L and Klatt, NR}, title = {SARS-CoV-2 infection is associated with intestinal permeability, systemic inflammation, and microbial dysbiosis in hospitalized patients.}, journal = {Microbiology spectrum}, volume = {12}, number = {11}, pages = {e0068024}, pmid = {39345212}, issn = {2165-0497}, mesh = {Humans ; *COVID-19/microbiology ; *Dysbiosis/microbiology ; Male ; Female ; Middle Aged ; *SARS-CoV-2/isolation &amp; purification ; *Inflammation ; *Gastrointestinal Microbiome ; Aged ; Adult ; RNA, Ribosomal, 16S/genetics ; Permeability ; Cytokines/blood ; Hospitalization ; Bacteria/classification/isolation &amp; purification/genetics ; Intestinal Barrier Function ; }, abstract = {Coronavirus disease 2019 (COVID-19) and its associated severity have been linked to uncontrolled inflammation and may be associated with changes in the microbiome of mucosal sites including the gastrointestinal tract and oral cavity. These sites play an important role in host-microbe homeostasis, and disruption of epithelial barrier integrity during COVID-19 may potentially lead to exacerbated inflammation and immune dysfunction. Outcomes in COVID-19 are highly disparate, ranging from asymptomatic to fatal, and the impact of microbial dysbiosis on disease severity is unclear. Here, we obtained plasma, rectal swabs, oropharyngeal swabs, and nasal swabs from 86 patients hospitalized with COVID-19 and 12 healthy volunteers. We performed 16S rRNA sequencing to characterize the microbial communities in the mucosal swabs and measured concentrations of circulating cytokines, markers of gut barrier integrity, and fatty acids in the plasma samples. We compared these plasma concentrations and microbiomes between healthy volunteers and COVID-19 patients, some of whom had unfortunately died by the end of the study enrollment, and performed a correlation analysis between plasma variables and bacterial abundances. Rectal swabs of COVID-19 patients had reduced abundances of several commensal bacteria including Faecalibacterium prausnitzii and an increased abundance of the opportunistic pathogens Eggerthella lenta and Hungatella hathewayi. Furthermore, the oral pathogen Scardovia wiggsiae was more abundant in the oropharyngeal swabs of COVID-19 patients who died. The abundance of both H. hathewayi and S. wiggsiae correlated with circulating inflammatory markers including IL-6, highlighting the possible role of the microbiome in COVID-19 severity and providing potential therapeutic targets for managing COVID-19.IMPORTANCEOutcomes in coronavirus disease 2019 (COVID-19) are highly disparate and are associated with uncontrolled inflammation; however, the individual factors that lead to this uncontrolled inflammation are not fully understood. Here, we report that severe COVID-19 is associated with systemic inflammation, microbial translocation, and microbial dysbiosis. The rectal and oropharyngeal microbiomes of COVID-19 patients were characterized by a decreased abundance of commensal bacteria and an increased abundance of opportunistic pathogens, which positively correlated with markers of inflammation and microbial translocation. These microbial perturbations may, therefore, contribute to disease severity in COVID-19 and highlight the potential for microbiome-based interventions in improving COVID-19 outcomes.}, }
@article {pmid39342083, year = {2024}, author = {Wang, X and Yao, S and Yang, X and Li, Y and Yu, Z and Huang, J and Wang, J}, title = {Peritoneal dialysis promotes microbial-driven biosynthesis pathways of sesquiterpenes and triterpenes compounds in end-stage renal disease patients.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {377}, pmid = {39342083}, issn = {1471-2180}, support = {32170071//National Natural Science Foundation of China/ ; 32300051//National Natural Science Foundation of China/ ; 2022JJ40663//Natural Science Foundation of Hunan Province/ ; C2023045//Hunan Province Traditional Chinese Medicine Research Program Project/ ; }, mesh = {Humans ; *Kidney Failure, Chronic/therapy/metabolism/microbiology ; *Gastrointestinal Microbiome ; *Peritoneal Dialysis ; *Sesquiterpenes/metabolism ; Male ; Female ; *Feces/microbiology ; Middle Aged ; *Triterpenes/metabolism ; Bacteria/metabolism/classification/genetics/isolation &amp; purification ; Biosynthetic Pathways ; Adult ; Metagenomics ; Aged ; }, abstract = {The concept of the gut-kidney axis is gaining significant attention due to the close relationship between gut microbiota and kidney disease. Peritoneal dialysis is recognized as a crucial renal replacement therapy for end-stage renal disease (ESRD). The alterations in gut microbiota and related mechanisms after receiving this dialysis method are not fully understood. This study conducted shotgun metagenomic sequencing on fecal samples from 11 end-stage renal disease patients who did not receive dialysis (ESRD_N) and 7 patients who received peritoneal dialysis (ESRD_P). After quality control and correlation analysis of the data, our study is aimed at exploring the impact of peritoneal dialysis on the gut microbiota and health of ESRD patients. Our research findings indicate that the complexity and aggregation characteristics of gut microbiota interactions increase in ESRD_P. In addition, the gut microbiota drives the biosynthesis pathways of sesquiterpenes and triterpenes in ESRD_P patients, which may contribute to blood purification and improve circulation. Therefore, our research will lay the foundation for the prevention and treatment of ESRD.}, }
@article {pmid39341037, year = {2024}, author = {Vogs, C and Lindqvist, D and Wai Tang, S and Gugescu, L and Alenius, H and Wincent, E}, title = {Transcriptomic and functional effects from a chemical mixture based on the exposure profile in Baltic Sea salmon, on metabolic and immune functions in zebrafish embryo.}, journal = {Environment international}, volume = {192}, number = {}, pages = {109018}, doi = {10.1016/j.envint.2024.109018}, pmid = {39341037}, issn = {1873-6750}, mesh = {Animals ; *Zebrafish ; *Water Pollutants, Chemical/toxicity ; *Transcriptome/drug effects ; *Salmon ; Embryo, Nonmammalian/drug effects ; Hydrocarbons, Halogenated/toxicity ; Gene Expression Profiling ; }, abstract = {The Baltic Sea is one of the world's most contaminated seas with long-standing adverse health status of its wildlife such as the Baltic Sea salmon, resulting in reduced fecundity and increased mortality. While adverse health effects have been reported among wild fish from the Baltic Sea, the toxicity mechanisms underlying these adversities, and the chemical effect drivers mediating them are poorly understood. To address this knowledge gap, we utilized the zebrafish (Danio rerio) embryo model to determine molecular and functional effects brought on by exposure to a technical mixture including 9 organohalogen compounds detected in serum from wild-caught Baltic Sea salmon. To align with the salmon exposure scenario, an internal dose regimen was opted to establish same relative proportions of the compounds in the zebrafish (whole body) as observed in the salmon serum. Through transcriptomic profiling, we identified dose-dependent effects on immune system and metabolism as two critical functions overlapping with adverse effects observed in wild fish from the Baltic Sea. We then determined likely effect drivers by comparing gene responses of the mixture with those of individual mixture components. Aligned with our transcriptome results, the number of total macrophages was reduced and the zebrafish's ability to respond to a tissue damage suppressed in a dose-dependent manner. This study brings forth a key advancement in delineating the impact of chemical pollutants on the health of wild fish in the Baltic Sea.}, }
@article {pmid39340867, year = {2024}, author = {Moghaddam, HS and Abkar, L and Fowler, SJ}, title = {Making waves: From tap to gut- exploring the impact of drinking water on gut microbiota.}, journal = {Water research}, volume = {267}, number = {}, pages = {122503}, doi = {10.1016/j.watres.2024.122503}, pmid = {39340867}, issn = {1879-2448}, mesh = {*Drinking Water/microbiology ; *Gastrointestinal Microbiome ; Humans ; Diet ; }, abstract = {Drinking water (DW) harbours diverse microbial species and chemical attributes. Water comprises the greatest portion of our daily diet, ingested both on its own and used in the preparation of food. DW is our major source of liquids, which is vital to maintaining homeostasis, and can also supply essential minerals. Limited evidence suggests that DW plays a role in shaping the gut microbiome, which implies that it may impact human health. Despite its significant contribution to diet, DW is often overlooked in studies examining dietary influences on the gut microbiota. This perspective explores our current understanding of the link between DW and the gut microbiota - an area of human microbiome science that has been surprisingly understudied. Existing studies reveal links between DW source, microbiota composition, and gut health, emphasizing the need for comprehensive investigations. Understanding the interplay between DW and gut microbiota holds potential for tailored interventions to enhance human health.}, }
@article {pmid39339787, year = {2024}, author = {Fraiz, GM and Bonifácio, DB and Lacerda, UV and Cardoso, RR and Corich, V and Giacomini, A and Martino, HSD and Echeverría, SE and Barros, FAR and Milagro, FI and Bressan, J}, title = {Green Tea Kombucha Impacts Inflammation and Salivary Microbiota in Individuals with Excess Body Weight: A Randomized Controlled Trial.}, journal = {Nutrients}, volume = {16}, number = {18}, pages = {}, pmid = {39339787}, issn = {2072-6643}, support = {CAPE 507/2019 - APQ-00035-20//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais/ ; CB12/03/30002//Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition/ ; 001//Coordena&#xe7;&#xe3;o de Aperfeicoamento de Pessoal de N&#xed;vel Superior/ ; }, mesh = {Humans ; *Saliva/microbiology ; Male ; Female ; *Inflammation ; Adult ; *Microbiota ; Kombucha Tea ; Middle Aged ; Weight Loss ; Tea ; Overweight/microbiology ; Body Mass Index ; Caloric Restriction ; Body Composition ; }, abstract = {BACKGROUND: Green tea kombucha (GTK) is a fermented beverage with promising health benefits, but few studies proved its impact on human health. Thus, we aimed to investigate the impact of GTK on weight loss, inflammation, and salivary microbiota in individuals with excess body weight.<br><br>METHODS: This is a randomized controlled clinical trial that lasted 10 weeks with two groups of individuals with excess body weight: control (CG; n = 29; caloric restriction) and kombucha (KG; n = 30; caloric restriction + 200 mL GTK). Body composition, anthropometry, saliva, and blood collection were performed in the beginning and end of the intervention. Plasma interleukins were determined by flow cytometry. Salivary microbiota was analyzed by 16S rRNA sequencing.<br><br>RESULTS: Both groups decreased weight, BMI, and body fat (p < 0.001) after the intervention, but there were no differences between groups. The KG reduced lipid accumulation product (LAP) (p = 0.029). Both groups decreased IL-1&#x3b2; and IL-8, but IL-6 increased in the CG (p = 0.023) compared to the kombucha group. Alpha and beta diversity of salivary microbiota increased in the KG. Moreover, the KG presented lower Bacillota/Bacteroidota ratio (p = 0.028), and BMI was positively associated with the Bacillota phylum.<br><br>CONCLUSIONS: GTK did not enhance weight loss, but it decreased the LAP. GTK helped in the inflammatory profile and induced positive changes in oral microbiota composition.}, }
@article {pmid39337688, year = {2024}, author = {Fleshner, L and Roster, K and Farabi, B and Hirani, R and Tepper, K and Pitchumoni, CS and Safai, B and Marmon, S}, title = {Follicular Skin Disorders, Inflammatory Bowel Disease, and the Microbiome: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {25}, number = {18}, pages = {}, pmid = {39337688}, issn = {1422-0067}, mesh = {Humans ; *Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; Hidradenitis Suppurativa/microbiology ; *Inflammatory Bowel Diseases/microbiology ; Microbiota ; Skin/microbiology ; Skin Diseases/microbiology ; }, abstract = {Follicular skin disorders, including hidradenitis suppurativa (HS), frequently coexist with systemic autoinflammatory diseases, such as inflammatory bowel disease (IBD) and its subtypes, Crohn's disease and ulcerative colitis. Previous studies suggest that dysbiosis of the human gut microbiome may serve as a pathogenic link between HS and IBD. However, the role of the microbiome (gut, skin, and blood) in the context of IBD and various follicular disorders remains underexplored. Here, we performed a systematic review to investigate the relationship between follicular skin disorders, IBD, and the microbiome. Of the sixteen included studies, four evaluated the impact of diet on the microbiome in HS patients, highlighting a possible link between gut dysbiosis and yeast-exclusion diets. Ten studies explored bacterial colonization and HS severity with specific gut and skin microbiota, including Enterococcus and Veillonella. Two studies reported on immunological or serological biomarkers in HS patients with autoinflammatory disease, including IBD, and identified common markers including elevated cytokines and T-lymphocytes. Six studies investigated HS and IBD patients concurrently. Our systematic literature review highlights the complex interplay between the human microbiome, IBD, and follicular disorders with a particular focus on HS. The results indicate that dietary modifications hold promise as a therapeutic intervention to mitigate the burden of HS and IBD. Microbiota analyses and the identification of key serological biomarkers are crucial for a deeper understanding of the impact of dysbiosis in these conditions. Future research is needed to more thoroughly delineate the causal versus associative roles of dysbiosis in patients with both follicular disorders and IBD.}, }
@article {pmid39337215, year = {2024}, author = {Falara, E and Metallinou, D and Nanou, C and Vlachou, M and Diamanti, A}, title = {Perinatal Exposure to Tobacco Smoke and Its Association with the Maternal and Offspring Microbiome: A Systematic Review.}, journal = {Healthcare (Basel, Switzerland)}, volume = {12}, number = {18}, pages = {}, pmid = {39337215}, issn = {2227-9032}, support = {The APC was partially funded by the "Special Account for Research Grants" of the University of West Attica, Athens, Greece.//The APC was partially funded by the "Special Account for Research Grants" of the University of West Attica, Athens, Greece./ ; }, abstract = {BACKGROUND: The human microbiome, comprising trillions of microorganisms, significantly influences human health and disease. During critical periods like the perinatal phase, the microbiome undergoes significant changes, impacting lifelong health. Tobacco smoke, a known environmental pollutant, has adverse effects on health, particularly during pregnancy. Despite this, its association with the perinatal microbiome remains understudied.<br><br>METHODS: We conducted a systematic review to integrate findings on perinatal tobacco smoke exposure and its association with the maternal and neonatal microbiomes. We conducted a comprehensive literature search in the PubMed, Scopus, and Web of Science databases from January 2000 to February 2024. We selected studies that met predefined inclusion criteria and performed data extraction.<br><br>RESULTS: The review included eight studies that revealed diverse associations of perinatal tobacco exposure with the maternal and neonatal microbiome. Active smoking during pregnancy was linked to alterations in microbiome composition and diversity in children. Maternal smoking correlated with increased Firmicutes abundance and decreased Akkermansia muciniphila abundance in offspring. Additionally, exposure to thirdhand smoke in neonatal intensive care units was related to infant microbiome diversity. Infants exposed to tobacco smoke showed various microbial changes, suggesting potential implications for childhood health outcomes, including obesity risk.<br><br>CONCLUSIONS: Perinatal exposure to tobacco smoke exerts significant influence on the maternal and neonatal microbiomes, with potential implications for long-term health outcomes. Addressing socioeconomic and psychological barriers to smoking cessation, implementing stricter smoking regulations, and promoting public health campaigns are essential steps towards reducing tobacco-related harm during the perinatal period. Further longitudinal studies and standardized assessment methods are needed to validate these findings and guide the development of effective preventive measures.}, }
@article {pmid39335616, year = {2024}, author = {Xiang, B and Zhang, Q and Wu, H and Lin, J and Xu, Z and Zhang, M and Zhu, L and Hu, J and Zhi, M}, title = {Impact of Mild COVID-19 History on Oral-Gut Microbiota and Serum Metabolomics in Adult Patients with Crohn's Disease: Potential Beneficial Effects.}, journal = {Biomedicines}, volume = {12}, number = {9}, pages = {}, pmid = {39335616}, issn = {2227-9059}, support = {2014008 (MZ)//the Sun Yat-sen University Clinical Research 5010 Program/ ; 82270544 (MZ)//the National Natural Science Foundation of China/ ; SL2022B03J00237 (MZ)//the Bureau of Science and Technology of Guangzhou Municipality/ ; 2022JBGS06 (MZ)//"Jie Bang Gua Shuai" project of The Sixth Affiliated Hospital of Sun Yat-sen University/ ; 2019ZT08Y464 (LZ)//Guangdong Province "Pearl River Talent Plan" Innovation and Entrepreneurship Team Project/ ; 2020B1111170004 (MZ)//the program of Guangdong Provincial Clinical Research Center for Digestive Diseases/ ; }, abstract = {The impact of coronavirus disease 2019 (COVID-19) history on Crohn's disease (CD) is unknown. This investigation aimed to examine the effect of COVID-19 history on the disease course, oral-gut microbiota, and serum metabolomics in patients with CD. In this study, oral-gut microbiota and serum metabolomic profiles in 30 patients with CD and a history of mild COVID-19 (positive group, PG), 30 patients with CD without COVID-19 history (negative group, NG), and 60 healthy controls (HC) were assessed using 16S rDNA sequencing and targeted metabolomics. During follow-up, the CD activity index showed a stronger decrease in the PG than in the NG (p = 0.0496). PG patients demonstrated higher α-diversity and distinct β-diversity clustering in both salivary and fecal microbiota compared to NG and HC individuals. Notably, the gut microbiota composition in the PG patients showed a significantly greater similarity to that of HC than NG individuals. The interaction between oral and intestinal microbiota in the PG was reduced. Moreover, serum metabolome analysis revealed significantly increased anti-inflammatory metabolites, including short-chain fatty acids and N-Acetylserotonin, among PG patients; meanwhile, inflammation-related metabolites such as arachidonic acid were significantly reduced in this group. Our data suggest that the gut microbiota mediates a potential beneficial effect of a mild COVID-19 history in CD patients.}, }
@article {pmid39334849, year = {2024}, author = {Mukherjee, S and Verma, A and Kong, L and Rengan, AK and Cahill, DM}, title = {Advancements in Green Nanoparticle Technology: Focusing on the Treatment of Clinical Phytopathogens.}, journal = {Biomolecules}, volume = {14}, number = {9}, pages = {}, pmid = {39334849}, issn = {2218-273X}, mesh = {*Nanoparticles/chemistry/therapeutic use ; Humans ; *Anti-Bacterial Agents/pharmacology/chemistry/therapeutic use ; Green Chemistry Technology/methods ; Plant Diseases/microbiology/prevention &amp; control ; }, abstract = {Opportunistic pathogenic microbial infections pose a significant danger to human health, which forces people to use riskier, more expensive, and less effective drugs compared to traditional treatments. These may be attributed to several factors, such as overusing antibiotics in medicine and lack of sanitization in hospital settings. In this context, researchers are looking for new options to combat this worrying condition and find a solution. Nanoparticles are currently being utilized in the pharmaceutical sector; however, there is a persistent worry regarding their potential danger to human health due to the usage of toxic chemicals, which makes the utilization of nanoparticles highly hazardous to eukaryotic cells. Multiple nanoparticle-based techniques are now being developed, offering essential understanding regarding the synthesis of components that play a crucial role in producing anti-microbial nanotherapeutic pharmaceuticals. In this regard, green nanoparticles are considered less hazardous than other forms, providing potential options for avoiding the extensive harm to the human microbiome that is prevalent with existing procedures. This review article aims to comprehensively assess the current state of knowledge on green nanoparticles related to antibiotic activity as well as their potential to assist antibiotics in treating opportunistic clinical phytopathogenic illnesses.}, }
@article {pmid39333709, year = {2024}, author = {Crunkhorn, S}, title = {Identifying antimicrobials in the human microbiome.}, journal = {Nature reviews. Drug discovery}, volume = {23}, number = {11}, pages = {816}, pmid = {39333709}, issn = {1474-1784}, }
@article {pmid39333588, year = {2024}, author = {Garcia-Vello, P and Tytgat, HLP and Elzinga, J and Van Hul, M and Plovier, H and Tiemblo-Martin, M and Cani, PD and Nicolardi, S and Fragai, M and De Castro, C and Di Lorenzo, F and Silipo, A and Molinaro, A and de Vos, WM}, title = {The lipooligosaccharide of the gut symbiont Akkermansia muciniphila exhibits a remarkable structure and TLR signaling capacity.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8411}, pmid = {39333588}, issn = {2041-1723}, support = {AdG 250172//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {*Lipopolysaccharides ; *Akkermansia ; Animals ; *Signal Transduction ; *Toll-Like Receptor 4/metabolism ; Humans ; *Toll-Like Receptor 2/metabolism ; Mice ; Symbiosis ; Mice, Inbred C57BL ; Lipid A/metabolism/chemistry ; Interleukin-10/metabolism ; Gastrointestinal Microbiome ; Liver/metabolism/microbiology ; Female ; }, abstract = {The cell-envelope of Gram-negative bacteria contains endotoxic lipopolysaccharides (LPS) that are recognized by the innate immune system via Toll-Like Receptors (TLRs). The intestinal mucosal symbiont Akkermansia muciniphila is known to confer beneficial effects on the host and has a Gram-negative architecture. Here we show that A. muciniphila LPS lacks the O-polysaccharide repeating unit, with the resulting lipooligosaccharide (LOS) having unprecedented structural and signaling properties. The LOS consists of a complex glycan chain bearing two distinct undeca- and hexadecasaccharide units each containing three 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo) residues. The lipid A moiety appears as a mixture of differently phosphorylated and acylated species and carries either linear or branched acyl moieties. Peritoneal injection of the LOS in mice increased higher gene expression of liver TLR2 than TLR4 (100-fold) and induced high IL-10 gene expression. A. muciniphila LOS was found to signal both through TLR4 and TLR2, whereas lipid A only induced TLR2 in a human cell line. We propose that the unique structure of the A. muciniphila LOS allows interaction with TLR2, thus generating an anti-inflammatory response as to compensate for the canonical inflammatory signaling associated with LOS and TLR4, rationalizing its beneficial host interaction.}, }
@article {pmid39333143, year = {2024}, author = {Wang, B and Wang, T and Du, X and Li, J and Wang, J and Wu, P}, title = {Microbe-drug association prediction model based on graph convolution and attention networks.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {22327}, pmid = {39333143}, issn = {2045-2322}, support = {145209125//Basic scientific research operations of universities affiliated with Heilongjiang Province/ ; }, mesh = {Humans ; *Deep Learning ; Microbiota ; Computational Biology/methods ; Neural Networks, Computer ; Drug Discovery/methods ; Pharmaceutical Preparations ; }, abstract = {The human microbiome plays a key role in drug development and precision medicine, but understanding its complex interactions with drugs remains a challenge. Identifying microbe-drug associations not only enhances our understanding of their mechanisms but also aids in drug discovery and repurposing. Traditional experiments are expensive and time-consuming, making computational methods for predicting microbe-drug associations a new trend. Currently, computational methods specifically designed for this task are still scarce. Therefore, to address the shortcomings of traditional experimental methods in predicting potential microbe-drug associations, this paper proposes a new prediction model named GCNATMDA. The model combines two deep learning models, Graph Convolutional Network and Graph Attention Network, and aims to reveal potential relationships between microbes and drugs by learning related features. Thus improve the efficiency and accuracy of prediction. We first integrated the microbe-drug association matrix from the existing dataset, and then combined the calculated microbe-drug characteristic matrix as the model input. The GCN module is used to dig deeper into the potential characterization of microbes and drugs, while the GAT module further learns the more complex interactions between them and generates the corresponding score matrix. The experimental results show that the GCNATMDA model achieves 96.59% and 93.01% in AUC and AUPR evaluation indexes, respectively, which is significantly better than the existing prediction models. In addition, the reliability of the prediction results is verified by a series of experiments.}, }
@article {pmid39333099, year = {2024}, author = {Hickman, B and Salonen, A and Ponsero, AJ and Jokela, R and Kolho, KL and de Vos, WM and Korpela, K}, title = {Gut microbiota wellbeing index predicts overall health in a cohort of 1000 infants.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8323}, pmid = {39333099}, issn = {2041-1723}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Infant ; *Feces/microbiology ; Female ; Male ; Infant, Newborn ; Cohort Studies ; Longitudinal Studies ; Child, Preschool ; Bifidobacterium/isolation &amp; purification ; Bacteroides/isolation &amp; purification ; }, abstract = {The human gut microbiota is central in regulating all facets of host physiology, and in early life it is thought to influence the host's immune system and metabolism, affecting long-term health. However, longitudinally monitored cohorts with parallel analysis of faecal samples and health data are scarce. In our observational study we describe the gut microbiota development in the first 2 years of life and create a gut microbiota wellbeing index based on the microbiota development and health data in a cohort of nearly 1000 infants using clustering and trajectory modelling. We show that infants' gut microbiota development is highly predictable, following one of five trajectories, dependent on infant exposures, and predictive of later health outcomes. We characterise the natural healthy gut microbiota trajectory and several different dysbiotic trajectories associated with different health outcomes. Bifidobacterium and Bacteroides appear as early keystone organisms, directing microbiota development and consistently predicting positive health outcomes. A microbiota wellbeing index, based on the healthy development trajectory, is predictive of general health over the first 5 years. The results indicate that gut microbiota succession is part of infant physiological development, predictable, and malleable. This information can be utilised to improve the predictions of individual health risks.}, }
@article {pmid39331660, year = {2024}, author = {Pasqualini, J and Facchin, S and Rinaldo, A and Maritan, A and Savarino, E and Suweis, S}, title = {Emergent ecological patterns and modelling of gut microbiomes in health and in disease.}, journal = {PLoS computational biology}, volume = {20}, number = {9}, pages = {e1012482}, pmid = {39331660}, issn = {1553-7358}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/genetics ; Models, Biological ; Computational Biology ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Recent advancements in next-generation sequencing have revolutionized our understanding of the human microbiome. Despite this progress, challenges persist in comprehending the microbiome's influence on disease, hindered by technical complexities in species classification, abundance estimation, and data compositionality. At the same time, the existence of macroecological laws describing the variation and diversity in microbial communities irrespective of their environment has been recently proposed using 16s data and explained by a simple phenomenological model of population dynamics. We here investigate the relationship between dysbiosis, i.e. in unhealthy individuals there are deviations from the "regular" composition of the gut microbial community, and the existence of macro-ecological emergent law in microbial communities. We first quantitatively reconstruct these patterns at the species level using shotgun data, and addressing the consequences of sampling effects and statistical errors on ecological patterns. We then ask if such patterns can discriminate between healthy and unhealthy cohorts. Concomitantly, we evaluate the efficacy of different statistical generative models, which incorporate sampling and population dynamics, to describe such patterns and distinguish which are expected by chance, versus those that are potentially informative about disease states or other biological drivers. A critical aspect of our analysis is understanding the relationship between model parameters, which have clear ecological interpretations, and the state of the gut microbiome, thereby enabling the generation of synthetic compositional data that distinctively represent healthy and unhealthy individuals. Our approach, grounded in theoretical ecology and statistical physics, allows for a robust comparison of these models with empirical data, enhancing our understanding of the strengths and limitations of simple microbial models of population dynamics.}, }
@article {pmid39327438, year = {2024}, author = {Schmartz, GP and Rehner, J and Gund, MP and Keller, V and Molano, LG and Rupf, S and Hannig, M and Berger, T and Flockerzi, E and Seitz, B and Fleser, S and Schmitt-Grohé, S and Kalefack, S and Zemlin, M and Kunz, M and Götzinger, F and Gevaerd, C and Vogt, T and Reichrath, J and Diehl, L and Hecksteden, A and Meyer, T and Herr, C and Gurevich, A and Krug, D and Hegemann, J and Bozhueyuek, K and Gulder, TAM and Fu, C and Beemelmanns, C and Schattenberg, JM and Kalinina, OV and Becker, A and Unger, M and Ludwig, N and Seibert, M and Stein, ML and Hanna, NL and Martin, MC and Mahfoud, F and Krawczyk, M and Becker, SL and Müller, R and Bals, R and Keller, A}, title = {Decoding the diagnostic and therapeutic potential of microbiota using pan-body pan-disease microbiomics.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {8261}, pmid = {39327438}, issn = {2041-1723}, mesh = {Humans ; *Microbiota/genetics ; *Metagenome/genetics ; *Metagenomics/methods ; Bacteria/genetics/isolation &amp; purification/classification ; Feces/microbiology ; Male ; Female ; Multigene Family ; Saliva/microbiology ; Adult ; }, abstract = {The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.3 gigabases. Collected from 515 patients, these samples yield an average of 3.7 metagenomes per patient. Our results suggest significant microbial variations across diseases and specimen types, including unexpected anatomical sites. We identify 583 unexplored species-level genome bins (SGBs) of which 189 are significantly disease-associated. Of note, the existence of microbial resistance genes in one specimen was indicative of the same resistance genes in other specimens of the same patient. Annotated and previously undescribed SGBs collectively harbor 28,315 potential biosynthetic gene clusters (BGCs), with 1050 significant correlations to diseases. Our combinatorial approach identifies distinct SGBs and BGCs, emphasizing the value of pan-body pan-disease microbiomics as a source for diagnostic and therapeutic strategies.}, }
@article {pmid39322959, year = {2024}, author = {Wirbel, J and Essex, M and Forslund, SK and Zeller, G}, title = {A realistic benchmark for differential abundance testing and confounder adjustment in human microbiome studies.}, journal = {Genome biology}, volume = {25}, number = {1}, pages = {247}, pmid = {39322959}, issn = {1474-760X}, mesh = {Humans ; *Microbiota ; *Benchmarking ; RNA, Ribosomal, 16S/genetics ; Computer Simulation ; }, abstract = {BACKGROUND: In microbiome disease association studies, it is a fundamental task to test which microbes differ in their abundance between groups. Yet, consensus on suitable or optimal statistical methods for differential abundance testing is lacking, and it remains unexplored how these cope with confounding. Previous differential abundance benchmarks relying on simulated datasets did not quantitatively evaluate the similarity to real data, which undermines their recommendations.<br><br>RESULTS: Our simulation framework implants calibrated signals into real taxonomic profiles, including signals mimicking confounders. Using several whole&#xa0;meta-genome and 16S rRNA gene amplicon datasets, we validate that our simulated data resembles real data from disease association studies much more than in previous benchmarks. With extensively parametrized simulations, we benchmark the performance of nineteen differential abundance methods and further evaluate the best ones on confounded simulations. Only classic statistical methods (linear models, the Wilcoxon test, t-test), limma, and fastANCOM properly control false discoveries at relatively high sensitivity. When additionally considering confounders, these issues are exacerbated, but we find that adjusted differential abundance testing can effectively mitigate them. In a large cardiometabolic disease dataset, we showcase that failure to account for covariates such as medication causes spurious association in real-world applications.<br><br>CONCLUSIONS: Tight error control is critical for microbiome association studies. The unsatisfactory performance of many differential abundance methods and the persistent danger of unchecked confounding suggest these contribute to a lack of reproducibility among such studies. We have open-sourced our simulation and benchmarking software to foster a much-needed consolidation of statistical methodology for microbiome research.}, }
@article {pmid39322314, year = {2024}, author = {Van Hul, M and Cani, PD and Petitfils, C and De Vos, WM and Tilg, H and El-Omar, EM}, title = {What defines a healthy gut microbiome?.}, journal = {Gut}, volume = {73}, number = {11}, pages = {1893-1908}, pmid = {39322314}, issn = {1468-3288}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {The understanding that changes in microbiome composition can influence chronic human diseases and the efficiency of therapies has driven efforts to develop microbiota-centred therapies such as first and next generation probiotics, prebiotics and postbiotics, microbiota editing and faecal microbiota transplantation. Central to microbiome research is understanding how disease impacts microbiome composition and vice versa, yet there is a problematic issue with the term 'dysbiosis', which broadly links microbial imbalances to various chronic illnesses without precision or definition. Another significant issue in microbiome discussions is defining 'healthy individuals' to ascertain what characterises a healthy microbiome. This involves questioning who represents the healthiest segment of our population-whether it is those free from illnesses, athletes at peak performance, individuals living healthily through regular exercise and good nutrition or even elderly adults or centenarians who have been tested by time and achieved remarkable healthy longevity.This review advocates for delineating 'what defines a healthy microbiome?' by considering a broader range of factors related to human health and environmental influences on the microbiota. A healthy microbiome is undoubtedly linked to gut health. Nevertheless, it is very difficult to pinpoint a universally accepted definition of 'gut health' due to the complexities of measuring gut functionality besides the microbiota composition. We must take into account individual variabilities, the influence of diet, lifestyle, host and environmental factors. Moreover, the challenge in distinguishing causation from correlation between gut microbiome and overall health is presented.The review also highlights the resource-heavy nature of comprehensive gut health assessments, which hinders their practicality and broad application. Finally, we call for continued research and a nuanced approach to better understand the intricate and evolving concept of gut health, emphasising the need for more precise and inclusive definitions and methodologies in studying the microbiome.}, }
@article {pmid39320132, year = {2024}, author = {Bosland, MC and Gordon, T and Solomon, JJ and Shore, RE and Lippmann, M}, title = {Seventy-five years of impactful environmental and occupational health research at the Nelson Institute of Environmental Medicine at New York University.}, journal = {Annals of the New York Academy of Sciences}, volume = {1540}, number = {1}, pages = {147-165}, doi = {10.1111/nyas.15226}, pmid = {39320132}, issn = {1749-6632}, mesh = {Humans ; Academies and Institutes/history ; Biomedical Research/history/trends ; *Environmental Health/history ; *Environmental Medicine/history/trends ; History, 20th Century ; History, 21st Century ; New York ; New York City ; *Occupational Health/history ; Universities/history ; }, abstract = {Founded in 1947 as the Institute of Industrial Medicine, the Nelson Institute and Department of Environmental Medicine at New York University (NYU) Grossman School of Medicine (NYUGSOM) was supported by a National Institute of Environmental Health Science (NIEHS) Center Grant for over 56 years. Nelson Institute researchers generated 75 years of impactful research in environmental and occupational health, radiation effects, toxicology, and cancer. Environmental health research is continuing at NYUGSOM in its departments of medicine and population health. The objective of this historical commentary is to highlight the major achievements of the Nelson Institute and the department in the context of its history at facilities in Sterling Forest, Tuxedo, NY and Manhattan, NY. Aspects of our discussion include leadership, physical facilities, and research in many areas, including air pollution, health effects of environmental radiation exposures, inhalation toxicology methodology, carcinogenesis by chemicals, metals, and hormones, cancer chemoprevention, human microbiome, ecotoxicology, epidemiology, biostatistics, and community health concerns. The research of the institute and department benefited from unique facilities, strong leadership focused on team-based science, and outstanding investigators, students, and staff. A major lasting contribution has been the training of hundreds of graduate students and postdoctoral fellows, many of whom have been and are training the next generation of environmental and occupational health researchers at various institutions.}, }
@article {pmid39315152, year = {2024}, author = {Zheng, B and Xu, J and Zhang, Y and Qin, J and Yuan, D and Fan, T and Wu, W and Chen, Y and Jiang, Y}, title = {MBCN: A novel reference database for Effcient Metagenomic analysis of human gut microbiome.}, journal = {Heliyon}, volume = {10}, number = {18}, pages = {e37422}, pmid = {39315152}, issn = {2405-8440}, abstract = {Metagenomic shotgun sequencing data can identify microbes and their proportions. But metagenomic shotgun data profiling results obtained from multiple projects using different reference databases are difficult to compare and apply meta-analysis. Our work aims to create a novel collection of human gut prokaryotic genomes, named Microbiome Collection Navigator (MBCN). 2379 human gut metagenomic samples are screened, and 16,785 metagenome-assembled genomes (MAGs) are assembled using a standardized pipeline. In addition, MAGs are combined with the representative genomes from public prokaryotic genomes collections to cluster, and pan-genomes for each cluster's genomes are constructed to build Kraken2 and Bracken databases. The databases built by MBCN are more comprehensive and accurate for profiling metagenomic reads comparing with other collections on simulated reads and virtual bio-projects. We profile 1082 human gut metagenomic samples with MBCN database and organize profiles and metadata on the web program. Meanwhile, using MBCN as a reference database, we also develop a unified, standardized, and systematic metagenomic analysis pipeline and platform, named MicrobiotaCN (http://www.microbiota.cn) and common statistical and visualization tools for microbiome research are integrated into the web program. Taken together, MBCN and MicrobiotaCN can be a valuable resource and a powerful tool that allows researchers to perform metagenomic analysis by a unified pipeline efficiently.}, }
@article {pmid39313228, year = {2024}, author = {Kirtipal, N and Seo, Y and Son, J and Lee, S}, title = {Systems Biology of Human Microbiome for the Prediction of Personal Glycaemic Response.}, journal = {Diabetes &amp; metabolism journal}, volume = {48}, number = {5}, pages = {821-836}, pmid = {39313228}, issn = {2233-6087}, support = {//Ministry of Science ICT/ ; 2021R1C1C1006336//National Research Foundation of Korea/ ; 2021M3A9G8022959//National Research Foundation of Korea/ ; RS-2024-00419699//National Research Foundation of Korea/ ; //Korea Health Industry Development Institute/ ; HR22C141105//Ministry of Health and Welfare/ ; 2024-ER2108-00//Korea National Institute of Health/ ; 2024-ER0608-00//Korea National Institute of Health/ ; //GIST Research Institute/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Precision Medicine/methods ; *Systems Biology/methods ; Machine Learning ; Dysbiosis ; Blood Glucose/analysis ; Diabetes Mellitus/microbiology ; Diabetes Mellitus, Type 2/microbiology ; Hypoglycemic Agents/therapeutic use ; }, abstract = {The human gut microbiota is increasingly recognized as a pivotal factor in diabetes management, playing a significant role in the body's response to treatment. However, it is important to understand that long-term usage of medicines like metformin and other diabetic treatments can result in problems, gastrointestinal discomfort, and dysbiosis of the gut flora. Advanced sequencing technologies have improved our understanding of the gut microbiome's role in diabetes, uncovering complex interactions between microbial composition and metabolic health. We explore how the gut microbiota affects glucose metabolism and insulin sensitivity by examining a variety of -omics data, including genomics, transcriptomics, epigenomics, proteomics, metabolomics, and metagenomics. Machine learning algorithms and genome-scale modeling are now being applied to find microbiological biomarkers associated with diabetes risk, predicted disease progression, and guide customized therapy. This study holds promise for specialized diabetic therapy. Despite significant advances, some concerns remain unanswered, including understanding the complex relationship between diabetes etiology and gut microbiota, as well as developing user-friendly technological innovations. This mini-review explores the relationship between multiomics, precision medicine, and machine learning to improve our understanding of the gut microbiome's function in diabetes. In the era of precision medicine, the ultimate goal is to improve patient outcomes through personalized treatments.}, }
@article {pmid39307902, year = {2024}, author = {Ma, Z and Zuo, T and Frey, N and Rangrez, AY}, title = {A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation.}, journal = {Signal transduction and targeted therapy}, volume = {9}, number = {1}, pages = {237}, pmid = {39307902}, issn = {2059-3635}, support = {RA 2717/4-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 1289/17-1//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; }, mesh = {Humans ; *Microbiota/genetics ; Probiotics/therapeutic use ; Symbiosis/genetics ; }, abstract = {The human microbiome is a complex and dynamic system that plays important roles in human health and disease. However, there remain limitations and theoretical gaps in our current understanding of the intricate relationship between microbes and humans. In this narrative review, we integrate the knowledge and insights from various fields, including anatomy, physiology, immunology, histology, genetics, and evolution, to propose a systematic framework. It introduces key concepts such as the 'innate and adaptive genomes', which enhance genetic and evolutionary comprehension of the human genome. The 'germ-free syndrome' challenges the traditional 'microbes as pathogens' view, advocating for the necessity of microbes for health. The 'slave tissue' concept underscores the symbiotic intricacies between human tissues and their microbial counterparts, highlighting the dynamic health implications of microbial interactions. 'Acquired microbial immunity' positions the microbiome as an adjunct to human immune systems, providing a rationale for probiotic therapies and prudent antibiotic use. The 'homeostatic reprogramming hypothesis' integrates the microbiome into the internal environment theory, potentially explaining the change in homeostatic indicators post-industrialization. The 'cell-microbe co-ecology model' elucidates the symbiotic regulation affecting cellular balance, while the 'meta-host model' broadens the host definition to include symbiotic microbes. The 'health-illness conversion model' encapsulates the innate and adaptive genomes' interplay and dysbiosis patterns. The aim here is to provide a more focused and coherent understanding of microbiome and highlight future research avenues that could lead to a more effective and efficient healthcare system.}, }
@article {pmid39306588, year = {2025}, author = {Sahin, TK and Sonmezer, MC}, title = {The role of the microbiome in head and neck squamous cell cancers.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {282}, number = {2}, pages = {623-637}, pmid = {39306588}, issn = {1434-4726}, mesh = {Humans ; *Microbiota ; *Squamous Cell Carcinoma of Head and Neck/microbiology/therapy ; *Head and Neck Neoplasms/microbiology/therapy ; }, abstract = {The human microbiome has garnered tremendous interest in the field of oncology, and microbiota studies in head and neck oncology has also flourished. Given the increasing incidence and mortality of HNSCC, as well as the suboptimal outcomes of available treatments, there is an urgent need for innovative approaches involving the microbiome. This review evaluates the intricate relationship between the microbiome and HNSCC, highlighting the potential of the microbiome as a marker for cancer detection, its role in malignancy, and its impact on the efficacy of conventional treatments like chemotherapy and radiotherapy. The review also explores the effects of treatment modalities on the microbiome and discusses the potential of microbiome alterations to predict and influence treatment toxicities such as mucositis and xerostomia. Further research is warranted to characterize the microbiome-HNSCC association, which holds promise for advancing early diagnosis, enhancing prognostic accuracy, and personalizing treatment strategies to improve patient outcomes. The exploration of the microbiome in clinical trials indicates a burgeoning subject of microbiome-focused therapies, heralding a new frontier in most cancer care.}, }
@article {pmid39304775, year = {2024}, author = {Ray, K}, title = {A resource for the food microbiome and its links with the human microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {21}, number = {11}, pages = {746}, pmid = {39304775}, issn = {1759-5053}, }
@article {pmid39303118, year = {2024}, author = {Doré, J and Sansonetti, PJ}, title = {[The human microbiome: 340 years of history, 140 years of interrogations, technological innovations and emergence of "microbial medicine"].}, journal = {Medecine sciences : M/S}, volume = {40}, number = {8-9}, pages = {654-660}, doi = {10.1051/medsci/2024101}, pmid = {39303118}, issn = {1958-5381}, mesh = {Humans ; Gastrointestinal Microbiome/physiology ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Inventions/history/trends ; *Microbiota/physiology ; Symbiosis ; History, 17th Century ; }, abstract = {For 350 years, we have known that the human body hosts microbes, then called "animalcules". For over a century, following the demonstration of the role of some of these microbes in diseases, questions have arisen about the role of the largely predominant ones colonizing human skin and mucous surfaces, particularly the rich microbial ecosystem of the intestine, the gut microbiota. From the invention of germ-free life - axenism - which experimentally validated the human-microbe symbiosis, resulting from a long coevolution, to the development of anaerobic culture methods, then to the invention of molecular diagnosis, deep sequencing opening up metagenomic and omics approaches in general, a remarkable race has taken place between technological innovations and conceptual advances. This race, beyond the exhaustive description of the microbiota in its intra- and inter-human diversity, and the essential symbiotic functions of the microbiome, has paved the way for a new field of medicine: microbial medicine.}, }
@article {pmid39300165, year = {2024}, author = {Bisht, V and Das, B and Hussain, A and Kumar, V and Navani, NK}, title = {Understanding of probiotic origin antimicrobial peptides: a sustainable approach ensuring food safety.}, journal = {NPJ science of food}, volume = {8}, number = {1}, pages = {67}, pmid = {39300165}, issn = {2396-8370}, abstract = {The practice of preserving and adding value to food dates back to over 10,000 BCE, when unintentional microbial-driven chemical reactions imparted flavor and extended the shelf life of fermented foods. The process evolved, and with the urbanization of society, significant shifts in dietary habits emerged, accompanied by sporadic food poisoning incidents. The repercussions of the COVID-19 pandemic have intensified the search for antibiotic alternatives owing to the rise in antibiotic-resistant pathogens, emphasizing the exploration of probiotic-origin antimicrobial peptides to alleviate human microbiome collateral damage. Often termed 'molecular knives', these peptides outstand as potent antimicrobials due to their compatibility with innate microflora, amenability to bioengineering, target specificity, versatility and rapidity in molecular level mode of action. This review centres on bacteriocins sourced from lactic acid bacteria found in ethnic fermented foods, accentuating their desirable attributes, technological applications as nanobiotics and potential future applications in the modern context of ensuring food safety.}, }
@article {pmid39292000, year = {2024}, author = {Kilgore, PB and Sha, J and Hendrix, EK and Neil, BH and Lawrence, WS and Peel, JE and Hittle, L and Woolston, J and Sulakvelidze, A and Schwartz, JA and Chopra, AK}, title = {A bacteriophage cocktail targeting Yersinia pestis provides strong post-exposure protection in a rat pneumonic plague model.}, journal = {Microbiology spectrum}, volume = {12}, number = {11}, pages = {e0094224}, pmid = {39292000}, issn = {2165-0497}, support = {T32 AI141349/AI/NIAID NIH HHS/United States ; HHSN272201700040I/AI/NIAID NIH HHS/United States ; T32 AI060549/AI/NIAID NIH HHS/United States ; AI 141349//HHS | National Institutes of Health (NIH)/ ; HHSN272201700040I/75N93022F00003//HHS | National Institutes of Health (NIH)/ ; }, mesh = {Animals ; *Yersinia pestis ; *Plague/prevention &amp; control/microbiology ; Rats ; *Bacteriophages/physiology/genetics ; *Disease Models, Animal ; *Phage Therapy/methods ; Female ; Post-Exposure Prophylaxis/methods ; }, abstract = {Yersinia pestis, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, Y. pestis is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug-resistant strains. Indeed, antibiotic-resistant strains (e.g., strains carrying multidrug-resistant or MDR plasmids) have been isolated in various countries and endemic areas. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing Y. pestis infections. This includes infections by antigenically distinct strains for which vaccines (none FDA approved yet) may not be effective and those that cannot be managed by currently available antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by Y. pestis CO92. YPP-401 is a four-phage preparation effective against a panel of at least 68 genetically diverse Y. pestis strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ~88% protection when delivered 18 h post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies provide proof-of-concept that YPP-401 could be an innovative, safe, and effective approach for managing Y. pestis infections, including those caused by naturally occurring or intentionally developed multidrug-resistant strains.IMPORTANCECurrently, there are no FDA-approved plague vaccines. Since antibiotic-resistant strains of Y. pestis have emerged or are being intentionally developed to be used as a biothreat agent, new treatment modalities are direly needed. Phage therapy provides a viable option against potentially antibiotic-resistant strains. Additionally, phages are nontoxic and have been approved by the FDA for use in the food industry. Our study provides the first evidence of the protective effect of a cocktail of four phages against pneumonic plague, the most severe form of disease. When treatment was initiated 18 h post infection by either the intranasal or intraperitoneal route in Brown Norway rats, up to 87.5% protection was observed. The phage cocktail had a minimal impact on a representative human microbiome panel, unlike antibiotics. This study provides strong proof-of-concept data for the further development of phage-based therapy to treat plague.}, }
@article {pmid39283061, year = {2024}, author = {McBurney, MI and Cho, CE}, title = {Understanding the role of the human gut microbiome in overweight and obesity.}, journal = {Annals of the New York Academy of Sciences}, volume = {1540}, number = {1}, pages = {61-88}, doi = {10.1111/nyas.15215}, pmid = {39283061}, issn = {1749-6632}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Obesity/microbiology/metabolism ; *Overweight/microbiology ; Probiotics ; Prebiotics/administration &amp; dosage ; Fecal Microbiota Transplantation ; Diet ; }, abstract = {The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host-microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities.}, }
@article {pmid39273475, year = {2024}, author = {Larson, J and Sather, B and Wang, L and Westrum, J and Tokmina-Lukaszewska, M and Pauley, J and Copié, V and McDermott, TR and Bothner, B}, title = {Metalloproteomics Reveals Multi-Level Stress Response in Escherichia coli When Exposed to Arsenite.}, journal = {International journal of molecular sciences}, volume = {25}, number = {17}, pages = {}, pmid = {39273475}, issn = {1422-0067}, support = {P42ES031007//University of North Carolina's Superfund Program/ ; DE-SC0020246//U.S. Department of Energy/ ; S10 OD028650/OD/NIH HHS/United States ; MCB 1714556//National Science Foundation/ ; P42 ES031007/ES/NIEHS NIH HHS/United States ; R24 GM137786/GM/NIGMS NIH HHS/United States ; R24GM137786/GM/NIGMS NIH HHS/United States ; P20 GM103474/GM/NIGMS NIH HHS/United States ; }, mesh = {*Arsenites/toxicity ; *Escherichia coli/genetics/metabolism/drug effects ; *Escherichia coli Proteins/genetics/metabolism ; *Proteomics/methods ; *Stress, Physiological ; *Gene Expression Regulation, Bacterial/drug effects ; *Operon/genetics ; Metalloproteins/metabolism/genetics ; Humans ; }, abstract = {The arsRBC operon encodes a three-protein arsenic resistance system. ArsR regulates the transcription of the operon, while ArsB and ArsC are involved in exporting trivalent arsenic and reducing pentavalent arsenic, respectively. Previous research into Agrobacterium tumefaciens 5A has demonstrated that ArsR has regulatory control over a wide range of metal-related proteins and metabolic pathways. We hypothesized that ArsR has broad regulatory control in other Gram-negative bacteria and set out to test this. Here, we use differential proteomics to investigate changes caused by the presence of the arsR gene in human microbiome-relevant Escherichia coli during arsenite (As[III]) exposure. We show that ArsR has broad-ranging impacts such as the expression of TCA cycle enzymes during As[III] stress. Additionally, we found that the Isc [Fe-S] cluster and molybdenum cofactor assembly proteins are upregulated regardless of the presence of ArsR under these same conditions. An important finding from this differential proteomics analysis was the identification of response mechanisms that were strain-, ArsR-, and arsenic-specific, providing new clarity to this complex regulon. Given the widespread occurrence of the arsRBC operon, these findings should have broad applicability across microbial genera, including sensitive environments such as the human gastrointestinal tract.}, }
@article {pmid39271424, year = {2024}, author = {Bokulich, NA and Robeson, MS}, title = {Bioinformatics challenges for profiling the microbiome in cancer: pitfalls and opportunities.}, journal = {Trends in microbiology}, volume = {32}, number = {12}, pages = {1163-1166}, doi = {10.1016/j.tim.2024.08.011}, pmid = {39271424}, issn = {1878-4380}, support = {R01 CA143130/CA/NCI NIH HHS/United States ; R01 CA245083/CA/NCI NIH HHS/United States ; R01 CA282198/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms/microbiology ; *Microbiota ; *Computational Biology/methods ; *Metagenomics/methods ; *Machine Learning ; Sequence Analysis, DNA/methods ; }, abstract = {Increasing evidence suggests that the human microbiome plays an important role in cancer risk and treatment. Untargeted 'omics' techniques have accelerated research into microbiome-cancer interactions, supporting the discovery of novel associations and mechanisms. However, these techniques require careful selection and use to avoid biases and other pitfalls. In this essay, we discuss selected challenges involved in the analysis of microbiome data in the context of cancer, including the application of machine learning (ML). We focus on DNA sequencing-based (e.g., metagenomics) methods, but many of the pitfalls and opportunities generalize to other omics technologies as well. We advocate for extended training opportunities, community standards, and best practices for sharing data and code to advance transparency and reproducibility in cancer microbiome research.}, }
@article {pmid39256307, year = {2024}, author = {Rastegar, S and Skurnik, M and Niaz, H and Tadjrobehkar, O and Samareh, A and Hosseini-Nave, H and Sabouri, S}, title = {Isolation, characterization, and potential application of Acinetobacter baumannii phages against extensively drug-resistant strains.}, journal = {Virus genes}, volume = {60}, number = {6}, pages = {725-736}, pmid = {39256307}, issn = {1572-994X}, support = {KMU.AC.IR.400000652//Hossein Hosseini-Nave1/ ; }, mesh = {*Acinetobacter baumannii/virology/drug effects ; *Genome, Viral/genetics ; *Bacteriophages/genetics/isolation &amp; purification/classification/physiology ; *Drug Resistance, Multiple, Bacterial ; *Host Specificity ; *Anti-Bacterial Agents/pharmacology ; Acinetobacter Infections/microbiology ; Phage Therapy ; Sewage/virology/microbiology ; Humans ; }, abstract = {One of the significant issues in treating bacterial infections is the increasing prevalence of extensively drug-resistant (XDR) strains of Acinetobacter baumannii. In the face of limited or no viable treatment options for extensively drug-resistant (XDR) bacteria, there is a renewed interest in utilizing bacteriophages as a treatment option. Three Acinetobacter phages (vB_AbaS_Ftm, vB_AbaS_Eva, and vB_AbaS_Gln) were identified from hospital sewage and analyzed for their morphology, host ranges, and their genome sequences were determined and annotated. These phages and vB_AbaS_SA1 were combined to form a phage cocktail. The antibacterial effects of this cocktail and its combinations with selected antimicrobial agents were evaluated against the XDR A. baumannii strains. The phages exhibited siphovirus morphology. Out of a total of 30 XDR A. baumannii isolates, 33% were sensitive to vB_AbaS_Ftm, 30% to vB_AbaS_Gln, and 16.66% to vB_AbaS_Eva. When these phages were combined with antibiotics, they demonstrated a synergistic effect. The genome sizes of vB_AbaS_Ftm, vB_AbaS_Eva, and vB_AbaS_Gln were 48487, 50174, and 50043 base pairs (bp), respectively, and showed high similarity. Phage cocktail, when combined with antibiotics, showed synergistic effects on extensively drug-resistant (XDR) strains of A. baumannii. However, the need for further study to fully understand the mechanisms of action and potential limitations of using these phages is highlighted.}, }
@article {pmid39256189, year = {2024}, author = {Yılmaz, SS and Kuşkucu, MA and Çakan, H and Aygün, G}, title = {Effective use of skin microbiome signatures for fingerprint identification.}, journal = {Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI)}, volume = {30}, number = {9}, pages = {e70052}, pmid = {39256189}, issn = {1600-0846}, support = {28100//Research Fund of Istanbul University-Cerrahpa&#x15f;a/ ; }, mesh = {Humans ; *Microbiota/genetics ; *Skin/microbiology ; Adult ; Male ; Female ; Staphylococcus epidermidis/isolation &amp; purification/genetics ; Ribotyping/methods ; Dermatoglyphics ; RNA, Ribosomal, 16S/genetics ; Young Adult ; Minisatellite Repeats ; }, abstract = {BACKGROUND: Recent advances have increased the importance of the human microbiome, including the skin microbiome. Despite the hand microbiome research, the factors affecting the composition of the hand microbiome and their personal characteristics are incompletely known.<br><br>OBJECTIVES: Despite changing environmental factors and personal variation, we aimed to indicate the interpersonal distinction between skin microbiota using simple and rapid molecular methods.<br><br>METHODS: Over a non-consecutive 10-day period, samples were taken from 10 adult individuals, and ribotyping analysis of the 16S and 23S genes of S. epidermidis was performed on each skin sample. Additionally, EcoRI and HindIII enzyme reactions and variable number tandem repeat (VNTR) reactions of S. epidermidis obtained from DNA samples were performed. The skin microbiomes of individuals were evaluated along with the microbiome profiles left on the surfaces they touched.<br><br>RESULTS: In the environmental samples taken, it has been observed that people preserve their core skin microbiota characters and carry them to their environment. It was determined that the highest similarity rate was 77.14%, and the lowest similarity rate was 31.74%.<br><br>CONCLUSION: Our study showed that the core skin microbiota retains its characteristics and leaves traces in environments. The fact that the personal microbiome remains unchanged despite environmental differences and has characteristic features has shown that it can be used in forensic sciences to distinguish individuals from each other. These results with simple and rapid methods further increased the importance and significance of the study. The findings indicate that personal skin microbiota can provide a significant contribution to criminal investigations by increasing accuracy and reliability, especially in forensic analyses.}, }
@article {pmid39255394, year = {2024}, author = {Ginsberg, SD and Blaser, MJ}, title = {Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {Supplement_2}, pages = {S141-S149}, pmid = {39255394}, issn = {1537-6613}, support = {//Emch Foundation/ ; //Infectious Diseases Society of America/ ; U01 AI122285/AI/NIAID NIH HHS/United States ; U01 AI122285/NH/NIH HHS/United States ; R01 AG072599/AG/NIA NIH HHS/United States ; //C &amp; D Fund/ ; }, mesh = {Animals ; Humans ; *Alzheimer Disease/microbiology/physiopathology ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; Brain/microbiology/pathology/physiopathology ; *Gastrointestinal Microbiome/drug effects/physiology ; Disease Models, Animal ; Brain-Gut Axis/drug effects/physiology ; }, abstract = {Alzheimer's disease (AD) is a neurodegenerative disorder with limited therapeutic options. Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration. AD and Alzheimer's disease-related dementias (ADRD) are recognized as spectrum disorders with complex pathobiology. AD/ADRD onset begins before overt clinical signs, but initiation triggers remain undefined. We posit that disruption of the normal gut microbiome in early life leads to a pathological cascade within septohippocampal and cortical brain circuits. We propose investigation to understand how early-life microbiota changes may lead to hallmark AD pathology in established AD/ADRD models. Specifically, we hypothesize that antibiotic exposure in early life leads to exacerbated AD-like disease endophenotypes that may be amenable to specific microbiological interventions. We propose suitable models for testing these hypotheses.}, }
@article {pmid39255040, year = {2024}, author = {Sanches Santos Rizzo Zuttion, M and Parimon, T and Bora, SA and Yao, C and Lagree, K and Gao, CA and Wunderink, RG and Kitsios, GD and Morris, A and Zhang, Y and McVerry, BJ and Modes, ME and Marchevsky, AM and Stripp, BR and Soto, CM and Wang, Y and Merene, K and Cho, S and Victor, BL and Vujkovic-Cvijin, I and Gupta, S and Cassel, SL and Sutterwala, FS and Devkota, S and Underhill, DM and Chen, P}, title = {Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia.}, journal = {The Journal of clinical investigation}, volume = {134}, number = {21}, pages = {}, pmid = {39255040}, issn = {1558-8238}, support = {R03 HL162655/HL/NHLBI NIH HHS/United States ; F32 HL162377/HL/NHLBI NIH HHS/United States ; K23 HL169815/HL/NHLBI NIH HHS/United States ; U19 AI135964/AI/NIAID NIH HHS/United States ; P01 HL154998/HL/NHLBI NIH HHS/United States ; U01 TR003528/TR/NCATS NIH HHS/United States ; KL2 TR001882/TR/NCATS NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R01 HL164177/HL/NHLBI NIH HHS/United States ; R01 HL159953/HL/NHLBI NIH HHS/United States ; P01 HL114453/HL/NHLBI NIH HHS/United States ; R01 LM013337/LM/NLM NIH HHS/United States ; R01 HL155759/HL/NHLBI NIH HHS/United States ; R01 HL163646/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Eosinophils/immunology ; Humans ; *Anti-Bacterial Agents/pharmacology ; *Methicillin-Resistant Staphylococcus aureus/immunology ; *Lung/immunology/pathology ; *Influenza, Human/immunology/drug therapy ; Female ; *Orthomyxoviridae Infections/immunology/drug therapy ; Male ; Pneumonia, Bacterial/immunology/drug therapy ; Pneumonia, Staphylococcal/immunology/drug therapy ; }, abstract = {A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated that antibiotic treatment during influenza infection caused a fungal dysbiosis that drove lung eosinophilia and impaired MRSA clearance. Finally, we evaluated 3 cohorts of hospitalized patients and found that eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs, thereby increasing the risk of developing a secondary bacterial infection.}, }
@article {pmid39254049, year = {2024}, author = {Harris, RM and Pace, F and Kuntz, TM and Morgan, XC and Hyland, P and Summers, K and McDermott, E and Blumen, K and Watnick, PI}, title = {Testosterone treatment impacts the intestinal microbiome of transgender individuals.}, journal = {mSphere}, volume = {9}, number = {10}, pages = {e0055724}, pmid = {39254049}, issn = {2379-5042}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Testosterone ; Male ; *Transgender Persons ; Female ; Pilot Projects ; *Feces/microbiology ; Adult ; Metagenomics ; Middle Aged ; Glutamic Acid/metabolism ; Bacteria/classification/genetics/drug effects/metabolism/isolation &amp; purification ; }, abstract = {Medical modulation of sex hormone levels is a cornerstone of treatment for many conditions that impact well-being, including cancer, fertility/infertility, gender dysphoria, and chronic metabolic diseases such as diabetes and obesity. The microbial residents of the intestine, known as the microbiota, interact with sex hormones in the intestine, and there is correlative evidence that this interaction is bidirectional. Based on these published findings, we hypothesized that transgender individuals receiving exogenous testosterone as part of their gender-affirming medical treatment might undergo changes in their intestinal microbiome. To test this, we collected 26 stool samples from nine individuals before and up to 8 months after initiation of treatment with exogenous testosterone and subjected these samples to metagenomic analysis. While no species were significantly associated with the duration of testosterone therapy, pathways that generate glutamate increased in abundance, while those that consume glutamate decreased. Glutamate is a precursor of arginine, and testosterone is known to increase levels of arginine and its metabolites in the plasma. We hypothesize that testosterone increases the uptake of glutamate by enterocytes, thus decreasing access of the microbiota to this amino acid. While this pilot study establishes the impact of testosterone therapy on the intestinal microbiome, a more comprehensive study is necessary to establish the impact of testosterone-driven metagenomic shifts on the stool metatranscriptome, the stool metabolome, and the plasma metabolome.IMPORTANCEThe human intestine is inhabited by a large community of microbes known as the microbiome. Members of the microbiome consume the diet along with their human host. Thus, the metabolomes of the host and microbe are intricately linked. Testosterone alters the plasma metabolome. In particular, plasma levels of arginine and its metabolites and testosterone are positively correlated. To investigate the impact of exogenous testosterone on the microbiome, we analyzed the stool metagenomes of transgender individuals before and after the initiation of testosterone treatment. In this pilot project, we found a modest impact on the microbiome community structure but an increase in the abundance of metabolic pathways that generate glutamate and spare glutamate consumption. We propose that the host uses glutamate to generate arginine, decreasing the amount available for the microbiome.}, }
@article {pmid39251326, year = {2025}, author = {Zhou, Q and Lei, L and Cheng, J and Chen, J and Du, Y and Zhang, X and Li, Q and Li, C and Deng, H and Wong, CC and Zhuang, B and Li, G and Bai, X}, title = {Microbiota-induced S100A11-RAGE axis underlies immune evasion in right-sided colon adenomas and is a therapeutic target to boost anti-PD1 efficacy.}, journal = {Gut}, volume = {74}, number = {2}, pages = {214-228}, pmid = {39251326}, issn = {1468-3288}, mesh = {Animals ; *Colonic Neoplasms/immunology/pathology/microbiology/drug therapy ; *Adenoma/immunology/pathology/microbiology/drug therapy ; Mice ; Humans ; *Gastrointestinal Microbiome/immunology ; *S100 Proteins/metabolism ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors ; *Receptor for Advanced Glycation End Products/metabolism ; Myeloid-Derived Suppressor Cells/immunology ; Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Goblet Cells ; *Immune Evasion ; }, abstract = {BACKGROUND: Tumourigenesis in right-sided and left-sided colons demonstrated distinct features.<br><br>OBJECTIVE: We aimed to characterise the differences between the left-sided and right-sided adenomas (ADs) representing the early stage of colonic tumourigenesis.<br><br>DESIGN: Single-cell and spatial transcriptomic datasets were analysed to reveal alterations between right-sided and left-sided colon ADs. Cells, animal experiments and clinical specimens were used to verify the results.<br><br>RESULTS: Single-cell analysis revealed that in right-sided ADs, there was a significant reduction of goblet cells, and these goblet cells were dysfunctional with attenuated mucin biosynthesis and defective antigen presentation. An impairment of the mucus barrier led to biofilm formation in crypts and subsequent bacteria invasion into right-sided ADs. The regions spatially surrounding the crypts with biofilm occupation underwent an inflammatory response by lipopolysaccharide (LPS) and an apoptosis process, as revealed by spatial transcriptomics. A distinct S100A11[+] epithelial cell population in the right-sided ADs was identified, and its expression level was induced by bacterial LPS and peptidoglycan. S100A11 expression facilitated tumour growth in syngeneic immunocompetent mice with increased myeloid-derived suppressor cells (MDSC) but reduced cytotoxic CD8+ T cells. Targeting S100A11 with well-tolerated antagonists of its receptor for advanced glycation end product (RAGE) (Azeliragon) significantly impaired tumour growth and MDSC infiltration, thereby boosting the efficacy of anti-programmed cell death protein 1 therapy in colon cancer.<br><br>CONCLUSION: Our findings unravelled that dysfunctional goblet cells and consequential bacterial translocation activated the S100A11-RAGE axis in right-sided colon ADs, which recruits MDSCs to promote immune evasion. Targeting this axis by Azeliragon improves the efficacy of immunotherapy in colon cancer.}, }
@article {pmid39244168, year = {2025}, author = {Govender, P and Ghai, M}, title = {Population-specific differences in the human microbiome: Factors defining the diversity.}, journal = {Gene}, volume = {933}, number = {}, pages = {148923}, doi = {10.1016/j.gene.2024.148923}, pmid = {39244168}, issn = {1879-0038}, mesh = {Humans ; Asian People ; Bacteria/genetics/classification ; Bacteriophages/genetics ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; *Microbiota ; White People ; Black People ; }, abstract = {Differences in microbial communities at different body habitats define the microbiome composition of the human body. The gut, oral, skin vaginal fluid and tissue microbiome, are pivotal for human development and immune response and cross talk between these microbiomes is evident. Population studies reveal that various factors, such as host genetics, diet, lifestyle, aging, and geographical location are strongly associated with population-specific microbiome differences. The present review discusses the factors that shape microbiome diversity in humans, and microbiome differences in African, Asian and Caucasian populations. Gut microbiome studies show that microbial species Bacteroides is commonly found in individuals living in Western countries (Caucasian populations), while Prevotella is prevalent in non-Western countries (African and Asian populations). This association is mainly due to the high carbohydrate, high fat diet in western countries in contrast to high fibre, low fat diets in African/ Asian regions. Majority of the microbiome studies focus on the bacteriome component; however, interesting findings reveal that increased bacteriophage richness, which makes up the virome component, correlates with decreased bacterial diversity, and causes microbiome dysbiosis. An increase of Caudovirales (bacteriophages) is associated with a decrease in enteric bacteria in inflammatory bowel diseases. Future microbiome studies should evaluate the interrelation between bacteriome and virome to fully understand their significance in the pathogenesis and progression of human diseases. With ethnic health disparities becoming increasingly apparent, studies need to emphasize on the association of population-specific microbiome differences and human diseases, to develop microbiome-based therapeutics. Additionally, targeted phage therapy is emerging as an attractive alternative to antibiotics for bacterial infections. With rapid rise in microbiome research, focus should be on standardizing protocols, advanced bioinformatics tools, and reducing sequencing platform related biases. Ultimately, integration of multi-omics data (genomics, transcriptomics, proteomics and metabolomics) will lead to precision models for personalized microbiome therapeutics advancement.}, }
@article {pmid39243797, year = {2025}, author = {Rodriguez, J and Hassani, Z and Alves Costa Silva, C and Betsou, F and Carraturo, F and Fasano, A and Israelsen, M and Iyappan, A and Krag, A and Metwaly, A and Schierwagen, R and Trebicka, J and Zwart, H and Doré, J and Cordaillat-Simmons, M and Druart, C and , }, title = {State of the art and the future of microbiome-based biomarkers: a multidisciplinary Delphi consensus.}, journal = {The Lancet. Microbe}, volume = {6}, number = {2}, pages = {100948}, doi = {10.1016/j.lanmic.2024.07.011}, pmid = {39243797}, issn = {2666-5247}, mesh = {Humans ; *Biomarkers/analysis ; Delphi Technique ; *Microbiota ; Consensus ; Surveys and Questionnaires ; }, abstract = {Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts' confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.}, }
@article {pmid39240756, year = {2024}, author = {Torrillo, PA and Lieberman, TD}, title = {Reversions mask the contribution of adaptive evolution in microbiomes.}, journal = {eLife}, volume = {13}, number = {}, pages = {}, pmid = {39240756}, issn = {2050-084X}, support = {DP2 GM140922/GM/NIGMS NIH HHS/United States ; 1DP2GM140922-01/NH/NIH HHS/United States ; Graduate Research Fellowship Program//National Science Foundation/ ; }, mesh = {*Mutation ; *Evolution, Molecular ; Selection, Genetic ; Genome, Bacterial ; Microbiota/genetics ; Gastrointestinal Microbiome/genetics ; Bacteroides/genetics ; Adaptation, Physiological/genetics ; Models, Genetic ; Bacteria/genetics/classification ; }, abstract = {When examining bacterial genomes for evidence of past selection, the results depend heavily on the mutational distance between chosen genomes. Even within a bacterial species, genomes separated by larger mutational distances exhibit stronger evidence of purifying selection as assessed by dN/dS, the normalized ratio of nonsynonymous to synonymous mutations. Here, we show that the classical interpretation of this scale dependence, weak purifying selection, leads to problematic mutation accumulation when applied to available gut microbiome data. We propose an alternative, adaptive reversion model with opposite implications for dynamical intuition and applications of dN/dS. Reversions that occur and sweep within-host populations are nearly guaranteed in microbiomes due to large population sizes, short generation times, and variable environments. Using analytical and simulation approaches, we show that adaptive reversion can explain the dN/dS decay given only dozens of locally fluctuating selective pressures, which is realistic in the context of Bacteroides genomes. The success of the adaptive reversion model argues for interpreting low values of dN/dS obtained from long timescales with caution as they may emerge even when adaptive sweeps are frequent. Our work thus inverts the interpretation of an old observation in bacterial evolution, illustrates the potential of mutational reversions to shape genomic landscapes over time, and highlights the importance of studying bacterial genomic evolution on short timescales.}, }
@article {pmid39238383, year = {2024}, author = {Sanyal, S and Nigam, K and Singh, S and Lohani, P and Dwivedi, M}, title = {Pathophysiological and Clinical Potential of Human Microbiome: Microbe-based Therapeutic Insights.}, journal = {Current pharmaceutical biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0113892010314433240823113111}, pmid = {39238383}, issn = {1873-4316}, abstract = {The human microbiota represents the community and diverse population of microbes within the human body, which comprises approximately 100 trillion micro-organisms. They exist in the human gastrointestinal tract and various other organs and are now considered virtual body organs. It is mainly represented by bacteria but also includes viruses, fungi, and protozoa. Although there is a heritable component to the gut microbiota, environmental factors related to diet, drugs, and anthropometry determine the composition of the microbiota. Besides the gastrointestinal tract, the human body also harbours microbial communities in the skin, oral and nasal cavities, and reproductive tract. The current review demonstrates the role of gut microbiota and its involvement in processing food, drugs, and immune responses. The discussion focuses on the implications of human microbiota in developing several diseases, such as gastrointestinal infections, metabolic disorders, malignancies, etc., through symbiotic relationships. The microbial population may vary depending on the pathophysiological condition of an individual and thus may be exploited as a therapeutic and clinical player. Further, we need a more thorough investigation to establish the correlation between microbes and pathophysiology in humans and propose them as potential therapeutic targets.}, }
@article {pmid39235252, year = {2024}, author = {Sweet, P and Burroughs, M and Jang, S and Contreras, L}, title = {TolRad, a model for predicting radiation tolerance using Pfam annotations, identifies novel radiosensitive bacterial species from reference genomes and MAGs.}, journal = {Microbiology spectrum}, volume = {12}, number = {10}, pages = {e0383823}, pmid = {39235252}, issn = {2165-0497}, support = {HDTRA1-17-1-0025//DOD | Defense Threat Reduction Agency (DTRA)/ ; FA9550-20-1-0131//DOD | USAF | AMC | Air Force Office of Scientific Research (AFOSR)/ ; W911NF22S0002//DNI | Intelligence Advanced Research Projects Activity (IARPA)/ ; }, mesh = {*Radiation Tolerance/genetics ; *Bacteria/genetics/radiation effects/classification ; *Genome, Bacterial ; Humans ; Radiation, Ionizing ; Bacterial Proteins/genetics/metabolism ; Microbiota/genetics/radiation effects ; Proteome ; Metagenome ; Molecular Sequence Annotation ; }, abstract = {UNLABELLED: The trait of ionizing radiation (IR) tolerance is variable between bacterium, with species succumbing to acute doses as low as 60 Gy and extremophiles able to survive doses exceeding 10,000 Gy. While survival screens have identified multiple highly radioresistant bacteria, such systemic searches have not been conducted for IR-sensitive bacteria. The taxonomy-level diversity of IR sensitivity is poorly understood, as are genetic elements that influence IR sensitivity. Using the protein domain (Pfam) frequencies from 61 bacterial species with experimentally determined D10 values (the dose at which only 10% of the population survives), we trained TolRad, a random forest binary classifier, to distinguish between radiosensitive (D10 < 200 Gy) and radiation-tolerant (D10 > 200 Gy) bacteria. On untrained species, TolRad had an accuracy of 0.900. We applied TolRad to 152 UniProt-hosted bacterial proteomes associated with the human microbiome, including 37 strains from the ATCC Human Microbiome Collection, and classified 34 species as radiosensitive. Whereas IR-sensitive species (D10 < 200 Gy) in the training data set had been confined to the phylum Proteobacterium, this initial TolRad screen identified radiosensitive bacteria in two additional phyla. We experimentally validated the predicted radiosensitivity of a Bacteroidota species from the human microbiome. To demonstrate that TolRad can be applied to metagenome-assembled genomes (MAGs), we tested the accuracy of TolRad on Egg-NOG assembled proteomes (0.965) and partial proteomes. Finally, three collections of MAGs were screened using TolRad, identifying further phyla with radiosensitive species and suggesting that environmental conditions influence the abundance of radiosensitive bacteria.<br><br>IMPORTANCE: Bacterial species have vast genetic diversity, allowing for life in extreme environments and the conduction of complex chemistry. The ability to harness the full potential of bacterial diversity is hampered by the lack of high-throughput experimental or bioinformatic methods for characterizing bacterial traits. Here, we present a computational model that uses de novo-generated genome annotations to classify a bacterium as tolerant of ionizing radiation (IR) or as radiosensitive. This model allows for rapid screening of bacterial communities for low-tolerance species that are of interest for both mechanistic studies into bacterial sensitivity to IR and biomarkers of IR exposure.}, }
@article {pmid39233526, year = {2024}, author = {Kim, TH and Cho, BK and Lee, DH}, title = {Synthetic Biology-Driven Microbial Therapeutics for Disease Treatment.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {10}, pages = {1947-1958}, pmid = {39233526}, issn = {1738-8872}, mesh = {*Synthetic Biology/methods ; Humans ; Animals ; *Gastrointestinal Microbiome ; Metabolic Diseases/therapy/microbiology ; Gastrointestinal Diseases/therapy/microbiology ; Neoplasms/therapy/microbiology ; Biosensing Techniques ; Biological Therapy/methods ; Bacteria/genetics/metabolism ; }, abstract = {The human microbiome, consisting of microorganisms that coexist symbiotically with the body, impacts health from birth. Alterations in gut microbiota driven by factors such as diet and medication can contribute to diseases beyond the gut. Synthetic biology has paved the way for engineered microbial therapeutics, presenting promising treatments for a variety of conditions. Using genetically encoded biosensors and dynamic regulatory tools, engineered microbes can produce and deliver therapeutic agents, detect biomarkers, and manage diseases. This review organizes engineered microbial therapeutics by disease type, emphasizing innovative strategies and recent advancements. The scope of diseases includes gastrointestinal disorders, cancers, metabolic diseases, infections, and other ailments. Synthetic biology facilitates precise targeting and regulation, improving the efficacy and safety of these therapies. With promising results in animal models, engineered microbial therapeutics provide a novel alternative to traditional treatments, heralding a transformative era in diagnostics and treatment for numerous diseases.}, }
@article {pmid39232070, year = {2024}, author = {Jang, H and Koh, H}, title = {A unified web cloud computing platform MiMedSurv for microbiome causal mediation analysis with survival responses.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {20650}, pmid = {39232070}, issn = {2045-2322}, support = {2021R1C1C1013861//National Research Foundation of Korea/ ; }, mesh = {Humans ; *Microbiota ; *Cloud Computing ; *Internet ; Software ; Survival Analysis ; }, abstract = {In human microbiome studies, mediation analysis has recently been spotlighted as a practical and powerful analytic tool to survey the causal roles of the microbiome as a mediator to explain the observed relationships between a medical treatment/environmental exposure and a human disease. We also note that, in a clinical research, investigators often trace disease progression sequentially in time; as such, time-to-event (e.g., time-to-disease, time-to-cure) responses, known as survival responses, are prevalent as a surrogate variable for human health or disease. In this paper, we introduce a web cloud computing platform, named as microbiome mediation analysis with survival responses (MiMedSurv), for comprehensive microbiome mediation analysis with survival responses on user-friendly web environments. MiMedSurv is an extension of our prior web cloud computing platform, named as microbiome mediation analysis (MiMed), for survival responses. The two main features that are well-distinguished are as follows. First, MiMedSurv conducts some baseline exploratory non-mediational survival analysis, not involving microbiome, to survey the disparity in survival response between medical treatments/environmental exposures. Then, MiMedSurv identifies the mediating roles of the microbiome in various aspects: (i) as a microbial ecosystem using ecological indices (e.g., alpha and beta diversity indices) and (ii) as individual microbial taxa in various hierarchies (e.g., phyla, classes, orders, families, genera, species). To illustrate its use, we survey the mediating roles of the gut microbiome between antibiotic treatment and time-to-type 1 diabetes. MiMedSurv is freely available on our web server (http://mimedsurv.micloud.kr).}, }
@article {pmid39230701, year = {2024}, author = {Hera, MR and Liu, S and Wei, W and Rodriguez, JS and Ma, C and Koslicki, D}, title = {Metagenomic functional profiling: to sketch or not to sketch?.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {Suppl 2}, pages = {ii165-ii173}, pmid = {39230701}, issn = {1367-4811}, support = {R01 GM146462/GM/NIGMS NIH HHS/United States ; R01GM146462/GF/NIH HHS/United States ; }, mesh = {*Metagenomics/methods ; *Software ; *Algorithms ; *Metagenome/genetics ; Humans ; Microbiota/genetics ; Databases, Genetic ; }, abstract = {MOTIVATION: Functional profiling of metagenomic samples is essential to decipher the functional capabilities of microbial communities. Traditional and more widely used functional profilers in the context of metagenomics rely on aligning reads against a known reference database. However, aligning sequencing reads against a large and fast-growing database is computationally expensive. In general, k-mer-based sketching techniques have been successfully used in metagenomics to address this bottleneck, notably in taxonomic profiling. In this work, we describe leveraging FracMinHash (implemented in sourmash, a publicly available software), a k-mer-sketching algorithm, to obtain functional profiles of metagenome samples.<br><br>RESULTS: We show how pieces of the sourmash software (and the resulting FracMinHash sketches) can be put together in a pipeline to functionally profile a metagenomic sample. We named our pipeline fmh-funprofiler. We report that the functional profiles obtained using this pipeline demonstrate comparable completeness and better purity compared to the profiles obtained using other alignment-based methods when applied to simulated metagenomic data. We also report that fmh-funprofiler is 39-99&#xd7; faster in wall-clock time, and consumes up to 40-55&#xd7; less memory. Coupled with the KEGG database, this method not only replicates fundamental biological insights but also highlights novel signals from the Human Microbiome Project datasets.<br><br>This fast and lightweight metagenomic functional profiler is freely available and can be accessed here: https://github.com/KoslickiLab/fmh-funprofiler. All scripts of the analyses we present in this manuscript can be found on GitHub.}, }
@article {pmid39230353, year = {2025}, author = {Bland, CM and Love, BL and Jones, BM}, title = {Human microbiome: Impact of newly approved treatments on C. difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {82}, number = {4}, pages = {174-183}, doi = {10.1093/ajhp/zxae249}, pmid = {39230353}, issn = {1535-2900}, mesh = {Humans ; *Clostridium Infections/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Clostridioides difficile ; *Microbiota/physiology ; *Gastrointestinal Microbiome/physiology/drug effects ; Drug Approval ; }, abstract = {PURPOSE: The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice.<br><br>SUMMARY: The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies.<br><br>CONCLUSION: Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.}, }
@article {pmid39230261, year = {2024}, author = {Tu, V and Ren, Y and Tanes, C and Mukhopadhyay, S and Daniel, SG and Li, H and Bittinger, K}, title = {A quantitative approach to measure and predict microbiome response to antibiotics.}, journal = {mSphere}, volume = {9}, number = {9}, pages = {e0048824}, pmid = {39230261}, issn = {2379-5042}, support = {SAP # 4100068710//Pennsylvania Department of Health (PA DOH)/ ; //Children's Hospital of Philadelphia (CHOP)/ ; }, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology ; *Microbiota/drug effects/genetics ; *RNA, Ribosomal, 16S/genetics ; *Bacteria/drug effects/genetics/classification ; Gastrointestinal Microbiome/drug effects/genetics ; Metagenomics/methods ; Microbial Sensitivity Tests/methods ; Skin/microbiology ; Mouth/microbiology ; Software ; }, abstract = {UNLABELLED: Although antibiotics induce sizable perturbations in the human microbiome, we lack a systematic and quantitative method to measure and predict the microbiome's response to specific antibiotics. Here, we introduce such a method, which takes the form of a microbiome response index (MiRIx) for each antibiotic. Antibiotic-specific MiRIx values quantify the overall susceptibility of the microbiota to an antibiotic, based on databases of bacterial phenotypes and published data on intrinsic antibiotic susceptibility. We applied our approach to five published microbiome studies that carried out antibiotic interventions with vancomycin, metronidazole, ciprofloxacin, amoxicillin, and doxycycline. We show how MiRIx can be used in conjunction with existing microbiome analytical approaches to gain a deeper understanding of the microbiome response to antibiotics. Finally, we generate antibiotic response predictions for the oral, skin, and gut microbiome in healthy humans. Our approach is implemented as open-source software and is readily applied to microbiome data sets generated by 16S rRNA marker gene sequencing or shotgun metagenomics.<br><br>IMPORTANCE: Antibiotics are potent influencers of the human microbiome and can be a source for enduring dysbiosis and antibiotic resistance in healthcare. Existing microbiome data analysis methods can quantify perturbations of bacterial communities but cannot evaluate whether the differences are aligned with the expected activity of a specific antibiotic. Here, we present a novel method to quantify and predict antibiotic-specific microbiome changes, implemented in a ready-to-use software package. This has the potential to be a critical tool to broaden our understanding of the relationship between the microbiome and antibiotics.}, }
@article {pmid39227641, year = {2024}, author = {Donnelly, SC and Varela-Mattatall, GE and Hassan, S and Sun, Q and Gelman, N and Thiessen, JD and Thompson, RT and Prato, FS and Burton, JP and Goldhawk, DE}, title = {Bacterial association with metals enables in vivo monitoring of urogenital microbiota using magnetic resonance imaging.}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1079}, pmid = {39227641}, issn = {2399-3642}, support = {ALLRP576699-22//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en G&#xe9;nie du Canada)/ ; }, mesh = {Humans ; *Magnetic Resonance Imaging/methods ; *Microbiota ; Female ; Bacteria/metabolism/isolation &amp; purification ; Metals/metabolism ; Urogenital System/microbiology ; Manganese/metabolism/analysis ; }, abstract = {Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. Here we investigate longitudinal and transverse MRI relaxation rates and found significant differences between several bacterial strains. Common commensal strains of lactobacilli display notably high MRI relaxation rates, partially explained by elevated cellular manganese content, while other species contain more iron than manganese. Lactobacillus crispatus show particularly high values, 4-fold greater than any other species; up to 60-fold greater signal than relevant tissue background; and a linear relationship between relaxation rate and fraction of live cells. Different bacterial strains have detectable, repeatable MRI relaxation rates that in the future may enable monitoring of their persistence in the human body for enhanced molecular imaging.}, }
@article {pmid39226354, year = {2024}, author = {Chimileski, S and Borisy, GG and Dewhirst, FE and Mark Welch, JL}, title = {Tip extension and simultaneous multiple fission in a filamentous bacterium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {37}, pages = {e2408654121}, pmid = {39226354}, issn = {1091-6490}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; DE022586//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; 2245229//NSF | ENG | Division of Emerging Frontiers and Multidisciplinary Activities (EFMA)/ ; }, mesh = {*Peptidoglycan/metabolism ; Corynebacterium/metabolism/growth &amp; development ; Biofilms/growth &amp; development ; Cell Division ; Humans ; Dental Plaque/microbiology ; }, abstract = {Organisms display an immense variety of shapes, sizes, and reproductive strategies. At microscopic scales, bacterial cell morphology and growth dynamics are adaptive traits that influence the spatial organization of microbial communities. In one such community-the human dental plaque biofilm-a network of filamentous Corynebacterium matruchotii cells forms the core of bacterial consortia known as hedgehogs, but the processes that generate these structures are unclear. Here, using live-cell time-lapse microscopy and fluorescent D-amino acids to track peptidoglycan biosynthesis, we report an extraordinary example of simultaneous multiple division within the domain Bacteria. We show that C. matruchotii cells elongate at one pole through tip extension, similar to the growth strategy of soil-dwelling Streptomyces bacteria. Filaments elongate rapidly, at rates more than five times greater than other closely related bacterial species. Following elongation, many septa form simultaneously, and each cell divides into 3 to 14 daughter cells, depending on the length of the mother filament. The daughter cells then nucleate outgrowth of new thinner vegetative filaments, generating the classic "whip handle" morphology of this taxon. Our results expand the known diversity of bacterial cell cycles and help explain how this filamentous bacterium can compete for space, access nutrients, and form important interspecies interactions within dental plaque.}, }
@article {pmid39221598, year = {2024}, author = {Divakara, N and Dempsey, Z and Saraswati, C and Garssen, J and Silva, D and Keelan, JA and Christophersen, CT and Cooper, MN and Prescott, SL and Palmer, DJ and Verhasselt, V and Macchiaverni, P}, title = {Effect of maternal prebiotic supplementation on human milk immunological composition: Insights from the SYMBA study.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {35}, number = {9}, pages = {e14226}, doi = {10.1111/pai.14226}, pmid = {39221598}, issn = {1399-3038}, support = {RA/1/3027/386//WA Child Research Fund (WACRF)/ ; //Family Larsson-Rosenquist Foundation/ ; //National Health and Medical Research Council/ ; //Telethon Kids Institute Ascend Fellowship/ ; //Telethon-Perth Children's Hospital Research Fund/ ; //Paul Ramsay Foundation/ ; //Commonwealth Government of Australia/ ; //NHMRC Medical Research Future Fund (MRFF)/ ; }, mesh = {Humans ; *Milk, Human/immunology/chemistry ; *Prebiotics/administration &amp; dosage ; Female ; Double-Blind Method ; *Dietary Supplements ; Pregnancy ; Infant ; Adult ; Male ; Lactation/immunology ; Oligosaccharides/administration &amp; dosage ; Infant, Newborn ; Breast Feeding ; Cytokines/metabolism ; }, abstract = {BACKGROUND: Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM.<br><br>METHODS: The study was nested within the SYMBA double-blind randomized controlled trial (ACTRN12615001075572), which investigated the effects of maternal prebiotic (short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides) supplementation from <21&#x2009;weeks gestation during pregnancy until 6 months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n&#x2009;=&#x2009;46) or placebo (n&#x2009;=&#x2009;54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4, and 6&#x2009;months.<br><br>RESULTS: Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. At 2&#x2009;months, HM of prebiotic-supplemented women had decreased levels of TGF-&#x3b2;1 and TSLP (95% CI: -17.4 [-29.68, -2.28] and -57.32 [-94.22, -4.7] respectively) and increased levels of sCD14 (95% CI: 1.81 [0.17, 3.71]), when compared to the placebo group. At 4&#x2009;months, IgG1 was lower in the prebiotic group (95% CI: -1.55 [-3.55, -0.12]) compared to placebo group.<br><br>CONCLUSION: This exploratory study shows that prebiotic consumption by lactating mothers selectively alters specific immunomodulatory proteins in HM. This finding is crucial for understanding how prebiotic dietary recommendations for pregnant and lactating women can modify the immune properties of HM and potentially influence infant health outcomes through immune support from breastfeeding.}, }
@article {pmid39218882, year = {2024}, author = {Zhuang, Z and Lin, J and Wan, Z and Weng, J and Yuan, Z and Xie, Y and Liu, Z and Xie, P and Mao, S and Wang, Z and Wang, X and Huang, M and Luo, Y and Yu, H}, title = {Radiogenomic profiling of global DNA methylation associated with molecular phenotypes and immune features in glioma.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {352}, pmid = {39218882}, issn = {1741-7015}, mesh = {Humans ; *Glioma/genetics/immunology ; *DNA Methylation/genetics ; Female ; *Magnetic Resonance Imaging ; Male ; *Brain Neoplasms/genetics/diagnostic imaging/immunology/pathology ; Middle Aged ; Adult ; Machine Learning ; Phenotype ; Aged ; Biomarkers, Tumor/genetics ; }, abstract = {BACKGROUND: The radiogenomic analysis has provided valuable imaging biomarkers with biological insights for gliomas. The radiogenomic markers for molecular profile such as DNA methylation remain to be uncovered to assist the molecular diagnosis and tumor treatment.<br><br>METHODS: We apply the machine learning approaches to identify the magnetic resonance imaging (MRI) features that are associated with molecular profiles in 146 patients with gliomas, and the fitting models for each molecular feature (MoRad) are developed and validated. To provide radiological annotations for the molecular profiles, we devise two novel approaches called radiomic oncology (RO) and radiomic set enrichment analysis (RSEA).<br><br>RESULTS: The generated MoRad models perform well for profiling each molecular feature with radiomic features, including mutational, methylation, transcriptional, and protein profiles. Among them, the MoRad models have a remarkable performance in quantitatively mapping global DNA methylation. With RO and RSEA approaches, we find that global DNA methylation could be reflected by the heterogeneity in volumetric and textural features of enhanced regions in T2-weighted MRI. Finally, we demonstrate the associations of global DNA methylation with clinicopathological, molecular, and immunological features, including histological grade, mutations of IDH and ATRX, MGMT methylation, multiple methylation-high subtypes, tumor-infiltrating lymphocytes, and long-term survival outcomes.<br><br>CONCLUSIONS: Global DNA methylation is highly associated with radiological profiles in glioma. Radiogenomic global methylation is an imaging-based quantitative molecular biomarker that is associated with specific consensus molecular subtypes and immune features.}, }
@article {pmid39214080, year = {2024}, author = {Carlino, N and Blanco-Míguez, A and Punčochář, M and Mengoni, C and Pinto, F and Tatti, A and Manghi, P and Armanini, F and Avagliano, M and Barcenilla, C and Breselge, S and Cabrera-Rubio, R and Calvete-Torre, I and Coakley, M and Cobo-Díaz, JF and De Filippis, F and Dey, H and Leech, J and Klaassens, ES and Knobloch, S and O'Neil, D and Quijada, NM and Sabater, C and Skírnisdóttir, S and Valentino, V and Walsh, L and ,  and Alvarez-Ordóñez, A and Asnicar, F and Fackelmann, G and Heidrich, V and Margolles, A and Marteinsson, VT and Rota Stabelli, O and Wagner, M and Ercolini, D and Cotter, PD and Segata, N and Pasolli, E}, title = {Unexplored microbial diversity from 2,500 food metagenomes and links with the human microbiome.}, journal = {Cell}, volume = {187}, number = {20}, pages = {5775-5795.e15}, doi = {10.1016/j.cell.2024.07.039}, pmid = {39214080}, issn = {1097-4172}, mesh = {Humans ; *Metagenome/genetics ; *Gastrointestinal Microbiome/genetics ; Microbiota/genetics ; Food Microbiology ; Metagenomics/methods ; Bacteria/genetics/classification ; }, abstract = {Complex microbiomes are part of the food we eat and influence our own microbiome, but their diversity remains largely unexplored. Here, we generated the open access curatedFoodMetagenomicData (cFMD) resource by integrating 1,950 newly sequenced and 583 public food metagenomes. We produced 10,899 metagenome-assembled genomes spanning 1,036 prokaryotic and 108 eukaryotic species-level genome bins (SGBs), including 320 previously undescribed taxa. Food SGBs displayed significant microbial diversity within and between food categories. Extension to >20,000 human metagenomes revealed that food SGBs accounted on average for 3% of the adult gut microbiome. Strain-level analysis highlighted potential instances of food-to-gut transmission and intestinal colonization (e.g., Lacticaseibacillus paracasei) as well as SGBs with divergent genomic structures in food and humans (e.g., Streptococcus gallolyticus and Limosilactobabillus mucosae). The cFMD expands our knowledge on food microbiomes, their role in shaping the human microbiome, and supports future uses of metagenomics for food quality, safety, and authentication.}, }
@article {pmid39211550, year = {2024}, author = {Chung, RS and Wong, S and Lin, D and Kokot, NC and Sinha, UK and Han, AY}, title = {Mechanisms of crosstalk between the oropharyngeal microbiome and human papillomavirus in oropharyngeal carcinogenesis: a mini review.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1425545}, pmid = {39211550}, issn = {2234-943X}, abstract = {Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Notably, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is on the rise, accounting for 70% of all OPSCC cases. Persistent high-risk HPV infection is linked to various cancers, but HPV infection alone is not sufficient to cause cancer. Advances in next-generation sequencing have improved our understanding of changes in the human microbiome of cancerous environments. Yet, there remains a dearth of knowledge on the impact of HPV-microbiome crosstalk in HPV-positive OPSCC. In this review, we examine what is known about the oropharyngeal microbiome and the compositional shifts in this microbiome in HPV-positive OPSCC. We also review potential mechanisms of crosstalk between HPV and specific microorganisms. Additional research is needed to understand these interactions and their roles on cancer development and progression.}, }
@article {pmid39207108, year = {2024}, author = {Crouch, AL and Monsey, L and Rambeau, M and Ramos, C and Yracheta, JM and Anderson, MZ}, title = {Metagenomic discovery of microbial eukaryotes in stool microbiomes.}, journal = {mBio}, volume = {15}, number = {10}, pages = {e0206324}, pmid = {39207108}, issn = {2150-7511}, support = {//Ohio State University (OSU)/ ; 2046863//National Science Foundation (NSF)/ ; //Chan Zuckerberg Initiative (CZI)/ ; }, mesh = {Humans ; *Metagenomics/methods ; *Feces/microbiology ; *Eukaryota/genetics/classification/isolation &amp; purification ; Gastrointestinal Microbiome/genetics ; Metagenome ; Fungi/genetics/classification/isolation &amp; purification ; Sequence Analysis, DNA/methods ; Microbiota/genetics ; }, abstract = {Host-associated microbiota form complex microbial communities that are increasingly associated with host behavior and disease. While these microbes include bacterial, archaeal, viral, and eukaryotic constituents, most studies have focused on bacteria due to their dominance in the human host and available tools for investigation. Accumulating evidence suggests microbial eukaryotes in the microbiome play pivotal roles in host health, but our understandings of these interactions are limited to a few readily identifiable taxa because of technical limitations in unbiased eukaryote exploration. Here, we combined cell sorting, optimized eukaryotic cell lysis, and shotgun sequencing to accelerate metagenomic discovery and analysis of host-associated microbial eukaryotes. Using synthetic communities with a 1% microbial eukaryote representation, the eukaryote-optimized cell lysis and DNA recovery method alone yielded a 38-fold increase in eukaryotic DNA. Automated sorting of eukaryotic cells from stool samples of healthy adults increased the number of microbial eukaryote reads in metagenomic pools by up to 28-fold compared to commercial kits. Read frequencies for identified fungi increased by 10,000× on average compared to the Human Microbiome Project and allowed for the identification of novel taxa, de novo assembly of contigs from previously unknown microbial eukaryotes, and gene prediction from recovered genomic segments. These advances pave the way for the unbiased inclusion of microbial eukaryotes in deciphering determinants of health and disease in the host-associated microbiome.IMPORTANCEMicrobial eukaryotes are common constituents of the human gut where they can contribute to local ecology and host health, but they are often overlooked in microbiome studies. The lack of attention is due to current technical limitations that are heavily biased or poorly recovered DNA from microbial eukaryotes. We developed a method to increase the representation of these eukaryotes in metagenomic sequencing of microbiome samples that allows to improve their detection compared to prior methods and allows for the identification of new species. Application of the technique to gut microbiome samples improved detection of fungi, protists, and helminths. New eukaryotic taxa and their encoded genes could be identified by sequencing a small number of samples. This approach can improve the inclusion of eukaryotes into microbiome research.}, }
@article {pmid39206540, year = {2024}, author = {Walker, M and Federico, E and Espinoza, JL and Dupont, CL}, title = {Unveiling Molecular Diversity in Cerebral Thrombi via Spatial Transcriptomics.}, journal = {Stroke}, volume = {55}, number = {10}, pages = {e266-e268}, pmid = {39206540}, issn = {1524-4628}, support = {R01 AI170111/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Gene Expression Profiling ; *Intracranial Thrombosis/genetics ; *Transcriptome ; }, }
@article {pmid39206530, year = {2024}, author = {Gupta, CL and Jaganathasamy, N and Madkaikar, M}, title = {Microbiome in sickle cell disease: Pathophysiology and therapeutic insights.}, journal = {British journal of haematology}, volume = {205}, number = {4}, pages = {1279-1287}, doi = {10.1111/bjh.19736}, pmid = {39206530}, issn = {1365-2141}, mesh = {*Anemia, Sickle Cell/therapy/microbiology/complications/physiopathology ; Humans ; *Gastrointestinal Microbiome ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; }, abstract = {Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis. We explore how microbiome changes may contribute to vaso-occlusive crises and other complications, along with the possible associations of specific microbial taxa or markers with disease crises and clinical outcomes. Additionally, we discuss the potential of microbiome-targeted interventions, including probiotics, dietary modifications, and faecal microbiota transplantation, in managing SCD complications and improving patient outcomes. Understanding the intricate relationship between the microbiome and SCD could lead to innovative therapeutic strategies and personalized interventions for better managing the disease. This review underscores the importance of further microbiome research and its integration into holistic SCD care.}, }
@article {pmid39203520, year = {2024}, author = {Maslennikov, R and Benuni, N and Levshina, A and Adzhieva, F and Demina, T and Kucher, A and Pervushova, E and Yuryeva, E and Poluektova, E and Zolnikova, O and Kozlov, E and Sigidaev, A and Ivashkin, V}, title = {Effect of Saccharomyces boulardii on Liver Diseases: A Systematic Review.}, journal = {Microorganisms}, volume = {12}, number = {8}, pages = {}, pmid = {39203520}, issn = {2076-2607}, abstract = {We aimed to systematize the results of published studies on the use of Saccharomyces boulardii (SB) for the treatment of various liver disorders (CRD42022378050). Searches were conducted using PubMed and Scopus on 1 August 2022. The PubMed search was updated on 15 June 2024. The review included sixteen studies: ten experimental animal studies (EASs) and six randomized controlled trials (RCTs). The CNCM I-745 strain was used in 68.8% of the included studies. SB reduced the severity of many manifestations of cirrhosis, and lowered the Child-Pugh scores in RCT. SB reduced the serum concentrations of TNF-α, IL-1β, IL-6, and IL-4 in animals with metabolic dysfunction-associated steatotic liver disease (MASLD); lowered the serum TNF-α and IL-6 levels in experimental cirrhosis in rats; and reduced the CRP levels in decompensated cirrhosis. The EAS of MASLD revealed that SB reduced liver steatosis and inflammation and lowered the liver expression of genes of TNF-α, IL-1β, interferon-γ, and IL-10. In studies on experimental cirrhosis and MASLD, SB reduced the liver expression of genes of TGF-β, α-SMA, and collagen as well as liver fibrosis. SB reduced the abundance of Escherichia (Proteobacteria), increased the abundance of Bacteroidetes in the gut microbiota, prevented an increase in intestinal barrier permeability, and reduced bacterial translocation and endotoxemia.}, }
@article {pmid39203484, year = {2024}, author = {Węgrzyn, K and Jasińska, A and Janeczek, K and Feleszko, W}, title = {The Role of Postbiotics in Asthma Treatment.}, journal = {Microorganisms}, volume = {12}, number = {8}, pages = {}, pmid = {39203484}, issn = {2076-2607}, abstract = {In recent years, there has been abundant research concerning human microbiome and its impact on the host's health. Studies have shown that not only the commensal bacteria itself, but also postbiotics, understood as inanimate microorganisms, possibly with the presence of their components, may themselves have an effect on various elements of human physiology. In this review, we take a closer look at the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today's world and a serious subject of concern. Through altering patients' immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given the greatly promising findings in terms of their immunomodulating potential.}, }
@article {pmid39201629, year = {2024}, author = {Kim, JH and Seo, H and Kim, S and Rahim, MA and Jo, S and Barman, I and Tajdozian, H and Sarafraz, F and Song, HY and Song, YS}, title = {Different Prostatic Tissue Microbiomes between High- and Low-Grade Prostate Cancer Pathogenesis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {16}, pages = {}, pmid = {39201629}, issn = {1422-0067}, support = {RS-2024-00333544//National Research Foundation of Korea/ ; RS-2023-00219563//National Research Foundation of Korea/ ; Soonchunhyang University Research Fund//Soonchunhyang University/ ; }, mesh = {Male ; Humans ; *Prostatic Neoplasms/microbiology/pathology ; *Microbiota ; *Neoplasm Grading ; Bacteria/classification/genetics ; Prostate/microbiology/pathology ; Middle Aged ; Aged ; High-Throughput Nucleotide Sequencing ; Cell Proliferation ; Cell Line, Tumor ; }, abstract = {Numerous human pathologies, such as neoplasia, are related to particular bacteria and changes in microbiome constituents. To investigate the association between an imbalance of bacteria and prostate carcinoma, the microbiome and gene functionality from tissues of patients with high-grade prostate tumor (HGT) and low-grade prostate tumor (LGT) were compared utilizing next-generation sequencing (NGS) technology. The results showed abnormalities in the bacterial profiles between the HGT and LGT specimens, indicating alterations in the make-up of bacterial populations and gene functionalities. The HGT specimens showed higher frequencies of Cutibacterium, Pelomonas, and Corynebacterium genera than the LGT specimens. Cell proliferation and cytokine assays also showed a significant proliferation of prostate cancer cells and elevated cytokine levels in the cells treated with Cutibacterium, respectively, supporting earlier findings. In summary, the HGT and LGT specimens showed differences in bacterial populations, suggesting that different bacterial populations might characterize high-grade and low-grade prostate malignancies.}, }
@article {pmid39191760, year = {2024}, author = {Hartikainen, AK and Jalanka, J and Lahtinen, P and Ponsero, AJ and Mertsalmi, T and Finnegan, L and Crispie, F and Cotter, PD and Arkkila, P and Satokari, R}, title = {Fecal microbiota transplantation influences microbiota without connection to symptom relief in irritable bowel syndrome patients.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {73}, pmid = {39191760}, issn = {2055-5008}, support = {316338//Academy of Finland (Suomen Akatemia)/ ; 323156//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {*Irritable Bowel Syndrome/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; *RNA, Ribosomal, 16S/genetics ; Female ; Male ; Adult ; Treatment Outcome ; *Gastrointestinal Microbiome ; Middle Aged ; Feces/microbiology ; Metagenomics/methods ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {Imbalanced microbiota may contribute to the pathophysiology of irritable bowel syndrome (IBS), thus fecal microbiota transplantation (FMT) has been suggested as a potential treatment. Previous studies on the relationship between clinical improvement and microbiota after FMT have been inconclusive. In this study, we used 16S rRNA gene amplicon and shotgun metagenomics data from a randomized, placebo controlled FMT trial on 49 IBS patients to analyze changes after FMT in microbiota composition and its functional potential, and to identify connections between microbiota and patients' clinical outcome. As a result, we found that the successful modulation of microbiota composition and functional profiles by FMT from a healthy donor was not associated with the resolution of symptoms in IBS patients. Notably, a donor derived strain of Prevotella copri dominated the microbiota in those patients in the FMT group who had a low relative abundance of P. copri pre-FMT. The results highlight the multifactorial nature of IBS and the role of recipient's microbiota in the colonization of donor's strains.}, }
@article {pmid39188957, year = {2024}, author = {Xiang, B and Hu, J and Zhang, M and Zhi, M}, title = {The involvement of oral bacteria in inflammatory bowel disease.}, journal = {Gastroenterology report}, volume = {12}, number = {}, pages = {goae076}, pmid = {39188957}, issn = {2052-0034}, abstract = {Microorganisms play an important role in the pathogenesis of inflammatory bowel disease (IBD). The oral cavity, the second-largest microbial niche, is connected to the gastro-intestinal tract. Ectopic gut colonization by oral microbes is a signature of IBD. Current studies suggest that patients with IBD often report more oral manifestations and these oral issues are closely linked with disease activity. Murine studies have indicated that several oral microbes exacerbate intestinal inflammation. Moreover, intestinal inflammation can promote oral microbial dysbiosis and the migration of oral microbes to the gastro-intestinal tract. The reciprocal consequences of oral microbial dysbiosis and IBD, specifically through metabolic alterations, have not yet been elucidated. In this review, we summarize the relationship between oral bacteria and IBD from multiple perspectives, including clinical manifestations, microbial dysbiosis, and metabolic alterations, and find that oral pathogens increase anti-inflammatory metabolites and decrease inflammation-related metabolites.}, }
@article {pmid39172744, year = {2024}, author = {Cabrera, LE and Jokiranta, ST and Mäki, S and Miettinen, S and Kant, R and Kareinen, L and Sironen, T and Pietilä, JP and Kantele, A and Kekäläinen, E and Lindgren, H and Mattila, P and Kipar, A and Vapalahti, O and Strandin, T}, title = {The assembly of neutrophil inflammasomes during COVID-19 is mediated by type I interferons.}, journal = {PLoS pathogens}, volume = {20}, number = {8}, pages = {e1012368}, pmid = {39172744}, issn = {1553-7374}, mesh = {*COVID-19/immunology ; Humans ; *Neutrophils/immunology/metabolism ; *Interferon Type I/metabolism/immunology ; *Inflammasomes/immunology/metabolism ; Animals ; *SARS-CoV-2/immunology ; Mice ; Male ; Female ; Middle Aged ; Immunity, Innate ; Adult ; Mice, Inbred C57BL ; }, abstract = {The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from SARS-CoV-2 infected mice, in comparison to non-infected healthy controls. In addition, we investigated the inflammasome formation potential in neutrophils from patients and mice upon SARS-CoV-2 infection. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. Notably, low-density granulocytes (LDGs) from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. Moreover, PMNs from severe COVID-19 patients showed heightened nigericin-induced caspase1 activation, but reduced responsiveness to exogenous inflammasome priming. Furthermore, IFN-I emerged as a priming stimulus for neutrophil inflammasomes. These findings suggest a potential role for neutrophil inflammasomes in driving inflammation during severe COVID-19. Altogether, these findings open promising avenues for targeted therapeutic interventions to mitigate the pathological processes associated with the disease.}, }
@article {pmid39163860, year = {2024}, author = {Torres, MDT and Brooks, EF and Cesaro, A and Sberro, H and Gill, MO and Nicolaou, C and Bhatt, AS and de la Fuente-Nunez, C}, title = {Mining human microbiomes reveals an untapped source of peptide antibiotics.}, journal = {Cell}, volume = {187}, number = {19}, pages = {5453-5467.e15}, doi = {10.1016/j.cell.2024.07.027}, pmid = {39163860}, issn = {1097-4172}, mesh = {Humans ; Animals ; Mice ; *Anti-Bacterial Agents/pharmacology ; *Microbiota/drug effects ; *Antimicrobial Peptides/pharmacology/chemistry ; Metagenome ; Female ; Open Reading Frames ; Bacteria/drug effects/genetics/classification ; Prevotella/drug effects ; }, abstract = {Drug-resistant bacteria are outpacing traditional antibiotic discovery efforts. Here, we computationally screened 444,054 previously reported putative small protein families from 1,773 human metagenomes for antimicrobial properties, identifying 323 candidates encoded in small open reading frames (smORFs). To test our computational predictions, 78 peptides were synthesized and screened for antimicrobial activity in vitro, with 70.5% displaying antimicrobial activity. As these compounds were different compared with previously reported antimicrobial peptides, we termed them smORF-encoded peptides (SEPs). SEPs killed bacteria by targeting their membrane, synergizing with each other, and modulating gut commensals, indicating a potential role in reconfiguring microbiome communities in addition to counteracting pathogens. The lead candidates were anti-infective in both murine skin abscess and deep thigh infection models. Notably, prevotellin-2 from Prevotella copri presented activity comparable to the commonly used antibiotic polymyxin B. Our report supports the existence of hundreds of antimicrobials in the human microbiome amenable to clinical translation.}, }
@article {pmid39160377, year = {2024}, author = {Li, Q and Liu, D and Liang, M and Zhu, Y and Yousaf, M and Wu, Y}, title = {Mechanism of probiotics in the intervention of colorectal cancer: a review.}, journal = {World journal of microbiology &amp; biotechnology}, volume = {40}, number = {10}, pages = {306}, pmid = {39160377}, issn = {1573-0972}, mesh = {*Probiotics/therapeutic use ; Humans ; *Colorectal Neoplasms/microbiology/prevention &amp; control/therapy ; *Gastrointestinal Microbiome ; Apoptosis ; Animals ; Bacteria/metabolism ; }, abstract = {The human microbiome interacts with the host mainly in the intestinal lumen, where putrefactive bacteria are suggested to promote colorectal cancer (CRC). In contrast, probiotics and their isolated components and secreted substances, display anti-tumor properties due to their ability to modulate gut microbiota composition, promote apoptosis, enhance immunity, resist oxidation and alter metabolism. Probiotics help to form a solid intestinal barrier against damaging agents via altering the gut microbiota and preventing harmful microbes from colonization. Probiotic strains that specifically target essential proteins involved in the process of apoptosis can overcome CRC resistance to apoptosis. They can increase the production of anti-inflammatory cytokines, essential in preventing carcinogenesis, and eliminate cancer cells by activating T cell-mediated immune responses. There is a clear indication that probiotics optimize the antioxidant system, decrease radical generation, and detect and degrade potential carcinogens. In this review, the pathogenic mechanisms of pathogens in CRC and the recent insights into the mechanism of probiotics in CRC prevention and therapy are discussed to provide a reference for the actual application of probiotics in CRC.}, }
@article {pmid39152482, year = {2024}, author = {Luo, W and Zhao, M and Dwidar, M and Gao, Y and Xiang, L and Wu, X and Medema, MH and Xu, S and Li, X and Schäfer, H and Chen, M and Feng, R and Zhu, Y}, title = {Microbial assimilatory sulfate reduction-mediated H2S: an overlooked role in Crohn's disease development.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {152}, pmid = {39152482}, issn = {2049-2618}, support = {82370551//National Natural Science Foundation of China/ ; 82270579//National Natural Science Foundation of China/ ; 82100577//National Natural Science Foundation of China/ ; 2024GXNSFFA010009//Natural Science Foundation of Guangxi Zhuang Autonomous Region/ ; }, mesh = {*Crohn Disease/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Hydrogen Sulfide/metabolism ; Animals ; Mice ; *Sulfates/metabolism ; Escherichia coli/genetics/metabolism ; Feces/microbiology ; Dysbiosis/microbiology ; Colon/microbiology ; Metagenomics ; Oxidation-Reduction ; Disease Models, Animal ; Female ; }, abstract = {BACKGROUND: H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota.<br><br>RESULTS: Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants &#x2206;cysJ and &#x2206;cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives.<br><br>CONCLUSIONS: Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract.}, }
@article {pmid39148051, year = {2024}, author = {Zhu, H and Hao, H and Yu, L}, title = {Identification of microbe-disease signed associations via multi-scale variational graph autoencoder based on signed message propagation.}, journal = {BMC biology}, volume = {22}, number = {1}, pages = {172}, pmid = {39148051}, issn = {1741-7007}, support = {62072353//National Natural Science Foundation of China/ ; 62272065//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Microbiota ; Computational Biology/methods ; Algorithms ; Disease ; }, abstract = {BACKGROUND: Plenty of clinical and biomedical research has unequivocally highlighted the tremendous significance of the human microbiome in relation to human health. Identifying microbes associated with diseases is crucial for early disease diagnosis and advancing precision medicine.<br><br>RESULTS: Considering that the information about changes in microbial quantities under fine-grained disease states helps to enhance a comprehensive understanding of the overall data distribution, this study introduces MSignVGAE, a framework for predicting microbe-disease sign associations using signed message propagation. MSignVGAE employs a graph variational autoencoder to model noisy signed association data and extends the multi-scale concept to enhance representation capabilities. A novel strategy for propagating signed message in signed networks addresses heterogeneity and consistency among nodes connected by signed edges. Additionally, we utilize the idea of denoising autoencoder to handle the noise in similarity feature information, which helps overcome biases in the fused similarity data. MSignVGAE represents microbe-disease associations as a heterogeneous graph using similarity information as node features. The multi-class classifier XGBoost is utilized to predict sign associations between diseases and microbes.<br><br>CONCLUSIONS: MSignVGAE achieves AUROC and AUPR values of 0.9742 and 0.9601, respectively. Case studies on three diseases demonstrate that MSignVGAE can effectively capture a comprehensive distribution of associations by leveraging signed information.}, }
@article {pmid39146817, year = {2025}, author = {Caukwell, J and Assenza, S and Hassan, KA and Neilan, BA and Clulow, AJ and Salvati Manni, L and Fong, WK}, title = {Lipidic drug delivery systems are responsive to the human microbiome.}, journal = {Journal of colloid and interface science}, volume = {677}, number = {Pt B}, pages = {293-302}, doi = {10.1016/j.jcis.2024.07.216}, pmid = {39146817}, issn = {1095-7103}, mesh = {Humans ; *Staphylococcus aureus/drug effects ; *Microbiota/drug effects ; *Drug Delivery Systems ; Glycerides/chemistry ; Drug Liberation ; Lipids/chemistry ; Nanostructures/chemistry ; Drug Carriers/chemistry ; Particle Size ; }, abstract = {In vitro and in vivo tests for therapeutic agents are typically conducted in sterile environments, but many target areas for drug delivery are home to thousands of microbial species. Here, we examine the behaviour of lipidic nanomaterials after exposure to representative strains of four bacterial species found in the gastrointestinal tract and skin. Small angle X-ray scattering measurements show that the nanostructure of monoolein cubic and inverse hexagonal phases are transformed, respectively, into inverse hexagonal and inverse micellar cubic phases upon exposure to a strain of live Staphylococcus aureus often present on skin and mucosa. Further investigation demonstrates that enzymatic hydrolysis and cell membrane lipid transfer are both likely responsible for this effect. The structural responses to S. aureus are rapid and significantly reduce the rate of drug release from monoolein-based nanomaterials. These findings are the first to demonstrate how a key species in the live human microbiome can trigger changes in the structure and drug release properties of lipidic nanomaterials. The effect appears to be strain specific, varies from patient to patient and body region to body region, and is anticipated to affect the bioapplication of monoglyceride-based formulations.}, }
@article {pmid39146797, year = {2024}, author = {Castells-Nobau, A and Mayneris-Perxachs, J and Fernández-Real, JM}, title = {Unlocking the mind-gut connection: Impact of human microbiome on cognition.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {8}, pages = {1248-1263}, doi = {10.1016/j.chom.2024.07.019}, pmid = {39146797}, issn = {1934-6069}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Cognition/physiology ; *Brain-Gut Axis/physiology ; Brain/physiology/microbiology ; Bacteria ; Metabolic Diseases/microbiology ; }, abstract = {This perspective explores the current understanding of the gut microbiota's impact on cognitive function in apparently healthy humans and in individuals with metabolic disease. We discuss how alterations in gut microbiota can influence cognitive processes, focusing not only on bacterial composition but also on often overlooked components of the gut microbiota, such as bacteriophages and eukaryotes, as well as microbial functionality. We examine the mechanisms through which gut microbes might communicate with the central nervous system, highlighting the complexity of these interactions. We provide a comprehensive overview of the emerging field of microbiota-gut-brain interactions and its significance for cognitive health. Additionally, we summarize novel therapeutic strategies designed to promote cognitive resilience and reduce the risk of cognitive disorders, focusing on interventions that target the gut microbiota. An in-depth understanding of the microbiome-brain axis is imperative for developing innovative treatments aimed at improving cognitive health.}, }
@article {pmid39143108, year = {2024}, author = {Grahnemo, L and Kambur, O and Lahti, L and Jousilahti, P and Niiranen, T and Knight, R and Salomaa, V and Havulinna, AS and Ohlsson, C}, title = {Associations between gut microbiota and incident fractures in the FINRISK cohort.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {69}, pmid = {39143108}, issn = {2055-5008}, support = {NNF 190C0055250 and 22OC0078421//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; KAW 2015.0317//Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation)/ ; 101096347/ERC_/European Research Council/International ; LU2021-0096//IngaBritt och Arne Lundbergs Forskningsstiftelse (Ingabritt and Arne Lundberg Research Foundation)/ ; 2020-01392//Vetenskapsr&#xe5;det (Swedish Research Council)/ ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; Male ; Female ; *Fractures, Bone/microbiology/epidemiology/etiology ; Middle Aged ; Finland/epidemiology ; Aged ; Bacteria/classification/genetics/isolation &amp; purification ; Metagenome ; Cohort Studies ; Incidence ; Metagenomics/methods ; Proteobacteria/genetics/isolation &amp; purification ; Risk Factors ; Adult ; }, abstract = {The gut microbiota (GM) can regulate bone mass, but its association with incident fractures is unknown. We used Cox regression models to determine whether the GM composition is associated with incident fractures in the large FINRISK 2002 cohort (n = 7043, 1092 incident fracture cases, median follow-up time 18 years) with information on GM composition and functionality from shotgun metagenome sequencing. Higher alpha diversity was associated with decreased fracture risk (hazard ratio [HR] 0.92 per standard deviation increase in Shannon index, 95% confidence interval 0.87-0.96). For beta diversity, the first principal component was associated with fracture risk (Aitchison distance, HR 0.90, 0.85-0.96). In predefined phyla analyses, we observed that the relative abundance of Proteobacteria was associated with increased fracture risk (HR 1.14, 1.07-1.20), while the relative abundance of Tenericutes was associated with decreased fracture risk (HR 0.90, 0.85-0.96). Explorative sub-analyses within the Proteobacteria phylum showed that higher relative abundance of Gammaproteobacteria was associated with increased fracture risk. Functionality analyses showed that pathways related to amino acid metabolism and lipopolysaccharide biosynthesis associated with fracture risk. The relative abundance of Proteobacteria correlated with pathways for amino acid metabolism, while the relative abundance of Tenericutes correlated with pathways for butyrate synthesis. In conclusion, the overall GM composition was associated with incident fractures. The relative abundance of Proteobacteria, especially Gammaproteobacteria, was associated with increased fracture risk, while the relative abundance of Tenericutes was associated with decreased fracture risk. Functionality analyses demonstrated that pathways known to regulate bone health may underlie these associations.}, }
@article {pmid39139405, year = {2024}, author = {Attaye, I and Witjes, JJ and Koopen, AM and van der Vossen, EWJ and Zwirs, D and Wortelboer, K and Collard, D and Kemper, EM and Winkelmeijer, M and Holst, JJ and Hazen, SL and Kuipers, F and Stroes, ESG and Groen, AK and de Vos, WM and Nieuwdorp, M and Herrema, H}, title = {Oral Anaerobutyricum soehngenii augments glycemic control in type 2 diabetes.}, journal = {iScience}, volume = {27}, number = {8}, pages = {110455}, pmid = {39139405}, issn = {2589-0042}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; }, abstract = {This randomized, double-blind, placebo-controlled trial investigated the impact of 14-day Anaerobutyricum soehngenii L2-7 supplementation on postprandial glucose levels in 25 White Dutch males with type 2 diabetes (T2D) on stable metformin therapy. The primary endpoint was the effect of A. soehngenii versus placebo on glucose excursions and variability as determined by continuous glucose monitoring. Secondary endpoints were changes in ambulatory 24-h blood pressure, incretins, circulating metabolites and excursions of plasma short-chain fatty acids (SCFAs) and bile acids upon a standardized meal. Results showed that A. soehngenii supplementation for 14 days significantly improved glycemic variability and mean arterial blood pressure, without notable changes in SCFAs, bile acids, incretin levels, or anthropometric parameters as compared to placebo-treated controls. Although well-tolerated and effective in improving glycemic control in the intervention group, further research in larger and more diverse populations is needed to generalize these findings.}, }
@article {pmid39137463, year = {2024}, author = {Fang, Q and Qiu, T and Ye, T and Feng, Z and Tian, X and Cao, Y and Bai, J and Liu, Y}, title = {Prenatal ozone exposure and variations of the gut microbiome: Evidence from a Chinese mother-infant cohort.}, journal = {Ecotoxicology and environmental safety}, volume = {283}, number = {}, pages = {116861}, doi = {10.1016/j.ecoenv.2024.116861}, pmid = {39137463}, issn = {1090-2414}, mesh = {Humans ; *Ozone/toxicity ; *Gastrointestinal Microbiome/drug effects ; Female ; Pregnancy ; China ; Cohort Studies ; Adult ; Infant, Newborn ; *Maternal Exposure/adverse effects ; *Prenatal Exposure Delayed Effects/microbiology ; Air Pollutants/toxicity ; Infant ; Male ; Child, Preschool ; RNA, Ribosomal, 16S/genetics ; East Asian People ; }, abstract = {BACKGROUND: The gut microbiome is central to human health, but the potential impact of ozone (O3) exposure on its establishment in early life has not been thoroughly examined. Therefore, this study aimed to investigate the relationship between prenatal O3 exposure and the variations of the human gut microbiome during the first two years of life.<br><br>DESIGN: A cohort study design was used. Pregnant women in the third trimester were recruited from an obstetric clinic, and long-term follow-ups were conducted after delivery. The gut microbiome was analyzed using the 16&#x202f;S rRNA V3-V4 gene regions. Functional pathway analyses of gut microbial communities in neonates were performed using Tax4fun. The average concentrations of ambient O3 and other air pollutants from pregnancy to delivery were calculated using the China High Air Pollutants (CHAP) dataset, based on the permanent residential addresses of participants. Multiple linear regression and mixed linear models were utilized to investigate the associations between prenatal O3 exposure and gut microbiome features.<br><br>RESULTS: Prenatal O3 exposure did not significantly affect the gut microbial alpha diversity of mothers and neonates. However, it was found to be positively associated with the gut microbial alpha diversity in 24-month-old infants. Prenatal O3 exposure explained 13.1&#x202f;% of the variation in neonatal gut microbial composition. After controlling for potential covariates, prenatal O3 exposure was associated with neonatal-specific gut microbial taxa and functional pathways. Furthermore, the mixed linear models showed that prenatal O3 exposure was negatively associated with variations of Streptococcus (p-value = 0.001, q-value = 0.005), Enterococcus (p-value = 0.001, q-value = 0.005), Escherichia-Shigella (p-value = 0.010, q-value = 0.025), and Bifidobacterium (p-value = 0.003, q-value = 0.010).<br><br>CONCLUSIONS: This study is the first to examine the effects of prenatal O3 exposure on gut microbial homeostasis and variations. It demonstrates that prenatal O3 exposure is associated with variations in certain aspects of the gut microbiome. These findings provide novel insights into the dynamics and establishment of the human microbiome during the first two years of life.}, }
@article {pmid39125810, year = {2024}, author = {Rezzani, R and Favero, G and Cominelli, G and Pinto, D and Rinaldi, F}, title = {Skin Aging and the Upcoming Role of Ferroptosis in Geroscience.}, journal = {International journal of molecular sciences}, volume = {25}, number = {15}, pages = {}, pmid = {39125810}, issn = {1422-0067}, mesh = {*Ferroptosis ; Humans ; *Skin Aging ; Iron/metabolism ; Animals ; Skin/metabolism/pathology ; Aging/metabolism ; Geriatrics ; }, abstract = {The skin is considered the most important organ system in mammals, and as the population ages, it is important to consider skin aging and anti-aging therapeutic strategies. Exposure of the skin to various insults induces significant changes throughout our lives, differentiating the skin of a young adult from that of an older adult. These changes are caused by a combination of intrinsic and extrinsic aging. We report the interactions between skin aging and its metabolism, showing that the network is due to several factors. For example, iron is an important nutrient for humans, but its level increases with aging, inducing deleterious effects on cellular functions. Recently, it was discovered that ferroptosis, or iron-dependent cell death, is linked to aging and skin diseases. The pursuit of new molecular targets for ferroptosis has recently attracted attention. Prevention of ferroptosis is an effective therapeutic strategy for the treatment of diseases, especially in old age. However, the pathological and biological mechanisms underlying ferroptosis are still not fully understood, especially in skin diseases such as melanoma and autoimmune diseases. Only a few basic studies on regulated cell death exist, and the challenge is to turn the studies into clinical applications.}, }
@article {pmid39122010, year = {2024}, author = {Hashimoto, Y and Ishigami, K and Hassaninasab, A and Kishi, K and Kumano, T and Kobayashi, M}, title = {Curcumin degradation in a soil microorganism: Screening and characterization of a β-diketone hydrolase.}, journal = {The Journal of biological chemistry}, volume = {300}, number = {9}, pages = {107647}, pmid = {39122010}, issn = {1083-351X}, mesh = {*Curcumin/metabolism/analogs &amp; derivatives/chemistry ; *Soil Microbiology ; *Rhodococcus/enzymology/genetics/metabolism ; Humans ; Bacterial Proteins/metabolism/genetics/chemistry ; Hydrolases/metabolism/chemistry/genetics ; Ketones/metabolism/chemistry ; Substrate Specificity ; }, abstract = {Curcumin is a plant-derived secondary metabolite exhibiting antitumor, neuroprotective, antidiabetic activities, and so on. We previously isolated Escherichia coli as an enterobacterium exhibiting curcumin-converting activity from human feces, and discovered an enzyme showing this activity (CurA) and named it NADPH-dependent curcumin/dihydrocurcumin reductase. From soil, here, we isolated a curcumin-degrading microorganism (No. 34) using the screening medium containing curcumin as the sole carbon source and identified as Rhodococcus sp. A curcumin-degrading enzyme designated as CurH was purified from this strain and characterized, and compared with CurA. CurH catalyzed hydrolytic cleavage of a carbon-carbon bond in the β-diketone moiety of curcumin and its analogs, yielding two products bearing a methyl ketone terminus and a carboxylic acid terminus, respectively. These findings demonstrated that a curcumin degradation reaction catalyzed by CurH in the soil environment was completely different from the one catalyzed by CurA in the human microbiome. Of all the curcumin analogs tested, suitable substrates for the enzyme were curcuminoids (i.e., curcumin and bisdemethoxycurcumin) and tetrahydrocurcuminoids. Thus, we named this enzyme curcuminoid hydrolase. The deduced amino acid sequence of curH exhibited similarity to those of members of acetyl-CoA C-acetyltransferase family. Considering results of oxygen isotope analyses and a series of site-directed mutagenesis experiments on our enzyme, we propose a possible catalytic mechanism of CurH, which is unique and distinct from those of enzymes degrading β-diketone moieties such as β-diketone hydrolases known so far.}, }
@article {pmid39119866, year = {2024}, author = {Schweitzer, M and Wlasak, M and Wassermann, B and Marcher, F and Poglitsch, C and Pirker, J and Berg, G}, title = {'Tiny Biome Tales': A gamified review about the influence of lifestyle choices on the human microbiome.}, journal = {Microbial biotechnology}, volume = {17}, number = {8}, pages = {e14544}, pmid = {39119866}, issn = {1751-7915}, support = {//Federal Ministry of Education, Science and Research, Austria/ ; }, mesh = {Humans ; *Microbiota ; *Video Games ; *Life Style ; Female ; Pregnancy ; Adult ; }, abstract = {In the last two decades, new discoveries from microbiome research have changed our understanding of human health. It became evident that daily habits and lifestyle choices shape the human microbiome and ultimately determine health or disease. Therefore, we developed 'Tiny Biome Tales' (https://microbiome.gamelabgraz.at/), a science pedagogy video game designed like a scientific review based exclusively on peer-reviewed articles, to teach about the influence of lifestyle choices on the human microbiome during pregnancy, early and adult life, and related health consequences. Despite the scientific character, it can be played by a broad audience. Here, we also present a scientific assessment and showed that playing the game significantly contributed to knowledge gain. The innovative style of the 'gamified review' represents an ideal platform to disseminate future findings from microbiome research by updating existing and adding new scenes to the game.}, }
@article {pmid39114281, year = {2024}, author = {Manske, S}, title = {The Microbiome: A Foundation for Integrative Medicine.}, journal = {Integrative medicine (Encinitas, Calif.)}, volume = {23}, number = {3}, pages = {28-31}, pmid = {39114281}, issn = {1546-993X}, abstract = {CONTEXT: No organ system better integrates interconnectivity across specialties and disciplines than the microbiome. Scientific focus is shifting from microbes as harbingers of disease toward microbes as symbiotic, balanced, commensal ecologies.<br><br>OBJECTIVE: The study intended to discuss and examine the human microbiome, including its development in early life; its impact on various physiological processes that occur throughout the body; and its relationship to dysbiosis; and to investigate microbial mechanisms with clinical applicability across medical specialties.<br><br>SETTING: The study took place at Biocidin Botanicals in Watsonville CA, USA.<br><br>RESULTS: Accumulating research upholds the human microbiome as both a predictive biomarker for disease risk and a viable treatment option for modulating the course of illness. Prebiotic and probiotic interventions continue to demonstrate clinical utility, particularly for gastrointestinal, dermatological, inflammatory, metabolic, and mental-health disorders.<br><br>CONCLUSIONS: Just as germ theory revolutionized infection control in the twentieth century, microbiome systems science stands to transform the conceptualization of health as the balanced coexistence of human and microbial cells in the twenty-first century.}, }
@article {pmid39113194, year = {2024}, author = {Tae, IH and Lee, J and Kang, Y and Lee, JM and Park, K and Yang, H and Kim, HW and Ko, JH and Park, DS and Kim, DS and Son, MY and Cho, HS}, title = {Induction of Cell Death by Bifidobacterium infantis DS1685 in Colorectal and Breast Cancers via SMAD4/TGF-Beta Activation.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {8}, pages = {1698-1704}, pmid = {39113194}, issn = {1738-8872}, mesh = {Humans ; *Smad4 Protein/metabolism/genetics ; *Breast Neoplasms/pathology/metabolism ; *Colorectal Neoplasms/microbiology/pathology ; Cell Line, Tumor ; *Transforming Growth Factor beta/metabolism ; *Bifidobacterium longum subspecies infantis/metabolism/genetics ; Female ; Cell Death/drug effects ; Cell Proliferation/drug effects ; Probiotics ; Antineoplastic Agents/pharmacology ; }, abstract = {Therapeutic advancements in treatments for cancer, a leading cause of mortality worldwide, have lagged behind the increasing incidence of this disease. There is a growing interest in multifaceted approaches for cancer treatment, such as chemotherapy, targeted therapy, and immunotherapy, but due to their low efficacy and severe side effects, there is a need for the development of new cancer therapies. Recently, the human microbiome, which is comprised of various microorganisms, has emerged as an important research field due to its potential impact on cancer treatment. Among these microorganisms, Bifidobacterium infantis has been shown to significantly improve the efficacy of various anticancer drugs. However, research on the role of B. infantis in cancer treatment remains insufficient. Thus, in this study, we explored the anticancer effect of treatment with B. infantis DS1685 supernatant (BI sup) in colorectal and breast cancer cell lines. Treatment with BI sup induced SMAD4 expression to suppress cell growth in colon and breast cancer cells. Furthermore, a decrease in tumor cohesion was observed through the disruption of the regulation of EMT-related genes by BI sup in 3D spheroid models. Based on these findings, we anticipate that BI sup could play an adjunctive role in cancer therapy, and future cotreatment of BI sup with various anticancer drugs may lead to synergistic effects in cancer treatment.}, }
@article {pmid39113097, year = {2024}, author = {Gray, SM and Moss, AD and Herzog, JW and Kashiwagi, S and Liu, B and Young, JB and Sun, S and Bhatt, AP and Fodor, AA and Balfour Sartor, R}, title = {Mouse adaptation of human inflammatory bowel diseases microbiota enhances colonization efficiency and alters microbiome aggressiveness depending on the recipient colonic inflammatory environment.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {147}, pmid = {39113097}, issn = {2049-2618}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; NSF Cooperative Agreement No. EEC-2133504//The Engineering Research Centers Program of the National Science Foundation/ ; T32DK007737//NIH/NIDDK/ ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases/microbiology ; *Disease Models, Animal ; *Dysbiosis/microbiology ; *Interleukin-10/genetics ; Colitis/microbiology ; Feces/microbiology ; Colon/microbiology ; Mice, Knockout ; Mice, Inbred C57BL ; Female ; Bacteria/classification/genetics/isolation &amp; purification ; Inflammation ; Male ; }, abstract = {BACKGROUND: Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis.<br><br>RESULTS: Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10[-/-] mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10[-/-] mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10[-/-] host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10[-/-] mice than the distinct microbiota reassembled in non-inflamed WT hosts.<br><br>CONCLUSIONS: Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer. Video Abstract.}, }
@article {pmid39110597, year = {2024}, author = {Fu, Y and Yu, S and Li, J and Lao, Z and Yang, X and Lin, Z}, title = {DeepMineLys: Deep mining of phage lysins from human microbiome.}, journal = {Cell reports}, volume = {43}, number = {8}, pages = {114583}, doi = {10.1016/j.celrep.2024.114583}, pmid = {39110597}, issn = {2211-1247}, mesh = {Humans ; *Microbiota ; *Bacteriophages/genetics/metabolism ; Data Mining ; Viral Proteins/metabolism ; Neural Networks, Computer ; Animals ; Muramidase/metabolism ; Escherichia coli/genetics/metabolism ; }, abstract = {Vast shotgun metagenomics data remain an underutilized resource for novel enzymes. Artificial intelligence (AI) has increasingly been applied to protein mining, but its conventional performance evaluation is interpolative in nature, and these trained models often struggle to extrapolate effectively when challenged with unknown data. In this study, we present a framework (DeepMineLys [deep mining of phage lysins from human microbiome]) based on the convolutional neural network (CNN) to identify phage lysins from three human microbiome datasets. When validated with an independent dataset, our method achieved an F1-score of 84.00%, surpassing existing methods by 20.84%. We expressed 16 lysin candidates from the top 100 sequences in E. coli, confirming 11 as active. The best one displayed an activity 6.2-fold that of lysozyme derived from hen egg white, establishing it as the most potent lysin from the human microbiome. Our study also underscores several important issues when applying AI to biology questions. This framework should be applicable for mining other proteins.}, }
@article {pmid39109977, year = {2024}, author = {Xiao, Y and Louwies, T and Mars, RAT and Kashyap, PC}, title = {The Human Microbiome-A Physiologic Perspective.}, journal = {Comprehensive Physiology}, volume = {14}, number = {3}, pages = {5491-5519}, doi = {10.1002/cphy.c230013}, pmid = {39109977}, issn = {2040-4603}, mesh = {Humans ; *Microbiota/physiology ; Gastrointestinal Microbiome/physiology ; }, abstract = {The human microbiome consists of the microorganisms associated with the body, such as bacteria, fungi, archaea, protozoa, and viruses, along with their gene content and products. These microbes are abundant in the digestive, respiratory, renal/urinary, and reproductive systems. While microbes found in other organs/tissues are often associated with diseases, some reports suggest their presence even in healthy individuals. Lack of microbial colonization does not indicate a lack of microbial influence, as their metabolites can affect distant locations through circulation. In a healthy state, these microbes maintain a mutualistic relationship and help shape the host's physiological functions. Unlike the host's genetic content, microbial gene content and expression are dynamic and influenced by factors such as ethnicity, genetic background, sex, age, lifestyle/diet, and psychological/physical conditions. Therefore, defining a healthy microbiome becomes challenging as it is context dependent and can vary over time for an individual. Although differences in microbial composition have been observed in various diseases, these changes may reflect host alterations rather than causing the disease itself. As the field is evolving, there is increased emphasis on understanding when changes in the microbiome are an important component of pathogenesis rather than the consequence of a disease state. This article focuses on the microbial component in the digestive and respiratory tracts-the primary sites colonized by microorganisms-and the physiological functions of microbial metabolites in these systems. It also discusses their physiological functions in the central nervous and cardiovascular systems, which have no microorganism colonization under healthy conditions based on human studies. © 2024 American Physiological Society. Compr Physiol 14:5491-5519, 2024.}, }
@article {pmid39107044, year = {2025}, author = {Trepka, KR and Olson, CA and Upadhyay, V and Zhang, C and Turnbaugh, PJ}, title = {Pharma[e]cology: How the Gut Microbiome Contributes to Variations in Drug Response.}, journal = {Annual review of pharmacology and toxicology}, volume = {65}, number = {1}, pages = {355-373}, pmid = {39107044}, issn = {1545-4304}, support = {K08 HL165106/HL/NHLBI NIH HHS/United States ; R01 CA255116/CA/NCI NIH HHS/United States ; R01 DK114034/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; R01 AR074500/AR/NIAMS NIH HHS/United States ; T32 GM007618/GM/NIGMS NIH HHS/United States ; R01 AT011117/AT/NCCIH NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Animals ; Pharmaceutical Preparations/metabolism/administration &amp; dosage ; Neoplasms/drug therapy/microbiology ; Heart Diseases/drug therapy/microbiology ; Nervous System Diseases/drug therapy/microbiology ; }, abstract = {Drugs represent our first, and sometimes last, line of defense for many diseases, yet despite decades of research we still do not fully understand why a given drug works in one patient and fails in the next. The human gut microbiome is one of the missing puzzle pieces, due to its ability to parallel and extend host pathways for drug metabolism, along with more complex host-microbiome interactions. Herein, we focus on the well-established links between the gut microbiome and drugs for heart disease and cancer, plus emerging data on neurological disease. We highlight the interdisciplinary methods that are available and how they can be used to address major remaining knowledge gaps, including the consequences of microbial drug metabolism for treatment outcomes. Continued progress in this area promises fundamental biological insights into humans and their associated microbial communities and strategies for leveraging the microbiome to improve the practice of medicine.}, }
@article {pmid39102545, year = {2024}, author = {Duncan, RP and Moustafa, DA and Lewin, GR and Diggle, FL and Bomberger, JM and Whiteley, M and Goldberg, JB}, title = {Improvement of a mouse infection model to capture Pseudomonas aeruginosa chronic physiology in cystic fibrosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {33}, pages = {e2406234121}, pmid = {39102545}, issn = {1091-6490}, support = {K99 DE031018/DE/NIDCR NIH HHS/United States ; WHITELE20A0//Cystic Fibrosis Fouondation/ ; }, mesh = {*Cystic Fibrosis/microbiology/complications ; *Pseudomonas aeruginosa/physiology/pathogenicity ; Animals ; *Pseudomonas Infections/microbiology ; Mice ; *Disease Models, Animal ; Humans ; Respiratory Tract Infections/microbiology ; Host-Pathogen Interactions ; Sputum/microbiology ; }, abstract = {Laboratory models are central to microbiology research, advancing the understanding of bacterial physiology by mimicking natural environments, from soil to the human microbiome. When studying host-bacteria interactions, animal models enable investigators to examine bacterial dynamics associated with a host, and in the case of human infections, animal models are necessary to translate basic research into clinical treatments. Efforts toward improving animal infection models are typically based on reproducing host genotypes/phenotypes and disease manifestations, leaving a gap in how well the physiology of microbes reflects their behavior in a human host. Understanding bacterial physiology is vital because it dictates host response and bacterial interactions with antimicrobials. Thus, our goal was to develop an animal model that accurately recapitulates bacterial physiology in human infection. The system we chose to model was a chronic Pseudomonas aeruginosa respiratory infection in cystic fibrosis (CF). To accomplish this goal, we leveraged a framework that we recently developed to evaluate model accuracy by calculating the percentage of bacterial genes that are expressed similarly in a model to how they are expressed in their infection environment. We combined two complementary models of P. aeruginosa infection-an in vitro synthetic CF sputum model (SCFM2) and a mouse acute pneumonia model. This combined model captured the chronic physiology of P. aeruginosa in CF better than the standard mouse infection model, showing the power of a data-driven approach to refining animal models. In addition, the results of this work challenge the assumption that a chronic infection model requires long-term colonization.}, }
@article {pmid39100447, year = {2024}, author = {Kakkar, A and Kandwal, G and Nayak, T and Jaiswal, LK and Srivastava, A and Gupta, A}, title = {Engineered bacteriophages: A panacea against pathogenic and drug resistant bacteria.}, journal = {Heliyon}, volume = {10}, number = {14}, pages = {e34333}, pmid = {39100447}, issn = {2405-8440}, abstract = {Antimicrobial resistance (AMR) is a major global concern; antibiotics and other regular treatment methods have failed to overcome the increasing number of infectious diseases. Bacteriophages (phages) are viruses that specifically target/kill bacterial hosts without affecting other human microbiome. Phage therapy provides optimism in the current global healthcare scenario with a long history of its applications in humans that has now reached various clinical trials. Phages in clinical trials have specific requirements of being exclusively lytic, free from toxic genes with an enhanced host range that adds an advantage to this requisite. This review explains in detail the various phage engineering methods and their potential applications in therapy. To make phages more efficient, engineering has been attempted using techniques like conventional homologous recombination, Bacteriophage Recombineering of Electroporated DNA (BRED), clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, CRISPY-BRED/Bacteriophage Recombineering with Infectious Particles (BRIP), chemically accelerated viral evolution (CAVE), and phage genome rebooting. Phages are administered in cocktail form in combination with antibiotics, vaccines, and purified proteins, such as endolysins. Thus, phage therapy is proving to be a better alternative for treating life-threatening infections, with more specificity and fewer detrimental consequences.}, }
@article {pmid39092808, year = {2024}, author = {Jokela, R and Pärnänen, KM and Ponsero, AJ and Lahti, L and Kolho, KL and de Vos, WM and Salonen, A}, title = {A cohort study in family triads: impact of gut microbiota composition and early life exposures on intestinal resistome during the first two years of life.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2383746}, pmid = {39092808}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/genetics ; Infant ; Female ; *Feces/microbiology ; Male ; Cohort Studies ; *Anti-Bacterial Agents/pharmacology ; *Bacteria/genetics/classification/drug effects/isolation &amp; purification ; Infant, Newborn ; Bacteroides/genetics/drug effects/growth &amp; development ; Child, Preschool ; Metagenome ; Drug Resistance, Bacterial/genetics ; }, abstract = {Antibiotic resistance genes (ARGs) are prevalent in the infant gut microbiota and make up the intestinal resistome, representing a community ARG reservoir. This study focuses on the dynamics and persistence of ARGs in the early gut microbiota, and the effect of early exposures therein. We leveraged 2,328 stool metagenomes from 475 children in the HELMi cohort and the available parental samples to study the diversity, dynamics, and intra-familial sharing of the resistome during the first two years of life. We found higher within-family similarity of the gut resistome composition and ARG load in infant-mother pairs, and between spouses, but not in father-infant pairs. Early gut microbiota composition and development correlated with the ARG load; Bacteroides correlated positively and Bifidobacterium negatively with the load, reflecting the typical resistance levels in these taxa. Caesarean delivered infants harbored lower ARG loads, partly reflecting the scarcity of Bacteroides compared to vaginally delivered. Exposure to intrapartum or post-natal antibiotics showed only modest associations with the ARG load and composition, mainly before 12 months. Our results indicate that the resistome is strongly driven by the normal development of the microbiota in early life, and suggest importance of longer evolution of ARGs over effects of recent antibiotic exposure.}, }
@article {pmid39086645, year = {2024}, author = {Xie, S and Meng, Q and Wang, L}, title = {The effect of gut microbiome and plasma metabolome on systemic sclerosis: a bidirectional two-sample Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1427195}, pmid = {39086645}, issn = {1664-302X}, abstract = {BACKGROUND: Cellular and molecular biology, combined with research on the human microbiome and metabolome, have provided new insights into the pathogenesis of systemic sclerosis (SSc). However, most studies on gut microbiota (GM) and metabolome in SSc are observational studies. The impact of confounding factors and reverse causation leads to different insights. To shed light on this matter, we utilized Mendelian randomization (MR) to determine the causal effect of GM/metabolites on SSc.<br><br>METHODS: Based on summary-level data from genome-wide association studies, bidirectional Two-sample MR was conducted involving 196 GM, 1400 plasma metabolism, and 9,095 SSc. Inverse Variance Weighting (IVW) was mainly used for effect estimation.<br><br>RESULTS: Forward MR analysis found that three GM and two plasma metabolites are causally related to SSc. IVW results showed Victivallaceae (family) (OR, 1.469; 95%CI, 1.099-1.963; p&#x2009;=&#x2009;0.009) and LachnospiraceaeUCG004 (genus) (OR, 1.548; 95%CI, 1.020-2.349; p&#x2009;=&#x2009;0.04) were risk factor of SSc. Conversely, Prevotella7 (genus) (OR, 0.759; 95%CI, 0.578-0.997; p&#x2009;=&#x2009;0.048)was a protective factor of SSc. The results on plasma metabolites indicated that Pregnenediol disulfate (C21H34O8S2) levels (OR, 1.164; 95%CI, 1.006-1.347; p&#x2009;=&#x2009;0.041)was a risk factor of SSc, while Sphingomyelin (d18:1/19:0, d19:1/18:0) levels (OR, 0.821; 95%CI, 0.677-0.996; p&#x2009;=&#x2009;0.045)was a protective factor of SSc. Reverse MR analysis did not find causally relationship between SSc and the above GM/plasma metabolites.<br><br>CONCLUSION: Our results revealed the causally effect between GM/plasma metabolites and SSc. These findings provided new insights into the mechanism of SSc. In particular, we demonstrated Prevotella7 was a protective factor of SSc despite its controversial role in SSc in previous researches.}, }
@article {pmid39085612, year = {2024}, author = {Roje, B and Zhang, B and Mastrorilli, E and Kovačić, A and Sušak, L and Ljubenkov, I and Ćosić, E and Vilović, K and Meštrović, A and Vukovac, EL and Bučević-Popović, V and Puljiz, &#x17d; and Karaman, I and Terzić, J and Zimmermann, M}, title = {Gut microbiota carcinogen metabolism causes distal tissue tumours.}, journal = {Nature}, volume = {632}, number = {8027}, pages = {1137-1144}, pmid = {39085612}, issn = {1476-4687}, mesh = {Animals ; Female ; Humans ; Male ; Mice ; Biotransformation ; *Carcinogenesis/chemically induced/metabolism/pathology ; *Carcinogens/chemistry/metabolism/pharmacokinetics/toxicity ; *Gastrointestinal Microbiome/physiology ; Germ-Free Life ; Mice, Inbred C57BL ; *Nitrosamines/chemistry/metabolism/pharmacokinetics/toxicity ; *Urinary Bladder Neoplasms/chemically induced/etiology/metabolism/pathology/prevention &amp; control ; Disease Susceptibility ; }, abstract = {Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development[1,2]. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics[3]. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites[4,5], the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice[6,7]. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer.}, }
@article {pmid39073834, year = {2024}, author = {Scheperjans, F and Levo, R and Bosch, B and Lääperi, M and Pereira, PAB and Smolander, OP and Aho, VTE and Vetkas, N and Toivio, L and Kainulainen, V and Fedorova, TD and Lahtinen, P and Ortiz, R and Kaasinen, V and Satokari, R and Arkkila, P}, title = {Fecal Microbiota Transplantation for Treatment of Parkinson Disease: A Randomized Clinical Trial.}, journal = {JAMA neurology}, volume = {81}, number = {9}, pages = {925-938}, pmid = {39073834}, issn = {2168-6157}, mesh = {Humans ; *Parkinson Disease/therapy ; Middle Aged ; Male ; *Fecal Microbiota Transplantation/methods ; Female ; Aged ; Double-Blind Method ; Adult ; Treatment Outcome ; Dysbiosis/therapy ; }, abstract = {IMPORTANCE: Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) has shown promising effects in preclinical PD models.<br><br>OBJECTIVE: To assess the safety and symptomatic efficacy of colonic single-dose anaerobically prepared FMT.<br><br>This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 and June 2023 with a follow-up period of 12 months at 4 hospitals in Finland. Patients with PD aged 35 to 75 years in Hoehn &amp; Yahr stage 1-3 with a mild to moderate symptom burden and dysbiosis of fecal microbiota were included. Of 229 patients screened, 48 were randomized and 47 received the intervention. One patient discontinued due to worsening of PD symptoms. Two further patients were excluded before analysis and 45 were included in the intention-to-treat analysis.<br><br>INTERVENTION: Participants were randomized in a 2:1 ratio to receive FMT or placebo via colonoscopy.<br><br>MAIN OUTCOMES AND MEASURES: The primary end point was the change of Movement Disorder Society Unified Parkinson's Disease Rating Scale parts I-III (part III off medication) at 6 months. Safety was assessed by recording adverse events (AEs).<br><br>RESULTS: The median (IQR) age was 65 (52.5-70.0) years in the placebo group and 66 (59.25-69.75) years in the FMT group; 9 (60.0%) and 16 (53.3%) patients were male in the placebo group and the FMT group, respectively. The primary outcome did not differ between the groups (0.97 points, 95% CI, -5.10 to 7.03, P&#x2009;=&#x2009;.75). Gastrointestinal AEs were more frequent in the FMT group (16 [53%] vs 1 [7%]; P&#x2009;=&#x2009;.003). Secondary outcomes and post hoc analyses showed stronger increase of dopaminergic medication and improvement of certain motor and nonmotor outcomes in the placebo group. Microbiota changes were more pronounced after FMT but differed by donor. Nevertheless, dysbiosis status was reversed more frequently in the placebo group.<br><br>CONCLUSIONS AND RELEVANCE: FMT was safe but did not offer clinically meaningful improvements. Further studies-for example, through modified FMT approaches or bowel cleansing-are warranted regarding the specific impact of donor microbiota composition and dysbiosis conversion on motor and nonmotor outcomes as well as medication needs in PD.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04854291.}, }
@article {pmid39069614, year = {2024}, author = {Dwaraka, VB and Aronica, L and Carreras-Gallo, N and Robinson, JL and Hennings, T and Carter, MM and Corley, MJ and Lin, A and Turner, L and Smith, R and Mendez, TL and Went, H and Ebel, ER and Sonnenburg, ED and Sonnenburg, JL and Gardner, CD}, title = {Unveiling the epigenetic impact of vegan vs. omnivorous diets on aging: insights from the Twins Nutrition Study (TwiNS).}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {301}, pmid = {39069614}, issn = {1741-7015}, support = {R01 AG082056/AG/NIA NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Epigenesis, Genetic ; *Diet, Vegan ; Female ; *DNA Methylation ; Male ; *Aging/genetics ; Middle Aged ; Aged ; Diet ; Twins/genetics ; Diet, Vegetarian ; }, abstract = {BACKGROUND: Geroscience focuses on interventions to mitigate molecular changes associated with aging. Lifestyle modifications, medications, and social factors influence the aging process, yet the complex molecular mechanisms require an in-depth exploration of the epigenetic landscape. The specific epigenetic clock and predictor effects of a vegan diet, compared to an omnivorous diet, remain underexplored despite potential impacts on aging-related outcomes.<br><br>METHODS: This study examined the impact of an entirely plant-based or healthy omnivorous diet over 8 weeks on blood DNA methylation in paired twins. Various measures of epigenetic age acceleration (PC GrimAge, PC PhenoAge, DunedinPACE) were assessed, along with system-specific effects (Inflammation, Heart, Hormone, Liver, and Metabolic). Methylation surrogates of clinical, metabolite, and protein markers were analyzed to observe diet-specific shifts.<br><br>RESULTS: Distinct responses were observed, with the vegan cohort exhibiting significant decreases in overall epigenetic age acceleration, aligning with anti-aging effects of plant-based diets. Diet-specific shifts were noted in the analysis of methylation surrogates, demonstrating the influence of diet on complex trait prediction through DNA methylation markers. An epigenome-wide analysis revealed differentially methylated loci specific to each diet, providing insights into the affected pathways.<br><br>CONCLUSIONS: This study suggests that a short-term vegan diet is associated with epigenetic age benefits and reduced calorie intake. The use of epigenetic biomarker proxies (EBPs) highlights their potential for assessing dietary impacts and facilitating personalized nutrition strategies for healthy aging. Future research should explore the long-term effects of vegan diets on epigenetic health and overall well-being, considering the importance of proper nutrient supplementation.<br><br>TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05297825.}, }
@article {pmid39069097, year = {2024}, author = {Skolnick, S}, title = {Prospecting for para-endogenous anxiolytics in the human microbiome: Some promising pathways.}, journal = {Pharmacology, biochemistry, and behavior}, volume = {244}, number = {}, pages = {173842}, doi = {10.1016/j.pbb.2024.173842}, pmid = {39069097}, issn = {1873-5177}, mesh = {Humans ; *Anti-Anxiety Agents/pharmacology/therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Anxiety Disorders/drug therapy/microbiology/metabolism ; Pregnanolone/therapeutic use/pharmacology ; Animals ; Anxiety/drug therapy/microbiology ; }, abstract = {The gut microbiome is a vast, variable, and largely unexplored component of human biology that sits at the intersection of heritable and environmental factors, and represents a rich source of novel chemistry that is already known to be compatible with the human body. This alone would make it a promising place to search for new therapeutics, but recent work has also identified gut microbiome abnormalities in patients with a number of psychiatric disorders, including anxiety disorders-suggesting that not only treatments, but cures may lie therein. Here, we'll discuss two known "para-endogenous" anxiolytics-γ-hydroxybutyrate and the neurosteroid allopregnanolone-which have recently been discovered to be produced by the microbiome.}, }
@article {pmid39068184, year = {2024}, author = {de Jonge, PA and van den Born, BH and Zwinderman, AH and Nieuwdorp, M and Dutilh, BE and Herrema, H}, title = {Phylogeny and disease associations of a widespread and ancient intestinal bacteriophage lineage.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {6346}, pmid = {39068184}, issn = {2041-1723}, support = {955974//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 955974//EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)/ ; 0915018201002//ZonMw (Netherlands Organisation for Health Research and Development)/ ; 015.017.050//ZonMw (Netherlands Organisation for Health Research and Development)/ ; 390713860//Deutsche Forschungsgemeinschaft (German Research Foundation)/ ; 2019.82.004//Diabetes Fonds (Dutch Diabetes Research Foundation)/ ; }, mesh = {Humans ; *Phylogeny ; *Bacteriophages/genetics/isolation &amp; purification/classification ; *Gastrointestinal Microbiome/genetics ; Genome, Viral/genetics ; Metagenome/genetics ; Virome/genetics ; Inflammatory Bowel Diseases/virology ; Biodiversity ; Diabetes Mellitus, Type 2/virology ; Female ; Male ; Europe ; Netherlands ; Adult ; }, abstract = {Viruses are core components of the human microbiome, impacting health through interactions with gut bacteria and the immune system. Most human microbiome viruses are bacteriophages, which exclusively infect bacteria. Until recently, most gut virome studies focused on low taxonomic resolution (e.g., viral operational taxonomic units), hampering population-level analyses. We previously identified an expansive and widespread bacteriophage lineage in inhabitants of Amsterdam, the Netherlands. Here, we study their biodiversity and evolution in various human populations. Based on a phylogeny using sequences from six viral genome databases, we propose the Candidatus order Heliusvirales. We identify heliusviruses in 82% of 5441 individuals across 39 studies, and in nine metagenomes from humans that lived in Europe and North America between 1000 and 5000 years ago. We show that a large lineage started to diversify when Homo sapiens first appeared some 300,000 years ago. Ancient peoples and modern hunter-gatherers have distinct Ca. Heliusvirales populations with lower richness than modern urbanized people. Urbanized people suffering from type 1 and type 2 diabetes, as well as inflammatory bowel disease, have higher Ca. Heliusvirales richness than healthy controls. We thus conclude that these ancient core members of the human gut virome have thrived with increasingly westernized lifestyles.}, }
@article {pmid39066214, year = {2024}, author = {Alipour-Khezri, E and Skurnik, M and Zarrini, G}, title = {Pseudomonas aeruginosa Bacteriophages and Their Clinical Applications.}, journal = {Viruses}, volume = {16}, number = {7}, pages = {}, pmid = {39066214}, issn = {1999-4915}, mesh = {*Pseudomonas aeruginosa/virology ; Humans ; *Pseudomonas Infections/microbiology/therapy ; *Phage Therapy ; *Cystic Fibrosis/microbiology ; *Pseudomonas Phages/genetics/physiology ; Animals ; Bacteriophages/physiology/genetics ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {Antimicrobial resistance poses a serious risk to contemporary healthcare since it reduces the number of bacterial illnesses that may be treated with antibiotics, particularly for patients with long-term conditions like cystic fibrosis (CF). People with a genetic predisposition to CF often have recurrent bacterial infections in their lungs due to a buildup of sticky mucus, necessitating long-term antibiotic treatment. Pseudomonas aeruginosa infections are a major cause of CF lung illness, and P. aeruginosa airway isolates are frequently resistant to many antibiotics. Bacteriophages (also known as phages), viruses that infect bacteria, are a viable substitute for antimicrobials to treat P. aeruginosa infections in individuals with CF. Here, we reviewed the utilization of P. aeruginosa bacteriophages both in vivo and in vitro, as well as in the treatment of illnesses and diseases, and the outcomes of the latter.}, }
@article {pmid39065154, year = {2024}, author = {Merra, G and Gualtieri, P and La Placa, G and Frank, G and Della Morte, D and De Lorenzo, A and Di Renzo, L}, title = {The Relationship between Exposome and Microbiome.}, journal = {Microorganisms}, volume = {12}, number = {7}, pages = {}, pmid = {39065154}, issn = {2076-2607}, abstract = {Currently, exposome studies include a raft of different monitoring tools, including remote sensors, smartphones, omics analyses, distributed lag models, etc. The similarity in structure between the exposome and the microbiota plus their functions led us to pose three pertinent questions from this viewpoint, looking at the actual relationship between the exposome and the microbiota. In terms of the exposome, a bistable equilibrium between health and disease depends on constantly dealing with an ever-changing totality of exposures that together shape an individual from conception to death. Regarding scientific knowledge, the exposome is still lagging in certain areas, like the importance of microorganisms in the equation. The human microbiome is defined as an aggregate assemblage of gut commensals that are hosted by our surfaces related to the external environment. Commensals' resistance to a variety of environmental exposures, such as antibiotic administration, confirms that a layer of these organisms is protected within the host. The exposome is a conceptual framework defined as the environmental component of the science-inspired systems ideology that shifts from a specificity-based medical approach to reasoning in terms of complexity. A parallel concept in population health research and precision public health is the human flourishing index, which aims to account for the numerous environmental factors that affect individual and population well-being beyond ambient pollution.}, }
@article {pmid39064765, year = {2024}, author = {Bui, TPN}, title = {The Human Microbiome as a Therapeutic Target for Metabolic Diseases.}, journal = {Nutrients}, volume = {16}, number = {14}, pages = {}, pmid = {39064765}, issn = {2072-6643}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology/drug effects ; *Metabolic Diseases/microbiology/therapy ; Symbiosis ; Dysbiosis ; Probiotics/therapeutic use ; Host Microbial Interactions/physiology ; }, abstract = {The human microbiome functions as a separate organ in a symbiotic relationship with the host. Disruption of this host-microbe symbiosis can lead to serious health problems. Modifications to the composition and function of the microbiome have been linked to changes in host metabolic outcomes. Industrial lifestyles with high consumption of processed foods, alcoholic beverages and antibiotic use have significantly altered the gut microbiome in unfavorable ways. Therefore, understanding the causal relationship between the human microbiome and host metabolism will provide important insights into how we can better intervene in metabolic health. In this review, I will discuss the potential use of the human microbiome as a therapeutic target to improve host metabolism.}, }
@article {pmid39063655, year = {2024}, author = {Mpakosi, A and Sokou, R and Theodoraki, M and Kaliouli-Antonopoulou, C}, title = {Neonatal Gut Mycobiome: Immunity, Diversity of Fungal Strains, and Individual and Non-Individual Factors.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {39063655}, issn = {2075-1729}, abstract = {The human gastrointestinal ecosystem, or microbiome (comprising the total bacterial genome in an environment), plays a crucial role in influencing host physiology, immune function, metabolism, and the gut-brain axis. While bacteria, fungi, viruses, and archaea are all present in the gastrointestinal ecosystem, research on the human microbiome has predominantly focused on the bacterial component. The colonization of the human intestine by microbes during the first two years of life significantly impacts subsequent composition and diversity, influencing immune system development and long-term health. Early-life exposure to pathogens is crucial for establishing immunological memory and acquired immunity. Factors such as maternal health habits, delivery mode, and breastfeeding duration contribute to gut dysbiosis. Despite fungi's critical role in health, particularly for vulnerable newborns, research on the gut mycobiome in infants and children remains limited. Understanding early-life factors shaping the gut mycobiome and its interactions with other microbial communities is a significant research challenge. This review explores potential factors influencing the gut mycobiome, microbial kingdom interactions, and their connections to health outcomes from childhood to adulthood. We identify gaps in current knowledge and propose future research directions in this complex field.}, }
@article {pmid39061954, year = {2024}, author = {Zhao, Y and Li, C and Wu, K and Chen, H and Wang, Q and Xiao, Y and Yao, S and Hong, A and Zhang, M and Lei, S and Yang, W and Zhong, S and Umar, A and Huang, J and Yu, Z}, title = {Exploring the Impact of Short Term Travel on Gut Microbiota and Probiotic Bacteria Mediated Stability.}, journal = {Biomedicines}, volume = {12}, number = {7}, pages = {}, pmid = {39061954}, issn = {2227-9059}, support = {32170071//National Natural Science Foundation of China/ ; 32300051//National Natural Science Foundation of China/ ; 2023CXQD059//Central South University Innovation-Driven Research Programme/ ; }, abstract = {Although travelers are frequently accompanied by abdominal discomfort and even diarrhea, not every trip can cause this issue. Many studies have reported that intestinal microbes play an important role in it. However, little is known about the reason for the dynamics of these intestinal microbes. Here, we delved into the effects of short-term travel on the gut microbiota of 12 healthy individuals. A total of 72 fecal samples collected before and after one-week travel, alongside non-traveling controls, underwent amplicon sequencing and a series of bioinformatic analyses. We found that travel significantly increased intra-individual gut microbiota fluctuations without diarrhea symptoms. In addition, the initial composition of the gut microbiota before travel emerged as a crucial factor in understanding these fluctuations. Travelers with stable microbiota exhibited an enrichment of specific probiotic bacteria (Agathobaculum, Faecalibacterium, Bifidobacterium, Roseburia, Lactobacillus) before travel. Another batch of data validated their predictive role in distinguishing travelers with and without the gut microbial disorder. This work provided valuable insights into understanding the relationship between gut microbiota and travel. It offered a microbiota-centric perspective and a potential avenue for interventions to preserve gut health during travel.}, }
@article {pmid39061792, year = {2024}, author = {D'Ambrosio, A and Altomare, A and Boscarino, T and Gori, M and Balestrieri, P and Putignani, L and Del Chierico, F and Carotti, S and Cicala, M and Guarino, MPL and Piemonte, V}, title = {Mathematical Modeling of Vedolizumab Treatment's Effect on Microbiota and Intestinal Permeability in Inflammatory Bowel Disease Patients.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {11}, number = {7}, pages = {}, pmid = {39061792}, issn = {2306-5354}, support = {N.A.//Takeda Italia S.p.A./ ; }, abstract = {Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn's Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before (t0), after 24 weeks of (t1) and after 52 weeks of (t2) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at t0, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with Roseburia abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of Roseburia, albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model's satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions.}, }
@article {pmid39053136, year = {2024}, author = {Gholamzad, A and Khakpour, N and Hashemi, SMA and Goudarzi, Y and Ahmadi, P and Gholamzad, M and Mohammadi, M and Hashemi, M}, title = {Exploring the virome: An integral part of human health and disease.}, journal = {Pathology, research and practice}, volume = {260}, number = {}, pages = {155466}, doi = {10.1016/j.prp.2024.155466}, pmid = {39053136}, issn = {1618-0631}, mesh = {Humans ; *Virome ; *Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/virology ; }, abstract = {The human microbiome is a complex network of microorganisms that includes viruses, bacteria, and fungi. The gut virome is an essential component of the immune system, which is responsible for regulating the growth and responses of the host's immune system. The virome maintains a crucial role in the development of numerous diseases, including inflammatory bowel disease (IBD), Crohn's disease, and neurodegenerative disorders. The human virome has emerged as a promising biomarker and therapeutic target. This comprehensive review summarizes the present understanding of the virome and its implications in matters of health and disease, with a focus on the Human Microbiome Project.}, }
@article {pmid39043386, year = {2024}, author = {Duller, S and Moissl-Eichinger, C}, title = {Archaea in the Human Microbiome and Potential Effects on Human Infectious Disease.}, journal = {Emerging infectious diseases}, volume = {30}, number = {8}, pages = {1505-1513}, pmid = {39043386}, issn = {1080-6059}, mesh = {Humans ; *Archaea/genetics ; *Microbiota ; Communicable Diseases/microbiology ; }, abstract = {Archaea represent a separate domain of life, next to bacteria and eukarya. As components of the human microbiome, archaea have been associated with various diseases, including periodontitis, endodontic infections, small intestinal bacterial overgrowth, and urogenital tract infections. Archaea are generally considered nonpathogenic; the reasons are speculative because of limited knowledge and gene annotation challenges. Nevertheless, archaeal syntrophic principles that shape global microbial networks aid both archaea and potentially pathogenic bacteria. Evaluating archaea interactions remains challenging, requiring clinical studies on inflammatory potential and the effects of archaeal metabolism. Establishing a culture collection is crucial for investigating archaea functions within the human microbiome, which could improve health outcomes in infectious diseases. We summarize potential reasons for archaeal nonpathogenicity, assess the association with infectious diseases in humans, and discuss the necessary experimental steps to enable mechanistic studies involving archaea.}, }
@article {pmid39041015, year = {2024}, author = {Brame, JE and Liddicoat, C and Abbott, CA and Cando-Dumancela, C and Fickling, NW and Robinson, JM and Breed, MF}, title = {Urban sports fields support higher levels of soil butyrate and butyrate-producing bacteria than urban nature parks.}, journal = {Ecology and evolution}, volume = {14}, number = {7}, pages = {e70057}, pmid = {39041015}, issn = {2045-7758}, abstract = {Butyrate-producing bacteria colonise the gut of humans and non-human animals, where they produce butyrate, a short-chain fatty acid with known health benefits. Butyrate-producing bacteria also reside in soils and soil bacteria can drive the assembly of airborne bacterial communities (the aerobiome). Aerobiomes in urban greenspaces are important reservoirs of butyrate-producing bacteria as they supplement the human microbiome, but soil butyrate producer communities have rarely been examined in detail. Here, we studied soil metagenome taxonomic and functional profiles and soil physicochemical data from two urban greenspace types: sports fields (n = 11) and nature parks (n = 22). We also developed a novel method to quantify soil butyrate and characterised the in situ activity of butyrate-producing bacteria. We show that soil butyrate was higher in sports fields than nature parks and that sports fields also had significantly higher relative abundances of the terminal butyrate production genes buk and butCoAT than nature parks. Soil butyrate positively correlated with buk gene abundance (but not butCoAT). Soil moisture (r = .50), calcium (r = -.62), iron (ρ = .54), ammonium nitrogen (ρ = .58) and organic carbon (r = .45) had the strongest soil abiotic effects on soil butyrate concentrations and iron (ρ = .56) and calcium (ρ = -.57) had the strongest soil abiotic effects on buk read abundances. Overall, our findings contribute important new insights into the role of sports fields as key exposure reservoirs of butyrate producing bacteria, with important implications for the provision of microbiome-mediated human health benefits via butyrate.}, }
@article {pmid39040076, year = {2024}, author = {Onwuka, S and Bravo-Merodio, L and Gkoutos, GV and Acharjee, A}, title = {Explainable AI-prioritized plasma and fecal metabolites in inflammatory bowel disease and their dietary associations.}, journal = {iScience}, volume = {27}, number = {7}, pages = {110298}, pmid = {39040076}, issn = {2589-0042}, abstract = {Fecal metabolites effectively discriminate inflammatory bowel disease (IBD) and show differential associations with diet. Metabolomics and AI-based models, including explainable AI (XAI), play crucial roles in understanding IBD. Using datasets from the UK Biobank and the Human Microbiome Project Phase II IBD Multi'omics Database (HMP2 IBDMDB), this study uses multiple machine learning (ML) classifiers and Shapley additive explanations (SHAP)-based XAI to prioritize plasma and fecal metabolites and analyze their diet correlations. Key findings include the identification of discriminative metabolites like glycoprotein acetyl and albumin in plasma, as well as nicotinic acid metabolites andurobilin in feces. Fecal metabolites provided a more robust disease predictor model (AUC [95%]: 0.93 [0.87-0.99]) compared to plasma metabolites (AUC [95%]: 0.74 [0.69-0.79]), with stronger and more group-differential diet-metabolite associations in feces. The study validates known metabolite associations and highlights the impact of IBD on the interplay between gut microbial metabolites and diet.}, }
@article {pmid39031651, year = {2025}, author = {Liu, Y and Yang, H and Wang, P and Shi, Y and Shi, R and Zhang, S and Zhao, Y and Lan, J and Ge, S}, title = {Correlation between short-chain fatty acids and peri-implant disease: A cross-sectional study.}, journal = {Journal of periodontology}, volume = {96}, number = {1}, pages = {21-29}, doi = {10.1002/JPER.23-0682}, pmid = {39031651}, issn = {1943-3670}, support = {82100977//National Natural Science Foundation of China/ ; 2022LHM-KFKT004//Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research/ ; }, mesh = {Humans ; Cross-Sectional Studies ; Male ; Middle Aged ; Female ; *Fatty Acids, Volatile/analysis ; *Peri-Implantitis/metabolism ; *Dental Implants/adverse effects ; Aged ; Adult ; *Gingival Crevicular Fluid/chemistry ; Propionates/analysis ; Acetic Acid/analysis ; Gas Chromatography-Mass Spectrometry ; Chromatography, High Pressure Liquid ; Stomatitis/metabolism ; Pentanoic Acids ; Hemiterpenes ; }, abstract = {BACKGROUND: To explore the correlation between short-chain fatty acids (SCFAs) in the peri-implant sulcular fluid (PISF) and peri-implant diseases.<br><br>METHODS: PISF samples were obtained from implants that have been placed for at least 5&#xa0;years, and peri-implant clinical parameters were examined. Gas chromatography-mass spectrometry and high-performance liquid chromatography were used to detect SCFAs in PISF. The correlation between SCFAs and clinical parameters was analyzed by Spearman's correlation. SCFAs related to peri-implant disease were identified by logistic regression and ranked by random forest analysis.<br><br>RESULTS: Eighty-six implants were divided into a peri-implant health group (PIH-group, 35 implants), peri-implant mucositis group (PIM-group, 25 implants), and peri-implantitis group (PI-group, 26 implants) according to clinical and radiographic examination results. The PIM-group had significantly lower formic acid detection rate than the other two groups (p&#xa0;<&#xa0;0.001). The PIM-group had significantly higher levels of acetic, propionic, and isovaleric acids than the PIH-group (p&#xa0;<&#xa0;0.05). The PI-group had significantly higher levels of propionic, butyric, isobutyric, valeric, and isovaleric acids than the PIH-group (p&#xa0;<&#xa0;0.05). The PI-group had significantly higher levels of butyric, isobutyric, and isovaleric acids than the PIM-group (p&#xa0;<&#xa0;0.05). SCFAs (apart from hexanoic and succinic acids) were significantly and positively correlated with clinical parameters (p&#xa0;<&#xa0;0.05). SCFAs related to peri-implant disease were ranked as follows: butyric, isovaleric, isobutyric, propionic, acetic, formic, and lactic acids.<br><br>CONCLUSIONS: Elevated specific SCFAs are correlated with peri-implant disease. Recognition of this correlation may help in early identification of peri-implant disease and guide further clinical interventions.}, }
@article {pmid39030525, year = {2024}, author = {Lu, L and Li, F and Gao, Y and Kang, S and Li, J and Guo, J}, title = {Microbiome in radiotherapy: an emerging approach to enhance treatment efficacy and reduce tissue injury.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {30}, number = {1}, pages = {105}, pmid = {39030525}, issn = {1528-3658}, support = {31920210037//Fundamental Research Funds for Central Universities of the Central South University/ ; No. xbmuyjrc202217//Northwest Minzu University/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/radiation effects ; *Neoplasms/radiotherapy/microbiology/immunology/therapy ; *Probiotics/therapeutic use ; *Radiotherapy/adverse effects/methods ; Animals ; Microbiota/radiation effects ; Radiation Injuries/microbiology/therapy/etiology ; Treatment Outcome ; }, abstract = {Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.}, }
@article {pmid39030408, year = {2024}, author = {Gilbert, JA and Hartmann, EM}, title = {The indoors microbiome and human health.}, journal = {Nature reviews. Microbiology}, volume = {22}, number = {12}, pages = {742-755}, pmid = {39030408}, issn = {1740-1534}, mesh = {Humans ; *Microbiota ; Air Microbiology ; Air Pollution, Indoor ; Built Environment ; }, abstract = {Indoor environments serve as habitat for humans and are replete with various reservoirs and niches for microorganisms. Microorganisms enter indoor spaces with their human and non-human hosts, as well as via exchange with outdoor sources, such as ventilation and plumbing. Once inside, many microorganisms do not survive, especially on dry, barren surfaces. Even reduced, this microbial biomass has critical implications for the health of human occupants. As urbanization escalates, exploring the intersection of the indoor environment with the human microbiome and health is increasingly vital. The indoor microbiome, a complex ecosystem of microorganisms influenced by human activities and environmental factors, plays a pivotal role in modulating infectious diseases and fostering healthy immune development. Recent advancements in microbiome research shed light on this unique ecological system, highlighting the need for innovative approaches in creating health-promoting living spaces. In this Review, we explore the microbial ecology of built environments - places where humans spend most of their lives - and its implications for immune, endocrine and neurological health. We further propose strategies to harness the indoor microbiome for better health outcomes.}, }
@article {pmid39026867, year = {2024}, author = {Rudzite, M and O'Toole, GA}, title = {An energy coupling factor transporter of Streptococcus sanguinis impacts antibiotic susceptibility as well as metal and membrane homeostasis.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39026867}, issn = {2692-8205}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; R01 AI155424/AI/NIAID NIH HHS/United States ; }, abstract = {Streptococcus sanguinis is a prevalent member of human microbiome capable of acting as a causative agent of oral and respiratory infections. S. sanguinis competitive success within the infection niche is dependent on acquisition of metal ions and vitamins. Among the systems that bacteria use for micronutrient uptake is the energy coupling factor (ECF) transporter system EcfAAT. Here we describe physiological changes arising from EcfAAT transporter disruption. We found that EcfAAT contributes to S. sanguinis antibiotic sensitivity as well as metal and membrane homeostasis. Specifically, our work found that disruption of EcfAAT results in increased polymyxin susceptibility. We performed assessment of cell-associated metal content and found depletion of iron, magnesium, and manganese. Furthermore, membrane composition analysis revealed significant enrichment in unsaturated fatty acid species resulting in increased membrane fluidity. Our results demonstrate how disruption of a single EcfAAT transporter can have broad consequences on bacterial cell homeostasis. ECF transporters are of interest within the context of infection biology in bacterial species other than streptococci, hence work described here will further the understanding of how micronutrient uptake systems contribute to bacterial pathogenesis.}, }
@article {pmid39026688, year = {2024}, author = {Agnew, A and Humm, E and Zhou, K and Gunsalus, RP and Zhou, ZH}, title = {Reconstruction and identification of the native PLP synthase complex from Methanosarcina acetivorans lysate.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.07.09.602819}, pmid = {39026688}, issn = {2692-8205}, abstract = {Many protein-protein interactions behave differently in biochemically purified forms as compared to their in vivo states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here we apply the bottom-up structural proteomics method, cryoID , toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through the cryoID approach, we successfully reconstructed and identified the native Methanosarcina acetivorans pyridoxal 5'-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryoEM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryoEM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37 amino acid insertion present in these prior cases. This study demonstrates the potential of applying the cryoID workflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.}, }
@article {pmid39023173, year = {2024}, author = {Ivashkin, V and Maev, I and Poluektova, E and Sinitsa, A and Avalueva, E and Mnatsakanyan, M and Simanenkov, V and Karpeeva, J and Kopylova, D and Kuprina, I and Kucheryavyy, Y and Lapina, T and Solovyeva, O and Soom, M and Cheremushkina, N and Maevskaya, E and Maslennikov, R}, title = {Efficacy and Safety of Postbiotic Contained Inactivated Lactobacillus reuteri (Limosilactobacillus reuteri) DSM 17648 as Adjuvant Therapy in the Eradication of Helicobacter pylori in Adults With Functional Dyspepsia: A Randomized Double-Blind Placebo-Controlled Trial.}, journal = {Clinical and translational gastroenterology}, volume = {15}, number = {9}, pages = {e1}, pmid = {39023173}, issn = {2155-384X}, mesh = {Humans ; Double-Blind Method ; *Limosilactobacillus reuteri ; *Dyspepsia/microbiology/diagnosis/drug therapy/therapy ; Male ; Female ; *Helicobacter Infections/drug therapy/diagnosis/therapy/microbiology ; Adult ; *Helicobacter pylori/isolation &amp; purification ; *Probiotics/administration &amp; dosage/adverse effects/therapeutic use ; Middle Aged ; *Amoxicillin/administration &amp; dosage/adverse effects/therapeutic use ; *Clarithromycin/administration &amp; dosage/therapeutic use/adverse effects ; *Drug Therapy, Combination ; Treatment Outcome ; *Anti-Bacterial Agents/adverse effects/administration &amp; dosage/therapeutic use ; *Quality of Life ; Esomeprazole/administration &amp; dosage/adverse effects/therapeutic use ; Young Adult ; }, abstract = {INTRODUCTION: Increasing the effectiveness of eradication therapy is an important task in gastroenterology. The aim of this study was to evaluate the efficacy and safety of postbiotic containing inactivated (nonviable) Limosilactobacillus (Lactobacillus) reuteri DSM 17648 (Pylopass) as adjuvant treatment of Helicobacter pylori eradication in patients with functional dyspepsia (FD).<br><br>METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel study included H. pylori -positive patients with FD. The postbiotic group received Pylopass 200 mg bid for 14 days in combination with eradication therapy (esomeprazole 20 mg bid + amoxicillin 1,000 mg bid + clarithromycin 500 mg bid for 14 days) and another 14 days after the completion of eradication therapy. The study was registered in the ISRCTN registry (ISRCTN20716052).<br><br>RESULTS: Eradication efficiency was 96.7% for the postbiotic group vs 86.0% for the placebo group (P = 0.039). Both groups showed significant improvements in quality of life and reduction of most gastrointestinal symptoms with no significant differences between groups. The overall number of digestive adverse effects in the postbiotic group was lower than in the placebo group. Serious adverse effects were not registered.<br><br>DISCUSSION: The postbiotic containing inactivated L. reuteri DSM 17648 significantly improves the effectiveness of H. pylori eradication therapy in FD and decreases overall number of digestive adverse effects of this therapy.}, }
@article {pmid39022135, year = {2020}, author = {Jiang, J and Warren, CM and Browning, RL and Ciaccio, CE and Gupta, RS}, title = {Food allergy epidemiology and racial and/or ethnic differences.}, journal = {Journal of food allergy}, volume = {2}, number = {1}, pages = {11-16}, pmid = {39022135}, issn = {2689-0275}, abstract = {In recent decades, immunoglobulin E (IgE) mediated food allergy has become a growing public health concern. Converging evidence from cross-sectional prevalence studies, health care utilization records, and cohort studies indicate that food allergies are increasingly prevalent and often severe. Although IgE-mediated food allergy has long been considered a predominantly pediatric concern, analysis of recent self-reported data suggests that food allergies may be more prevalent among adult populations than previously acknowledged, with many reported cases of adult-onset allergies as well as persistent childhood-onset allergies. Results of studies also suggest that food allergy-related health care utilization is increasing as more individuals seek emergency treatment for food-induced anaphylaxis. Analysis of epidemiologic data also indicates that the burden of food allergies is unequally distributed. Published prevalence rates are highest in Western countries, e.g., the United States, United Kingdom, and Australia. Within these countries, there also is heterogeneity across racial and/or ethnic groups, with non-White and second-generation immigrant populations disproportionately affected. Importantly, such observations can shed light on the etiology of food allergy and inform improved clinical management, treatment, and prevention efforts. For example, there is a growing consensus that earlier introduction of allergenic foods, e.g., peanut, promotes oral tolerance and can dramatically reduce food allergy risk. In addition, much attention has been paid to the potentially deleterious effects of cutaneous allergen exposure, e.g., through eczematous skin, which can skew the immune response away from tolerance and toward allergic sensitization, thereby increasing food allergy risk. Furthermore, there is a growing appreciation for the potential protective effects of diverse microbial exposures, given mounting evidence for the immunomodulatory effects of the human microbiome. Also, when considering the geographic variability in the prevalence of certain food and environmental allergies as well as their structural similarities at the molecular level, it is believed that co-sensitization between food and environmental allergens may be a key driver of rising food allergy prevalence.}, }
@article {pmid39015605, year = {2024}, author = {Sermsaksasithorn, P and Asawanonda, P and Phutrakool, P and Ondee, T and Chariyavilaskul, P and Payungporn, S and Pongpirul, K and Hirankarn, N}, title = {Efficacy and Safety of Cannabis Transdermal Patch for Alleviating Psoriasis Symptoms: Protocol for a Randomized Controlled Trial (CanPatch).}, journal = {Medical cannabis and cannabinoids}, volume = {7}, number = {1}, pages = {99-110}, pmid = {39015605}, issn = {2504-3889}, abstract = {INTRODUCTION: Current topical treatments for psoriasis offer limited efficacy and are associated with long-term adverse effects in a subset of patients, highlighting the need for new therapeutic options. Cannabidiol (CBD), a non-psychoactive cannabinoid derived from Cannabis sativa L., has shown potential in reversing psoriasis pathology through its action on skin receptors in preclinical studies. Given the promising properties of CBD, transdermal patches containing this compound represent a novel approach to psoriasis treatment. However, comprehensive data on their efficacy and safety remain scarce.<br><br>METHODS: We outline a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of CBD transdermal patches with minimal tetrahydrocannabinol (THC) in 60 patients with mild to moderate plaque-type psoriasis at a university hospital in Thailand (n = 60). This study aims to evaluate the changes in the local psoriasis severity index (LPSI), itch score via a visual analog scale, and occurrence of adverse events on day 0, 30, 60, and 90 of the study. Additionally, we will examine the alteration in the skin, gut, and oral microbiome in a subset of participants to explore potential correlations with treatment outcomes. The primary outcome will focus on the difference in LPSI scores at the end of the study period, employing an intention-to-treat analysis. Multivariate logistic regression will be used to identify baseline clinical and microbiological predictors of treatment response.<br><br>CONCLUSION: This study aims to investigate the efficacy and safety of CBD transdermal patches in alleviating the symptoms of psoriasis. The results of this study may highlight a novel topical treatment option that reduces suffering in patients with psoriasis. We also designed to provide a holistic evaluation by considering both clinical outcomes and the underlying biological mechanisms, including the interaction with the human microbiome. Through this trial, we aim to contribute valuable insights into personalized psoriasis management strategies.}, }
@article {pmid39013264, year = {2024}, author = {Kim, J and Park, S and Kim, SJ and Yoo, I and Kim, H and Hwang, S and Sim, KM and Kim, I and Jun, E}, title = {High-throughput drug screening using a library of antibiotics targeting cancer cell lines that are resistant and sensitive to gemcitabine.}, journal = {Biochemical and biophysical research communications}, volume = {730}, number = {}, pages = {150369}, doi = {10.1016/j.bbrc.2024.150369}, pmid = {39013264}, issn = {1090-2104}, mesh = {*Gemcitabine ; *Deoxycytidine/analogs &amp; derivatives/pharmacology ; Humans ; *High-Throughput Screening Assays/methods ; *Drug Resistance, Neoplasm/drug effects ; Cell Line, Tumor ; *Anti-Bacterial Agents/pharmacology ; *Drug Screening Assays, Antitumor/methods ; Puromycin/pharmacology ; Antimetabolites, Antineoplastic/pharmacology ; Drug Synergism ; Antineoplastic Agents/pharmacology ; Small Molecule Libraries/pharmacology ; }, abstract = {Gemcitabine is a nucleoside analog widely used as an anticancer agent against several types of cancer. Although gemcitabine sometimes shows excellent effectiveness, cancer cells are often poorly responsive to or resistant to the drug. Recently, specific strains or dysbiosis of the human microbiome were correlated with drug reactivity and resistance acquisition. Therefore, we aimed to identify antibiotic compounds that can modulate the microbiome to enhance the responsiveness to gemcitabine. To achieve this, we confirmed the gemcitabine responsiveness based on public data and conducted drug screening on a set of 250 antibiotics compounds. Subsequently, we performed experiments to investigate whether the selected compounds could enhance the responsiveness to gemcitabine. First, we grouped a total of seven tumor cell lines into resistant and sensitive group based on the IC50 value (1 μM) of gemcitabine obtained from the public data. Second, we performed high-throughput screening with compound treatments, identifying seven compounds from the resistant group and five from the sensitive group based on dose dependency. Finally, the combination of the selected compound, puromycin dihydrochloride, with gemcitabine in gemcitabine-resistant cell lines resulted in extensive cell death and a significant increase in cytotoxic efficacy. Additionally, mRNA levels associated with cell viability and stemness were reduced. Through this study, we screened antibiotics to further improve the efficacy of existing anticancer drugs and overcome resistance. By combining existing anticancer agents and antibiotic substances, we hope to establish various drug combination therapies and ultimately improve cancer treatment efficacy.}, }
@article {pmid39011022, year = {2024}, author = {Sarkar, P and Chintaluri, S and Sarkar, S and Unnisa, M and Jakkampudi, A and Mulukutla, AP and Kumari, S and Reddy, DN and Talukdar, R}, title = {Evaluation of the Crosstalk Between the Host Mycobiome and Bacteriome in Patients with Chronic Pancreatitis.}, journal = {Indian journal of microbiology}, volume = {64}, number = {2}, pages = {603-617}, pmid = {39011022}, issn = {0046-8991}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {UNLABELLED: The human microbiome is a diverse consortium of microbial kingdoms that play pivotal roles in host health and diseases. We previously reported a dysbiotic bacteriome in chronic pancreatitis patients with diabetes (CPD) compared with patients with it's nondiabetic (CPND) phenotype. In this study, we extended our exploration to elucidate the intricate interactions between the mycobiome, bacteriome, and hosts' plasma metabolome with the disease phenotypes. A total of 25 participants (CPD, n = 7; CPND, n = 10; healthy control, n = 8) were recruited for the study. We observed elevated species richness in both the bacterial and fungal profiles within the CP diabetic cohort compared to the nondiabetic CP phenotype and healthy control cohorts. Notably, the CP group displayed heterogeneous fungal diversity, with only 40% of the CP nondiabetic patients and 20% of the CP diabetic patients exhibiting common core gut fungal profiles. Specific microbial taxa alterations were identified, including a reduction in Bifidobacterium adolescentis and an increase in the prevalence of Aspergillus penicilloides and Klebsiella sp. in the disease groups. In silico analysis revealed the enrichment of pathways related to lipopolysaccharide (LPS), apoptosis, and peptidase, as well as reduced counts of the genes responsible for carbohydrate metabolism in the CP groups. Additionally, distinct plasma metabolome signatures were observed, with CPD group exhibiting higher concentrations of sugars and glycerolipids, while the CPND cohort displayed elevated levels of amino acids in their blood. The fatty acid-binding protein (FABP) concentration was notably greater in the CPD group than in the HC group (4.220 vs. 1.10 ng/ml, p = 0.04). Furthermore, compared with healthy controls, disease groups exhibited fewer correlations between key fungal taxa (Aspergillus sp., Candida sp.) and bacterial taxa (Prevotella copri, Bifidobacteria sp., Rumminococcaceae). Our study unveils, for the first time, a dysbiotic mycobiome and emphasizes unique host bacterial-mycobial interactions in CP patient with diabetes, potentially influencing disease severity. These findings provide crucial insights for future mechanistic studies aiming to unravel the determinants of disease severity in this complex clinical context.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-024-01207-8.}, }
@article {pmid39009231, year = {2024}, author = {Réthi-Nagy, Z and Juhász, S}, title = {Microbiome's Universe: Impact on health, disease and cancer treatment.}, journal = {Journal of biotechnology}, volume = {392}, number = {}, pages = {161-179}, doi = {10.1016/j.jbiotec.2024.07.002}, pmid = {39009231}, issn = {1873-4863}, mesh = {Humans ; *Neoplasms/therapy/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Dysbiosis/microbiology/therapy ; Microbiota ; Animals ; }, abstract = {The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.}, }
@article {pmid39006241, year = {2024}, author = {Hu, Y and Zhang, R and Li, J and Wang, H and Wang, M and Ren, Q and Fang, Y and Tian, L}, title = {Association Between Gut and Nasal Microbiota and Allergic Rhinitis: A Systematic Review.}, journal = {Journal of asthma and allergy}, volume = {17}, number = {}, pages = {633-651}, pmid = {39006241}, issn = {1178-6965}, abstract = {Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.}, }
@article {pmid39002973, year = {2024}, author = {Vich Vila, A and Zhang, J and Liu, M and Faber, KN and Weersma, RK}, title = {Untargeted faecal metabolomics for the discovery of biomarkers and treatment targets for inflammatory bowel diseases.}, journal = {Gut}, volume = {73}, number = {11}, pages = {1909-1920}, pmid = {39002973}, issn = {1468-3288}, mesh = {Humans ; *Inflammatory Bowel Diseases/metabolism ; *Metabolomics/methods ; *Feces/chemistry/microbiology ; *Biomarkers/metabolism/analysis ; *Gastrointestinal Microbiome/physiology ; Bile Acids and Salts/metabolism ; }, abstract = {The gut microbiome has been recognised as a key component in the pathogenesis of inflammatory bowel diseases (IBD), and the wide range of metabolites produced by gut bacteria are an important mechanism by which the human microbiome interacts with host immunity or host metabolism. High-throughput metabolomic profiling and novel computational approaches now allow for comprehensive assessment of thousands of metabolites in diverse biomaterials, including faecal samples. Several groups of metabolites, including short-chain fatty acids, tryptophan metabolites and bile acids, have been associated with IBD. In this Recent Advances article, we describe the contribution of metabolomics research to the field of IBD, with a focus on faecal metabolomics. We discuss the latest findings on the significance of these metabolites for IBD prognosis and therapeutic interventions and offer insights into the future directions of metabolomics research.}, }
@article {pmid38997154, year = {2024}, author = {Rysbekov, K and Abrakhmanova, S and Satybaeva, R and Starosvetova, Y and Kushugulova, A}, title = {Helicobacter pylori eradication therapy for children.}, journal = {Drug metabolism and personalized therapy}, volume = {39}, number = {2}, pages = {59-67}, pmid = {38997154}, issn = {2363-8915}, mesh = {Humans ; *Helicobacter Infections/drug therapy ; *Helicobacter pylori/drug effects/isolation &amp; purification ; Child ; Male ; Female ; *Drug Therapy, Combination ; *Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; *Vitamin D/administration &amp; dosage/blood ; Adolescent ; Treatment Outcome ; Proton Pump Inhibitors/administration &amp; dosage/therapeutic use ; Child, Preschool ; Amoxicillin/administration &amp; dosage/therapeutic use ; }, abstract = {OBJECTIVES: The research aims to investigate the effect of vitamin D supplementation on the efficacy of Helicobacter pylori eradication therapy and to find new drug combinations for the eradication of the bacterium.<br><br>METHODS: A total of 128 children participated in the research. They were distributed under the following criteria: group A were children who tested positive for H.&#xa0;pylori and were treated with the standard so-called triple therapy including vitamin D; group B were children who tested positive for H.&#xa0;pylori and received the standard triple therapy without including vitamin D in the treatment; and group C were children who tested negative for H.&#xa0;pylori. After endoscopic examination, additional venous blood samples were taken from the children to determine vitamin D levels. A controlled study was carried out 45&#xa0;days after the initial treatment.<br><br>RESULTS: The overall success rate of eradication therapy was 84.1&#x202f;%. In group A, the success rate of treatment was 93.5&#x202f;%, contrary to group B, where the success rate was 75&#x202f;%. Although there was a difference in the percentage of H.&#xa0;pylori eradication therapy in the main group compared to the control group, there was no significant difference in group B. The success rate of eradication is p=0.082.<br><br>CONCLUSIONS: Following the research results, the addition of vitamin D to the standard triple therapy regimen for H.&#xa0;pylori had no effect. It can therefore be concluded that vitamin D does not significantly increase the efficacy of eradication therapy.}, }
@article {pmid38996003, year = {2024}, author = {Byndloss, M and Devkota, S and Duca, F and Hendrik Niess, J and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L}, title = {The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.}, journal = {Diabetes care}, volume = {47}, number = {9}, pages = {1491-1508}, pmid = {38996003}, issn = {1935-5548}, support = {//Novo Nordisk/ ; R01 DK123446/DK/NIDDK NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; DP1 DK130687/DK/NIDDK NIH HHS/United States ; R01 DK131104/DK/NIDDK NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology ; Diabetes Mellitus/microbiology ; }, abstract = {This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.}, }
@article {pmid38992611, year = {2024}, author = {Chen, L and Li, Q and Huang, X and Li, Z}, title = {Association between sleep duration and possible sarcopenia in middle-aged and elderly Chinese individuals: evidence from the China health and retirement longitudinal study.}, journal = {BMC geriatrics}, volume = {24}, number = {1}, pages = {594}, pmid = {38992611}, issn = {1471-2318}, support = {2021B1515140026//The Guangdong Basic and Applied Basic Research Fund Local Incubation Projects/ ; 20211800904952//Dongguan City Social Science and Technology Development Project (Key)/ ; 202206010142//The Key Project of Guangzhou Science and Technology Program, China/ ; 2023B1212060018//The Science and Technology Planning Project of Guangdong Province, China/ ; }, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology ; East Asian People ; Longitudinal Studies ; Prevalence ; *Sarcopenia/epidemiology/diagnosis/physiopathology ; *Sleep Duration ; Time Factors ; }, abstract = {BACKGROUND: Sarcopenia is a common cause of disability in the aging population, and managing sarcopenia is an important step in building intrinsic capacity and promoting healthy aging. A growing body of evidence suggests that sleep deprivation may be a mediator of the development of sarcopenia. The purpose of this study was to explore the longitudinal association between sleep duration and possible sarcopenia using data from a national sample.<br><br>METHODS: Two waves of data from the CHARLS database for 2011 and 2015 were used in this study. All possible sarcopenia participants met the Asia Working Group for Sarcopenia 2019 (AWGS 2019) diagnostic criteria. Sleep duration was assessed using a self-report questionnaire, and sleep duration was categorized as short (&#x2264;&#x2009;6&#xa0;h), medium (6-8&#xa0;h), or long (>&#x2009;8&#xa0;h) based on previous studies. Longitudinal associations between sleep duration and possible sarcopenia will be calculated by univariate and multifactorial logistic regression analyses and expressed as odds ratios (ORs) and 95% confidence intervals (CIs).<br><br>RESULTS: A total of 5654 individuals participated in the follow-up study, with a prevalence of possible sarcopenia of 53.72% (578) in the short sleep duration group, 38.29% (412) in the medium sleep duration group, and 7.99% (86) in the long sleep duration group. According to the crude model of the second-wave follow-up study, short sleep durations were significantly more strongly associated with possible sarcopenia than were medium and long sleep durations (OR: 1.35, 95% CI: 1.17-1.55, P&#x2009;=&#x2009;0.000). The association between short sleep duration and possible sarcopenia was maintained even after adjustment for covariates such as age, gender, residence, education level, BMI, smoking status, alcohol consumption and comorbidities (OR: 1.18, 95% CI: 1.02-1.36, P&#x2009;=&#x2009;0.029). In the subgroup analysis, short sleep duration was associated with low grip strength (OR: 1.20, 95% CI: 1.02-1.41, P&#x2009;=&#x2009;0.031).<br><br>CONCLUSIONS: Sleep deprivation may be closely associated with the development of possible sarcopenia in middle-aged and elderly people, which provides new insights and ideas for sarcopenia intervention, and further studies are needed to reveal the underlying mechanisms involved.}, }
@article {pmid38987933, year = {2024}, author = {Zhao, Y and Bitzer, A and Power, JJ and Belikova, D and Torres Salazar, BO and Adolf, LA and Gerlach, D and Krismer, B and Heilbronner, S}, title = {Nasal commensals reduce Staphylococcus aureus proliferation by restricting siderophore availability.}, journal = {The ISME journal}, volume = {18}, number = {1}, pages = {}, pmid = {38987933}, issn = {1751-7370}, support = {TTU 08.708_00//German Center of Infection Research/ ; //Deutsche Forschungsgemeinschaft/ ; //German Research Foundation/ ; 2124-390838134/EXC-2124/1-05.002_0//Germany's Excellence Strategy-EXC/ ; 8180207//National Natural Science Foundation of China/ ; PRJNA1028639//NCBI/ ; }, mesh = {*Siderophores/metabolism ; *Staphylococcus aureus/metabolism/growth &amp; development ; Humans ; Animals ; *Staphylococcal Infections/microbiology ; Microbiota ; Mice ; Nasal Cavity/microbiology ; Iron/metabolism ; Symbiosis ; Microbial Interactions ; Bacteria/metabolism/classification/growth &amp; development ; Nose/microbiology ; }, abstract = {The human microbiome is critically associated with human health and disease. One aspect of this is that antibiotic-resistant opportunistic bacterial pathogens, such as methicillin-resistant Staphylococcus aureus, can reside within the nasal microbiota, which increases the risk of infection. Epidemiological studies of the nasal microbiome have revealed positive and negative correlations between non-pathogenic species and S. aureus, but the underlying molecular mechanisms remain poorly understood. The nasal cavity is iron-limited, and bacteria are known to produce iron-scavenging siderophores to proliferate in such environments. Siderophores are public goods that can be consumed by all members of a bacterial community. Accordingly, siderophores are known to mediate bacterial competition and collaboration, but their role in the nasal microbiome is unknown. Here, we show that siderophore acquisition is crucial for S. aureus nasal colonization in vivo. We screened 94 nasal bacterial strains from seven genera for their capacity to produce siderophores as well as to consume the siderophores produced by S. aureus. We found that 80% of the strains engaged in siderophore-mediated interactions with S. aureus. Non-pathogenic corynebacterial species were found to be prominent consumers of S. aureus siderophores. In co-culture experiments, consumption of siderophores by competitors reduced S. aureus growth in an iron-dependent fashion. Our data show a wide network of siderophore-mediated interactions between the species of the human nasal microbiome and provide mechanistic evidence for inter-species competition and collaboration impacting pathogen proliferation. This opens avenues for designing nasal probiotics to displace S. aureus from the nasal cavity of humans.}, }
@article {pmid38987811, year = {2024}, author = {Won, C and Yim, SS}, title = {Emerging methylation-based approaches in microbiome engineering.}, journal = {Biotechnology for biofuels and bioproducts}, volume = {17}, number = {1}, pages = {96}, pmid = {38987811}, issn = {2731-3654}, support = {G04220037//KAIST/ ; N10230105//KAIST/ ; N11230043//KAIST/ ; N10240028//KAIST/ ; N10240039//KAIST/ ; }, abstract = {Bacterial epigenetics, particularly through DNA methylation, exerts significant influence over various biological processes such as DNA replication, uptake, and gene regulation in bacteria. In this review, we explore recent advances in characterizing bacterial epigenomes, accompanied by emerging strategies that harness bacterial epigenetics to elucidate and engineer diverse bacterial species with precision and effectiveness. Furthermore, we delve into the potential of epigenetic modifications to steer microbial functions and influence community dynamics, offering promising opportunities for understanding and modulating microbiomes. Additionally, we investigate the extensive diversity of DNA methyltransferases and emphasize their potential utility in the context of the human microbiome. In summary, this review highlights the potential of DNA methylation as a powerful toolkit for engineering microbiomes.}, }
@article {pmid38979233, year = {2024}, author = {Dong, PT and Shi, W and He, X and Borisy, GG}, title = {Adhesive interactions within microbial consortia can be differentiated at the single-cell level through expansion microscopy.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38979233}, issn = {2692-8205}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE030943/DE/NIDCR NIH HHS/United States ; T90 DE026110/DE/NIDCR NIH HHS/United States ; }, abstract = {Investigating microbe-microbe interactions at the single-cell level is critical to unraveling the ecology and dynamics of microbial communities. In many situations, microbes assemble themselves into densely packed multi-species biofilms. The density and complexity pose acute difficulties for visualizing individual cells and analyzing their interactions. Here, we address this problem through an unconventional application of expansion microscopy, which allows for the 'decrowding' of individual bacterial cells within a multispecies community. Expansion microscopy generally has been carried out under isotropic expansion conditions and used as a resolution-enhancing method. In our variation of expansion microscopy, we carry out expansion under heterotropic conditions; that is, we expand the space between bacterial cells but not the space within individual cells. The separation of individual bacterial cells from each other reflects the competition between the expansion force pulling them apart and the adhesion force holding them together. We employed heterotropic expansion microscopy to study the relative strength of adhesion in model biofilm communities. These included mono and dual-species Streptococcus biofilms, and a three-species synthetic community (Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sanguinis) under conditions that facilitated interspecies coaggregation. Using adhesion mutants, we investigated the interplay between F. nucleatum outer membrane protein RadD and different Streptococcus species. We also examined the Schaalia-TM7 epibiont association. Quantitative proximity analysis was used to evaluate the separation of individual microbial members. Our study demonstrates that heterotropic expansion microscopy can 'decrowd' dense biofilm communities, improve visualization of individual bacterial members, and enable analysis of microbe-microbe adhesive interactions at the single-cell level.}, }
@article {pmid38977511, year = {2024}, author = {Rahim, MA and Seo, H and Kim, S and Barman, I and Ghorbanian, F and Hossain, MS and Shuvo, MSH and Lee, S and Song, HY}, title = {Exploring the potential of Lactocaseibacillus rhamnosus PMC203 in inducing autophagy to reduce the burden of Mycobacterium tuberculosis.}, journal = {Medical microbiology and immunology}, volume = {213}, number = {1}, pages = {14}, pmid = {38977511}, issn = {1432-1831}, support = {RS-2023-00219563//National Research Foundation of Korea/ ; Soonchunhyang University Research Fund//Soonchunhyang University/ ; 20018499//Korean Ministry of Trade, Industry, and Energy (MOTIE, Korea)/ ; }, mesh = {*Autophagy ; *Mycobacterium tuberculosis/genetics ; *Lacticaseibacillus rhamnosus/physiology/metabolism ; *Probiotics ; *Macrophages/microbiology ; Humans ; Lysosomes/metabolism ; Microtubule-Associated Proteins/metabolism/genetics ; Bacterial Load ; Tuberculosis/microbiology ; }, abstract = {Mycobacterium tuberculosis, a lethal pathogen in human history, causes millions of deaths annually, which demands the development of new concepts of drugs. Considering this fact, earlier research has explored the anti-tuberculosis potential of a probiotic strain, Lactocaseibacillus rhamnosus PMC203, leading to a subsequent focus on the molecular mechanism involved in its effect, particularly on autophagy. In this current study, immunoblotting-based assay exhibited a remarkable expression of autophagy marker LC3-II in the PMC203 treated group compared to an untreated group. A remarkable degradation of p62 was also noticed within treated cells compared to control. Furthermore, the immunofluorescence-based assay showed significant fold change in fluorescence intensity for alexa-647-LC3 and alexa-488-LC3, whereas p62 was degraded noticeably. Moreover, lysosomal biogenesis generation was elevated significantly in terms of LAMP1 and acidic vesicular organelles. As a result, PMC203-induced autophagy played a vital role in reducing M. tuberculosis burden within the macrophages in treated groups compared to untreated group. A colony -forming unit assay also revealed a significant reduction in M. tuberculosis in the treated cells over time. Additionally, the candidate strain significantly upregulated the expression of autophagy induction and lysosomal biogenesis genes. Together, these results could enrich our current knowledge of probiotics-mediated autophagy in tuberculosis and suggest its implications for innovatively managing tuberculosis.}, }
@article {pmid38967872, year = {2024}, author = {Lyytinen, OL and Dapuliga, C and Wallinger, D and Patpatia, S and Audu, BJ and Kiljunen, SJ}, title = {Three novel Enterobacter cloacae bacteriophages for therapeutic use from Ghanaian natural waters.}, journal = {Archives of virology}, volume = {169}, number = {8}, pages = {156}, pmid = {38967872}, issn = {1432-8798}, mesh = {*Enterobacter cloacae/virology/drug effects ; Ghana ; *Bacteriophages/genetics/isolation &amp; purification/physiology/classification ; *Anti-Bacterial Agents/pharmacology ; Phage Therapy/methods ; Genome, Viral ; Enterobacteriaceae Infections/therapy/microbiology ; Drug Resistance, Multiple, Bacterial ; Finland ; Humans ; Microbial Sensitivity Tests ; Ciprofloxacin/pharmacology ; Meropenem/pharmacology ; }, abstract = {Infections caused by multidrug-resistant (MDR) bacteria are a growing global concern. Enterobacter cloacae complex (ECC) species are particularly adept at developing antibiotic resistance. Phage therapy is proposed as an alternative treatment for pathogens that no longer respond to antibiotics. Unfortunately, ECC phages are understudied when compared to phages of many other bacterial species. In this Ghanaian-Finnish study, we isolated two ECC strains from ready-to-eat food samples and three novel phages from natural waters against these strains. We sequenced the genomic DNA of the novel Enterobacter phages, fGh-Ecl01, fGh-Ecl02, and fGh-Ecl04, and assessed their therapeutic potential. All of the phages were found to be lytic, easy to propagate, and lacking any toxic, integrase, or antibiotic resistance genes and were thus considered suitable for therapy purposes. They all were found to be related to T4-type viruses: fGh-Ecl01 and fGh-Ecl04 to karamviruses and fGh-Ecl02 to agtreviruses. Testing of Finnish clinical ECC strains showed promising susceptibility to these novel phages. As many as 61.1% of the strains were susceptible to fGh-Ecl01 and fGh-Ecl04, and 7.4% were susceptible to fGh-Ecl02. Finally, we investigated the susceptibility of the newly isolated ECC strains to three antibiotics - meropenem, ciprofloxacin, and cefepime - in combination with the novel phages. The use of phages and antibiotics together had synergistic effects. When using an antibiotic-phage combination, even low concentrations of antibiotics fully inhibited the growth of bacteria.}, }
@article {pmid38963518, year = {2025}, author = {Wang, B and Luan, J and Zhao, W and Yu, J and Li, A and Li, X and Zhong, X and Cao, H and Wang, R and Liu, B and Lu, S and Shi, M}, title = {Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.}, journal = {Cellular oncology (Dordrecht, Netherlands)}, volume = {48}, number = {1}, pages = {139-159}, pmid = {38963518}, issn = {2211-3436}, support = {2021YFA0717002//National Key Research and Development Program of China/ ; 22-3-7-smjk-8-nsh//Funds for Qingdao Science and Technology Benefit People Demonstration Guide Special Project/ ; }, mesh = {Humans ; *Stomach Neoplasms/microbiology/blood/pathology/metabolism ; *Gastric Mucosa/microbiology/pathology/metabolism ; Male ; Female ; Middle Aged ; Helicobacter pylori ; *Metabolome ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Aged ; *Metabolomics/methods ; Helicobacter Infections/microbiology ; Carcinogenesis/pathology ; Multiomics ; }, abstract = {PURPOSE: As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis.<br><br>METHODS: Gastric biopsies from different stomach microhabitats (n&#x2009;=&#x2009;70) were subjected to 16S rRNA gene sequencing, and blood samples (n&#x2009;=&#x2009;95) were subjected to untargeted metabolome (gas chromatography&#x2012;mass spectrometry, GC&#x2012;MS) analyses. The datasets were analysed using various bioinformatics approaches.<br><br>RESULTS: The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer.<br><br>CONCLUSION: The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.}, }
@article {pmid38962127, year = {2024}, author = {Lange, E and Kranert, L and Krüger, J and Benndorf, D and Heyer, R}, title = {Microbiome modeling: a beginner's guide.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1368377}, pmid = {38962127}, issn = {1664-302X}, abstract = {Microbiomes, comprised of diverse microbial species and viruses, play pivotal roles in human health, environmental processes, and biotechnological applications and interact with each other, their environment, and hosts via ecological interactions. Our understanding of microbiomes is still limited and hampered by their complexity. A concept improving this understanding is systems biology, which focuses on the holistic description of biological systems utilizing experimental and computational methods. An important set of such experimental methods are metaomics methods which analyze microbiomes and output lists of molecular features. These lists of data are integrated, interpreted, and compiled into computational microbiome models, to predict, optimize, and control microbiome behavior. There exists a gap in understanding between microbiologists and modelers/bioinformaticians, stemming from a lack of interdisciplinary knowledge. This knowledge gap hinders the establishment of computational models in microbiome analysis. This review aims to bridge this gap and is tailored for microbiologists, researchers new to microbiome modeling, and bioinformaticians. To achieve this goal, it provides an interdisciplinary overview of microbiome modeling, starting with fundamental knowledge of microbiomes, metaomics methods, common modeling formalisms, and how models facilitate microbiome control. It concludes with guidelines and repositories for modeling. Each section provides entry-level information, example applications, and important references, serving as a valuable resource for comprehending and navigating the complex landscape of microbiome research and modeling.}, }
@article {pmid38955124, year = {2024}, author = {Maryam,  and Rehman, MU and Hussain, I and Tayara, H and Chong, KT}, title = {A graph neural network approach for predicting drug susceptibility in the human microbiome.}, journal = {Computers in biology and medicine}, volume = {179}, number = {}, pages = {108729}, doi = {10.1016/j.compbiomed.2024.108729}, pmid = {38955124}, issn = {1879-0534}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Neural Networks, Computer ; Microbiota/drug effects ; Machine Learning ; Deep Learning ; }, abstract = {Recent studies have illuminated the critical role of the human microbiome in maintaining health and influencing the pharmacological responses of drugs. Clinical trials, encompassing approximately 150 drugs, have unveiled interactions with the gastrointestinal microbiome, resulting in the conversion of these drugs into inactive metabolites. It is imperative to explore the field of pharmacomicrobiomics during the early stages of drug discovery, prior to clinical trials. To achieve this, the utilization of machine learning and deep learning models is highly desirable. In this study, we have proposed graph-based neural network models, namely GCN, GAT, and GINCOV models, utilizing the SMILES dataset of drug microbiome. Our primary objective was to classify the susceptibility of drugs to depletion by gut microbiota. Our results indicate that the GINCOV surpassed the other models, achieving impressive performance metrics, with an accuracy of 93% on the test dataset. This proposed Graph Neural Network (GNN) model offers a rapid and efficient method for screening drugs susceptible to gut microbiota depletion and also encourages the improvement of patient-specific dosage responses and formulations.}, }
@article {pmid38951769, year = {2024}, author = {Ranta, K and Skurnik, M and Kiljunen, S}, title = {fENko-Kae01 is a flagellum-specific jumbo phage infecting Klebsiella aerogenes.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {234}, pmid = {38951769}, issn = {1471-2180}, mesh = {*Bacteriophages/genetics/classification/isolation &amp; purification/physiology ; *Genome, Viral ; *Flagella/virology/genetics ; *Enterobacter aerogenes/virology/genetics ; *Host Specificity ; Whole Genome Sequencing ; Myoviridae/genetics/isolation &amp; purification/classification/physiology ; }, abstract = {BACKGROUND: Klebsiella aerogenes is an opportunistic pathogen that causes a wide variety of infections. Due to the rising problem of antibiotic resistance, novel antibiotics and strategies to combat bacterial infections are needed. Host-specific bacteriophages are natural enemies of bacteria and can be used in phage therapy as an alternative form of treatment against bacterial infections. Jumbo phages are defined as phages with genomes larger than 200 kb. Relatively few studies have been done on jumbo phages compared to smaller phages.<br><br>RESULTS: A novel phage, fENko-Kae01, was isolated from a commercial phage cocktail. Genomic analysis revealed that fENko-Kae01 is a lytic jumbo phage with a 360&#xa0;kb genome encoding 578 predicted genes. No highly similar phage genomes were identified and fENko-Kae01 may be a completely new genus representative. No known genes associated with lysogenic life cycle, bacterial virulence, or antibiotic resistance were identified. The phage had myovirus morphology and a narrow host range. Phage resistant bacterial mutants emerged under phage selection. Whole genome sequencing revealed that the biogenesis of the flagellum was affected in four mutants and the lack of functional flagellum was confirmed in motility assays. Furthermore, phage fENKo-Kae01 failed to adsorb on the non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor.<br><br>CONCLUSIONS: fENko-Kae01 is a novel jumbo bacteriophage that is considered safe for phage therapy. fENko-Kae01 uses the flagellum as the phage-binding receptor and may represent a completely novel genus.}, }
@article {pmid38950441, year = {2025}, author = {Chen, Y}, title = {Beyond Meta-Omics: Functional Genomics in Future Marine Microbiome Research.}, journal = {Annual review of marine science}, volume = {17}, number = {1}, pages = {577-592}, doi = {10.1146/annurev-marine-020123-100931}, pmid = {38950441}, issn = {1941-0611}, mesh = {*Microbiota/genetics ; *Genomics/methods ; Oceans and Seas ; }, abstract = {When President Bill Clinton and Francis Collins, then the director of the National Human Genome Research Institute, celebrated the near completion of the human genome sequence at the White House in the summer of 2000, it is unlikely that they or anyone else could have predicted the blossoming of meta-omics in the following two decades and their applications in modern human microbiome and environmental microbiome research. This transformation was enabled by the development of high-throughput sequencing technologies and sophisticated computational biology tools and bioinformatics software packages. Today, environmental meta-omics has undoubtedly revolutionized our understanding of ocean ecosystems, providing the genetic blueprint of oceanic microscopic organisms. In this review, I discuss the importance of functional genomics in future marine microbiome research and advocate a position for a gene-centric, bottom-up approach in modern oceanography. I propose that a synthesis of multidimensional approaches is required for a better understanding of the true functionality of the marine microbiome.}, }
@article {pmid38948147, year = {2024}, author = {Guan, Y and Wu, D and Wang, H and Liu, NN}, title = {Microbiome-driven anticancer therapy: A step forward from natural products.}, journal = {mLife}, volume = {3}, number = {2}, pages = {219-230}, pmid = {38948147}, issn = {2770-100X}, abstract = {Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome-driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.}, }
@article {pmid38945961, year = {2024}, author = {Kim, N and Ma, J and Kim, W and Kim, J and Belenky, P and Lee, I}, title = {Genome-resolved metagenomics: a game changer for microbiome medicine.}, journal = {Experimental &amp; molecular medicine}, volume = {56}, number = {7}, pages = {1501-1512}, pmid = {38945961}, issn = {2092-6413}, support = {R01 DK125382/DK/NIDDK NIH HHS/United States ; HI19C1344//Korea Health Industry Development Institute (KHIDI)/ ; }, mesh = {Humans ; *Metagenomics/methods ; *Metagenome ; *Microbiota/genetics ; Bacteria/genetics/classification ; Animals ; Genome, Bacterial ; Gastrointestinal Microbiome/genetics ; }, abstract = {Recent substantial evidence implicating commensal bacteria in human diseases has given rise to a new domain in biomedical research: microbiome medicine. This emerging field aims to understand and leverage the human microbiota and derivative molecules for disease prevention and treatment. Despite the complex and hierarchical organization of this ecosystem, most research over the years has relied on 16S amplicon sequencing, a legacy of bacterial phylogeny and taxonomy. Although advanced sequencing technologies have enabled cost-effective analysis of entire microbiota, translating the relatively short nucleotide information into the functional and taxonomic organization of the microbiome has posed challenges until recently. In the last decade, genome-resolved metagenomics, which aims to reconstruct microbial genomes directly from whole-metagenome sequencing data, has made significant strides and continues to unveil the mysteries of various human-associated microbial communities. There has been a rapid increase in the volume of whole metagenome sequencing data and in the compilation of novel metagenome-assembled genomes and protein sequences in public depositories. This review provides an overview of the capabilities and methods of genome-resolved metagenomics for studying the human microbiome, with a focus on investigating the prokaryotic microbiota of the human gut. Just as decoding the human genome and its variations marked the beginning of the genomic medicine era, unraveling the genomes of commensal microbes and their sequence variations is ushering us into the era of microbiome medicine. Genome-resolved metagenomics stands as a pivotal tool in this transition and can accelerate our journey toward achieving these scientific and medical milestones.}, }
@article {pmid38944815, year = {2024}, author = {Del Chierico, F and Masi, L and Petito, V and Baldelli, V and Puca, P and Benvenuto, R and Fidaleo, M and Palucci, I and Lopetuso, LR and Caristo, ME and Carrozza, C and Giustiniani, MC and Nakamichi, N and Kato, Y and Putignani, L and Gasbarrini, A and Pani, G and Scaldaferri, F}, title = {Solute Transporter OCTN1/Slc22a4 Affects Disease Severity and Response to Infliximab in Experimental Colitis: Role of Gut Microbiota and Immune Modulation.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {12}, pages = {2259-2270}, pmid = {38944815}, issn = {1536-4844}, support = {GR-2016-02364891//Italian Ministry of Health/ ; }, mesh = {Animals ; *Infliximab/therapeutic use ; Mice ; *Colitis/chemically induced/drug therapy/immunology/microbiology ; *Gastrointestinal Microbiome/drug effects ; *Mice, Knockout ; *Mice, Inbred C57BL ; *Disease Models, Animal ; *Dextran Sulfate ; *Organic Cation Transport Proteins/genetics ; Gastrointestinal Agents/pharmacology/therapeutic use ; Severity of Illness Index ; Symporters/genetics/metabolism ; Dysbiosis ; Immunity, Mucosal ; }, abstract = {BACKGROUND: Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies. The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and mucosal immunity in response to infliximab therapy in murine colitis.<br><br>METHODS: A dextran sodium sulphate model of colitis was used to assess the clinical efficacy of infliximab administered intravenously in ocnt1 gene knockout mice and their C57BL/6 controls. Stool, colon, and mesenteric lymph node samples were collected to evaluate differences in gut microbiota composition, histology, and T cell populations, respectively.<br><br>RESULTS: Octn1 -/- influences the microbiota profile and is associated with a worse dysbiosis in mice with colitis. Infliximab treatment attenuates colitis-associated dysbiosis, with an increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1-/- mice have milder disease and a higher baseline percentage of Treg, Tmemory, Th2 and Th17 cells.<br><br>CONCLUSIONS: Our data support the murine model to study OCTN1 genetic contribution to inflammatory bowel diseases. This could be the first step towards the recognition of this membrane transporter as a biomarker in inflammatory conditions and a predictor of response to therapies.}, }
@article {pmid38942021, year = {2024}, author = {Chen, W and Li, Y and Wang, W and Gao, S and Hu, J and Xiang, B and Wu, D and Jiao, N and Xu, T and Zhi, M and Zhu, L and Zhu, R}, title = {Enhanced microbiota profiling in patients with quiescent Crohn's disease through comparison with paired healthy first-degree relatives.}, journal = {Cell reports. Medicine}, volume = {5}, number = {7}, pages = {101624}, pmid = {38942021}, issn = {2666-3791}, mesh = {Humans ; *Crohn Disease/microbiology/genetics ; Female ; Male ; Adult ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Family ; Middle Aged ; Case-Control Studies ; Fatty Acids, Volatile/metabolism ; Young Adult ; Metabolome ; Microbiota/genetics ; }, abstract = {Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.}, }
@article {pmid38935049, year = {2024}, author = {Bai, X and Nielsen, SD and Kunisaki, KM and Trøseid, M}, title = {Pulmonary comorbidities in people with HIV- the microbiome connection.}, journal = {Current opinion in HIV and AIDS}, volume = {19}, number = {5}, pages = {246-252}, doi = {10.1097/COH.0000000000000871}, pmid = {38935049}, issn = {1746-6318}, mesh = {Humans ; *HIV Infections/complications/microbiology/epidemiology ; *Microbiota ; *Comorbidity ; *Lung Diseases/microbiology/epidemiology/complications ; *Dysbiosis/microbiology ; Lung/microbiology/physiopathology ; }, abstract = {PURPOSE OF REVIEW: To report recent evidence on associations between human microbiome, particularly airway and gut, and pulmonary comorbidities in people with HIV (PWH). Furthermore, we explore how changes in the microbiome may contribute to pulmonary immune dysregulation and higher rates of pulmonary comorbidities among PWH. Finally, we propose future directions in the field.<br><br>RECENT FINDINGS: Increased risk of pulmonary comorbidities and rapid lung function decline have been reported in even well treated PWH. Altered microbiota profiles have been reported in PWH with pulmonary comorbidities and rapid lung function decline as compared to those without. The most consistent data have been the association between HIV-related pulmonary comorbidities, lung and oral microbiota dysbiosis, which has been also associated with distinct respiratory mucosal inflammatory profiles and short-term mortality. However, a possible causal link remains to be elucidated.<br><br>SUMMARY: Associations between the lung and oral microbiome, HIV-associated pulmonary comorbidities and rapid lung function decline have been reported in recent studies. Yet the underlying mechanism underpinning the observed associations is largely unknown and substantial knowledge gaps remain. Future research is warranted to unveil the role and mechanism of human microbiome from different anatomical compartments in relation to pulmonary comorbidities in PWH.}, }
@article {pmid38932188, year = {2024}, author = {Alipour-Khezri, E and Moqadami, A and Barzegar, A and Mahdavi, M and Skurnik, M and Zarrini, G}, title = {Bacteriophages and Green Synthesized Zinc Oxide Nanoparticles in Combination Are Efficient against Biofilm Formation of Pseudomonas aeruginosa.}, journal = {Viruses}, volume = {16}, number = {6}, pages = {}, pmid = {38932188}, issn = {1999-4915}, mesh = {*Zinc Oxide/pharmacology ; *Pseudomonas aeruginosa/virology/drug effects/physiology ; *Biofilms/drug effects ; *Metal Nanoparticles/chemistry ; Green Chemistry Technology ; Bacteriophages/physiology ; Anti-Bacterial Agents/pharmacology ; Nanoparticles/chemistry ; }, abstract = {Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, Pseudomonas aeruginosa, another biofilm-forming pathogen, is a problem in many parts of the world. Zinc oxide (ZnO) and other metal nanoparticles (NPs) are biologically active and also possess anti-biofilm properties. ZnO-NPs were prepared by the green synthesis method using orange peels. The vibrational peaks of the ZnO-NPs were analyzed using FTIR analysis, and their size and morphological properties were determined using scanning electron microscopy (SEM). The ability of the ZnO-NPs to reduce or eliminate P. aeruginosa biofilm alone or in combination with phages PB10 and PA19 was investigated. The P. aeruginosa cells were effectively killed in the preformed 48 h biofilms during a 24 h incubation with the ZnO-NP-phage combination, in comparison with the control or ZnO-NPs alone. The treatments on growing biofilms were most efficient in the final stages of biofilm development. All five treatment groups showed a significant biofilm reduction compared to the control group (p < 0.0001) at 48 h of incubation. The influence of the ZnO-NPs and phages on the quorum sensing system of P. aeruginosa was monitored by quantitative real-time PCR (qRT-PCR) of the autoinducer biosynthesis gene lasI. While the ZnO-NPs repressed the lasI gene transcription, the phages slightly activated it at 24 and 48 h of incubation. Also, the effect of the ZnO-NPs and phage PA19 on the viability of HFF2 cells was investigated and the results showed that the combination of NPs with PA19 reduced the toxic effect of ZnO-NPs and also stimulated the growth in normal cells.}, }
@article {pmid38930571, year = {2024}, author = {Sprague, KL and Rajakaruna, S and Bandow, B and Burchat, N and Bottomley, M and Sampath, H and Paliy, O}, title = {Gut Microbiota Fermentation of Digested Almond-Psyllium-Flax Seed-Based Artisan Bread Promotes Mediterranean Diet-Resembling Microbial Community.}, journal = {Microorganisms}, volume = {12}, number = {6}, pages = {}, pmid = {38930571}, issn = {2076-2607}, support = {R01 DK126963/DK/NIDDK NIH HHS/United States ; DBI-1335772//National Science Foundation/ ; }, abstract = {Different modifications of the standard bread recipe have been proposed to improve its nutritional and health benefits. Here, we utilized the in vitro Human Gut Simulator (HGS) to assess the fermentation of one such artisan bread by human gut microbiota. Dried and milled bread, composed of almond flour, psyllium husks, and flax seeds as its three main ingredients, was first subjected to an in vitro protocol designed to mimic human oro-gastro-intestinal digestion. The bread digest was then supplied to complex human gut microbial communities, replacing the typical Western diet-based medium (WM) of the GHS system. Switching the medium from WM to bread digest resulted in statistically significant alterations in the community structure, encoded functions, produced short-chain fatty acids, and available antioxidants. The abundances of dietary fiber degraders Enterocloster, Mitsuokella, and Prevotella increased; levels of Gemmiger, Faecalibacterium, and Blautia decreased. These community alterations resembled the previously revealed differences in the distal gut microbiota of healthy human subjects consuming typical Mediterranean vs. Western-pattern diets. Therefore, the consumption of bread high in dietary fiber and unsaturated fatty acids might recapitulate the beneficial effects of the Mediterranean diet on the gut microbiota.}, }
@article {pmid38930451, year = {2024}, author = {Balleza-Alejandri, LR and Peña-Durán, E and Beltrán-Ramírez, A and Reynoso-Roa, AS and Sánchez-Abundis, LD and García-Galindo, JJ and Suárez-Rico, DO}, title = {Decoding the Gut Microbiota-Gestational Diabetes Link: Insights from the Last Seven Years.}, journal = {Microorganisms}, volume = {12}, number = {6}, pages = {}, pmid = {38930451}, issn = {2076-2607}, abstract = {The human microbiome, a complex ecosystem of bacteria, viruses, and protozoans living in symbiosis with the host, plays a crucial role in human health, influencing everything from metabolism to immune function. Dysbiosis, or an imbalance in this ecosystem, has been linked to various health issues, including diabetes and gestational diabetes (GD). In diabetes, dysbiosis affects the function of adipose tissue, leading to the release of adipokines and cytokines, which increase inflammation and insulin resistance. During pregnancy, changes to the microbiome can exacerbate glucose intolerance, a common feature of GD. Over the past years, burgeoning insights into the gut microbiota have unveiled its pivotal role in human health. This article comprehensively reviews literature from the last seven years, highlighting the association between gut microbiota dysbiosis and GD, as well as the metabolism of antidiabetic drugs and the potential influences of diet and probiotics. The underlying pathophysiological mechanisms discussed include the impact of dysbiosis on systemic inflammation and the interplay with genetic and environmental factors. By focusing on recent studies, the importance of considering microbial health in the prevention and treatment of GD is emphasized, providing insights into future research directions and clinical applications to improve maternal-infant health outcomes.}, }
@article {pmid38929681, year = {2024}, author = {Lee, J and Kim, H and Park, JS}, title = {Beyond the Bile: Exploring the Microbiome and Metabolites in Cholangiocarcinoma.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {6}, pages = {}, pmid = {38929681}, issn = {2075-1729}, support = {N/A//INHA UNIVERSITY HOSPITAL Research Grant/ ; N/A//Shihwa medical center research fund/ ; }, abstract = {INTRODUCTION: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results.<br><br>METHODS: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells.<br><br>RESULTS: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis.<br><br>CONCLUSIONS: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC.}, }
@article {pmid38927134, year = {2024}, author = {Martins, D and Silva, C and Ferreira, AC and Dourado, S and Albuquerque, A and Saraiva, F and Batista, AB and Castro, P and Leite-Moreira, A and Barros, AS and Miranda, IM}, title = {Unravelling the Gut Microbiome Role in Cardiovascular Disease: A Systematic Review and a Meta-Analysis.}, journal = {Biomolecules}, volume = {14}, number = {6}, pages = {}, pmid = {38927134}, issn = {2218-273X}, support = {UIDB/00051/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; UIDP/00051/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; 2021.06947.BD//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; *Cardiovascular Diseases/microbiology/metabolism ; Bacteria/metabolism/classification/genetics ; Methylamines/metabolism/blood ; }, abstract = {A notable shift in understanding the human microbiome's influence on cardiovascular disease (CVD) is underway, although the causal association remains elusive. A systematic review and meta-analysis were conducted to synthesise current knowledge on microbial taxonomy and metabolite variations between healthy controls (HCs) and those with CVD. An extensive search encompassing three databases identified 67 relevant studies (2012-2023) covering CVD pathologies from 4707 reports. Metagenomic and metabolomic data, both qualitative and quantitative, were obtained. Analysis revealed substantial variability in microbial alpha and beta diversities. Moreover, specific changes in bacterial populations were shown, including increased Streptococcus and Proteobacteria and decreased Faecalibacterium in patients with CVD compared with HC. Additionally, elevated trimethylamine N-oxide levels were reported in CVD cases. Biochemical parameter analysis indicated increased fasting glucose and triglycerides and decreased total cholesterol and low- and high-density lipoprotein cholesterol levels in diseased individuals. This study revealed a significant relationship between certain bacterial species and CVD. Additionally, it has become clear that there are substantial inconsistencies in the methodologies employed and the reporting standards adhered to in various studies. Undoubtedly, standardising research methodologies and developing extensive guidelines for microbiome studies are crucial for advancing the field.}, }
@article {pmid38926732, year = {2024}, author = {Li, Q and Huang, Z and Yang, H and Tang, J and Zuo, T and Yang, Q and Huang, Z and Guo, Q and Li, M and Gao, X and Chao, K}, title = {Intestinal mRNA expression profiles associated with mucosal healing in ustekinumab-treated Crohn's disease patients: bioinformatics analysis and prospective cohort validation.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {595}, pmid = {38926732}, issn = {1479-5876}, support = {2022JBGS05//the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; 2022JBGS03//the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; 2020B1111170004//the program of Guangdong Provincial Clinical Research Center for Digestive Diseases/ ; 1010CG(2023)-12//the Sixth Affiliated Hospital of Sun Yat-Sen University Clinical Research-'1010' Program/ ; }, mesh = {Adult ; Female ; Humans ; Male ; Cluster Analysis ; *Computational Biology/methods ; *Crohn Disease/genetics/drug therapy ; Gene Expression Profiling ; Gene Ontology ; Intestinal Mucosa/metabolism/pathology ; Prospective Studies ; Reproducibility of Results ; *RNA, Messenger/genetics/metabolism ; ROC Curve ; Transcriptome/genetics ; *Ustekinumab/therapeutic use/pharmacology ; }, abstract = {BACKGROUND: Variations exist in the response of patients with Crohn's disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD.<br><br>METHODS: The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset.<br><br>RESULTS: A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers.<br><br>CONCLUSIONS: Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients.<br><br>TRIAL REGISTRATION: Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www.<br><br>CLINICALTRIALS: gov .}, }
@article {pmid38924840, year = {2024}, author = {Yang, Y and Olah, P and Radai, Z and Maia, G and Salava, A and Salo, V and Barker, J and Lauerma, A and Andersson, B and Homey, B and Fyhrquist, N and Alenius, H}, title = {Exploratory multi-omics analysis reveals host-microbe interactions associated with disease severity in psoriatic skin.}, journal = {EBioMedicine}, volume = {105}, number = {}, pages = {105222}, pmid = {38924840}, issn = {2352-3964}, mesh = {Humans ; *Psoriasis/microbiology/genetics/metabolism ; *Metagenomics/methods ; *Skin/microbiology/metabolism/pathology ; Female ; Male ; Adult ; *Severity of Illness Index ; *Host Microbial Interactions/genetics ; *Microbiota ; Middle Aged ; Cross-Sectional Studies ; Metagenome ; Gene Expression Profiling ; Transcriptome ; Gene Regulatory Networks ; Host-Pathogen Interactions/genetics ; Computational Biology/methods ; Multiomics ; }, abstract = {BACKGROUND: Psoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in Pso, yet a comprehensive multi-omics analysis of host-microbe interactions is still lacking. To bridge this gap, we conducted an exploratory study by adopting the integrated approach that combines whole metagenomic shotgun sequencing with skin transcriptomics.<br><br>METHODS: This was a cross-sectional study, adult patients with plaque-type Psoriasis (Pso) and healthy volunteers were included. Skin microbiota samples and biopsies were collected from both lesional and non-lesional skin areas on the lower back. Weighted Gene Correlation Network Analysis (WGCNA) was employed for co-expression network analysis, and cell deconvolution was conducted to estimate cell fractions. Taxonomic and functional features of the microbiome were identified using whole metagenomic shotgun sequencing. Association between host genes and microbes was analyzed using Spearman correlation.<br><br>FINDINGS: Host anti-viral responses and interferon-related networks were identified and correlated with the severity of psoriasis. The skin microbiome showed a greater prevalence of Corynebacterium simulans in the PASI severe-moderate groups, which correlated with interferon-induced host genes. Two distinct psoriatic clusters with varying disease severities were identified. Variations in the expression of cell apoptosis-associated antimicrobial peptides (AMPs) and microbial aerobic respiration I pathway may partly account for these differences in disease severity.<br><br>INTERPRETATION: Our multi-omics analysis revealed for the first time anti-viral responses and the presence of C.&#xa0;simulans associated with psoriasis severity. It also identified two psoriatic subtypes with distinct AMP and metabolic pathway expression. Our study provides new insights into understanding the host-microbe interaction in psoriasis and lays the groundwork for developing subtype-specific strategies for managing this chronic skin disease.<br><br>FUNDING: The research has received funding from the FP7 (MAARS-Grant 261366) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. GAM was supported by a scholarship provided by CAPES-PRINT, financed by the Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior - CAPES (Brazilian Government Agency). The authors thank all patients who participated in our study.}, }
@article {pmid38923832, year = {2024}, author = {Del Giudice, G and Serra, A and Pavel, A and Torres Maia, M and Saarimäki, LA and Fratello, M and Federico, A and Alenius, H and Fadeel, B and Greco, D}, title = {A Network Toxicology Approach for Mechanistic Modelling of Nanomaterial Hazard and Adverse Outcomes.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {32}, pages = {e2400389}, pmid = {38923832}, issn = {2198-3844}, support = {309329//EU FP7 project "NANOSOLUTIONS"/ ; 322761//Academy of Finland/ ; 101137742//EU project "INSIGHT"/ ; 101008099//CompSafeNano project/ ; 101043848/ERC_/European Research Council/International ; }, mesh = {*Nanostructures/toxicity ; *Adverse Outcome Pathways ; Humans ; Systems Biology/methods ; Animals ; Toxicology/methods ; }, abstract = {Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response. Hence, systems theory states that interactions store more information than individual elements, leading to the adoption of network based models to represent complex systems in many fields of life sciences. Here, they develop a network-based approach to characterize toxicological responses in the context of a biological system, inferring biological system specific networks. They directly link molecular alterations to the adverse outcome pathway (AOP) framework, establishing direct connections between omics data and toxicologically relevant phenotypic events. They apply this framework to a dataset including 31 engineered nanomaterials with different physicochemical properties in two different in vitro and one in vivo models and demonstrate how the biological system is the driving force of the observed response. This work highlights the potential of network-based methods to significantly improve their understanding of toxicological mechanisms from a systems biology perspective and provides relevant considerations and future data-driven approaches for the hazard assessment of nanomaterials and other advanced materials.}, }
@article {pmid38912690, year = {2024}, author = {Byndloss, M and Devkota, S and Duca, F and Niess, JH and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L}, title = {The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.}, journal = {Diabetes}, volume = {73}, number = {9}, pages = {1391-1410}, pmid = {38912690}, issn = {1939-327X}, support = {PID2020-119536RB-I00//Spanish Ministry of Science, Innovation and Universities MICIU/AEI/ ; 2020 (09150182010020)//ZONMW-VICI/ ; P30 ES005022/ES/NIEHS NIH HHS/United States ; //Novo Nordisk Foundation/ ; DP1 DK130687/DK/NIDDK NIH HHS/United States ; CEX2021-001189-S/10.13039/501100011033//Severo Ochoa Center of Excellence/ ; 1DP1 DK130687/DK/NIDDK NIH HHS/United States ; 310030_219210//Swiss National Science Foundation (SNSF)/ ; R01 DK123446/DK/NIDDK NIH HHS/United States ; 875534//European Union&#xe2;&#x20ac;&#x2122;s Innovative Medicine Initiative/ ; R01 DK131104/DK/NIDDK NIH HHS/United States ; 2020 (2020.10.002)//DFN-DON/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Diabetes Mellitus, Type 2/microbiology/metabolism/therapy ; Translational Research, Biomedical ; }, abstract = {This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.}, }
@article {pmid38910152, year = {2024}, author = {Byndloss, M and Devkota, S and Duca, F and Niess, JH and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L}, title = {The gut microbiota and diabetes: research, translation, and clinical applications - 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.}, journal = {Diabetologia}, volume = {67}, number = {9}, pages = {1760-1782}, pmid = {38910152}, issn = {1432-0428}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 DK131104/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 2/microbiology/metabolism ; Translational Research, Biomedical ; }, abstract = {This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.}, }
@article {pmid38909617, year = {2024}, author = {Kullberg, RFJ and Wikki, I and Haak, BW and Kauko, A and Galenkamp, H and Peters-Sengers, H and Butler, JM and Havulinna, AS and Palmu, J and McDonald, D and Benchraka, C and Abdel-Aziz, MI and Prins, M and Maitland van der Zee, AH and van den Born, BJ and Jousilahti, P and de Vos, WM and Salomaa, V and Knight, R and Lahti, L and Nieuwdorp, M and Niiranen, T and Wiersinga, WJ}, title = {Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies.}, journal = {The Lancet. Microbe}, volume = {5}, number = {9}, pages = {100864}, doi = {10.1016/S2666-5247(24)00079-X}, pmid = {38909617}, issn = {2666-5247}, mesh = {Humans ; Middle Aged ; Adult ; *Hospitalization/statistics &amp; numerical data ; Male ; Female ; *Gastrointestinal Microbiome/physiology ; Aged ; Finland/epidemiology ; *Butyrates/metabolism ; *RNA, Ribosomal, 16S/genetics/analysis ; Netherlands/epidemiology ; Young Adult ; *Bacteria/genetics/classification/isolation &amp; purification ; Feces/microbiology ; Adolescent ; Communicable Diseases/microbiology/epidemiology ; Cohort Studies ; Risk Factors ; }, abstract = {BACKGROUND: Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts.<br><br>METHODS: In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards.<br><br>FINDINGS: We profiled gut microbiota from 10&#x2009;699 participants (4248 [39&#xb7;7%] from the derivation cohort and 6451&#xa0;[60&#xb7;3%] from the validation cohort). 602 (5&#xb7;6%) participants (152 [3&#xb7;6%] from the derivation cohort; 450 [7&#xb7;0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0&#xb7;041; validation p=0&#xb7;0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0&#xb7;75 [95% CI 0&#xb7;60-0&#xb7;94] per 10% increase in butyrate producers, p=0&#xb7;013; validation cohort 0&#xb7;86 [0&#xb7;77-0&#xb7;96] per 10% increase, p=0&#xb7;0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities.<br><br>INTERPRETATION: Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections.<br><br>FUNDING: Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation.}, }
@article {pmid38904934, year = {2024}, author = {Peer, A and Samuelson, DR}, title = {The Role of the Microbiome in Allergy, Asthma, and Occupational Lung Disease.}, journal = {Current allergy and asthma reports}, volume = {24}, number = {8}, pages = {415-423}, pmid = {38904934}, issn = {1534-6315}, support = {P50 AA030407/AA/NIAAA NIH HHS/United States ; R01 DK131990/DK/NIDDK NIH HHS/United States ; R01-DK131990-01/DK/NIDDK NIH HHS/United States ; P50-AA030407/AA/NIAAA NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/immunology ; *Asthma/immunology/microbiology ; *Hypersensitivity/immunology/microbiology ; *Occupational Diseases/microbiology/immunology ; Occupational Exposure/adverse effects ; Lung Diseases/microbiology/immunology ; }, abstract = {PURPOSE OF REVIEW: The human commensal microbiota is now widely accepted as a key regulator of human health and disease. The composition of the mucosal associated microbiota has been shown to play a critical role in the lung health. The role of the mucosal microbiota in the development and severity of allergy, asthma, and occupational lung disease is only beginning to take shape. However, advances in our understanding of these links have tremendous potential to led to new clinical interventions to reduce allergy, asthma, and occupational lung disease morbidity.<br><br>RECENT FINDINGS: We review recent work describing the relationship and role of the commensal microbiota in the development of allergy, asthma, and occupational lung disease. Our review primarily focuses on occupational exposures and the effects of the microbiome, both in composition and function. Data generated from these studies may lead to the development of interventions targeted at establishing and maintaining a healthy microbiota. We also highlight the role of environmental exposures and the effects on the commensal microbial community and their potential association with occupational lung disease. This review explores the current research describing the role of the human microbiome in the regulation of pulmonary health and disease, with a specific focus on the role of the mucosal microbiota in the development of allergy, asthma, and occupational lung disease.}, }
@article {pmid38899893, year = {2024}, author = {He, J and Ma, M and Xu, Z and Guo, J and Chen, H and Yang, X and Chen, P and Liu, G}, title = {Association between semen microbiome disorder and sperm DNA damage.}, journal = {Microbiology spectrum}, volume = {12}, number = {8}, pages = {e0075924}, pmid = {38899893}, issn = {2165-0497}, support = {81971759//MOST | National Natural Science Foundation of China (NSFC)/ ; 82171604//MOST | National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Male ; Humans ; *Microbiota/genetics ; *Spermatozoa/microbiology/metabolism ; *DNA Fragmentation ; *DNA Damage ; Adult ; *Semen/microbiology ; *RNA, Ribosomal, 16S/genetics ; *Infertility, Male/microbiology/metabolism ; Lactobacillus/genetics/metabolism/isolation &amp; purification ; Bacteria/genetics/classification/isolation &amp; purification/metabolism ; Semen Analysis ; }, abstract = {DNA fragmentation index (DFI), a new biomarker to diagnose male infertility, is closely associated with poor reproductive outcomes. Previous research reported that seminal microbiome correlated with sperm DNA integrity, suggesting that the microbiome may be one of the causes of DNA damage in sperm. However, it has not been elucidated how the microbiota exerts their effects. Here, we used a combination of 16S rRNA sequencing and untargeted metabolomics techniques to investigate the role of microbiota in high sperm DNA fragmentation index (HDFI). We report that increased specific microbial profiles contribute to high sperm DNA fragmentation, thus implicating the seminal microbiome as a new therapeutic target for HDFI patients. Additionally, we found that the amount of Lactobacillus species was altered: Lactobacillus iners was enriched in HDFI patients, shedding light on the potential influence of L. iners on male reproductive health. Finally, we also identified enrichment of the acetyl-CoA fermentation to butanoate II and purine nucleobase degradation I in the high sperm DNA fragmentation samples, suggesting that butanoate may be the target metabolite of sperm DNA damage. These findings provide valuable insights into the complex interplay between microbiota and sperm quality in HDFI patients, laying the foundation for further research and potential clinical interventions.IMPORTANCEThe DNA fragmentation index (DFI) is a measure of sperm DNA fragmentation. Because high sperm DNA fragmentation index (HDFI) has been strongly associated with adverse reproductive outcomes, this has been linked to the seminal microbiome. Because the number of current treatments for HDFI is limited and most of them have no clear efficacy, it is critical to understand how semen microbiome exerts their effects on sperm DNA. Here, we evaluated the semen microbiome and its metabolites in patients with high and low sperm DNA fragmentation. We found that increased specific microbial profiles contribute to high sperm DNA fragmentation. In particular, Lactobacillus iners was uniquely correlated with high sperm DNA fragmentation. Additionally, butanoate may be the target metabolite produced by the microbiome to damage sperm DNA. Our findings support the interaction between semen microbiome and sperm DNA damage and suggest that seminal microbiome should be a new therapeutic target for HDFI patients.}, }
@article {pmid38898695, year = {2024}, author = {Wisgrill, L and Martens, A and Kasbauer, R and Eigenschink, M and Pummer, L and Redlberger-Fritz, M and Végvári, &#xc1; and Warth, B and Berger, A and Fyhrquist, N and Alenius, H}, title = {Network analysis reveals age- and virus-specific circuits in nasal epithelial cells of extremely premature infants.}, journal = {Allergy}, volume = {79}, number = {11}, pages = {3062-3081}, doi = {10.1111/all.16196}, pmid = {38898695}, issn = {1398-9995}, support = {[10.47379/LS20025]//Vienna Science and Technology Fund/ ; 2020-02090//Vetenskapsr&#xe5;det/ ; }, mesh = {Humans ; *Nasal Mucosa/virology/immunology/cytology ; *Infant, Extremely Premature/immunology ; Infant, Newborn ; *Immunity, Innate ; *Epithelial Cells/immunology/virology ; Age Factors ; Influenza A virus/immunology ; Respiratory Syncytial Virus Infections/immunology ; Adult ; }, abstract = {BACKGROUND AND OBJECTIVES: Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health-care burdens. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms.<br><br>METHODS: Using a trans-well pseudostratified nasal epithelial cell system, we examined age-dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches.<br><br>RESULTS: Our studies revealed differences in innate-receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular-viral networks, emphasizing highly relevant virus-specific pathways, independent of viral replication kinetics.<br><br>CONCLUSION: This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers crucial insights that allow for a deeper understanding of age-related differences in nasal epithelial cell immunity following respiratory virus infections.}, }
@article {pmid38898021, year = {2024}, author = {Zhu, B and Edwards, DJ and Spaine, KM and Edupuganti, L and Matveyev, A and Serrano, MG and Buck, GA}, title = {The association of maternal factors with the neonatal microbiota and health.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {5260}, pmid = {38898021}, issn = {2041-1723}, support = {R01HD092415//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; UH3AI083263//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; UH3 AI083263/AI/NIAID NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54HD080784//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; }, mesh = {Humans ; Female ; Infant, Newborn ; Pregnancy ; *Feces/microbiology ; *Microbiota ; Adult ; Cesarean Section ; Premature Birth/microbiology ; Gastrointestinal Microbiome/physiology ; Mouth/microbiology ; Rectum/microbiology ; Male ; }, abstract = {The human microbiome plays a crucial role in human health. However, the influence of maternal factors on the neonatal microbiota remains obscure. Herein, our observations suggest that the neonatal microbiotas, particularly the buccal microbiota, change rapidly within 24-48 h of birth but begin to stabilize by 48-72 h after parturition. Network analysis clustered over 200 maternal factors into thirteen distinct groups, and most associated factors were in the same group. Multiple maternal factor groups were associated with the neonatal buccal, rectal, and stool microbiotas. Particularly, a higher maternal inflammatory state and a lower maternal socioeconomic position were associated with a higher alpha diversity of the neonatal buccal microbiota and beta diversity of the neonatal stool microbiota was influenced by maternal diet and cesarean section by 24-72 h postpartum. The risk of admission of a neonate to the newborn intensive care unit was associated with preterm birth as well as higher cytokine levels and probably higher alpha diversity of the maternal buccal microbiota.}, }
@article {pmid38892281, year = {2024}, author = {Bose, D and Saha, P and Roy, S and Trivedi, A and More, M and Klimas, N and Tuteja, A and Chatterjee, S}, title = {A Double-Humanized Mouse Model for Studying Host Gut Microbiome-Immune Interactions in Gulf War Illness.}, journal = {International journal of molecular sciences}, volume = {25}, number = {11}, pages = {}, pmid = {38892281}, issn = {1422-0067}, support = {I01 CX001923/CX/CSRD VA/United States ; I01CX0001923//United States Department of Veterans Affairs/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Persian Gulf Syndrome/immunology/microbiology ; Humans ; Mice ; *Disease Models, Animal ; *Cytokines/metabolism ; Fecal Microbiota Transplantation ; }, abstract = {Unraveling the multisymptomatic Gulf War Illness (GWI) pathology and finding an effective cure have eluded researchers for decades. The chronic symptom persistence and limitations for studying the etiologies in mouse models that differ significantly from those in humans pose challenges for drug discovery and finding effective therapeutic regimens. The GWI exposome differs significantly in the study cohorts, and the above makes it difficult to recreate a model closely resembling the GWI symptom pathology. We have used a double engraftment strategy for reconstituting a human immune system coupled with human microbiome transfer to create a humanized-mouse model for GWI. Using whole-genome shotgun sequencing and blood immune cytokine enzyme linked immunosorbent assay (ELISA), we show that our double humanized mice treated with Gulf War (GW) chemicals show significantly altered gut microbiomes, similar to those reported in a Veteran cohort of GWI. The results also showed similar cytokine profiles, such as increased levels of IL-1β, IL-6, and TNF R-1, in the double humanized model, as found previously in a human cohort. Further, a novel GWI Veteran fecal microbiota transfer was used to create a second alternative model that closely resembled the microbiome and immune-system-associated pathology of a GWI Veteran. A GWI Veteran microbiota transplant in humanized mice showed a human microbiome reconstitution and a systemic inflammatory pathology, as reflected by increases in interleukins 1β, 6, 8 (IL-1β, IL-6, IL-8), tumor necrosis factor receptor 1 (TNF R-1), and endotoxemia. In conclusion, though preliminary, we report a novel in vivo model with a human microbiome reconstitution and an engrafted human immune phenotype that may help to better understand gut-immune interactions in GWI.}, }
@article {pmid38890378, year = {2024}, author = {Khawaja, T and Mäklin, T and Kallonen, T and Gladstone, RA and Pöntinen, AK and Mero, S and Thorpe, HA and Samuelsen, &#xd8; and Parkhill, J and Izhar, M and Akhtar, MW and Corander, J and Kantele, A}, title = {Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {5196}, pmid = {38890378}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; AMRIWA//Academy of Finland (Suomen Akatemia)/ ; 206194/WT_/Wellcome Trust/United Kingdom ; EuroHPC//Academy of Finland (Suomen Akatemia)/ ; }, mesh = {Pakistan/epidemiology ; Humans ; *Escherichia coli/genetics/drug effects/isolation &amp; purification ; *Anti-Bacterial Agents/pharmacology ; *Escherichia coli Infections/epidemiology/microbiology/drug therapy ; *Drug Resistance, Multiple, Bacterial/genetics ; *High-Throughput Nucleotide Sequencing ; Feces/microbiology ; Female ; Male ; Genome, Bacterial/genetics ; Adult ; Genetic Variation ; Middle Aged ; Young Adult ; Phylogeny ; Adolescent ; Child ; }, abstract = {Multi-drug resistant (MDR) E. coli constitute a major public health burden globally, reaching the highest prevalence in the global south yet frequently flowing with travellers to other regions. However, our comprehension of the entire genetic diversity of E. coli colonising local populations remains limited. We quantified this diversity, its associated antimicrobial resistance (AMR), and assessed the impact of antibiotic use by recruiting 494 outpatients and 423 community dwellers in the Punjab province, Pakistan. Rectal swab and stool samples were cultured on CLED agar and DNA extracted from plate sweeps was sequenced en masse to capture both the genetic and AMR diversity of E. coli. We assembled 5,247 E. coli genomes from 1,411 samples, displaying marked genetic diversity in gut colonisation. Compared with high income countries, the Punjabi population generally showed a markedly different distribution of genetic lineages and AMR determinants, while use of antibiotics elevated the prevalence of well-known globally circulating MDR clinical strains. These findings implicate that longitudinal multi-regional genomics-based surveillance of both colonisation and infections is a prerequisite for developing mechanistic understanding of the interplay between ecology and evolution in the maintenance and dissemination of (MDR) E. coli.}, }
@article {pmid38890150, year = {2024}, author = {Fu, C and Zhang, Y and Liang, L and Lin, H and Shan, K and Liu, F and Feng, N}, title = {The microbiota in patients with interstitial cystitis/bladder pain syndrome: a systematic review.}, journal = {BJU international}, volume = {134}, number = {6}, pages = {869-880}, doi = {10.1111/bju.16439}, pmid = {38890150}, issn = {1464-410X}, support = {THRCJH20200104//Wuxi Taihu Lake Talent Plan, Leading Talents in Medical and Health Profession Project/ ; }, mesh = {*Cystitis, Interstitial/microbiology ; Humans ; *Microbiota ; Female ; Gastrointestinal Microbiome ; Vagina/microbiology ; }, abstract = {OBJECTIVE: To comprehensively review and critically assess the literature on microbiota differences between patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) and normal controls and to provide clinical practice guidelines.<br><br>MATERIALS AND METHODS: In this systematic review, we evaluated previous research on microbiota disparities between IC/BPS and normal controls, as well as distinctions among IC/BPS subgroups. A comprehensive literature search was conducted across PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Relevant studies were shortlisted based on predetermined inclusion and exclusion criteria, followed by quality assessment. The primary focus was identifying specific taxonomic variations among these cohorts.<br><br>RESULTS: A total of 12 studies met the selection criteria. Discrepancies were adjudicated by a third reviewer. The Newcastle-Ottawa Scale was used to assess study quality. Predominantly, the studies focused on disparities in urine microbiota between IC/BPS patients and normal controls, with one study examining gut microbiota differences between the groups, and two studies exploring vaginal microbiota distinctions. Unfortunately, analyses of discrepancies in other microbiota were limited. Our findings revealed evidence of distinct bacterial abundance variations, particularly involving Lactobacillus, alongside variations in specific metabolites among IC/BPS patients compared to controls.<br><br>CONCLUSIONS: Currently, there is evidence suggesting significant variations in the diversity and species composition of the urinary microbiota between individuals diagnosed with IC/BPS and control groups. In the foreseeable future, urologists should consider urine microbiota dysbiosis as a potential aetiology for IC, with potential clinical implications for diagnosis and treatment.}, }
@article {pmid38884446, year = {2024}, author = {Moussa, AY}, title = {Streptomyces Endophytes in Edible Plants: New Insights into their Chemistry and Health Benefits.}, journal = {Chemistry &amp; biodiversity}, volume = {21}, number = {10}, pages = {e202400888}, doi = {10.1002/cbdv.202400888}, pmid = {38884446}, issn = {1612-1880}, mesh = {*Streptomyces/chemistry/metabolism/isolation &amp; purification ; *Endophytes/chemistry/metabolism ; Humans ; *Plants, Edible/chemistry/microbiology ; Anti-Bacterial Agents/pharmacology/chemistry/isolation &amp; purification ; }, abstract = {Streptomyces is the largest source of microbial antibiotics with about 50 % of marketed antimicrobial drugs originating from this genus. Endophytic streptomyces are the link between medicinal plants and the microbial world. Endophytic Streptomyces in edible plants were not targeted before despite their uniqueness and importance. In this review, we analyzed the chemical diversity of more than 150 compounds belonging to endophytic Streptomyces chemical classes such as alkaloids, polyketides, peptides, macrolides and terpenes and their biological activities. This analysis showed a dominant antimicrobial effect for most of the isolated compounds and highlighted an underestimated diversity to be studied or repurposed for other biological activities. Return to edible plants use and conducting toxicity studies to rationalize their nutraceutical potential based on their beneficial endophytes is urged. Although there are many studies for non-vertebrates, the nutraceutical potential of these plants is expected to improve the gut microbiota since they are enriched with bioactive compounds from streptomyces species. This is the first review to discuss edible plants associated streptomyces, and we prospect that many studies will follow to unravel the mysterious health benefits of streptomyces in the human microbiome and encourage the revival of a correct lifestyle for the sake of a healthier microbiome.}, }
@article {pmid38882496, year = {2024}, author = {Zhang, Z and Zhang, HL and Yang, DH and Hao, Q and Yang, HW and Meng, DL and Meindert de Vos, W and Guan, LL and Liu, SB and Teame, T and Gao, CC and Ran, C and Yang, YL and Yao, YY and Ding, QW and Zhou, ZG}, title = {Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects.}, journal = {iMeta}, volume = {3}, number = {2}, pages = {e181}, pmid = {38882496}, issn = {2770-596X}, abstract = {Lactobacillus rhamnosus GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3-GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2-GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3-GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.}, }
@article {pmid38882486, year = {2024}, author = {Wu, D and Guan, YX and Li, CH and Zheng, Q and Yin, ZJ and Wang, H and Liu, NN}, title = {"Nutrient-fungi-host" tripartite interaction in cancer progression.}, journal = {iMeta}, volume = {3}, number = {2}, pages = {e170}, pmid = {38882486}, issn = {2770-596X}, abstract = {The human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer-related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue-resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside.}, }
@article {pmid38878076, year = {2024}, author = {Jawanda, IK and Soni, T and Kumari, S and Prabha, V}, title = {The evolving facets of vaginal microbiota transplantation: reinvigorating the unexplored frontier amid complex challenges.}, journal = {Archives of microbiology}, volume = {206}, number = {7}, pages = {306}, pmid = {38878076}, issn = {1432-072X}, mesh = {Animals ; Female ; Humans ; Anti-Bacterial Agents/therapeutic use ; *Dysbiosis/microbiology/therapy ; Lactobacillus ; *Microbiota ; *Probiotics/administration &amp; dosage ; *Vagina/microbiology ; }, abstract = {In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as "eubiosis," as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.}, }
@article {pmid38874821, year = {2024}, author = {Wu, K and Chen, J and Lin, J and Zhu, E and Xu, X and Yan, X and Ju, L and Huang, M and Zhang, Y}, title = {The role of ferroptosis in DM-induced liver injury.}, journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine}, volume = {37}, number = {5}, pages = {1191-1200}, pmid = {38874821}, issn = {1572-8773}, mesh = {Animals ; *Ferroptosis ; Male ; Rats ; *Receptors, Transferrin/metabolism ; *Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism ; Diabetes Mellitus, Experimental/metabolism/pathology/chemically induced ; Rats, Sprague-Dawley ; Liver/pathology/metabolism ; Streptozocin ; Superoxide Dismutase/metabolism ; Glutathione/metabolism ; Cation Transport Proteins/metabolism/genetics ; Malondialdehyde/metabolism ; Iron/metabolism ; Ferroportin ; }, abstract = {The liver damage caused by Diabetes Mellitus (DM) has attracted increasing attention in recent years. Liver injury in DM can be caused by ferroptosis, a form of cell death caused by iron overload. However, the role of iron transporters in this context is still not clear. Herein, we attempted to shed light on the pathophysiological mechanism of ferroptosis. DM was induced in 8-week-old male rats by streptozotocin (STZ) before assessment of the degree of liver injury. Together with histopathological changes, variations in glutathione peroxidase 4 (GPX4), glutathione (GSH), superoxide dismutase (SOD), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), ferritin light chain (FTL), ferroportin and Prussian blue staining, were monitored in rat livers before and after treatment with Fer-1. In the liver of STZ-treated rats, GSH and SOD levels decreased, whereas those of malondialdehyde (MDA) increased. Expression of TFR1, FTH and FTL increased whereas that of glutathione peroxidase 4 (GPX4) and ferroportin did not change significantly. Prussian blue staining showed that iron levels increased. Histopathology showed liver fibrosis and decreased glycogen content. Fer-1 treatment reduced iron and MDA levels but GSH and SOD levels were unchanged. Expression of FTH and FTL was reduced whereas that of ferroportin showed a mild decrease. Fer-1 treatment alleviated liver fibrosis, increased glycogen content and mildly improved liver function. Our study demonstrates that ferroptosis is involved in DM-induced liver injury. Regulating the levels of iron transporters may become a new therapeutic strategy in ferroptosis-induced liver injury.}, }
@article {pmid38873568, year = {2024}, author = {Shang, Z and Pai, L and Patil, S}, title = {Unveiling the dynamics of gut microbial interactions: a review of dietary impact and precision nutrition in gastrointestinal health.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1395664}, pmid = {38873568}, issn = {2296-861X}, abstract = {The human microbiome, a dynamic ecosystem within the gastrointestinal tract, plays a pivotal role in shaping overall health. This review delves into six interconnected sections, unraveling the intricate relationship between diet, gut microbiota, and their profound impact on human health. The dance of nutrients in the gut orchestrates a complex symphony, influencing digestive processes and susceptibility to gastrointestinal disorders. Emphasizing the bidirectional communication between the gut and the brain, the Brain-Gut Axis section highlights the crucial role of dietary choices in physical, mental, and emotional well-being. Autoimmune diseases, particularly those manifesting in the gastrointestinal tract, reveal the delicate balance disrupted by gut microbiome imbalances. Strategies for reconciling gut microbes through diets, precision nutrition, and clinical indications showcase promising avenues for managing gastrointestinal distress and revolutionizing healthcare. From the Low-FODMAP diet to neuro-gut interventions, these strategies provide a holistic understanding of the gut's dynamic world. Precision nutrition, as a groundbreaking discipline, holds transformative potential by tailoring dietary recommendations to individual gut microbiota compositions, reshaping the landscape of gastrointestinal health. Recent advancements in clinical indications, including exact probiotics, fecal microbiota transplantation, and neuro-gut interventions, signify a new era where the gut microbiome actively participates in therapeutic strategies. As the microbiome takes center stage in healthcare, a paradigm shift toward personalized and effective treatments for gastrointestinal disorders emerges, reflecting the symbiotic relationship between the human body and its microbial companions.}, }
@article {pmid38873138, year = {2024}, author = {Chi, J and Ye, J and Zhou, Y}, title = {A GLM-based zero-inflated generalized Poisson factor model for analyzing microbiome data.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1394204}, pmid = {38873138}, issn = {1664-302X}, abstract = {MOTIVATION: High-throughput sequencing technology facilitates the quantitative analysis of microbial communities, improving the capacity to investigate the associations between the human microbiome and diseases. Our primary motivating application is to explore the association between gut microbes and obesity. The complex characteristics of microbiome data, including high dimensionality, zero inflation, and over-dispersion, pose new statistical challenges for downstream analysis.<br><br>RESULTS: We propose a GLM-based zero-inflated generalized Poisson factor analysis (GZIGPFA) model to analyze microbiome data with complex characteristics. The GZIGPFA model is based on a zero-inflated generalized Poisson (ZIGP) distribution for modeling microbiome count data. A link function between the generalized Poisson rate and the probability of excess zeros is established within the generalized linear model (GLM) framework. The latent parameters of the GZIGPFA model constitute a low-rank matrix comprising a low-dimensional score matrix and a loading matrix. An alternating maximum likelihood algorithm is employed to estimate the unknown parameters, and cross-validation is utilized to determine the rank of the model in this study. The proposed GZIGPFA model demonstrates superior performance and advantages through comprehensive simulation studies and real data applications.}, }
@article {pmid38868076, year = {2024}, author = {Takallu, S and Aiyelabegan, HT and Zomorodi, AR and Alexandrovna, KV and Aflakian, F and Asvar, Z and Moradi, F and Behbahani, MR and Mirzaei, E and Sarhadi, F and Vakili-Ghartavol, R}, title = {Nanotechnology improves the detection of bacteria: Recent advances and future perspectives.}, journal = {Heliyon}, volume = {10}, number = {11}, pages = {e32020}, pmid = {38868076}, issn = {2405-8440}, abstract = {Nanotechnology has advanced significantly, particularly in biomedicine, showing promise for nanomaterial applications. Bacterial infections pose persistent public health challenges due to the lack of rapid pathogen detection methods, resulting in antibiotic overuse and bacterial resistance, threatening the human microbiome. Nanotechnology offers a solution through nanoparticle-based materials facilitating early bacterial detection and combating resistance. This study explores recent research on nanoparticle development for controlling microbial infections using various nanotechnology-driven detection methods. These approaches include Surface Plasmon Resonance (SPR) Sensors, Surface-Enhanced Raman Scattering (SERS) Sensors, Optoelectronic-based sensors, Bacteriophage-Based Sensors, and nanotechnology-based aptasensors. These technologies provide precise bacteria detection, enabling targeted treatment and infection prevention. Integrating nanoparticles into detection approaches holds promise for enhancing patient outcomes and mitigating harmful bacteria spread in healthcare settings.}, }
@article {pmid38866914, year = {2024}, author = {Heinzel, S and Jureczek, J and Kainulainen, V and Nieminen, AI and Suenkel, U and von Thaler, AK and Kaleta, C and Eschweiler, GW and Brockmann, K and Aho, VTE and Auvinen, P and Maetzler, W and Berg, D and Scheperjans, F}, title = {Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13513}, pmid = {38866914}, issn = {2045-2322}, support = {675915//Germany Research Society/ ; 310835//Research Council of Finland/ ; }, mesh = {Humans ; *Leukocyte L1 Antigen Complex/analysis/metabolism ; *Feces/microbiology/chemistry ; *Dysbiosis/diagnosis ; *Gastrointestinal Microbiome ; Aged ; Female ; Male ; *Biomarkers/blood/analysis ; Middle Aged ; Cohort Studies ; Inflammatory Bowel Diseases/blood/metabolism/microbiology ; }, abstract = {Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0-50 μg/g; n = 602), moderate (> 50-100 μg/g; n = 64) and high (> 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.}, }
@article {pmid38862605, year = {2024}, author = {}, title = {The human microbiome and immune response shift during spaceflight.}, journal = {Nature microbiology}, volume = {9}, number = {7}, pages = {1640-1641}, pmid = {38862605}, issn = {2058-5276}, mesh = {*Space Flight ; Humans ; *Microbiota/immunology ; Immunity ; Weightlessness ; Gastrointestinal Microbiome/immunology ; }, }
@article {pmid38862604, year = {2024}, author = {Tierney, BT and Kim, J and Overbey, EG and Ryon, KA and Foox, J and Sierra, MA and Bhattacharya, C and Damle, N and Najjar, D and Park, J and Garcia Medina, JS and Houerbi, N and Meydan, C and Wain Hirschberg, J and Qiu, J and Kleinman, AS and Al-Ghalith, GA and MacKay, M and Afshin, EE and Dhir, R and Borg, J and Gatt, C and Brereton, N and Readhead, BP and Beyaz, S and Venkateswaran, KJ and Wiseman, K and Moreno, J and Boddicker, AM and Zhao, J and Lajoie, BR and Scott, RT and Altomare, A and Kruglyak, S and Levy, S and Church, GM and Mason, CE}, title = {Longitudinal multi-omics analysis of host microbiome architecture and immune responses during short-term spaceflight.}, journal = {Nature microbiology}, volume = {9}, number = {7}, pages = {1661-1675}, pmid = {38862604}, issn = {2058-5276}, support = {R01 CA249054/CA/NCI NIH HHS/United States ; R01 MH117406/MH/NIMH NIH HHS/United States ; NNX14AH50G//NASA | Johnson Space Center (JSC)/ ; NNX16AO69A//NASA | Johnson Space Center (JSC)/ ; R01MH117406//U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01 ES032638/ES/NIEHS NIH HHS/United States ; R01 AI151059/AI/NIAID NIH HHS/United States ; P30 CA045508/CA/NCI NIH HHS/United States ; }, mesh = {*Space Flight ; Humans ; Longitudinal Studies ; *Microbiota/immunology ; *Metagenomics ; *Astronauts ; *Bacteria/classification/genetics/immunology ; Male ; Gene Expression Profiling ; Adult ; Middle Aged ; Female ; Transcriptome ; Multiomics ; }, abstract = {Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning.}, }
@article {pmid38862602, year = {2024}, author = {Osbelt, L and Almási, &#xc9;DH and Wende, M and Kienesberger, S and Voltz, A and Lesker, TR and Muthukumarasamy, U and Knischewski, N and Nordmann, E and Bielecka, AA and Giralt-Zúñiga, M and Kaganovitch, E and Kühne, C and Baier, C and Pietsch, M and Müsken, M and Greweling-Pils, MC and Breinbauer, R and Flieger, A and Schlüter, D and Müller, R and Erhardt, M and Zechner, EL and Strowig, T}, title = {Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms.}, journal = {Nature microbiology}, volume = {9}, number = {7}, pages = {1792-1811}, pmid = {38862602}, issn = {2058-5276}, support = {DOC 50/FWF_/Austrian Science Fund FWF/Austria ; 01KI1824//Joint Programming Initiative on Antimicrobial Resistance (Joint Programming Initiative for Antimicrobial Resistance)/ ; }, mesh = {*Klebsiella oxytoca/genetics/metabolism ; Animals ; Mice ; *Salmonella Infections/microbiology ; *Salmonella typhimurium/genetics/metabolism/growth &amp; development/drug effects ; Humans ; Disease Models, Animal ; Enterotoxins/metabolism/genetics ; Female ; Mice, Inbred C57BL ; Klebsiella Infections/microbiology ; Microbiota ; Gastrointestinal Microbiome ; Antibiosis ; Benzodiazepinones ; }, abstract = {The Klebsiella oxytoca species complex is part of the human microbiome, especially during infancy and childhood. K. oxytoca species complex strains can produce enterotoxins, namely, tilimycin and tilivalline, while also contributing to colonization resistance (CR). The relationship between these seemingly contradictory roles is not well understood. Here, by coupling ex vivo assays with CRISPR-mutagenesis and various mouse models, we show that K. oxytoca provides CR against Salmonella Typhimurium. In vitro, the antimicrobial activity against various Salmonella strains depended on tilimycin production and was induced by various simple carbohydrates. In vivo, CR against Salmonella depended on toxin production in germ-free mice, while it was largely toxin-independent in mice with residual microbiota. This was linked to the relative levels of toxin-inducing carbohydrates in vivo. Finally, dulcitol utilization was essential for toxin-independent CR in gnotobiotic mice. Together, this demonstrates that nutrient availability is key to both toxin-dependent and substrate-driven competition between K. oxytoca and Salmonella.}, }
@article {pmid38855423, year = {2024}, author = {Zhang, L and Wu, R and Ma, T and Fu, W and Chen, J and Li, L and He, Q}, title = {Investigation on the Therapeutic Mechanism of Danbie Capsules for Endometriosis: A Network Pharmacology Approach.}, journal = {International journal of general medicine}, volume = {17}, number = {}, pages = {2557-2574}, pmid = {38855423}, issn = {1178-7074}, abstract = {OBJECTIVE: To explore the active substances and targets of Danbie Capsules in Endometriosis therapy.<br><br>METHODS: This study was conducted through TCMSP and published literature screened and obtained 183 active substances of Danbie Capsules, combined and intersected with Endometriosis target genes collected and screened in the GEO database, obtained 24 target genes for Endometriosis treatment, and mapped the target network map of Danbie Capsules active substances against Endometriosis. The network was analyzed with the aid of Cytoscape version 3.9.1. With the aid of the platform of the STRING data analysis, PPI network analysis was conducted on 24 anti-Endometriosis targets of the Danbie Capsules.<br><br>RESULTS: The research results obtained three critical active substances, namely, Quercetin, &#x3b2;-sitosterol, and Luteolin. Seven critical targets were identified, and two representative genes (TP53 and AKT1) have been verified in Macromolecular docking and immunohistochemical verification.<br><br>CONCLUSION: The active substances of Danbie Capsules in the treatment of Endometriosis are Quercetin, &#x3b2;-sitosterol and Luteolin, and the main targets are TP53 and AKT1.}, }
@article {pmid38854053, year = {2024}, author = {Byrne, SR and DeMott, MS and Yuan, Y and Ghanegolmohammadi, F and Kaiser, S and Fox, JG and Alm, EJ and Dedon, PC}, title = {Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38854053}, issn = {2692-8205}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; T32 ES007020/ES/NIEHS NIH HHS/United States ; }, abstract = {BACKGROUND: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically-reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by dnd and ssp gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications.<br><br>RESULTS: Exploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5-10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m[6]dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor's Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Firmicutes, Actinobacteria, and Proteobacteria, which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies.<br><br>CONCLUSIONS: The results of our studies provide a benchmark for understanding the behavior of an abundant and chemically-reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.}, }
@article {pmid38849871, year = {2024}, author = {Lu, W and Aihaiti, A and Abudukeranmu, P and Liu, Y and Gao, H}, title = {Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {545}, pmid = {38849871}, issn = {1479-5876}, mesh = {Humans ; *Digestive System Neoplasms/microbiology/therapy ; *Bacteria/metabolism ; Gastrointestinal Microbiome ; Animals ; }, abstract = {Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.}, }
@article {pmid38849503, year = {2024}, author = {Kingsley, SF and Seo, Y and Wood, A and Wani, KA and Gonzalez, X and Irazoqui, J and Finkel, SE and Tissenbaum, HA}, title = {Glucose-fed microbiota alters C. elegans intestinal epithelium and increases susceptibility to multiple bacterial pathogens.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {13177}, pmid = {38849503}, issn = {2045-2322}, support = {T32 AI095213/AI/NIAID NIH HHS/United States ; W911NF1210321//U.S. Army Research Office/ ; R35 GM149284/GM/NIGMS NIH HHS/United States ; 5R21AG067317//National Institutes of Aging,United States/ ; R21 AI169842/AI/NIAID NIH HHS/United States ; R01 GM101056/GM/NIGMS NIH HHS/United States ; }, mesh = {*Caenorhabditis elegans/microbiology ; Animals ; *Glucose/metabolism ; *Intestinal Mucosa/microbiology/metabolism ; *Gastrointestinal Microbiome ; *Escherichia coli ; Reactive Oxygen Species/metabolism ; Longevity ; Disease Susceptibility ; }, abstract = {Overconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota, strongly associated with our overall health, has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspecies C. elegans/E. coli system, where E. coli are subjected to high sugar, then consumed by the bacterivore host C. elegans to become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan (locomotion), reduced stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased concentration of reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose-fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar, such as a Western diet, has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases.}, }
@article {pmid38846023, year = {2024}, author = {Jones, J and Murphy, CP and Sleator, RD and Culligan, EP}, title = {An exploratory in silico analysis of bacteriocin gene clusters in the urobiome.}, journal = {Microbiome research reports}, volume = {3}, number = {2}, pages = {24}, pmid = {38846023}, issn = {2771-5965}, abstract = {Background: The role of the urobiome in health and disease remains an understudied area compared to the rest of the human microbiome. Enhanced culturing techniques and next-generation sequencing technologies have identified the urobiome as an untapped source of potentially novel antimicrobials. The aim of this study was to screen the urobiome for genes encoding bacteriocin production. Methods: The genomes of 181 bacterial urobiome isolates were screened in silico for the presence of bacteriocin gene clusters using the bacteriocin mining tool BAGEL4 and secondary metabolite screening tool antiSMASH7. Results: From these isolates, an initial 263 areas of interest were identified, manually annotated, and evaluated for potential bacteriocin gene clusters. This resulted in 32 isolates containing 80 potential bacteriocin gene clusters, of which 72% were identified as class II, 13.75% as class III, 8.75% as class I, and 5% as unclassified bacteriocins. Conclusion: Overall, 53 novel variants were discovered, including nisin, gassericin, ubericin, and colicins.}, }
@article {pmid38843312, year = {2024}, author = {Davison, C and Tallman, S and de Ste-Croix, M and Antonio, M and Oggioni, MR and Kwambana-Adams, B and Freund, F and Beleza, S}, title = {Long-term evolution of Streptococcus mitis and Streptococcus pneumoniae leads to higher genetic diversity within rather than between human populations.}, journal = {PLoS genetics}, volume = {20}, number = {6}, pages = {e1011317}, pmid = {38843312}, issn = {1553-7404}, mesh = {*Streptococcus mitis/genetics ; Humans ; *Streptococcus pneumoniae/genetics ; *Genetic Variation ; *Evolution, Molecular ; *Genome, Bacterial ; Phylogeny ; Genetics, Population ; }, abstract = {Evaluation of the apportionment of genetic diversity of human bacterial commensals within and between human populations is an important step in the characterization of their evolutionary potential. Recent studies showed a correlation between the genomic diversity of human commensal strains and that of their host, but the strength of this correlation and of the geographic structure among human populations is a matter of debate. Here, we studied the genomic diversity and evolution of the phylogenetically related oro-nasopharyngeal healthy-carriage Streptococcus mitis and Streptococcus pneumoniae, whose lifestyles range from stricter commensalism to high pathogenic potential. A total of 119 S. mitis genomes showed higher within- and among-host variation than 810 S. pneumoniae genomes in European, East Asian and African populations. Summary statistics of the site-frequency spectrum for synonymous and non-synonymous variation and ABC modelling showed this difference to be due to higher ancestral bacterial population effective size (Ne) in S. mitis, whose genomic variation has been maintained close to mutation-drift equilibrium across (at least many) generations, whereas S. pneumoniae has been expanding from a smaller ancestral bacterial population. Strikingly, both species show limited differentiation among human populations. As genetic differentiation is inversely proportional to the product of effective population size and migration rate (Nem), we argue that large Ne have led to similar differentiation patterns, even if m is very low for S. mitis. We conclude that more diversity within than among human populations and limited population differentiation must be common features of the human microbiome due to large Ne.}, }
@article {pmid38841413, year = {2024}, author = {Manrique, P and Montero, I and Fernandez-Gosende, M and Martinez, N and Cantabrana, CH and Rios-Covian, D}, title = {Past, present, and future of microbiome-based therapies.}, journal = {Microbiome research reports}, volume = {3}, number = {2}, pages = {23}, pmid = {38841413}, issn = {2771-5965}, abstract = {Technological advances in studying the human microbiome in depth have enabled the identification of microbial signatures associated with health and disease. This confirms the crucial role of microbiota in maintaining homeostasis and the host health status. Nowadays, there are several ways to modulate the microbiota composition to effectively improve host health; therefore, the development of therapeutic treatments based on the gut microbiota is experiencing rapid growth. In this review, we summarize the influence of the gut microbiota on the development of infectious disease and cancer, which are two of the main targets of microbiome-based therapies currently being developed. We analyze the two-way interaction between the gut microbiota and traditional drugs in order to emphasize the influence of gut microbial composition on drug effectivity and treatment response. We explore the different strategies currently available for modulating this ecosystem to our benefit, ranging from 1st generation intervention strategies to more complex 2nd generation microbiome-based therapies and their regulatory framework. Lastly, we finish with a quick overview of what we believe is the future of these strategies, that is 3rd generation microbiome-based therapies developed with the use of artificial intelligence (AI) algorithms.}, }
@article {pmid38838470, year = {2024}, author = {Matharu, D and Ponsero, AJ and Lengyel, M and Meszaros-Matwiejuk, A and Kolho, KL and de Vos, WM and Molnar-Gabor, D and Salonen, A}, title = {Human milk oligosaccharide composition is affected by season and parity and associates with infant gut microbiota in a birth mode dependent manner in a Finnish birth cohort.}, journal = {EBioMedicine}, volume = {104}, number = {}, pages = {105182}, pmid = {38838470}, issn = {2352-3964}, mesh = {Humans ; *Milk, Human/chemistry/metabolism ; *Gastrointestinal Microbiome ; *Oligosaccharides/metabolism/analysis ; Female ; Finland ; Infant ; *Parity ; *Seasons ; Birth Cohort ; Metagenomics/methods ; Pregnancy ; Infant, Newborn ; Adult ; Metagenome ; Male ; Feces/microbiology ; }, abstract = {BACKGROUND: Human milk oligosaccharides (HMOs), their determinants, infant gut microbiota and health are under extensive research; however, seldom jointly addressed. Leveraging data from the HELMi birth cohort, we investigated them collectively, considering maternal and infant secretor status.<br><br>METHODS: HMO composition in breastmilk collected 3 months postpartum (n&#xa0;=&#xa0;350 mothers) was profiled using high-performance liquid chromatography. Infant gut microbiota taxonomic and functional development was studied at 3, 6, and 12 months (n&#xa0;=&#xa0;823 stool samples) via shotgun metagenomic sequencing, focusing on HMO metabolism via glycoside hydrolase (GH) analysis. Maternal and infant secretor statuses were identified through phenotyping and genotyping, respectively. Child health, emphasizing allergies and antibiotics as proxies for infectious diseases, was recorded until 2 years.<br><br>FINDINGS: Mother's parity, irritable bowel syndrome, gestational diabetes, and season of milk collection associated with HMO composition. Neither maternal nor infant secretor status associated with infant gut microbiota, except for a few taxa linked to individual HMOs. Analysis stratified for birth mode revealed distinct patterns between the infant gut microbiota and HMOs. Child health parameters were not associated to infant or maternal secretor status.<br><br>INTERPRETATION: This comprehensive exploration unveils intricate links between secretor genotype, maternal factors, HMO composition, infant microbiota, and child health. Understanding these nuanced relationships is paramount for refining strategies to optimize early life nutrition and its enduring impact on long-term health.<br><br>FUNDING: Sweet Crosstalk EU H2020 MSCA ITN, Academy of Finland, Mary and Georg C. Ehrnrooth Foundation, P&#xe4;ivikki and Sakari Sohlberg Foundation, and Tekes.}, }
@article {pmid38830891, year = {2024}, author = {Lopes, W and Amor, DR and Gore, J}, title = {Cooperative growth in microbial communities is a driver of multistability.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4709}, pmid = {38830891}, issn = {2041-1723}, mesh = {*Microbiota/physiology ; Humans ; *Microbial Interactions ; Bacteria/genetics/classification/metabolism/growth &amp; development ; Glutamic Acid/metabolism ; Models, Biological ; Coculture Techniques ; }, abstract = {Microbial communities often exhibit more than one possible stable composition for the same set of external conditions. In the human microbiome, these persistent changes in species composition and abundance are associated with health and disease states, but the drivers of these alternative stable states remain unclear. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A biochemical screening reveals that glutamate either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.}, }
@article {pmid38828147, year = {2024}, author = {Tan, J and Zhang, J and Hu, C and Wang, G and Ren, Q and Wang, C and Dan, J and Zeng, Z and Hu, J and Zhu, W and Liang, J and Cai, J and Liu, Y and Yan, G and Lin, Y}, title = {Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK‒STAT pathway.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {6}, pages = {2554-2566}, pmid = {38828147}, issn = {2211-3835}, abstract = {Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.}, }
@article {pmid38826830, year = {2024}, author = {Sahle, Z and Engidaye, G and Shenkute Gebreyes, D and Adenew, B and Abebe, TA}, title = {Fecal microbiota transplantation and next-generation therapies: A review on targeting dysbiosis in metabolic disorders and beyond.}, journal = {SAGE open medicine}, volume = {12}, number = {}, pages = {20503121241257486}, pmid = {38826830}, issn = {2050-3121}, abstract = {The human microbiome, particularly the gut microbiome, has emerged as a central determinant of health and disease. Dysbiosis, an imbalance in the microbial composition of the gut, is associated with a variety of metabolic and other diseases, highlighting the potential for microbiota-targeted treatments. Fecal microbiota transplantation has received considerable attention as a promising therapy to modulate the gut microbiome and restore microbial homeostasis. However, challenges remain, including standardization, safety, and long-term efficacy. This review summarizes current knowledge on fecal microbiota transplantation and describes the next generation therapies targeting microbiome. This review looked at the mechanistic understanding of fecal microbiota transplantation and alternative strategies, elucidating their potential role in improving dysbiosis-associated metabolic disorders, such as obesity, and type 2 diabetes and others. Additionally, this review discussed the growing application of therapies targeting the gut microbiome. Insights from clinical trials, preclinical studies, and emerging technologies provide a comprehensive overview of the evolving landscape of microbiome-based interventions. Through a critical assessment of current advances and prospects, this review aims to highlight the therapeutic potential of targeting gut microbiome and pave the way for innovative approaches in precision medicine and personalized treatments.}, }
@article {pmid38823201, year = {2024}, author = {Kasperek, MC and Velasquez Galeas, A and Caetano-Silva, ME and Xie, Z and Ulanov, A and La Frano, M and Devkota, S and Miller, MJ and Allen, JM}, title = {Microbial aromatic amino acid metabolism is modifiable in fermented food matrices to promote bioactivity.}, journal = {Food chemistry}, volume = {454}, number = {}, pages = {139798}, doi = {10.1016/j.foodchem.2024.139798}, pmid = {38823201}, issn = {1873-7072}, mesh = {Humans ; *Fermented Foods/analysis/microbiology ; *Fermentation ; *Amino Acids, Aromatic/metabolism ; *Receptors, Aryl Hydrocarbon/metabolism ; Lactobacillales/metabolism ; Lactates/metabolism ; }, abstract = {Ingestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity relates to microbial metabolites derived from aromatic amino acids, termed aryl-lactates. Using targeted metabolomics, we established the presence of aryl-lactates in commercially available fermented foods. After pinpointing fermented food-associated lactic acid bacteria that produce high levels of aryl-lactates, we identified fermentation conditions to increase aryl-lactate production in food matrices up to 5 × 10[3] fold vs. standard fermentation conditions. Using ex vivo reporter assays, we found that food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and commercial products. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance AhR bioactivity of fermented foods to be leveraged to improve human health.}, }
@article {pmid38820745, year = {2024}, author = {Haange, SB and Riesbeck, S and Aldehoff, AS and Engelmann, B and Jensen Pedersen, K and Castaneda-Monsalve, V and Rolle-Kampczyk, U and von Bergen, M and Jehmlich, N}, title = {Chemical mixture effects on the simplified human intestinal microbiota: Assessing xenobiotics at environmentally realistic concentrations.}, journal = {Journal of hazardous materials}, volume = {474}, number = {}, pages = {134683}, doi = {10.1016/j.jhazmat.2024.134683}, pmid = {38820745}, issn = {1873-3336}, mesh = {Humans ; *Xenobiotics/toxicity/metabolism ; *Fluorocarbons/toxicity ; *Gastrointestinal Microbiome/drug effects ; *Fatty Acids, Volatile/metabolism ; *Benzhydryl Compounds/toxicity ; Phenols/toxicity ; Bioreactors ; Sulfones/toxicity ; Environmental Pollutants/toxicity ; }, abstract = {The microbial community present in our intestines is pivotal for converting indigestible substances into vital nutrients and signaling molecules such as short-chain fatty acids (SCFAs). These compounds have considerable influence over our immune system and the development of diverse human diseases. However, ingested environmental contaminants, known as xenobiotics, can upset the delicate balance of the microbial gut community and enzymatic processes, consequently affecting the host organism. In our study, we employed an in vitro bioreactor model system based on the simplified human microbiome model (SIHUMIx) to investigate the direct effects of specific xenobiotics, such as perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA) or bisphenol S (BPS) and bisphenol F (BPF), either individually or in combination, on the microbiota. We observed increased SCFA production, particularly acetate and butyrate, with PFAS exposure. Metaproteomics revealed pathway alterations across treatments, including changes in vitamin synthesis and fatty acid metabolism with BPX. This study underscores the necessity of assessing the combined effects of xenobiotics to better safeguard public health. It emphasizes the significance of considering adverse effects on the microbiome in the risk assessment of environmental chemicals.}, }
@article {pmid38819500, year = {2024}, author = {Solasaari, T and Korpela, K and Lommi, S and Hyvönen, S and Gardemeister, S and Merras-Salmio, L and Salonen, A and de Vos, WM and Kolho, KL}, title = {Bowel function in a prospective cohort of 1052 healthy term infants up to 4 months of age.}, journal = {European journal of pediatrics}, volume = {183}, number = {8}, pages = {3557-3565}, pmid = {38819500}, issn = {1432-1076}, support = {32510//the Academy of Finland/ ; 5851//the Finnish Medical Foundation/ ; 5044//Signe and Ane Gyllenberg Foundation/ ; 329/31/2015//Tekes/ ; }, mesh = {Humans ; *Defecation/physiology ; Prospective Studies ; Infant ; Male ; Female ; *Breast Feeding/statistics &amp; numerical data ; Infant, Newborn ; Feces/chemistry ; Surveys and Questionnaires ; Infant Formula ; Crying/physiology ; }, abstract = {The purpose of this study is to describe the defecation pattern of healthy infants up to 17 weeks of age. We included 1052 healthy term infants from the prospective HELMi cohort (NCT03996304). Parents filled in recurring online questionnaires on feeding, gastrointestinal function, and crying weekly for the first 17 weeks of life. Defecation frequency was highest at the age of 3 weeks (a median of 4 times/day, interquartile range (IQR) 2.9-5). At each time point, the median defecation frequency of breastfed infants was higher than that of infants receiving formula (e.g., at week 17 a median of 2 times/day, IQR 0.9-3.6, and a median of 1.1, IQR 0.6-1.4, respectively). The dominant color of the stool was most often yellow or light brown. Nearly black stools were reported in the first week of life in 3.4%. Nearly half (47.4%) of the infants had green stool color dominating for at least 1 week, with comparable frequency among breastfed (47.7%) and formula-fed (45.2%) infants. Green stools were associated with a higher defecation frequency (linear mixed-effect model p < 0.0001). Occasional blood in stool was reported in 9.3% and recurrent blood in 5.2% of the infants with no difference in stool consistency. Hard stools were rare (≤ 1%). Conclusion: This study enlightens the spectrum of defecation patterns in healthy term infants during the first 17 weeks of life. A better understanding of bowel function helps healthcare professionals distinguish normal from abnormal when addressing defecation, the color of stools, and the type of feeding. What is Known: • Breastfed infants have more frequent and more yellow-colored stools than formula-fed infants. • Stools with green color are often suggested by the parents or even by medical professionals to indicate disease or discomfort in early life. What is New: • Nearly half of the healthy term infants had green stool dominating for at least one week during the first 17 weeks and occasional blood was reported in almost 10% of the infants during this period. • Data on normal variation in bowel function and stool may serve primary health care professionals when educating the families and caretakers of infants.}, }
@article {pmid38818295, year = {2024}, author = {Efremova, I and Maslennikov, R and Poluektova, E and Medvedev, O and Kudryavtseva, A and Krasnov, G and Fedorova, M and Romanikhin, F and Zharkova, M and Zolnikova, O and Bagieva, G and Ivashkin, V}, title = {Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis.}, journal = {World journal of hepatology}, volume = {16}, number = {5}, pages = {822-831}, pmid = {38818295}, issn = {1948-5182}, abstract = {BACKGROUND: The gut-liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate.<br><br>AIM: To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection.<br><br>METHODS: This study included 48 patients with Child-Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii) for 3 months.<br><br>RESULTS: Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child-Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child-Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child-Pugh scores (P = 0.046), as well as a higher level of the Child-Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis.<br><br>CONCLUSION: The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut-liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.}, }
@article {pmid38817603, year = {2024}, author = {Warren, A and Nyavor, Y and Zarabian, N and Mahoney, A and Frame, LA}, title = {The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1365673}, pmid = {38817603}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Brain-Gut Axis/immunology ; *Neuroinflammatory Diseases/immunology/microbiology/etiology ; *Brain/immunology/microbiology ; }, abstract = {IMPORTANCE: Research is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis (MS).<br><br>OBSERVATIONS: Generally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer's disease, followed by Parkinson's disease, and then little in MS. The data for MS is encouraging despite this.<br><br>CONCLUSIONS AND RELEVANCE: While the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.}, }
@article {pmid38814902, year = {2024}, author = {Ezra, S and Bashan, A}, title = {Network impact of a single-time-point microbial sample.}, journal = {PloS one}, volume = {19}, number = {5}, pages = {e0301683}, pmid = {38814902}, issn = {1932-6203}, mesh = {Humans ; *Microbiota ; Female ; Pregnancy ; Diabetes, Gestational/microbiology ; }, abstract = {The human microbiome plays a crucial role in determining our well-being and can significantly influence human health. The individualized nature of the microbiome may reveal host-specific information about the health state of the subject. In particular, the microbiome is an ecosystem shaped by a tangled network of species-species and host-species interactions. Thus, analysis of the ecological balance of microbial communities can provide insights into these underlying interrelations. However, traditional methods for network analysis require many samples, while in practice only a single-time-point microbial sample is available in clinical screening. Recently, a method for the analysis of a single-time-point sample, which evaluates its 'network impact' with respect to a reference cohort, has been applied to analyze microbial samples from women with Gestational Diabetes Mellitus. Here, we introduce different variations of the network impact approach and systematically study their performance using simulated 'samples' fabricated via the Generalized Lotka-Volttera model of ecological dynamics. We show that the network impact of a single sample captures the effect of the interactions between the species, and thus can be applied to anomaly detection of shuffled samples, which are 'normal' in terms of species abundance but 'abnormal' in terms of species-species interrelations. In addition, we demonstrate the use of the network impact in binary and multiclass classifications, where the reference cohorts have similar abundance profiles but different species-species interactions. Individualized analysis of the human microbiome has the potential to improve diagnosis and personalized treatments.}, }
@article {pmid38811534, year = {2024}, author = {Elzinga, J and Narimatsu, Y and de Haan, N and Clausen, H and de Vos, WM and Tytgat, HLP}, title = {Binding of Akkermansia muciniphila to mucin is O-glycan specific.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {4582}, pmid = {38811534}, issn = {2041-1723}, support = {737.016.003//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; 024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; Spinoza Grant Willem M de Vos//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; FEMS-GO-2021-069//Federation of European Microbiological Societies (FEMS)/ ; 0071658//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NA//Lundbeckfonden (Lundbeck Foundation)/ ; GlycoSkin H2020-ERC; 772735//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; }, mesh = {*Akkermansia/metabolism ; Humans ; *Mucins/metabolism ; *Polysaccharides/metabolism ; Neuraminidase/metabolism ; Protein Binding ; Glycosylation ; Disaccharides/metabolism ; Verrucomicrobia/metabolism ; Epitopes/metabolism ; Bacterial Adhesion ; }, abstract = {The intestinal anaerobic bacterium Akkermansia muciniphila is specialized in the degradation of mucins, which are heavily O-glycosylated proteins that constitute the major components of the mucus lining the intestine. Despite that adhesion to mucins is considered critical for the persistence of A. muciniphila in the human intestinal tract, our knowledge of how this intestinal symbiont recognizes and binds to mucins is still limited. Here, we first show that the mucin-binding properties of A. muciniphila are independent of environmental oxygen concentrations and not abolished by pasteurization. We then dissected the mucin-binding properties of pasteurized A. muciniphila by use of a recently developed cell-based mucin array that enables display of the tandem repeats of human mucins with distinct O-glycan patterns and structures. We found that A. muciniphila recognizes the unsialylated LacNAc (Galβ1-4GlcNAcβ1-R) disaccharide selectively on core2 and core3 O-glycans. This disaccharide epitope is abundantly found on human colonic mucins capped by sialic acids, and we demonstrated that endogenous A. muciniphila neuraminidase activity can uncover the epitope and promote binding. In summary, our study provides insights into the mucin-binding properties important for colonization of a key mucin-foraging bacterium.}, }
@article {pmid38809163, year = {2024}, author = {Chang, CJ and Liu, B and Liebmann, JM and Cioffi, GA and Winn, BJ}, title = {Glaucoma and the Human Microbiome.}, journal = {Journal of glaucoma}, volume = {33}, number = {8}, pages = {529-538}, doi = {10.1097/IJG.0000000000002448}, pmid = {38809163}, issn = {1536-481X}, mesh = {Humans ; *Glaucoma/microbiology/physiopathology ; *Microbiota/physiology ; Intraocular Pressure/physiology ; Dysbiosis ; Gastrointestinal Microbiome/physiology ; }, abstract = {PURPOSE OF REVIEW: To explore a view of the human microbiome as an interconnected, functional, dynamic system that may be linked to the pathogenesis and progression of glaucoma.<br><br>METHODS: A literature review was undertaken that included publications from 1966 to 2023.<br><br>RESULTS: Bacterial lipopolysaccharides (LPS) activate toll-like receptors (TLR) and mediate the human immune response. The LPS-TLR4 pathway is a potential avenue for the ocular, gut, and oral microbiomes to interface and/or influence ocular disease. Studies of gut dysbiosis have shown that alterations in the healthy microbiota can predispose the host to immune-mediated inflammatory and neurodegenerative conditions, while oral and ocular surface dysbiosis has been correlated with glaucoma. While developmental exposure to commensal microflora has shown to be necessary for the autoimmune and neurodegenerative responses to elevated intraocular pressure to take place, commensal bacterial products like short-chain fatty acids have regulatory effects protective against glaucoma.<br><br>SUMMARY: Alterations to human microbiotas have been associated with changes in intestinal permeability, gene regulation, immune cell differentiation, and neural functioning, which may predispose the host to glaucoma. Select microbes have been highlighted for their potential contributions to glaucoma disease progression or protection, raising the potential for microbiota-based treatment modalities. Current topical glaucoma treatments may disrupt the ocular surface microbiota, potentially having ramifications on host health. Further study of the relationships between human microbiome and glaucoma is needed.}, }
@article {pmid38809053, year = {2024}, author = {Selma-Royo, M and Ricci, L and Golzato, D and Servais, C and Nabinejad, A and Armanini, F and Asnicar, F and Pinto, F and Tamburini, S and Segata, N}, title = {Draft genome sequences of multiple bacterial strains isolated from human feces.}, journal = {Microbiology resource announcements}, volume = {13}, number = {7}, pages = {e0030724}, pmid = {38809053}, issn = {2576-098X}, abstract = {Bacterial isolation is necessary for functional and mechanistic analyses, and the increased human microbiome diversity revealed by metagenomic sequencing is expanding the relevant cultivation targets. Here, we report 46 draft genome sequences of bacterial isolates obtained from fecal samples of healthy adults in Trento and Milan (Italy), including strains from seven taxonomically uncharacterized species.}, }
@article {pmid38808120, year = {2024}, author = {Wang, T and Li, L and Figeys, D and Liu, YY}, title = {Pairing metagenomics and metaproteomics to characterize ecological niches and metabolic essentiality of gut microbiomes.}, journal = {ISME communications}, volume = {4}, number = {1}, pages = {ycae063}, pmid = {38808120}, issn = {2730-6151}, support = {U01 HL089856/HL/NHLBI NIH HHS/United States ; }, abstract = {The genome of a microorganism encodes its potential functions that can be implemented through expressed proteins. It remains elusive how a protein's selective expression depends on its metabolic essentiality to microbial growth or its ability to claim resources as ecological niches. To reveal a protein's metabolic or ecological role, we developed a computational pipeline, which pairs metagenomics and metaproteomics data to quantify each protein's gene-level and protein-level functional redundancy simultaneously. We first illustrated the idea behind the pipeline using simulated data of a consumer-resource model. We then validated it using real data from human and mouse gut microbiome samples. In particular, we analyzed ABC-type transporters and ribosomal proteins, confirming that the metabolic and ecological roles predicted by our pipeline agree well with prior knowledge. Finally, we performed in vitro cultures of a human gut microbiome sample and investigated how oversupplying various sugars involved in ecological niches influences the community structure and protein abundance. The presented results demonstrate the performance of our pipeline in identifying proteins' metabolic and ecological roles, as well as its potential to help us design nutrient interventions to modulate the human microbiome.}, }
@article {pmid38806600, year = {2024}, author = {Kwon, KM and Kim, EH and Sim, KH and Lee, YJ and Kang, EJ and Han, KH and Jin, JS and Kim, DK and Ahn, JH and Hwang, IH}, title = {Phenylacetic acid, an anti-vaginitis metabolite produced by the vaginal symbiotic bacterium Chryseobacterium gleum.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {12226}, pmid = {38806600}, issn = {2045-2322}, support = {2017R1D1A3B06035312//National Research Foundation of Korea/ ; 2020R1I1A3073660//National Research Foundation of Korea/ ; 2017R1C1B5073761//National Research Foundation of Korea/ ; }, mesh = {Female ; Animals ; *Phenylacetates/metabolism/pharmacology ; *Vagina/microbiology ; Mice ; Humans ; *Chryseobacterium/metabolism ; Candida albicans/metabolism/drug effects ; Symbiosis ; Hydrogen-Ion Concentration ; Gardnerella vaginalis/metabolism/drug effects ; Disease Models, Animal ; Vaginitis/microbiology/metabolism/drug therapy ; }, abstract = {The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.}, }
@article {pmid38805126, year = {2024}, author = {Mahoney, D}, title = {The Role of the Human Microbiome in Epithelial Ovarian Cancer.}, journal = {Advances in experimental medicine and biology}, volume = {1452}, number = {}, pages = {97-105}, pmid = {38805126}, issn = {0065-2598}, mesh = {Humans ; Female ; *Ovarian Neoplasms/microbiology ; *Carcinoma, Ovarian Epithelial/microbiology/pathology ; *Microbiota/physiology ; }, abstract = {Ovarian cancer is the fifth-leading cause of cancer deaths among women due to the absence of available screening methods to identify early disease. Thus, prevention and early disease detection investigations are of high priority, surrounding a critical window of opportunity to better understand important pathogenic mechanisms of disease progression. Microorganisms modulate molecular interactions in humans that can influence states of health and disease, including ovarian cancer. While the mechanisms of infectious microbial invasion that trigger the immune-inflammatory axis are well studied in cancer research, the complex interactions that promote the transition of noninfectious healthy microbes to pathobiont expansion are less understood. As traditional research has focused on the influences of infectious pathogens on ovarian cancer development and progression, the impact of noninfectious microbes has gained scientific attention. The objective of this chapter is to summarize current evidence on the role of microbiota in epithelial ovarian cancer throughout disease.}, }
@article {pmid38795687, year = {2024}, author = {Quesada, S and Rosso, AD and Mascardi, F and Soler-Rivero, V and Aguilera, P and Mascuka, SN and Boiro, A and Arenielo, E and Vijoditz, G and Ferreyra-Mufarregue, LR and Caputo, MF and Cimolai, MC and Coluccio Leskow, F and Penas-Steinhardt, A and Belforte, FS}, title = {Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223-3p and gut microbiota in transkingdom dynamics.}, journal = {Molecular immunology}, volume = {171}, number = {}, pages = {77-92}, doi = {10.1016/j.molimm.2024.05.004}, pmid = {38795687}, issn = {1872-9142}, mesh = {Humans ; *MicroRNAs/genetics ; *Lupus Erythematosus, Systemic/microbiology/immunology ; *Gastrointestinal Microbiome ; *Feces/microbiology ; Female ; Adult ; *Biomarkers/metabolism ; Male ; Middle Aged ; Immunosuppressive Agents/therapeutic use ; }, abstract = {Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223-3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223-3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.}, }
@article {pmid38792733, year = {2024}, author = {Putrino, A and Marinelli, E and Galeotti, A and Ferrazzano, GF and Ciribè, M and Zaami, S}, title = {A Journey into the Evolution of Human Host-Oral Microbiome Relationship through Ancient Dental Calculus: A Scoping Review.}, journal = {Microorganisms}, volume = {12}, number = {5}, pages = {}, pmid = {38792733}, issn = {2076-2607}, abstract = {One of the most promising areas of research in palaeomicrobiology is the study of the human microbiome. In particular, ancient dental calculus helps to reconstruct a substantial share of oral microbiome composition by mapping together human evolution with its state of health/oral disease. This review aims to trace microbial characteristics in ancient dental calculus to describe the evolution of the human host-oral microbiome relationship in oral health or disease in children and adults. Following the PRISMA-Extension for Scoping Reviews guidelines, the main scientific databases (PubMed, Scopus, Lilacs, Cochrane Library) have been drawn upon. Eligibility criteria were established, and all the data collected on a purpose-oriented collection form were analysed descriptively. From the initial 340 records, only 19 studies were deemed comprehensive enough for the purpose of this review. The knowledge of the composition of ancient oral microbiomes has broadened over the past few years thanks to increasingly well-performing decontamination protocols and additional analytical avenues. Above all, metagenomic sequencing, also implemented by state-of-the-art bioinformatics tools, allows for the determination of the qualitative-quantitative composition of microbial species associated with health status and caries/periodontal disease. Some microbial species, especially periodontal pathogens, do not appear to have changed in history, while others that support caries disease or oral health could be connected to human evolution through lifestyle and environmental contributing factors.}, }
@article {pmid38792577, year = {2024}, author = {Koo, H and Morrow, CD}, title = {Bacteroidales-Specific Antimicrobial Genes Can Influence the Selection of the Dominant Fecal Strain of Bacteroides vulgatus and Bacteroides uniformis from the Gastrointestinal Tract Microbial Community.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {5}, pages = {}, pmid = {38792577}, issn = {2075-1729}, abstract = {Bacteroides vulgatus and Bacteroides uniformis are known to be abundant in the human fecal microbial community. Although these strains typically remain stable over time in humans, disruption of this microbial community following antibiotics resulted in the transient change to new strains suggesting that a complex, dynamic strain community exists in humans. To further study the selection of dominant fecal microbial strains from the gastrointestinal tract (GIT) community, we analyzed three longitudinal metagenomic sequencing data sets using BLAST+ to identify genes encoding Bacteroidales-specific antimicrobial proteins (BSAP) that have known functions to restrict species-specific replication of B. uniformis (BSAP-2) or B. vulgatus (BSAP-3) and have been postulated to provide a competitive advantage in microbial communities. In the HMP (Human Microbiome Project) data set, we found fecal samples from individuals had B. vulgatus or B. uniformis with either complete or deleted BSAP genes that did not change over time. We also examined fecal samples from two separate longitudinal data sets of individuals who had been given either single or multiple antibiotics. The BSAP gene pattern from most individuals given either single or multiple antibiotics recovered to be the same as the pre-antibiotic strain. However, in a few individuals, we found incomplete BSAP-3 genes at early times during the recovery that were replaced by B. vulgatus with the complete BSAP-3 gene, consistent with the function of the BSAP to specifically restrict Bacteroides spp. The results of these studies provide insights into the fluxes that occur in the Bacteroides spp. GIT community following perturbation and the dynamics of the selection of a dominant fecal strain of Bacteroides spp.}, }
@article {pmid38791599, year = {2024}, author = {Olteanu, G and Ciucă-Pană, MA and Busnatu, &#x218;S and Lupuliasa, D and Neacșu, SM and Mititelu, M and Musuc, AM and Ioniță-Mîndrican, CB and Boroghină, SC}, title = {Unraveling the Microbiome-Human Body Axis: A Comprehensive Examination of Therapeutic Strategies, Interactions and Implications.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791599}, issn = {1422-0067}, mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Microbiota ; Animals ; Human Body ; Host Microbial Interactions/physiology ; }, abstract = {This review scrutinizes the intricate interplay between the microbiome and the human body, exploring its multifaceted dimensions and far-reaching implications. The human microbiome, comprising diverse microbial communities inhabiting various anatomical niches, is increasingly recognized as a critical determinant of human health and disease. Through an extensive examination of current research, this review elucidates the dynamic interactions between the microbiome and host physiology across multiple organ systems. Key topics include the establishment and maintenance of microbiota diversity, the influence of host factors on microbial composition, and the bidirectional communication pathways between microbiota and host cells. Furthermore, we delve into the functional implications of microbiome dysbiosis in disease states, emphasizing its role in shaping immune responses, metabolic processes, and neurological functions. Additionally, this review discusses emerging therapeutic strategies aimed at modulating the microbiome to restore host-microbe homeostasis and promote health. Microbiota fecal transplantation represents a groundbreaking therapeutic approach in the management of dysbiosis-related diseases, offering a promising avenue for restoring microbial balance within the gut ecosystem. This innovative therapy involves the transfer of fecal microbiota from a healthy donor to an individual suffering from dysbiosis, aiming to replenish beneficial microbial populations and mitigate pathological imbalances. By synthesizing findings from diverse fields, this review offers valuable insights into the complex relationship between the microbiome and the human body, highlighting avenues for future research and clinical interventions.}, }
@article {pmid38791230, year = {2024}, author = {Pérez-Pérez, ME and Nieto-Torres, E and Bollain-Y-Goytia, JJ and Delgadillo-Ruíz, L}, title = {Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {10}, pages = {}, pmid = {38791230}, issn = {1422-0067}, support = {the F002 Support for scientific, technological and innovation activities//This work was supported by the F002 Support for scientific, technological and innovation activities. Zacatecas Council of Science./ ; }, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; *Anti-Citrullinated Protein Antibodies/immunology/metabolism ; *Arthritis, Rheumatoid/immunology/microbiology ; Case-Control Studies ; *Citrullination ; Citrulline/metabolism ; Cross-Sectional Studies ; Hydrolases/metabolism ; *Microbiota ; Protein-Arginine Deiminase Type 2/metabolism ; Protein-Arginine Deiminase Type 4/metabolism ; *Protein-Arginine Deiminases/metabolism/genetics ; }, abstract = {The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are associated with autoimmunity. Peptidylarginine deiminase (PAD) enzymes can citrullinate self-proteins related to rheumatoid arthritis (RA) that induce the production of anti-citrullinated protein antibodies (ACPAs) and lead to inflammation and joint damage. The present investigation was carried out to demonstrate the expression of homologs of PADs or arginine deiminases (ADs) and citrullinated proteins in members of the human microbiota. To achieve the objective, we used 17 microbial strains and specific polyclonal antibodies (pAbs) of the synthetic peptide derived from residues 100-200 of human PAD2 (anti-PAD2 pAb), and the recombinant fragment of amino acids 326 and 611 of human PAD4 (anti-PAD4 pAb), a human anti-citrulline pAb, and affinity ACPAs of an RA patient. Western blot (WB), enzyme-linked immunosorbent assay (ELISA), elution, and a test with Griess reagent were used. This is a cross-sectional case-control study on patients diagnosed with RA and control subjects. Inferential statistics were applied using the non-parametric Kruskal-Wallis test and Mann-Whitney U test generated in the SPSS program. Some members of phyla Firmicutes and Proteobacteria harbor homologs of PADs/ADs and citrullinated antigens that are reactive to the ACPAs of RA patients. Microbial citrullinome and homolog enzymes of PADs/ADs are extensive in the human microbiome and are involved in the production of ACPAs. Our findings suggest a molecular link between microorganisms of a dysbiotic microbiota and RA pathogenesis.}, }
@article {pmid38788999, year = {2024}, author = {Filippo, D and Guardone, L and Listorti, V and Elisabetta, R}, title = {Microbiome in cancer: A comparative analysis between humans and dogs.}, journal = {Veterinary journal (London, England : 1997)}, volume = {305}, number = {}, pages = {106145}, doi = {10.1016/j.tvjl.2024.106145}, pmid = {38788999}, issn = {1532-2971}, mesh = {Dogs ; Animals ; Humans ; *Dog Diseases/microbiology ; *Neoplasms/veterinary/microbiology ; Gastrointestinal Microbiome ; Microbiota ; Dysbiosis/veterinary ; Female ; }, abstract = {Cancer is a major cause of death in humans and animals worldwide. While cancer survival rates have increased over recent decades, further research to identify risk factors for the onset and progression of disease, and safe and highly efficacious treatments, is needed. Spontaneous tumours in pets represent an excellent model for neoplastic disease in humans. In this regard, dogs are an interesting species, as the divergence between the dog and human genome is low, humans and dogs have important similarities in the development and functioning of the immune system, and both species often share the same physical environment. There is also a higher homology between the canine and human microbiome than murine model. This review aims to describe and organize recently published information on canine microbiome assemblages and their relationship with the onset and progression of colorectal cancer, breast cancer and lymphoma, and to compare this with human disease. In both species, dysbiosis can induce variations in the gut microbiota that strongly influence shifts in status between health and disease. This can produce an inflammatory state, potentially leading to neoplasia, especially in the intestine, thus supporting canine studies in comparative oncology. Intestinal dysbiosis can also alter the efficacy and side effects of cancer treatments. Fewer published studies are available on changes in the relevant microbiomes in canine lymphoma and mammary cancer, and further research in this area could improve our understanding of the role of microbiota in the development of these cancers.}, }
@article {pmid38788190, year = {2024}, author = {Mishra, AK and Mahmud, I and Lorenzi, PL and Jenq, RR and Wargo, JA and Ajami, NJ and Peterson, CB}, title = {TARO: tree-aggregated factor regression for microbiome data integration.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {6}, pages = {}, pmid = {38788190}, issn = {1367-4811}, support = {R01 CA244845/CA/NCI NIH HHS/United States ; R01 HL158796/HL/NHLBI NIH HHS/United States ; R01 HL158796/NH/NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Software ; Metabolomics/methods ; Colorectal Neoplasms/microbiology/metabolism ; Gastrointestinal Microbiome ; Algorithms ; }, abstract = {MOTIVATION: Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns.<br><br>RESULTS: We propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information on the taxonomic tree structure to flexibly aggregate rare features. We demonstrate through simulation studies that TARO accurately recovers a low-rank coefficient matrix and identifies relevant features. We applied TARO to microbiome and metabolomic profiles gathered from subjects being screened for colorectal cancer to understand how gut microrganisms shape intestinal metabolite abundances.<br><br>The R package TARO implementing the proposed methods is available online at https://github.com/amishra-stats/taro-package.}, }
@article {pmid38782975, year = {2024}, author = {McKee, K and Bassis, CM and Golob, J and Palazzolo, B and Sen, A and Comstock, SS and Rosas-Salazar, C and Stanford, JB and O'Connor, T and Gern, JE and Paneth, N and Dunlop, AL and , }, title = {Host factors are associated with vaginal microbiome structure in pregnancy in the ECHO Cohort Consortium.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {11798}, pmid = {38782975}, issn = {2045-2322}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; U24OD023382//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; U2C OD023375/OD/NIH HHS/United States ; UH3 OD023271/OD/NIH HHS/United States ; UH3 OD023282/OD/NIH HHS/United States ; UH3OD023282//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023287/OD/NIH HHS/United States ; U24 OD023319/OD/NIH HHS/United States ; UH3 OD023305/OD/NIH HHS/United States ; UH3 OD023288/OD/NIH HHS/United States ; UH3OD023249//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; U24OD023319//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023268/OD/NIH HHS/United States ; UH3 OD023328/OD/NIH HHS/United States ; R01 NR014800/NR/NINR NIH HHS/United States ; U24 OD023382/OD/NIH HHS/United States ; UH3 OD023313/OD/NIH HHS/United States ; UH3 OD023289/OD/NIH HHS/United States ; UH3 OD023249/OD/NIH HHS/United States ; UH3 OD023389/OD/NIH HHS/United States ; UH3 OD023290/OD/NIH HHS/United States ; UH3OD023251//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023285/OD/NIH HHS/United States ; UH3 OD023275/OD/NIH HHS/United States ; P30 ES001247/ES/NIEHS NIH HHS/United States ; UH3 OD023318/OD/NIH HHS/United States ; UH3 OD023248/OD/NIH HHS/United States ; U2COD023375//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023253/OD/NIH HHS/United States ; UH3 OD023272/OD/NIH HHS/United States ; UH3 OD023347/OD/NIH HHS/United States ; UH3OD023318//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3 OD023251/OD/NIH HHS/United States ; UH3 OD023279/OD/NIH HHS/United States ; UH3OD023285//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; K01 AI153558/AI/NIAID NIH HHS/United States ; U19 AI104317/AI/NIAID NIH HHS/United States ; R24 ES029490/ES/NIEHS NIH HHS/United States ; UH3 OD023244/OD/NIH HHS/United States ; UH3 OD023320/OD/NIH HHS/United States ; U24 ES029490/ES/NIEHS NIH HHS/United States ; UH3 OD023349/OD/NIH HHS/United States ; UH3 OD023337/OD/NIH HHS/United States ; UG3 OD023318/OD/NIH HHS/United States ; }, mesh = {Humans ; Female ; Pregnancy ; *Vagina/microbiology ; *Microbiota/genetics ; Adult ; *RNA, Ribosomal, 16S/genetics ; Cohort Studies ; Young Adult ; }, abstract = {Using pooled vaginal microbiota data from pregnancy cohorts (N = 683 participants) in the Environmental influences on Child Health Outcomes (ECHO) Program, we analyzed 16S rRNA gene amplicon sequences to identify clinical and demographic host factors that associate with vaginal microbiota structure in pregnancy both within and across diverse cohorts. Using PERMANOVA models, we assessed factors associated with vaginal community structure in pregnancy, examined whether host factors were conserved across populations, and tested the independent and combined effects of host factors on vaginal community state types (CSTs) using multinomial logistic regression models. Demographic and social factors explained a larger amount of variation in the vaginal microbiome in pregnancy than clinical factors. After adjustment, lower education, rather than self-identified race, remained a robust predictor of L. iners dominant (CST III) and diverse (CST IV) (OR = 8.44, 95% CI = 4.06-17.6 and OR = 4.18, 95% CI = 1.88-9.26, respectively). In random forest models, we identified specific taxonomic features of host factors, particularly urogenital pathogens associated with pregnancy complications (Aerococcus christensenii and Gardnerella spp.) among other facultative anaerobes and key markers of community instability (L. iners). Sociodemographic factors were robustly associated with vaginal microbiota structure in pregnancy and should be considered as sources of variation in human microbiome studies.}, }
@article {pmid38781679, year = {2024}, author = {Mangalea, MR and Halpin, AL and Haile, M and Elkins, CA and McDonald, LC}, title = {Decolonization and Pathogen Reduction Approaches to Prevent Antimicrobial Resistance and Healthcare-Associated Infections.}, journal = {Emerging infectious diseases}, volume = {30}, number = {6}, pages = {1069-1076}, pmid = {38781679}, issn = {1080-6059}, mesh = {Humans ; *Cross Infection/prevention &amp; control/microbiology ; *Drug Resistance, Bacterial ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Microbiota/drug effects ; Bacterial Infections/prevention &amp; control/microbiology ; Infection Control/methods ; Bacteria/drug effects ; }, abstract = {Antimicrobial resistance in healthcare-associated bacterial pathogens and the infections they cause are major public health threats affecting nearly all healthcare facilities. Antimicrobial-resistant bacterial infections can occur when colonizing pathogenic bacteria that normally make up a small fraction of the human microbiota increase in number in response to clinical perturbations. Such infections are especially likely when pathogens are resistant to the collateral effects of antimicrobial agents that disrupt the human microbiome, resulting in loss of colonization resistance, a key host defense. Pathogen reduction is an emerging strategy to prevent transmission of, and infection with, antimicrobial-resistant healthcare-associated pathogens. We describe the basis for pathogen reduction as an overall prevention strategy, the evidence for its effectiveness, and the role of the human microbiome in colonization resistance that also reduces the risk for infection once colonized. In addition, we explore ideal attributes of current and future pathogen-reducing approaches.}, }
@article {pmid38779566, year = {2024}, author = {Scanu, M and Toto, F and Petito, V and Masi, L and Fidaleo, M and Puca, P and Baldelli, V and Reddel, S and Vernocchi, P and Pani, G and Putignani, L and Scaldaferri, F and Del Chierico, F}, title = {An integrative multi-omic analysis defines gut microbiota, mycobiota, and metabolic fingerprints in ulcerative colitis patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1366192}, pmid = {38779566}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative/microbiology/metabolism ; *Gastrointestinal Microbiome ; Male ; Adult ; Female ; *Bacteria/classification/isolation &amp; purification/metabolism/genetics ; Middle Aged ; *Metabolomics/methods ; *RNA, Ribosomal, 16S/genetics ; *Gas Chromatography-Mass Spectrometry ; *Feces/microbiology ; *Fungi/classification/isolation &amp; purification/metabolism ; Dysbiosis/microbiology ; Metabolome ; Aged ; Young Adult ; Solid Phase Microextraction ; Mycobiome ; Multiomics ; }, abstract = {BACKGROUND: Ulcerative colitis (UC) is a multifactorial chronic inflammatory bowel disease (IBD) that affects the large intestine with superficial mucosal inflammation. A dysbiotic gut microbial profile has been associated with UC. Our study aimed to characterize the UC gut bacterial, fungal, and metabolic fingerprints by omic approaches.<br><br>METHODS: The 16S rRNA- and ITS2-based metataxonomics and gas chromatography-mass spectrometry/solid phase microextraction (GC-MS/SPME) metabolomic analysis were performed on stool samples of 53 UC patients and 37 healthy subjects (CTRL). Univariate and multivariate approaches were applied to separated and integrated omic data, to define microbiota, mycobiota, and metabolic signatures in UC. The interaction between gut bacteria and fungi was investigated by network analysis.<br><br>RESULTS: In the UC cohort, we reported the increase of Streptococcus, Bifidobacterium, Enterobacteriaceae, TM7-3, Granulicatella, Peptostreptococcus, Lactobacillus, Veillonella, Enterococcus, Peptoniphilus, Gemellaceae, and phenylethyl alcohol; and we also reported the decrease of Akkermansia; Ruminococcaceae; Ruminococcus; Gemmiger; Methanobrevibacter; Oscillospira; Coprococus; Christensenellaceae; Clavispora; Vishniacozyma; Quambalaria; hexadecane; cyclopentadecane; 5-hepten-2-ol, 6 methyl; 3-carene; caryophyllene; p-Cresol; 2-butenal; indole, 3-methyl-; 6-methyl-3,5-heptadiene-2-one; 5-octadecene; and 5-hepten-2-one, 6 methyl. The integration of the multi-omic data confirmed the presence of a distinctive bacterial, fungal, and metabolic fingerprint in UC gut microbiota. Moreover, the network analysis highlighted bacterial and fungal synergistic and/or divergent interkingdom interactions.<br><br>CONCLUSION: In this study, we identified intestinal bacterial, fungal, and metabolic UC-associated biomarkers. Furthermore, evidence on the relationships between bacterial and fungal ecosystems provides a comprehensive perspective on intestinal dysbiosis and ecological interactions between microorganisms in the framework of UC.}, }
@article {pmid38778221, year = {2024}, author = {Chen, Z and Lin, K and Yu, H}, title = {Reply to Qiao et al.}, journal = {British journal of cancer}, volume = {130}, number = {12}, pages = {1889}, pmid = {38778221}, issn = {1532-1827}, }
@article {pmid38774631, year = {2024}, author = {Dorst, M and Zeevenhooven, N and Wilding, R and Mende, D and Brandt, BW and Zaura, E and Hoekstra, A and Sheraton, VM}, title = {FAIR compliant database development for human microbiome data samples.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1384809}, pmid = {38774631}, issn = {2235-2988}, mesh = {Humans ; *Microbiota/genetics ; Databases, Factual ; Metadata ; Metagenome ; Information Dissemination ; Computational Biology/methods ; Metagenomics/methods ; Databases, Genetic ; }, abstract = {INTRODUCTION: Sharing microbiome data among researchers fosters new innovations and reduces cost for research. Practically, this means that the (meta)data will have to be standardized, transparent and readily available for researchers. The microbiome data and associated metadata will then be described with regards to composition and origin, in order to maximize the possibilities for application in various contexts of research. Here, we propose a set of tools and protocols to develop a real-time FAIR (Findable. Accessible, Interoperable and Reusable) compliant database for the handling and storage of human microbiome and host-associated data.<br><br>METHODS: The conflicts arising from privacy laws with respect to metadata, possible human genome sequences in the metagenome shotgun data and FAIR implementations are discussed. Alternate pathways for achieving compliance in such conflicts are analyzed. Sample traceable and sensitive microbiome data, such as DNA sequences or geolocalized metadata are identified, and the role of the GDPR (General Data Protection Regulation) data regulations are considered. For the construction of the database, procedures have been realized to make data FAIR compliant, while preserving privacy of the participants providing the data.<br><br>RESULTS AND DISCUSSION: An open-source development platform, Supabase, was used to implement the microbiome database. Researchers can deploy this real-time database to access, upload, download and interact with human microbiome data in a FAIR complaint manner. In addition, a large language model (LLM) powered by ChatGPT is developed and deployed to enable knowledge dissemination and non-expert usage of the database.}, }
@article {pmid38771520, year = {2024}, author = {Chaudhary, PP and Kaur, M and Myles, IA}, title = {Does "all disease begin in the gut"? The gut-organ cross talk in the microbiome.}, journal = {Applied microbiology and biotechnology}, volume = {108}, number = {1}, pages = {339}, pmid = {38771520}, issn = {1432-0614}, mesh = {Humans ; *Gastrointestinal Microbiome ; Microbiota ; Skin/microbiology ; Vagina/microbiology ; Lung/microbiology ; Mouth/microbiology ; Female ; Gastrointestinal Tract/microbiology ; }, abstract = {The human microbiome, a diverse ecosystem of microorganisms within the body, plays pivotal roles in health and disease. This review explores site-specific microbiomes, their role in maintaining health, and strategies for their upkeep, focusing on oral, lung, vaginal, skin, and gut microbiota, and their systemic connections. Understanding the intricate relationships between these microbial communities is crucial for unraveling mechanisms underlying human health. Recent research highlights bidirectional communication between the gut and distant microbiome sites, influencing immune function, metabolism, and disease susceptibility. Alterations in one microbiome can impact others, emphasizing their interconnectedness and collective influence on human physiology. The therapeutic potential of gut microbiota in modulating distant microbiomes offers promising avenues for interventions targeting various disorders. Through interdisciplinary collaboration and technological advancements, we can harness the power of the microbiome to revolutionize healthcare, emphasizing microbiome-centric approaches to promote holistic well-being while identifying areas for future research.}, }
@article {pmid38771144, year = {2024}, author = {Wang, P and Duan, F and Lv, Y and Man, S and Liu, S and Liu, Y}, title = {Long- and Intermediate-Term Ambient Particulate Pollution Is Associated with Increased Osteoarthritis Risk: A Population-Based Prospective Analysis.}, journal = {Environmental science &amp; technology}, volume = {58}, number = {22}, pages = {9536-9547}, doi = {10.1021/acs.est.3c10893}, pmid = {38771144}, issn = {1520-5851}, mesh = {Humans ; *Osteoarthritis/epidemiology ; *Particulate Matter ; Prospective Studies ; Air Pollution ; Male ; Air Pollutants ; Female ; Environmental Exposure ; Middle Aged ; Risk Factors ; Beijing/epidemiology ; Aged ; }, abstract = {Recent studies found the intrusion and retention of exogenous fine particles into joints, but epidemiological data for long- and intermediate-term exposure associations are scare. Here, all urban working, retired employee, and rural residents (16.78 million) in Beijing from January 1, 2011 to December 31, 2019 were included to investigate the effects of long- and intermediate-term ambient particulate exposure on development of osteoarthritis. We identified 1,742,067 participants as first-visit patients with osteoarthritis. For each interquartile range increase in annual PM2.5 (23.32 μg/m[3]) and PM10 (23.92 μg/m[3]) exposure concentration, the pooled hazard ratios were respectively 1.238 (95% CI: 1.228, 1.249) and 1.178 (95% CI: 1.168, 1.189) for first osteoarthritis outpatient visits. Moreover, age at first osteoarthritis outpatient visits significantly decreased by 4.52 (95% CI: 3.45 to 5.40) days per μg/m[3] for annual PM2.5 exposure at below 67.85 μg/m[3]. Finally, among the six constituents analyzed, black carbon appears to be the most important component associated with the association between PM2.5 exposure and the three osteoarthritis-related outcomes.}, }
@article {pmid38767067, year = {2024}, author = {Kalluçi, E and Preni, B and Dhamo, X and Noka, E and Bardhi, S and Macchia, A and Bonetti, G and Dhuli, K and Donato, K and Bertelli, M and Zambrano, LJM and Janaqi, S}, title = {A comparative study of supervised and unsupervised machine learning algorithms applied to human microbiome.}, journal = {La Clinica terapeutica}, volume = {175}, number = {3}, pages = {98-116}, doi = {10.7417/CT.2024.5051}, pmid = {38767067}, issn = {1972-6007}, mesh = {Humans ; *Supervised Machine Learning ; *Unsupervised Machine Learning ; *Microbiota/genetics ; *RNA, Ribosomal, 16S/genetics/analysis ; Colorectal Neoplasms/microbiology ; Gastrointestinal Microbiome/genetics ; Algorithms ; Feces/microbiology ; Adenoma/microbiology ; }, abstract = {BACKGROUND: The human microbiome, consisting of diverse bacte-rial, fungal, protozoan and viral species, exerts a profound influence on various physiological processes and disease susceptibility. However, the complexity of microbiome data has presented significant challenges in the analysis and interpretation of these intricate datasets, leading to the development of specialized software that employs machine learning algorithms for these aims.<br><br>METHODS: In this paper, we analyze raw data taken from 16S rRNA gene sequencing from three studies, including stool samples from healthy control, patients with adenoma, and patients with colorectal cancer. Firstly, we use network-based methods to reduce dimensions of the dataset and consider only the most important features. In addition, we employ supervised machine learning algorithms to make prediction.<br><br>RESULTS: Results show that graph-based techniques reduces dimen-sion from 255 up to 78 features with modularity score 0.73 based on different centrality measures. On the other hand, projection methods (non-negative matrix factorization and principal component analysis) reduce dimensions to 7 features. Furthermore, we apply supervised machine learning algorithms on the most important features obtained from centrality measures and on the ones obtained from projection methods, founding that the evaluation metrics have approximately the same scores when applying the algorithms on the entire dataset, on 78 feature and on 7 features.<br><br>CONCLUSIONS: This study demonstrates the efficacy of graph-based and projection methods in the interpretation for 16S rRNA gene sequencing data. Supervised machine learning on refined features from both approaches yields comparable predictive performance, emphasizing specific microbial features-bacteroides, prevotella, fusobacterium, lysinibacillus, blautia, sphingomonas, and faecalibacterium-as key in predicting patient conditions from raw data.}, }
@article {pmid38743245, year = {2024}, author = {de Moraes, DC and Rollin-Pinheiro, R and Pinto, MDCFR and Domingos, LTS and Barreto-Bergter, E and Ferreira-Pereira, A}, title = {Antifungal activity of β-lapachone against a fluconazole-resistant Candida auris strain.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {55}, number = {3}, pages = {2593-2601}, pmid = {38743245}, issn = {1678-4405}, support = {Bolsa de Pesquisa Produtividade//Universidade Est&#xe1;cio de S&#xe1;/ ; Financial Code 001//CAPES/ ; }, mesh = {*Naphthoquinones/pharmacology ; *Antifungal Agents/pharmacology ; *Drug Resistance, Fungal/drug effects ; *Microbial Sensitivity Tests ; *Fluconazole/pharmacology ; *Biofilms/drug effects ; Humans ; *Candida auris/drug effects/genetics ; Amphotericin B/pharmacology ; Candidiasis/microbiology/drug therapy ; }, abstract = {Candida spp. can be found in the human microbiome. However, immunocompromised patients are likely to develop invasive Candida infections, with mortality rates higher than 50%. The discovery of C. auris, a species that rapidly acquire antifungal resistance, increased the concern about Candida infections. The limited number of antifungal agents and the high incidence of resistance to them make imperative the development of new antifungal drugs. β-lapachone is a biological active naphthoquinone that displays antifungal activity against C. albicans and C. glabrata. The aim of this study was to evaluate if this substance affects C. auris growth and elucidate its mechanism of action. A fluconazole-resistant C. auris isolate was used in this study. The antifungal activity of β-lapachone was determined through microbroth dilution assays, and its mechanism of action was evaluated using fluorescent probes. Interaction with fluconazole and amphotericin B was assessed by disk diffusion assay and checkerboard. β-lapachone inhibited planktonic C. auris cell growth by 92.7%, biofilm formation by 84.9%, and decrease the metabolism of preformed biofilms by 87.1% at 100 µg/ml. At 100 µg/ml, reductions of 30% and 59% of Calcofluor White and Nile red fluorescences were observed, indicating that β-lapachone affects cell wall chitin and neutral lipids content, respectively. Also, the ratio 590 nm/529 nm of JC-1 decreased 52%, showing that the compound affects mitochondria. No synergism was observed between β-lapachone and fluconazole or amphotericin B. Data show that β-lapachone may be a promising candidate to be used as monotherapy to treat C. auris resistant infections.}, }
@article {pmid38740909, year = {2024}, author = {Han, S and Guiberson, ER and Li, Y and Sonnenburg, JL}, title = {High-throughput identification of gut microbiome-dependent metabolites.}, journal = {Nature protocols}, volume = {19}, number = {7}, pages = {2180-2205}, pmid = {38740909}, issn = {1750-2799}, support = {F32AG062119//U.S. Department of Health &amp; Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; R01-DK085025//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; 5T32AI007328-35//U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; R01-DK101674//U.S. Department of Health &amp; Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases)/ ; 085025/WT_/Wellcome Trust/United Kingdom ; DP1 AT009892/AT/NCCIH NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Metabolomics/methods ; Chromatography, Liquid/methods ; *Mass Spectrometry/methods ; Metabolome ; Computational Biology/methods ; Bacteria/metabolism ; }, abstract = {A significant hurdle that has limited progress in microbiome science has been identifying and studying the diverse set of metabolites produced by gut microbes. Gut microbial metabolism produces thousands of difficult-to-identify metabolites, which present a challenge to study their roles in host biology. In recent years, mass spectrometry-based metabolomics has become one of the core technologies for identifying small metabolites. However, metabolomics expertise, ranging from sample preparation to instrument use and data analysis, is often lacking in academic labs. Most targeted metabolomics methods provide high levels of sensitivity and quantification, while they are limited to a panel of predefined molecules that may not be informative to microbiome-focused studies. Here we have developed a gut microbe-focused and wide-spectrum metabolomic protocol using liquid chromatography-mass spectrometry and bioinformatic analysis. This protocol enables users to carry out experiments from sample collection to data analysis, only requiring access to a liquid chromatography-mass spectrometry instrument, which is often available at local core facilities. By applying this protocol to samples containing human gut microbial metabolites, spanning from culture supernatant to human biospecimens, our approach enables high-confidence identification of >800 metabolites that can serve as candidate mediators of microbe-host interactions. We expect this protocol will lower the barrier to tracking gut bacterial metabolism in vitro and in mammalian hosts, propelling hypothesis-driven mechanistic studies and accelerating our understanding of the gut microbiome at the chemical level.}, }
@article {pmid38740509, year = {2024}, author = {Paone, P and Latousakis, D and Terrasi, R and Vertommen, D and Jian, C and Borlandelli, V and Suriano, F and Johansson, MEV and Puel, A and Bouzin, C and Delzenne, NM and Salonen, A and Juge, N and Florea, BI and Muccioli, GG and Overkleeft, H and Van Hul, M and Cani, PD}, title = {Human milk oligosaccharide 2'-fucosyllactose protects against high-fat diet-induced obesity by changing intestinal mucus production, composition and degradation linked to changes in gut microbiota and faecal proteome profiles in mice.}, journal = {Gut}, volume = {73}, number = {10}, pages = {1632-1649}, pmid = {38740509}, issn = {1468-3288}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Obesity/metabolism/microbiology/prevention &amp; control ; *Gastrointestinal Microbiome/drug effects ; *Trisaccharides/metabolism ; Mice ; *Feces/microbiology/chemistry ; Humans ; Milk, Human/metabolism/chemistry ; Intestinal Mucosa/metabolism ; Proteome/metabolism/analysis ; Mucus/metabolism ; Male ; Mice, Inbred C57BL ; Mucins/metabolism ; }, abstract = {OBJECTIVE: To decipher the mechanisms by which the major human milk oligosaccharide (HMO), 2'-fucosyllactose (2'FL), can affect body weight and fat mass gain on high-fat diet (HFD) feeding in mice. We wanted to elucidate whether 2'FL metabolic effects are linked with changes in intestinal mucus production and secretion, mucin glycosylation and degradation, as well as with the modulation of the gut microbiota, faecal proteome and endocannabinoid (eCB) system.<br><br>RESULTS: 2'FL supplementation reduced HFD-induced obesity and glucose intolerance. These effects were accompanied by several changes in the intestinal mucus layer, including mucus production and composition, and gene expression of secreted and transmembrane mucins, glycosyltransferases and genes involved in mucus secretion. In addition, 2'FL increased bacterial glycosyl hydrolases involved in mucin glycan degradation. These changes were linked to a significant increase and predominance of bacterial genera Akkermansia and Bacteroides, different faecal proteome profile (with an upregulation of proteins involved in carbon, amino acids and fat metabolism and a downregulation of proteins involved in protein digestion and absorption) and, finally, to changes in the eCB system. We also investigated faecal proteomes from lean and obese humans and found similar changes observed comparing lean and obese mice.<br><br>CONCLUSION: Our results show that the HMO 2'FL influences host metabolism by modulating the mucus layer, gut microbiota and eCB system and propose the mucus layer as a new potential target for the prevention of obesity and related disorders.}, }
@article {pmid38740275, year = {2024}, author = {Long, AR and Mortara, EL and Mendoza, BN and Fink, EC and Sacco, FX and Ciesla, MJ and Stack, TMM}, title = {Sequence similarity network analysis of drug- and dye-modifying azoreductase enzymes found in the human gut microbiome.}, journal = {Archives of biochemistry and biophysics}, volume = {757}, number = {}, pages = {110025}, pmid = {38740275}, issn = {1096-0384}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Nitroreductases/metabolism/genetics ; *Gastrointestinal Microbiome ; *NADH, NADPH Oxidoreductases/metabolism/genetics/chemistry ; Coloring Agents/metabolism ; Molecular Docking Simulation ; Substrate Specificity ; Sulfasalazine ; Bacterial Proteins/metabolism/genetics/chemistry ; Kinetics ; Clostridiales/enzymology/genetics ; Azo Compounds/metabolism/chemistry ; }, abstract = {Drug metabolism by human gut microbes is often exemplified by azo bond reduction in the anticolitic prodrug sulfasalazine. Azoreductase activity is often found in incubations with cell cultures or ex vivo gut microbiome samples and contributes to the xenobiotic metabolism of drugs and food additives. Applying metagenomic studies to personalized medicine requires knowledge of the genes responsible for sulfasalazine and other drug metabolism, and candidate genes and proteins for drug modifications are understudied. A representative gut-abundant azoreductase from Anaerotignum lactatifermentan DSM 14214 efficiently reduces sulfasalazine and another drug, phenazopyridine, but could not reduce all azo-bonded drugs in this class. We used enzyme kinetics to characterize this enzyme for its NADH-dependent reduction of these drugs and food additives and performed computational docking to provide the groundwork for understanding substrate specificity in this family. We performed an analysis of the Flavodoxin-like fold InterPro family (IPR003680) by computing a sequence similarity network to classify distinct subgroups of the family and then performed chemically-guided functional profiling to identify proteins that are abundant in the NIH Human Microbiome Project dataset. This strategy aims to reduce the number of unique azoreductases needed to characterize one protein family in the diverse set of potential drug- and dye-modifying activities found in the human gut microbiome.}, }
@article {pmid38736265, year = {2024}, author = {Pang, Z and Korpela, R and Vapaatalo, H}, title = {Local aldosterone release and CYP11B2 expression in response to angiotensin peptides, glucose, and potassium - an ex vivo study on murine colon.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {75}, number = {2}, pages = {185-194}, doi = {10.26402/jpp.2024.2.07}, pmid = {38736265}, issn = {1899-1505}, mesh = {Animals ; Male ; Mice ; *Aldosterone/metabolism ; Angiotensin I/physiology ; Angiotensin II/physiology ; Angiotensin III/physiology ; *Colon/metabolism/drug effects ; *Cytochrome P-450 CYP11B2/metabolism ; *Glucose/metabolism ; Peptide Fragments/physiology ; *Potassium/metabolism ; }, abstract = {We have previously described local aldosterone synthesis in mouse colon. In the renin-angiotensin-aldosterone system (RAAS), angiotensin II (Ang II) peptide is the physiological factor which stimulates aldosterone synthesis in the adrenal glands. We have recently demonstrated that Ang II stimulates aldosterone synthesis also in mouse colon. Here, we conducted a 75-min ex vivo incubation of murine colonic tissue and evaluated the effects of three other Ang peptides, Ang I (1 μM), Ang III (0.1 μM) and Ang (1-7) (0.1 μM) on aldosterone synthesis. As a possible mechanism, their effects on tissue levels of the rate-limiting enzyme, aldosterone synthase (CYP11B2) were measured by ELISA and Western blot. Ang III significantly elevated the amount of tissue CYP11B2 protein in colon. The values of released aldosterone in colon tissue incubation were increased over the control in the presence of Ang I, II or III, however, being statistically non-significant. In Western blot analysis, the values of tissue CYP11B2 protein content were elevated by Ang I and II. Ang (1-7) alone in colon did not influence CYP11B2 protein levels in the incubation experiment but showed higher aldosterone release without statistical significance. Ang (1-7) showed an antagonistic effect towards Ang II in release of aldosterone in adrenal gland. An overall estimation of a single peptide (three measured variables), the results were always in an increasing direction. The responses of aldosterone synthesis to high levels of glucose (44 mM) and potassium (18.8 mM) as physiological stimulators in vivo were investigated in the colon incubation. Glucose, equal to four times the concentration of the control buffer in the incubation, showed higher values of aldosterone release in colon than control without statistical significance similarly to the effect seen in adrenal glands. Increasing the concentration of potassium in the incubation buffer exerted no effect on colonic aldosterone production. Intriguingly, no correlation was found between aldosterone release and the tissue CYP11B2 protein content in colon. In summary, the response of colonic aldosterone synthesis to different Ang peptides resembles, but is not identical to, the situation in the adrenal glands.}, }
@article {pmid38734968, year = {2024}, author = {Ma, Y and Zhao, Y and Zhang, X}, title = {Factors affecting neutrophil functions during sepsis: human microbiome and epigenetics.}, journal = {Journal of leukocyte biology}, volume = {116}, number = {4}, pages = {672-688}, doi = {10.1093/jleuko/qiae107}, pmid = {38734968}, issn = {1938-3673}, mesh = {Humans ; *Neutrophils/immunology ; *Sepsis/immunology/microbiology/genetics ; *Epigenesis, Genetic ; *Microbiota/immunology ; *DNA Methylation ; Extracellular Traps/immunology ; }, abstract = {Sepsis is a severe disease that occurs when the body's immune system reacts excessively to infection. The body's response, which includes an intense antibacterial reaction, can damage its tissues and organs. Neutrophils are the major components of white blood cells in circulation, play a vital role in innate immunity while fighting against infections, and are considered a feature determining sepsis classification. There is a plethora of basic research detailing neutrophil functioning, among which, the study of neutrophil extracellular traps is providing novel insights into mechanisms and treatments of sepsis. This review explores their functions, dysfunctions, and influences in the context of sepsis. The interplay between neutrophils and the human microbiome and the impact of DNA methylation on neutrophil function in sepsis are crucial areas of study. The interaction between neutrophils and the human microbiome is complex, particularly in the context of sepsis, where dysbiosis may occur. We highlight the importance of deciphering neutrophils' functional alterations and their epigenetic features in sepsis because it is critical for defining sepsis endotypes and opening up the possibility for novel diagnostic methods and therapy. Specifically, epigenetic signatures are pivotal since they will provide a novel implication for a sepsis diagnostic method when used in combination with the cell-free DNA. Research is exploring how specific patterns of DNA methylation in neutrophils, detectable in cell-free DNA, could serve as biomarkers for the early detection of sepsis.}, }
@article {pmid38732595, year = {2024}, author = {Luiskari, L and Lindén, J and Lehto, M and Salmenkari, H and Korpela, R}, title = {Ketogenic Diet Protects from Experimental Colitis in a Mouse Model Regardless of Dietary Fat Source.}, journal = {Nutrients}, volume = {16}, number = {9}, pages = {}, pmid = {38732595}, issn = {2072-6643}, support = {N/A//Mary och Georg C. Ehrnrooths Stiftelse/ ; N/A//Finnish Cultural Foundation/ ; N/A//Finnish Concordia Fund/ ; N/A//Finska L&#xe4;kares&#xe4;llskapet/ ; #NNFOC0013659//Novo Nordisk Foundation/ ; N/A//Wilhelm and Else Stockmann Foundation/ ; }, mesh = {Animals ; *Diet, Ketogenic ; *Colitis/chemically induced/diet therapy ; Male ; *Mice, Inbred C57BL ; *Disease Models, Animal ; *Dextran Sulfate ; Mice ; *Dietary Fats/adverse effects ; *Colon/pathology/metabolism ; Permeability ; Tight Junction Proteins/metabolism ; Interleukin-1beta/metabolism ; Intestinal Mucosa/pathology/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Fatty Acids ; Dextrans ; Fluorescein-5-isothiocyanate/*analogs &amp; derivatives ; }, abstract = {While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets impacts intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate-dextran (FITC-dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC-dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source.}, }
@article {pmid38729090, year = {2024}, author = {Richter, D and Piel, J}, title = {Novel types of RiPP-modifying enzymes.}, journal = {Current opinion in chemical biology}, volume = {80}, number = {}, pages = {102463}, doi = {10.1016/j.cbpa.2024.102463}, pmid = {38729090}, issn = {1879-0402}, mesh = {*Protein Processing, Post-Translational ; Humans ; *Peptides/metabolism/chemistry ; Ribosomes/metabolism ; Biological Products/metabolism/chemistry ; Animals ; Enzymes/metabolism/chemistry ; }, abstract = {Novel discoveries in natural product biosynthesis reveal hidden bioactive compounds and expand our knowledge in enzymology. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly growing class of natural products featuring diverse non-canonical amino acids introduced by maturation enzymes as a class-defining characteristic. Underexplored RiPP sources, such as the human microbiome, the oceans, uncultured microorganisms, and plants are rich hunting grounds for novel enzymology. Unusual α- and β-amino acids, peptide cleavages, lipidations, diverse macrocyclizations, and other features expand the range of chemical groups that are installed in RiPPs by often promiscuous enzymes. This review highlights the search for novelty in RiPP enzymology in the past two years, with respect to the discovery of new biochemical modifications but also towards novel applications.}, }
@article {pmid38718217, year = {2024}, author = {Nicholson, LK and Kofonow, JM and Robertson, CE and Wright, T and Li, Q and Gardner, EM and Frank, DN and Janoff, EN}, title = {Clinical and Microbial Determinants of Upper Respiratory Colonization With Streptococcus pneumoniae and Native Microbiota in People With Human Immunodeficiency Virus Type 1 and Control Adults.}, journal = {The Journal of infectious diseases}, volume = {230}, number = {6}, pages = {1456-1465}, pmid = {38718217}, issn = {1537-6613}, support = {R01 AI108479/AI/NIAID NIH HHS/United States ; //Pfizer/ ; //Veterans Affairs Research Service/ ; R01 AI108479/NH/NIH HHS/United States ; }, mesh = {Humans ; *Streptococcus pneumoniae/isolation &amp; purification/genetics ; Male ; Adult ; Female ; *Pneumococcal Infections/microbiology ; *HIV Infections/complications/microbiology ; *Nasopharynx/microbiology/virology ; *Microbiota ; Middle Aged ; *HIV-1/genetics ; RNA, Ribosomal, 16S/genetics ; Oropharynx/microbiology/virology ; Respiratory Tract Infections/microbiology/virology/epidemiology ; }, abstract = {BACKGROUND: The substantial risk for respiratory and invasive infections with Streptococcus pneumoniae (Spn) among people with HIV-1 (PWH) begins with asymptomatic colonization. The frequency of Spn colonization among US adults with and without HIV-1 infection is not well characterized in the conjugate vaccine era.<br><br>METHODS: We determined Spn colonization frequency by culture and specific lytA gene quantitative polymerase chain reaction (PCR) and microbiota profile by 16S ribosomal RNA gene sequencing in nasopharyngeal (NP) and oropharyngeal (OP) DNA from 138 PWH and 93 control adults and associated clinical characteristics.<br><br>RESULTS: The frequencies of Spn colonization among PWH and controls did not differ (11.6% vs 8.6%, respectively; P = .46) using combined results of culture and PCR, independent of vaccination or behavioral risks. PWH showed altered microbiota composition (ie, &#x3b2;-diversity; NP: P = .0028, OP: P = .0098), decreased &#x3b1;-diversity (NP: P = .024, OP: P = .0045), and differences in the relative abundance of multiple bacterial taxa. Spn colonization was associated with altered &#x3b2;-diversity in the nasopharynx (P = .011) but not oropharynx (P = .21).<br><br>CONCLUSIONS: Despite widespread conjugate vaccine and antiretroviral use, frequencies of Spn colonization among PWH and controls are currently consistent with those reported in the preconjugate era. The persistently increased risk of pneumococcal disease despite antiretroviral therapy may relate to behavioral and immunologic variables other than colonization.}, }
@article {pmid38717446, year = {2024}, author = {Akouris, PP and Stuivenberg, GA and Chmiel, JA and Kiattiburut, W and Poon, A and Reid, G and Burton, JP}, title = {Ethanolamine enhances adhesion, promotes microcompartment formation, and modulates gene expression in Levilactobacillus brevis ATCC 14869.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2350778}, pmid = {38717446}, issn = {1949-0984}, mesh = {*Ethanolamine/metabolism ; *Gene Expression Regulation, Bacterial ; *Bacterial Adhesion/drug effects ; *Levilactobacillus brevis/genetics/metabolism ; Humans ; Bacterial Proteins/genetics/metabolism ; Gastrointestinal Microbiome ; Animals ; Virulence/genetics ; }, abstract = {Ethanolamine is an abundant compound in the gastrointestinal tract and a valuable source of carbon and nitrogen for pathogenic bacteria harboring ethanolamine utilization (eut) genes. Eut-positive pathogens can consume free ethanolamine to outcompete commensal microbes, which often lack eut genes, and establish infection. Ethanolamine can also act as a host recognition signal for eut-positive pathogens to upregulate virulence genes during colonization. Therefore, reducing free ethanolamine titers may represent a novel approach to preventing infection by eut-positive pathogens. Interestingly, the commensal microorganism Levilactobacillus brevis ATCC 14869 was found to encode over 18 eut genes within its genome. This led us to hypothesize that L. brevis can compete with eut-positive pathogens by clearing free ethanolamine from the environment. Our results demonstrate that despite being unable to metabolize ethanolamine under most conditions, L. brevis ATCC 14869 responds to the compound by increasing the expression of genes encoding proteins involved in microcompartment formation and adhesion to the intestinal epithelial barrier. The improved intestinal adhesion of L. brevis in the presence of ethanolamine also enhanced the exclusion of eut-positive pathogens from adhering to intestinal epithelial cells. These findings support further studies to test whether L. brevis ATCC 14869 can counter enteric pathogens and prevent or reduce the severity of infections. Overall, the metabolic capabilities of L. brevis ATCC 14869 offer a unique opportunity to add to the armamentarium of antimicrobial therapies as well as our understanding of the mechanisms used by beneficial microbes to sense and adapt to host microenvironments.}, }
@article {pmid38717124, year = {2024}, author = {Yadegar, A and Bar-Yoseph, H and Monaghan, TM and Pakpour, S and Severino, A and Kuijper, EJ and Smits, WK and Terveer, EM and Neupane, S and Nabavi-Rad, A and Sadeghi, J and Cammarota, G and Ianiro, G and Nap-Hill, E and Leung, D and Wong, K and Kao, D}, title = {Fecal microbiota transplantation: current challenges and future landscapes.}, journal = {Clinical microbiology reviews}, volume = {37}, number = {2}, pages = {e0006022}, pmid = {38717124}, issn = {1098-6618}, support = {PJT168954//Canadian Government | Canadian Institutes of Health Research (CIHR)/ ; //NIHR | NIHR Nottingham Biomedical Research Centre (BRC)/ ; }, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; Clostridium Infections/therapy/microbiology ; Inflammatory Bowel Diseases/therapy/microbiology ; Animals ; }, abstract = {SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent Clostridioides difficile infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research. However, the complex and variable nature of FMT makes it challenging to address its precise functionality and to assess clinical efficacy and safety in different disease contexts. In this review, we outline clinical applications, efficacy, durability, and safety of FMT and provide a comprehensive assessment of its procedural and administration aspects. The clinical applications of FMT in children and cancer immunotherapy are also described. We focus on data from human studies in IBD in contrast with rCDI to delineate the putative mechanisms of this treatment in IBD as a model, including colonization resistance and functional restoration through bacterial engraftment, modulating effects of virome/phageome, gut metabolome and host interactions, and immunoregulatory actions of FMT. Furthermore, we comprehensively review omics technologies, metagenomic approaches, and bioinformatics pipelines to characterize complex microbial communities and discuss their limitations. FMT regulatory challenges, ethical considerations, and pharmacomicrobiomics are also highlighted to shed light on future development of tailored microbiome-based therapeutics.}, }
@article {pmid38711478, year = {2024}, author = {Ramkumar, D and Marty, A and Ramkumar, J and Rosencranz, H and Vedantham, R and Goldman, M and Meyer, E and Steinmetz, J and Weckle, A and Bloedorn, K and Rosier, C}, title = {Food for thought: Making the case for food produced via regenerative agriculture in the battle against non-communicable chronic diseases (NCDs).}, journal = {One health (Amsterdam, Netherlands)}, volume = {18}, number = {}, pages = {100734}, pmid = {38711478}, issn = {2352-7714}, abstract = {Non-communicable diseases (NCDs) pose a global health challenge, leading to substantial morbidity, mortality, and economic strain. Our review underscores the escalating incidence of NCDs worldwide and highlights the potential of regenerative agriculture (RA) products in mitigating these diseases. We also explore the efficacy of dietary interventions in NCD management and prevention, emphasizing the superiority of plant-based diets over those high in processed foods and red meat. Examining the role of the gut microbiome in various diseases, including liver disorders, allergies, metabolic syndrome, inflammatory bowel disease, and colon cancer, we find compelling evidence implicating its influence on disease development. Notably, dietary modifications can positively affect the gut microbiome, fostering a symbiotic relationship with the host and making this a critical strategy in disease prevention and treatment. Investigating agricultural practices, we identify parallels between soil/plant and human microbiome studies, suggesting a crucial link between soil health, plant- and animal-derived food quality, and human well-being. Conventional/Industrial agriculture (IA) practices, characterized in part by use of chemical inputs, have adverse effects on soil microbiome diversity, food quality, and ecosystems. In contrast, RA prioritizes soil health through natural processes, and includes avoiding synthetic inputs, crop rotation, and integrating livestock. Emerging evidence suggests that food from RA systems surpasses IA-produced food in quality and nutritional value. Recognizing the interconnection between human, plant, and soil microbiomes, promoting RA-produced foods emerges as a strategy to improve human health and environmental sustainability. By mitigating climate change impacts through carbon sequestration and water cycling, RA offers dual benefits for human and planetary health and well-being. Emphasizing the pivotal role of diet and agricultural practices in combating NCDs and addressing environmental concerns, the adoption of regional RA systems becomes imperative. Increasing RA integration into local food systems can enhance food quality, availability, and affordability while safeguarding human health and the planet's future.}, }
@article {pmid38710286, year = {2024}, author = {Zhao, F and Wang, J}, title = {Another piece of puzzle for the human microbiome: the gut virome under dietary modulation.}, journal = {Journal of genetics and genomics = Yi chuan xue bao}, volume = {51}, number = {10}, pages = {983-996}, doi = {10.1016/j.jgg.2024.04.013}, pmid = {38710286}, issn = {1673-8527}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Virome/genetics ; *Diet ; Bacteriophages/genetics/physiology ; Bacteria/genetics/classification/virology ; Gene Transfer, Horizontal ; Viruses/genetics ; }, abstract = {The virome is the most abundant and highly variable microbial consortium in the gut. Because of difficulties in isolating and culturing gut viruses and the lack of reference genomes, the virome has remained a relatively elusive aspect of the human microbiome. In recent years, studies on the virome have accumulated growing evidence showing that the virome is diet-modulated and widely involved in regulating health. Here, we review the responses of the gut virome to dietary intake and the potential health implications, presenting changes in the gut viral community and preferences of viral members to particular diets. We further discuss how viral-bacterial interactions and phage lifestyle shifts shape the gut microbiota. We also discuss the specific functions conferred by diet on the gut virome and bacterial community in the context of horizontal gene transfer, as well as the import of new viral members along with the diet. Collating these studies will expand our understanding of the dietary regulation of the gut virome and inspire dietary interventions and health maintenance strategies targeting the gut microbiota.}, }
@article {pmid38709058, year = {2024}, author = {Geaman, W and Choi, BI and Kaindl, J and Gonzalez, C and Wolfe, AJ}, title = {Microbroth dilution method for antibiotic susceptibility testing of fastidious and anaerobic bacteria of the urinary microbiome.}, journal = {Microbiology spectrum}, volume = {12}, number = {6}, pages = {e0031424}, pmid = {38709058}, issn = {2165-0497}, support = {//Pathnostics/ ; }, mesh = {Humans ; *Microbial Sensitivity Tests/methods ; *Anti-Bacterial Agents/pharmacology ; *Microbiota/drug effects ; *Bacteria, Anaerobic/drug effects/isolation &amp; purification ; Urine/microbiology ; Urinary Tract Infections/microbiology ; Bacteria/drug effects/isolation &amp; purification/growth &amp; development ; Culture Media/chemistry ; }, abstract = {UNLABELLED: Bacterial isolates from the human urinary microbiome have been extensively studied for their antibiotic resistance; however, little work has been done on those isolates that are difficult to grow in vitro. This study was designed to qualify a serum-based medium, New York City Broth III (NYCIII), and a broth microdilution method to determine the antibiotic susceptibility of previously underreported or undescribed microbes that have a difficult time growing in standard Mueller-Hinton broth. Here, we demonstrate that NYCIII microbroth dilution can be an effective method for the determination of antibiotic susceptibility of species found in the human urinary microbiome. We show that this method serves well to characterize fastidious and anaerobic urinary microbes that have no Clinical and Laboratory Standards Institute (CLSI) guidelines, including several in the families Aerococcaceae, Lactobacillaceae, or Actinomycetaceae. Previous studies using expanded quantitative urine culture reveal that urine samples from clinical patients are commonly polymicrobial in composition. Thus, we test whether NYCIII can serve as a viable harmonized medium, capable of supporting antibiotic susceptibility testing in a range of fastidious, non-fastidious, and anaerobic urinary microbes. We propose this methodology to be standardized comparable to CLSI standards to allow for resistance testing in uncharacterized urinary bacteria.<br><br>IMPORTANCE: Antibiotic susceptibilities of fastidious and anaerobic bacteria of the human urinary microbiome are largely underreported due to difficulty in growing them in the lab environment. The current standard medium, Muller-Hinton broth, has difficulty supporting the growth of many of these species, leaving microbiologists without a standardized method. To address this need, this study offers a methodology to survey susceptibilities in a high-throughput manner of these understudied microbes with a proposed harmonized medium, NYCIII, which is capable of supporting the growth of both fastidious and non-fastidious urinary microbes. Broader standardization of this method can allow for the development of antibiotic-resistant breakpoints of the many uncharacterized urinary microbes.}, }
@article {pmid38707185, year = {2024}, author = {Koudokpon, H and Legba, BB and Dougnon, V and Mero, S and Bankole, H and Haukka, K}, title = {Strengthening clinical bacteriology laboratory diagnostics to combat sepsis and antimicrobial resistance in Benin: a train-the-trainer approach.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1281418}, pmid = {38707185}, issn = {2296-858X}, abstract = {INTRODUCTION: Improved laboratory diagnostics is needed to support sepsis diagnosis and combat increasing antibiotic resistance in Benin. We trained clinical laboratory experts and technicians to improve their skills in accurate and up-to-date diagnostics.<br><br>METHODS: A Train-the-Trainer (TtT) approach was used to design the course that combines theoretical and practical laboratory skills, specifically addressing the knowledge gaps we had previously identified in our national survey. Pedagogical methods were student-centered, including peer learning, use of online materials, practical laboratory work and pre-and post-course tests.<br><br>RESULTS: We first trained 10 trainers who in turn trained 40 laboratory technicians from across the country, from both public and private clinical and veterinary laboratories. The trainers also prepared standard operation procedures for blood culture and antibiotic susceptibility testing based on international standards. Three months after the training, follow-up visits were made to the laboratories where the implementation of the new skills was evaluated. The progress of the participants observed during the course and the implementation of the new skills afterwards proved the training to be effective.<br><br>DISCUSSION: The professional networks created during the training, the empowerment that utilizes local knowledge resources, and the government support for our initiative can be expected to bring sustainability to the initiative and support the participation of Beninese laboratories in international surveillance programs in the future.}, }
@article {pmid38706561, year = {2024}, author = {Alagiakrishnan, K and Morgadinho, J and Halverson, T}, title = {Approach to the diagnosis and management of dysbiosis.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1330903}, pmid = {38706561}, issn = {2296-861X}, abstract = {All microorganisms like bacteria, viruses and fungi that reside within a host environment are considered a microbiome. The number of bacteria almost equal that of human cells, however, the genome of these bacteria may be almost 100 times larger than the human genome. Every aspect of the physiology and health can be influenced by the microbiome living in various parts of our body. Any imbalance in the microbiome composition or function is seen as dysbiosis. Different types of dysbiosis are seen and the corresponding symptoms depend on the site of microbial imbalance. The contribution of the intestinal and extra-intestinal microbiota to influence systemic activities is through interplay between different axes. Whole body dysbiosis is a complex process involving gut microbiome and non-gut related microbiome. It is still at the stage of infancy and has not yet been fully understood. Dysbiosis can be influenced by genetic factors, lifestyle habits, diet including ultra-processed foods and food additives, as well as medications. Dysbiosis has been associated with many systemic diseases and cannot be diagnosed through standard blood tests or investigations. Microbiota derived metabolites can be analyzed and can be useful in the management of dysbiosis. Whole body dysbiosis can be addressed by altering lifestyle factors, proper diet and microbial modulation. The effect of these interventions in humans depends on the beneficial microbiome alteration mostly based on animal studies with evolving evidence from human studies. There is tremendous potential for the human microbiome in the diagnosis, treatment, and prognosis of diseases, as well as, for the monitoring of health and disease in humans. Whole body system-based approach to the diagnosis of dysbiosis is better than a pure taxonomic approach. Whole body dysbiosis could be a new therapeutic target in the management of various health conditions.}, }
@article {pmid38702623, year = {2024}, author = {Shen, S and Liu, X and Huang, J and Sun, Y and Liu, B and Song, W and Meng, L and Du, M and Feng, Q}, title = {Efficacy of a mouthwash containing ε-poly-L-lysine, funme peptides and domiphen in reducing halitosis and supragingival plaque: a randomized clinical trial.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {525}, pmid = {38702623}, issn = {1472-6831}, support = {2021SFGC0502//the "Tang Scholar" Program, Major Innovation Projects in Shandong Province/ ; ZR2022QH278//Natural Science Foundation of Shandong Province/ ; tsqn202306369//Construction Engineering Special Fund of "Taishan Scholars" of Shandong Province/ ; ZR2021JQ29//Excellent Young Scientist Foundation of Shandong Province/ ; 2019//Taishan Young Scientist Project of Shandong Province/ ; 2021GXRC021//Periodontitis innovation team of Jinan City/ ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; 2021ZDSYS18//Key Technology Research and Development Program of Shandong Province/ ; 2021SFGC0502//Shandong Province Major Scientifc and Technical Innovation Project/ ; }, mesh = {Humans ; *Halitosis/prevention &amp; control/drug therapy/microbiology ; *Mouthwashes/therapeutic use ; *Dental Plaque/microbiology/prevention &amp; control ; Double-Blind Method ; Male ; Female ; *Polylysine/therapeutic use ; Adult ; Microbial Sensitivity Tests ; Young Adult ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Porphyromonas gingivalis/drug effects ; Fusobacterium nucleatum/drug effects ; Fibroblasts/drug effects ; Peptides/therapeutic use/pharmacology ; Aggregatibacter actinomycetemcomitans/drug effects ; Streptococcus mutans/drug effects ; }, abstract = {OBJECTIVE: To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial.<br><br>MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial.<br><br>RESULTS: The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC&#x2009;<&#x2009;1.56% (v/v) and the MBC&#x2009;<&#x2009;3.13% (v/v), and the mouthwash containing this combination did not inhibit the viability of human gingival fibroblasts at the test concentrations. The clinical trial showed that the test group displayed notably lower volatile sulfur compounds (VSCs) at 0, 10, 24&#xa0;h, and 7 d post-mouthwash (P&#x2009;<&#x2009;0.05), compared with the baseline. After 7 days, the VSC levels of the and control groups were reduced by 50.27% and 32.12%, respectively, and notably cutting severe halitosis by 57.03% in the test group. Additionally, the Plaque Index (PLI) of the test and control group decreased by 54.55% and 8.38%, respectively, and there was a significant difference in PLI between the two groups after 7 days (P&#x2009;<&#x2009;0.01).<br><br>CONCLUSIONS: The combination of &#x3b5;-PL, FP and domiphen demonstrated potent inhibitory and bactericidal effects against the tested oral pathogens, and the newly formulated mouthwash added with the combination exhibited anti-dental plaque and anti-halitosis properties in a clinical trial and was safe.<br><br>TRIAL REGISTRATION: The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2300073816, Date: 21/07/2023).}, }
@article {pmid38700829, year = {2024}, author = {Jang, CS and Kim, H and Kim, D and Han, B}, title = {MicroPredict: predicting species-level taxonomic abundance of whole-shotgun metagenomic data using only 16S amplicon sequencing data.}, journal = {Genes &amp; genomics}, volume = {46}, number = {6}, pages = {701-712}, pmid = {38700829}, issn = {2092-9293}, mesh = {*RNA, Ribosomal, 16S/genetics ; *Metagenomics/methods ; Humans ; *Microbiota/genetics ; Machine Learning ; Whole Genome Sequencing/methods ; Metagenome/genetics ; Bacteria/genetics/classification ; }, abstract = {BACKGROUND: The importance of the human microbiome in the analysis of various diseases is emerging. The two main methods used to profile the human microbiome are 16S rRNA gene sequencing (16S sequencing) and whole-genome shotgun sequencing (WGS). Owing to the full coverage of the genome in sequencing, WGS has multiple advantages over 16S sequencing, including higher taxonomic profiling resolution at the species-level and functional profiling analysis. However, 16S sequencing remains widely used because of its relatively low cost. Although WGS is the standard method for obtaining accurate species-level data, we found that 16S sequencing data contained rich information to predict high-resolution species-level abundances with reasonable accuracy.<br><br>OBJECTIVE: In this study, we proposed MicroPredict, a method for accurately predicting WGS-comparable species-level abundance data using 16S taxonomic profile data.<br><br>METHODS: We employed a mixed model using two key strategies: (1) modeling both sample- and species-specific information for predicting WGS abundances, and (2) accounting for the possible correlations among different species.<br><br>RESULTS: We found that MicroPredict outperformed the other machine learning methods.<br><br>CONCLUSION: We expect that our approach will help researchers accurately approximate the species-level abundances of microbiome profiles in datasets for which only cost-effective 16S sequencing has been applied.}, }
@article {pmid38697697, year = {2024}, author = {Araujo, R and Merino-Ribas, A and Pereira, L and Campos, J and Silva, N and Alencastre, IS and Pestana, M and Sampaio-Maia, B}, title = {The urogenital microbiome in chronic kidney disease patients on peritoneal dialysis.}, journal = {Nefrologia}, volume = {44}, number = {2}, pages = {194-203}, doi = {10.1016/j.nefroe.2024.04.004}, pmid = {38697697}, issn = {2013-2514}, mesh = {Humans ; Female ; Male ; *Peritoneal Dialysis/adverse effects ; Middle Aged ; *Microbiota ; *Renal Insufficiency, Chronic/microbiology/therapy/complications ; Aged ; Urogenital System/microbiology ; Adult ; Feces/microbiology ; }, abstract = {INTRODUCTION AND OBJECTIVES: Diabetes, dyslipidemia, older age, gender, urinary tract infections, and recent antibiotic intake have been associated with a decrease in the urobiome richness and other fluctuations in this microbiome. Gut and blood microbiome have been reported to be altered in patients with chronic kidney disease (CKD), and specifically in peritoneal dialysis (PD) patients. Still, there are currently no studies describing the urogenital microbiome in CKD-PD patients. In this study we characterized the urobiome profile in 46 PD patients and analyzed its clinical and inflammatory parameters.<br><br>MATERIALS AND METHODS: Mid-stream urine, fecal and blood samples were collected from 46 patients undergoing PD at Centro Hospitalar Universit&#xe1;rio de S&#xe3;o Jo&#xe3;o (CHUSJ) in Porto, Portugal. Exclusion criteria were age under 18 years old, inability to give informed consent, history of infection in the last three months, and antibiotic intake in the last three months. The microbiome communities were analyzed by amplification and sequencing of the V3-V4 region of the bacterial 16S rRNA gene. Correlations with the patients' clinical data and inflammatory profile were performed.<br><br>RESULTS: CKD-PD patients presented a unique urobiome profile dominated by Bacillota, Actinomycetota and Pseudomonadota and characterized by a lower Shannon diversity than fecal and blood microbiome. The taxonomic profiles of urogenital samples were organized in multiple subtypes dominated by populations of Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, being similar to other non-PD-CKD patients. Gender, sCD14, residual diuresis and history of peritonitis were significantly associated to variations in the urobiome. Although not reaching statistical significance, diabetes and the time on PD also showed association with particular taxonomic groups. Depletion of Gardnerella, Staphylococcus, Corynebacterium, Lactobacillus or Dermabacter populations correlated with CKD-PD patients with history of diabetes, history of peritonitis and altered levels of sCD14.<br><br>CONCLUSIONS: Our results highlight urogenital microbiome as a potential partner and/or marker in the overall health state of CKD-PD patients.}, }
@article {pmid38695302, year = {2024}, author = {Roussel, C and Sola, M and Lessard-Lord, J and Nallabelli, N and Généreux, P and Cavestri, C and Azeggouar Wallen, O and Villano, R and Raymond, F and Flamand, N and Silvestri, C and Di Marzo, V}, title = {Human gut microbiota and their production of endocannabinoid-like mediators are directly affected by a dietary oil.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2335879}, pmid = {38695302}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Bacteria/classification/metabolism/isolation &amp; purification/genetics ; *Endocannabinoids/metabolism ; Colon/microbiology/metabolism ; Ileum/microbiology/metabolism ; Fatty Acids, Omega-3/metabolism ; Plant Oils/metabolism/pharmacology ; Dietary Supplements ; Adult ; Male ; }, abstract = {Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) and the gut microbiome affect each other. We investigated the impact of supplementation with Buglossoides arvensis oil (BO), rich in stearidonic acid (SDA), on the human gut microbiome. Employing the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), we simulated the ileal and ascending colon microbiomes of four donors. Our results reveal two distinct microbiota clusters influenced by BO, exhibiting shared and contrasting shifts. Notably, Bacteroides and Clostridia abundance underwent similar changes in both clusters, accompanied by increased propionate production in the colon. However, in the ileum, cluster 2 displayed a higher metabolic activity in terms of BO-induced propionate levels. Accordingly, a triad of bacterial members involved in propionate production through the succinate pathway, namely Bacteroides, Parabacteroides, and Phascolarctobacterium, was identified particularly in this cluster, which also showed a surge of second-generation probiotics, such as Akkermansia, in the colon. Finally, we describe for the first time the capability of gut bacteria to produce N-acyl-ethanolamines, and particularly the SDA-derived N-stearidonoyl-ethanolamine, following BO supplementation, which also stimulated the production of another bioactive endocannabinoid-like molecule, commendamide, in both cases with variations across individuals. Spearman correlations enabled the identification of bacterial genera potentially involved in endocannabinoid-like molecule production, such as, in agreement with previous reports, Bacteroides in the case of commendamide. This study suggests that the potential health benefits on the human microbiome of certain dietary oils may be amenable to stratified nutrition strategies and extend beyond n-3 PUFAs to include microbiota-derived endocannabinoid-like mediators.}, }
@article {pmid38694799, year = {2024}, author = {Zhang, Y and Xue, G and Wang, F and Zhang, J and Xu, L and Yu, C}, title = {The impact of antibiotic exposure on antibiotic resistance gene dynamics in the gut microbiota of inflammatory bowel disease patients.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1382332}, pmid = {38694799}, issn = {1664-302X}, abstract = {BACKGROUND: While antibiotics are commonly used to treat inflammatory bowel disease (IBD), their widespread application can disturb the gut microbiota and foster the emergence and spread of antibiotic resistance. However, the dynamic changes to the human gut microbiota and direction of resistance gene transmission under antibiotic effects have not been clearly elucidated.<br><br>METHODS: Based on the Human Microbiome Project, a total of 90 fecal samples were collected from 30 IBD patients before, during and after antibiotic treatment. Through the analysis workflow of metagenomics, we described the dynamic process of changes in bacterial communities and resistance genes pre-treatment, during and post-treatment. We explored potential consistent relationships between gut microbiota and resistance genes, and established gene transmission networks among species before and after antibiotic use.<br><br>RESULTS: Exposure to antibiotics can induce alterations in the composition of the gut microbiota in IBD patients, particularly a reduction in probiotics, which gradually recovers to a new steady state after cessation of antibiotics. Network analyses revealed intra-phylum transfers of resistance genes, predominantly between taxonomically close organisms. Specific resistance genes showed increased prevalence and inter-species mobility after antibiotic cessation.<br><br>CONCLUSION: This study demonstrates that antibiotics shape the gut resistome through selective enrichment and promotion of horizontal gene transfer. The findings provide insights into ecological processes governing resistance gene dynamics and dissemination upon antibiotic perturbation of the microbiota. Optimizing antibiotic usage may help limit unintended consequences like increased resistance in gut bacteria during IBD management.}, }
@article {pmid38690563, year = {2024}, author = {Karaman, I and Pathak, A and Bayik, D and Watson, DC}, title = {Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy.}, journal = {Pathogens &amp; immunity}, volume = {9}, number = {1}, pages = {56-90}, pmid = {38690563}, issn = {2469-2964}, support = {K99 CA277242/CA/NCI NIH HHS/United States ; R00 CA277242/CA/NCI NIH HHS/United States ; }, abstract = {There are a growing number of studies linking the composition of the human microbiome to disease states and treatment responses, especially in the context of cancer. This has raised significant interest in developing microbes and microbial products as cancer immunotherapeutics that mimic or recapitulate the beneficial effects of host-microbe interactions. Bacterial extracellular vesicles (bEVs) are nano-sized, membrane-bound particles secreted by essentially all bacteria species and contain a diverse bioactive cargo of the producing cell. They have a fundamental role in facilitating interactions among cells of the same species, different microbial species, and even with multicellular host organisms in the context of colonization (microbiome) and infection. The interaction of bEVs with the immune system has been studied extensively in the context of infection and suggests that bEV effects depend largely on the producing species. They thus provide functional diversity, while also being nonreplicative, having inherent cell-targeting qualities, and potentially overcoming natural barriers. These characteristics make them highly appealing for development as cancer immunotherapeutics. Both natively secreted and engineered bEVs are now being investigated for their application as immunotherapeutics, vaccines, drug delivery vehicles, and combinations of the above, with promising early results. This suggests that both the intrinsic immunomodulatory properties of bEVs and their ability to be modified could be harnessed for the development of next-generation microbe-inspired therapies. Nonetheless, there remain major outstanding questions regarding how the observed preclinical effectiveness will translate from murine models to primates, and humans in particular. Moreover, research into the pharmacology, toxicology, and mass manufacturing of this potential novel therapeutic platform is still at early stages. In this review, we highlight the breadth of bEV interactions with host cells, focusing on immunologic effects as the main mechanism of action of bEVs currently in preclinical development. We review the literature on ongoing efforts to develop natively secreted and engineered bEVs from a variety of bacterial species for cancer therapy and finally discuss efforts to overcome outstanding challenges that remain for clinical translation.}, }
@article {pmid38688858, year = {2024}, author = {Sminia, TJ and Aalvink, S and de Jong, H and Tempelaars, MH and Zuilhof, H and Abee, T and de Vos, WM and Tytgat, HLP and Wennekes, T}, title = {Probing Peptidoglycan Synthesis in the Gut Commensal Akkermansia Muciniphila with Bioorthogonal Chemical Reporters.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {25}, number = {19}, pages = {e202400037}, doi = {10.1002/cbic.202400037}, pmid = {38688858}, issn = {1439-7633}, support = {//Netherlands Foundation for Scientific Research (NWO)/ ; 722.011.006//VENI/ ; 723.014.005//VIDI/ ; //Laboratory of Microbiology/ ; //Soehngen Institute of Anaerobic Microbiology/ ; //SIAM/ ; 024.002.002//NWO/ ; //NWO/ ; //WMdV/ ; //Laboratory of Biochemistry, Wageningen University/ ; }, mesh = {*Peptidoglycan/metabolism/chemistry/biosynthesis ; *Akkermansia/metabolism ; *Gastrointestinal Microbiome ; Humans ; Molecular Probes/chemistry/metabolism ; Click Chemistry ; Cyclopropanes/chemistry/metabolism ; }, abstract = {Our gut microbiota directly influences human physiology in health and disease. The myriad of surface glycoconjugates in both the bacterial cell envelope and our gut cells dominate the microbiota-host interface and play a critical role in host response and microbiota homeostasis. Among these, peptidoglycan is the basic glycan polymer offering the cell rigidity and a basis on which many other glycoconjugates are anchored. To directly study peptidoglycan in gut commensals and obtain the molecular insight required to understand their functional activities we need effective techniques like chemical probes to label peptidoglycan in live bacteria. Here we report a chemically guided approach to study peptidoglycan in a key mucin-degrading gut microbiota member of the Verrucomicrobia phylum, Akkermansia muciniphila. Two novel non-toxic tetrazine click-compatible peptidoglycan probes with either a cyclopropene or isonitrile handle allowed for the detection and imaging of peptidoglycan synthesis in this intestinal species.}, }
@article {pmid38687072, year = {2024}, author = {Nagpal, S and Mande, SS and Hooda, H and Dutta, U and Taneja, B}, title = {EnsembleSeq: a workflow towards real-time, rapid, and simultaneous multi-kingdom-amplicon sequencing for holistic and resource-effective microbiome research at scale.}, journal = {Microbiology spectrum}, volume = {12}, number = {6}, pages = {e0415023}, pmid = {38687072}, issn = {2165-0497}, support = {OLP2306//CSIR-Institute of Genomics and Integrative Biology/ ; }, mesh = {Humans ; *RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Bacteria/genetics/classification/isolation &amp; purification ; *Saliva/microbiology ; *Fungi/genetics/classification/isolation &amp; purification ; Workflow ; DNA, Bacterial/genetics ; High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, DNA/methods ; DNA, Fungal/genetics ; }, abstract = {UNLABELLED: Bacterial communities are often concomitantly present with numerous microorganisms in the human body and other natural environments. Amplicon-based microbiome studies have generally paid skewed attention, that too at a rather shallow genus level resolution, to the highly abundant bacteriome, with interest now forking toward the other microorganisms, particularly fungi. Given the generally sparse abundance of other microbes in the total microbiome, simultaneous sequencing of amplicons targeting multiple microbial kingdoms could be possible even with full multiplexing. Guiding studies are currently needed for performing and monitoring multi-kingdom-amplicon sequencing and data capture at scale. Aiming to address these gaps, amplification of full-length bacterial 16S rRNA gene and entire fungal internal-transcribed spacer (ITS) region was performed for human saliva samples (n = 96, including negative and positive controls). Combined amplicon DNA libraries were prepared for nanopore sequencing using a major fraction of 16S molecules and a minor fraction of ITS amplicons. Sequencing was performed in a single run of an R10.4.1 flow cell employing the latest V14 chemistry. An approach for real-time monitoring of the species saturation using dynamic rarefaction was designed as a guiding determinant of optimal run time. Real-time saturation monitoring for both bacterial and fungal species enabled the completion of sequencing within 30 hours, utilizing less than 60% of the total nanopores. Approximately 5 million high quality (HQ) taxonomically assigned reads were generated (~4.2 million bacterial and 0.7 million fungal), providing a wider (beyond bacteriome) snapshot of human oral microbiota at species-level resolution. Among the more than 400 bacterial and 240 fungal species identified in the studied samples, the species of Streptococcus (e.g., Streptococcus mitis and Streptococcus oralis) and Candida (e.g., Candida albicans and Candida tropicalis) were observed to be the dominating microbes in the oral cavity, respectively. This conformed well with the previous reports of the human oral microbiota. EnsembleSeq provides a proof-of-concept toward the identification of both fungal and bacterial species simultaneously in a single fully multiplexed nanopore sequencing run in a time- and resource-effective manner. Details of this workflow, along with the associated codebase, are provided to enable large-scale application for a holistic species-level microbiome study.<br><br>IMPORTANCE: Human microbiome is a sum total of a variety of microbial genomes (including bacteria, fungi, protists, viruses, etc.) present in and on the human body. Yet, a majority of amplicon-based microbiome studies have largely remained skewed toward bacteriome as an assumed proxy of the total microbiome, primarily at a shallow genus level. Cost, time, effort, data quality/management, and importantly lack of guiding studies often limit progress in the direction of moving beyond bacteriome. Here, EnsembleSeq presents a proof-of-concept toward concomitantly capturing multiple-kingdoms of microorganisms (bacteriome and mycobiome) in a fully multiplexed (96-sample) single run of long-read amplicon sequencing. In addition, the workflow captures dynamic tracking of species-level saturation in a time- and resource-effective manner.}, }
@article {pmid38687061, year = {2024}, author = {Kallio, S and Jian, C and Korpela, K and Kukkonen, AK and Salonen, A and Savilahti, E and Kuitunen, M and M de Vos, W}, title = {Early-life gut microbiota associates with allergic rhinitis during 13-year follow-up in a Finnish probiotic intervention cohort.}, journal = {Microbiology spectrum}, volume = {12}, number = {6}, pages = {e0413523}, pmid = {38687061}, issn = {2165-0497}, support = {308253//Research Council of Finland (AKA)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/administration &amp; dosage ; *Rhinitis, Allergic/microbiology ; Female ; Finland/epidemiology ; Adolescent ; Child, Preschool ; Male ; Infant ; Child ; Follow-Up Studies ; *Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Pregnancy ; Infant, Newborn ; Cohort Studies ; Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {Perinatal and early-life factors reported to affect risk of allergic diseases may be mediated by changes in the gut microbiota. Here, we explored the associations between the infant gut microbiota and allergic morbidity in childhood until 13 years of age in a subgroup of the FLORA probiotic intervention cohort. A mixture of four probiotic strains with galacto-oligosaccharides was administrated to the mothers from the 36th week of the pregnancy and later to their infants until 6 months of age. The infants were monitored for the manifestations of atopic eczema, food allergy, allergic rhinitis, and asthma by a pediatrician at 2 and 5 years of age; the allergic status was subsequently verified by a questionnaire at 10 and 13 years of age. The fecal microbiota at 3 months was profiled by 16S rRNA amplicon sequencing targeting the V3-V4 region, with and without adjusting for potentially important early-life factors. Overall, the positive diagnosis for allergic rhinitis between 2 and 13 years was associated with microbiota composition both in non-adjusted and adjusted models. This association was more pronounced in children born to one parent with confirmed atopic diseases compared to those who had two atopic parents and was characterized by a lower relative abundance of Bifidobacterium and Escherichia/Shigella spp. and a higher proportion of Bacteroides. While the probiotic and galacto-oligosaccharides intervention in the entire cohort was previously shown to reduce the prevalence of eczema to a certain extent, no associations were found between the 3-month gut microbiota and childhood eczema in the studied sub-cohort.IMPORTANCEAllergic diseases have increased in prevalence during the past decades globally. Although probiotics have been considered a promising strategy for preventing certain allergy related symptoms, studies connecting the infant gut microbiota and later life allergic morbidity in various populations remain limited. The present study supports an association between the infant microbiota and allergic morbidity after first years of life, which has been rarely examined.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT00298337).}, }
@article {pmid38686448, year = {2024}, author = {Zhang, Y and Miao, D and Su, M and Tang, Y and Zhou, M and Yu, Y and Guo, X and Wu, D}, title = {Synergistic Drug-Loaded Shear-Thinning Star Polymer Hydrogel Facilitates Gastrointestinal Lesion Resection and Promotes Wound Healing.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {26}, pages = {e2309586}, pmid = {38686448}, issn = {2198-3844}, support = {2023B0303000025//Guangdong Major Project of Basic and Applied Basic Research/ ; 51925308//National Natural Science Foundation of China/ ; 2022YFA1304000//National Key Research and Development Program of China/ ; SL2023B03J00112//Science and Technology Program of Guangzhou/ ; KY012021209//GDPH Supporting Fund for Talent Program/ ; KY0120240026//GDPH Supporting Fund for Talent Program/ ; 2024A1515011636//Guangdong Basic and Applied Basic Research Foundation/ ; 23yxqntd002//Fundamental Research Funds for the Central Universities, Sun Yat-sen University/ ; //Guangdong Basic Research Center of Excellence for Functional Molecular Engineering/ ; }, mesh = {Animals ; *Wound Healing/drug effects ; Swine ; *Hydrogels/chemistry ; *Polymers/chemistry ; Polyethylene Glycols/chemistry ; Disease Models, Animal ; Methacrylates/chemistry ; Anti-Bacterial Agents/pharmacology/administration &amp; dosage ; }, abstract = {Easy injection, long-lasting barrier, and drug loading are the critical properties of submucosal injection materials for endoscopic surgery. However, conventional injectable polymers face challenges in simultaneously attaining these properties due to the inherent conflict between injectability and in situ stability. Here, a multi-arm star polymer hydrogel (denoted as βCP hydrogel) with long-lasting submucosal barrier (exceeding 120 min), rapid hemostasis, and sustained antibacterial properties is successfully developed by grafting poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA) side-chains from β-CD via atom transfer radical polymerization (ATRP). During the onset of shearing, βCP hydrogel experiences the unwinding of polymer side-chains between neighboring star polymers, which facilitates the process of endoscopic injectability. After submucosal injection, βCP hydrogel undergoes the winding of polymer side-chains, thereby establishing a long-lasting barrier cushion. Meanwhile, owing to its distinctive structures with a hydrophobic inner cavity and an outer layer of hydrophilic polymer side-chains, βCP hydrogel enables simultaneous loading and on-demand release of diverse categories of drugs. This unique performance can adapt to the diverse demands during different stages of wound healing in a porcine endoscopic surgery model. These results indicate an appealing prospect for new application of star polymers as a good submucosal injection material in endoscopic treatments.}, }
@article {pmid38680911, year = {2024}, author = {Chen See, JR and Leister, J and Wright, JR and Kruse, PI and Khedekar, MV and Besch, CE and Kumamoto, CA and Madden, GR and Stewart, DB and Lamendella, R}, title = {Clostridioides difficile infection is associated with differences in transcriptionally active microbial communities.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1398018}, pmid = {38680911}, issn = {1664-302X}, support = {R16 AI182344/AI/NIAID NIH HHS/United States ; }, abstract = {Clostridioides difficile infection (CDI) is responsible for around 300,000 hospitalizations yearly in the United States, with the associated monetary cost being billions of dollars. Gut microbiome dysbiosis is known to be important to CDI. To the best of our knowledge, metatranscriptomics (MT) has only been used to characterize gut microbiome composition and function in one prior study involving CDI patients. Therefore, we utilized MT to investigate differences in active community diversity and composition between CDI+ (n = 20) and CDI- (n = 19) samples with respect to microbial taxa and expressed genes. No significant (Kruskal-Wallis, p > 0.05) differences were detected for richness or evenness based on CDI status. However, clustering based on CDI status was significant for both active microbial taxa and expressed genes datasets (PERMANOVA, p ≤ 0.05). Furthermore, differential feature analysis revealed greater expression of the opportunistic pathogens Enterocloster bolteae and Ruminococcus gnavus in CDI+ compared to CDI- samples. When only fungal sequences were considered, the family Saccharomycetaceae expressed more genes in CDI-, while 31 other fungal taxa were identified as significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) associated with CDI+. We also detected a variety of genes and pathways that differed significantly (Kruskal-Wallis p ≤ 0.05, log(LDA) ≥ 2) based on CDI status. Notably, differential genes associated with biofilm formation were expressed by C. difficile. This provides evidence of another possible contributor to C. difficile's resistance to antibiotics and frequent recurrence in vivo. Furthermore, the greater number of CDI+ associated fungal taxa constitute additional evidence that the mycobiome is important to CDI pathogenesis. Future work will focus on establishing if C. difficile is actively producing biofilms during infection and if any specific fungal taxa are particularly influential in CDI.}, }
@article {pmid38677439, year = {2024}, author = {Luo, X and Hounmanou, YMG and Ndayisenga, F and Yu, Z}, title = {Spontaneous fermentation mitigates the frequency of genes encoding antimicrobial resistance spreading from the phyllosphere reservoir to the diet.}, journal = {The Science of the total environment}, volume = {931}, number = {}, pages = {172712}, doi = {10.1016/j.scitotenv.2024.172712}, pmid = {38677439}, issn = {1879-1026}, mesh = {*Fermentation ; *Microbiota/drug effects ; Bacteria/genetics ; Genes, Bacterial ; Metagenome ; Drug Resistance, Bacterial/genetics ; Drug Resistance, Microbial/genetics ; Vegetables/microbiology ; Humans ; Diet ; }, abstract = {The phyllosphere microbiome of vegetable products constitutes an important reservoir for multidrug resistant bacteria and Antibiotic Resistance Genes (ARG). Vegetable products including fermented products such as Paocai therefore may serve as a shuttle for extrinsic microorganisms with ARGs into the gut of consumers. Here we study the effect of fermentation on Paocai ARG dissemination by metagenomic analysis. Microbial abundance and diversity of the Paocai microbiome were diminished during fermentation, which correlated with the reduction of abundance in ARGs. Specifically, as fermentation progressed, Enterobacterales overtook Pseudomonadales as the predominant ARG carriers, and Lactobacillales and Enterobacteriales became the determinants of Paocai resistome variation. Moreover, the dual effect of microbes and metal resistance genes (MRGs) was the major contributor driving Paocai resistome dynamics. We recovered several metagenome-assembled genomes (MAGs) carrying acquired ARGs in the phyllosphere microbiome. ARGs of potential clinical and epidemiological relevance such as tet M and emrB-qacA, were mainly hosted by non-dominant bacterial genera. Overall, our study provides evidence that changes in microbial community composition by fermentation aid in constraining ARG dispersal from raw ingredients to the human microbiome but does not eliminate them.}, }
@article {pmid38674588, year = {2024}, author = {Brogna, C and Bisaccia, DR and Costanzo, V and Lettieri, G and Montano, L and Viduto, V and Fabrowski, M and Cristoni, S and Prisco, M and Piscopo, M}, title = {Who Is the Intermediate Host of RNA Viruses? A Study Focusing on SARS-CoV-2 and Poliovirus.}, journal = {Microorganisms}, volume = {12}, number = {4}, pages = {}, pmid = {38674588}, issn = {2076-2607}, abstract = {The COVID-19 pandemic has sparked a surge in research on microbiology and virology, shedding light on overlooked aspects such as the infection of bacteria by RNA virions in the animal microbiome. Studies reveal a decrease in beneficial gut bacteria during COVID-19, indicating a significant interaction between SARS-CoV-2 and the human microbiome. However, determining the origins of the virus remains complex, with observed phenomena such as species jumps adding layers to the narrative. Prokaryotic cells play a crucial role in the disease's pathogenesis and transmission. Analyzing previous studies highlights intricate interactions from clinical manifestations to the use of the nitrogen isotope test. Drawing parallels with the history of the Poliovirus underscores the need to prioritize investigations into prokaryotic cells hosting RNA viruses.}, }
@article {pmid38674238, year = {2024}, author = {Hernández-Zulueta, J and Bolaños-Chang, AJ and Santa Cruz-Pavlovich, FJ and Valero Rodríguez, AD and Lizárraga Madrigal, A and Del Rio-Murillo, XI and Navarro-Partida, J and Gonzalez-De la Rosa, A}, title = {Microbial Dynamics in Ophthalmic Health: Exploring the Interplay between Human Microbiota and Glaucoma Pathogenesis.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {4}, pages = {}, pmid = {38674238}, issn = {1648-9144}, mesh = {Humans ; *Glaucoma/microbiology ; *Microbiota/physiology ; *Dysbiosis/complications/immunology ; Mouth/microbiology ; Gastrointestinal Microbiome/physiology ; Eye/microbiology ; Neurodegenerative Diseases/microbiology ; }, abstract = {The human microbiome has a crucial role in the homeostasis and health of the host. These microorganisms along with their genes are involved in various processes, among these are neurological signaling, the maturation of the immune system, and the inhibition of opportunistic pathogens. In this sense, it has been shown that a healthy ocular microbiota acts as a barrier against the entry of pathogens, contributing to the prevention of infections. In recent years, a relationship has been suggested between microbiota dysbiosis and the development of neurodegenerative diseases. In patients with glaucoma, it has been observed that the microbiota of the ocular surface, intraocular cavity, oral cavity, stomach, and gut differ from those observed in healthy patients, which may suggest a role in pathology development, although the evidence remains limited. The mechanisms involved in the relationship of the human microbiome and this neurodegenerative disease remain largely unknown. For this reason, the present review aims to show a broad overview of the influence of the structure and composition of the human oral and gut microbiota and relate its dysbiosis to neurodegenerative diseases, especially glaucoma.}, }
@article {pmid38669195, year = {2024}, author = {Sengupta, S and Pabbaraja, S and Mehta, G}, title = {Natural products from the human microbiome: an emergent frontier in organic synthesis and drug discovery.}, journal = {Organic &amp; biomolecular chemistry}, volume = {22}, number = {20}, pages = {4006-4030}, doi = {10.1039/d4ob00236a}, pmid = {38669195}, issn = {1477-0539}, mesh = {Humans ; *Biological Products/pharmacology/chemistry/chemical synthesis/metabolism ; *Drug Discovery ; *Microbiota/drug effects ; Anti-Bacterial Agents/pharmacology/chemical synthesis/chemistry ; }, abstract = {Often referred to as the "second genome", the human microbiome is at the epicenter of complex inter-habitat biochemical networks like the "gut-brain axis", which has emerged as a significant determinant of cognition, overall health and well-being, as well as resistance to antibiotics and susceptibility to diseases. As part of a broader understanding of the nexus between the human microbiome, diseases and microbial interactions, whether encoded secondary metabolites (natural products) play crucial signalling roles has been the subject of intense scrutiny in the recent past. A major focus of these activities involves harvesting the genomic potential of the human microbiome via bioinformatics guided genome mining and culturomics. Through these efforts, an impressive number of structurally intriguing antibiotics, with enhanced chemical diversity vis-à-vis conventional antibiotics have been isolated from human commensal bacteria, thereby generating considerable interest in their total synthesis and expanding their therapeutic space for drug discovery. These developments augur well for the discovery of new drugs and antibiotics, particularly in the context of challenges posed by mycobacterial resistance and emerging new diseases. The current landscape of various synthetic campaigns and drug discovery initiatives on antibacterial natural products from the human microbiome is captured in this review with an intent to stimulate further activities in this interdisciplinary arena among the new generation.}, }
@article {pmid38668878, year = {2024}, author = {Farfour, E and Vasse, M and Vallée, A}, title = {Oligella spp.: A systematic review on an uncommon urinary pathogen.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {43}, number = {6}, pages = {1037-1050}, pmid = {38668878}, issn = {1435-4373}, mesh = {Humans ; *Microbial Sensitivity Tests ; *Urinary Tract Infections/microbiology ; *Anti-Bacterial Agents/pharmacology ; Gram-Negative Bacterial Infections/microbiology/diagnosis ; }, abstract = {BACKGROUND: Oligella is an uncommon Gram-negative coccobacillus that was first thought to belong to the urogenital tract. The genus Oligella comprises two species that were recovered from various samples worldwide.<br><br>METHODS: We perform a systematic review focusing on Oligella microbiological characteristics, habitat, role in Human microbiome and infection, and antimicrobial susceptibility.<br><br>RESULTS: In humans, Oligella is mainly found as part of the microbiome of individuals with predisposing conditions. Oligella were also associated with invasive infections in patients with underlying diseases. Nevertheless, their prevalence remains to determine. Oligella culture requires up to 48&#xa0;h on agar media in vitro, while urinary samples are usually incubated for 24&#xa0;h. Consequently, microbiologists should be prompt to prolong the incubation of agar media when the direct examination showed Gram-negative coccobacilli. Oligella is accurately identified using MALDI-TOF mass spectrometry, but biochemical methods often provided inconsistent results. Specific guidelines for antimicrobial susceptibility testing of Oligella lack but the incubation could require up to 48&#xa0;h of incubation. In contrast to O. urethralis, which is susceptible to third-generation cephalosporin, O. ureolytica is likely resistant to numerous antimicrobials. Genectic determinants of resistance were identified for beta-lactams and aminoglycosides.<br><br>CONCLUSION: Oligella is an uncommon pathogen that can be underrecognized. Microbiologists should be prompt to prolong the incubation of agar media plated with urines when the direct examination showed Gram-negative coccobacilli. Carbapenems should probably be given for the empirical treatment.}, }
@article {pmid38666212, year = {2024}, author = {Pujolassos, M and Susín, A and Calle, ML}, title = {Microbiome compositional data analysis for survival studies.}, journal = {NAR genomics and bioinformatics}, volume = {6}, number = {2}, pages = {lqae038}, pmid = {38666212}, issn = {2631-9268}, abstract = {The growing interest in studying the relationship between the human microbiome and our health has also extended to time-to-event studies where researchers explore the connection between the microbiome and the occurrence of a specific event of interest. The analysis of microbiome obtained through high throughput sequencing techniques requires the use of specialized Compositional Data Analysis (CoDA) methods designed to accommodate its compositional nature. There is a limited availability of statistical tools for microbiome analysis that incorporate CoDA, and this is even more pronounced in the context of survival analysis. To fill this methodological gap, we present coda4microbiome for survival studies, a new methodology for the identification of microbial signatures in time-to-event studies. The algorithm implements an elastic-net penalized Cox regression model adapted to compositional covariates. We illustrate coda4microbiome algorithm for survival studies with a case study about the time to develop type 1 diabetes for non-obese diabetic mice. Our algorithm identified a bacterial signature composed of 21 genera associated with diabetes development. coda4microbiome for survival studies is integrated in the R package coda4microbiome as an extension of the existing functions for cross-sectional and longitudinal studies.}, }
@article {pmid38663540, year = {2024}, author = {Liang, L and Zhang, J and Chen, J and Tian, Y and Li, W and Shi, M and Cheng, S and Zheng, Y and Wang, C and Liu, H and Yang, X and Ye, W}, title = {Bazedoxifene attenuates dextran sodium sulfate-induced colitis in mice through gut microbiota modulation and inhibition of STAT3 and NF-κB pathways.}, journal = {European journal of pharmacology}, volume = {974}, number = {}, pages = {176611}, doi = {10.1016/j.ejphar.2024.176611}, pmid = {38663540}, issn = {1879-0712}, mesh = {Animals ; *Dextran Sulfate ; *NF-kappa B/metabolism ; *STAT3 Transcription Factor/metabolism ; *Colitis/chemically induced/drug therapy/metabolism/microbiology/pathology ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Signal Transduction/drug effects ; Indoles/pharmacology/therapeutic use ; Mice, Inbred C57BL ; Disease Models, Animal ; Colon/drug effects/pathology/metabolism/microbiology ; Male ; Humans ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this study, we used a dual-luciferase-based screening of an FDA-approved drug library, identifying Bazedoxifene (BZA) as an inhibitor of the NF-κB pathway. We further investigated its therapeutic effects in a dextran sodium sulfate (DSS)-induced colitis model and explored its impact on gut microbiota regulation and the underlying molecular mechanisms. Our results showed that BZA significantly reduced DSS-induced colitis symptoms in mice, evidenced by decreased colon length shortening, lower histological scores, and increased expression of intestinal mucosal barrier-associated proteins, such as Claudin 1, Occludin, Zo-1, Mucin 2 (Muc2), and E-cadherin. Used independently, BZA showed therapeutic effects comparable to those of infliximab (IFX). In addition, BZA modulated the abundance of gut microbiota especially Bifidobacterium pseudolongum, and influenced microbial metabolite production. Crucially, BZA's alleviation of DSS-induced colitis in mice was linked to change in gut microbiota composition, as evidenced by in vivo gut microbiota depletion and fecal microbiota transplantation (FMT) mice model. Molecularly, BZA inhibited STAT3 and NF-κB activation in DSS-induced colitis in mice. In general, BZA significantly reduced DSS-induced colitis in mice through modulating the gut microbiota and inhibiting STAT3 and NF-κB activation, and its independent use demonstrated a therapeutic potential comparable to IFX. This study highlights gut microbiota's role in IBD drug development, offering insights for BZA's future development and its clinical applications.}, }
@article {pmid38658578, year = {2024}, author = {Pedrazzoli, E and Demozzi, M and Visentin, E and Ciciani, M and Bonuzzi, I and Pezzè, L and Lucchetta, L and Maule, G and Amistadi, S and Esposito, F and Lupo, M and Miccio, A and Auricchio, A and Casini, A and Segata, N and Cereseto, A}, title = {CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {3478}, pmid = {38658578}, issn = {2041-1723}, support = {U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {*Gene Editing/methods ; Humans ; *CRISPR-Cas Systems ; Animals ; Mice ; *Microbiota/genetics ; Dependovirus/genetics ; CRISPR-Associated Protein 9/metabolism/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics/metabolism ; Retina/metabolism ; Clostridiales/genetics/enzymology ; HEK293 Cells ; Genetic Vectors/metabolism/genetics ; }, abstract = {The expansion of the CRISPR-Cas toolbox is highly needed to accelerate the development of therapies for genetic diseases. Here, through the interrogation of a massively expanded repository of metagenome-assembled genomes, mostly from human microbiomes, we uncover a large variety (n = 17,173) of type II CRISPR-Cas loci. Among these we identify CoCas9, a strongly active and high-fidelity nuclease with reduced molecular size (1004 amino acids) isolated from an uncultivated Collinsella species. CoCas9 is efficiently co-delivered with its sgRNA through adeno associated viral (AAV) vectors, obtaining efficient in vivo editing in the mouse retina. With this study we uncover a collection of previously uncharacterized Cas9 nucleases, including CoCas9, which enriches the genome editing toolbox.}, }
@article {pmid38651909, year = {2024}, author = {Choi, BI and Fontes Noronha, M and Kaindl, J and Wolfe, AJ}, title = {Complete genome sequences of Aerococcus loyolae ATCC TSD-300[T], Aerococcus mictus ATCC TSD-301[T], and Aerococcus tenax ATCC TSD-302[T].}, journal = {Microbiology resource announcements}, volume = {13}, number = {6}, pages = {e0015624}, pmid = {38651909}, issn = {2576-098X}, support = {//Pathnostics/ ; }, abstract = {Previously identified under the single designation of Aerococcus urinae, three distinct taxonomic species have been distinguished as Aerococcus loyolae, Aerococcus mictus, and Aerococcus tenax. Here, we present the complete genome sequences of the type strains of these species assembled via a combination of short-read and long-read sequencing techniques.Registered at ClinicalTrials.gov (NCT01166438).}, }
@article {pmid38638832, year = {2024}, author = {Filardo, S and Di Pietro, M and Sessa, R}, title = {Current progresses and challenges for microbiome research in human health: a perspective.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1377012}, pmid = {38638832}, issn = {2235-2988}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Metagenome ; Metagenomics ; }, abstract = {It is becoming increasingly clear that the human microbiota, also known as "the hidden organ", possesses a pivotal role in numerous processes involved in maintaining the physiological functions of the host, such as nutrient extraction, biosynthesis of bioactive molecules, interplay with the immune, endocrine, and nervous systems, as well as resistance to the colonization of potential invading pathogens. In the last decade, the development of metagenomic approaches based on the sequencing of the bacterial 16s rRNA gene via Next Generation Sequencing, followed by whole genome sequencing via third generation sequencing technologies, has been one of the great advances in molecular biology, allowing a better profiling of the human microbiota composition and, hence, a deeper understanding of the importance of microbiota in the etiopathogenesis of different pathologies. In this scenario, it is of the utmost importance to comprehensively characterize the human microbiota in relation to disease pathogenesis, in order to develop novel potential treatment or preventive strategies by manipulating the microbiota. Therefore, this perspective will focus on the progress, challenges, and promises of the current and future technological approaches for microbiome profiling and analysis.}, }
@article {pmid38622344, year = {2025}, author = {Sarrazin-Gendron, R and Ghasemloo Gheidari, P and Butyaev, A and Keding, T and Cai, E and Zheng, J and Mutalova, R and Mounthanyvong, J and Zhu, Y and Nazarova, E and Drogaris, C and Erhart, K and ,  and ,  and Brouillette, A and Richard, G and Pitchford, R and Caisse, S and Blanchette, M and McDonald, D and Knight, R and Szantner, A and Waldispühl, J}, title = {Improving microbial phylogeny with citizen science within a mass-market video game.}, journal = {Nature biotechnology}, volume = {43}, number = {1}, pages = {76-84}, pmid = {38622344}, issn = {1546-1696}, support = {DP1 AT010885/AT/NCCIH NIH HHS/United States ; }, mesh = {*Citizen Science/methods ; *Video Games ; Humans ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Crowdsourcing ; }, abstract = {Citizen science video games are designed primarily for users already inclined to contribute to science, which severely limits their accessibility for an estimated community of 3 billion gamers worldwide. We created Borderlands Science (BLS), a citizen science activity that is seamlessly integrated within a popular commercial video game played by tens of millions of gamers. This integration is facilitated by a novel game-first design of citizen science games, in which the game design aspect has the highest priority, and a suitable task is then mapped to the game design. BLS crowdsources a multiple alignment task of 1 million 16S ribosomal RNA sequences obtained from human microbiome studies. Since its initial release on 7 April 2020, over 4 million players have solved more than 135 million science puzzles, a task unsolvable by a single individual. Leveraging these results, we show that our multiple sequence alignment simultaneously improves microbial phylogeny estimations and UniFrac effect sizes compared to state-of-the-art computational methods. This achievement demonstrates that hyper-gamified scientific tasks attract massive crowds of contributors and offers invaluable resources to the scientific community.}, }
@article {pmid38611633, year = {2024}, author = {Lintala, A and Vapalahti, O and Nousiainen, A and Kantele, A and Hepojoki, J}, title = {Whole Blood as a Sample Matrix in Homogeneous Time-Resolved Assay-Förster Resonance Energy Transfer-Based Antibody Detection.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {7}, pages = {}, pmid = {38611633}, issn = {2075-4418}, support = {FUDIS//Business Finland/ ; TYH2021315, TYH2021343//The Finnish Government Subsidy for Health Science Research/ ; none//The Finnish Medical Association/ ; 1336490, 336439 and 335527//Academy of Finland/ ; }, abstract = {The protein-L-utilizing Förster resonance energy transfer (LFRET) assay enables mix-and-read antibody detection, as demonstrated for sera from patients with, e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus, and orthohantavirus infections. In this study, we compared paired serum and whole blood (WB) samples of COVID-19 patients and SARS-CoV-2 vaccine recipients. We found that LFRET also detects specific antibodies in WB samples. In 44 serum-WB pairs from patients with laboratory-confirmed COVID-19, LFRET showed a strong correlation between the sample materials. By analyzing 89 additional WB samples, totaling 133 WB samples, we found that LFRET results were moderately correlated with enzyme-linked immunosorbent assay results for samples collected 2 to 14 months after receiving COVID-19 diagnosis. However, the correlation decreased for samples >14 months after receiving a diagnosis. When comparing the WB LFRET results to neutralizing antibody titers, a strong correlation emerged for samples collected 1 to 14 months after receiving a diagnosis. This study also highlights the versatility of LFRET in detecting antibodies directly from WB samples and suggests that it could be employed for rapidly assessing antibody responses to infectious agents or vaccines.}, }
@article {pmid38605646, year = {2024}, author = {Heston, SM and Hurst, JH and Kelly, MS}, title = {Understanding the influence of the microbiome on childhood infections.}, journal = {Expert review of anti-infective therapy}, volume = {22}, number = {7}, pages = {529-545}, pmid = {38605646}, issn = {1744-8336}, support = {K01 AI173398/AI/NIAID NIH HHS/United States ; K12 HD105253/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Child ; *Microbiota/physiology ; *Gastrointestinal Microbiome/physiology ; Adolescent ; Communicable Diseases/microbiology/immunology ; Vaccines/administration &amp; dosage/immunology ; Respiratory Tract Infections/microbiology/immunology ; Disease Susceptibility ; Animals ; Immune System/microbiology ; }, abstract = {INTRODUCTION: The microbiome is known to have a substantial impact on human health and disease. However, the impacts of the microbiome on immune system development, susceptibility to infectious diseases, and vaccine-elicited immune responses are emerging areas of interest.<br><br>AREAS COVERED: In this review, we provide an overview of development of the microbiome during childhood. We highlight available data suggesting that the microbiome is critical to maturation of the immune system and modifies susceptibility to a variety of infections during childhood and adolescence, including respiratory tract infections, Clostridioides difficile infection, and sexually transmitted infections. We discuss currently available and investigational therapeutics that have the potential to modify the microbiome to prevent or treat infections among children. Finally, we review the accumulating evidence that the gut microbiome influences vaccine-elicited immune responses among children.<br><br>EXPERT OPINION: Recent advances in sequencing technologies have led to an explosion of studies associating the human microbiome with the risk and severity of infectious diseases. As our knowledge of the extent to which the microbiome influences childhood infections continues to grow, microbiome-based diagnostics and therapeutics will increasingly be incorporated into clinical practice to improve the prevention, diagnosis, and treatment of infectious diseases among children.}, }
@article {pmid38601152, year = {2024}, author = {Soto-Dávila, M and Langlois Fiorotto, L and Heath, JW and Lumsden, JS and Reid, G and Dixon, B}, title = {The effects of Pediococcus acidilactici MA18/5M on growth performance, gut integrity, and immune response using in vitro and in vivo Pacific salmonid models.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1306458}, pmid = {38601152}, issn = {1664-3224}, mesh = {Animals ; *Pediococcus acidilactici ; *Probiotics/pharmacology ; Diet ; *Salmonidae ; Disease Resistance ; }, abstract = {Microbial management is central to aquaculture's efficiency. Pediococcus acidilactici MA18/5M has shown promising results promoting growth, modulation of the immune response, and disease resistance in many fishes. However, the mechanisms through which this strain confers health benefits in fish are poorly understood, particularly in Pacific salmonid models. Briefly, the aims of this study were to i) assess the protective effects of P. acidilactici MA18/5M by examining gut barrier function and the expression of tight junction (TJ) and immune genes in vitro and in vivo, and ii) to determine the protective effects of this strain against a common saltwater pathogen, Vibrio anguillarum J382. An in vitro model of the salmonid gut was employed utilizing the cell line RTgutGC. Barrier formation and integrity assessed by TEER measurements in RTgutGC, showed a significant decrease in resistance in cells exposed only to V. anguillarum J382 for 24 h, but pre-treatment with P. acidilactici MA18/5M for 48 h mitigated these effects. While P. acidilactici MA18/5M did not significantly upregulate tight junction and immune molecules, pre-treatment with this strain protected against pathogen-induced insults to the gut barrier. In particular, the expression of ocldn was significantly induced by V. anguillarum J382, suggesting that this molecule might play a role in the host response against this pathogen. To corroborate these observations in live fish, the effects of P. acidilactici MA18/5M was evaluated in Chinook salmon reared in real aquaculture conditions. Supplementation with P. acidilactici MA18/5M had no effect on Chinook salmon growth parameters after 10 weeks. Interestingly, histopathological results did not show alterations associated with P. acidilactici MA18/5M supplementation, indicating that this strain is safe to be used in the industry. Finally, the expression pattern of transcripts encoding TJ and immune genes in all the treatments suggest that variation in expression is more likely to be due to developmental processes rather than P. acidilactici MA18/5M supplementation. Overall, our results showed that P. acidilactici MA18/5M is a safe strain for use in fish production, however, to assess the effects on growth and immune response previously observed in other salmonid species, an assessment in adult fish is needed.}, }
@article {pmid38600604, year = {2024}, author = {Hong, A and Umar, A and Chen, H and Yu, Z and Huang, J}, title = {Advances in the study of the interaction between schistosome infections and the host's intestinal microorganisms.}, journal = {Parasites &amp; vectors}, volume = {17}, number = {1}, pages = {185}, pmid = {38600604}, issn = {1756-3305}, support = {2023JJ30651//Natural Science Foundation of Hunan Province/ ; 32300051//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Humans ; Schistosoma/physiology ; *Schistosomiasis/pathology ; *Liver Diseases ; }, abstract = {Schistosomiasis, also called bilharziasis, is a neglected tropical disease induced by schistosomes that infects hundreds of millions of people worldwide. In the life cycle of schistosomiasis, eggs are regarded as the main pathogenic factor, causing granuloma formation in the tissues and organs of hosts, which can cause severe gastrointestinal and liver granulomatous immune responses and irreversible fibrosis. Increasing evidence suggests that the gut microbiome influences the progression of schistosomiasis and plays a central role in liver disease via the gut-liver axis. When used as pharmaceutical supplements or adjunctive therapy, probiotics have shown promising results in preventing, mitigating, and even treating schistosomiasis. This review elucidates the potential mechanisms of this three-way parasite-host-microbiome interaction by summarizing schistosome-mediated intestinal flora disorders, local immune changes, and host metabolic changes, and elaborates the important role of the gut microbiome in liver disease after schistosome infection through the gut-liver axis. Understanding the mechanisms behind this interaction may aid in the discovery of probiotics as novel therapeutic targets and sustainable control strategies for schistosomiasis.}, }
@article {pmid38594499, year = {2024}, author = {Franceschetti, L and Lodetti, G and Blandino, A and Amadasi, A and Bugelli, V}, title = {Exploring the role of the human microbiome in forensic identification: opportunities and challenges.}, journal = {International journal of legal medicine}, volume = {138}, number = {5}, pages = {1891-1905}, pmid = {38594499}, issn = {1437-1596}, mesh = {Humans ; *Microbiota ; *Skin/microbiology ; RNA, Ribosomal, 16S/genetics ; DNA Fingerprinting ; Metagenomics/methods ; }, abstract = {Forensic microbiology is rapidly emerging as a novel tool for human identification. The human microbiome, comprising diverse microbial communities including fungi, bacteria, protozoa, and viruses, is unique to each individual, offering a new dimension to forensic investigations. While traditional identification methods primarily rely on DNA profiling and fingerprint analysis, they face limitations when complete DNA or fingerprints profiles are unattainable or degraded. In this context, the microbial signatures of the human skin microbiome present a promising alternative due to their resilience to environmental stresses and individual-specific composition. This review explores the potential of microbiome analysis in forensic human identification, evaluating its applications, advantages, limitations, and future prospects. The uniqueness of an individual's microbial community, particularly the skin microbiota, can provide distinctive biological markers for identification purposes, while technological advancements like 16 S rRNA sequencing and metagenomic shotgun sequencing are enhancing the specificity of microbial identification, enabling detailed analysis of these complex ecological communities. Despite these promising findings, current research has not yet achieved a level of identification probability that could establish microbial analysis as a stand-alone evidence tool. Therefore, it is presently considered ancillary to traditional methods, contributing to a more comprehensive biological profile of individuals.}, }
@article {pmid38593705, year = {2024}, author = {Jian, C and Sorensen, N and Lutter, R and Albers, R and de Vos, W and Salonen, A and Mercenier, A}, title = {The impact of daily supplementation with rhamnogalacturonan-I on the gut microbiota in healthy adults: A randomized controlled trial.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {174}, number = {}, pages = {116561}, doi = {10.1016/j.biopha.2024.116561}, pmid = {38593705}, issn = {1950-6007}, mesh = {Humans ; *Pectins/administration &amp; dosage/pharmacology ; *Gastrointestinal Microbiome/drug effects ; Male ; Adult ; Double-Blind Method ; Female ; *Dietary Supplements ; *Healthy Volunteers ; Young Adult ; Rhinovirus/drug effects ; Middle Aged ; Feces/microbiology ; Bifidobacterium/drug effects ; }, abstract = {Pectin and its derivatives have been shown to modulate immune signaling as well as gut microbiota in preclinical studies, which may constitute the mechanisms by which supplementation of specific pectic polysaccharides confers protection against viral respiratory infections. In a double-blind, placebo-controlled rhinovirus (RV16) challenge study, healthy volunteers were randomized to consume placebo (0.0 g/day) (N = 46), low-dose (0.3 g/day) (N = 49) or high-dose (1.5 g/day) (N = 51) of carrot derived rhamnogalacturonan-I (cRG-I) for eight weeks and they were subsequently challenged with RV-16. Here, the effect of 8-week cRG-I supplementation on the gut microbiota was studied. While the overall gut microbiota composition in the population was generally unaltered by this very low dose of fibre, the relative abundance of Bifidobacterium spp. (mainly B. adolescentis and B. longum) was significantly increased by both doses of cRG-1. Moreover, daily supplementation of cRG-I led to a dose-dependent reduction in inter- and intra-individual microbiota heterogeneity, suggesting a stabilizing effect on the gut microbiota. The severity of respiratory symptoms did not directly correlate with the cRG-I-induced microbial changes, but several dominant groups of the Ruminococcaceae family and microbiota richness were positively associated with a reduced and hence desired post-infection response. Thus, the present results on the modulation of the gut microbiota composition support the previously demonstrated immunomodulatory and protective effect of cRG-I during a common cold infection.}, }
@article {pmid38593079, year = {2024}, author = {Zhong, Q and Liao, B and Liu, J and Shen, W and Wang, J and Wei, L and Ma, Y and Dong, PT and Bor, B and McLean, JS and Chang, Y and Shi, W and Cen, L and Wu, M and Liu, J and Li, Y and He, X and Le, S}, title = {Episymbiotic Saccharibacteria TM7x modulates the susceptibility of its host bacteria to phage infection and promotes their coexistence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {16}, pages = {e2319790121}, pmid = {38593079}, issn = {1091-6490}, support = {R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 GM110243/GM/NIGMS NIH HHS/United States ; R01 AI087946/AI/NIAID NIH HHS/United States ; R01 GM124378/GM/NIGMS NIH HHS/United States ; R01 AI152421/AI/NIAID NIH HHS/United States ; R01 DE030943/DE/NIDCR NIH HHS/United States ; R01 AI132818/AI/NIAID NIH HHS/United States ; R01 DE031274/DE/NIDCR NIH HHS/United States ; S10 OD023603/OD/NIH HHS/United States ; }, mesh = {Humans ; *Bacteriophages/physiology ; Symbiosis ; Bacteria/genetics ; }, abstract = {Bacteriophages (phages) play critical roles in modulating microbial ecology. Within the human microbiome, the factors influencing the long-term coexistence of phages and bacteria remain poorly investigated. Saccharibacteria (formerly TM7) are ubiquitous members of the human oral microbiome. These ultrasmall bacteria form episymbiotic relationships with their host bacteria and impact their physiology. Here, we showed that during surface-associated growth, a human oral Saccharibacteria isolate (named TM7x) protects its host bacterium, a Schaalia odontolytica strain (named XH001) against lytic phage LC001 predation. RNA-Sequencing analysis identified in XH001 a gene cluster with predicted functions involved in the biogenesis of cell wall polysaccharides (CWP), whose expression is significantly down-regulated when forming a symbiosis with TM7x. Through genetic work, we experimentally demonstrated the impact of the expression of this CWP gene cluster on bacterial-phage interaction by affecting phage binding. In vitro coevolution experiments further showed that the heterogeneous populations of TM7x-associated and TM7x-free XH001, which display differential susceptibility to LC001 predation, promote bacteria and phage coexistence. Our study highlights the tripartite interaction between the bacterium, episymbiont, and phage. More importantly, we present a mechanism, i.e., episymbiont-mediated modulation of gene expression in host bacteria, which impacts their susceptibility to phage predation and contributes to the formation of "source-sink" dynamics between phage and bacteria in biofilm, promoting their long-term coexistence within the human microbiome.}, }
@article {pmid38590477, year = {2024}, author = {Vijayan, S and Kandi, V and Palacholla, PS and Rajendran, R and Jarugu, C and Ca, J and Pravallika, M and Reddy, SC and Sucharitha, AS}, title = {Probiotics in Allergy and Immunological Diseases: A Comprehensive Review.}, journal = {Cureus}, volume = {16}, number = {3}, pages = {e55817}, pmid = {38590477}, issn = {2168-8184}, abstract = {Allergy and immunological disorders like autoimmune diseases are vastly prevalent worldwide. These conditions account for a substantial amount of personal and social burden. Such illnesses have lengthy, uncertain, and spotted courses with unpredictable exacerbations. A definite tendency for improving the overall quality of life of individuals suffering from such diseases is crucial to tackling these diseases, especially through diet or lifestyle modification. Further, interventions like microbiome-based therapeutics such as prebiotics or probiotics were explored. Changes in the microbial population were evident during the flare-up of autoimmune and allergic conditions. The realization that the human microbiome is a central player in immunological diseases is a hallmark of its potential usefulness in therapy for such illnesses. This review focuses on the intricate symphony in the orchestra of the human microbiome and the immune system. New therapeutic strategies involving probiotics appear to be the future of personalized medicine. Through this review, we explore the narrative of probiotics and reaffirm their use as therapeutic and preventive agents in immunological disorders.}, }
@article {pmid38590114, year = {2024}, author = {Rezzani, R and Favero, G and Gianò, M and Pinto, D and Labanca, M and van Noorden, CJF and Rinaldi, F}, title = {Transient Receptor Potential Channels in the Healthy and Diseased Blood-Brain Barrier.}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, volume = {72}, number = {4}, pages = {199-231}, pmid = {38590114}, issn = {1551-5044}, mesh = {Humans ; *Transient Receptor Potential Channels/metabolism ; Blood-Brain Barrier ; Endothelial Cells/metabolism ; TRPV Cation Channels ; *Nervous System Diseases ; }, abstract = {The large family of transient receptor potential (TRP) channels are integral membrane proteins that function as environmental sensors and act as ion channels after activation by mechanical (touch), physical (heat, pain), and chemical stimuli (pungent compounds such as capsaicin). Most TRP channels are localized in the plasma membrane of cells but some of them are localized in membranes of organelles and function as intracellular Ca[2+]-ion channels. TRP channels are involved in neurological disorders but their precise role(s) and relevance in these disorders are not clear. Endothelial cells of the blood-brain barrier (BBB) express TRP channels such as TRP vanilloid 1-4 and are involved in thermal detection by regulating BBB permeability. In neurological disorders, TRP channels in the BBB are responsible for edema formation in the brain. Therefore, drug design to modulate locally activity of TRP channels in the BBB is a hot topic. Today, the application of TRP channel antagonists against neurological disorders is still limited.}, }
@article {pmid38587593, year = {2024}, author = {Chung, IY and Kim, J and Koh, A}, title = {The Microbiome Matters: Its Impact on Cancer Development and Therapeutic Responses.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {62}, number = {3}, pages = {137-152}, pmid = {38587593}, issn = {1976-3794}, support = {KFRM 22A0301L1//Korean Fund for Regenerative Medicine (KFRM)/ ; 2023R1A2C1002876//National Research Foundation of Korea (NRF)/ ; 2021R1I1A1A01052756//National Research Foundation of Korea (NRF)/ ; 2021R1A6C101A390//the Basic Science Institute/ ; }, mesh = {Humans ; *Neoplasms/microbiology/therapy ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; Microbiota ; Bacteria/classification/genetics/isolation &amp; purification ; Carcinogenesis ; Immunotherapy ; Mouth/microbiology ; }, abstract = {In the evolving landscape of cancer research, the human microbiome emerges as a pivotal determinant reshaping our understanding of tumorigenesis and therapeutic responses. Advanced sequencing technologies have uncovered a vibrant microbial community not confined to the gut but thriving within tumor tissues. Comprising bacteria, viruses, and fungi, this diverse microbiota displays distinct signatures across various cancers, with most research primarily focusing on bacteria. The correlations between specific microbial taxa within different cancer types underscore their pivotal roles in driving tumorigenesis and influencing therapeutic responses, particularly in chemotherapy and immunotherapy. This review amalgamates recent discoveries, emphasizing the translocation of the oral microbiome to the gut as a potential marker for microbiome dysbiosis across diverse cancer types and delves into potential mechanisms contributing to cancer promotion. Furthermore, it highlights the adverse effects of the microbiome on cancer development while exploring its potential in fortifying strategies for cancer prevention and treatment.}, }
@article {pmid38586050, year = {2024}, author = {Ho, PY and Huang, KC}, title = {Challenges in quantifying functional redundancy and selection in microbial communities.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.26.586891}, pmid = {38586050}, issn = {2692-8205}, abstract = {Microbiomes can exhibit large variations in species abundances but high reproducibility in abundances of functional units, an observation often considered evidence for functional redundancy. Based on such reduction in functional variability, selection is hypothesized to act on functional units in these ecosystems. However, the link between functional redundancy and selection remains unclear. Here, we show that reduction in functional variability does not always imply selection on functional profiles. We propose empirical null models to account for the confounding effects of statistical averaging and bias toward environment-independent beneficial functions. We apply our models to existing data sets, and find that the abundances of metabolic groups within microbial communities from bromeliad foliage do not exhibit any evidence of the previously hypothesized functional selection. By contrast, communities of soil bacteria or human gut commensals grown in vitro are selected for metabolic capabilities. By separating the effects of averaging and functional bias on functional variability, we find that the appearance of functional selection in gut microbiome samples from the Human Microbiome Project is artifactual, and that there is no evidence of selection for any molecular function represented by KEGG orthology. These concepts articulate a basic framework for quantifying functional redundancy and selection, advancing our understanding of the mapping between microbiome taxonomy and function.}, }
@article {pmid38585738, year = {2024}, author = {Hunter, C and Dia, K and Boykins, J and Perry, K and Banerjee, N and Cuffee, J and Armstrong, E and Morgan, G and Banerjee, HN and Banerjee, A and Bhattacharya, S}, title = {An investigation for phylogenetic characterization of human Pancreatic cancer microbiome by 16SrDNA Sequencing and Bioinformatics techniques.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {38585738}, issn = {2693-5015}, support = {T34 GM100831/GM/NIGMS NIH HHS/United States ; }, abstract = {Pancreatic cancer is a significant public health concern, with increasing incidence rates and limited treatment options. Recent studies have highlighted the role of the human microbiome, particularly the gut microbiota, in the development and progression of this disease. Microbial dysbiosis, characterized by alterations in the composition and function of the gut microbiota, has been implicated in pancreatic carcinogenesis through mechanisms involving chronic inflammation, immune dysregulation, and metabolic disturbances. Researchers have identified specific microbial signatures associated with pancreatic cancer, offering potential biomarkers for early detection and prognostication. By leveraging advanced sequencing and bioinformatics tools, scientists have delineated differences in the gut microbiota between pancreatic cancer patients and healthy individuals, providing insights into disease pathogenesis and potential diagnostic strategies. Moreover, the microbiome holds promise as a therapeutic target in pancreatic cancer treatment. Interventions aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, have demonstrated potential in enhancing the efficacy of existing cancer therapies, including chemotherapy and immunotherapy. These approaches can influence immune responses, alter tumor microenvironments, and sensitize tumors to treatment, offering new avenues for improving patient outcomes and overcoming therapeutic resistance. Overall, understanding the complex interplay between the microbiome and pancreatic cancer is crucial for advancing our knowledge of disease mechanisms and identifying innovative therapeutic strategies. Here we report phylogenetic analysis of the 16S microbial sequences of the pancreatic cancer mice microbiome and corresponding age matched healthy mice microbiome. We successfully identified differentially abundance of microbiota in the pancreatic cancer.}, }
@article {pmid38585650, year = {2024}, author = {Kiljunen, S and Resch, G}, title = {Editorial: Standards in personalized phage therapy: from phage collection to phage production.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1376386}, doi = {10.3389/fcimb.2024.1376386}, pmid = {38585650}, issn = {2235-2988}, mesh = {*Bacteriophages/genetics ; *Phage Therapy ; Anti-Bacterial Agents ; }, }
@article {pmid38581020, year = {2024}, author = {Douillard, FP and Derman, Y and Jian, C and Korpela, K and Saxén, H and Salonen, A and de Vos, WM and Korkeala, H and Lindström, M}, title = {Case report: Aberrant fecal microbiota composition of an infant diagnosed with prolonged intestinal botulism.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {20}, pmid = {38581020}, issn = {1757-4749}, abstract = {BACKGROUND: Intestinal botulism is primarily reported in small babies as a condition known as infant botulism. The condition results from the ingestion of environmental or foodborne spores of botulinum neurotoxin (BoNT) producing Clostridia, usually Clostridium botulinum, and subsequent spore germination into active botulinum neurotoxinogenic cultures in the gut. It is generally considered that small babies are susceptible to C. botulinum colonization because of their immature gut microbiota. Yet, it is poorly understood which host factors contribute to the clinical outcome of intestinal botulism. We previously reported a case of infant botulism where the infant recovered clinically in six weeks but continued to secrete C. botulinum cells and/or BoNT in the feces for seven months.<br><br>CASE PRESENTATION: To further understand the microbial ecology behind this exceptionally long-lasting botulinum neurotoxinogenic colonization, we characterized the infant fecal microbiota using 16S rRNA gene amplicon sequencing over the course of disease and recovery. C. botulinum could be detected in the infant fecal samples at low levels through the acute phase of the disease and three months after recovery. Overall, we observed a temporal delay in the maturation of the infant fecal microbiota associated with a persistently high-level bifidobacterial population and a low level of Lachnospiraceae, Bacteroidaceae and Ruminococcaceae compared to healthy infants over time.<br><br>CONCLUSION: This study brings novel insights into the infant fecal composition associated with intestinal botulism and provides a basis for a more systematic analysis of the gut microbiota of infants diagnosed with botulism. A better understanding of the gut microbial ecology associated with infant botulism may support the development of prophylactic strategies against this life-threatening disease in small babies.}, }
@article {pmid38579936, year = {2024}, author = {Rivet-Noor, CR and Merchak, AR and Render, C and Gay, NM and Beiter, RM and Brown, RM and Keeler, A and Moreau, GB and Li, S and Olgun, DG and Steigmeyer, AD and Ofer, R and Phan, T and Vemuri, K and Chen, L and Mahoney, KE and Shin, JB and Malaker, SA and Deppmann, C and Verzi, MP and Gaultier, A}, title = {Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.}, journal = {Brain, behavior, and immunity}, volume = {119}, number = {}, pages = {665-680}, pmid = {38579936}, issn = {1090-2139}, support = {R01 DK126446/DK/NIDDK NIH HHS/United States ; T32 GM067543/GM/NIGMS NIH HHS/United States ; T32 GM149444/GM/NIGMS NIH HHS/United States ; R01 DC018842/DC/NIDCD NIH HHS/United States ; R01 DK121915/DK/NIDDK NIH HHS/United States ; T32 GM139787/GM/NIGMS NIH HHS/United States ; T32 NS115657/NS/NINDS NIH HHS/United States ; F31 AI174782/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Male ; Mice ; Behavior, Animal/physiology ; *Depression/metabolism/microbiology ; *Dysbiosis/metabolism/microbiology ; *Gastrointestinal Microbiome/physiology ; Hepatocyte Nuclear Factor 4/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mucins/metabolism ; *Stress, Psychological/metabolism/microbiology ; }, abstract = {Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in microbiome composition are associated with disease pathology. Stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes in the context of stress. Using a model of chronic stress, we show that the glycocalyx protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction of Muc13 is mediated by the Hnf4 transcription factor family. Finally, we determine that deleting Muc13 is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a novel regulator of mucin 13 expression.}, }
@article {pmid38577723, year = {2024}, author = {Kozajda, A and Miśkiewicz, E and Jeżak, K}, title = {Zoonotic bacteria in the vicinity of animal farms as a factor disturbing the human microbiome: a review.}, journal = {International journal of occupational medicine and environmental health}, volume = {37}, number = {2}, pages = {138-152}, pmid = {38577723}, issn = {1896-494X}, mesh = {Humans ; Animals ; *Microbiota ; Farms ; Livestock/microbiology ; Zoonoses/microbiology/transmission ; Environmental Exposure/adverse effects ; Air Microbiology ; Bacteria/isolation &amp; purification/classification ; }, abstract = {This review is aimed at summarizing the current state of knowledge about the relationship between environmental exposure to the bioaerosol emitted by intensive livestock farming and changes in the microbiome of people living in livestock farm vicinity. The PubMed, Scopus and Web of Science databases were searched by crossing keywords from the following 3 groups: a) "livestock," "animal farms," "animal breeding"; b) "microbiome," "resistome"; c) "livestock vicinity," "farm vicinity," "neighborhoods and health" in 2010-2022. Literature screening did not reveal any paper related to the full microbiome composition in the population studied. In the study, the authors included 7 papers (5 from the Netherlands, 1 from the USA, and 1 from China). The studies confirmed the carriage of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), livestockassociated MRSA (LA-MRSA MC398) and multidrug-resistant S. aureus (MDRSA) in the nasal microbiome of adults and children living within 500-2000 m from a livestock farm. Clostridium difficile, including LA-ribotype RT078 carriage, was detected in the intestinal microbiome of adults living within 500-1000 m. Extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae were confirmed in the intestinal microbiome of adults living within 500-6200 m. Knowledge on the composition of the microflora of people living in livestock farm vicinity is insufficient to conclude about changes in the microbiome caused by the environmental emission of bioaerosol. The carriage prevalence of the LA-bacteria, including both strains with antimicrobial resistance and antimicrobial resistance genes, confirms the presence of zoonotic bacteria in the human microflora in populations without occupational contact with animals. It cannot be ruled out that zoonotic bacteria, as a component of the microbiome, have a negative impact on people's health. Int J Occup Med Environ Health. 2024;37(2):138-52.}, }
@article {pmid38577200, year = {2024}, author = {Salvadori, M and Rosso, G}, title = {Update on the gut microbiome in health and diseases.}, journal = {World journal of methodology}, volume = {14}, number = {1}, pages = {89196}, pmid = {38577200}, issn = {2222-0682}, abstract = {The Human Microbiome Project, Earth Microbiome Project, and next-generation sequencing have advanced novel genome association, host genetic linkages, and pathogen identification. The microbiome is the sum of the microbes, their genetic information, and their ecological niche. This study will describe how millions of bacteria in the gut affect the human body in health and disease. The gut microbiome changes in relation with age, with an increase in Bacteroidetes and Firmicutes. Host and environmental factors affecting the gut microbiome are diet, drugs, age, smoking, exercise, and host genetics. In addition, changes in the gut microbiome may affect the local gut immune system and systemic immune system. In this study, we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases. Due to the high number of publications on the argument, from a methodologically point of view, we decided to select the best papers published in referred journals in the last 3 years. Then we selected the previously published papers. The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.}, }
@article {pmid38575895, year = {2024}, author = {Zhang, M and Zhao, Y and Umar, A and Zhang, H and Yang, L and Huang, J and Long, Y and Yu, Z}, title = {Comparative analysis of microbial composition and functional characteristics in dental plaque and saliva of oral cancer patients.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {411}, pmid = {38575895}, issn = {1472-6831}, support = {32170071 and 82273466//National Natural Science Foundation of China/ ; }, mesh = {Humans ; Saliva/microbiology ; *Dental Plaque/microbiology ; Bacteria/genetics ; *Mouth Neoplasms ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The oral cavity is home to various ecological niches, each with its own unique microbial composition. Understanding the microbial communities and gene composition in different ecological niches within the oral cavity of oral cancer (OC) patients is crucial for determining how these microbial populations contribute to disease progression.<br><br>METHODS: In this study, saliva and dental plaque samples were collected from patients with OC. Metagenomic sequencing was employed to analyze the microbial community classification and functional composition of the different sample groups.<br><br>RESULTS: The results of the study revealed significant differences in both the function and classification of microbial communities between saliva and dental plaque samples. The diversity of microbial species in saliva was found to be higher compared to &#xa0;that in&#xa0;plaque samples. Notably, Actinobacteria were enriched in the dental plaque of OC patients. Furthermore, the study identified several inter-group differential marker species, including Prevotella intermedia, Haemophilus parahaemolyticus, Actinomyces radius, Corynebacterium matruchitii, and Veillonella atypica. Additionally, 1,353 differential genes were annotated into 23 functional pathways. Interestingly, a significant correlation was observed between differentially labeled species and Herpes simplex virus 1 (HSV-1) infection, which may be related to the occurrence and development of cancer.<br><br>CONCLUSIONS: Significant differences in the microbial and genetic composition of saliva and dental plaque samples were observed in OC patients. Furthermore, pathogenic bacteria associated with oral diseases were predominantly enriched in saliva. The identification of inter-group differential biomarkers and pathways provide insights into the relationship between oral microbiota and the occurrence and development of OC.}, }
@article {pmid38575862, year = {2024}, author = {Zhang, M and Zhou, Y and Yao, S and Zhao, Y and Batool, SS and Huang, J and Jiang, L and Yan, D and Yan, W and Yu, Z}, title = {Effect of stress urinary incontinence on vaginal microbial communities.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {112}, pmid = {38575862}, issn = {1471-2180}, support = {32000054 and 32170071//National Natural Science Foundation of China/ ; }, mesh = {Female ; Humans ; *Urinary Incontinence, Stress/etiology ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Vagina/microbiology ; *Microbiota/genetics ; Lactobacillus/genetics ; Bacteria/genetics ; *Vaginal Diseases/complications ; }, abstract = {BACKGROUND: Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women's physical and mental health. Understanding the relationship between SUI and vaginal microbiota composition may help to prevent vaginal diseases, but research on the potential association between these conditions is limited.<br><br>RESULTS: This study employed 16S rRNA gene sequencing to explore the association between SUI and vaginal dysbiosis. In terms of the vaginal microbiota, both species richness and evenness were significantly higher in the SUI group. Additionally, the results of NMDS and species composition indicated that there were differences in the composition of the vaginal microbiota between the two groups. Specifically, compared to postpartum women without SUI (Non-SUI), the relative abundance of bacteria associated with bacterial dysbiosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the relative abundance of Lactobacillus decreased in SUI patients. Furthermore, the vaginal microbial co-occurrence network of SUI patients displayed higher connectivity, complexity, and clustering.<br><br>CONCLUSION: The study highlights the role of Lactobacillus in maintaining vaginal microbial homeostasis. It found a correlation between SUI and vaginal microbiota, indicating an increased risk of vaginal dysbiosis. The findings could enhance our understanding of the relationship between SUI and vaginal dysbiosis in postpartum women, providing valuable insights for preventing bacterial vaginal diseases and improving women's health.}, }
@article {pmid38569469, year = {2024}, author = {Caffrey, EB and Sonnenburg, JL and Devkota, S}, title = {Our extended microbiome: The human-relevant metabolites and biology of fermented foods.}, journal = {Cell metabolism}, volume = {36}, number = {4}, pages = {684-701}, pmid = {38569469}, issn = {1932-7420}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Fermented Foods ; *Microbiota ; *Gastrointestinal Microbiome ; Biology ; }, abstract = {One of the key modes of microbial metabolism occurring in the gut microbiome is fermentation. This energy-yielding process transforms common macromolecules like polysaccharides and amino acids into a wide variety of chemicals, many of which are relevant to microbe-microbe and microbe-host interactions. Analogous transformations occur during the production of fermented foods, resulting in an abundance of bioactive metabolites. In foods, the products of fermentation can influence food safety and preservation, nutrient availability, and palatability and, once consumed, may impact immune and metabolic status, disease expression, and severity. Human signaling pathways perceive and respond to many of the currently known fermented food metabolites, though expansive chemical novelty remains to be defined. Here we discuss several aspects of fermented food-associated microbes and metabolites, including a condensed history, current understanding of their interactions with hosts and host-resident microbes, connections with commercial probiotics, and opportunities for future research on human health and disease and food sustainability.}, }
@article {pmid38567073, year = {2024}, author = {Wojciechowska, D and Salamon, S and Wróblewska-Seniuk, K}, title = {It's time to shed some light on the importance of fungi in neonatal intensive care units: what do we know about the neonatal mycobiome?.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1355418}, pmid = {38567073}, issn = {1664-302X}, abstract = {The 21st century, thanks to the development of molecular methods, including DNA barcoding, using Sanger sequencing, and DNA metabarcoding, based on next-generation sequencing (NGS), is characterized by flourishing research on the human microbiome. Microbial dysbiosis is perceived as a new pathogenetic factor for neonatal diseases. Fungi are crucial, but neglected, components of the neonatal microbiome, which, despite their low abundance, significantly impact morbidity and mortality rates of premature infants hospitalized in Neonatal Intensive Care Units (NICUs). The neonatal mycobiome's composition and effect on health remain poorly studied research areas. Our knowledge about neonatal mycobiome, composed of limited genera, is mainly based on research on the bacterial microbiome. We presume it is influenced by clinical factors, including prematurity, antibiotic therapy, and type of delivery. Understanding these risk factors may be useful in prevention strategies against dysbiosis and invasive fungal infections. Despite the methodological challenges resulting from the biology of the fungal cell, this topic is an attractive area of research that may contribute to more effective treatment, especially of newborns from risk groups. In this mini review, we discuss the current state of knowledge, research gaps, study difficulties, and future research directions on the neonatal mycobiome, concerning potential future clinical applications.}, }
@article {pmid38565750, year = {2024}, author = {Núñez Casal, A}, title = {Race and indigeneity in human microbiome science: microbiomisation and the historiality of otherness.}, journal = {History and philosophy of the life sciences}, volume = {46}, number = {2}, pages = {17}, pmid = {38565750}, issn = {1742-6316}, support = {RYC2022-036985-I//Ministerio de Ciencia e Innovaci&#xf3;n/ ; }, mesh = {Humans ; *Microbiota ; United States ; Racial Groups ; }, abstract = {This article reformulates Stephan Helmreich´s the ¨microbiomisation of race¨ as the historiality of otherness in the foundations of human microbiome science. Through the lens of my ethnographic fieldwork of a transnational community of microbiome scientists that conducted a landmark human microbiome research on indigenous microbes and its affiliated and first personalised microbiome initiative, the American Gut Project, I follow and trace the key actors, experimental systems and onto-epistemic claims in the emergence of human microbiome science a decade ago. In doing so, I show the links between the reinscription of race, comparative research on the microbial genetic variation of human populations and the remining of bioprospected data for personalised medicine. In these unpredictable research movements, the microbiome of non-Western peoples and territories is much more than a side project or a specific approach within the field: it constitutes the nucleus of its experimental system, opening towards subsequent and cumulative research processes and knowledge production in human microbiome science. The article demonstrates that while human microbiome science is articulated upon the microbial 'makeup' of non-wester(nised) communities, societies, and locales, its results and therapeutics are only applicable to medical conditions affecting rich nations (i.e., inflammatory, autoimmune, and metabolic diseases). My reformulation of ¨microbiomisation of race¨ as the condition of possibility of human microbiome science reveals that its individual dimension is sustained by microbial DNA data from human populations through bioprospecting practices and gains meaning through personalised medicine initiatives, informal online networks of pseudoscientific and commodified microbial-related evidence.}, }
@article {pmid38563656, year = {2024}, author = {Zhu, J and Yin, J and Chen, J and Hu, M and Lu, W and Wang, H and Zhang, H and Chen, W}, title = {Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2336877}, pmid = {38563656}, issn = {1949-0984}, mesh = {Animals ; Mice ; Humans ; *Colitis, Ulcerative ; *Gastrointestinal Microbiome ; *Inflammatory Bowel Diseases ; *Colitis ; Machine Learning ; }, abstract = {Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.}, }
@article {pmid38560624, year = {2024}, author = {Wilson, NG and Hernandez-Leyva, A and Schwartz, DJ and Bacharier, LB and Kau, AL}, title = {The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.}, journal = {FEMS microbes}, volume = {5}, number = {}, pages = {xtae010}, pmid = {38560624}, issn = {2633-6685}, support = {F30 DK127584/DK/NIDDK NIH HHS/United States ; K08 AI113184/AI/NIAID NIH HHS/United States ; K08 AI159384/AI/NIAID NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; }, abstract = {Asthma is a common allergic airway disease that has been associated with the development of the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from a cross-sectional cohort of 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in adults and children 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways, which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. Several differentially abundant ARGs in the asthma cohort encode resistance to macrolide antibiotics, which are often prescribed to patients with asthma. Lastly, we found that ARG and virulence factor (VF) richness in the microbiome were correlated in both cohorts. ARG and VF pairs co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are coselected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment.}, }
@article {pmid38555606, year = {2024}, author = {Tutelyan, VA and Nikityuk, DB}, title = {[Key challenges in the dietary intake structure and cutting edge technologies for optimizing nutrition to protect the health of the Russian рopulation].}, journal = {Voprosy pitaniia}, volume = {93}, number = {1}, pages = {6-21}, doi = {10.33029/0042-8833-2024-93-1-6-21}, pmid = {38555606}, issn = {0042-8833}, support = {FGMF-2022-0001//The research was carried out using subsidies for the implementation of a state task/ ; }, mesh = {Humans ; *Nutritional Status ; *Food ; Food Safety/methods ; Russia ; Eating ; }, abstract = {This article presents an analysis of some of the results of the work of the Federal Research Center for Nutrition and Biotechnology (Center) in recent years, highlighting the most important, promising areas of Nutrition Science and Food Hygiene that need further development. The priority area of Center functioning is scientific support for the implementation of the Doctrine of Food Security of the Russian Federation (Decree of the President of the Russian Federation dated January 21, 2020 No. 20), Decree of the President of the Russian Federation dated July 21, 2020 No. 474 «On the national development goals of the Russian Federation for the period until 2030 «in terms of ensuring an increase in life expectancy and improving the life quality of the population, the Strategy for Improving the Quality of Food Products in the Russian Federation until 2030 (Order of the Government of the Russian Federation dated June 29, 2016 No. 1364-r). The Center coordinates all research on medical nutrition problems in the Russian Federation within the framework of the work of the Problem Commission on Nutrition Hygiene of the Scientific Council of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare, the Scientific Council of the Russian Academy of Sciences on Medical Nutrition Problems, the Scientific and Technical Committee of the Comprehensive Scientific Program «Priority Research in the Field of Nutrition of the Population», Profile Commission on Dietetics of the Expert Council in the Field of Health of the Ministry of Healthcare of Russian Federation, ensuring the implementation of their results with the participation of members of the Consortium "Healthcare, Nutrition, Demography". The most important area of the Center's work is scientific and expert support in the field of international and national technical regulation of the production and turnover of foods and raw materials, in particular, the work of the Russian national contact point of the Codex Alimentarius Commission (established by FAO and WHO), as well as the work of the Russian side in the Eurasian Economic Commission regarding the preparation of proposals for technical regulations of the Customs Union in the field of food safety, evaluation of draft technical regulations and amendments and additions to them.}, }
@article {pmid38555566, year = {2025}, author = {Kuehnast, T and Kumpitsch, C and Mohammadzadeh, R and Weichhart, T and Moissl-Eichinger, C and Heine, H}, title = {Exploring the human archaeome: its relevance for health and disease, and its complex interplay with the human immune system.}, journal = {The FEBS journal}, volume = {292}, number = {6}, pages = {1316-1329}, pmid = {38555566}, issn = {1742-4658}, support = {COE 7//Austrian Science Fund/ ; P 32697//Austrian Science Fund/ ; SFB F83//Austrian Science Fund/ ; }, mesh = {Humans ; *Archaea/immunology/genetics ; *Microbiota/immunology/genetics ; *Immune System/microbiology/immunology ; }, abstract = {This Review aims to coalesce existing knowledge on the human archaeome, a less-studied yet critical non-bacterial component of the human microbiome, with a focus on its interaction with the immune system. Despite a largely bacteria-centric focus in microbiome research, archaea present unique challenges and opportunities for understanding human health. We examine the archaeal distribution across different human body sites, such as the lower gastrointestinal tract (LGT), upper aerodigestive tract (UAT), urogenital tract (UGT), and skin. Variability in archaeal composition exists between sites; methanogens dominate the LGT, while Nitrososphaeria are prevalent on the skin and UAT. Archaea have yet to be classified as pathogens but show associations with conditions such as refractory sinusitis and vaginosis. In the LGT, methanogenic archaea play critical metabolic roles by converting bacterial end-products into methane, correlating with various health conditions, including obesity and certain cancers. Finally, this work looks at the complex interactions between archaea and the human immune system at the molecular level. Recent research has illuminated the roles of specific archaeal molecules, such as RNA and glycerolipids, in stimulating immune responses via innate immune receptors like Toll-like receptor 8 (TLR8) and 'C-type lectin domain family 4 member E' (CLEC4E; also known as MINCLE). Additionally, metabolic by-products of archaea, specifically methane, have demonstrated immunomodulatory effects through anti-inflammatory and anti-oxidative pathways. Despite these advancements, the mechanistic underpinnings of how archaea influence immune activity remain a fertile area for further investigation.}, }
@article {pmid38553666, year = {2024}, author = {Ma, ZS}, title = {Towards a unified medical microbiome ecology of the OMU for metagenomes and the OTU for microbes.}, journal = {BMC bioinformatics}, volume = {25}, number = {1}, pages = {137}, pmid = {38553666}, issn = {1471-2105}, mesh = {Animals ; Humans ; Metagenome ; *Microbiota/genetics ; *Gastrointestinal Microbiome ; Biodiversity ; Sequence Analysis, DNA ; Metagenomics/methods ; }, abstract = {BACKGROUND: Metagenomic sequencing technologies offered unprecedented opportunities and also challenges to microbiology and microbial ecology particularly. The technology has revolutionized the studies of microbes and enabled the high-profile human microbiome and earth microbiome projects. The terminology-change from microbes to microbiomes signals that our capability to count and classify microbes (microbiomes) has achieved the same or similar level as we can for the biomes (macrobiomes) of plants and animals (macrobes). While the traditional investigations of macrobiomes have usually been conducted through naturalists' (Linnaeus &amp; Darwin) naked eyes, and aerial and satellite images (remote-sensing), the large-scale investigations of microbiomes have been made possible by DNA-sequencing-based metagenomic technologies. Two major types of metagenomic sequencing technologies-amplicon sequencing and whole-genome (shotgun sequencing)-respectively generate two contrastingly different categories of metagenomic reads (data)-OTU (operational taxonomic unit) tables representing microorganisms and OMU (operational metagenomic unit), a new term coined in this article to represent various cluster units of metagenomic genes.<br><br>RESULTS: The ecological science of microbiomes based on the OTU representing microbes has been unified with the classic ecology of macrobes (macrobiomes), but the unification based on OMU representing metagenomes has been rather limited. In a previous series of studies, we have demonstrated the applications of several classic ecological theories (diversity, composition, heterogeneity, and biogeography) to the studies of metagenomes. Here I push the envelope for the unification of OTU and OMU again by demonstrating the applications of metacommunity assembly and ecological networks to the metagenomes of human gut microbiomes. Specifically, the neutral theory of biodiversity (Sloan's near neutral model), Ning et al.stochasticity framework, core-periphery network, high-salience skeleton network, special trio-motif, and positive-to-negative ratio are applied to analyze the OMU tables from whole-genome sequencing technologies, and demonstrated with seven human gut metagenome datasets from the human microbiome project.<br><br>CONCLUSIONS: All of the ecological theories demonstrated previously and in this article, including diversity, composition, heterogeneity, stochasticity, and complex network analyses, are equally applicable to OMU metagenomic analyses, just as to OTU analyses. Consequently, I strongly advocate the unification of OTU/OMU (microbiomes) with classic ecology of plants and animals (macrobiomes) in the context of medical ecology.}, }
@article {pmid38550775, year = {2024}, author = {Monteiro, JS and Kaushik, K and de Arruda, JAA and Georgakopoulou, E and Vieira, AT and Silva, TA and Devadiga, D and Anyanechi, CE and Shetty, S}, title = {Fungal footprints in oral cancer: unveiling the oral mycobiome.}, journal = {Frontiers in oral health}, volume = {5}, number = {}, pages = {1360340}, pmid = {38550775}, issn = {2673-4842}, abstract = {Oral squamous cell carcinoma (OSCC) is the most common type of head and neck cancer, with a high mortality rate. There is growing evidence supporting a link between oral cancer and the microbiome. The microbiome can impact various aspects of cancer, such as pathogenesis, diagnosis, treatment, and prognosis. While there is existing information on bacteria and its connection to oral cancer, the fungi residing in the oral cavity represent a significant component of the microbiome that remains in its early stages of exploration and understanding. Fungi comprise a minuscule part of the human microbiome called the mycobiome. Mycobiome is ubiquitous in the human body but a weakened immune system offers a leeway space for fungi to showcase its virulence. The role of mycobiome as a colonizer, facilitator, or driver of carcinogenesis is still ambiguous. Reactivating the mycobiome that undergoes collateral damage associated with cancer treatment can be watershed event in cancer research. The coordinated, virulent, non-virulent behavior of the fungi once they reach a critical density must be hacked, considering its diagnostic, prognostic and therapeutic implications in cancer. This review highlights the diversity of the mycobiome and its potential role in oral cancer.}, }
@article {pmid38549112, year = {2024}, author = {Edwin, NR and Fitzpatrick, AH and Brennan, F and Abram, F and O'Sullivan, O}, title = {An in-depth evaluation of metagenomic classifiers for soil microbiomes.}, journal = {Environmental microbiome}, volume = {19}, number = {1}, pages = {19}, pmid = {38549112}, issn = {2524-6372}, support = {SFI/16/RC/3835//VistaMilk/ ; Ref: 2020019//Teagasc Walsh Scholarship Programme/ ; }, abstract = {BACKGROUND: Recent endeavours in metagenomics, exemplified by projects such as the human microbiome project and TARA Oceans, have illuminated the complexities of microbial biomes. A robust bioinformatic pipeline and meticulous evaluation of their methodology have contributed to the success of these projects. The soil environment, however, with its unique challenges, requires a specialized methodological exploration to maximize microbial insights. A notable limitation in soil microbiome studies is the dearth of soil-specific reference databases available to classifiers that emulate the complexity of soil communities. There is also a lack of in-vitro mock communities derived from soil strains that can be assessed for taxonomic classification accuracy.<br><br>RESULTS: In this study, we generated a custom in-silico mock community containing microbial genomes commonly observed in the soil microbiome. Using this mock community, we simulated shotgun sequencing data to evaluate the performance of three leading metagenomic classifiers: Kraken2 (supplemented with Bracken, using a custom database derived from GTDB-TK genomes along with its own default database), Kaiju, and MetaPhlAn, utilizing their respective default databases for a robust analysis. Our results highlight the importance of optimizing taxonomic classification parameters, database selection, as well as analysing trimmed reads and contigs. Our study showed that classifiers tailored to the specific taxa present in our samples led to fewer errors compared to broader databases including microbial eukaryotes, protozoa, or human genomes, highlighting the effectiveness of targeted taxonomic classification. Notably, an optimal classifier performance was achieved when applying a relative abundance threshold of 0.001% or 0.005%. The Kraken2 supplemented with bracken, with a custom database demonstrated superior precision, sensitivity, F1 score, and overall sequence classification. Using a custom database, this classifier classified 99% of in-silico reads and 58% of real-world soil shotgun reads, with the latter identifying previously overlooked phyla using a custom database.<br><br>CONCLUSION: This study underscores the potential advantages of in-silico methodological optimization in metagenomic analyses, especially when deciphering the complexities of soil microbiomes. We demonstrate that the choice of classifier and database significantly impacts microbial taxonomic profiling. Our findings suggest that employing Kraken2 with Bracken, coupled with a custom database of GTDB-TK genomes and fungal genomes at a relative abundance threshold of 0.001% provides optimal accuracy in soil shotgun metagenome analysis.}, }
@article {pmid38543670, year = {2024}, author = {Tosado-Rodríguez, E and Alvarado-Vélez, I and Romaguera, J and Godoy-Vitorino, F}, title = {Vaginal Microbiota and HPV in Latin America: A Narrative Review.}, journal = {Microorganisms}, volume = {12}, number = {3}, pages = {}, pmid = {38543670}, issn = {2076-2607}, support = {U54 CA096297/CA/NCI NIH HHS/United States ; U54 MD007587/MD/NIMHD NIH HHS/United States ; U54MD007600/MD/NIMHD NIH HHS/United States ; P20GM103475/GM/NIGMS NIH HHS/United States ; U54 MD007600/MD/NIMHD NIH HHS/United States ; CA096297/CA/NCI NIH HHS/United States ; U54MD007587/GM/NIGMS NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; }, abstract = {With the expansion of human microbiome studies in the last 15 years, we have realized the immense implications of microbes in human health. The human holobiont is now accepted, given the commensal relationships with bacteria, fungi, parasites, viruses, and human cells. The cervicovaginal microbiota is a specific case within the human microbiome where diversity is lower to maintain a chemical barrier of protection against infections. This narrative review focuses on the vaginal microbiome. It summarizes key findings on how native bacteria protect women from disease or predispose them to damaging inflammatory processes with an emphasis on the role of HPV infections in Latin America, one of the world's regions with the highest cervical cancer prevalence.}, }
@article {pmid38543514, year = {2024}, author = {Efremova, I and Maslennikov, R and Medvedev, O and Kudryavtseva, A and Avdeeva, A and Krasnov, G and Romanikhin, F and Diatroptov, M and Fedorova, M and Poluektova, E and Levshina, A and Ivashkin, V}, title = {Gut Microbiota and Biomarkers of Intestinal Barrier Damage in Cirrhosis.}, journal = {Microorganisms}, volume = {12}, number = {3}, pages = {}, pmid = {38543514}, issn = {2076-2607}, abstract = {Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut microbiota in cirrhosis. The blood levels of DAO were inversely correlated with blood levels of claudin 3, lipopolysaccharide (LPS), presepsin, TNF-α, and the severity of cirrhosis according to Child-Pugh scores. The blood level of I-FABP was directly correlated with the blood level of claudin 3 but not with that of DAO. Patients with small intestinal bacterial overgrowth (SIBO) had lower DAO levels than patients without SIBO. There was no significant difference in claudin 3 levels and I-FABP detection rates between patients with and without SIBO. The DAO level was directly correlated with the abundance of Akkermansiaceae, Akkermansia, Allisonella, Clostridiaceae, Dialister, Lactobacillus, Muribaculaceae, Negativibacillus, Ruminococcus, Thiomicrospiraceae, Verrucomicrobiae, and Verrucomicrobiota; and it was inversely correlated with the abundance of Anaerostipes, Erysipelatoclostridium, and Vibrio. The I-FABP level was directly correlated with Anaerostipes, Bacteroidia, Bacteroidota, Bilophila, Megamonas, and Selenomonadaceae; and it was inversely correlated with the abundance of Brucella, Pseudomonadaceae, Pseudomonas, and Vibrionaceae. The claudin 3 level was directly correlated with Anaerostipes abundance and was inversely correlated with the abundance of Brucella, Coriobacteriia, Eggerthellaceae, and Lactobacillus.}, }
@article {pmid38542770, year = {2024}, author = {Nikoloudaki, O and Pinto, D and Acin Albiac, M and Celano, G and Da Ros, A and De Angelis, M and Rinaldi, F and Gobbetti, M and Di Cagno, R}, title = {Exploring the Gut Microbiome and Metabolome in Individuals with Alopecia Areata Disease.}, journal = {Nutrients}, volume = {16}, number = {6}, pages = {}, pmid = {38542770}, issn = {2072-6643}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome/genetics ; *Alopecia Areata ; Metabolome ; Feces/chemistry ; Biomarkers/analysis ; RNA, Ribosomal, 16S/genetics ; }, abstract = {In recent years, heightened attention has been devoted to unravelling the intricate interplay between genetic and environmental factors shaping the gut microbiota and its significance for human health. This study delves into exploring the plausible connection between Alopecia Areata (AA), an autoimmune disease, and the dynamics of the gut microbiome. Examining a cohort of healthy adults and individuals with AA, both the gut microbiota composition and volatile organic compound (VOC) metabolites from faeces and urine were analysed. While overall microbiota composition showed no significant differences, intra-individual variability revealed distinctions related to age, gender, and pathology status, with AA individuals exhibiting reduced species richness and evenness. Differential abundance analysis identified microbial biomarkers for AA, notably Firmicutes, Lachnospirales, and Blautia, while Coprococcus stood out for healthy individuals. The Data Integration Analysis for Biomarker discovery using Latent Components (DIABLO) method further supported these findings including metabolite biomarkers, such as esters of branched chain fatty acids and branched chain amino acids as predictors for AA, suggesting potential links to oxidative stress. Despite certain limitations, the study highlights the complexity of the gut microbiome and its metabolites in the context of AA, while the biomarkers identified could be useful starting points for upcoming studies.}, }
@article {pmid38542455, year = {2024}, author = {Mak, AL and Augustijn, QJJ and Heymann, CJF and Havik, S and Verdoes, X and Rios-Morales, M and Bosmans, LA and Verheij, J and Meijnikman, AS and de Jonge, PA and Herrema, H and de Vos, WM and Nieuwdorp, M and Grefhorst, A and Holleboom, AG}, title = {Anaerobutyricum soehngenii Reduces Hepatic Lipogenic Pathways and Increases Intestinal Gluconeogenic Gene Expression in Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD) Mice.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542455}, issn = {1422-0067}, mesh = {Male ; Animals ; Mice ; Mice, Inbred C57BL ; Base Composition ; Gluconeogenesis ; Phylogeny ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; *Fatty Liver/etiology/genetics ; *Metabolic Diseases ; Butyrates ; Gene Expression ; Phosphatidate Phosphatase ; *Clostridiales ; }, abstract = {Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing health problem for which no therapy exists to date. The modulation of the gut microbiome may have treatment potential for MASLD. Here, we investigated Anaerobutyricum soehngenii, a butyrate-producing anaerobic bacterium with beneficial effects in metabolic syndrome, in a diet-induced MASLD mouse model. Male C57BL/6J mice received a Western-type high-fat diet and water with 15% fructose (WDF) to induce MASLD and were gavaged with A. soehngenii (10[8] or 10[9] colony-forming units (CFU) 3 times per week) or a placebo for 6 weeks. The A. soehngenii gavage increased the cecal butyrate concentrations. Although there was no effect on histological MASLD scores, A. soehngenii improved the glycemic response to insulin. In the liver, the WDF-associated altered expression of three genes relevant to the MASLD pathophysiology was reversed upon treatment with A. soehngenii: Lipin-1 (Lpin1), insulin-like growth factor binding protein 1 (Igfbp1) and Interleukin 1 Receptor Type 1 (Il1r1). A. soehngenii administration also increased the intestinal expression of gluconeogenesis and fructolysis genes. Although these effects did not translate into significant histological improvements in MASLD, these results provide a basis for combined gut microbial approaches to induce histological improvements in MASLD.}, }
@article {pmid38542265, year = {2024}, author = {Uzelac, M and Xin, R and Ongkeko, WM}, title = {Microbiome Dysbiosis Is Associated with Castration Resistance and Cancer Stemness in Metastatic Prostate Cancer.}, journal = {International journal of molecular sciences}, volume = {25}, number = {6}, pages = {}, pmid = {38542265}, issn = {1422-0067}, support = {RG096651//UC San Diego Academic Senate/ ; }, mesh = {Male ; Humans ; *Prostatic Neoplasms, Castration-Resistant/pathology ; Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases ; Dysbiosis ; Castration ; Receptors, Androgen/metabolism ; }, abstract = {Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration resistance often develops during the course of treatment, but its pathogenesis is poorly understood. This study explores the human microbiome for its implications in castration resistance and metastasis in prostate cancer. RNA sequencing data were downloaded for the bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These included both metastatic and adjacent normal biopsies. These sequences were mapped to bacterial sequences, yielding species-level counts. A vast majority of species were found to be significantly underabundant in the CRPC samples. Of these, numerous were found to correlate with the expression of known markers of castration resistance, including AR, PI3K, and AKT. Castration resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for a relation to these species. EGFR and SLC3A2 were widely downregulated, with a greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration resistance and stemness in prostate cancer. By considering the microbiome's importance in these factors, we may better understand the highly aggressive and highly invasive nature of castration-resistant prostate cancer, allowing for the needed improvements in the treatment of this disease.}, }
@article {pmid38530031, year = {2024}, author = {Cao, B and Wang, X and Yin, W and Gao, Z and Xia, B}, title = {The human microbiota is a beneficial reservoir for SARS-CoV-2 mutations.}, journal = {mBio}, volume = {15}, number = {5}, pages = {e0318723}, pmid = {38530031}, issn = {2150-7511}, support = {22QA1411000//STCSM | Science and Technology Innovation Plan Of Shanghai Science and Technology Commission/ ; }, mesh = {Humans ; *SARS-CoV-2/genetics/immunology ; *Mutation ; *COVID-19/virology/immunology ; *Spike Glycoprotein, Coronavirus/genetics/immunology ; *Microbiota/genetics ; Bacteria/genetics/classification ; }, abstract = {UNLABELLED: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations are rapidly emerging. In particular, beneficial mutations in the spike (S) protein, which can either make a person more infectious or enable immunological escape, are providing a significant obstacle to the prevention and treatment of pandemics. However, how the virus acquires a high number of beneficial mutations in a short time remains a mystery. We demonstrate here that variations of concern may be mutated due in part to the influence of the human microbiome. We searched the National Center for Biotechnology Information database for homologous fragments (HFs) after finding a mutation and the six neighboring amino acids in a viral mutation fragment. Among the approximate 8,000 HFs obtained, 61 mutations in S and other outer membrane proteins were found in bacteria, accounting for 62% of all mutation sources, which is 12-fold higher than the natural variable proportion. A significant proportion of these bacterial species-roughly 70%-come from the human microbiota, are mainly found in the lung or gut, and share a composition pattern with COVID-19 patients. Importantly, SARS-CoV-2 RNA-dependent RNA polymerase replicates corresponding bacterial mRNAs harboring mutations, producing chimeric RNAs. SARS-CoV-2 may collectively pick up mutations from the human microbiota that change the original virus's binding sites or antigenic determinants. Our study clarifies the evolving mutational mechanisms of SARS-CoV-2.<br><br>IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations are rapidly emerging, in particular advantageous mutations in the spike (S) protein, which either increase transmissibility or lead to immune escape and are posing a major challenge to pandemic prevention and treatment. However, how the virus acquires a high number of advantageous mutations in a short time remains a mystery. Here, we provide evidence that the human microbiota is a reservoir of advantageous mutations and aids mutational evolution and host adaptation of SARS-CoV-2. Our findings demonstrate a conceptual breakthrough on the mutational evolution mechanisms of SARS-CoV-2 for human adaptation. SARS-CoV-2 may grab advantageous mutations from the widely existing microorganisms in the host, which is undoubtedly an "efficient" manner. Our study might open a new perspective to understand the evolution of virus mutation, which has enormous implications for comprehending the trajectory of the COVID-19 pandemic.}, }
@article {pmid38528457, year = {2024}, author = {Buetas, E and Jordán-López, M and López-Roldán, A and D'Auria, G and Martínez-Priego, L and De Marco, G and Carda-Diéguez, M and Mira, A}, title = {Full-length 16S rRNA gene sequencing by PacBio improves taxonomic resolution in human microbiome samples.}, journal = {BMC genomics}, volume = {25}, number = {1}, pages = {310}, pmid = {38528457}, issn = {1471-2164}, support = {PRE2019-088126//Spanish Ministry of Science and Innovation/ ; RTI2018- 102032-B-I00//The Spanish Ministry of Innovation and Science/ ; }, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Genes, rRNA ; Phylogeny ; Sequence Analysis, DNA/methods ; *Microbiota/genetics ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {BACKGROUND: Sequencing variable regions of the 16S rRNA gene (≃300 bp) with Illumina technology is commonly used to study the composition of human microbiota. Unfortunately, short reads are unable to differentiate between highly similar species. Considering that species from the same genus can be associated with health or disease it is important to identify them at the lowest possible taxonomic rank. Third-generation sequencing platforms such as PacBio SMRT, increase read lengths allowing to sequence the whole gene with the maximum taxonomic resolution. Despite its potential, full length 16S rRNA gene sequencing is not widely used yet. The aim of the current study was to compare the sequencing output and taxonomic annotation performance of the two approaches (Illumina short read sequencing and PacBio long read sequencing of 16S rRNA gene) in different human microbiome samples. DNA from saliva, oral biofilms (subgingival plaque) and faeces of 9 volunteers was isolated. Regions V3-V4 and V1-V9 were amplified and sequenced by Illumina Miseq and by PacBio Sequel II sequencers, respectively.<br><br>RESULTS: With both platforms, a similar percentage of reads was assigned to the genus level (94.79% and 95.06% respectively) but with PacBio a higher proportion of reads were further assigned to the species level (55.23% vs 74.14%). Regarding overall bacterial composition, samples clustered by niche and not by sequencing platform. In addition, all genera with&#x2009;>&#x2009;0.1% abundance were detected in both platforms for all types of samples. Although some genera such as Streptococcus tended to be observed at higher frequency in PacBio than in Illumina (20.14% vs 14.12% in saliva, 10.63% vs 6.59% in subgingival plaque biofilm samples) none of the differences were statistically significant when correcting for multiple testing.<br><br>CONCLUSIONS: The results presented in the current manuscript suggest that samples sequenced using Illumina and PacBio are mostly comparable. Considering that PacBio reads were assigned at the species level with higher accuracy than Illumina, our data support the use of PacBio technology for future microbiome studies, although a higher cost is currently required to obtain an equivalent number of reads per sample.}, }
@article {pmid38528097, year = {2024}, author = {Wang, B and Sun, F and Luan, Y}, title = {Comparison of the effectiveness of different normalization methods for metagenomic cross-study phenotype prediction under heterogeneity.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {7024}, pmid = {38528097}, issn = {2045-2322}, support = {2018YFA0703900//National Key Research and Development Program of China/ ; 2018YFA0703900//National Key Research and Development Program of China/ ; 11971264//National Science Foundation of China/ ; 11971264//National Science Foundation of China/ ; }, mesh = {Humans ; *Microbiota/genetics ; Metagenome ; Metagenomics ; Research Design ; Phenotype ; }, abstract = {The human microbiome, comprising microorganisms residing within and on the human body, plays a crucial role in various physiological processes and has been linked to numerous diseases. To analyze microbiome data, it is essential to account for inherent heterogeneity and variability across samples. Normalization methods have been proposed to mitigate these variations and enhance comparability. However, the performance of these methods in predicting binary phenotypes remains understudied. This study systematically evaluates different normalization methods in microbiome data analysis and their impact on disease prediction. Our findings highlight the strengths and limitations of scaling, compositional data analysis, transformation, and batch correction methods. Scaling methods like TMM show consistent performance, while compositional data analysis methods exhibit mixed results. Transformation methods, such as Blom and NPN, demonstrate promise in capturing complex associations. Batch correction methods, including BMC and Limma, consistently outperform other approaches. However, the influence of normalization methods is constrained by population effects, disease effects, and batch effects. These results provide insights for selecting appropriate normalization approaches in microbiome research, improving predictive models, and advancing personalized medicine. Future research should explore larger and more diverse datasets and develop tailored normalization strategies for microbiome data analysis.}, }
@article {pmid38526734, year = {2024}, author = {Wan, X and Skurnik, M}, title = {Multidisciplinary Methods for Screening Toxic Proteins from Phages and Their Potential Molecular Targets.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2793}, number = {}, pages = {237-256}, pmid = {38526734}, issn = {1940-6029}, mesh = {*Bacteriophages/genetics ; Genomics ; Bacteria ; Computational Biology/methods ; Bacterial Proteins/genetics ; }, abstract = {This chapter presents a comprehensive methodology for the identification, characterization, and functional analyses of potentially toxic hypothetical proteins of unknown function (toxHPUFs) in phages. The methods begin with in vivo toxicity verification of toxHPUFs in bacterial hosts, utilizing conventional drop tests and following growth curves. Computational methods for structural and functional predictions of toxHPUFs are outlined, incorporating the use of tools such as Phyre2, HHpred, and AlphaFold2. To ascertain potential targets, a comparative genomic approach is described using bioinformatics toolkits for sequence alignment and functional annotation. Moreover, steps are provided to predict protein-protein interactions and visualizing these using PyMOL. The culmination of these methods equips researchers with an effective pipeline to identify and analyze toxHPUFs and their potential targets, laying the groundwork for future experimental confirmations.}, }
@article {pmid38522483, year = {2024}, author = {Bijla, M and Saini, SK and Pathak, AK and Bharadwaj, KP and Sukhavasi, K and Patil, A and Saini, D and Yadav, R and Singh, S and Leeuwenburgh, C and Kumar, P}, title = {Microbiome interactions with different risk factors in development of myocardial infarction.}, journal = {Experimental gerontology}, volume = {189}, number = {}, pages = {112409}, doi = {10.1016/j.exger.2024.112409}, pmid = {38522483}, issn = {1873-6815}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Myocardial Infarction ; *Microbiota ; Risk Factors ; *Hypertension ; }, abstract = {Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.}, }
@article {pmid38513074, year = {2024}, author = {Khawaja, T and Kajova, M and Levonen, I and Pietilä, JP and Välimaa, H and Paajanen, J and Pakkanen, SH and Patjas, A and Montonen, R and Miettinen, S and Virtanen, J and Smura, T and Sironen, T and Fagerlund, R and Ugurlu, H and Iheozor-Ejiofor, R and Saksela, K and Vahlberg, T and Ranki, A and Vierikko, A and Ihalainen, J and Vapalahti, O and Kantele, A}, title = {Double-blinded, randomised, placebo-controlled trial of convalescent plasma for COVID-19: analyses by neutralising antibodies homologous to recipients' variants.}, journal = {Infectious diseases (London, England)}, volume = {56}, number = {6}, pages = {423-433}, doi = {10.1080/23744235.2024.2329957}, pmid = {38513074}, issn = {2374-4243}, mesh = {Humans ; Double-Blind Method ; *Antibodies, Neutralizing/blood/immunology ; Male ; *COVID-19/therapy/immunology ; Female ; Middle Aged ; Immunization, Passive/methods ; COVID-19 Serotherapy ; *Antibodies, Viral/blood/immunology ; *SARS-CoV-2/immunology ; Adult ; Aged ; Treatment Outcome ; }, abstract = {INTRODUCTION: Convalescent plasma (CP) emerged as potential treatment for COVID-19 early in the pandemic. While efficacy in hospitalised patients has been lacklustre, CP may be beneficial at the first stages of disease. Despite multiple new variants emerging, no trials have involved analyses on variant-specific antibody titres of CP.<br><br>METHODS: We recruited hospitalised COVID-19 patients within 10&#x2009;days of symptom onset and, employing a double-blinded approach, randomised them to receive 200&#x2009;ml convalescent plasma with high (HCP) or low (LCP) neutralising antibody (NAb) titre against the ancestral strain (Wuhan-like variant) or placebo in 1:1:1 ratio. Primary endpoints comprised intubation, corticosteroids for symptom aggravation, and safety assessed as serious adverse events. For a preplanned ad hoc analysis, the patients were regrouped by infused CP's NAb titers to variants infecting the recipients i.e. by titres of homologous HCP (hHCP) or LCP (hLCP).<br><br>RESULTS: Of the 57 patients, 18 received HCP, 19 LCP and 20 placebo, all groups smaller than planned. No significant differences were found for primary endpoints. In ad hoc analysis, hHCPrecipients needed significantly less respiratory support, and appeared to be given corticosteroids less frequently (1/14; 7.1%) than those receiving hLCP (9/23; 39.1%) or placebo (8/20; 40%), (p&#x2009;=&#x2009;0.077).<br><br>DISCUSSION: Our double-blinded, placebo-controlled CP therapy trial remained underpowered and does not allow any firm conclusions for early-stage hospitalised COVID-19 patients. Interestingly, however, regrouping by homologous - recipients' variant-specific - CP titres suggested benefits for hHCP. We encourage similar re-analysis of ongoing/previous larger CP studies.<br><br>TRIAL REGISTRATION: ClinTrials.gov identifier: NCT0473040.}, }
@article {pmid38510311, year = {2023}, author = {Gellman, RH and Olm, MR and Terrapon, N and Enam, F and Higginbottom, SK and Sonnenburg, JL and Sonnenburg, ED}, title = {Hadza Prevotella require diet-derived microbiota-accessible carbohydrates to persist in mice.}, journal = {Cell reports}, volume = {42}, number = {11}, pages = {}, pmid = {38510311}, issn = {2211-1247}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Mice ; *Microbiota ; Diet ; *Gastrointestinal Microbiome ; Carbohydrates ; Bacteroides ; Prevotella ; }, abstract = {Industrialization has transformed the gut microbiota, reducing the prevalence of Prevotella relative to Bacteroides. Here, we isolate Bacteroides and Prevotella strains from the microbiota of Hadza hunter-gatherers in Tanzania, a population with high levels of Prevotella. We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence of Prevotella copri but not Bacteroides thetaiotaomicron in vivo. Differences in carbohydrate metabolism gene content, expression, and in vitro growth reveal that Hadza Prevotella strains specialize in degrading plant carbohydrates, while Hadza Bacteroides isolates use both plant and host-derived carbohydrates, a difference mirrored in Bacteroides from non-Hadza populations. When competing directly, P. copri requires plant-derived MACs to maintain colonization in the presence of B. thetaiotaomicron, as a no-MAC diet eliminates P. copri colonization. Prevotella's reliance on plant-derived MACs and Bacteroides' ability to use host mucus carbohydrates could explain the reduced prevalence of Prevotella in populations consuming a low-MAC, industrialized diet.}, }
@article {pmid38506889, year = {2024}, author = {Koskenvuo, L and Lunkka, P and Varpe, P and Hyöty, M and Satokari, R and Haapamäki, C and Lepistö, A and Sallinen, V}, title = {Morbidity After Mechanical Bowel Preparation and Oral Antibiotics Prior to Rectal Resection: The MOBILE2 Randomized Clinical Trial.}, journal = {JAMA surgery}, volume = {159}, number = {6}, pages = {606-614}, pmid = {38506889}, issn = {2168-6262}, mesh = {Humans ; Male ; Female ; Double-Blind Method ; Middle Aged ; *Surgical Wound Infection/prevention &amp; control/epidemiology ; Aged ; *Anti-Bacterial Agents/administration &amp; dosage/therapeutic use ; *Rectal Neoplasms/surgery ; Administration, Oral ; Antibiotic Prophylaxis ; Preoperative Care/methods ; Neomycin/administration &amp; dosage/therapeutic use ; Cathartics/administration &amp; dosage ; Metronidazole/administration &amp; dosage/therapeutic use ; Proctectomy/adverse effects ; Rectum/surgery ; Surgical Wound Dehiscence/prevention &amp; control/etiology ; Elective Surgical Procedures/adverse effects ; }, abstract = {IMPORTANCE: Surgical site infections (SSIs)-especially anastomotic dehiscence-are major contributors to morbidity and mortality after rectal resection. The role of mechanical and oral antibiotics bowel preparation (MOABP) in preventing complications of rectal resection is currently disputed.<br><br>OBJECTIVE: To assess whether MOABP reduces overall complications and SSIs after elective rectal resection compared with mechanical bowel preparation (MBP) plus placebo.<br><br>This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 3 university hospitals in Finland between March 18, 2020, and October 10, 2022. Patients aged 18 years and older undergoing elective resection with primary anastomosis of a rectal tumor 15 cm or less from the anal verge on magnetic resonance imaging were eligible for inclusion. Outcomes were analyzed using a modified intention-to-treat principle, which included all patients who were randomly allocated to and underwent elective rectal resection with an anastomosis.<br><br>INTERVENTIONS: Patients were stratified according to tumor distance from the anal verge and neoadjuvant treatment given and randomized in a 1:1 ratio to receive MOABP with an oral regimen of neomycin and metronidazole (n&#x2009;=&#x2009;277) or MBP plus matching placebo tablets (n&#x2009;=&#x2009;288). All study medications were taken the day before surgery, and all patients received intravenous antibiotics approximately 30 minutes before surgery.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was overall cumulative postoperative complications measured using the Comprehensive Complication Index. Key secondary outcomes were SSI and anastomotic dehiscence within 30 days after surgery.<br><br>RESULTS: In all, 565 patients were included in the analysis, with 288 in the MBP plus placebo group (median [IQR] age, 69 [62-74] years; 190 males [66.0%]) and 277 in the MOABP group (median [IQR] age, 70 [62-75] years; 158 males [57.0%]). Patients in the MOABP group experienced fewer overall postoperative complications (median [IQR] Comprehensive Complication Index, 0 [0-8.66] vs 8.66 [0-20.92]; Wilcoxon effect size, 0.146; P&#x2009;<&#x2009;.001), fewer SSIs (23 patients [8.3%] vs 48 patients [16.7%]; odds ratio, 0.45 [95% CI, 0.27-0.77]), and fewer anastomotic dehiscences (16 patients [5.8%] vs 39 patients [13.5%]; odds ratio, 0.39 [95% CI, 0.21-0.72]) compared with patients in the MBP plus placebo group.<br><br>CONCLUSIONS AND RELEVANCE: Findings of this randomized clinical trial indicate that MOABP reduced overall postoperative complications as well as rates of SSIs and anastomotic dehiscences in patients undergoing elective rectal resection compared with MBP plus placebo. Based on these findings, MOABP should be considered as standard treatment in patients undergoing elective rectal resection.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04281667.}, }
@article {pmid38504586, year = {2024}, author = {Brogna, C and Montano, L and Zanolin, ME and Bisaccia, DR and Ciammetti, G and Viduto, V and Fabrowski, M and Baig, AM and Gerlach, J and Gennaro, I and Bignardi, E and Brogna, B and Frongillo, A and Cristoni, S and Piscopo, M}, title = {A retrospective cohort study on early antibiotic use in vaccinated and unvaccinated COVID-19 patients.}, journal = {Journal of medical virology}, volume = {96}, number = {3}, pages = {e29507}, doi = {10.1002/jmv.29507}, pmid = {38504586}, issn = {1096-9071}, mesh = {Humans ; *Anti-Bacterial Agents/therapeutic use ; *COVID-19/prevention &amp; control ; Rifaximin ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; COVID-19 Vaccines ; Retrospective Studies ; Anti-Inflammatory Agents, Non-Steroidal ; Adrenal Cortex Hormones ; Unvaccinated Persons ; }, abstract = {The bacteriophage behavior of SARS-CoV-2 during the acute and post-COVID-19 phases appears to be an important factor in the development of the disease. The early use of antibiotics seems to be crucial to inhibit disease progression-to prevent viral replication in the gut microbiome, and control toxicological production from the human microbiome. To study the impact of specific antibiotics on recovery from COVID-19 and long COVID (LC) taking into account: vaccination status, comorbidities, SARS-CoV-2 wave, time of initiation of antibiotic therapy and concomitant use of corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). A total of 211 COVID-19 patients were included in the study: of which 59 were vaccinated with mRNA vaccines against SARS-CoV-2 while 152 were unvaccinated. Patients were enrolled in three waves: from September 2020 to October 2022, corresponding to the emergence of the pre-Delta, Delta, and Omicron variants of the SARS-CoV-2 virus. The three criteria for enrolling patients were: oropharyngeal swab positivity or fecal findings; moderate symptoms with antibiotic intake; and measurement of blood oxygen saturation during the period of illness. The use of antibiotic combinations, such as amoxicillin with clavulanic acid (875 + 125 mg tablets, every 12 h) plus rifaximin (400 mg tablets every 12 h), as first choice, as suggested from the previous data, or azithromycin (500 mg tablets every 24 h), plus rifaximin as above, allows healthcare professionals to focus on the gut microbiome and its implications in COVID-19 disease during patient care. The primary outcome measured in this study was the estimated average treatment effect, which quantified the difference in mean recovery between patients receiving antibiotics and those not receiving antibiotics at 3 and 9 days after the start of treatment. In the analysis, both vaccinated and unvaccinated groups had a median illness duration of 7 days (interquartile range [IQR] 6-9 days for each; recovery crude hazard ratio [HR] = 0.94, p = 0.700). The median illness duration for the pre-Delta and Delta waves was 8 days (IQR 7-10 days), while it was shorter, 6.5 days, for Omicron (IQR 6-8 days; recovery crude HR = 1.71, p < 0.001). These results were confirmed by multivariate analysis. Patients with comorbidities had a significantly longer disease duration: median 8 days (IQR 7-10 days) compared to 7 days (IQR 6-8 days) for those without comorbidities (crude HR = 0.75, p = 0.038), but this result was not confirmed in multivariate analysis as statistical significance was lost. Early initiation of antibiotic therapy resulted in a significantly shorter recovery time (crude HR = 4.74, p < 0.001). Concomitant use of NSAIDs did not reduce disease duration and in multivariate analysis prolonged the disease (p = 0.041). A subgroup of 42 patients receiving corticosteroids for a median of 3 days (IQR 3-6 days) had a longer recovery time (median 9 days, IQR 8-10 days) compared to others (median 7 days, IQR 6-8 days; crude HR = 0.542, p < 0.001), as confirmed also by the adjusted HR. In this study, a statistically significant reduction in recovery time was observed among patients who received early antibiotic treatment. Early initiation of antibiotics played a crucial role in maintaining higher levels of blood oxygen saturation. In addition, it is worth noting that a significant number of patients who received antibiotics in the first 3 days and for a duration of 7 days, during the acute phase did not develop LC.}, }
@article {pmid38497260, year = {2024}, author = {Singh, A and Luallen, RJ}, title = {Understanding the factors regulating host-microbiome interactions using Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {379}, number = {1901}, pages = {20230059}, pmid = {38497260}, issn = {1471-2970}, support = {R35 GM146836/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Caenorhabditis elegans/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host-microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering health interventions. Caenorhabditis elegans has been a pioneering model organism for over 70 years but was largely studied in the absence of a microbiome. Recently, ecological sampling of wild nematodes has uncovered a large amount of natural genetic diversity as well as a slew of associated microbiota. The field has now explored the interactions of C. elegans with its associated gut microbiome, a defined and non-random microbial community, highlighting its suitability for dissecting host-microbiome interactions. This core microbiome is being used to study the impact of host genetics, age and stressors on microbiome composition. Furthermore, single microbiome species are being used to dissect molecular interactions between microbes and the animal gut. Being amenable to health altering genetic and non-genetic interventions, C. elegans has emerged as a promising system to generate and test new hypotheses regarding host-microbiome interactions, with the potential to uncover novel paradigms relevant to other systems. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.}, }
@article {pmid38491556, year = {2024}, author = {Elradi, M and Ahmed, AI and Saleh, AM and Abdel-Raouf, KMA and Berika, L and Daoud, Y and Amleh, A}, title = {Derivation of a novel antimicrobial peptide from the Red Sea Brine Pools modified to enhance its anticancer activity against U2OS cells.}, journal = {BMC biotechnology}, volume = {24}, number = {1}, pages = {14}, pmid = {38491556}, issn = {1472-6750}, mesh = {Animals ; Mice ; Humans ; Caspase 3/genetics/metabolism/pharmacology ; Survivin/genetics/metabolism/pharmacology ; Escherichia coli/metabolism ; Antimicrobial Peptides ; Cell Line, Tumor ; Indian Ocean ; Ki-67 Antigen/metabolism ; Staphylococcus aureus ; Apoptosis ; Peptides/pharmacology/metabolism ; *Antineoplastic Agents/pharmacology/chemistry ; *Anti-Infective Agents/pharmacology ; Annexins/pharmacology ; *Salts ; }, abstract = {Cancer associated drug resistance is a major cause for cancer aggravation, particularly as conventional therapies have presented limited efficiency, low specificity, resulting in long term deleterious side effects. Peptide based drugs have emerged as potential alternative cancer treatment tools due to their selectivity, ease of design and synthesis, safety profile, and low cost of manufacturing. In this study, we utilized the Red Sea metagenomics database, generated during AUC/KAUST Red Sea microbiome project, to derive a viable anticancer peptide (ACP). We generated a set of peptide hits from our library that shared similar composition to ACPs. A peptide with a homeodomain was selected, modified to improve its anticancer properties, verified to maintain high anticancer properties, and processed for further in-silico prediction of structure and function. The peptide's anticancer properties were then assessed in vitro on osteosarcoma U2OS cells, through cytotoxicity assay (MTT assay), scratch-wound healing assay, apoptosis/necrosis detection assay (Annexin/PI assay), RNA expression analysis of Caspase 3, KI67 and Survivin, and protein expression of PARP1. L929 mouse fibroblasts were also assessed for cytotoxicity treatment. In addition, the antimicrobial activity of the peptide was also examined on E coli and S. aureus, as sample representative species of the human bacterial microbiome, by examining viability, disk diffusion, morphological assessment, and hemolytic analysis. We observed a dose dependent cytotoxic response from peptide treatment of U2OS, with a higher tolerance in L929s. Wound closure was debilitated in cells exposed to the peptide, while annexin fluorescent imaging suggested peptide treatment caused apoptosis as a major mode of cell death. Caspase 3 gene expression was not altered, while KI67 and Survivin were both downregulated in peptide treated cells. Additionally, PARP-1 protein analysis showed a decrease in expression with peptide exposure. The peptide exhibited minimal antimicrobial activity on critical human microbiome species E. coli and S. aureus, with a low inhibition rate, maintenance of structural morphology and minimal hemolytic impact. These findings suggest our novel peptide displayed preliminary ACP properties against U2OS cells, through limited specificity, while triggering apoptosis as a primary mode of cell death and while having minimal impact on the microbiological species E. coli and S. aureus.}, }
@article {pmid38489954, year = {2024}, author = {Huang, Y and Zhang, R and Hong, X and Liu, S and Zhang, S and Guo, M and Shi, L and Li, Z and Liu, Y}, title = {Correlation between sarcopenia index and cognitive function in older adult women: A cross-sectional study using NHANES data.}, journal = {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}, volume = {122}, number = {}, pages = {73-79}, doi = {10.1016/j.jocn.2024.02.026}, pmid = {38489954}, issn = {1532-2653}, mesh = {Humans ; Female ; United States/epidemiology ; Aged ; *Sarcopenia/diagnosis/epidemiology ; Cross-Sectional Studies ; Nutrition Surveys ; Reproducibility of Results ; Cognition/physiology ; }, abstract = {OBJECTIVES: The Sarcopenia Index (SI) has the potential as a biomarker for sarcopenia, which is characterized by muscle loss. There is a clear association between sarcopenia and cognitive impairment. However, the relationship between SI and cognitive impairment is yet to be fully understood.<br><br>METHODS: We employed data extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2002. Our study encompassed individuals aged 65 to 80 who possessed accessible information regarding both SI and cognitive evaluations with a GFR&#xa0;&#x2265;&#xa0;90. Cognitive function was assessed using the digit symbol substitution test (DSST). SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L)*100. Employing multivariate modeling, we estimated the connection between SI and cognitive performance. Furthermore, to enhance the reliability of our data analysis, we categorized SI using tertiles and subsequently calculated the P-value for trend.<br><br>RESULTS: After adjustment for potential confounders, we found SI was significantly and positively correlated with cognitive function scores both in older female in the American population [&#x3b2;&#xa0;=&#xa0;0.160, 95&#xa0;% confidence interval (CI) 0.050 to 0.271, P&#xa0;=&#xa0;0.00461]. Similarly, when the total cognitive function score was treated as a categorical variable according to tertiles, higher SI was related to better total cognitive function scores in females [odds ratio (OR)&#xa0;=&#xa0;3.968, 95&#xa0;% CI 1.863 to 6.073, P&#xa0;=&#xa0;0.00025] following adjustment for confounders.<br><br>CONCLUSIONS: Higher SI was correlated with a lower prevalence of cognitive impairment among older adult women with normal kidney function.}, }
@article {pmid38484733, year = {2024}, author = {Zheng, J and Zhang, XM and Tang, W and Li, Y and Wang, P and Jin, J and Luo, Z and Fang, S and Yang, S and Wei, Z and Song, K and Huang, Z and Wang, Z and Zhu, Z and Shi, N and Xiao, D and Yuan, L and Shen, H and Huang, L and Li, B}, title = {An insular cortical circuit required for itch sensation and aversion.}, journal = {Current biology : CB}, volume = {34}, number = {7}, pages = {1453-1468.e6}, doi = {10.1016/j.cub.2024.02.060}, pmid = {38484733}, issn = {1879-0445}, mesh = {Humans ; *Insular Cortex ; *Sensation/physiology ; GABAergic Neurons/metabolism ; Histamine/adverse effects/metabolism ; Pruritus/chemically induced ; }, abstract = {Itch encompasses both sensory and emotional dimensions, with the two dimensions reciprocally exacerbating each other. However, whether a shared neural circuit mechanism governs both dimensions remains elusive. Here, we report that the anterior insular cortex (AIC) is activated by both histamine-dependent and -independent itch stimuli. The activation of AIC elicits aversive emotion and exacerbates pruritogen-induced itch sensation and aversion. Mechanistically, AIC excitatory neurons project to the GABAergic neurons in the dorsal bed nucleus of the stria terminalis (dBNST). Manipulating the activity of the AIC → dBNST pathway affects both itch sensation and itch-induced aversion. Our study discovers the shared neural circuit (AIC → dBNST pathway) underlying the itch sensation and aversion, highlights the critical role of the AIC as a central hub for the itch processing, and provides a framework to understand the neural mechanisms underlying the sensation and emotion interaction.}, }
@article {pmid38484036, year = {2024}, author = {Noto Guillen, M and Li, C and Rosener, B and Mitchell, A}, title = {Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics.}, journal = {Science (New York, N.Y.)}, volume = {384}, number = {6691}, pages = {93-100}, pmid = {38484036}, issn = {1095-9203}, support = {R01 AI170722/AI/NIAID NIH HHS/United States ; R35 GM133775/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Anti-Bacterial Agents/chemistry/classification/pharmacology ; Escherichia coli/drug effects/genetics ; Inhibitory Concentration 50 ; Microbial Sensitivity Tests ; *Microbiota/drug effects/genetics ; }, abstract = {Numerous nonantibiotic drugs have potent antibacterial activity and can adversely affect the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules that are consistent with the mode of action of their established classes, whereas nonantibiotics remained unconnected. Half of the nonantibiotics clustered into separate modules, potentially revealing shared and unexploited targets for new antimicrobials. Analysis of efflux systems revealed that they widely affect antibiotics and nonantibiotics alike, suggesting that the impact of nonantibiotics on antibiotic cross-resistance should be investigated closely in vivo.}, }
@article {pmid38479397, year = {2024}, author = {Zhou, X and Shen, X and Johnson, JS and Spakowicz, DJ and Agnello, M and Zhou, W and Avina, M and Honkala, A and Chleilat, F and Chen, SJ and Cha, K and Leopold, S and Zhu, C and Chen, L and Lyu, L and Hornburg, D and Wu, S and Zhang, X and Jiang, C and Jiang, L and Jiang, L and Jian, R and Brooks, AW and Wang, M and Contrepois, K and Gao, P and Rose, SMS and Tran, TDB and Nguyen, H and Celli, A and Hong, BY and Bautista, EJ and Dorsett, Y and Kavathas, PB and Zhou, Y and Sodergren, E and Weinstock, GM and Snyder, MP}, title = {Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.}, journal = {Cell host &amp; microbe}, volume = {32}, number = {4}, pages = {506-526.e9}, pmid = {38479397}, issn = {1934-6069}, support = {RM1 HG007735/HG/NHGRI NIH HHS/United States ; U54 DE023789/DE/NIDCR NIH HHS/United States ; K08 ES028825/ES/NIEHS NIH HHS/United States ; P30 AG059307/AG/NIA NIH HHS/United States ; R01 DK110186/DK/NIDDK NIH HHS/United States ; R01 AT010232/AT/NCCIH NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; K01 AG070310/AG/NIA NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; UL1 TR003142/TR/NCATS NIH HHS/United States ; F32 DK126287/DK/NIDDK NIH HHS/United States ; P30 AG066515/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Core Stability ; *Microbiota ; Skin/microbiology ; Host Microbial Interactions ; Biomarkers ; }, abstract = {To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.}, }
@article {pmid38477427, year = {2024}, author = {Zhang, J and Qi, H and Li, M and Wang, Z and Jia, X and Sun, T and Du, S and Su, C and Zhi, M and Du, W and Ouyang, Y and Wang, P and Huang, F and Jiang, H and Li, L and Bai, J and Wei, Y and Zhang, X and Wang, H and Zhang, B and Feng, Q}, title = {Diet Mediate the Impact of Host Habitat on Gut Microbiome and Influence Clinical Indexes by Modulating Gut Microbes and Serum Metabolites.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {19}, pages = {e2310068}, pmid = {38477427}, issn = {2198-3844}, support = {ZR202102230369//Excellent Scientist Foundation of Shandong Province/ ; P30 AG066615/AG/NIA NIH HHS/United States ; R01 HD038700/HD/NICHD NIH HHS/United States ; 2021SFGC0502//Major Innovation Projects in Shandong Province/ ; P30-DK056350/DK/NIDDK NIH HHS/United States ; R01 DK104371/DK/NIDDK NIH HHS/United States ; R01 AG065357/AG/NIA NIH HHS/United States ; R01-DK104371/DK/NIDDK NIH HHS/United States ; R01-HD30880//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; R01 HL108427/HL/NHLBI NIH HHS/United States ; D43 TW009077/TW/FIC NIH HHS/United States ; 82071122//National Natural Science Foundation of China/ ; 2021YFE0114200//Ministry of Science and Technology of the People's Republic of China/ ; R01-HD38700//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; P30 DK056350/DK/NIDDK NIH HHS/United States ; //National Young Scientist Project Foundation of China (2019)/ ; R24 HD050924/HD/NICHD NIH HHS/United States ; 2021GXRC021//Oral Microbiome Innovation Team of Jinan City/ ; //Program of Taishan Young from Shandong Province/ ; R01 HD030880/HD/NICHD NIH HHS/United States ; 2020KJK001//Oral Microbiome Innovation Team of Shandong Province/ ; D43 TW007709/TW/FIC NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diet/methods ; China ; Male ; Female ; Metabolome/physiology ; Adult ; Middle Aged ; Ecosystem ; }, abstract = {The impact of external factors on the human gut microbiota and how gut microbes contribute to human health is an intriguing question. Here, the gut microbiome of 3,224 individuals (496 with serum metabolome) with 109 variables is studied. Multiple analyses reveal that geographic factors explain the greatest variance of the gut microbiome and the similarity of individuals' gut microbiome is negatively correlated with their geographic distance. Main food components are the most important factors that mediate the impact of host habitats on the gut microbiome. Diet and gut microbes collaboratively contribute to the variation of serum metabolites, and correlate to the increase or decrease of certain clinical indexes. Specifically, systolic blood pressure is lowered by vegetable oil through increasing the abundance of Blautia and reducing the serum level of 1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1), but it is reduced by fruit intake through increasing the serum level of Blautia improved threonate. Besides, aging-related clinical indexes are also closely correlated with the variation of gut microbes and serum metabolites. In this study, the linkages of geographic locations, diet, the gut microbiome, serum metabolites, and physiological indexes in a Chinese population are characterized. It is proved again that gut microbes and their metabolites are important media for external factors to affect human health.}, }
@article {pmid38474213, year = {2024}, author = {Hong, BY and Driscoll, M and Gratalo, D and Jarvie, T and Weinstock, GM}, title = {Improved DNA Extraction and Amplification Strategy for 16S rRNA Gene Amplicon-Based Microbiome Studies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, pmid = {38474213}, issn = {1422-0067}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; Genes, rRNA ; Reproducibility of Results ; DNA, Bacterial/genetics ; *Microbiota/genetics ; Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {Next-generation sequencing technology has driven the rapid advancement of human microbiome studies by enabling community-level sequence profiling of microbiomes. Although all microbiome sequencing methods depend on recovering the DNA from a sample as a first critical step, lysis methods can be a major determinant of microbiome profile bias. Gentle enzyme-based DNA preparation methods preserve DNA quality but can bias the results by failing to open difficult-to-lyse bacteria. Mechanical methods like bead beating can also bias DNA recovery because the mechanical energy required to break tougher cell walls may shear the DNA of the more easily lysed microbes, and shearing can vary depending on the time and intensity of beating, influencing reproducibility. We introduce a non-mechanical, non-enzymatic, novel rapid microbial DNA extraction procedure suitable for 16S rRNA gene-based microbiome profiling applications that eliminates bead beating. The simultaneous application of alkaline, heat, and detergent ('Rapid' protocol) to milligram quantity samples provided consistent representation across the population of difficult and easily lysed bacteria equal to or better than existing protocols, producing sufficient high-quality DNA for full-length 16S rRNA gene PCR. The novel 'Rapid' method was evaluated using mock bacterial communities containing both difficult and easily lysed bacteria. Human fecal sample testing compared the novel Rapid method with a standard Human Microbiome Project (HMP) protocol for samples from lung cancer patients and controls. DNA recovered from both methods was analyzed using 16S rRNA gene sequencing of the V1V3 and V4 regions on the Illumina platform and the V1V9 region on the PacBio platform. Our findings indicate that the 'Rapid' protocol consistently yielded higher levels of Firmicutes species, which reflected the profile of the bacterial community structure more accurately, which was confirmed by mock community evaluation. The novel 'Rapid' DNA lysis protocol reduces population bias common to bead beating and enzymatic lysis methods, presenting opportunities for improved microbial community profiling, combined with the reduction in sample input to 10 milligrams or less, and it enables rapid transfer and simultaneous lysis of 96 samples in a standard plate format. This results in a 20-fold reduction in sample handling time and an overall 2-fold time advantage when compared to widely used commercial methods. We conclude that the novel 'Rapid' DNA extraction protocol offers a reliable alternative for preparing fecal specimens for 16S rRNA gene amplicon sequencing.}, }
@article {pmid38472421, year = {2024}, author = {Cai, J and Lin, K and Luo, T and Weng, J and Liu, H and Yuan, Z and Wan, Z and Han, J and Lin, J and Liu, X and Wang, X and Huang, M and Luo, Y and Yu, H}, title = {Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial.}, journal = {British journal of cancer}, volume = {130}, number = {9}, pages = {1434-1440}, pmid = {38472421}, issn = {1532-1827}, support = {No. 81972245, YL; No. 82173067, YL; No. 81902877, HY; No. 82272965, HY//National Natural Science Foundation of China (National Science Foundation of China)/ ; No. 2022A1515012656, HY; No.2021A1515010134, MH;No.2020A1515010036, XL//Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)/ ; }, mesh = {Humans ; *Rectal Neoplasms/therapy/pathology ; *Neoadjuvant Therapy/methods ; Male ; Female ; Middle Aged ; Aged ; Chemoradiotherapy/methods ; Adult ; Treatment Outcome ; Age of Onset ; }, abstract = {BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment.<br><br>METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs.<br><br>RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR&#x2009;=&#x2009;3.75, 95% CI&#x2009;=&#x2009;1.37-10.27; complications: HR&#x2009;=&#x2009;11.35, 95% CI&#x2009;=&#x2009;1.46-88.31) compared with late-onset group (pCR: OR&#x2009;=&#x2009;5.33, 95% CI&#x2009;=&#x2009;1.83-15.58; complications: HR&#x2009;=&#x2009;5.80, 95% CI&#x2009;=&#x2009;2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR&#x2009;=&#x2009;1.37, 95% CI&#x2009;=&#x2009;0.49-3.87) and DFS (HR&#x2009;=&#x2009;1.05, 95% CI&#x2009;=&#x2009;0.58-1.90) for early-onset patients.<br><br>CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.}, }
@article {pmid38471667, year = {2024}, author = {Ghelfenstein-Ferreira, T and Serris, A and Salmona, M and Lanternier, F and Alanio, A}, title = {Revealing the hidden interplay: The unexplored relationship between fungi and viruses beyond HIV, SARS-CoV-2, and influenza.}, journal = {Medical mycology}, volume = {62}, number = {4}, pages = {}, doi = {10.1093/mmy/myae021}, pmid = {38471667}, issn = {1460-2709}, mesh = {Humans ; SARS-CoV-2 ; *Influenza, Human/complications ; *COVID-19/complications/veterinary ; Ecosystem ; *Viruses ; Fungi ; *Pulmonary Aspergillosis/veterinary ; *HIV Infections/complications/veterinary ; }, abstract = {The complex interaction between viruses and fungi has profound implications, especially given the significant impact of these microorganisms on human health. While well-known examples such as HIV, influenza, and SARS-CoV-2 are recognized as risk factors for invasive fungal diseases, the relationship between viruses and fungi remains largely underexplored outside of these cases. Fungi and viruses can engage in symbiotic or synergistic interactions. Remarkably, some viruses, known as mycoviruses, can directly infect fungi, may influencing their phenotype and potentially their virulence. In addition, viruses and fungi can coexist within the human microbiome, a complex ecosystem of microorganisms. Under certain conditions, viral infection might predispose the host to an invasive fungal infection, as observed with influenza-associated pulmonary aspergillosis or COVID-19 associated pulmonary aspergillosis. We aim in this review to highlight potential connections between fungi and viruses (CMV and other herpesviruses, HTLV-1 and respiratory viruses), excluding SARS-CoV-2 and influenza.}, }
@article {pmid38467837, year = {2024}, author = {Bhosle, A and Bae, S and Zhang, Y and Chun, E and Avila-Pacheco, J and Geistlinger, L and Pishchany, G and Glickman, JN and Michaud, M and Waldron, L and Clish, CB and Xavier, RJ and Vlamakis, H and Franzosa, EA and Garrett, WS and Huttenhower, C}, title = {Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease.}, journal = {Molecular systems biology}, volume = {20}, number = {4}, pages = {338-361}, pmid = {38467837}, issn = {1744-4292}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 CA230551/CA/NCI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; *Inflammatory Bowel Diseases/drug therapy/metabolism ; *Colitis ; Metabolome ; Bile Acids and Salts ; }, abstract = {Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.}, }
@article {pmid38466102, year = {2024}, author = {Cheng, G and Westerholm, M and Schnürer, A}, title = {Complete genome sequence of Citroniella saccharovorans DSM 29873, isolated from human fecal sample.}, journal = {Microbiology resource announcements}, volume = {13}, number = {4}, pages = {e0001524}, pmid = {38466102}, issn = {2576-098X}, support = {2018-01341//Svenska Forskningsr&#xe5;det Formas (Formas)/ ; 948138//EC | European Research Council (ERC)/ ; 2018-01341//Svenska Forskningsr&#xe5;det Formas (Formas)/ ; }, abstract = {A complete genome was recovered from Citroniella saccharovorans, strain DSM 29873, using Oxford Nanopore Technologies. The genome assembly contains 1,413,868 bp with 30.23% G+C content. The species belongs to the family Peptoniphilaceae and, as of yet, is the only cultivated representative of the genus Citroniella.}, }
@article {pmid38465728, year = {2024}, author = {Michán-Doña, A and Vázquez-Borrego, MC and Michán, C}, title = {Are there any completely sterile organs or tissues in the human body? Is there any sacred place?.}, journal = {Microbial biotechnology}, volume = {17}, number = {3}, pages = {e14442}, pmid = {38465728}, issn = {1751-7915}, support = {PRYES223170ARJO//Fundaci&#xf3;n Cient&#xed;fica Asociaci&#xf3;n Espa&#xf1;ola Contra el C&#xe1;ncer/ ; PI22/01213//Instituto de Salud Carlos III/ ; }, mesh = {Humans ; *Human Body ; Sequence Analysis, DNA ; *Infertility ; DNA, Ribosomal/genetics ; RNA/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome comprises an ample set of organisms that inhabit and interact within the human body, contributing both positively and negatively to our health. In recent years, several research groups have described the presence of microorganisms in organs or tissues traditionally considered as 'sterile' under healthy and pathological conditions. In this sense, microorganisms have been detected in several types of cancer, including those in 'sterile' organs. But how can the presence of microorganisms be detected? In most studies, 16S and internal transcribed spacer (ITS) ribosomal DNA (rDNA) sequencing has led to the identification of prokaryotes and fungi. However, a major limitation of this technique is that it cannot distinguish between living and dead organisms. RNA-based methods have been proposed to overcome this limitation, as the shorter half-life of the RNA would identify only the transcriptionally active microorganisms, although perhaps not all the viable ones. In this sense, metaproteomic techniques or the search for molecular metabolic signatures could be interesting alternatives for the identification of living microorganisms. In summary, new technological advances are challenging the notion of 'sterile' organs in our body. However, to date, evidence for a structured living microbiome in most of these organs is scarce or non-existent. The implementation of new technological approaches will be necessary to fully understand the importance of the microbiome in these organs, which could pave the way for the development of a wide range of new therapeutic strategies.}, }
@article {pmid38464031, year = {2024}, author = {Zolfo, M and Silverj, A and Blanco-Míguez, A and Manghi, P and Rota-Stabelli, O and Heidrich, V and Jensen, J and Maharjan, S and Franzosa, E and Menni, C and Visconti, A and Pinto, F and Ciciani, M and Huttenhower, C and Cereseto, A and Asnicar, F and Kitano, H and Yamada, T and Segata, N}, title = {Discovering and exploring the hidden diversity of human gut viruses using highly enriched virome samples.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38464031}, issn = {2692-8205}, support = {U01 CA230551/CA/NCI NIH HHS/United States ; }, abstract = {Viruses are an abundant and crucial component of the human microbiome, but accurately discovering them via metagenomics is still challenging. Currently, the available viral reference genomes poorly represent the diversity in microbiome samples, and expanding such a set of viral references is difficult. As a result, many viruses are still undetectable through metagenomics even when considering the power of de novo metagenomic assembly and binning, as viruses lack universal markers. Here, we describe a novel approach to catalog new viral members of the human gut microbiome and show how the resulting resource improves metagenomic analyses. We retrieved >3,000 viral-like particles (VLP) enriched metagenomic samples (viromes), evaluated the efficiency of the enrichment in each sample to leverage the viromes of highest purity, and applied multiple analysis steps involving assembly and comparison with hundreds of thousands of metagenome-assembled genomes to discover new viral genomes. We reported over 162,000 viral sequences passing quality control from thousands of gut metagenomes and viromes. The great majority of the retrieved viral sequences (~94.4%) were of unknown origin, most had a CRISPR spacer matching host bacteria, and four of them could be detected in >50% of a set of 18,756 gut metagenomes we surveyed. We included the obtained collection of sequences in a new MetaPhlAn 4.1 release, which can quantify reads within a metagenome matching the known and newly uncovered viral diversity. Additionally, we released the viral database for further virome and metagenomic studies of the human microbiome.}, }
@article {pmid38460430, year = {2024}, author = {Karisola, P and Nikkola, V and Joronen, H and Ylianttila, L and Grönroos, M and Partonen, T and Snellman, E and Alenius, H}, title = {Narrow-band UVB radiation triggers diverse changes in the gene expression and induces the accumulation of M1 macrophages in human skin.}, journal = {Journal of photochemistry and photobiology. B, Biology}, volume = {253}, number = {}, pages = {112887}, doi = {10.1016/j.jphotobiol.2024.112887}, pmid = {38460430}, issn = {1873-2682}, mesh = {Female ; Humans ; *Proteasome Endopeptidase Complex/metabolism ; *Skin/radiation effects ; Ultraviolet Rays ; Erythema/etiology ; Macrophages ; Gene Expression ; }, abstract = {BACKGROUND: The underlying molecular mechanisms that determine the biological effects of UVB radiation exposure on human skin are still only partially comprehended.<br><br>OBJECTIVES: Our goal is to examine the human skin transcriptome and related molecular mechanisms following a single exposure to UVB in the morning versus evening.<br><br>METHODS: We exposed 20 volunteer females to four-fold standard erythema doses (SED4) of narrow-band UVB (309-313&#xa0;nm) in the morning or evening and studied skin transcriptome 24&#xa0;h after the exposure. We performed enrichment analyses of gene pathways, predicted changes in skin cell composition using cellular deconvolution, and correlated cell proportions with gene expression.<br><br>RESULTS: In the skin transcriptome, UVB exposure yielded 1384 differentially expressed genes (DEGs) in the morning and 1295 DEGs in the evening, of which the most statistically significant DEGs enhanced proteasome and spliceosome pathways. Unexposed control samples showed difference by 321 DEGs in the morning vs evening, which was related to differences in genes associated with the circadian rhythm. After the UVB exposure, the fraction of proinflammatory M1 macrophages was significantly increased at both timepoints, and this increase was positively correlated with pathways on Myc targets and mTORC1 signaling. In the evening, the skin clinical erythema was more severe and had stronger positive correlation with the number of M1 macrophages than in the morning after UVB exposure. The fractions of myeloid and plasmacytoid dendritic cells and CD8 T cells were significantly decreased in the morning but not in the evening.<br><br>CONCLUSIONS: NB-UVB-exposure causes changes in skin transcriptome, inhibiting cell division, and promoting proteasome activity and repair responses, both in the morning and in the evening. Inflammatory M1 macrophages may drive the UV-induced skin responses by exacerbating inflammation and erythema. These findings highlight how the same UVB exposure influences skin responses differently in morning versus evening and presents a possible explanation to the differences in gene expression in the skin after UVB irradiation at these two timepoints.}, }
@article {pmid38455087, year = {2024}, author = {Reid, G}, title = {A value chain to improve human, animal and insect health in developing countries.}, journal = {Microbiome research reports}, volume = {3}, number = {1}, pages = {10}, pmid = {38455087}, issn = {2771-5965}, }
@article {pmid38452522, year = {2024}, author = {Jones, JM and Reinke, SN and Mousavi-Derazmahalleh, M and Garssen, J and Jenmalm, MC and Srinivasjois, R and Silva, D and Keelan, J and Prescott, SL and Palmer, DJ and Christophersen, CT}, title = {Maternal prebiotic supplementation during pregnancy and lactation modifies the microbiome and short chain fatty acid profile of both mother and infant.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {4}, pages = {969-980}, doi = {10.1016/j.clnu.2024.02.030}, pmid = {38452522}, issn = {1532-1983}, mesh = {Female ; Humans ; Infant ; Pregnancy ; Dietary Supplements ; Fatty Acids, Volatile/metabolism ; Lactation ; *Microbiota ; Mothers ; Oligosaccharides ; Powders ; *Prebiotics ; RNA, Ribosomal, 16S ; Infant, Newborn ; }, abstract = {BACKGROUND &amp; AIMS: Improving maternal gut health in pregnancy and lactation is a potential strategy to improve immune and metabolic health in offspring and curtail the rising rates of inflammatory diseases linked to alterations in gut microbiota. Here, we investigate the effects of a maternal prebiotic supplement (galacto-oligosaccharides and fructo-oligosaccharides), ingested daily from <21 weeks' gestation to six months' post-partum, in a double-blinded, randomised placebo-controlled trial.<br><br>METHODS: Stool samples were collected at multiple timepoints from 74 mother-infant pairs as part of a larger, double-blinded, randomised controlled allergy intervention trial. The participants were randomised to one of two groups; with one group receiving 14.2&#xa0;g per day of prebiotic powder (galacto-oligosaccharides GOS and fructo-oligosaccharides FOS in ratio 9:1), and the other receiving a placebo powder consisting of 8.7&#xa0;g per day of maltodextrin. The faecal microbiota of both mother and infants were assessed based on the analysis of bacterial 16S rRNA gene (V4 region) sequences, and short chain fatty acid (SCFA) concentrations in stool.<br><br>RESULTS: Significant differences in the maternal microbiota profiles between baseline and either 28-weeks' or 36-weeks' gestation were found in the prebiotic supplemented women. Infant microbial beta-diversity also significantly differed between prebiotic and placebo groups at 12-months of age. Supplementation was associated with increased abundance of commensal Bifidobacteria in the maternal microbiota, and a reduction in the abundance of Negativicutes in both maternal and infant microbiota. There were also changes in SCFA concentrations with maternal prebiotics supplementation, including significant differences in acetic acid concentration between intervention and control groups from 20 to 28-weeks' gestation.<br><br>CONCLUSION: Maternal prebiotic supplementation of 14.2&#xa0;g per day GOS/FOS was found to favourably modify both the maternal and the developing infant gut microbiome. These results build on our understanding of the importance of maternal diet during pregnancy, and indicate that it is possible to intervene and modify the development of the infant microbiome by dietary modulation of the maternal gut microbiome.}, }
@article {pmid38452399, year = {2024}, author = {Lucchetti, M and Aina, KO and Grandmougin, L and Jäger, C and Pérez Escriva, P and Letellier, E and Mosig, AS and Wilmes, P}, title = {An Organ-on-Chip Platform for Simulating Drug Metabolism Along the Gut-Liver Axis.}, journal = {Advanced healthcare materials}, volume = {13}, number = {20}, pages = {e2303943}, doi = {10.1002/adhm.202303943}, pmid = {38452399}, issn = {2192-2659}, support = {P500PB_214405//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; CORE/C20/BM/14591557//Fonds National de la Recherche Luxembourg and Fondation Cancer/ ; 390713860//Deutsche Forschungsgemeinschaft/ ; 031 L0247A//Bundesministerium f&#xfc;r Bildung und Forschung/ ; 812954//H2020 Marie Sk&#x142;odowska-Curie Actions/ ; }, mesh = {Humans ; *Irinotecan/pharmacokinetics ; *Liver/metabolism ; *Gastrointestinal Microbiome/physiology ; Lab-On-A-Chip Devices ; Tandem Mass Spectrometry/methods ; Chromatography, Liquid/methods ; }, abstract = {The human microbiome significantly influences drug metabolism through the gut-liver axis, leading to modified drug responses and potential toxicity. Due to the complex nature of the human gut environment, the understanding of microbiome-driven impacts on these processes is limited. To address this, a multiorgan-on-a-chip (MOoC) platform that combines the human microbial-crosstalk (HuMiX) gut-on-chip (GoC) and the Dynamic42 liver-on-chip (LoC), mimicking the bidirectional interconnection between the gut and liver known as the gut-liver axis, is introduced. This platform supports the viability and functionality of intestinal and liver cells. In a proof-of-concept study, the metabolism of irinotecan, a widely used colorectal cancer drug, is imitated within the MOoC. Utilizing liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), irinotecan metabolites are tracked, confirming the platform's ability to represent drug metabolism along the gut-liver axis. Further, using the authors' gut-liver platform, it is shown that the colorectal cancer-associated gut bacterium, Escherichia coli, modifies irinotecan metabolism through the transformation of its inactive metabolite SN-38G into its toxic metabolite SN-38. This platform serves as a robust tool for investigating the intricate interplay between gut microbes and pharmaceuticals, offering a representative alternative to animal models and providing novel drug development strategies.}, }
@article {pmid38450162, year = {2024}, author = {Bragazzi, NL and Woldegerima, WA and Siri, A}, title = {Economic microbiology: exploring microbes as agents in economic systems.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1305148}, pmid = {38450162}, issn = {1664-302X}, abstract = {Microbial communities exhibit striking parallels with economic markets, resembling intricate ecosystems where microorganisms engage in resource exchange akin to human market transactions. This dynamic network of resource swapping mirrors economic trade in human markets, with microbes specializing in metabolic functions much like businesses specializing in goods and services. Cooperation and competition are central dynamics in microbial communities, with alliances forming for mutual benefit and species vying for dominance, similar to businesses seeking market share. The human microbiome, comprising trillions of microorganisms within and on our bodies, is not only a marker of socioeconomic status but also a critical factor contributing to persistent health inequalities. Social and economic factors shape the composition of the gut microbiota, impacting healthcare access and quality of life. Moreover, these microbes exert indirect influence over human decisions by affecting neurotransmitter production, influencing mood, behavior, and choices related to diet and emotions. Human activities significantly impact microbial communities, from dietary choices and antibiotic use to environmental changes, disrupting these ecosystems. Beyond their natural roles, humans harness microbial communities for various applications, manipulating their interactions and resource exchanges to achieve specific goals in fields like medicine, agriculture, and environmental science. In conclusion, the concept of microbial communities as biological markets offers valuable insights into their intricate functioning and adaptability. It underscores the profound interplay between microbial ecosystems and human health and behavior, with far-reaching implications for multiple disciplines. To paraphrase Alfred Marshall, "the Mecca of the economist lies in economic microbiology."}, }
@article {pmid38441984, year = {2024}, author = {Greenzaid, JD and Chan, LJ and Chandani, BM and Kiritsis, NR and Feldman, SR}, title = {Microbiome modulators for atopic eczema: a systematic review of experimental and investigational therapeutics.}, journal = {Expert opinion on investigational drugs}, volume = {33}, number = {4}, pages = {415-430}, doi = {10.1080/13543784.2024.2326625}, pmid = {38441984}, issn = {1744-7658}, mesh = {*Dermatitis, Atopic/drug therapy/microbiology ; Humans ; *Probiotics/administration &amp; dosage/pharmacology ; Animals ; *Microbiota ; *Severity of Illness Index ; *Biological Products/pharmacology/administration &amp; dosage ; Staphylococcus aureus/isolation &amp; purification/drug effects ; Skin/microbiology ; Gastrointestinal Microbiome ; Th2 Cells/immunology ; Antibodies, Monoclonal ; }, abstract = {INTRODUCTION: Atopic dermatitis (AD) is a common inflammatory cutaneous disease that arises due to dysregulation of the Th2 immune response, impaired skin barrier integrity, and dysbiosis of the skin and gut microbiota. An abundance of Staphylococcus aureus biofilms in AD lesions increases the Th2 immune response, and gut bacteria release breakdown products such as Short Chain Fatty Acids that regulate the systemic immune response.<br><br>AREAS COVERED: We aim to evaluate therapies that modulate the microbiome in humans and discuss the clinical implications of these treatments. We performed a review of the literature in which 2,673 records were screened, and describe the findings of 108 studies that were included after full-text review. All included studies discussed the effects of therapies on the human microbiome and AD severity. Oral probiotics, topical probiotics, biologics, and investigational therapies were included in our analysis.<br><br>EXPERT OPINION: Oral probiotics demonstrate mixed efficacy at relieving AD symptoms. Topical probiotics reduce S. aureus abundance in AD lesional skin, yet for moderate-severe disease, these therapies may not reduce AD severity scores to the standard of biologics. Dupilumab and tralokinumab target key inflammatory pathways in AD and modulate the skin microbiome, further improving disease severity.}, }
@article {pmid38441977, year = {2024}, author = {Chen, H and Huang, S and Zhao, Y and Sun, R and Wang, J and Yao, S and Huang, J and Yu, Z}, title = {Metagenomic analysis of the intestinal microbiome reveals the potential mechanism involved in Bacillus amyloliquefaciens in treating schistosomiasis japonica in mice.}, journal = {Microbiology spectrum}, volume = {12}, number = {4}, pages = {e0373523}, pmid = {38441977}, issn = {2165-0497}, support = {32300051//MOST | National Natural Science Foundation of China (NSFC)/ ; 32170071//MOST | National Natural Science Foundation of China (NSFC)/ ; 82102428//MOST | National Natural Science Foundation of China (NSFC)/ ; 2022JJ40663//HSTD | Natural Science Foundation of Hunan Province ()/ ; }, mesh = {Animals ; Mice ; *Schistosomiasis japonica/drug therapy ; *Gastrointestinal Microbiome ; *Bacillus amyloliquefaciens ; Urease ; *Schistosoma japonicum/genetics ; Bacteria/genetics ; }, abstract = {UNLABELLED: Schistosomiasis japonica is one of the neglected tropical diseases characterized by chronic hepatic, intestinal granulomatous inflammation and fibrosis, as well as dysbiosis of intestinal microbiome. Previously, the probiotic Bacillus amyloliquefaciens has been shown to alleviate the pathological injuries in mice infected with Schistosoma japonicum by improving the disturbance of the intestinal microbiota. However, the underlying mechanisms involved in this process remain unclear. In this study, metagenomics sequencing and functional analysis were employed to investigate the differential changes in taxonomic composition and functional genes of the intestinal microbiome in S. japonicum-infected mice treated with B. amyloliquefaciens. The results revealed that intervention with B. amyloliquefaciens altered the taxonomic composition of the intestinal microbiota at the species level in infected mice and significantly increased the abundance of beneficial bacteria. Moreover, the abundance of predicted genes in the intestinal microbiome was also significantly changed, and the abundance of xfp/xpk and genes translated to urease was significantly restored. Further analysis showed that Limosilactobacillus reuteri was positively correlated with several KEGG Orthology (KO) genes and metabolic reactions, which might play important roles in alleviating the pathological symptoms caused by S. japonicum infection, indicating that it has the potential to function as another effective therapeutic agent for schistosomiasis. These data suggested that treatment of murine schistosomiasis japonica by B. amyloliquefaciens might be induced by alterations in the taxonomic composition and functional gene of the intestinal microbiome in mice. We hope this study will provide adjuvant strategies and methods for the early prevention and treatment of schistosomiasis japonica.<br><br>IMPORTANCE: Targeted interventions of probiotics on gut microbiome were used to explore the mechanism of alleviating schistosomiasis japonica. Through metagenomic analysis, there were significant changes in the composition of gut microbiota in mice infected with Schistosoma japonicum and significant increase in the abundance of beneficial bacteria after the intervention of Bacillus amyloliquefaciens. At the same time, the abundance of functional genes was found to change significantly. The abundance of genes related to urease metabolism and xfp/xpk related to D-erythrose 4-phosphate production was significantly restored, highlighting the importance of Limosilactobacillus reuteri in the recovery and abundance of predicted genes of the gut microbiome. These results indicated potential regulatory mechanism between the gene function of gut microbiome and host immune response. Our research lays the foundation for elucidating the regulatory mechanism of probiotic intervention in alleviating schistosomiasis japonica, and provides potential adjuvant treatment strategies for early prevention and treatment of schistosomiasis japonica.}, }
@article {pmid38440794, year = {2024}, author = {Favero, G and Gianò, M and Franco, C and Pinto, D and van Noorden, CJF and Rinaldi, F and Rezzani, R}, title = {Relation Between Reactive Oxygen Species Production and Transient Receptor Potential Vanilloid1 Expression in Human Skin During Aging.}, journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society}, volume = {72}, number = {3}, pages = {157-171}, pmid = {38440794}, issn = {1551-5044}, mesh = {Adult ; Aged ; Humans ; Aging ; *Endothelial Cells/metabolism ; Epidermis ; Keratinocytes ; Reactive Oxygen Species/metabolism ; *Skin/metabolism ; }, abstract = {Skin sensitivity and impaired epidermal barrier function are associated with aging and are at least partly due to increased production of reactive oxygen species (ROS). Transient receptor potential vanilloid1 (TRPV1) is expressed in keratinocytes, fibroblasts, mast cells, and endothelial cells in skin. We investigated in skin biopsies of adult and elderly donors whether TRPV1 expression is involved in the skin aging process. We found that aging skin showed a strongly reduced epidermal thickness, strongly increased oxidative stress, protease expression, and mast cell degranulation and strongly increased TRPV1 expression both in epidermis and dermis. Based on our findings, the aging-related changes observed in the epidermis of the skin level are associated with increased ROS production, and hypothesized alterations in TRPV1 expression are mechanistically linked to this process.}, }
@article {pmid38436256, year = {2024}, author = {Ling, J and Hryckowian, AJ}, title = {Re-framing the importance of Group B Streptococcus as a gut-resident pathobiont.}, journal = {Infection and immunity}, volume = {92}, number = {9}, pages = {e0047823}, pmid = {38436256}, issn = {1098-5522}, support = {R35 GM150996/GM/NIGMS NIH HHS/United States ; R35GM150996//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; DGE-2137424//NSF | National Science Foundation Graduate Research Fellowship Program (GRFP)/ ; 1U48DP006383//UW-Madison Prevention Research Center/ ; Gift//Judy L. and Sal A. Troia/ ; }, mesh = {*Streptococcus agalactiae ; Humans ; *Streptococcal Infections/microbiology ; *Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/microbiology ; Animals ; }, abstract = {Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial species that causes disease in humans across the lifespan. While antibiotics are used to mitigate GBS infections, it is evident that antibiotics disrupt human microbiomes (which can predispose people to other diseases later in life), and antibiotic resistance in GBS is on the rise. Taken together, these unintended negative impacts of antibiotics highlight the need for precision approaches for minimizing GBS disease. One possible approach involves selectively depleting GBS in its commensal niches before it can cause disease at other body sites or be transmitted to at-risk individuals. One understudied commensal niche of GBS is the adult gastrointestinal (GI) tract, which may predispose colonization at other body sites in individuals at risk for GBS disease. However, a better understanding of the host-, microbiome-, and GBS-determined variables that dictate GBS GI carriage is needed before precise GI decolonization approaches can be developed. In this review, we synthesize current knowledge of the diverse body sites occupied by GBS as a pathogen and as a commensal. We summarize key molecular factors GBS utilizes to colonize different host-associated niches to inform future efforts to study GBS in the GI tract. We also discuss other GI commensals that are pathogenic in other body sites to emphasize the broader utility of precise de-colonization approaches for mitigating infections by GBS and other bacterial pathogens. Finally, we highlight how GBS treatments could be improved with a more holistic understanding of GBS enabled by continued GI-focused study.}, }
@article {pmid38432422, year = {2024}, author = {Murali, SK and Mansell, TJ}, title = {Next generation probiotics: Engineering live biotherapeutics.}, journal = {Biotechnology advances}, volume = {72}, number = {}, pages = {108336}, doi = {10.1016/j.biotechadv.2024.108336}, pmid = {38432422}, issn = {1873-1899}, mesh = {Humans ; *Probiotics/therapeutic use ; Prebiotics ; *Microbiota ; }, abstract = {The population dynamics of the human microbiome have been associated with inflammatory bowel disease, cancer, obesity, autoimmune diseases, and many other human disease states. An emerging paradigm in treatment is the administration of live engineered organisms, also called next-generation probiotics. However, the efficacy of these microbial therapies can be limited by the organism's overall performance in the harsh and nutrient-limited environment of the gut. In this review, we summarize the current state of the art use of bacterial and yeast strains as probiotics, highlight the recent development of genetic tools for engineering new therapeutic functions in these organisms, and report on the latest therapeutic applications of engineered probiotics, including recent clinical trials. We also discuss the supplementation of prebiotics as a method of manipulating the microbiome and improving the overall performance of engineered live biotherapeutics.}, }
@article {pmid38430912, year = {2024}, author = {Fang, S and Luo, Z and Wei, Z and Qin, Y and Zheng, J and Zhang, H and Jin, J and Li, J and Miao, C and Yang, S and Li, Y and Liang, Z and Yu, XD and Zhang, XM and Xiong, W and Zhu, H and Gan, WB and Huang, L and Li, B}, title = {Sexually dimorphic control of affective state processing and empathic behaviors.}, journal = {Neuron}, volume = {112}, number = {9}, pages = {1498-1517.e8}, doi = {10.1016/j.neuron.2024.02.001}, pmid = {38430912}, issn = {1097-4199}, mesh = {Animals ; Male ; Female ; Mice ; *Sex Characteristics ; *Empathy/physiology ; Piriform Cortex/physiology/metabolism ; Cues ; Mice, Inbred C57BL ; Affect/physiology ; Neurons/physiology/metabolism ; Behavior, Animal/physiology ; }, abstract = {Recognizing the affective states of social counterparts and responding appropriately fosters successful social interactions. However, little is known about how the affective states are expressed and perceived and how they influence social decisions. Here, we show that male and female mice emit distinct olfactory cues after experiencing distress. These cues activate distinct neural circuits in the piriform cortex (PiC) and evoke sexually dimorphic empathic behaviors in observers. Specifically, the PiC → PrL pathway is activated in female observers, inducing a social preference for the distressed counterpart. Conversely, the PiC → MeA pathway is activated in male observers, evoking excessive self-grooming behaviors. These pathways originate from non-overlapping PiC neuron populations with distinct gene expression signatures regulated by transcription factors and sex hormones. Our study unveils how internal states of social counterparts are processed through sexually dimorphic mechanisms at the molecular, cellular, and circuit levels and offers insights into the neural mechanisms underpinning sex differences in higher brain functions.}, }
@article {pmid38429112, year = {2024}, author = {Pust, MM and Rocha Castellanos, DM and Rzasa, K and Dame, A and Pishchany, G and Assawasirisin, C and Liss, A and Fernandez-Del Castillo, C and Xavier, RJ}, title = {Absence of a pancreatic microbiome in intraductal papillary mucinous neoplasm.}, journal = {Gut}, volume = {73}, number = {7}, pages = {1131-1141}, pmid = {38429112}, issn = {1468-3288}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; *Microbiota ; *Pancreatic Neoplasms/microbiology/pathology ; Aged ; Middle Aged ; *Pancreatic Intraductal Neoplasms/microbiology/pathology ; *RNA, Ribosomal, 16S ; Carcinoma, Pancreatic Ductal/microbiology/pathology ; Cyst Fluid/microbiology ; Adenocarcinoma, Mucinous/microbiology/pathology ; Aged, 80 and over ; Pancreas/microbiology ; Adult ; }, abstract = {OBJECTIVE: This study aims to validate the existence of a microbiome within intraductal papillary mucinous neoplasm (IPMN) that can be differentiated from the taxonomically diverse DNA background of next-generation sequencing procedures.<br><br>DESIGN: We generated 16S rRNA amplicon sequencing data to analyse 338 cyst fluid samples from 190 patients and 19 negative controls, the latter collected directly from sterile syringes in the operating room. A subset of samples (n=20) and blanks (n=5) were spiked with known concentrations of bacterial cells alien to the human microbiome to infer absolute abundances of microbial traces. All cyst fluid samples were obtained intraoperatively and included IPMNs with various degrees of dysplasia as well as other cystic neoplasms. Follow-up culturing experiments were conducted to assess bacterial growth for microbiologically significant signals.<br><br>RESULTS: Microbiome signatures of cyst fluid samples were inseparable from those of negative controls, with no difference in taxonomic diversity, and microbial community composition. In a patient subgroup that had recently undergone invasive procedures, a bacterial signal was evident. This outlier signal was not characterised by higher taxonomic diversity but by an increased dominance index of a gut-associated microbe, leading to lower taxonomic evenness compared with the background signal.<br><br>CONCLUSION: The 'microbiome' of IPMNs and other pancreatic cystic neoplasms does not deviate from the background signature of negative controls, supporting the concept of a sterile environment. Outlier signals may appear in a small fraction of patients following recent invasive endoscopic procedures. No associations between microbial patterns and clinical or cyst parameters were apparent.}, }
@article {pmid38426063, year = {2024}, author = {Argentini, C and Lugli, GA and Tarracchini, C and Fontana, F and Mancabelli, L and Viappiani, A and Anzalone, R and Angelini, L and Alessandri, G and Longhi, G and Bianchi, MG and Taurino, G and Bussolati, O and Milani, C and van Sinderen, D and Turroni, F and Ventura, M}, title = {Genomic and ecological approaches to identify the Bifidobacterium breve prototype of the healthy human gut microbiota.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1349391}, pmid = {38426063}, issn = {1664-302X}, abstract = {Members of the genus Bifidobacterium are among the first microorganisms colonizing the human gut. Among these species, strains of Bifidobacterium breve are known to be commonly transmitted from mother to her newborn, while this species has also been linked with activities supporting human wellbeing. In the current study, an in silico approach, guided by ecology- and phylogenome-based analyses, was employed to identify a representative strain of B. breve to be exploited as a novel health-promoting candidate. The selected strain, i.e., B. breve PRL2012, was found to well represent the genetic content and functional genomic features of the B. breve taxon. We evaluated the ability of PRL2012 to survive in the gastrointestinal tract and to interact with other human gut commensal microbes. When co-cultivated with various human gut commensals, B. breve PRL2012 revealed an enhancement of its metabolic activity coupled with the activation of cellular defense mechanisms to apparently improve its survivability in a simulated ecosystem resembling the human microbiome.}, }
@article {pmid38424056, year = {2024}, author = {Istvan, P and Birkeland, E and Avershina, E and Kværner, AS and Bemanian, V and Pardini, B and Tarallo, S and de Vos, WM and Rognes, T and Berstad, P and Rounge, TB}, title = {Exploring the gut DNA virome in fecal immunochemical test stool samples reveals associations with lifestyle in a large population-based study.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {1791}, pmid = {38424056}, issn = {2041-1723}, support = {198048//Kreftforeningen (Norwegian Cancer Society)/ ; 190179//Kreftforeningen (Norwegian Cancer Society)/ ; 2022067//Ministry of Health and Care Services | Helse S&#xf8;r-&#xd8;st RHF (Southern and Eastern Norway Regional Health Authority)/ ; }, mesh = {Humans ; Virome ; DNA Viruses/genetics ; *Viruses/genetics ; DNA ; *Colorectal Neoplasms/diagnosis/genetics ; }, abstract = {Stool samples for fecal immunochemical tests (FIT) are collected in large numbers worldwide as part of colorectal cancer screening programs. Employing FIT samples from 1034 CRCbiome participants, recruited from a Norwegian colorectal cancer screening study, we identify, annotate and characterize more than 18000 DNA viruses, using shotgun metagenome sequencing. Only six percent of them are assigned to a known taxonomic family, with Microviridae being the most prevalent viral family. Linking individual profiles to comprehensive lifestyle and demographic data shows 17/25 of the variables to be associated with the gut virome. Physical activity, smoking, and dietary fiber consumption exhibit strong and consistent associations with both diversity and relative abundance of individual viruses, as well as with enrichment for auxiliary metabolic genes. We demonstrate the suitability of FIT samples for virome analysis, opening an opportunity for large-scale studies of this enigmatic part of the gut microbiome. The diverse viral populations and their connections to the individual lifestyle uncovered herein paves the way for further exploration of the role of the gut virome in health and disease.}, }
@article {pmid38422909, year = {2024}, author = {Cena, JA and Belmok, A and Kyaw, CM and Dame-Teixeira, N}, title = {The Archaea domain: Exploring historical and contemporary perspectives with in silico primer coverage analysis for future research in Dentistry.}, journal = {Archives of oral biology}, volume = {161}, number = {}, pages = {105936}, doi = {10.1016/j.archoralbio.2024.105936}, pmid = {38422909}, issn = {1879-1506}, mesh = {Humans ; *Archaea/genetics ; Bacteria ; *Microbiota ; Mouth ; Dentistry ; Phylogeny ; }, abstract = {OBJECTIVE: The complete picture of how the human microbiome interacts with its host is still largely unknown, particularly concerning microorganisms beyond bacteria. Although existing in very low abundance and not directly linked to causing diseases, archaea have been detected in various sites of the human body, including the gastrointestinal tract, oral cavity, skin, eyes, respiratory and urinary systems. But what exactly are these microorganisms? In the early 1990 s, archaea were classified as a distinct domain of life, sharing a more recent common ancestor with eukaryotes than with bacteria. While archaea's presence and potential significance in Dentistry remain under-recognized, there are concerns that they may contribute to oral dysbiosis. However, detecting archaea in oral samples presents challenges, including difficulties in culturing, the selection of DNA extraction methods, primer design, bioinformatic analysis, and databases.<br><br>DESIGN: This is a comprehensive review on the oral archaeome, presenting an in-depth in silico analysis of various primers commonly used for detecting archaea in human body sites.<br><br>RESULTS: Among several primer pairs used for detecting archaea in human samples across the literature, only one specifically designed for detecting methanogenic archaea in stool samples, exhibited exceptional coverage levels for the domain and various archaea phyla.<br><br>CONCLUSIONS: Our in silico analysis underscores the need for designing new primers targeting not only methanogenic archaea but also nanoarchaeal and thaumarchaeota groups to gain a comprehensive understanding of the archaeal oral community. By doing so, researchers can pave the way for further advancements in the field of oral archaeome research.}, }
@article {pmid38419554, year = {2024}, author = {Korpela, K and Hurley, S and Ford, SA and Franklin, R and Byrne, S and Lunjani, N and Forde, B and Neogi, U and Venter, C and Walter, J and Hourihane, J and O'Mahony, L and , }, title = {Association between gut microbiota development and allergy in infants born during pandemic-related social distancing restrictions.}, journal = {Allergy}, volume = {79}, number = {7}, pages = {1938-1951}, doi = {10.1111/all.16069}, pmid = {38419554}, issn = {1398-9995}, support = {/SFI_/Science Foundation Ireland/Ireland ; //Childrens Health Ireland/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19/prevention &amp; control/epidemiology ; Infant ; Female ; *Hypersensitivity/epidemiology/etiology ; Male ; *SARS-CoV-2 ; Feces/microbiology ; Physical Distancing ; Pandemics ; Environmental Exposure/adverse effects ; Child, Preschool ; Cohort Studies ; }, abstract = {BACKGROUND: Several hypotheses link reduced microbial exposure to increased prevalence of allergies. Here we capitalize on the opportunity to study a cohort of infants (CORAL), raised during COVID-19 associated social distancing measures, to identify the environmental exposures and dietary factors that contribute to early life microbiota development and to examine their associations with allergic outcomes.<br><br>METHODS: Fecal samples were sequenced from infants at 6 (n&#x2009;=&#x2009;351) and repeated at 12 (n&#x2009;=&#x2009;343) months, using 16S sequencing. Published 16S data from pre-pandemic cohorts were included for microbiota comparisons. Online questionnaires collected epidemiological information on home environment, healthcare utilization, infant health, allergic diseases, and diet. Skin prick testing (SPT) was performed at 12 (n&#x2009;=&#x2009;343) and 24 (n&#x2009;=&#x2009;320) months of age, accompanied by atopic dermatitis and food allergy assessments.<br><br>RESULTS: The relative abundance of bifidobacteria was higher, while environmentally transmitted bacteria such as Clostridia was lower in CORAL infants compared to previous cohorts. The abundance of multiple Clostridia taxa correlated with a microbial exposure index. Plant based foods during weaning positively impacted microbiota development. Bifidobacteria levels at 6&#x2009;months of age, and relative abundance of butyrate producers at 12&#x2009;months of age, were negatively associated with AD and SPT positivity. The prevalence of allergen sensitization, food allergy, and AD did not increase over pre-pandemic levels.<br><br>CONCLUSIONS: Environmental exposures and dietary components significantly impact microbiota community assembly. Our results also suggest that vertically transmitted bacteria and appropriate dietary supports may be more important than exposure to environmental microbes alone for protection against allergic diseases in infancy.}, }
@article {pmid38416678, year = {2024}, author = {Schwartzman, JA and Lebreton, F and Salamzade, R and Shea, T and Martin, MJ and Schaufler, K and Urhan, A and Abeel, T and Camargo, ILBC and Sgardioli, BF and Prichula, J and Guedes Frazzon, AP and Giribet, G and Van Tyne, D and Treinish, G and Innis, CJ and Wagenaar, JA and Whipple, RM and Manson, AL and Earl, AM and Gilmore, MS}, title = {Global diversity of enterococci and description of 18 previously unknown species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {10}, pages = {e2310852121}, pmid = {38416678}, issn = {1091-6490}, support = {F32 GM121005/GM/NIGMS NIH HHS/United States ; P01 AI083214/AI/NIAID NIH HHS/United States ; R01 AI165519/AI/NIAID NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Enterococcus/genetics ; Anti-Bacterial Agents/pharmacology ; *Enterococcus faecium/genetics ; Enterococcus faecalis/genetics ; Phylogeny ; Microbial Sensitivity Tests ; *Gram-Positive Bacterial Infections ; Drug Resistance, Bacterial ; }, abstract = {Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving hosts and host diets. Over 60 enterococcal species are now known. Two species, Enterococcus faecalis and Enterococcus faecium, are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by >25%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition. Enterococcus faecalis and E. faecium were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus Enterococcus, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found.}, }
@article {pmid38409417, year = {2024}, author = {Raslan, MA and Raslan, SA and Shehata, EM and Mahmoud, AS and Viana, MVC and Aburjaile, F and Barh, D and Sabri, NA and Azevedo, V}, title = {Mass Spectrometry Applications to Study Human Microbiome.}, journal = {Advances in experimental medicine and biology}, volume = {1443}, number = {}, pages = {87-101}, pmid = {38409417}, issn = {0065-2598}, mesh = {Humans ; *Microbiota ; Mass Spectrometry/methods ; *Gastrointestinal Microbiome ; Metabolomics/methods ; High-Throughput Nucleotide Sequencing ; }, abstract = {Microbiotas are an adaptable component of ecosystems, including human ecology. Microorganisms influence the chemistry of their specialized niche, such as the human gut, as well as the chemistry of distant surroundings, such as other areas of the body. Metabolomics based on mass spectrometry (MS) is one of the primary methods for detecting and identifying small compounds generated by the human microbiota, as well as understanding the functional significance of these microbial metabolites. This book chapter gives basic knowledge on the kinds of untargeted mass spectrometry as well as the data types that may be generated in the context of microbiome study. While data analysis remains a barrier, the emphasis is on data analysis methodologies and integrative analysis, particularly the integration of microbiome sequencing data. Mass spectrometry (MS)-based techniques have resurrected culture methods for studying the human gut microbiota, filling in the gaps left by high-throughput sequencing methods in terms of culturing minor populations.}, }
@article {pmid38401105, year = {2024}, author = {Vijayanna, ST and Mane, S and Bhalerao, S and Jaideep, SS}, title = {Ayurvedic Therapies to Target the Microbiome: Evidence and Possibilities.}, journal = {Alternative therapies in health and medicine}, volume = {30}, number = {2}, pages = {76-83}, pmid = {38401105}, issn = {1078-6791}, mesh = {Humans ; Medicine, Ayurvedic ; *Microbiota ; *Gastrointestinal Microbiome ; India ; Life Style ; }, abstract = {CONTEXT: The microbiome is a constantly evolving entity, being influenced by diet, lifestyle, age, genetics, medication, and environment; keeping the microbiome in good health is a step toward better health for the body. Ayurveda emphasizes a healthy internal milieu that synchronizes with the circadian and seasonal rhythms, in addition to reacting to other stressors.<br><br>OBJECTIVE: The current review intended to provide an overview of Ayurvedic principles related to health and disease and their management and to briefly discuss the current understanding of the human microbiome and explore Ayurvedic herbs and therapies that have been studied for their effects on the microbiome.<br><br>DESIGN: The team included researchers in India and Canada. A Pubmed search was performed using the keywords Ayurveda therapies, Ayurvedic therapies, Gut microbiome, Panchakarma, Therapeutic purgation, Therapeutic emesis, medicated enema.<br><br>RESULTS: Research connecting Ayurvedic interventions and the gut microbiome is yet in a nascent stage. Several Ayurvedic herbs have been researched for their potential in altering the gut microbiome. Among the Ayurvedic therapies, virechana (therapeutic purgation) and basti (medicated enema) have been studied for their gut microbiome altering effects. However, the limited number of such studies prevents from drawing categorical conclusions currently, about the effects of Ayurvedic Panchakarma therapy on the human microbiome.<br><br>CONCLUSIONS: Studying where and how the Ayurvedic herbs and therapies can exert their influence on the human microbiome provides a challenging yet novel opportunity and can help address multiple health and disease conditions.}, }
@article {pmid38400752, year = {2024}, author = {He, Z and Xie, H and Xu, H and Wu, J and Zeng, W and He, Q and Jobin, C and Jin, S and Lan, P}, title = {Chemotherapy-induced microbiota exacerbates the toxicity of chemotherapy through the suppression of interleukin-10 from macrophages.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2319511}, pmid = {38400752}, issn = {1949-0984}, mesh = {Humans ; Mice ; Animals ; Oxaliplatin/toxicity ; Interleukin-10/genetics ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Macrophages ; *Probiotics/pharmacology/therapeutic use ; *Antineoplastic Agents/adverse effects ; }, abstract = {The gut microbiota has been shown to influence the efficacy and toxicity of chemotherapy, thereby affecting treatment outcomes. Understanding the mechanism by which microbiota affects chemotherapeutic toxicity would have a profound impact on cancer management. In this study, we report that fecal microbiota transplantation from oxaliplatin-exposed mice promotes toxicity in recipient mice. Splenic RNA sequencing and macrophage depletion experiment showed that the microbiota-induced toxicity of oxaliplatin in mice was dependent on macrophages. Furthermore, oxaliplatin-mediated toxicity was exacerbated in Il10[-/-] mice, but not attenuated in Rag1[-/-] mice. Adoptive transfer of macrophage into Il10[-/-] mice confirmed the role of macrophage-derived IL-10 in the improvement of oxaliplatin-induced toxicity. Depletion of fecal Lactobacillus and Bifidobacterium was associated with the exacerbation of oxaliplatin-mediated toxicity, whereas supplementation with these probiotics alleviated chemotherapy-induced toxicity. Importantly, IL-10 administration and probiotics supplementation did not attenuate the antitumor efficacy of chemotherapy. Clinically, patients with colorectal cancer exposed to oxaliplatin exhibited downregulation of peripheral CD45[+]IL-10[+] cells. Collectively, our findings indicate that microbiota-mediated IL-10 production influences tolerance to chemotherapy, and thus represents a potential clinical target.}, }
@article {pmid38398875, year = {2024}, author = {Simões, R and Ribeiro, AC and Dias, R and Freitas, V and Soares, S and Pérez-Gregorio, R}, title = {Unveiling the Immunomodulatory Potential of Phenolic Compounds in Food Allergies.}, journal = {Nutrients}, volume = {16}, number = {4}, pages = {}, pmid = {38398875}, issn = {2072-6643}, mesh = {Humans ; *Food Hypersensitivity ; Allergens ; Food ; Diet ; Phenols/pharmacology ; Mouth/pathology ; }, abstract = {Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.}, }
@article {pmid38397866, year = {2024}, author = {Longo, S and Del Chierico, F and Scanu, M and Toto, F and Legramante, JM and Rizza, S and Putignani, L and Federici, M}, title = {An Investigation of Metabolic Risk Factors and Gut Microbiota in Unexplained Syncope.}, journal = {Biomedicines}, volume = {12}, number = {2}, pages = {}, pmid = {38397866}, issn = {2227-9059}, support = {2017FM74HK//Ministry of University and Research (MUR) Progetti di Ricerca di Interesse Nazionale (PRIN)/ ; 875534//SOPHIA Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement/ ; ARS01_00876//PON BIO-D/ ; PE00000019//MUR-PNRR M4C2I1.3 PE6 project/ ; DM1062//RTDa contract/ ; }, abstract = {BACKGROUND: The pathogenesis of many syncopal episodes remains unexplained. Intestinal dysbiosis could be involved in the pathophysiological mechanisms of syncope due to its connection with the central nervous system via the microbiota-gut-brain axis. This pilot study aimed to explore the specific cardiometabolic risk factors and gut microbiota in unexplained syncope (US), compared to other types of syncope, to assess their similarity or verify their different origins.<br><br>METHODS: We studied 86 participants with syncope, who were divided into four groups: an orthostatic syncope group (OH, n = 24), a neuromediated syncope group (NMS, n = 26), a cardiological syncope group (CS, n = 9), and an unexplained syncope group (US, n = 27). We evaluated the anthropometric, clinical, and metabolic characteristics of the four groups; the &#x3b1;- and &#x3b2;-diversity; and the differences in the abundance of the microbial taxa.<br><br>RESULTS: The US group had a lower incidence of systolic hypertension at the first visit and a lower frequency of patients with nocturnal hypertension than the CS group. Compared to the OH and NMS groups, the US group had a higher incidence of carotid plaques and greater carotid intima-media thickness, respectively. The microbiota differed significantly between the US and CS groups, but not between the US group and the OH or NMS group.<br><br>CONCLUSIONS: We observed significant differences in the gut microbiota between CS and US. Future studies are necessary to evaluate the involvement of the gut microbiota in the complex pathogenesis of syncope and whether its analysis could support the interpretation of the pathophysiological mechasnisms underlying some episodes classifiable as US.}, }
@article {pmid38396668, year = {2024}, author = {Efremova, I and Maslennikov, R and Poluektova, E and Medvedev, O and Kudryavtseva, A and Krasnov, G and Fedorova, M and Romanikhin, F and Bakhitov, V and Aliev, S and Sedova, N and Kuropatkina, T and Ivanova, A and Zharkova, M and Pervushova, E and Ivashkin, V}, title = {Gut Microbiota and Biomarkers of Endothelial Dysfunction in Cirrhosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {4}, pages = {}, pmid = {38396668}, issn = {1422-0067}, support = {National Research Grant Russia 2019//Biocodex (France)/ ; }, mesh = {Humans ; *Hepatic Encephalopathy ; Ascites ; *Gastrointestinal Microbiome/genetics ; *Hypoalbuminemia ; RNA, Ribosomal, 16S ; Claudin-3 ; Endothelin-1 ; Nitrites ; Liver Cirrhosis/complications ; Biomarkers ; Sodium ; Dysbiosis/complications ; Peptide Fragments ; Lipopolysaccharide Receptors ; }, abstract = {Our aim was to study the association of endothelial dysfunction biomarkers with cirrhosis manifestations, bacterial translocation, and gut microbiota taxa. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of nitrite, big endothelin-1, asymmetric dimethylarginine (ADMA), presepsin, and claudin were measured as biomarkers of endothelial dysfunction, bacterial translocation, and intestinal barrier dysfunction. An echocardiography with simultaneous determination of blood pressure and heart rate was performed to evaluate hemodynamic parameters. Presepsin, claudin 3, nitrite, and ADMA levels were higher in cirrhosis patients than in controls. Elevated nitrite levels were associated with high levels of presepsin and claudin 3, the development of hemodynamic circulation, hypoalbuminemia, grade 2-3 ascites, overt hepatic encephalopathy, high mean pulmonary artery pressure, increased abundance of Proteobacteria and Erysipelatoclostridium, and decreased abundance of Oscillospiraceae, Subdoligranulum, Rikenellaceae, Acidaminococcaceae, Christensenellaceae, and Anaerovoracaceae. Elevated ADMA levels were associated with higher Child-Pugh scores, lower serum sodium levels, hypoalbuminemia, grade 2-3 ascites, milder esophageal varices, overt hepatic encephalopathy, lower mean pulmonary artery pressure, and low abundance of Erysipelotrichia and Erysipelatoclostridiaceae. High big endothelin-1 levels were associated with high levels of presepsin and sodium, low levels of fibrinogen and cholesterol, hypocoagulation, increased Bilophila and Coprobacillus abundances, and decreased Alloprevotella abundance.}, }
@article {pmid38394022, year = {2024}, author = {Mayes, C and Morar, N}, title = {Environmental Injustices within Us: The Case of the Human Microbiome and the Need for More Creative Bioethics.}, journal = {The American journal of bioethics : AJOB}, volume = {24}, number = {3}, pages = {67-70}, doi = {10.1080/15265161.2024.2303135}, pmid = {38394022}, issn = {1536-0075}, mesh = {Humans ; *Bioethics ; Social Justice/ethics ; *Microbiota ; }, }
@article {pmid38392903, year = {2024}, author = {Babar, S and Liu, E and Kaur, S and Hussain, J and Danaher, PJ and Anstead, GM}, title = {Pseudopropionibacterium propionicum as a Cause of Empyema; A Diagnosis with Next-Generation Sequencing.}, journal = {Pathogens (Basel, Switzerland)}, volume = {13}, number = {2}, pages = {}, pmid = {38392903}, issn = {2076-0817}, support = {n/a//MicroGenDX/ ; }, mesh = {Humans ; Male ; Aged ; *High-Throughput Nucleotide Sequencing ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Empyema/microbiology/diagnosis ; Gram-Positive Bacterial Infections/diagnosis/microbiology/drug therapy ; }, abstract = {Pseudopropionibacterium propionicum (P.p.) is an anaerobic, Gram-positive, branching beaded rod that is a component of the human microbiome. An infection of the thoracic cavity with P.p. can mimic tuberculosis (TB), nocardiosis, and malignancy. We present a case of a 77-year-old male who presented with dyspnea and a productive cough who was initially misdiagnosed with TB based on positive acid-fast staining of a pleural biopsy specimen and an elevated adenosine deaminase level of the pleural fluid. He was then diagnosed with nocardiosis based on the Gram stain of his pleural fluid that showed a Gram-positive beaded and branching rod. The pleural fluid specimen was culture-negative, but the diagnosis of thoracic P.p. infection was determined with next-generation sequencing (NGS). The patient was initially treated with imipenem and minocycline, then ceftriaxone and minocycline, and later changed to minocycline only. This report shows the utility of NGS in making a microbiological diagnosis when other techniques either failed to provide a result (culture) or gave misleading information (histopathologic exam, pleural fluid adenosine deaminase determination, and organism morphology on Gram stain).}, }
@article {pmid38392650, year = {2024}, author = {Kamel, M and Aleya, S and Alsubih, M and Aleya, L}, title = {Microbiome Dynamics: A Paradigm Shift in Combatting Infectious Diseases.}, journal = {Journal of personalized medicine}, volume = {14}, number = {2}, pages = {}, pmid = {38392650}, issn = {2075-4426}, support = {RGP2/343/44//Deanship of Scientific Research at King Khalid University/ ; }, abstract = {Infectious diseases have long posed a significant threat to global health and require constant innovation in treatment approaches. However, recent groundbreaking research has shed light on a previously overlooked player in the pathogenesis of disease-the human microbiome. This review article addresses the intricate relationship between the microbiome and infectious diseases and unravels its role as a crucial mediator of host-pathogen interactions. We explore the remarkable potential of harnessing this dynamic ecosystem to develop innovative treatment strategies that could revolutionize the management of infectious diseases. By exploring the latest advances and emerging trends, this review aims to provide a new perspective on combating infectious diseases by targeting the microbiome.}, }
@article {pmid38391403, year = {2024}, author = {Nguyen, M and Ahn, P and Dawi, J and Gargaloyan, A and Kiriaki, A and Shou, T and Wu, K and Yazdan, K and Venketaraman, V}, title = {The Interplay between Mycobacterium tuberculosis and Human Microbiome.}, journal = {Clinics and practice}, volume = {14}, number = {1}, pages = {198-213}, pmid = {38391403}, issn = {2039-7275}, abstract = {Tuberculosis (TB), a respiratory disease caused by Mycobacterium tuberculosis (Mtb), is a significant cause of mortality worldwide. The lung, a breeding ground for Mtb, was once thought to be a sterile environment, but has now been found to host its own profile of microbes. These microbes are critical in the development of the host immune system and can produce metabolites that aid in host defense against various pathogens. Mtb infection as well as antibiotics can shift the microbial profile, causing dysbiosis and dampening the host immune response. Additionally, increasing cases of drug resistant TB have impacted the success rates of the traditional therapies of isoniazid, rifampin, pyrazinamide, and ethambutol. Recent years have produced tremendous research into the human microbiome and its role in contributing to or attenuating disease processes. Potential treatments aimed at altering the gut-lung bacterial axis may offer promising results against drug resistant TB and help mitigate the effects of TB.}, }
@article {pmid38390467, year = {2024}, author = {Acosta-Pagán, K and Bolaños-Rosero, B and Pérez, C and Ortíz, AP and Godoy-Vitorino, F}, title = {Ecological competition in the oral mycobiome of Hispanic adults living in Puerto Rico associates with periodontitis.}, journal = {Journal of oral microbiology}, volume = {16}, number = {1}, pages = {2316485}, pmid = {38390467}, issn = {2000-2297}, support = {P20 GM103475/GM/NIGMS NIH HHS/United States ; U54 GM133807/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: Fungi are a major component of the human microbiome that only recently received attention. The imbalance of indigenous fungal communities and environmental fungi present in the oral cavity may have a role in oral dysbiosis, which could exacerbate oral inflammatory diseases. Methods: We performed a cross-sectional study and recruited 88 participants aged 21 to 49 from sexually transmitted infection clinics in Puerto Rico. A full-mouth periodontal examination following the NHANES protocol defined periodontal severity (CDC/AAP). ITS2 (fungal) genes were amplified and sequenced for mycobiota characterization of yeast and environmental fungi. Environmental outdoor spore levels were measured daily by the American Academy of Allergy Asthma and Immunology San Juan station and defined by quartiles as spore scores. Results: Our data indicate polymicrobial colonization of yeast and environmental fungi in the oral cavity. Dominant taxa associated with periodontal disease included Saccharomyces cerevisiae, Rigidoporus vinctus, and Aspergillus penicilloides, while Candida albicans were found to be ubiquitous. Fungal aerosols were found to impact the oral cavity biofilm, likely due to competition and neutralization by inhaled outdoor and indoor fungal spores. Conclusion: To our knowledge, this is the first report showcasing the ecological competition of measured outdoor environmental fungi with the human oral mycobiota.}, }
@article {pmid38390219, year = {2023}, author = {Mortazavi, SMJ and Said-Salman, I and Mortazavi, AR and El Khatib, S and Sihver, L}, title = {How the adaptation of the human microbiome to harsh space environment can determine the chances of success for a space mission to Mars and beyond.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1237564}, pmid = {38390219}, issn = {1664-302X}, abstract = {The ability of human cells to adapt to space radiation is essential for the well-being of astronauts during long-distance space expeditions, such as voyages to Mars or other deep space destinations. However, the adaptation of the microbiomes should not be overlooked. Microorganisms inside an astronaut's body, or inside the space station or other spacecraft, will also be exposed to radiation, which may induce resistance to antibiotics, UV, heat, desiccation, and other life-threatening factors. Therefore, it is essential to consider the potential effects of radiation not only on humans but also on their microbiomes to develop effective risk reduction strategies for space missions. Studying the human microbiome in space missions can have several potential benefits, including but not limited to a better understanding of the major effects space travel has on human health, developing new technologies for monitoring health and developing new radiation therapies and treatments. While radioadaptive response in astronauts' cells can lead to resistance against high levels of space radiation, radioadaptive response in their microbiome can lead to resistance against UV, heat, desiccation, antibiotics, and radiation. As astronauts and their microbiomes compete to adapt to the space environment. The microorganisms may emerge as the winners, leading to life-threatening situations due to lethal infections. Therefore, understanding the magnitude of the adaptation of microorganisms before launching a space mission is crucial to be able to develop effective strategies to mitigate the risks associated with radiation exposure. Ensuring the safety and well-being of astronauts during long-duration space missions and minimizing the risks linked with radiation exposure can be achieved by adopting this approach.}, }
@article {pmid38388538, year = {2024}, author = {Cao, Z and Fan, D and Sun, Y and Huang, Z and Li, Y and Su, R and Zhang, F and Li, Q and Yang, H and Zhang, F and Miao, Y and Lan, P and Wu, X and Zuo, T}, title = {The gut ileal mucosal virome is disturbed in patients with Crohn's disease and exacerbates intestinal inflammation in mice.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {1638}, pmid = {38388538}, issn = {2041-1723}, support = {82172323//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32100134//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82060107//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Humans ; Animals ; Mice ; *Crohn Disease/pathology ; Virome ; *Inflammatory Bowel Diseases/pathology ; Intestinal Mucosa/metabolism ; Ileum/pathology ; *Bacteriophages ; Bacteria ; Inflammation/pathology ; }, abstract = {Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn's disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.}, }
@article {pmid38384263, year = {2024}, author = {Li, L and Li, M and Chen, Y and Yu, Z and Cheng, P and Yu, Z and Cheng, W and Zhang, W and Wang, Z and Gao, X and Sun, H and Wang, X}, title = {Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1354447}, pmid = {38384263}, issn = {1664-302X}, abstract = {Akkermansia muciniphila is a gram-negative bacterium that colonizes the human gut, making up 3-5% of the human microbiome. A. muciniphila is a promising next-generation probiotic with clinical application prospects. Emerging studies have reported various beneficial effects of A. muciniphila including anti-cancer, delaying aging, reducing inflammation, improving immune function, regulating nervous system function, whereas knowledge on its roles and mechanism in infectious disease is currently unclear. In this review, we summarized the basic characteristics, genome and phenotype diversity, the influence of A. muciniphila and its derived components on infectious diseases, such as sepsis, virus infection, enteric infection, periodontitis and foodborne pathogen induced infections. We also provided updates on mechanisms how A. muciniphila protects intestinal barrier integrity and modulate host immune response. In summary, we believe that A. muciniphila is a promising therapeutic probiotic that may be applied for the treatment of a variety of infectious diseases.}, }
@article {pmid38383422, year = {2024}, author = {Gaire, TN and Scott, HM and Noyes, NR and Ericsson, AC and Tokach, MD and William, H and Menegat, MB and Vinasco, J and Nagaraja, TG and Volkova, VV}, title = {Temporal dynamics of the fecal microbiome in female pigs from early life through estrus, parturition, and weaning of the first litter of piglets.}, journal = {Animal microbiome}, volume = {6}, number = {1}, pages = {7}, pmid = {38383422}, issn = {2524-4671}, abstract = {BACKGROUND: Age-associated changes in the gastrointestinal microbiome of young pigs have been robustly described; however, the temporal dynamics of the fecal microbiome of the female pig from early life to first parity are not well understood. Our objective was to describe microbiome and antimicrobial resistance dynamics of the fecal microbiome of breeding sows from early life through estrus, parturition and weaning of the first litter of piglets (i.e., from 3 to 53 weeks of age).<br><br>RESULTS: Our analysis revealed that fecal bacterial populations in developing gilts undergo changes consistent with major maturation milestones. As the pigs progressed towards first estrus, the fecal bacteriome shifted from Rikenellaceae RC9 gut group- and UCG-002-dominated enterotypes to Treponema- and Clostridium sensu stricto 1-dominated enterotypes. After first estrus, the fecal bacteriome stabilized, with minimal changes in enterotype transition and associated microbial diversity from estrus to parturition and subsequent weaning of first litter piglets. Unlike bacterial communities, fecal fungal communities exhibited low diversity with high inter- and intra-pig variability and an increased relative abundance of certain taxa at parturition, including Candida spp. Counts of resistant fecal bacteria also fluctuated over time, and were highest in early life and subsequently abated as the pigs progressed to adulthood.<br><br>CONCLUSIONS: This study provides insights into how the fecal microbial community and antimicrobial resistance in female pigs change from three weeks of age throughout their first breeding lifetime. The fecal bacteriome enterotypes and diversity are found to be age-driven and established by the time of first estrus, with minimal changes observed during subsequent physiological stages, such as parturition and lactation, when compared to the earlier age-related shifts. The use of pigs as a model for humans is well-established, however, further studies are needed to understand how our results compare to the human microbiome dynamics. Our findings suggest that the fecal microbiome exhibited consistent changes across individual pigs and became more diverse with age, which is a beneficial characteristic for an animal model system.}, }
@article {pmid38376378, year = {2024}, author = {Kitamura, N and Kajihara, T and Volpiano, CG and Naung, M and Méric, G and Hirabayashi, A and Yano, H and Yamamoto, M and Yoshida, F and Kobayashi, T and Yamanashi, S and Kawamura, T and Matsunaga, N and Okochi, J and Sugai, M and Yahara, K}, title = {Exploring the effects of antimicrobial treatment on the gut and oral microbiomes and resistomes from elderly long-term care facility residents via shotgun DNA sequencing.}, journal = {Microbial genomics}, volume = {10}, number = {2}, pages = {}, pmid = {38376378}, issn = {2057-5858}, mesh = {Aged ; Humans ; Angiotensin Receptor Antagonists ; Cross-Sectional Studies ; Long-Term Care ; Angiotensin-Converting Enzyme Inhibitors ; DNA ; Sequence Analysis, DNA ; *Microbiota ; *Anti-Infective Agents ; }, abstract = {Monitoring antibiotic-resistant bacteria (ARB) and understanding the effects of antimicrobial drugs on the human microbiome and resistome are crucial for public health. However, no study has investigated the association between antimicrobial treatment and the microbiome-resistome relationship in long-term care facilities, where residents act as reservoirs of ARB but are not included in the national surveillance for ARB. We conducted shotgun metagenome sequencing of oral and stool samples from long-term care facility residents and explored the effects of antimicrobial treatment on the human microbiome and resistome using two types of comparisons: cross-sectional comparisons based on antimicrobial treatment history in the past 6 months and within-subject comparisons between stool samples before, during and 2-4 weeks after treatment using a single antimicrobial drug. Cross-sectional analysis revealed two characteristics in the group with a history of antimicrobial treatment: the archaeon Methanobrevibacter was the only taxon that significantly increased in abundance, and the total abundance of antimicrobial resistance genes (ARGs) was also significantly higher. Within-subject comparisons showed that taxonomic diversity did not decrease during treatment, suggesting that the effect of the prescription of a single antimicrobial drug in usual clinical treatment on the gut microbiota is likely to be smaller than previously thought, even among very elderly people. Additional analysis of the detection limit of ARGs revealed that they could not be detected when contig coverage was <2.0. This study is the first to report the effects of usual antimicrobial treatments on the microbiome and resistome of long-term care facility residents.}, }
@article {pmid38374338, year = {2024}, author = {Buiatte, V and Fonseca, A and Alonso Madureira, P and Nakashima Vaz, AC and Tizioto, PC and Centola Vidal, AM and Ganda, E and de Azevedo Ruiz, VL}, title = {A comparative study of the bacterial diversity and composition of nursery piglets' oral fluid, feces, and housing environment.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {4119}, pmid = {38374338}, issn = {2045-2322}, support = {2017/22184-7//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de S&#xe3;o Paulo/ ; 001//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; PEN04752//Hatch/ ; }, mesh = {Swine ; Animals ; Humans ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Housing ; Bacteria/genetics ; Feces/microbiology ; Firmicutes/genetics ; }, abstract = {The oral cavity is the portal of entry for many microorganisms that affect swine, and the swine oral fluid has been used as a specimen for the diagnosis of several infectious diseases. The oral microbiota has been shown to play important roles in humans, such as protection against non-indigenous bacteria. In swine, studies that have investigated the microbial composition of the oral cavity of pigs are scarce. This study aimed to characterize the oral fluid microbiota of weaned pigs from five commercial farms in Brazil and compare it to their respective fecal and environmental microbiotas. Bacterial compositions were determined by 16S rRNA gene sequencing and analyzed in R Studio. Oral fluid samples were significantly less diverse (alpha diversity) than pen floor and fecal samples (P < 0.01). Alpha diversity changed among farms in oral fluid and pen floor samples, but no differences were observed in fecal samples. Permutational ANOVA revealed that beta diversity was significantly different among sample types (P = 0.001) and farms (P = 0.001), with separation of sample types (feces, pen floor, and oral fluid) on the principal coordinates analysis. Most counts obtained from oral fluid samples were classified as Firmicutes (80.4%) and Proteobacteria (7.7%). The genera Streptococcus, members of the Pasteurellaceae family, and Veillonella were differentially abundant in oral fluid samples when compared to fecal samples, in which Streptococcus was identified as a core genus that was strongly correlated (SparCC) with other taxa. Firmicutes and Bacteroidota were the most relatively abundant phyla identified in fecal and pen floor samples, and Prevotella_9 was the most classified genus. No differentially abundant taxa were identified when comparing fecal samples and pen floor samples. We concluded that under the conditions of our study, the oral fluid microbiota of weaned piglets is different (beta diversity) and less diverse (alpha diversity) than the fecal and environmental microbiotas. Several differentially abundant taxa were identified in the oral fluid samples, and some have been described as important colonizers of the oral cavity in human microbiome studies. Further understanding of the relationship between the oral fluid microbiota and swine is necessary and would create opportunities for the development of innovative solutions that target the microbiota to improve swine health and production.}, }
@article {pmid38371926, year = {2024}, author = {Yang, MQ and Wang, ZJ and Zhai, CB and Chen, LQ}, title = {Research progress on the application of 16S rRNA gene sequencing and machine learning in forensic microbiome individual identification.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1360457}, pmid = {38371926}, issn = {1664-302X}, abstract = {Forensic microbiome research is a field with a wide range of applications and a number of protocols have been developed for its use in this area of research. As individuals host radically different microbiota, the human microbiome is expected to become a new biomarker for forensic identification. To achieve an effective use of this procedure an understanding of factors which can alter the human microbiome and determinations of stable and changing elements will be critical in selecting appropriate targets for investigation. The 16S rRNA gene, which is notable for its conservation and specificity, represents a potentially ideal marker for forensic microbiome identification. Gene sequencing involving 16S rRNA is currently the method of choice for use in investigating microbiomes. While the sequencing involved with microbiome determinations can generate large multi-dimensional datasets that can be difficult to analyze and interpret, machine learning methods can be useful in surmounting this analytical challenge. In this review, we describe the research methods and related sequencing technologies currently available for application of 16S rRNA gene sequencing and machine learning in the field of forensic identification. In addition, we assess the potential value of 16S rRNA and machine learning in forensic microbiome science.}, }
@article {pmid38371919, year = {2024}, author = {Wang, Q and Fan, X and Wu, S and Su, X}, title = {PM-CNN: microbiome status recognition and disease detection model based on phylogeny and multi-path neural network.}, journal = {Bioinformatics advances}, volume = {4}, number = {1}, pages = {vbae013}, pmid = {38371919}, issn = {2635-0041}, abstract = {MOTIVATION: The human microbiome, found throughout various body parts, plays a crucial role in health dynamics and disease development. Recent research has highlighted microbiome disparities between patients with different diseases and healthy individuals, suggesting the microbiome's potential in recognizing health states. Traditionally, microbiome-based status classification relies on pre-trained machine learning (ML) models. However, most ML methods overlook microbial relationships, limiting model performance.<br><br>RESULTS: To address this gap, we propose PM-CNN (Phylogenetic Multi-path Convolutional Neural Network), a novel phylogeny-based neural network model for multi-status classification and disease detection using microbiome data. PM-CNN organizes microbes based on their phylogenetic relationships and extracts features using a multi-path convolutional neural network. An ensemble learning method then fuses these features to make accurate classification decisions. We applied PM-CNN to human microbiome data for status and disease detection, demonstrating its significant superiority over existing ML models. These results provide a robust foundation for microbiome-based state recognition and disease prediction in future research and applications.<br><br>PM-CNN software is available at https://github.com/qdu-bioinfo/PM_CNN.}, }
@article {pmid38369542, year = {2024}, author = {Zou, S and Yang, C and Zhang, J and Zhong, D and Meng, M and Zhang, L and Chen, H and Fang, L}, title = {Multi-omic profiling reveals associations between the gut microbiome, host genome and transcriptome in patients with colorectal cancer.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {175}, pmid = {38369542}, issn = {1479-5876}, support = {82373512//National Natural Science Foundation of China/ ; 82222056//National Natural Science Foundation of China/ ; 82302910//National Natural Science Foundation of China/ ; 2022A1515012316//Natural Science Foundation of Guangdong Province/ ; 2021B1212010004//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Transcriptome/genetics ; *Colorectal Neoplasms/diagnosis ; Multiomics ; *Microbiota ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) is the leading cancer worldwide. Microbial agents have been considered to contribute to the pathogenesis of different disease. But the underlying relevance between CRC and microbiota remain unclear.<br><br>METHODS: We dissected the fecal microbiome structure and genomic and transcriptomic profiles of matched tumor and normal mucosa tissues from 41 CRC patients. Of which, the relationship between CRC-associated bacterial taxa and their significantly correlated somatic mutated gene was investigated by exome sequencing technology. Differentially expressed functional genes in CRC were clustered according to their correlation with differentially abundant species, following by annotation with DAVID. The composition of immune and stromal cell types was identified by XCELL.<br><br>RESULTS: We identified a set of 22 microbial gut species associated with CRC and estimate the relative abundance of KEGG ontology categories. Next, the interactions between CRC-related gut microbes and clinical phenotypes were evaluated. 4 significantly mutated gene: TP53, APC, KRAS, SMAD4 were pointed out and the associations with cancer related microbes were identified. Among them, Fusobacterium nucleatum positively corelated with different host metabolic pathways. Finally, we revealed that Fusobacterium nucleatum modified the tumor immune environment by TNFSF9 gene expression.<br><br>CONCLUSION: Collectively, our multi-omics data could help identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC.}, }
@article {pmid38361239, year = {2024}, author = {Mohamed, ME and Saqr, A and Staley, C and Onyeaghala, G and Teigen, L and Dorr, CR and Remmel, RP and Guan, W and Oetting, WS and Matas, AJ and Israni, AK and Jacobson, PA}, title = {Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation.}, journal = {Transplantation}, volume = {108}, number = {9}, pages = {1895-1910}, pmid = {38361239}, issn = {1534-6080}, support = {R01 AI140303/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Immunosuppressive Agents/pharmacokinetics/adverse effects ; *Gastrointestinal Microbiome/drug effects ; *Organ Transplantation/adverse effects ; Graft Rejection/prevention &amp; control/immunology/microbiology ; Animals ; }, abstract = {The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.}, }
@article {pmid38352704, year = {2024}, author = {Kadyan, S and Park, G and Hochuli, N and Miller, K and Wang, B and Nagpal, R}, title = {Resistant starches from dietary pulses improve neurocognitive health via gut-microbiome-brain axis in aged mice.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1322201}, pmid = {38352704}, issn = {2296-861X}, abstract = {INTRODUCTION: Cognitive decline is a common consequence of aging. Dietary patterns that lack fibers and are high in saturated fats worsen cognitive impairment by triggering pro-inflammatory pathways and metabolic dysfunctions. Emerging evidence highlights the neurocognitive benefits of fiber-rich diets and the crucial role of gut-microbiome-brain signaling. However, the mechanisms of this diet-microbiome-brain regulation remain largely unclear.<br><br>METHODS: Accordingly, we herein investigated the unexplored neuroprotective mechanisms of dietary pulses-derived resistant starch (RS) in improving aging-associated neurocognitive function in an aged (60-weeks old) murine model carrying a human microbiome.<br><br>RESULTS AND DISCUSSION: Following 20-weeks dietary regimen which included a western-style diet without (control; CTL) or with 5% w/w fortification with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin fiber (INU), we find that RS, particularly from LEN, ameliorate the cognitive impairments induced by western diet. Mechanistically, RS-mediated improvements in neurocognitive assessments are attributed to positive remodeling of the gut microbiome-metabolome arrays, which include increased short-chain fatty acids and reduced branched-chain amino acids levels. This microbiome-metabolite-brain signaling cascade represses neuroinflammation, cellular senescence, and serum leptin/insulin levels, while enhancing lipid metabolism through improved hepatic function. Altogether, the data demonstrate the prebiotic effects of RS in improving neurocognitive function via modulating the gut-brain axis.}, }
@article {pmid38352363, year = {2024}, author = {Zhou, X and Shen, X and Johnson, JS and Spakowicz, DJ and Agnello, M and Zhou, W and Avina, M and Honkala, A and Chleilat, F and Chen, SJ and Cha, K and Leopold, S and Zhu, C and Chen, L and Lyu, L and Hornburg, D and Wu, S and Zhang, X and Jiang, C and Jiang, L and Jiang, L and Jian, R and Brooks, AW and Wang, M and Contrepois, K and Gao, P and Schüssler-Fiorenza Rose, SM and Binh Tran, TD and Nguyen, H and Celli, A and Hong, BY and Bautista, EJ and Dorsett, Y and Kavathas, P and Zhou, Y and Sodergren, E and Weinstock, GM and Snyder, MP}, title = {Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.02.01.577565}, pmid = {38352363}, issn = {2692-8205}, abstract = {UNLABELLED: To understand dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune and clinical markers of microbiomes from four body sites in 86 participants over six years. We found that microbiome stability and individuality are body-site-specific and heavily influenced by the host. The stool and oral microbiome were more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. Also, we identified individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlated across body sites, suggesting systemic coordination influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals showed altered microbial stability and associations between microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.<br><br>STUDY HIGHLIGHTS: The stability of the human microbiome varies among individuals and body sites.Highly individualized microbial genera are more stable over time.At each of the four body sites, systematic interactions between the environment, the host and bacteria can be detected.Individuals with insulin resistance have lower microbiome stability, a more diversified skin microbiome, and significantly altered host-microbiome interactions.}, }
@article {pmid38347963, year = {2023}, author = {Jokiranta, ST and Miettinen, S and Salonen, S and Kareinen, L and Uusitalo, R and Korhonen, EM and Virtanen, J and Kivistö, I and Aaltonen, K and Mosselhy, DA and Lääveri, T and Kantele, A and Arstila, TP and Jarva, H and Vapalahti, O and Heinonen, S and Kekäläinen, E}, title = {Stable Levels of Antibodies Against Unrelated Toxoid Vaccines After COVID-19: COVID-19 Infection Does Not Affect Toxoid Vaccine Antibody Levels.}, journal = {Pathogens &amp; immunity}, volume = {8}, number = {2}, pages = {74-87}, pmid = {38347963}, issn = {2469-2964}, abstract = {BACKGROUND: Lymphopenia is common in COVID-19. This has raised concerns that COVID-19 could affect the immune system akin to measles infection, which causes immune amnesia and a reduction in protective antibodies.<br><br>METHODS: We recruited COVID-19 patients (n = 59) in Helsinki, Finland, and collected plasma samples on 2 to 3 occasions during and after infection. We measured IgG antibodies to diphtheria toxin, tetanus toxoid, and pertussis toxin, along with total IgG, SARS-CoV-2 spike protein IgG, and neutralizing antibodies. We also surveyed the participants for up to 17 months for long-term impaired olfaction as a proxy for prolonged post-acute COVID-19 symptoms.<br><br>RESULTS: No significant differences were found in the unrelated vaccine responses while the serological response against COVID-19 was appropriate. During the acute phase of the disease, the SARSCoV-2 IgG levels were lower in outpatients when compared to inpatients. SARS-CoV-2 serology kinetics matched expectations. In the acute phase, anti-tetanus and anti-diphtheria IgG levels were lower in patients with prolonged impaired olfaction during follow up than in those without.<br><br>CONCLUSIONS: We could not detect significant decline in overall humoral immunity during or after COVID-19 infection. In severe COVID-19, there appears to be a temporary decline in total IgG levels.}, }
@article {pmid38346516, year = {2024}, author = {Hou, C and Huang, M and Wang, P and Zhang, Q and Wang, G and Gao, S}, title = {Chronic exposure to 3,6-dichlorocarbazole exacerbates non-alcoholic fatty liver disease in zebrafish by disrupting lipid metabolism and inducing special lipid biomarker accumulation.}, journal = {Chemosphere}, volume = {352}, number = {}, pages = {141442}, doi = {10.1016/j.chemosphere.2024.141442}, pmid = {38346516}, issn = {1879-1298}, mesh = {Animals ; *Non-alcoholic Fatty Liver Disease/chemically induced ; Zebrafish/metabolism ; Lipid Metabolism ; Liver/metabolism ; Triglycerides/metabolism ; *Perciformes/metabolism ; Biomarkers/metabolism ; Diet, High-Fat ; *Carbazoles ; }, abstract = {Most previous studies have focused primarily on the adverse effects of environmental chemicals on organisms of good healthy. Although global prevalence of non-alcoholic fatty liver disease (NAFLD) has reached approximately 25%, the impact of environmentally persistent organic chemicals on organisms with NAFLD is substantially unknown. Polyhalogenated carbazoles (PHCZs) as emerging contaminants have been frequently detected in the environment and organisms. In this study, we investigated the impact of the most frequently detected PHCZs, 3,6-dichlorocarbazole (36-CCZ), on zebrafish with high-fat diet (HFD)-induced NAFLD. After 4 weeks exposure to environmentally relevant concentrations of 36-CCZ (0.16-0.45 μg/L), the accumulation of lipid in zebrafish liver dramatically increased, and the transcription of genes involved in lipid synthesis, transport and oxidation was significantly upregulated, demonstrating that 36-CCZ had exacerbated the NAFLD in zebrafish. Lipidomic analysis indicated that 36-CCZ had significantly affected liver lipid metabolic pathways, mainly including glycerolipids and glycerophospholipids. Additionally, fifteen lipids were identified as potential lipid biomarkers for 36-CCZ exacerbation of NAFLD, including diacylglycerols (DGs), triglycerides (TGs), phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidic acid (PA), and phosphatidylinositol (PI). These findings demonstrate that long-term exposure to 36-CCZ can promote the progression of NAFLD, which will contribute to raising awareness of the health risks of PHCZs.}, }
@article {pmid38339836, year = {2024}, author = {Stevens, R and Gorman, S and Arabiat, D and Christophersen, CT and Palmer, DJ}, title = {Associations between sun exposure, skin pH, and epidermal permeability in pregnancy: A longitudinal observational study.}, journal = {Photochemistry and photobiology}, volume = {100}, number = {5}, pages = {1519-1526}, doi = {10.1111/php.13920}, pmid = {38339836}, issn = {1751-1097}, mesh = {Humans ; Female ; Pregnancy ; Hydrogen-Ion Concentration ; Longitudinal Studies ; *Sunlight ; Adult ; *Permeability ; *Skin/metabolism/radiation effects ; *Epidermis/radiation effects/metabolism ; Seasons ; }, abstract = {Little is known about how sun exposure may affect the maternal skin barrier during pregnancy when many hormonal and physiological changes occur. In this longitudinal observational study, 50 pregnant women were recruited at 18-24 weeks' gestation, 25 in summer-autumn, and 25 in winter-spring. At three time points in pregnancy at 18-24, 28-30, and 36-38 weeks' gestation, participants completed a validated sun exposure questionnaire and had skin permeability and surface pH measured on the volar forearm. We identified an association between increased sun exposure and increased skin permeability at 18-24 weeks' gestation (β = 0.85, p = 0.01). Lower transepidermal water loss (decreased skin permeability), mean = 12.1 (SD = 5.1) at 28-30 weeks' gestation was observed, compared to mean = 12.6 (SD = 4.0) at 18-24 weeks' and mean = 13.7 (SD = 8.5) at 36-38 weeks' gestation (n = 27, β = -1.83, p = 0.007). Higher skin pH readings, mean = 5.80 (SD = 0.58) were found at 28-30 weeks' gestation, compared to mean = 5.25 (SD = 0.62) at 18-24 weeks' and mean = 5.47 (SD = 0.57) at 36-38 weeks' gestation (n = 27, β = 0.40, p = 0.004). These gestational fluctuations remained after adjusting for Fitzpatrick skin type, season, and sun exposure. We observed gestational fluctuations in both skin permeability and skin pH, with 28-30 weeks' gestation being a significant point of difference compared to mid- and late-pregnancy periods.}, }
@article {pmid38337613, year = {2024}, author = {Efremova, I and Maslennikov, R and Zharkova, M and Poluektova, E and Benuni, N and Kotusov, A and Demina, T and Ivleva, A and Adzhieva, F and Krylova, T and Ivashkin, V}, title = {Efficacy and Safety of a Probiotic Containing Saccharomyces boulardii CNCM I-745 in the Treatment of Small Intestinal Bacterial Overgrowth in Decompensated Cirrhosis: Randomized, Placebo-Controlled Study.}, journal = {Journal of clinical medicine}, volume = {13}, number = {3}, pages = {}, pmid = {38337613}, issn = {2077-0383}, abstract = {(1) Background: The aim was to evaluate the effectiveness of the probiotic containing Saccharomyces boulardii in the treatment of small intestinal bacterial overgrowth (SIBO) in patients with decompensated cirrhosis. (2) Methods: This was a blinded, randomized, placebo-controlled study. (3) Results: After 3 months of treatment, SIBO was absent in 80.0% of patients in the probiotic group and in 23.1% of patients in the placebo group (p = 0.002). The patients with eliminated SIBO had decreased frequency of ascites and hepatic encephalopathy, the increased platelets and albumin levels, the decreased blood levels of total bilirubin, biomarkers of bacterial translocation (lipopolysaccharide [LPS]) and systemic inflammation (C-reactive protein), and positive changes in markers of hyperdynamic circulation compared with the state at inclusion. There were no significant changes in the claudin 3 level (the intestinal barrier biomarker) in these patients. No significant changes were observed in the group of patients with persistent SIBO. The serum level of nitrate (endothelial dysfunction biomarker) was lower in patients with eradicated SIBO than in patients with persistent SIBO. One (5.3%) patient with eradicated SIBO and six (42.9%) patients with persistent SIBO died within the first year of follow-up (p = 0.007). (4) Conclusions: SIBO eradication was an independent predictor of a favorable prognosis during the first year of follow-up.}, }
@article {pmid38333568, year = {2024}, author = {Bai, R and Guo, J}, title = {Interactions and Implications of Klebsiella pneumoniae with Human Immune Responses and Metabolic Pathways: A Comprehensive Review.}, journal = {Infection and drug resistance}, volume = {17}, number = {}, pages = {449-462}, pmid = {38333568}, issn = {1178-6973}, abstract = {Klebsiella pneumoniae (K. pneumoniae), a significant contributor to the global challenge of antibiotic resistance, is not only a ubiquitous component of the human microbiome but also a potent pathogen capable of causing a spectrum of diseases. This review provides a thorough analysis of the intricate interactions between K. pneumoniae and the human immune system, elucidating its substantial impact on metabolic processes. We explore the mechanisms employed by K. pneumoniae to evade and manipulate immune responses, including molecular mimicry, immune modulation, and biofilm formation. The review further investigates the bacterium's influence on metabolic pathways, particularly glycolysis, highlighting how these interactions exacerbate disease severity. The emergence of multidrug-resistant and extremely drug-resistant strains within the Enterobacteriaceae family has heightened the public health crisis, underscoring the urgency for comprehensive research. We investigate the roles of the host's complement system, autophagy, cell death mechanisms, and various cytokines in combating K. pneumoniae infections, shedding light on areas that warrant further academic investigation. Additionally, the review discusses the challenges posed by K1- and K2-capsule polysaccharides in vaccine development due to their complex molecular structures and adhesive properties. Acknowledging the limited availability of effective antimicrobials, this review advocates for exploring alternative approaches such as immunotherapeutics, vaccinations, and phage therapy. We consolidate current knowledge on K. pneumoniae, covering classical and non-classical subtypes, antimicrobial resistance-mediated genes, virulence factors, and epidemiological trends in isolation and antibiotic resistance rates. This comprehensive review not only advances our understanding of K. pneumoniae but also underscores the imperative for ongoing research and collaborative efforts to develop new prevention and treatment strategies against this formidable pathogen.}, }
@article {pmid38328082, year = {2024}, author = {Gray, SM and Moss, AD and Herzog, JW and Kashiwagi, S and Liu, B and Young, JB and Sun, S and Bhatt, A and Fodor, AA and Balfour Sartor, R}, title = {Mouse Adaptation of Human Inflammatory Bowel Diseases Microbiota Enhances Colonization Efficiency and Alters Microbiome Aggressiveness Depending on Recipient Colonic Inflammatory Environment.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38328082}, issn = {2692-8205}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; }, abstract = {Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis. Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10[-/-] mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10[-/-] mice. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10[-/-] host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10[-/-] mice than the distinct microbiota reassembled in non-inflamed WT hosts. Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer.}, }
@article {pmid38318164, year = {2024}, author = {Piazzesi, A and Pane, S and Del Chierico, F and Romani, L and Campana, A and Palma, P and Putignani, L}, title = {The pediatric gut bacteriome and virome in response to SARS-CoV-2 infection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1335450}, pmid = {38318164}, issn = {2235-2988}, mesh = {Adult ; Humans ; Child ; *COVID-19 ; Virome ; SARS-CoV-2/genetics ; *Microbiota ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {INTRODUCTION: Since the beginning of the SARS-CoV-2 pandemic in early 2020, it has been apparent that children were partially protected from both infection and the more severe forms of the disease. Many different mechanisms have been proposed to explain this phenomenon, including children's frequent exposure to other upper respiratory infections and vaccines, and which inflammatory cytokines they are more likely to produce in response to infection. Furthermore, given the presence of SARS-CoV-2 in the intestine and its ability to infect enterocytes, combined with the well described immunomodulatory capabilities of the microbiome, another potential contributing factor may be the presence of certain protective microbial members of the gut microbiota (GM).<br><br>METHODS: We performed shotgun metagenomic sequencing and profiled both the bacteriome and virome of the GM of pediatric SARS-CoV-2 patients compared to healthy, age-matched subjects.<br><br>RESULTS: We found that, while pediatric patients do share some pro-inflammatory microbial signatures with adult patients, they also possess a distinct microbial signature of protective bacteria previously found to be negatively correlated with SARS-CoV-2 infectivity and COVID-19 severity. COVID-19 was also associated with higher fecal Cytomegalovirus load, and with shifts in the relative abundances of bacteriophages in the GM. Furthermore, we address how the preventative treatment of COVID-19 patients with antibiotics, a common practice especially in the early days of the pandemic, affected the bacteriome and virome, as well as the abundances of antimicrobial resistance and virulence genes in these patients.<br><br>DISCUSSION: To our knowledge, this is the first study to address the bacteriome, virome, and resistome of pediatric patients in response to COVID-19 and to preventative antibiotics use.}, }
@article {pmid38308184, year = {2024}, author = {Li, K and Zhang, J and Lyu, H and Yang, J and Wei, W and Wang, Y and Luo, H and Zhang, Y and Jiang, X and Yi, H and Wang, M and Zhang, C and Wu, K and Xiao, L and Wen, W and Xu, H and Li, G and Wan, Y and Yang, F and Yang, R and Fu, X and Qin, B and Zhou, Z and Zhang, H and Lee, MH}, title = {CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {11}, number = {14}, pages = {e2306827}, pmid = {38308184}, issn = {2198-3844}, support = {2020YFA0803300//National Key Research and Development Program/ ; 2018YFC0910300//National Key Research and Development Program/ ; 82203243//National Natural Science Foundation of China/ ; 82204411//National Natural Science Foundation of China/ ; 81971999//National Natural Science Foundation of China/ ; 2023A1515030245//Natural Science Foundation of Guangdong Province/ ; 2020A1515110076//Natural Science Foundation of Guangdong Province/ ; //"President Specific Funding" of The Sixth Affiliated Hospital, Sun Yat-sen University/ ; 2020B1111170004//Guangdong Provincial Clinical Research Center for Digestive Diseases/ ; //National Key Clinical Discipline/ ; }, mesh = {Humans ; *Carcinoma, Hepatocellular/metabolism ; Cholesterol/metabolism ; *Hydroxymethylglutaryl-CoA Synthase/metabolism ; *Liver Neoplasms/metabolism ; Nuclear Proteins/metabolism ; *Repressor Proteins/metabolism ; Tumor Microenvironment ; Ubiquitin/metabolism ; *YAP-Signaling Proteins/metabolism ; }, abstract = {Cholesterol metabolism has important roles in maintaining membrane integrity and countering the development of diseases such as obesity and cancers. Cancer cells sustain cholesterol biogenesis for their proliferation and microenvironment reprograming even when sterols are abundant. However, efficacy of targeting cholesterol metabolism for cancer treatment is always compromised. Here it is shown that CSN6 is elevated in HCC and is a positive regulator of hydroxymethylglutaryl-CoA synthase 1 (HMGCS1) of mevalonate (MVA) pathway to promote tumorigenesis. Mechanistically, CSN6 antagonizes speckle-type POZ protein (SPOP) ubiquitin ligase to stabilize HMGCS1, which in turn activates YAP1 to promote tumor growth. In orthotopic liver cancer models, targeting CSN6 and HMGCS1 hinders tumor growth in both normal and high fat diet. Significantly, HMGCS1 depletion improves YAP inhibitor efficacy in patient derived xenograft models. The results identify a CSN6-HMGCS1-YAP1 axis mediating tumor outgrowth in HCC and propose a therapeutic strategy of targeting non-alcoholic fatty liver diseases- associated HCC.}, }
@article {pmid38297837, year = {2024}, author = {Wang, SH and Zheng, T and Fawzi, NL}, title = {Structure and interactions of prion-like domains in transcription factor Efg1 phase separation.}, journal = {Biophysical journal}, volume = {123}, number = {11}, pages = {1481-1493}, pmid = {38297837}, issn = {1542-0086}, support = {R01 GM147677/GM/NIGMS NIH HHS/United States ; }, mesh = {*Protein Domains ; *Fungal Proteins/metabolism/chemistry/genetics ; Candida albicans/metabolism ; Prions/metabolism/chemistry ; Transcriptional Elongation Factors/metabolism/chemistry/genetics ; Transcription Factors/metabolism/chemistry/genetics ; Phase Separation ; DNA-Binding Proteins ; }, abstract = {Candida albicans, a prominent member of the human microbiome, can make an opportunistic switch from commensal coexistence to pathogenicity accompanied by an epigenetic shift between the white and opaque cell states. This transcriptional switch is under precise regulation by a set of transcription factors (TFs), with Enhanced Filamentous Growth Protein 1 (Efg1) playing a central role. Previous research has emphasized the importance of Efg1's prion-like domain (PrLD) and the protein's ability to undergo phase separation for the white-to-opaque transition of C. albicans. However, the underlying molecular mechanisms of Efg1 phase separation have remained underexplored. In this study, we delved into the biophysical basis of Efg1 phase separation, revealing the significant contribution of both N-terminal (N) and C-terminal (C) PrLDs. Through NMR structural analysis, we found that Efg1 N-PrLD and C-PrLD are mostly disordered but have prominent partial α-helical secondary structures in both domains. NMR titration experiments suggest that the partially helical structures in N-PrLD act as hubs for self-interaction as well as Efg1 interaction with RNA. Using condensed-phase NMR spectroscopy, we uncovered diverse amino acid interactions underlying Efg1 phase separation. Particularly, we highlight the indispensable role of tyrosine residues within the transient α-helical structures of PrLDs particularly in the N-PrLD compared to the C-PrLD in stabilizing phase separation. Our study provides evidence that the transient α-helical structure is present in the phase-separated state and highlights the particular importance of aromatic residues within these structures for phase separation. Together, these results enhance the understanding of C. albicans transcription factor interactions that lead to virulence and provide a crucial foundation for potential antifungal therapies targeting the transcriptional switch.}, }
@article {pmid38297075, year = {2024}, author = {Zhao, L and Cunningham, CM and Andruska, AM and Schimmel, K and Ali, MK and Kim, D and Gu, S and Chang, JL and Spiekerkoetter, E and Nicolls, MR}, title = {Rat microbial biogeography and age-dependent lactic acid bacteria in healthy lungs.}, journal = {Lab animal}, volume = {53}, number = {2}, pages = {43-55}, pmid = {38297075}, issn = {1548-4475}, support = {R01 HL095686/HL/NHLBI NIH HHS/United States ; R01 HL158714/HL/NHLBI NIH HHS/United States ; R01 HL138473/HL/NHLBI NIH HHS/United States ; T32 HL098049/HL/NHLBI NIH HHS/United States ; I01 BX005628/BX/BLRD VA/United States ; }, mesh = {Humans ; Rats ; Animals ; Bacteria ; *Lactobacillales ; Lung/microbiology ; *Microbiota/genetics ; }, abstract = {The laboratory rat emerges as a useful tool for studying the interaction between the host and its microbiome. To advance principles relevant to the human microbiome, we systematically investigated and defined the multitissue microbial biogeography of healthy Fischer 344 rats across their lifespan. Microbial community profiling data were extracted and integrated with host transcriptomic data from the Sequencing Quality Control consortium. Unsupervised machine learning, correlation, taxonomic diversity and abundance analyses were performed to determine and characterize the rat microbial biogeography and identify four intertissue microbial heterogeneity patterns (P1-P4). We found that the 11 body habitats harbored a greater diversity of microbes than previously suspected. Lactic acid bacteria (LAB) abundance progressively declined in lungs from breastfed newborn to adolescence/adult, and was below detectable levels in elderly rats. Bioinformatics analyses indicate that the abundance of LAB may be modulated by the lung-immune axis. The presence and levels of LAB in lungs were further evaluated by PCR in two validation datasets. The lung, testes, thymus, kidney, adrenal and muscle niches were found to have age-dependent alterations in microbial abundance. The 357 microbial signatures were positively correlated with host genes in cell proliferation (P1), DNA damage repair (P2) and DNA transcription (P3). Our study established a link between the metabolic properties of LAB with lung microbiota maturation and development. Breastfeeding and environmental exposure influence microbiome composition and host health and longevity. The inferred rat microbial biogeography and pattern-specific microbial signatures could be useful for microbiome therapeutic approaches to human health and life quality enhancement.}, }
@article {pmid38293115, year = {2024}, author = {Zheludev, IN and Edgar, RC and Lopez-Galiano, MJ and de la Peña, M and Babaian, A and Bhatt, AS and Fire, AZ}, title = {Viroid-like colonists of human microbiomes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38293115}, issn = {2692-8205}, support = {R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; R35 GM130366/GM/NIGMS NIH HHS/United States ; }, abstract = {Here, we describe the "Obelisks," a previously unrecognised class of viroid-like elements that we first identified in human gut metatranscriptomic data. "Obelisks" share several properties: (i) apparently circular RNA ~1kb genome assemblies, (ii) predicted rod-like secondary structures encompassing the entire genome, and (iii) open reading frames coding for a novel protein superfamily, which we call the "Oblins". We find that Obelisks form their own distinct phylogenetic group with no detectable sequence or structural similarity to known biological agents. Further, Obelisks are prevalent in tested human microbiome metatranscriptomes with representatives detected in ~7% of analysed stool metatranscriptomes (29/440) and in ~50% of analysed oral metatranscriptomes (17/32). Obelisk compositions appear to differ between the anatomic sites and are capable of persisting in individuals, with continued presence over >300 days observed in one case. Large scale searches identified 29,959 Obelisks (clustered at 90% nucleotide identity), with examples from all seven continents and in diverse ecological niches. From this search, a subset of Obelisks are identified to code for Obelisk-specific variants of the hammerhead type-III self-cleaving ribozyme. Lastly, we identified one case of a bacterial species (Streptococcus sanguinis) in which a subset of defined laboratory strains harboured a specific Obelisk RNA population. As such, Obelisks comprise a class of diverse RNAs that have colonised, and gone unnoticed in, human, and global microbiomes.}, }
@article {pmid38292856, year = {2023}, author = {Aguirre-García, MM and Amedei, A and Hernández-Ruiz, P and Gómez-García, AP and Niccolai, E and Moreno-Rodríguez, AM and Pinto-Cardoso, S and Alviter-Plata, A and Escalona-Montaño, AR and Ordaz-Robles, ER and González-Salazar, MDC and Springall Del Villar, R and Berrios-Bárcenas, EA and Ávila-Vanzzini, N}, title = {Cytokine and microbiota profiles in obesity-related hypertension patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1325261}, pmid = {38292856}, issn = {2235-2988}, mesh = {Adult ; Humans ; Overweight/complications/microbiology ; Cytokines ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; Obesity/complications/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; *Hypertension/complications ; }, abstract = {BACKGROUND: Systemic arterial hypertension is linked to a heightened risk of cardiovascular diseases on a global scale. In Mexico, nearly half of adults in vulnerable conditions experience hypertension. Imbalance in the oral and intestinal microbiota composition has been observed in patients with hypertension, documented by a decrease of bacteria producing short-chain fatty acids, which play a critical role in blood pressure regulation.<br><br>AIM: To examine the cytokines' profile and assess the characteristics of oral and gut microbiota in obesity-related hypertension in Mexican patients.<br><br>METHODS: A cross-sectional, observational, and analytical study was carried out. Twenty-two patients were categorized by their body mass index (BMI) as overweight and obese, and the diagnosis of primary hypertension. DNA from supragingival dental plaque and feces samples was used to carry out 16S rRNA sequencing. Additionally, 13 cytokines were quantified.<br><br>RESULTS: In the oral microbiota, Kluyvera was found to be significantly enriched in obese compared to overweight patients. Instead, the gut microbiota was dominated by Firmicutes. However, the correlation between certain genera and proinflammatory cytokines was noted.<br><br>CONCLUSION: This exploratory study provides insights into the complex relationship between the oral and gut microbiota and their association with systemic inflammation in obesity-related hypertension.}, }
@article {pmid38292760, year = {2024}, author = {Candeliere, F and Sola, L and Raimondi, S and Rossi, M and Amaretti, A}, title = {Good and bad dispositions between archaea and bacteria in the human gut: New insights from metagenomic survey and co-occurrence analysis.}, journal = {Synthetic and systems biotechnology}, volume = {9}, number = {1}, pages = {88-98}, pmid = {38292760}, issn = {2405-805X}, abstract = {Archaea are an understudied component of the human microbiome. In this study, the gut archaeome and bacteriome of 60 healthy adults from different region were analyzed by whole-genome shotgun sequencing. Archaea were ubiquitously found in a wide range of abundances, reaching up to 7.2 %. The dominant archaeal phylum was Methanobacteriota, specifically the family Methanobacteriaceae, encompassing more than 50 % of Archaea in 50 samples. The previously underestimated Thermoplasmatota, mostly composed of Methanomassiliicoccaceae, dominated in 10 subjects (>50 %) and was present in all others except one. Halobacteriota, the sole other archaeal phylum, occurred in negligible concentration, except for two samples (4.6-4.8 %). This finding confirmed that the human gut archaeome is primarily composed of methanogenic organisms and among the known methanogenic pathway: i) hydrogenotrophic reduction of CO2 is the predominant, being the genus Methanobrevibacter and the species Methanobrevibacter smithii the most abundant in the majority of the samples; ii) the second pathway, that involved Methanomassiliicoccales, was the hydrogenotrophic reduction of methyl-compounds; iii) dismutation of acetate or methyl-compounds seemed to be absent. Co-occurrence analysis allowed to unravel correlations between Archaea and Bacteria that shapes the overall structure of the microbial community, allowing to depict a clearer picture of the human gut archaeome.}, }
@article {pmid38289047, year = {2024}, author = {Romani, L and Del Chierico, F and Pane, S and Ristori, MV and Pirona, I and Guarrasi, V and Cotugno, N and Bernardi, S and Lancella, L and Perno, CF and Rossi, P and Villani, A and Campana, A and Palma, P and Putignani, L and , }, title = {Exploring nasopharyngeal microbiota profile in children affected by SARS-CoV-2 infection.}, journal = {Microbiology spectrum}, volume = {12}, number = {3}, pages = {e0300923}, pmid = {38289047}, issn = {2165-0497}, support = {//Ministero della Salute (Italy Ministry of Health)/ ; 202003_Bioarte_Putignani//The BioArte Limited/ ; Current Research funds//Italian Ministry of Health/ ; }, mesh = {Adult ; Humans ; Child ; *COVID-19 ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2/genetics ; *Microbiota/genetics ; Nasopharynx ; Streptococcus/genetics ; }, abstract = {UNLABELLED: The relationship between COVID-19 and nasopharyngeal (NP) microbiota has been investigated mainly in the adult population. We explored the NP profile of children affected by COVID-19, compared to healthy controls (CTRLs). NP swabs of children with COVID-19, collected between March and September 2020, were investigated at the admission (T0), 72 h to 7 days (T1), and at the discharge (T2) of the patients. NP microbiota was analyzed by 16S rRNA targeted-metagenomics. Data from sequencing were investigated by QIIME 2.0 and PICRUSt 2. Multiple machine learning (ML) models were exploited to classify patients compared to CTRLs. The NP microbiota of COVID-19 patients (N = 71) was characterized by reduction of α-diversity compared to CTRLs (N = 59). The NP microbiota of COVID-19 cohort appeared significantly enriched in Streptococcus, Haemophilus, Staphylococcus, Veillonella, Enterococcus, Neisseria, Moraxella, Enterobacteriaceae, Gemella, Bacillus, and reduced in Faecalibacterium, Akkermansia, Blautia, Bifidobacterium, Ruminococcus, and Bacteroides, compared to CTRLs (FDR < 0.001). Exploiting ML models, Enterococcus, Pseudomonas, Streptococcus, Capnocytopagha, Tepidiphilus, Porphyromonas, Staphylococcus, and Veillonella resulted as NP microbiota biomarkers, in COVID-19 patients. No statistically significant differences were found comparing the NP microbiota profile of COVID-19 patients during the time-points or grouping patients on the basis of high, medium, and low viral load (VL). This evidence provides specific pathobiont signatures of the NP microbiota in pediatric COVID-19 patients, and the reduction of anaerobic protective commensals. Our data suggest that the NP microbiota may have a specific disease-related signature since infection onset without changes during disease progression, regardless of the SARS-CoV-2 VL.<br><br>IMPORTANCE: Since the beginning of pandemic, we know that children are less susceptible to severe COVID-19 disease. A potential role of the nasopharyngeal (NP) microbiota has been hypothesized but to date, most of the studies have been focused on adults. We studied the NP microbiota modifications in children affected by SARS-CoV-2 infection showing a specific NP microbiome profile, mainly composed by pathobionts and almost missing protective anaerobic commensals. Moreover, in our study, specific microbial signatures appear since the first days of infection independently from SARS-CoV-2 viral load.}, }
@article {pmid38287978, year = {2023}, author = {Rinaldi, F and Chirico, R and Trink, A and Pinto, D}, title = {Corrigendum: Resistance and pseudo-resistance to permethrin phenomena: the importance of controlling scabies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1358427}, doi = {10.3389/fcimb.2023.1358427}, pmid = {38287978}, issn = {2235-2988}, abstract = {[This corrects the article DOI: 10.3389/fcimb.2023.1297337.].}, }
@article {pmid38276099, year = {2024}, author = {Zerekidze, A and Li, M and Refisch, A and Shameya, J and Sobanski, T and Walter, M and Wagner, G}, title = {Impact of Toxoplasma gondii and Human Microbiome on Suicidal Behavior: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {13}, number = {2}, pages = {}, pmid = {38276099}, issn = {2077-0383}, support = {01EE2305F//Federal Ministry of Education and Research (Bundesministerium f&#xfc;r Bildung und Forschung [BMBF]) and the ministry of Th&#xfc;ringen within the initial phase of the German Center for Mental Health (DZPG)/ ; }, abstract = {BACKGROUND: Suicide remains a persistent global health challenge, resisting widespread prevention efforts. According to previous findings, toxoplasmosis is particularly associated with altered decision making, which could lead to risk-taking behavior, thereby increasing the likelihood for suicidal behavior (SB). In addition, discussion about the role of microbiome in psychiatric disorders has emerged lately, which also makes it relevant to investigate its role in the context of SB. Therefore, two systematic reviews are integrated in this paper, and the existing knowledge is comprehensively summarized regarding the association between microbial pathogens and SB.<br><br>METHODS: We conducted a systematic search with keywords including SB and Toxoplasma gondii (Suicid* AND Toxoplasm*) and microbiome (Suicid* AND Microbiome AND Microbiota) throughout PubMed and Scopus to retrieve related studies up to 9 November 2023, identifying 24 eligible records. The subjects of the included studies had to have fulfilled the criteria of an SB disorder as defined by DSM-5, and death cases needed to have been defined as suicide.<br><br>RESULTS: Most studies reported significant association between toxoplasmosis and SB, suggesting a higher likelihood of SB in the infected population. Regarding the microbiome, only very few studies investigated an association between SB and alterations in the microbiome. Based on six included studies, there were some indications of a link between changes in the microbiome and SB.<br><br>CONCLUSION: The cognitive aspects of decision making in T. gondii-infected individuals with SB should be further investigated to unravel the underlying mechanisms. Further sufficiently powered studies are needed to establish a link between SB and alterations in the microbiome.}, }
@article {pmid38274095, year = {2023}, author = {Roszczenko-Jasińska, P and Giełdoń, A and Mazur, D and Spodzieja, M and Plichta, M and Czaplewski, C and Bal, W and Jagusztyn-Krynicka, EK and Bartosik, D}, title = {Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1335704}, pmid = {38274095}, issn = {2296-889X}, abstract = {Introduction: Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiotic therapies face challenges due to increasing antibiotic resistance and patient non-compliance, necessitating the exploration of alternative treatment approaches. In this study, we focused on Hp0231 (DsbK), an essential component of the H. pylori Dsb (disulfide bond) oxidative pathway, and investigated peptide-based inhibition as a potential therapeutic strategy. Methods: Three inhibitory peptides designed by computational modeling were evaluated for their effectiveness using a time-resolved fluorescence assay. We also examined the binding affinity between Hp0231 and the peptides using microscale thermophoresis. Results and discussion: Our findings demonstrate that in silico-designed synthetic peptides can effectively inhibit Hp0231-mediated peptide oxidation. Targeting Hp0231 oxidase activity could attenuate H. pylori virulence without compromising bacterial viability. Therefore, peptide-based inhibitors of Hp0231 could be candidates for the development of new targeted strategy, which does not influence the composition of the natural human microbiome, but deprive the bacterium of its pathogenic properties.}, }
@article {pmid38269610, year = {2024}, author = {Xuan, P and Gu, J and Cui, H and Wang, S and Toshiya, N and Liu, C and Zhang, T}, title = {Multi-scale topology and position feature learning and relationship-aware graph reasoning for prediction of drug-related microbes.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {2}, pages = {}, pmid = {38269610}, issn = {1367-4811}, support = {62372282//Natural Science Foundation of China/ ; NTF22032//STU Scientific Research Initiation/ ; LH2023F044//Natural Science Foundation of Heilongjiang Province/ ; }, mesh = {Humans ; *Neural Networks, Computer ; *Semantics ; Software ; }, abstract = {MOTIVATION: The human microbiome may impact the effectiveness of drugs by modulating their activities and toxicities. Predicting candidate microbes for drugs can facilitate the exploration of the therapeutic effects of drugs. Most recent methods concentrate on constructing of the prediction models based on graph reasoning. They fail to sufficiently exploit the topology and position information, the heterogeneity of multiple types of nodes and connections, and the long-distance correlations among nodes in microbe-drug heterogeneous graph.<br><br>RESULTS: We propose a new microbe-drug association prediction model, NGMDA, to encode the position and topological features of microbe (drug) nodes, and fuse the different types of features from neighbors and the whole heterogeneous graph. First, we formulate the position and topology features of microbe (drug) nodes by t-step random walks, and the features reveal the topological neighborhoods at multiple scales and the position of each node. Second, as the features of nodes are high-dimensional and sparse, we designed an embedding enhancement strategy based on supervised fully connected autoencoders to form the embeddings with representative features and the more discriminative node distributions. Third, we propose an adaptive neighbor feature fusion module, which fuses features of neighbors by the constructed position- and topology-sensitive heterogeneous graph neural networks. A novel self-attention mechanism is developed to estimate the importance of the position and topology of each neighbor to a target node. Finally, a heterogeneous graph feature fusion module is constructed to learn the long-distance correlations among the nodes in the whole heterogeneous graph by a relationship-aware graph transformer. Relationship-aware graph transformer contains the strategy for encoding the connection relationship types among the nodes, which is helpful for integrating the diverse semantics of these connections. The extensive comparison experimental results demonstrate NGMDA's superior performance over five state-of-the-art prediction methods. The ablation experiment shows the contributions of the multi-scale topology and position feature learning, the embedding enhancement strategy, the neighbor feature fusion, and the heterogeneous graph feature fusion. Case studies over three drugs further indicate that NGMDA has ability in discovering the potential drug-related microbes.<br><br>Source codes and Supplementary Material are available at https://github.com/pingxuan-hlju/NGMDA.}, }
@article {pmid38268162, year = {2024}, author = {Park, JS}, title = {[Microbiome and Biliary Tract Cancer].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {83}, number = {1}, pages = {1-5}, doi = {10.4166/kjg.2023.135}, pmid = {38268162}, issn = {2233-6869}, mesh = {Humans ; Dysbiosis/complications ; *Biliary Tract Neoplasms/diagnosis/etiology ; *Biliary Tract ; *Gallbladder Diseases ; *Microbiota ; }, abstract = {Biliary tract cancers encompass a group of malignancies that affect the bile ducts and gallbladder and are associated with a poor prognosis, often due to late diagnosis and limited treatment options. The incidence of biliary tract cancer has been increasing gradually, underscoring the need for a better understanding of its pathogenesis and potential risk factors. Research suggests that biliary tract cancer may develop through a combination of genetic and epigenetic alterations, as well as environmental factors. The role of microbial exposure and the human microbiome in the pathogenesis of biliary tract cancer is an emerging area of interest. Traditionally, the biliary tree was considered sterile under normal conditions, but recent studies have identified associations between specific microbiological patterns and inflammatory biliary diseases and cancer. The human microbiome plays a crucial role in maintaining host homeostasis and interacting with the host's immune system. Dysbiosis, or an imbalance in the microbiome composition, has been implicated in the development of various diseases, including cancer. Hence, dysbiosis in the biliary tract might trigger the pathogenesis of biliary tract cancer. Advances in next-generation sequencing technology have provided researchers with a more comprehensive view of the microbiota and their potential roles in health and disease, providing more evidence of the relationship between the microbiota and biliary tract cancer. This review summarizes the latest evidence of the microbiome that would be associated with biliary tract cancer.}, }
@article {pmid38264887, year = {2024}, author = {Inglis, LK and Roach, MJ and Edwards, RA}, title = {Prophages: an integral but understudied component of the human microbiome.}, journal = {Microbial genomics}, volume = {10}, number = {1}, pages = {}, pmid = {38264887}, issn = {2057-5858}, support = {RC2 DK116713/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Prophages ; *Bacteriophages ; Genome, Bacterial ; *Microbiota ; DNA ; }, abstract = {Phages integrated into a bacterial genome - called prophages - continuously monitor the vigour of the host bacteria to determine when to escape the genome and to protect their host from other phage infections, and they may provide genes that promote bacterial growth. Prophages are essential to almost all microbiomes, including the human microbiome. However, most human microbiome studies have focused on bacteria, ignoring free and integrated phages, so we know little about how these prophages affect the human microbiome. To address this gap in our knowledge, we compared the prophages identified in 14 987 bacterial genomes isolated from human body sites to characterize prophage DNA in the human microbiome. Here, we show that prophage DNA is ubiquitous, comprising on average 1-5 % of each bacterial genome. The prophage content per genome varies with the isolation site on the human body, the health of the human and whether the disease was symptomatic. The presence of prophages promotes bacterial growth and sculpts the microbiome. However, the disparities caused by prophages vary throughout the body.}, }
@article {pmid38259963, year = {2023}, author = {Rubio-Garcia, E and Ferrando, N and Martin, N and Ballesté-Delpierre, C and Miró, JM and Paredes, R and Casals-Pascual, C and Vila, J}, title = {In vitro antibacterial activity of antiretroviral drugs on key commensal bacteria from the human microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1306430}, pmid = {38259963}, issn = {2235-2988}, mesh = {Female ; Humans ; *HIV Infections/drug therapy ; *Methicillin-Resistant Staphylococcus aureus ; *Microbiota ; Bacteria ; Anti-Retroviral Agents/pharmacology ; Anti-Bacterial Agents/pharmacology ; }, abstract = {INTRODUCTION: Antiretroviral therapy has improved life expectancy in HIV-infected patients. However, people living with HIV under antiretroviral therapy are at higher risks of developing chronic complications and acquiring multidrug resistant bacteria than healthy population. These factors have been associated with shifts in gut microbiome composition and immune activation. It is unclear how antiretroviral drugs affect gut microbiota composition, but it has been observed that antiretroviral treatment is not able to fully restore gut health after HIV infection. Additionally, some antiretroviral drugs have shown antibacterial activity suggesting that these drugs could have a direct impact on the human microbiome composition.<br><br>METHODS: We determined the in vitro antibacterial activity of 16 antiretroviral drugs against a set of key clinically relevant and human commensal bacterial strains.<br><br>RESULTS: Our results demonstrate that 5 antiretroviral drugs have in vitro antibacterial activity against gut and vaginal human commensal bacteria. Zidovudine has antibacterial activity against Escherichia coli, Klebsiella pneumoniae and Prevotella bivia, abacavir against Gardnerella vaginalis, efavirenz against G. vaginalis and P. bivia and bictegravir against Enterococcus spp. and G. vaginalis. Moreover, we describe for the first time that elvitegravir has antibacterial activity against G. vaginalis and P. bivia and, most importantly, against vancomycin-resistant Enterococcus spp. and methicillin-resistant Staphylococcus aureus strains with MIC values of 4-16 and 4 &#xb5;g/mL, respectively showing high level of effectiveness against the tested multidrug-resistant bacteria.<br><br>DISCUSSION: Our results underscore that some antiretroviral drugs may influence the human microbiota composition. In addition, we report the potential use of elvitegravir to treat multidrug-resistant Gram-positive bacteria warranting the need of clinical studies to repurpose this antiretroviral drug.}, }
@article {pmid38257864, year = {2023}, author = {Marsiglia, R and Marangelo, C and Vernocchi, P and Scanu, M and Pane, S and Russo, A and Guanziroli, E and Del Chierico, F and Valeriani, M and Molteni, F and Putignani, L}, title = {Gut Microbiota Ecological and Functional Modulation in Post-Stroke Recovery Patients: An Italian Study.}, journal = {Microorganisms}, volume = {12}, number = {1}, pages = {}, pmid = {38257864}, issn = {2076-2607}, abstract = {Ischemic stroke (IS) can be caused by perturbations of the gut-brain axis. An imbalance in the gut microbiota (GM), or dysbiosis, may be linked to several IS risk factors and can influence the brain through the production of different metabolites, such as short-chain fatty acids (SCFAs), indole and derivatives. This study examines ecological changes in the GM and its metabolic activities after stroke. Fecal samples of 10 IS patients were compared to 21 healthy controls (CTRLs). GM ecological profiles were generated via 16S rRNA taxonomy as functional profiles using metabolomics analysis performed with a gas chromatograph coupled to a mass spectrometer (GC-MS). Additionally fecal zonulin, a marker of gut permeability, was measured using an enzyme-linked immuno assay (ELISA). Data were analyzed using univariate and multivariate statistical analyses and correlated with clinical features and biochemical variables using correlation and nonparametric tests. Metabolomic analyses, carried out on a subject subgroup, revealed a high concentration of fecal metabolites, such as SCFAs, in the GM of IS patients, which was corroborated by the enrichment of SCFA-producing bacterial genera such as Bacteroides, Christensellaceae, Alistipes and Akkermansia. Conversely, indole and 3-methyl indole (skatole) decreased compared to a subset of six CTRLs. This study illustrates how IS might affect the gut microbial milieu and may suggest potential microbial and metabolic biomarkers of IS. Expanded populations of Akkermansia and enrichment of acetic acid could be considered potential disease phenotype signatures.}, }
@article {pmid38256183, year = {2024}, author = {Filippou, C and Themistocleous, SC and Marangos, G and Panayiotou, Y and Fyrilla, M and Kousparou, CA and Pana, ZD and Tsioutis, C and Johnson, EO and Yiallouris, A}, title = {Microbial Therapy and Breast Cancer Management: Exploring Mechanisms, Clinical Efficacy, and Integration within the One Health Approach.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38256183}, issn = {1422-0067}, mesh = {Animals ; Humans ; *One Health ; Treatment Outcome ; Estrogens ; Cognition ; *Neoplasms ; }, abstract = {This comprehensive review elucidates the profound relationship between the human microbiome and breast cancer management. Recent findings highlight the significance of microbial alterations in tissue, such as the gut and the breast, and their role in influencing the breast cancer risk, development, progression, and treatment outcomes. We delve into how the gut microbiome can modulate systemic inflammatory responses and estrogen levels, thereby impacting cancer initiation and therapeutic drug efficacy. Furthermore, we explore the unique microbial diversity within breast tissue, indicating potential imbalances brought about by cancer and highlighting specific microbes as promising therapeutic targets. Emphasizing a holistic One Health approach, this review underscores the importance of integrating insights from human, animal, and environmental health to gain a deeper understanding of the complex microbe-cancer interplay. As the field advances, the strategic manipulation of the microbiome and its metabolites presents innovative prospects for the enhancement of cancer diagnostics and therapeutics. However, rigorous clinical trials remain essential to confirm the potential of microbiota-based interventions in breast cancer management.}, }
@article {pmid38256159, year = {2024}, author = {Rezzani, R and Gianò, M and Pinto, D and Rinaldi, F and van Noorden, CJF and Favero, G}, title = {Hepatic Alterations in a BTBR T + Itpr3tf/J Mouse Model of Autism and Improvement Using Melatonin via Mitigation Oxidative Stress, Inflammation and Ferroptosis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {2}, pages = {}, pmid = {38256159}, issn = {1422-0067}, support = {ARRS P1-0245//Slovenian Research Agency/ ; J3-2526//Slovenian Research Agency/ ; }, mesh = {Humans ; Animals ; Mice ; *Autistic Disorder/drug therapy/genetics ; Kelch-Like ECH-Associated Protein 1 ; *Melatonin/pharmacology/therapeutic use ; *Autism Spectrum Disorder/drug therapy/genetics ; *Ferroptosis ; NF-E2-Related Factor 2/genetics ; Liver ; Inflammation/drug therapy ; Oxidative Stress ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Autism spectrum disorder (ASD) is a complicated neurodevelopmental disorder, and its etiology is not well understood. It is known that genetic and nongenetic factors determine alterations in several organs, such as the liver, in individuals with this disorder. The aims of the present study were to analyze morphological and biological alterations in the liver of an autistic mouse model, BTBR T + Itpr3tf/J (BTBR) mice, and to identify therapeutic strategies for alleviating hepatic impairments using melatonin administration. We studied hepatic cytoarchitecture, oxidative stress, inflammation and ferroptosis in BTBR mice and used C57BL6/J mice as healthy control subjects. The mice were divided into four groups and then treated and not treated with melatonin, respectively. BTBR mice showed (a) a retarded development of livers and (b) iron accumulation and elevated oxidative stress and inflammation. We demonstrated that the expression of ferroptosis markers, the transcription factor nuclear factor erythroid-related factor 2 (NFR2), was upregulated, and the Kelch-like ECH-associated protein 1 (KEAP1) was downregulated in BTBR mice. Then, we evaluated the effects of melatonin on the hepatic alterations of BTBR mice; melatonin has a positive effect on liver cytoarchitecture and metabolic functions.}, }
@article {pmid38249228, year = {2023}, author = {Bhattacharjee, P and Karim, KA and Khan, Z}, title = {Harnessing the Microbiome: A Comprehensive Review on Advancing Therapeutic Strategies for Rheumatic Diseases.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50964}, pmid = {38249228}, issn = {2168-8184}, abstract = {Rheumatic diseases are a group of disorders that affect the joints, muscles, and bones. These diseases, such as rheumatoid arthritis, lupus, and psoriatic arthritis, can cause pain, stiffness, and swelling, leading to reduced mobility and disability. Recent studies have identified the microbiome, the diverse community of microorganisms that live in and on the human body, as a potential factor in the development and progression of rheumatic diseases. Harnessing the microbiome offers a promising new avenue for developing therapeutic strategies for these debilitating conditions. There is growing interest in the role of oral and gut microbiomes in the management of rheumatoid arthritis and other autoimmune disease. Microbial metabolites have immunomodulatory properties that could be exploited for rheumatic disorders. A wide range of microorganisms are present in the oral cavity and are found to be vulnerable to the effects of the environment. The physiology and ecology of the microbiota become intimately connected with those of the host, and they critically influence the promotion of health or progression toward disease. This article aims to provide a comprehensive overview of the current state of knowledge on oral and gut microbiome and its potential future role in the management of rheumatic diseases. This article will also discuss newer treatment strategies such as bioinformatic analyses and fecal transplantation.}, }
@article {pmid38247937, year = {2024}, author = {Kim, J and Jang, H and Koh, H}, title = {MiMultiCat: A Unified Cloud Platform for the Analysis of Microbiome Data with Multi-Categorical Responses.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {38247937}, issn = {2306-5354}, support = {2021R1C1C1013861//National Research Foundation of Korea/ ; }, abstract = {The field of the human microbiome is rapidly growing due to the recent advances in high-throughput sequencing technologies. Meanwhile, there have also been many new analytic pipelines, methods and/or tools developed for microbiome data preprocessing and analytics. They are usually focused on microbiome data with continuous (e.g., body mass index) or binary responses (e.g., diseased vs. healthy), yet multi-categorical responses that have more than two categories are also common in reality. In this paper, we introduce a new unified cloud platform, named MiMultiCat, for the analysis of microbiome data with multi-categorical responses. The two main distinguishing features of MiMultiCat are as follows: First, MiMultiCat streamlines a long sequence of microbiome data preprocessing and analytic procedures on user-friendly web interfaces; as such, it is easy to use for many people in various disciplines (e.g., biology, medicine, public health). Second, MiMultiCat performs both association testing and prediction modeling extensively. For association testing, MiMultiCat handles both ecological (e.g., alpha and beta diversity) and taxonomical (e.g., phylum, class, order, family, genus, species) contexts through covariate-adjusted or unadjusted analysis. For prediction modeling, MiMultiCat employs the random forest and gradient boosting algorithms that are well suited to microbiome data while providing nice visual interpretations. We demonstrate its use through the reanalysis of gut microbiome data on obesity with body mass index categories. MiMultiCat is freely available on our web server.}, }
@article {pmid38247589, year = {2023}, author = {Garba, Z and Kaboré, B and Bonkoungou, IJO and Natama, MH and Rouamba, T and Haukka, K and Kirveskari, JP and Tinto, H and Sangaré, L and Barro, N and Kantele, A}, title = {Phenotypic Detection of Carbapenemase and AmpC-β-Lactamase Production among Extended Spectrum β-Lactamase (ESBL)-Producing Escherichia coli and Klebsiella spp. Isolated from Clinical Specimens.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {1}, pages = {}, pmid = {38247589}, issn = {2079-6382}, support = {FA4-DGD program//Belgium Directorate General for Development Cooperation (DGD) through the collaborative framework agreement 4 between Clinical Research Unit of Nanoro (CRUN), Burkina Faso and Institute of Tropical Medicine of Antwerp (ITM), Belgium and the Academy of Fin/ ; 318642//Academy of Finland through the AMRIWA project/ ; //Finnish institutions (FinELib)/ ; }, abstract = {Introduction: Data on antimicrobial resistance (AMR) are sparse across numerous African countries, as microbiological analyses are not routinely conducted and surveillance data are not collected. Accordingly, clinical samples are not routinely tested for carbapenem-resistant bacteria and, therefore, the general understanding of their prevalence in the region remains limited. Methods: Between January 2020 and June 2022, we collected extended spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-PE) isolates from five hospitals in Burkina Faso. After an initial culture on ESBL-selective media, the species were identified using API20E and isolates were tested against 13 antimicrobial agents using the disc diffusion method on Mueller-Hinton (MH) agar. ESBL production was confirmed via a double-disc synergy test. Production of carbapenemases and AmpC-β-lactamases and phenotypic co-resistance were determined. Results: Among the 473 ESBL-PE, 356 were ESBL-E. coli (ESBL-Ec) and 117 were Klebsiella spp. (ESBL-K). Of these isolates, 5.3% were carbapenemase and 5.3% were AmpC-β-lactamase-positive. Three types of carbapenemases were identified: 19 NDM, 3 OXA-48-like and 1 VIM. Two isolates produced both NDM and OXA-48-like carbapenemases. Carbapenemase producers were detected at all levels of healthcare. Co-resistance rates were up to 85% for aminoglycosides, 90% for sulfonamides, 95% for fluoroquinolones and 25% for chloramphenicol. Fosfomycin resistance was 6% for ESBL-Ec and 49% for ESBL-K (49%). Conclusions: Some of the ESBL-Ec and ESBL-K co-produced carbapenemases and/or AmpC-β-lactamases at all healthcare levels and in various sample types with high co-resistance rates to non-betalactams. Carbapenem resistance is no longer rare, calling for testing in routine diagnostics, a comprehensive resistance surveillance system and infection control within healthcare.}, }
@article {pmid38246848, year = {2024}, author = {Liu, Y and Fachrul, M and Inouye, M and Méric, G}, title = {Harnessing human microbiomes for disease prediction.}, journal = {Trends in microbiology}, volume = {32}, number = {7}, pages = {707-719}, doi = {10.1016/j.tim.2023.12.004}, pmid = {38246848}, issn = {1878-4380}, support = {RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; }, mesh = {Humans ; *Microbiota ; Risk Factors ; Cardiovascular Diseases/microbiology ; }, abstract = {The human microbiome has been increasingly recognized as having potential use for disease prediction. Predicting the risk, progression, and severity of diseases holds promise to transform clinical practice, empower patient decisions, and reduce the burden of various common diseases, as has been demonstrated for cardiovascular disease or breast cancer. Combining multiple modifiable and non-modifiable risk factors, including high-dimensional genomic data, has been traditionally favored, but few studies have incorporated the human microbiome into models for predicting the prospective risk of disease. Here, we review research into the use of the human microbiome for disease prediction with a particular focus on prospective studies as well as the modulation and engineering of the microbiome as a therapeutic strategy.}, }
@article {pmid38246133, year = {2024}, author = {Chulenbayeva, L and Ganzhula, Y and Kozhakhmetov, S and Jarmukhanov, Z and Nurgaziyev, M and Nurgozhina, A and Muhanbetzhanov, N and Sergazy, S and Zhetkenev, S and Borykbay, Z and Tkachev, V and Urazova, S and Vinogradova, E and Kushugulova, A}, title = {The Trajectory of Successful Aging: Insights from Metagenome and Cytokine Profiling.}, journal = {Gerontology}, volume = {70}, number = {4}, pages = {390-407}, pmid = {38246133}, issn = {1423-0003}, mesh = {Aged, 80 and over ; Humans ; *Metagenome ; Aging ; *Microbiota ; Longevity ; Cytokines ; }, abstract = {INTRODUCTION: The longevity is influenced by genetic, environmental, and lifestyle factors. The specific changes that occur in the gut microbiome during the aging process, and their relationship to longevity and immune function, have not yet been fully understood. The ongoing research of other microbiome based on longevity cohort in Kazakhstan provides preliminary information on longevity-related aging, where cytokine expression is associated with specific microbial communities and microbial functions.<br><br>METHODS: Metagenomic shotgun sequencing study of 40 long-lived individuals aged 90 years and over was carried out, who were conditionally healthy and active, able to serve themselves, without a history of serious infection and cancer, who had not taken any antimicrobials, including probiotics. Blood serum was analyzed for clinical and laboratory characteristics. The cytokine and chemokine profile in serum and stool samples was assessed using multiplex analysis.<br><br>RESULTS: We found a significant increase in the expression of pro-inflammatory cytokines IL-1a, IL-6, 12p70, IP-10, IFN&#x3b1;2, IL-15, TNFa, as well as chemokines MIP-1a/CCL3 and MIP-1b/CCL4, chemokine motif ligands MCP-3/CCL7 and MDC/CCL22(1c). Nonagenerians and centenarians demonstrated a greater diversity of core microbiota genera and showed an elevated prevalence of the genera Bacteroides, Clostridium, Escherichia, and Alistipes. Conversely, there was a decrease in the abundance of the genera Ruminococcus, Fusicatenibacter, Dorea, as well as the species Fusicatenibacter saccharivorans. Furthermore, functional analysis revealed that the microbiome in long-lived group has a high capacity for lipid metabolism, amino acid degradation, and potential signs of chronic inflammatory status.<br><br>CONCLUSION: Long-lived individuals exhibit an immune system imbalance and observed changes in the composition of the gut microbiota at the genus level between to the two age-groups. Age-related changes in the gut microbiome, metabolic functions of the microbial community, and chronic inflammation all contribute to immunosenescence. In turn, the inflammatory state and microbial composition of the gut is related to nutritional status.}, }
@article {pmid38243767, year = {2024}, author = {Zudock, KK and Player, R and Ernlund, A and Timm, CM and English, CE and Ellis, MW and Tribble, DR and Merrell, DS and Bennett, JW and Millar, EV}, title = {Dynamics of the Oral Microbiome During Initial Military Training at Fort Benning, Georgia.}, journal = {Military medicine}, volume = {189}, number = {7-8}, pages = {e1753-e1759}, pmid = {38243767}, issn = {1930-613X}, support = {IAA Y1-Al-5072//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; HU0001190002//Defense Health Agency/ ; }, mesh = {Humans ; *Microbiota/physiology ; Male ; *Military Personnel/statistics &amp; numerical data ; Female ; Cohort Studies ; Georgia/epidemiology ; Mouth/microbiology ; RNA, Ribosomal, 16S/analysis ; }, abstract = {INTRODUCTION: Military trainees are at increased risk for infectious disease outbreaks because of the unique circumstances of the training environment (e.g., close proximity areas and physiologic/psychologic stress). Standard medical countermeasures in military training settings include routine immunization (e.g., influenza and adenovirus) as well as chemoprophylaxis [e.g., benzathine penicillin G (Bicillin) for the prevention of group A streptococcal disease] for pathogens associated with outbreaks in these settings. In a population of U.S. Army Infantry trainees, we evaluated changes in the oral microbiome during a 14-week military training cycle.<br><br>MATERIALS AND METHODS: Trainees were enrolled in an observational cohort study in 2015-2016. In 2015, Bicillin was administered to trainees to ameliorate the risk of group A Streptococcus outbreaks, whereas in 2016, trainees did not receive a Bicillin inoculation. Oropharyngeal swabs were collected from participants at days 0, 7, 14, 28, 56, and 90 of training. Swabs were collected, flash frozen, and stored. DNA was extracted from swabs, and amplicon sequencing of the 16s rRNA gene was performed. Microbiome dynamics were evaluated using the QIIME 2 workflow along with DADA2, SINA with SILVA, and an additional processing in R.<br><br>RESULTS: We observed that microbiome samples from the baseline (day 0) visit were distinct from one another, whereas samples collected on day 14 exhibited significant microbiome convergence. Day 14 convergence was coincident with an increase in DNA sequences associated with Streptococcus, though there was not a significant difference between Streptococcus abundance over time between 2015 and 2016 (P&#x2009;=&#x2009;.07), suggesting that Bicillin prophylaxis did not significantly impact overall Streptococcus abundance.<br><br>CONCLUSIONS: The temporary convergence of microbiomes is coincident with a rise in communicable infections in this population. The dynamic response of microbiomes during initial military training supports similar observations in the literature of transient convergence of the human microbiome under cohabitation in the time frame including in this experiment. This population and the associated longitudinal studies allow for controlled studies of human microbiome under diverse conditions.}, }
@article {pmid38239365, year = {2023}, author = {Kim, S and Chun, SH and Cheon, YH and Kim, M and Kim, HO and Lee, H and Hong, ST and Park, SJ and Park, MS and Suh, YS and Lee, SI}, title = {Peptoniphilus gorbachii alleviates collagen-induced arthritis in mice by improving intestinal homeostasis and immune regulation.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1286387}, pmid = {38239365}, issn = {1664-3224}, mesh = {Mice ; Humans ; Animals ; *Arthritis, Experimental ; *Arthritis, Rheumatoid ; Disease Models, Animal ; Cytokines/metabolism ; *Firmicutes ; }, abstract = {INTRODUCTION: The intricate connection between gut microbiota and rheumatoid arthritis (RA) pathogenesis has gained prominence, although the specific microbial species contributing to RA development remain largely unknown. Recent studies have sought to comprehensively explore alterations in the human microbiome, focusing on identifying disease-related microbial species through blood analysis. Consequently, this study aimed to identify RA-associated microbial species using a serum microbial array system and to investigate the efficacy and underlying mechanisms of potential microbial species for RA treatment.<br><br>METHODS: Serum immunoglobulin M levels against 384 intestinal microbial species were assessed using a microbial microarray in patients with RA and healthy individuals. We investigated the therapeutic potential of the identified microbial candidate regarding arthritis development, immune responses, gut barrier function, and gut microbiome using a collagen-induced arthritis (CIA) mouse model.<br><br>RESULTS: Our findings revealed significant alterations in antibody levels against 36 microbial species in patients with RA compared to healthy individuals. Notably, the antibody levels against Peptoniphilus gorbachii (PG) were decreased in patients with RA and exhibited an inverse correlation with RA disease activity. In vitro experiments demonstrated that PG produced acetate and butyrate, while exhibiting anti-inflammatory properties. In CIA mice, PG administration suppressed arthritis symptoms, reduced the accumulation of inflammatory monocytes in the mesenteric lymph nodes, and downregulated gene expression of pro-inflammatory cytokines in the ileum. Additionally, PG supplementation restored intestinal barrier integrity and partially resolved gut microbial dysbiosis in CIA mice. The fecal microbiota in PG-treated mice corresponded to improved intestinal barrier integrity and reduced inflammatory responses.<br><br>CONCLUSION: This study highlights the potential of serum-based detection of anti-microbial antibodies to identify microbial targets at the species level for RA treatment. Moreover, our findings suggest that PG, identified through the microbial microarray analysis, holds therapeutic potential for RA by restoring intestinal barrier integrity and suppressing the immunologic response associated with RA.}, }
@article {pmid38235259, year = {2024}, author = {Zhang, G and Le Souëf, P}, title = {The influence of modern living conditions on the human microbiome and potential therapeutic opportunities for allergy prevention.}, journal = {The World Allergy Organization journal}, volume = {17}, number = {1}, pages = {100857}, pmid = {38235259}, issn = {1939-4551}, abstract = {Modern living conditions and the recent surge in global urbanization have transformed the human microbiome. This transformation is believed to be a significant factor in the recent spike of common chronic inflammatory diseases like asthma and allergies worldwide, evident in both developed and developing nations. Immigrants from less developed regions who settle in highly urbanized and affluent areas present an ideal demographic for research. Investigating immigrant populations can yield valuable insights, particularly when studying microbiome changes that occur as individuals transition from areas with low asthma prevalence to regions with a high prevalence of the condition. The application of prebiotics and probiotics as potential treatments for asthma and allergies faces challenges. This is due to the complex interplay of numerous factors that contribute to their aetiology. Exploring the interaction between the human microbiome and potential epigenetic changes in specific populations, such as immigrants adapting to new, urbanized environments, may offer crucial insights. Such research could underscore the role of prebiotics and probiotics in preventing allergic conditions. Recognizing the changes in the human microbiome in the context of a Western/modern environment might be essential in addressing the increasing prevalence of allergic diseases. Persistent research in this domain is pivotal for devising effective interventions such as dietary supplementation with prebiotics and probiotics.}, }
@article {pmid38233502, year = {2024}, author = {Chopra, A and Franco-Duarte, R and Rajagopal, A and Choowong, P and Soares, P and Rito, T and Eberhard, J and Jayasinghe, TN}, title = {Exploring the presence of oral bacteria in non-oral sites of patients with cardiovascular diseases using whole metagenomic data.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1476}, pmid = {38233502}, issn = {2045-2322}, support = {2022.00340.CEECIND//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; "Contrato-Programa" UIDB/04050/2020//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Humans ; *Cardiovascular Diseases ; *Microbiota/genetics ; Bacteria/genetics ; Metagenome ; *Plaque, Atherosclerotic ; }, abstract = {Cardiovascular diseases (CVDs) encompass various conditions affecting the heart and its blood vessels and are often linked with oral microbes. Our data analysis aimed to identify oral bacteria from other non-oral sites (i.e., gut, arterial plaque and cultured blood) that could be linked with CVDs. Taxonomic profiling identified bacteria to the species level and compared with the Human Oral Microbiome Database (HOMD). The oral bacteria in the gut, cultured blood and arterial plaque samples were catalogued, with their average frequency calculated for each sample. Additionally, data were filtered by comparison with the Human Microbiome Project (HMP) database. We identified 17,243 microbial species, of which 410 were present in the HOMD database and further denominated as "oral", and were found in at least one gut sample, but only 221 and 169 species were identified in the cultured blood and plaque samples, respectively. Of the 410 species, 153 were present solely in oral-associated environments after comparison with the HMP database, irrespective of their presence in other body sites. Our results suggest a potential connection between the presence of specific species of oral bacterial and occurrence of CVDs. Detecting these oral bacterial species in non-oral sites of patients with CVDs could help uncover the link between oral health and general health, including cardiovascular conditions via bacterial translocation.}, }
@article {pmid38229087, year = {2024}, author = {Federico, A and Möbus, L and Al-Abdulraheem, Z and Pavel, A and Fortino, V and Del Giudice, G and Alenius, H and Fyhrquist, N and Greco, D}, title = {Integrative network analysis suggests prioritised drugs for atopic dermatitis.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {64}, pmid = {38229087}, issn = {1479-5876}, support = {101043848//HORIZON EUROPE European Research Council/ ; 322761//Academy of Finland/ ; 821511//HORIZON EUROPE Innovative Medicines Initiative 2 Joint Undertaking (JU)/ ; }, mesh = {Humans ; *Dermatitis, Atopic/drug therapy/genetics ; Skin ; Gene Expression Profiling ; Phenotype ; Biomarkers ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease whose pathophysiology involves the interplay between genetic and environmental factors, ultimately leading to dysfunction of the epidermis. While several treatments are effective in symptom management, many existing therapies offer only temporary relief and often come with side effects. For this reason, the formulation of an effective therapeutic plan is challenging and there is a need for more effective and targeted treatments that address the root causes of the condition. Here, we hypothesise that modelling the complexity of the molecular buildup of the atopic dermatitis can be a concrete means to drive drug discovery.<br><br>METHODS: We preprocessed, harmonised and integrated publicly available transcriptomics datasets of lesional and non-lesional skin from AD patients. We inferred co-expression network models of both AD lesional and non-lesional skin and exploited their interactional properties by integrating them with a priori knowledge in order to extrapolate a robust AD disease module. Pharmacophore-based virtual screening was then utilised to build a tailored library of compounds potentially active for AD.<br><br>RESULTS: In this study, we identified a core disease module for AD, pinpointing known and unknown molecular determinants underlying the skin lesions. We identified skin- and immune-cell type signatures expressed by the disease module, and characterised the impaired cellular functions underlying the complex phenotype of atopic dermatitis. Therefore, by investigating the connectivity of genes belonging to the AD module, we prioritised novel putative biomarkers of the disease. Finally, we defined a tailored compound library by characterising the therapeutic potential of drugs targeting genes within the disease module to facilitate and tailor future drug discovery efforts towards novel pharmacological strategies for AD.<br><br>CONCLUSIONS: Overall, our study reveals a core disease module providing unprecedented information about genetic, transcriptional and pharmacological relationships that foster drug discovery in atopic dermatitis.}, }
@article {pmid38228159, year = {2024}, author = {Nenciarini, S and Renzi, S and di Paola, M and Meriggi, N and Cavalieri, D}, title = {Ascomycetes yeasts: The hidden part of human microbiome.}, journal = {WIREs mechanisms of disease}, volume = {16}, number = {3}, pages = {e1641}, doi = {10.1002/wsbm.1641}, pmid = {38228159}, issn = {2692-9368}, support = {G84I18000160002//Regione Toscana/ ; 36954/7303/18//Ministero delle Politiche Agricole Alimentari e Forestali/ ; 529051018//Joint Programming Initiative A healthy diet for a healthy life/ ; JTC-2017-7//Joint Programming Initiative A healthy diet for a healthy life/ ; }, mesh = {Humans ; *Ascomycota/genetics ; Mycobiome/genetics ; Microbiota ; Metagenomics/methods ; Candida/genetics/isolation &amp; purification ; Gastrointestinal Microbiome ; }, abstract = {The fungal component of the microbiota, the mycobiota, has been neglected for a long time due to its poor richness compared to bacteria. Limitations in fungal detection and taxonomic identification arise from using metagenomic approaches, often borrowed from bacteriome analyses. However, the relatively recent discoveries of the ability of fungi to modulate the host immune response and their involvement in human diseases have made mycobiota a fundamental component of the microbial communities inhabiting the human host, deserving some consideration in host-microbe interaction studies and in metagenomics. Here, we reviewed recent data on the identification of yeasts of the Ascomycota phylum across human body districts, focusing on the most representative genera, that is, Saccharomyces and Candida. Then, we explored the key factors involved in shaping the human mycobiota across the lifespan, ranging from host genetics to environment, diet, and lifestyle habits. Finally, we discussed the strengths and weaknesses of culture-dependent and independent methods for mycobiota characterization. Overall, there is still room for some improvements, especially regarding fungal-specific methodological approaches and bioinformatics challenges, which are still critical steps in mycobiota analysis, and to advance our knowledge on the role of the gut mycobiota in human health and disease. This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Environmental Factors Infectious Diseases > Environmental Factors.}, }
@article {pmid38227345, year = {2024}, author = {Grasso, G and Bianciotto, V and Marmeisse, R}, title = {Paleomicrobiology: Tracking the past microbial life from single species to entire microbial communities.}, journal = {Microbial biotechnology}, volume = {17}, number = {1}, pages = {e14390}, pmid = {38227345}, issn = {1751-7915}, support = {//Alliance Sorbonne Universit&#xe9;/ ; ATM 2021//Mus&#xe9;um National d'Histoire Naturelle/ ; Bando Da Vinci 2022//Universit&#xe0; Italo Francese/ ; }, mesh = {Humans ; *Microbiota ; DNA ; Microbial Consortia ; }, abstract = {By deciphering information encoded in degraded ancient DNA extracted from up to million-years-old samples, molecular paleomicrobiology enables to objectively retrace the temporal evolution of microbial species and communities. Assembly of full-length genomes of ancient pathogen lineages allows not only to follow historical epidemics in space and time but also to identify the acquisition of genetic features that represent landmarks in the evolution of the host-microbe interaction. Analysis of microbial community DNA extracted from essentially human paleo-artefacts (paleofeces, dental calculi) evaluates the relative contribution of diet, lifestyle and geography on the taxonomic and functional diversity of these guilds in which have been identified species that may have gone extinct in today's human microbiome. As for non-host-associated environmental samples, such as stratified sediment cores, analysis of their DNA illustrates how and at which pace microbial communities are affected by local or widespread environmental disturbance. Description of pre-disturbance microbial diversity patterns can aid in evaluating the relevance and effectiveness of remediation policies. We finally discuss how recent achievements in paleomicrobiology could contribute to microbial biotechnology in the fields of medical microbiology and food science to trace the domestication of microorganisms used in food processing or to illustrate the historic evolution of food processing microbial consortia.}, }
@article {pmid38225565, year = {2024}, author = {Rojas-Velazquez, D and Kidwai, S and Kraneveld, AD and Tonda, A and Oberski, D and Garssen, J and Lopez-Rincon, A}, title = {Methodology for biomarker discovery with reproducibility in microbiome data using machine learning.}, journal = {BMC bioinformatics}, volume = {25}, number = {1}, pages = {26}, pmid = {38225565}, issn = {1471-2105}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Autism Spectrum Disorder ; Reproducibility of Results ; *Diabetes Mellitus, Type 2/genetics ; *Biomedical Research ; Machine Learning ; Biomarkers ; *Microbiota/genetics ; }, abstract = {BACKGROUND: In recent years, human microbiome studies have received increasing attention as this field is considered a potential source for clinical applications. With the advancements in omics technologies and AI, research focused on the discovery for potential biomarkers in the human microbiome using machine learning tools has produced positive outcomes. Despite the promising results, several issues can still be found in these studies such as datasets with small number of samples, inconsistent results, lack of uniform processing and methodologies, and other additional factors lead to lack of reproducibility in biomedical research. In this work, we propose a methodology that combines the DADA2 pipeline for 16s rRNA sequences processing and the Recursive Ensemble Feature Selection (REFS) in multiple datasets to increase reproducibility and obtain robust and reliable results in biomedical research.<br><br>RESULTS: Three experiments were performed analyzing microbiome data from patients/cases in Inflammatory Bowel Disease (IBD), Autism Spectrum Disorder (ASD), and Type 2 Diabetes (T2D). In each experiment, we found a biomarker signature in one dataset and applied to 2 other as further validation. The effectiveness of the proposed methodology was compared with other feature selection methods such as K-Best with F-score and random selection as a base line. The Area Under the Curve (AUC) was employed as a measure of diagnostic accuracy and used as a metric for comparing the results of the proposed methodology with other feature selection methods. Additionally, we use the Matthews Correlation Coefficient (MCC) as a metric to evaluate the performance of the methodology as well as for comparison with other feature selection methods.<br><br>CONCLUSIONS: We developed a methodology for reproducible biomarker discovery for 16s rRNA microbiome sequence analysis, addressing the issues related with data dimensionality, inconsistent results and validation across independent datasets. The findings from the three experiments, across 9 different datasets, show that the proposed methodology achieved higher accuracy compared to other feature selection methods. This methodology is a first approach to increase reproducibility, to provide robust and reliable results.}, }
@article {pmid38224872, year = {2024}, author = {Kau, AL and Rosen, AL and Rosas-Salazar, C}, title = {Can Therapeutic Targeting of the Human Microbiome Influence Asthma Management? A Pro/Con Debate.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {12}, number = {4}, pages = {863-869}, doi = {10.1016/j.jaip.2023.12.053}, pmid = {38224872}, issn = {2213-2201}, mesh = {Humans ; *Microbiota ; *Asthma/therapy ; *Gastrointestinal Microbiome ; Respiratory System ; Inflammation ; }, abstract = {Asthma is a clinically heterogeneous disease, and despite substantial improvements in therapies, there remains an unmet need for well-tolerated, effective treatments. Observational studies have demonstrated that alterations in the respiratory and gut microbiome are associated with the development of asthma and its severity. These findings are supported by preclinical models demonstrating that respiratory and gut microbes can alter airway inflammation. Therapeutic approaches to target the human microbiome have been increasingly applied to a wide range of acute and chronic diseases, but there are currently no microbiome-based therapeutics approved for the treatment of asthma. This clinical commentary addresses the future role of microbiome-based therapeutics in asthma management from both a pro and con perspective. We examine (1) the prospects for clinical studies demonstrating a causal relationship between the human microbiome and the severity of asthma; (2) the challenges and potential solutions for designing, testing, and implementing a microbiome-based therapeutic; and (3) the possibility of microbiome-based therapeutics for conditions comorbid to asthma. We conclude by identifying research priorities that will help determine the future of microbiome-based therapeutics for the management of asthma.}, }
@article {pmid38222203, year = {2023}, author = {Torres, AR and Morris, S and Benson, M and Wilkinson, C and Lyon, R}, title = {Stimulation of Pro-inflammatory Cytokines in Mixed Cultures of Peripheral Blood Mononuclear Cells and Anaerobic Bacteria.}, journal = {Cureus}, volume = {15}, number = {12}, pages = {e50586}, pmid = {38222203}, issn = {2168-8184}, abstract = {In the last couple of decades, much progress has been made in studying bacteria living in humans. However, there is much more to learn about bacteria immune cell interactions. Here, we show that anaerobic bacteria do not grow when cultured overnight with human cells under atmospheric air. Air contains about 18% oxygen, which inhibits the growth of these bacteria while supporting the cultivation of human cells. The bacteria cultured with human peripheral blood mononuclear cells (PBMCs) inflamed with phytohemagglutinin (PHA) greatly increased the production of proinflammatory cytokines like tumor necrosis factor-alpha (TNFα) while inhibiting the production of monocyte chemoattractant protein-1 (MCP-1), an important chemokine.}, }
@article {pmid38219382, year = {2024}, author = {Whyte, M and Douwes, J and Ranta, A}, title = {Green space and stroke: A scoping review of the evidence.}, journal = {Journal of the neurological sciences}, volume = {457}, number = {}, pages = {122870}, doi = {10.1016/j.jns.2024.122870}, pmid = {38219382}, issn = {1878-5883}, mesh = {Humans ; Parks, Recreational ; Cross-Sectional Studies ; *Air Pollution ; *Stroke/epidemiology/therapy ; Exercise ; Environmental Exposure ; }, abstract = {BACKGROUND: Global industrialisation and urbanisation has led to an increased interest in the link between the environment and health. Stroke is a major cause of morbidity and mortality, and there is increased evidence that environmental factors may affect both the incidence and severity of stroke. This review summarises the evidence for relationship between green space exposure and stroke incidence and outcomes.<br><br>METHODS: We conducted a literature search in Medline and Scopus until 1 August 2023, and screened references of relevant articles. Selected articles were appraised for their relevance, and critically reviewed. The findings were thematically categorised.<br><br>RESULTS: Of the 1342 papers identified, 27 were included. These involved a mix of study designs (cohort, cross-sectional, quasi-experimental, time stratified case crossover and ecological). There was consistent evidence indicating a protective association between green space exposure and disability and stroke-related death with mortality hazard ratios between 0.66 and 0.95. Most studies also showed that green space was inversely associated with stroke risk, with risk estimates from studies showing a protective effect ranging between 0.4 and 0.98; however, results were more mixed and some did not reach statistical significance. The moderating effects of green spaces on ambient temperatures, noise and air pollution, and psychosocial health plus greater enjoyment and opportunity for exercise and enrichment of the human microbiome may underly these associations.<br><br>CONCLUSION: There is likely some protective effect of green space on stroke, with the benefits most convincingly shown for post-stroke outcomes. More research is recommended to confirm the protective association between green space exposure and reduced stroke risk.}, }
@article {pmid38215690, year = {2024}, author = {Zeng, W and Wu, J and Xie, H and Xu, H and Liang, D and He, Q and Yang, X and Liu, C and Gong, J and Zhang, Q and Luo, Z and Chen, Y and He, Z and Lan, P}, title = {Enteral nutrition promotes the remission of colitis by gut bacteria-mediated histidine biosynthesis.}, journal = {EBioMedicine}, volume = {100}, number = {}, pages = {104959}, pmid = {38215690}, issn = {2352-3964}, mesh = {Humans ; Animals ; Mice ; Enteral Nutrition ; Interleukin-10/genetics ; Histidine ; *Colitis/etiology/therapy ; *Crohn Disease/microbiology ; Bacteria/genetics ; Disease Models, Animal ; DNA, Ribosomal ; *Firmicutes ; }, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) is an important alternative strategy for patients with Crohn's disease (CD), and during this process, microbiota alterations have been observed. However, the underlying mechanisms by which EEN reduces intestinal inflammation are currently unclear.<br><br>METHODS: The therapeutic potential of enteral nutrition (EN) was assessed using various mouse models. Fecal full-length 16S rDNA sequencing analysis and several CD metagenome datasets were used to identify the candidate therapeutic bacteria Faecalibaculum rodentium (F.&#xa0;rodentium). Whole genome sequencing of F.&#xa0;rodentium and widely-targeted metabolome analysis of the supernatant showed that EN-induced F.&#xa0;rodentium accumulation protected against colitis via histidine biosynthesis.<br><br>FINDINGS: The therapeutic potential of EN therapy was observed in both dextran sulfate sodium (DSS)-induced colitis and Il10[-/-] spontaneous colitis mouse models. Accumulation of F.&#xa0;rodentium after EN therapy was determined using full-length 16S rDNA sequencing and verified with several metagenome datasets from patients with CD. Colonization of an isolated F.&#xa0;rodentium could reduce colitis in Il10[-/-] mice. Significant histidine enrichment was observed in the F.&#xa0;rodentium culture supernatant, and a series of histidine biosynthesis genes were observed in the F.&#xa0;rodentium genome. Engineered Escherichia coli Nissle 1917 (EcN), encoding the heterologous hisG of F.&#xa0;rodentium (EcN-hisG), which was a key driver of histidine biosynthesis in F.&#xa0;rodentium, was found to protect against colitis.<br><br>INTERPRETATION: This study suggests that EN-induced F.&#xa0;rodentium accumulation protects against colitis in mice via gut bacteria-mediated histidine biosynthesis.<br><br>FUNDING: A full list of funding bodies can be found in the Acknowledgements section.}, }
@article {pmid38215640, year = {2024}, author = {Li, J and Li, Y and Zhou, L and Li, C and Liu, J and Liu, D and Fu, Y and Wang, Y and Tang, J and Zhou, L and Tan, S and Wang, L}, title = {The human microbiome and benign prostatic hyperplasia: Current understandings and clinical implications.}, journal = {Microbiological research}, volume = {281}, number = {}, pages = {127596}, doi = {10.1016/j.micres.2023.127596}, pmid = {38215640}, issn = {1618-0623}, mesh = {Male ; Aged ; Middle Aged ; Humans ; *Prostatic Hyperplasia/etiology/metabolism ; Inflammation ; *Metabolic Syndrome/complications ; *Microbiota ; }, abstract = {The research of the human microbiome in the preceding decade has yielded novel perspectives on human health and diseases. Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly males, which negatively affects the life quality. Existing evidence has indicated that the human microbiome, including urinary, intra-prostate, gut, oral and blood microbiome may exert a significant impact on the natural progression of BPH. The dysbiosis of the microbiome may induce inflammation at either a local or systemic level, thereby affecting the BPH. Moreover, metabolic syndrome (MetS) caused by the microbiome can also be involved in the development of BPH. Additionally, alterations in the microbiome composition during the senility process may serve as another cause of the BPH. Here, we summarize the influence of human microbiome on BPH and explore how the microbiome is linked to BPH through inflammation, MetS, and senility. In addition, we propose promising areas of investigation and discuss the implications for advancing therapeutic approaches.}, }
@article {pmid38214604, year = {2024}, author = {Hartikainen, AK and Khan, I and Karjalainen, EK and Renkonen-Sinisalo, L and Arkkila, P and Jalanka, J and Lepistö, AH and Satokari, R}, title = {Microbiota and mucosal gene expression of fecal microbiota transplantation or placebo treated patients with chronic pouchitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2295445}, pmid = {38214604}, issn = {1949-0984}, mesh = {Humans ; Fecal Microbiota Transplantation/adverse effects ; *Pouchitis/therapy/metabolism ; *Colitis, Ulcerative/therapy ; *Gastrointestinal Microbiome ; *Microbiota ; Gene Expression ; Feces ; }, abstract = {Altered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host-microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor's microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient's luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.}, }
@article {pmid38212576, year = {2024}, author = {Osadchiy, V and Belarmino, A and Kianian, R and Sigalos, JT and Ancira, JS and Kanie, T and Mangum, SF and Tipton, CD and Hsieh, TM and Mills, JN and Eleswarapu, SV}, title = {Semen microbiota are dramatically altered in men with abnormal sperm parameters.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1068}, pmid = {38212576}, issn = {2045-2322}, mesh = {Humans ; Male ; Cross-Sectional Studies ; Fertility ; *Infertility, Male ; *Lactobacillus ; *Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; }, abstract = {There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.}, }
@article {pmid38211733, year = {2024}, author = {Huang, X and Kantonen, J and Nowlan, K and Nguyen, NA and Jokiranta, ST and Kuivanen, S and Heikkilä, N and Mahzabin, S and Kantele, A and Vapalahti, O and Myllykangas, L and Heinonen, S and Mäyränpää, MI and Strandin, T and Kekäläinen, E}, title = {Mucosal-Associated Invariant T Cells are not susceptible in vitro to SARS-CoV-2 infection but accumulate into the lungs of COVID-19 patients.}, journal = {Virus research}, volume = {341}, number = {}, pages = {199315}, pmid = {38211733}, issn = {1872-7492}, mesh = {Humans ; *Mucosal-Associated Invariant T Cells ; *COVID-19 ; Angiotensin-Converting Enzyme 2 ; Leukocytes, Mononuclear ; SARS-CoV-2 ; Lung ; *Lymphopenia ; }, abstract = {Prolonged T cell lymphopenia is common in COVID-19, caused by SARS-CoV-2. While the mechanisms of lymphopenia during COVID-19 remain elusive, it is especially pronounced in a specialized innate-like T cell population called Mucosal Associated Invariant T cells (MAITs). MAITs has been suggested to express Angiotensin-Converting Enzyme 2 (ACE2), which is the well-known cellular receptor for SARS-CoV-2. However, it is still unclear if SARS-CoV-2 can infect or affect MAIT cells directly. In this study, we performed multicolor flow cytometry on peripheral blood mononuclear cells obtained from COVID-19 patients to assess the frequencies of CD8[+]Vα7.2[+]CD161[+] MAIT subsets at acute and convalescent disease phases. The susceptibility of MAITs and T cells to direct exposure by SARS-CoV-2 was analysed using cells isolated from healthy donor buffy coats by viability assays, virus-specific RT-PCR, and flow cytometry. In situ lung immunofluorescence was used to evaluate retention of T cells, especially MAIT cells, in lung tissues during acute COVID-19. Our study confirms previous reports indicating that circulating MAITs are activated, and their frequency is declined in patients with acute SARS-CoV-2 infection, whereas an accumulation of MAITs and T cells was seen in the lung tissue of individuals with fatal COVID-19. However, despite a fraction of MAITs found to express ACE2, no evidence for the susceptibility of MAITs for direct infection or activation by SARS-CoV-2 particles was observed. Thus, their activation and decline in the circulation is most likely explained by indirect mechanisms involving other immune cells and cytokine-induced pro-inflammatory environment but not by direct exposure to viral particles at the infection site.}, }
@article {pmid38211629, year = {2024}, author = {Pan, D and Chung, S and Nielsen, E and Niederman, MS}, title = {Aspiration Pneumonia.}, journal = {Seminars in respiratory and critical care medicine}, volume = {45}, number = {2}, pages = {237-245}, doi = {10.1055/s-0043-1777772}, pmid = {38211629}, issn = {1098-9048}, mesh = {Humans ; Aged ; *Pneumonia, Aspiration/etiology/prevention &amp; control ; *Pneumonia/complications ; *Deglutition Disorders/therapy/complications ; Risk Factors ; *Respiratory Tract Infections/complications ; }, abstract = {Aspiration pneumonia is a lower respiratory tract infection that results from inhalation of foreign material, often gastric and oropharyngeal contents. It is important to distinguish this from a similar entity, aspiration with chemical pneumonitis, as treatment approaches may differ. An evolving understanding of the human microbiome has shed light on the pathogenesis of aspiration pneumonia, suggesting that dysbiosis, repetitive injury, and inflammatory responses play a role in its development. Risk factors for aspiration events involve a complex interplay of anatomical and physiological dysfunctions in the nervous, gastrointestinal, and pulmonary systems. Current treatment strategies have shifted away from anaerobic organisms as leading pathogens. Prevention of aspiration pneumonia primarily involves addressing oropharyngeal dysphagia, a significant risk factor for aspiration pneumonia, particularly among elderly individuals and those with cognitive and neurodegenerative disorders.}, }
@article {pmid38206940, year = {2024}, author = {Rogers, MB and Harner, A and Buhay, M and Firek, B and Methé, B and Morris, A and Palmer, OMP and Promes, SB and Sherwin, RL and Southerland, L and Vieira, AR and Yende, S and Morowitz, MJ and Huang, DT}, title = {The salivary microbiota of patients with acute lower respiratory tract infection-A multicenter cohort study.}, journal = {PloS one}, volume = {19}, number = {1}, pages = {e0290062}, pmid = {38206940}, issn = {1932-6203}, mesh = {Adult ; Humans ; Prospective Studies ; *Microbiota ; *Respiratory Tract Infections/microbiology ; *Gastrointestinal Microbiome ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The human microbiome contributes to health and disease, but the oral microbiota is understudied relative to the gut microbiota. The salivary microbiota is easily accessible, underexplored, and may provide insight into response to infections. We sought to determine the composition, association with clinical features, and heterogeneity of the salivary microbiota in patients with acute lower respiratory tract infection (LRTI). We conducted a multicenter prospective cohort study of 147 adults with acute LRTI presenting to the emergency department of seven hospitals in three states (Pennsylvania, Michigan, and Ohio) between May 2017 and November 2018. Salivary samples were collected in the emergency department, at days 2-5 if hospitalized, and at day 30, as well as fecal samples if patients were willing. We compared salivary microbiota profiles from patients to those of healthy adult volunteers by sequencing and analyzing bacterial 16-rRNA. Compared to healthy volunteers, the salivary microbiota of patients with LRTI was highly distinct and strongly enriched with intestinal anaerobes such as Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae (e.g., mean 10% relative abundance of Bacteroides vs < 1% in healthy volunteers). Within the LRTI population, COPD exacerbation was associated with altered salivary microbiota composition compared to other LRTI conditions. The largest determinant of microbiota variation within the LRTI population was geography (city in which the hospital was located).}, }
@article {pmid38205958, year = {2024}, author = {Örmälä-Tiznado, A-M and Allander, L and Maatallah, M and Kabir, MH and Brisse, S and Sandegren, L and Patpatia, S and Coorens, M and Giske, CG}, title = {Molecular characteristics, fitness, and virulence of high-risk and non-high-risk clones of carbapenemase-producing Klebsiella pneumoniae.}, journal = {Microbiology spectrum}, volume = {12}, number = {2}, pages = {e0403622}, pmid = {38205958}, issn = {2165-0497}, support = {2016-02889//Vetenskapsr&#xe5;det (VR)/ ; }, mesh = {Animals ; Virulence/genetics ; *Klebsiella pneumoniae/genetics ; *Klebsiella Infections/microbiology ; Bacterial Proteins/genetics ; beta-Lactamases/genetics ; Virulence Factors/genetics ; Larva ; Clone Cells ; Anti-Bacterial Agents/therapeutic use ; Microbial Sensitivity Tests ; }, abstract = {Extensively drug-resistant (XDR) Klebsiella pneumoniae inflict a notable burden on healthcare worldwide. Of specific concern are strains producing carbapenem-hydrolyzing enzymes, as the therapeutic options for these strains are still very limited. Specific sequence types of K. pneumoniae have been noted for their epidemic occurrence globally, but the mechanisms behind the success of specific clones remain unclear. Herein, we have characterized 20 high-risk clones (HiRCs) and 10 non-HiRCs of XDR K. pneumoniae, exploring factors connected to the epidemiological success of some clones. Isolates were subjected to core genome multilocus sequence typing analysis to determine the clonal relationships of the isolates and subsequently characterized with regard to features known to be linked to overall bacterial fitness and virulence. The genomes were analyzed in silico for capsule types, O antigens, virulence factors, antimicrobial resistance genes, prophages, and CRISPR-Cas loci. In vitro growth experiments were conducted to retrieve proxies for absolute and relative fitness for 11 HiRC and 9 non-HiRC isolates selected based on the clonal groups they belonged to, and infections in a Galleria mellonella insect model were used to evaluate the virulence of the isolates in vivo. This study did not find evidence that virulence factors, prophages, CRISPR-Cas loci, or fitness measured in vitro alone would contribute to the global epidemiological success of specific clones of carbapenemase-producing XDR K. pneumoniae. However, this study did find the HiRC group to be more virulent than the non-HiRC group when measured in vivo in a model with G. mellonella. This suggests that the virulence and epidemiological success of certain clones of K. pneumoniae cannot be explained by individual traits investigated in this study and thus warrant further experiments in the future.IMPORTANCEHerein, we explored potential explanations for the successfulness of some epidemic or high-risk clones of carbapenemase-producing Klebsiella pneumoniae. We found differences in mortality in a larva model but found no clear genomic differences in known virulence markers. Most of the research on virulence in K. pneumoniae has been focused on hypervirulent strains, but here, we try to understand differences within the group of highly resistant strains. The results from the larva virulence model could be used to design experiments in higher animals. Moreover, the data could provide further support to a differentiated infection control approach against extensively drug-resistant strains, based on their classification as high-risk clones.}, }
@article {pmid38205031, year = {2024}, author = {Troci, A and Philippen, S and Rausch, P and Rave, J and Weyland, G and Niemann, K and Jessen, K and Schmill, LP and Aludin, S and Franke, A and Berg, D and Bang, C and Bartsch, T}, title = {Disease- and stage-specific alterations of the oral and fecal microbiota in Alzheimer's disease.}, journal = {PNAS nexus}, volume = {3}, number = {1}, pages = {pgad427}, pmid = {38205031}, issn = {2752-6542}, abstract = {Microbial communities in the intestinal tract are suggested to impact the ethiopathogenesis of Alzheimer's disease (AD). The human microbiome might modulate neuroinflammatory processes and contribute to neurodegeneration in AD. However, the microbial compositions in patients with AD at different stages of the disease are still not fully characterized. We used 16S rRNA analyses to investigate the oral and fecal microbiota in patients with AD and mild cognitive impairment (MCI; n = 84), at-risk individuals (APOE4 carriers; n = 17), and healthy controls (n = 50) and investigated the relationship of microbial communities and disease-specific markers via multivariate- and network-based approaches. We found a slightly decreased diversity in the fecal microbiota of patients with AD (average Chao1 diversity for AD = 212 [SD = 66]; for controls = 215 [SD = 55]) and identified differences in bacterial abundances including Bacteroidetes, Ruminococcus, Sutterella, and Porphyromonadaceae. The diversity in the oral microbiota was increased in patients with AD and at-risk individuals (average Chao1 diversity for AD = 174 [SD = 60], for at-risk group = 195 [SD = 49]). Gram-negative proinflammatory bacteria including Haemophilus, Neisseria, Actinobacillus, and Porphyromonas were dominant oral bacteria in patients with AD and MCI and the abundance correlated with the cerebrospinal fluid biomarker. Taken together, we observed a strong shift in the fecal and the oral communities of patients with AD already prominent in prodromal and, in case of the oral microbiota, in at-risk stages. This indicates stage-dependent alterations in oral and fecal microbiota in AD which may contribute to the pathogenesis via a facilitated intestinal and systemic inflammation leading to neuroinflammation and neurodegeneration.}, }
@article {pmid38204788, year = {2024}, author = {Rintarhat, P and Cho, YJ and Koh, H and Park, S and Lee, EJ and Lim, H and Noh, J and Lee, DW and Jung, WH}, title = {Assessment of DNA extraction methods for human gut mycobiome analysis.}, journal = {Royal Society open science}, volume = {11}, number = {1}, pages = {231129}, pmid = {38204788}, issn = {2054-5703}, abstract = {The gut mycobiome plays an important role in the health and disease of the human gut, but its exact function is still under investigation. While there is a wealth of information available on the bacterial community of the human gut microbiome, research on the fungal community is still relatively limited. In particular, technical methodologies for mycobiome analysis, especially the DNA extraction method for human faecal samples, varied in different studies. In the current study, two commercial kits commonly used in DNA extraction, the QIAamp® Fast DNA Stool Mini Kit and DNeasy PowerSoil Pro Kit, and one manual method, the International Human Microbiome Standards Protocol Q, were compared. Furthermore, the effectiveness of two different bead-beating machines, the Mini-Beadbeater-16 and FastPrep-24[TM] 5G, was compared in parallel. A mock fungal community with a known composition of fungal strains was also generated and included to compare different DNA extraction methods. Our results suggested that the method using the DNeasy PowerSoil Pro Kit and Mini-Beadbeater-16 provides the best results to extract DNA from human faecal samples. Based on our data, we propose a standard operating procedure for DNA extraction from human faecal samples for mycobiome analysis.}, }
@article {pmid38204360, year = {2024}, author = {Kiran, A and Hanachi, M and Alsayed, N and Fassatoui, M and Oduaran, OH and Allali, I and Maslamoney, S and Meintjes, A and Zass, L and Rocha, JD and Kefi, R and Benkahla, A and Ghedira, K and Panji, S and Mulder, N and Fadlelmola, FM and Souiai, O}, title = {The African Human Microbiome Portal: a public web portal of curated metagenomic metadata.}, journal = {Database : the journal of biological databases and curation}, volume = {2024}, number = {}, pages = {}, pmid = {38204360}, issn = {1758-0463}, support = {U24 HG006941/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Metadata ; Metagenome ; Databases, Factual ; Metagenomics ; *Microbiota/genetics ; }, abstract = {There is growing evidence that comprehensive and harmonized metadata are fundamental for effective public data reusability. However, it is often challenging to extract accurate metadata from public repositories. Of particular concern is the metagenomic data related to African individuals, which often omit important information about the particular features of these populations. As part of a collaborative consortium, H3ABioNet, we created a web portal, namely the African Human Microbiome Portal (AHMP), exclusively dedicated to metadata related to African human microbiome samples. Metadata were collected from various public repositories prior to cleaning, curation and harmonization according to a pre-established guideline and using ontology terms. These metadata sets can be accessed at https://microbiome.h3abionet.org/. This web portal is open access and offers an interactive visualization of 14 889 records from 70 bioprojects associated with 72 peer reviewed research articles. It also offers the ability to download harmonized metadata according to the user's applied filters. The AHMP thereby supports metadata search and retrieve operations, facilitating, thus, access to relevant studies linked to the African Human microbiome. Database URL: https://microbiome.h3abionet.org/.}, }
@article {pmid38201850, year = {2023}, author = {Toivio, L and Launonen, H and Lindén, J and Lehto, M and Vapaatalo, H and Salmenkari, H and Korpela, R}, title = {Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice.}, journal = {Nutrients}, volume = {16}, number = {1}, pages = {}, pmid = {38201850}, issn = {2072-6643}, support = {N/A//Finnish Concordia Fund/ ; N/A//Finnish Cultural Foundation/ ; N/A//Mary and Georg C. Ehrnrooth's Foundation/ ; N/A//Finska L&#xe4;kares&#xe4;llskapet/ ; N/A//Paulo Foundation/ ; N/A//Maud Kuistila Memorial Foundation/ ; #NNFOC0013659//Novo Nordisk (Finland)/ ; N/A//Wilhelm and Else Stockmann Foundation/ ; }, mesh = {Male ; Animals ; Mice ; Mice, Inbred C57BL ; *Diet, Ketogenic ; Claudins/genetics ; Iohexol ; Intestinal Barrier Function ; Interleukin-6/genetics ; Linoleic Acid ; Tight Junction Proteins/genetics ; Alkaline Phosphatase ; }, abstract = {Ketogenic diets (KDs) have been studied in preclinical models of intestinal diseases. However, little is known of how the fat source of these diets influences the intestinal barrier. Herein, we studied the impact of four-week feeding with KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) on paracellular permeability of the intestine to iohexol in healthy male C57BL/6J mice. We investigated jejunal and colonic tight junction protein expression, histological changes, and inflammatory markers (Il1b, Il6, Tnf, and Lcn2), as well as the activity and expression of intestinal alkaline phosphatase (IAP) in feces and jejunal tissue, respectively, and plasma lipopolysaccharide. KDs did not change intestinal permeability to iohexol after two or twenty-six days of feeding regardless of fat quality. SFA-KD, but not LA-KD, upregulated the colonic expression of tight junction proteins claudin-1 and -4, as well as the activity of IAP. Both KDs resulted in increased epithelial vacuolation in jejunum, and this was pronounced in SFA-KD. Jejunal Il1β expression was lower and colonic Il6 expression higher in LA-KD compared to SFA-KD. In colon, Tnf mRNA was increased in LA-KD when compared to controls. Overall, the results suggest that KDs do not influence intestinal permeability to iohexol but elicit changes in colonic tight junction proteins and inflammatory markers in both jejunum and colon. Future research will show whether these changes become of importance upon proinflammatory insults.}, }
@article {pmid38201695, year = {2023}, author = {Savitskaya, I and Zhantlessova, S and Kistaubayeva, A and Ignatova, L and Shokatayeva, D and Sinyavskiy, Y and Kushugulova, A and Digel, I}, title = {Prebiotic Cellulose-Pullulan Matrix as a "Vehicle" for Probiotic Biofilm Delivery to the Host Large Intestine.}, journal = {Polymers}, volume = {16}, number = {1}, pages = {}, pmid = {38201695}, issn = {2073-4360}, support = {AP09259491//the Ministry of Science and Higher Education of the Republic of Kazakhstan/ ; }, abstract = {This study describes the development of a new combined polysaccharide-matrix-based technology for the immobilization of Lactobacillus rhamnosus GG (LGG) bacteria in biofilm form. The new composition allows for delivering the bacteria to the digestive tract in a manner that improves their robustness compared with planktonic cells and released biofilm cells. Granules consisting of a polysaccharide matrix with probiotic biofilms (PMPB) with high cell density (>9 log CFU/g) were obtained by immobilization in the optimized nutrient medium. Successful probiotic loading was confirmed by fluorescence microscopy and scanning electron microscopy. The developed prebiotic polysaccharide matrix significantly enhanced LGG viability under acidic (pH 2.0) and bile salt (0.3%) stress conditions. Enzymatic extract of feces, mimicking colon fluid in terms of cellulase activity, was used to evaluate the intestinal release of probiotics. PMPB granules showed the ability to gradually release a large number of viable LGG cells in the model colon fluid. In vivo, the oral administration of PMPB granules in rats resulted in the successful release of probiotics in the colon environment. The biofilm-forming incubation method of immobilization on a complex polysaccharide matrix tested in this study has shown high efficacy and promising potential for the development of innovative biotechnologies.}, }
@article {pmid38200571, year = {2024}, author = {Xu, H and Wang, T and Miao, Y and Qian, M and Yang, Y and Wang, S}, title = {MK-BMC: a Multi-Kernel framework with Boosted distance metrics for Microbiome data for Classification.}, journal = {Bioinformatics (Oxford, England)}, volume = {40}, number = {1}, pages = {}, pmid = {38200571}, issn = {1367-4811}, support = {R01 LM013061/LM/NLM NIH HHS/United States ; //Department of Biostatistics, Columbia University/ ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Phylogeny ; }, abstract = {MOTIVATION: Research on human microbiome has suggested associations with human health, opening opportunities to predict health outcomes using microbiome. Studies have also suggested that diverse forms of taxa such as rare taxa that are evolutionally related and abundant taxa that are evolutionally unrelated could be associated with or predictive of a health outcome. Although prediction models were developed for microbiome data, no prediction models currently exist that use multiple forms of microbiome-outcome associations.<br><br>RESULTS: We developed MK-BMC, a Multi-Kernel framework with Boosted distance Metrics for Classification using microbiome data. We propose to first boost widely used distance metrics for microbiome data using taxon-level association signal strengths to up-weight taxa that are potentially associated with an outcome of interest. We then propose a multi-kernel prediction model with one kernel capturing one form of association between taxa and the outcome, where a kernel measures similarities of microbiome compositions between pairs of samples being transformed from a proposed boosted distance metric. We demonstrated superior prediction performance of (i) boosted distance metrics for microbiome data over original ones and (ii) MK-BMC over competing methods through extensive simulations. We applied MK-BMC to predict thyroid, obesity, and inflammatory bowel disease status using gut microbiome data from the American Gut Project and observed much-improved prediction performance over that of competing methods. The learned kernel weights help us understand contributions of individual microbiome signal forms nicely.<br><br>Source code together with a sample input dataset is available at https://github.com/HXu06/MK-BMC.}, }
@article {pmid38198280, year = {2024}, author = {Zhao, Z and Wang, J and Yu, H and Wang, X}, title = {Guide for phenotype-specific profiling of DNA G-quadruplex-regulated genes.}, journal = {STAR protocols}, volume = {5}, number = {1}, pages = {102820}, pmid = {38198280}, issn = {2666-1667}, mesh = {*DNA/genetics ; *G-Quadruplexes ; Phenotype ; }, abstract = {DNA G-quadruplex (G4) is a non-canonical four-stranded secondary structure that has been shown to play a role in epigenetic modulation of gene expression. Here, we present a primer on phenotype-specific profiling of DNA G-quadruplex-regulated genes. We provide guidance on in silico exploration of G4-related genes and phenotypes, and in vitro and in vivo validation of the relationship between G4 and phenotype. We describe commonly utilized techniques and detail critical steps involved in determining the phenotype-specific G4-regulated genes for subsequent investigations.}, }
@article {pmid38195358, year = {2024}, author = {Andary, CM and Al, KF and Chmiel, JA and Gibbons, S and Daisley, BA and Parvathy, SN and Maleki Vareki, S and Bowdish, DME and Silverman, MS and Burton, JP}, title = {Dissecting mechanisms of fecal microbiota transplantation efficacy in disease.}, journal = {Trends in molecular medicine}, volume = {30}, number = {3}, pages = {209-222}, doi = {10.1016/j.molmed.2023.12.005}, pmid = {38195358}, issn = {1471-499X}, mesh = {Humans ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Clostridioides difficile ; *Microbiota ; *Clostridium Infections/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has emerged as an alternative or adjunct experimental therapy for microbiome-associated diseases following its success in the treatment of recurrent Clostridioides difficile infections (rCDIs). However, the mechanisms of action involved remain relatively unknown. The term 'dysbiosis' has been used to describe microbial imbalances in relation to disease, but this traditional definition fails to consider the complex cross-feeding networks that define the stability of the microbiome. Emerging research transitions toward the targeted restoration of microbial functional networks in treating different diseases. In this review, we explore potential mechanisms responsible for the efficacy of FMT and future therapeutic applications, while revisiting definitions of 'dysbiosis' in favor of functional network restoration in rCDI, inflammatory bowel diseases (IBDs), metabolic diseases, and cancer.}, }
@article {pmid38194793, year = {2024}, author = {Kompoura, V and Karapantzou, I and Mitropoulou, G and Parisis, NA and Gkalpinos, VK and Anagnostou, VA and Tsiailanis, AD and Vasdekis, EP and Koutsaliaris, IK and Tsouka, AN and Karapetsi, L and Madesis, P and Letsiou, S and Florou, D and Koukkou, AI and Barbouti, A and Tselepis, AD and Kourkoutas, Y and Tzakos, AG}, title = {Exploiting the beneficial effects of Salvia officinalis L. extracts in human health and assessing their activity as potent functional regulators of food microbiota.}, journal = {Food chemistry}, volume = {441}, number = {}, pages = {138175}, doi = {10.1016/j.foodchem.2023.138175}, pmid = {38194793}, issn = {1873-7072}, mesh = {Humans ; *Salvia officinalis/chemistry ; Hydrogen Peroxide ; Plant Extracts/chemistry ; Phytochemicals/analysis ; Antioxidants/chemistry ; }, abstract = {Salvia officinalis L. has attracted scientific and industrial interest due to its pharmacological properties. However, its detailed phytochemical profile and its correlation with beneficial effects in the human microbiome and oxidative stress remained elusive. To unveil this, S. officinalis was collected from the region of Epirus and its molecular identity was verified with DNA barcoding. Phytochemical profile for both aqueous and ethanol-based extracts was determined by high-pressure liquid chromatography-tandem mass spectrometry and 103 phytochemicals were determined. The effect of S. officinalis extracts as functional regulators of food microbiota by stimulating the growth of Lacticaseibacillus rhamnosus strains and by suppressing evolution of pathogenic bacteria was verified. Furthermore, we recorded that both extracts exhibited a significant cellular protection against H2O2-induced DNA damage. Finally, both extracts exhibited strong inhibitory effect towards LDL oxidation. This study provides a comprehensive characterization of S. officinalis on its phytochemical components as also its potential impact in human microbiome and oxidative stress.}, }
@article {pmid38192800, year = {2024}, author = {Zhang, W and Tang, R and Yin, Y and Chen, J and Yao, L and Liu, B}, title = {Microbiome signatures in ischemic stroke: A systematic review.}, journal = {Heliyon}, volume = {10}, number = {1}, pages = {e23743}, pmid = {38192800}, issn = {2405-8440}, abstract = {Microbial structural changes and dysfunction play an important role in the development of cerebral ischemia. We searched PubMed, Embase, Web of Science, and Cochrane Library and conducted a systematic review to assess the relationship between the human microbiome and ischemic stroke. A total of 24 studies were included, and the intestinal bacterial communities detected in both stroke and healthy people were dominated by 4 main phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Significant diversity (alpha and beta) in patients with ischemic versus nonischemic stroke was observed in nine out of 18 studies, and 3 studies showed that the severity of ischemic stroke affected microbial diversity. The imbalance of bacteria that produce short-chain fatty acids (SCFAs) changes the bacterial metabolic pathway, and disorders in the level of bacterial metabolites (trimethylamine N-oxide TMAO) lead to significant changes in intestinal flora function, which may aggravate the severity of stroke and affect its prognosis. Further studies are needed to explore the relationship between the microbiome and ischemic stroke.}, }
@article {pmid38192296, year = {2023}, author = {Vernocchi, P and Marangelo, C and Guerrera, S and Del Chierico, F and Guarrasi, V and Gardini, S and Conte, F and Paci, P and Ianiro, G and Gasbarrini, A and Vicari, S and Putignani, L}, title = {Gut microbiota functional profiling in autism spectrum disorders: bacterial VOCs and related metabolic pathways acting as disease biomarkers and predictors.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1287350}, pmid = {38192296}, issn = {1664-302X}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder. Major interplays between the gastrointestinal (GI) tract and the central nervous system (CNS) seem to be driven by gut microbiota (GM). Herein, we provide a GM functional characterization, based on GM metabolomics, mapping of bacterial biochemical pathways, and anamnestic, clinical, and nutritional patient metadata.<br><br>METHODS: Fecal samples collected from children with ASD and neurotypical children were analyzed by gas-chromatography mass spectrometry coupled with solid phase microextraction (GC-MS/SPME) to determine volatile organic compounds (VOCs) associated with the metataxonomic approach by 16S rRNA gene sequencing. Multivariate and univariate statistical analyses assessed differential VOC profiles and relationships with ASD anamnestic and clinical features for biomarker discovery. Multiple web-based and machine learning (ML) models identified metabolic predictors of disease and network analyses correlated GM ecological and metabolic patterns.<br><br>RESULTS: The GM core volatilome for all ASD patients was characterized by a high concentration of 1-pentanol, 1-butanol, phenyl ethyl alcohol; benzeneacetaldehyde, octadecanal, tetradecanal; methyl isobutyl ketone, 2-hexanone, acetone; acetic, propanoic, 3-methyl-butanoic and 2-methyl-propanoic acids; indole and skatole; and o-cymene. Patients were stratified based on age, GI symptoms, and ASD severity symptoms. Disease risk prediction allowed us to associate butanoic acid with subjects older than 5 years, indole with the absence of GI symptoms and low disease severity, propanoic acid with the ASD risk group, and p-cymene with ASD symptoms, all based on the predictive CBCL-EXT scale. The HistGradientBoostingClassifier model classified ASD patients vs. CTRLs by an accuracy of 89%, based on methyl isobutyl ketone, benzeneacetaldehyde, phenyl ethyl alcohol, ethanol, butanoic acid, octadecane, acetic acid, skatole, and tetradecanal features. LogisticRegression models corroborated methyl isobutyl ketone, benzeneacetaldehyde, phenyl ethyl alcohol, skatole, and acetic acid as ASD predictors.<br><br>CONCLUSION: Our results will aid the development of advanced clinical decision support systems (CDSSs), assisted by ML models, for advanced ASD-personalized medicine, based on omics data integrated into electronic health/medical records. Furthermore, new ASD screening strategies based on GM-related predictors could be used to improve ASD risk assessment by uncovering novel ASD onset and risk predictors.}, }
@article {pmid38188629, year = {2023}, author = {Marzano, V and Mortera, SL and Marangelo, C and Piazzesi, A and Rapisarda, F and Pane, S and Del Chierico, F and Vernocchi, P and Romani, L and Campana, A and Palma, P and Putignani, L and , }, title = {The metaproteome of the gut microbiota in pediatric patients affected by COVID-19.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1327889}, pmid = {38188629}, issn = {2235-2988}, mesh = {Adult ; Humans ; Child ; *Gastrointestinal Microbiome ; *COVID-19 ; *Microbiota ; Adjuvants, Immunologic ; Algorithms ; }, abstract = {INTRODUCTION: The gut microbiota (GM) play a significant role in the infectivity and severity of COVID-19 infection. However, the available literature primarily focuses on adult patients and it is known that the microbiota undergoes changes throughout the lifespan, with significant alterations occurring during infancy and subsequently stabilizing during adulthood. Moreover, children have exhibited milder symptoms of COVID-19 disease, which has been associated with the abundance of certain protective bacteria. Here, we examine the metaproteome of pediatric patients to uncover the biological mechanisms that underlie this protective effect of the GM.<br><br>METHODS: We performed nanoliquid chromatography coupled with tandem mass spectrometry on a high resolution analytical platform, resulting in label free quantification of bacterial protein groups (PGs), along with functional annotations via COG and KEGG databases by MetaLab-MAG. Additionally, taxonomic assignment was possible through the use of the lowest common ancestor algorithm provided by Unipept software.<br><br>RESULTS: A COVID-19 GM functional dissimilarity respect to healthy subjects was identified by univariate analysis. The alteration in COVID-19 GM function is primarily based on bacterial pathways that predominantly involve metabolic processes, such as those related to tryptophan, butanoate, fatty acid, and bile acid biosynthesis, as well as antibiotic resistance and virulence.<br><br>DISCUSSION: These findings highlight the mechanisms by which the pediatric GM could contribute to protection against the more severe manifestations of the disease in children. Uncovering these mechanisms can, therefore, have important implications in the discovery of novel adjuvant therapies for severe COVID-19.}, }
@article {pmid38187050, year = {2023}, author = {Feng, K and Ren, F and Xing, Z and Zhao, Y and Yang, C and Liu, J and Shang, Q and Wang, X and Wang, X}, title = {Microbiome and its implications in oncogenesis: a Mendelian randomization perspective.}, journal = {American journal of cancer research}, volume = {13}, number = {12}, pages = {5785-5804}, pmid = {38187050}, issn = {2156-6976}, abstract = {The human microbiome, an intricate ecological network, has garnered significant attention due to its potential implications in oncogenesis. This paper delves into the multifaceted relationships between the microbiome, its metabolites, and cancer development, emphasizing the human intestinal tract as the primary microbial habitat. Highlighting the potential causative associations between microbial disturbances and cancer progression, we underscore the role of specific bacterial strains in various cancers, such as stomach and colorectal cancer. Traditional causality assessment methods, like randomized controlled trials (RCTs), have limitations. Therefore, we advocate using Mendelian Randomization (MR) as a powerful alternative to study causal relationships, leveraging genetic variants as instrumental variables. With the proliferation of genome-wide association studies, MR harnesses genetic variations to infer causality, which is especially beneficial when addressing confounders like diet and lifestyle that can skew microbial research. We systematically review MR's application in understanding the microbiome-cancer nexus, emphasizing its strengths and challenges. While MR offers a unique perspective on causality, it faces hurdles like horizontal pleiotropy and weak instrumental variable bias. Integrating MR with multi-omics data, encompassing genomics, transcriptomics, proteomics, and metabolomics, holds promise for future research, potentially heralding groundbreaking discoveries in microbiology and genetics. This comprehensive review underscores the critical role of the human microbiome in oncogenesis and champions MR as an indispensable tool for advancing our understanding in this domain.}, }
@article {pmid38182316, year = {2024}, author = {Mir, TUG and Manhas, S and Khurshid Wani, A and Akhtar, N and Shukla, S and Prakash, A}, title = {Alterations in microbiome of COVID-19 patients and its impact on forensic investigations.}, journal = {Science &amp; justice : journal of the Forensic Science Society}, volume = {64}, number = {1}, pages = {81-94}, doi = {10.1016/j.scijus.2023.12.002}, pmid = {38182316}, issn = {1876-4452}, mesh = {Female ; Humans ; *COVID-19 ; *Microbiota ; Forensic Sciences ; Skin ; }, abstract = {The human microbiome is vital for maintaining human health and has garnered substantial attention in recent years, particularly in the context of the coronavirus disease 2019 (COVID-19) outbreak. Studies have underscored significant alterations in the microbiome of COVID-19 patients across various body niches, including the gut, respiratory tract, oral cavity, skin, and vagina. These changes manifest as shifts in microbiota composition, characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. Such microbiome transformations may play a pivotal role in influencing the course and severity of COVID-19, potentially contributing to the inflammatory response. This ongoing relationship between COVID-19 and the human microbiome serves as a compelling subject of research, underscoring the necessity for further investigations into the underlying mechanisms and their implications for patient health. Additionally, these alterations in the microbiome may have significant ramifications for forensic investigations, given the microbiome's potential in establishing individual characteristics. Consequently, changes in the microbiome could introduce a level of complexity into forensic determinations. As research progresses, a more profound understanding of the human microbiome within the context of COVID-19 may offer valuable insights into disease prevention, treatment strategies, and its potential applications in forensic science. Consequently, this paper aims to provide an overarching review of microbiome alterations due to COVID-19 and the associated impact on forensic applications, bridging the gap between the altered microbiome of COVID-19 patients and the challenges forensic investigations may encounter when analyzing this microbiome as a forensic biomarker.}, }
@article {pmid38181740, year = {2024}, author = {Sarkar, A and McInroy, CJA and Harty, S and Raulo, A and Ibata, NGO and Valles-Colomer, M and Johnson, KV and Brito, IL and Henrich, J and Archie, EA and Barreiro, LB and Gazzaniga, FS and Finlay, BB and Koonin, EV and Carmody, RN and Moeller, AH}, title = {Microbial transmission in the social microbiome and host health and disease.}, journal = {Cell}, volume = {187}, number = {1}, pages = {17-43}, pmid = {38181740}, issn = {1097-4172}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R35 GM138284/GM/NIGMS NIH HHS/United States ; K22 CA258960/CA/NCI NIH HHS/United States ; R01 GM134376/GM/NIGMS NIH HHS/United States ; R01 AG071684/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Microbiota ; Noncommunicable Diseases ; *Social Factors ; *Symbiosis ; Virulence ; }, abstract = {Although social interactions are known to drive pathogen transmission, the contributions of socially transmissible host-associated mutualists and commensals to host health and disease remain poorly explored. We use the concept of the social microbiome-the microbial metacommunity of a social network of hosts-to analyze the implications of social microbial transmission for host health and disease. We investigate the contributions of socially transmissible microbes to both eco-evolutionary microbiome community processes (colonization resistance, the evolution of virulence, and reactions to ecological disturbance) and microbial transmission-based processes (transmission of microbes with metabolic and immune effects, inter-specific transmission, transmission of antibiotic-resistant microbes, and transmission of viruses). We consider the implications of social microbial transmission for communicable and non-communicable diseases and evaluate the importance of a socially transmissible component underlying canonically non-communicable diseases. The social transmission of mutualists and commensals may play a significant, under-appreciated role in the social determinants of health and may act as a hidden force in social evolution.}, }
@article {pmid38174103, year = {2024}, author = {Kantele, A and Paajanen, J and Pietilä, JP and Vapalahti, O and Pakkanen, SH and Lääveri, T}, title = {Long COVID-associated symptoms prevalent in both SARS-CoV-2 positive and negative individuals: A prospective follow-up study.}, journal = {New microbes and new infections}, volume = {56}, number = {}, pages = {101209}, pmid = {38174103}, issn = {2052-2975}, abstract = {BACKGROUND: Research into persistent symptoms among SARS-CoV-2-positive i.e. CoV(+) patients mostly focuses on hospitalized individuals. Our prospective follow-up study compares long COVID-associated symptoms among laboratory-confirmed CoV(+) and SARS-CoV-2 negative [CoV(-)] individuals.<br><br>METHODS: SARS-CoV-2 RT-PCR-tested volunteers were recruited into four cohorts: 1) CoV(+) outpatients, 2) CoV(-) outpatients, 3) CoV(+) intensive care unit (ICU) inpatients, and 4) CoV(+) non-ICU inpatients. Neutralizing antibodies were assessed and questionnaires filled in at enrolment and days 90-120, 121-180, 181-270, 271-365, and 365-533.<br><br>RESULTS: Of the 1326 participants, 1191 were CoV(+): 46 ICU, 123 non-ICU, and 1022 outpatients; 135 were CoV(-) outpatient controls. Both CoV(+) outpatients and CoV(-) controls showed high overall symptom rates at all time points. More prevalent among CoV(+) than CoV(-) outpatients were only impaired olfaction and taste; many others proved more frequent for CoV(-) participants. At &#x2265;181 days, fatigue, dyspnoea, various neuropsychological symptoms and several others were recorded more often for CoV(+) inpatients than outpatients.<br><br>CONCLUSIONS: Long COVID-associated symptoms were more frequent among hospitalized than non-hospitalized CoV(+) participants. As for outpatients, only impaired olfaction and taste showed higher rates in the CoV(+) group; some symptoms proved even more common among those CoV(-). Besides suggesting low long COVID prevalences for outpatients, our results highlight the weight of negative controls.}, }
@article {pmid38172625, year = {2024}, author = {Vill, AC and Rice, EJ and De Vlaminck, I and Danko, CG and Brito, IL}, title = {Precision run-on sequencing (PRO-seq) for microbiome transcriptomics.}, journal = {Nature microbiology}, volume = {9}, number = {1}, pages = {241-250}, pmid = {38172625}, issn = {2058-5276}, support = {R01 GM147731/GM/NIGMS NIH HHS/United States ; R01 HG009309/HG/NHGRI NIH HHS/United States ; R01 HG010346/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Escherichia coli/genetics ; *RNA, Guide, CRISPR-Cas Systems ; DNA-Directed RNA Polymerases/genetics ; RNA/genetics ; Gene Expression Profiling ; }, abstract = {Bacteria respond to environmental stimuli through precise regulation of transcription initiation and elongation. Bulk RNA sequencing primarily characterizes mature transcripts, so to identify actively transcribed loci we need to capture RNA polymerase (RNAP) complexed with nascent RNA. However, such capture methods have only previously been applied to culturable, genetically tractable organisms such as E. coli and B. subtilis. Here we apply precision run-on sequencing (PRO-seq) to profile nascent transcription in cultured E. coli and diverse uncultured bacteria. We demonstrate that PRO-seq can characterize the transcription of small, structured, or post-transcriptionally modified RNAs, which are often absent from bulk RNA-seq libraries. Applying PRO-seq to the human microbiome highlights taxon-specific RNAP pause motifs and pause-site distributions across non-coding RNA loci that reflect structure-coincident pausing. We also uncover concurrent transcription and cleavage of CRISPR guide RNAs and transfer RNAs. We demonstrate the utility of PRO-seq for exploring transcriptional dynamics in diverse microbial communities.}, }
@article {pmid38170633, year = {2024}, author = {Meynier, M and Daugey, V and Mallaret, G and Gervason, S and Meleine, M and Barbier, J and Aissouni, Y and Lolignier, S and Bonnet, M and Ardid, D and De Vos, WM and Van Hul, M and Suenaert, P and Brochot, A and Cani, PD and Carvalho, FA}, title = {Pasteurized akkermansia muciniphila improves irritable bowel syndrome-like symptoms and related behavioral disorders in mice.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2298026}, pmid = {38170633}, issn = {1949-0984}, mesh = {Maternal Deprivation ; Akkermansia ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; Animals ; Verrucomicrobia/physiology ; Mice ; }, abstract = {Gut - brain communications disorders in irritable bowel syndrome (IBS) are associated with intestinal microbiota composition, increased gut permeability, and psychosocial disturbances. Symptoms of IBS are difficult to medicate, and hence much research is being made into alternative approaches. This study assesses the potential of a treatment with pasteurized Akkermansia muciniphila for alleviating IBS-like symptoms in two mouse models of IBS with different etiologies. Two clinically relevant animal models were used to mimic IBS-like symptoms in C57BL6/J mice: the neonatal maternal separation (NMS) paradigm and the Citrobacter rodentium infection model. In both models, gut permeability, colonic sensitivity, fecal microbiota composition and colonic IL-22 expression were evaluated. The cognitive performance and emotional state of the animals were also assessed by several tests in the C. rodentium infection model. The neuromodulation ability of pasteurized A. muciniphila was assessed on primary neuronal cells from mice dorsal root ganglia using a ratiometric calcium imaging approach. The administration of pasteurized A. muciniphila significantly reduced colonic hypersensitivity in both IBS mouse models, accompanied by a reinforcement of the intestinal barrier function. Beneficial effects of pasteurized A. muciniphila treatment have also been observed on anxiety-like behavior and memory defects in the C. rodentium infection model. Finally, a neuroinhibitory effect exerted by pasteurized A. muciniphila was observed on neuronal cells stimulated with two algogenic substances such as capsaicin and inflammatory soup. Our findings demonstrate novel anti-hyperalgesic and neuroinhibitory properties of pasteurized A. muciniphila, which therefore may have beneficial effects in relieving pain and anxiety in subjects with IBS.}, }
@article {pmid38168274, year = {2023}, author = {Liu, R and Wang, Y and Cheng, D}, title = {Micro-DeMix: A mixture beta-multinomial model for investigating the fecal microbiome compositions.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168274}, issn = {2692-8205}, support = {R01 GM145772/GM/NIGMS NIH HHS/United States ; }, abstract = {Extensive research has uncovered the involvement of the human gut microbiome in various facets of human health, including metabolism, nutrition, physiology, and immune function. Researchers often study fecal microbiota as a proxy for understanding the gut microbiome. However, it has been demonstrated that this approach may not suffice to yield a comprehensive understanding of the entire gut microbial community. Emerging research is revealing the heterogeneity of the gut microbiome across different gastrointestinal (GI) locations in both composition and functions. While spatial metagenomics approach has been developed to address these variations in mice, limitations arise when applying it to human-subject research, primarily due to its invasive nature. With these restrictions, we introduce Micro-DeMix, a mixture beta-multinomial model that decomposes the fecal microbiome at compositional level to understand the heterogeneity of the gut microbiome across various GI locations and extract meaningful insights about the biodiversity of the gut microbiome. Moreover, Micro-DeMix facilitates the discovery of differentially abundant microbes between GI regions through a hypothesis testing framework. We utilize the Inflammatory Bowel Disease (IBD) data from the NIH Integrative Human Microbiome Project to demonstrate the effectiveness and efficiency of the proposed Micro-DeMix.}, }
@article {pmid38166904, year = {2024}, author = {Luan, J and Zhang, F and Suo, L and Zhang, W and Li, Y and Yu, X and Liu, B and Cao, H}, title = {Analyzing lung cancer risks in patients with impaired pulmonary function through characterization of gut microbiome and metabolites.}, journal = {BMC pulmonary medicine}, volume = {24}, number = {1}, pages = {1}, pmid = {38166904}, issn = {1471-2466}, support = {grant no. tsqn202103196//Taishan Scholars Program of Shandong Province/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Lung Neoplasms ; Metabolomics/methods ; Feces ; Biomarkers ; RNA, Ribosomal, 16S/genetics ; *Multiple Pulmonary Nodules ; }, abstract = {BACKGROUND: Lung cancer (LC) is one of the most devastating diseases worldwide, there is growing studies confirm the role of impaired lung function in LC susceptibility. Moreover, gut microbiota dysbiosis is associated with LC severity. Whether alterations in gut microbiota and metabolites are associated with long-term lung dysfunction in LC patients remain unclear. Our study aimed to analyze the risk factors in LC patients with impaired pulmonary function based on the characteristics of the gut microbiome and metabolites.<br><br>METHODS: Fecal samples from 55 LC patients and 28 benign pulmonary nodules patients were collected. Pulmonary ventilation function was graded according to the American Thoracic Society/ European Respiratory Society (ATS/ERS) method. LC patients were divided into 3 groups, including 20 patients with normal lung ventilation, 23 patients with mild pulmonary ventilation dysfunction and 12 patients with moderate or above pulmonary ventilation dysfunction. The fecal samples were analyzed using 16&#xa0;S rRNA gene amplicon sequencing and metabolomics.<br><br>RESULTS: The gut microbiome composition between LC patients and benign pulmonary nodules patients presented clearly differences based on Partial Least Squares Discriminant Analysis (PLS-DA). Pulmonary ventilation function was positively correlated with LC tumor stage, the richness and diversity of the gut microbiota in LC patients with moderate or above pulmonary ventilation dysfunction increased significantly, characterized by increased abundance of Subdoligranulum and Romboutsia. The metabolomics analysis revealed 69 differential metabolites, which were mainly enriched in beta-Alanine metabolism, styrene degradation and pyrimidine metabolism pathway. The area under the curve (AUC) combining the gut microbiome and metabolites was 90% (95% CI: 79-100%), indicating that the two species and four metabolites might regarded as biomarkers to assess the prediction of LC patients with impaired pulmonary function.<br><br>CONCLUSIONS: Our results showed that microbiome and metabolomics analyses provide important candidate to be used as clinically diagnostic biomarkers and therapeutic targets related to lung cancer with impaired pulmonary function.}, }
@article {pmid38165929, year = {2024}, author = {van Nes, EH and Pujoni, DGF and Shetty, SA and Straatsma, G and de Vos, WM and Scheffer, M}, title = {A tiny fraction of all species forms most of nature: Rarity as a sticky state.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {121}, number = {2}, pages = {e2221791120}, pmid = {38165929}, issn = {1091-6490}, mesh = {Animals ; Humans ; *Ecosystem ; Biodiversity ; Biomass ; *Microbiota ; Trees ; Stochastic Processes ; }, abstract = {Using data from a wide range of natural communities including the human microbiome, plants, fish, mushrooms, rodents, beetles, and trees, we show that universally just a few percent of the species account for most of the biomass. This is in line with the classical observation that the vast bulk of biodiversity is very rare. Attempts to find traits allowing the tiny fraction of abundant species to escape rarity have remained unsuccessful. Here, we argue that this might be explained by the fact that hyper-dominance can emerge through stochastic processes. We demonstrate that in neutrally competing groups of species, rarity tends to become a trap if environmental fluctuations result in gains and losses proportional to abundances. This counter-intuitive phenomenon arises because absolute change tends to zero for very small abundances, causing rarity to become a "sticky state", a pseudoattractor that can be revealed numerically in classical ball-in-cup landscapes. As a result, the vast majority of species spend most of their time in rarity leaving space for just a few others to dominate the neutral community. However, fates remain stochastic. Provided that there is some response diversity, roles occasionally shift as stochastic events or natural enemies bring an abundant species down allowing a rare species to rise to dominance. Microbial time series spanning thousands of generations support this prediction. Our results suggest that near-neutrality within niches may allow numerous rare species to persist in the wings of the dominant ones. Stand-ins may serve as insurance when former key species collapse.}, }
@article {pmid38163940, year = {2023}, author = {Jabłońska-Trypuć, A}, title = {The Role of the Microbiome in Inflammation and Carcinogenesis.}, journal = {Frontiers in bioscience (Elite edition)}, volume = {15}, number = {4}, pages = {28}, doi = {10.31083/j.fbe1504028}, pmid = {38163940}, issn = {1945-0508}, support = {WZ/WB-II&#x15a;/6/2022//Ministry of Education and Science, Poland/ ; }, mesh = {Humans ; *Microbiota/physiology ; Inflammation ; Carcinogenesis ; *Neoplasms ; Tumor Microenvironment ; }, abstract = {Inflammation has been confirmed to exist in the tumor microenvironment, while the risk of cancer occurrence increases in cases of chronic inflammation. It is estimated that approximately 10% to 20% of cancers are associated with chronic infections and attendant inflammation. Bacteria, both pathogenic and commensal, viruses, and fungi actively participate in the development and maintenance of inflammation and tumor growth in humans. The exposome, which is a sum of human environmental exposures, such as industrial diet, consumed drugs, and toxins, affects the composition and function of the human microbiome, which could lead to dysbiosis and disorders in tissue homeostasis through different mechanisms, including the intensification of the immune response, activation and abnormal proliferation, and disruption to epithelial barrier integrity. Presently, science remains at the stage of revealing the complexity associated with the mechanisms involved in building relationships that cover the microbiome-inflammation-tumor, yet it is already known how important it is to care for microbial homeostasis of the organism.}, }
@article {pmid38160303, year = {2024}, author = {Sapoval, N and Tanevski, M and Treangen, TJ}, title = {KombOver: Efficient k-core and K-truss based characterization of perturbations within the human gut microbiome.}, journal = {Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing}, volume = {29}, number = {}, pages = {506-520}, pmid = {38160303}, issn = {2335-6936}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; DNA Copy Number Variations ; Computational Biology ; *Microbiota/genetics ; Metagenome ; Metagenomics/methods ; }, abstract = {The microbes present in the human gastrointestinal tract are regularly linked to human health and disease outcomes. Thanks to technological and methodological advances in recent years, metagenomic sequencing data, and computational methods designed to analyze metagenomic data, have contributed to improved understanding of the link between the human gut microbiome and disease. However, while numerous methods have been recently developed to extract quantitative and qualitative results from host-associated microbiome data, improved computational tools are still needed to track microbiome dynamics with short-read sequencing data. Previously we have proposed KOMB as a de novo tool for identifying copy number variations in metagenomes for characterizing microbial genome dynamics in response to perturbations. In this work, we present KombOver (KO), which includes four key contributions with respect to our previous work: (i) it scales to large microbiome study cohorts, (ii) it includes both k-core and K-truss based analysis, (iii) we provide the foundation of a theoretical understanding of the relation between various graph-based metagenome representations, and (iv) we provide an improved user experience with easier-to-run code and more descriptive outputs/results. To highlight the aforementioned benefits, we applied KO to nearly 1000 human microbiome samples, requiring less than 10 minutes and 10 GB RAM per sample to process these data. Furthermore, we highlight how graph-based approaches such as k-core and K-truss can be informative for pinpointing microbial community dynamics within a myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) cohort. KO is open source and available for download/use at: https://github.com/treangenlab/komb.}, }
@article {pmid38159991, year = {2024}, author = {Ebeling, M and Derka, S and Baudrexl, J and Sakkas, A and Scheurer, M and Wilde, F and Schramm, A and Pietzka, S}, title = {Ibuprofen Reduces 5-Year Overall Survival of Head and Neck Cancer Patients With Immunotherapy - A Retrospective Case-controlled Real-World Data Analysis of 10,000 Patients.}, journal = {Anticancer research}, volume = {44}, number = {1}, pages = {313-322}, doi = {10.21873/anticanres.16814}, pmid = {38159991}, issn = {1791-7530}, mesh = {Humans ; Infant, Newborn ; *Carcinoma/drug therapy ; Cyclooxygenase Inhibitors/adverse effects ; Data Analysis ; *Ductus Arteriosus, Patent/chemically induced/drug therapy ; Ibuprofen/therapeutic use ; Immunotherapy ; Indomethacin ; Infant, Low Birth Weight ; Infant, Premature ; Proton Pump Inhibitors/therapeutic use ; Retrospective Studies ; Case-Control Studies ; }, abstract = {BACKGROUND/AIM: Resistance to immunotherapy can be explained by an abnormal microbiome of the gut. In Europe in particular, the use of ibuprofen, with or without proton-pump inhibitors to protect the gastric mucosa, is widespread. This study aimed to investigate the impact of ibuprofen use on the effectiveness of immunotherapy in patients with head and neck carcinoma.<br><br>PATIENTS AND METHODS: Data from patients with head and neck carcinoma (ICD-10-Codes: C00-C14) receiving pembrolizumab, from the TriNetX network, were analyzed. Two groups were formed for the analyses: Cohort I received ibuprofen at least once within 6 months before and after immunotherapy, whereas patients in cohort II received ibuprofen with proton-pump inhibitors or no ibuprofen at all. Cohorts I and II were matched 1:1 with respect to age, sex, lymph node metastases, nicotine dependence, alcohol dependence, and body mass index (BMI). The primary outcome was death and a Kaplan-Meier analysis was performed, and the risk ratio (RR), odds ratio (OR), and hazard ratio (HR) were calculated.<br><br>RESULTS: The analysis showed that 823 patients with ibuprofen and 724 patients without ibuprofen died within 5 years, showing a significant risk difference of 5.3% (p=0.001). The RR was 1.137 [95% confidence interval (CI)=1.053-1.227], OR was 1.245 (95% CI=1.093-1.418), and HR was 1.202 (95%CI=1.088-1.329).<br><br>CONCLUSION: Ibuprofen significantly decreases the drug effectiveness of immunotherapy and may be related to changes in the human microbiome. However, further prospective, randomized, and double-blind studies are needed to validate our data and to adequately address confounders.}, }
@article {pmid40741483, year = {2024}, author = {Hunter, C and Dia, K and Boykins, J and Perry, K and Banerjee, N and Cuffee, J and Armstrong, E and Morgan, G and Banerjee, HN and Banerjee, A and Bhattacharya, S}, title = {An investigation for phylogenetic characterization of human pancreatic cancer microbiome by 16S rDNA sequencing and bioinformatics techniques.}, journal = {Journal of solid tumors}, volume = {14}, number = {1}, pages = {1-9}, pmid = {40741483}, issn = {1925-4067}, support = {T34 GM100831/GM/NIGMS NIH HHS/United States ; }, abstract = {Pancreatic cancer is a significant public health concern, with increasing incidence rates and limited treatment options. Recent studies have highlighted the role of the human microbiome, particularly the gut microbiota, in the development and progression of this disease. Microbial dysbiosis, characterized by alterations in the composition and function of the gut microbiota, has been implicated in pancreatic carcinogenesis through mechanisms involving chronic inflammation, immune dysregulation, and metabolic disturbances. Researchers have identified specific microbial signatures associated with pancreatic cancer, offering potential biomarkers for early detection and prognostication. By leveraging advanced sequencing and bioinformatics tools, scientists have delineated differences in the gut microbiota between pancreatic cancer patients and healthy individuals, providing insights into disease pathogenesis and potential diagnostic strategies. Moreover, the microbiome holds promise as a therapeutic target in pancreatic cancer treatment. Interventions aimed at modulating the microbiome, such as probiotics, prebiotics, and fecal microbiota transplantation, have demonstrated potential in enhancing the efficacy of existing cancer therapies, including chemotherapy and immunotherapy. These approaches can influence immune responses, alter tumor microenvironments, and sensitize tumors to treatment, offering new avenues for improving patient outcomes and overcoming therapeutic resistance. Overall, understanding the complex interplay between the microbiome and pancreatic cancer is crucial for advancing our knowledge of disease mechanisms and identifying innovative therapeutic strategies. Here we report phylogenetic analysis of the 16S rDNA microbial sequences of the pancreatic cancer mice microbiome and corresponding age matched healthy mice microbiome. We successfully identified differentially abundant microbiota in pancreatic cancer.}, }
@article {pmid40687607, year = {2024}, author = {Zhou, J and Gui, J and Viles, WD and Chen, H and Li, S and Madan, JC and Coker, MO and Hoen, AG}, title = {Identifying stationary microbial interaction networks based on irregularly spaced longitudinal 16S rRNA gene sequencing data.}, journal = {Frontiers in microbiomes}, volume = {3}, number = {}, pages = {}, pmid = {40687607}, issn = {2813-4338}, support = {P20 GM125498/GM/NIGMS NIH HHS/United States ; P20 GM130454/GM/NIGMS NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; U19 AI145825/AI/NIAID NIH HHS/United States ; }, abstract = {INTRODUCTION: The microbial interactions within the human microbiome are complex, and few methods are available to identify these interactions within a longitudinal microbial abundance framework. Existing methods typically impose restrictive constraints, such as requiring long sequences and equal spacing, on the data format which in many cases are violated.<br><br>METHODS: To identify microbial interaction networks (MINs) with general longitudinal data settings, we propose a stationary Gaussian graphical model (SGGM) based on 16S rRNA gene sequencing data. In the SGGM, data can be arbitrarily spaced, and there are no restrictions on the length of data sequences from a single subject. Based on the SGGM, EM-type algorithms are devised to compute the L1-penalized maximum likelihood estimate of MINs. The algorithms employ the classical graphical LASSO algorithm as the building block and can be implemented efficiently.<br><br>RESULTS: Extensive simulation studies show that the proposed algorithms can significantly outperform the conventional algorithms if the correlations among the longitudinal data are reasonably high. When the assumptions in the SGGM areviolated, e.g., zero inflation or data from heterogeneous microbial communities, the proposed algorithms still demonstrate robustness and perform better than the other existing algorithms. The algorithms are applied to a 16S rRNA gene sequencing data set from patients with cystic fibrosis. The results demonstrate strong evidence of an association between the MINs and the phylogenetic tree, indicating that the genetically related taxa tend to have more/stronger interactions. These results strengthen the existing findings in literature.<br><br>DISCUSSION: The proposed algorithms can potentially be used to explore the network structure in genome, metabolome etc. as well.}, }
@article {pmid38149262, year = {2023}, author = {Wang, Y and Shojaie, A and Randolph, T and Knight, P and Ma, J}, title = {GENERALIZED MATRIX DECOMPOSITION REGRESSION: ESTIMATION AND INFERENCE FOR TWO-WAY STRUCTURED DATA.}, journal = {The annals of applied statistics}, volume = {17}, number = {4}, pages = {2944-2969}, pmid = {38149262}, issn = {1932-6157}, support = {R01 GM129512/GM/NIGMS NIH HHS/United States ; U19 CA203654/CA/NCI NIH HHS/United States ; T32 GM135117/GM/NIGMS NIH HHS/United States ; R01 GM145772/GM/NIGMS NIH HHS/United States ; P50 CA228944/CA/NCI NIH HHS/United States ; R01 HL155417/HL/NHLBI NIH HHS/United States ; R01 GM133848/GM/NIGMS NIH HHS/United States ; }, abstract = {Motivated by emerging applications in ecology, microbiology, and neuroscience, this paper studies high-dimensional regression with two-way structured data. To estimate the high-dimensional coefficient vector, we propose the generalized matrix decomposition regression (GMDR) to efficiently leverage auxiliary information on row and column structures. GMDR extends the principal component regression (PCR) to two-way structured data, but unlike PCR, GMDR selects the components that are most predictive of the outcome, leading to more accurate prediction. For inference on regression coefficients of individual variables, we propose the generalized matrix decomposition inference (GMDI), a general high-dimensional inferential framework for a large family of estimators that include the proposed GMDR estimator. GMDI provides more flexibility for incorporating relevant auxiliary row and column structures. As a result, GMDI does not require the true regression coefficients to be sparse, but constrains the coordinate system representing the regression coefficients according to the column structure. GMDI also allows dependent and heteroscedastic observations. We study the theoretical properties of GMDI in terms of both the type-I error rate and power and demonstrate the effectiveness of GMDR and GMDI in simulation studies and an application to human microbiome data.}, }
@article {pmid38149226, year = {2023}, author = {Sharifzadeh, SS and Lotfali, E and Lesan, S and Farrokhnia, T}, title = {Antifungal Effect of Probiotic Lactobacillus casei on Drug-Resistant Oral Candida albicans Isolated from Patients with Hematological Malignancy: an in vitro Study.}, journal = {Journal of dentistry (Shiraz, Iran)}, volume = {24}, number = {4}, pages = {389-394}, pmid = {38149226}, issn = {2345-6485}, abstract = {STATEMENT OF THE PROBLEM: Candida albicans (C. albicans) is recognized as the most common opportunistic pathogen in patients with an impaired immune system, and due to the frequent use of antifungal medicine, a variety of drug-resistant species are developing. Probiotics are a part of the human microbiome and natural competitors of Candida by producing lactic acid, low pH, and other secreted metabolites. The role of probiotics in preventing fungal infections has always been discussed.<br><br>PURPOSE: This study aimed to investigate the antifungal effect of Lactobacillus casei (L. casei) on fluconazole- and amphotericin B-resistant C. albicans species isolated from the oral cavity of acute myeloid leukemia patients.<br><br>MATERIALS AND METHOD: In this experimental study, eight strains of fluconazole- and amphotericin B-resistant C. albicans were used. The antifungal effects of probiotic L. casei and nystatin were measured by the co-aggregation method 1, 2, and 4 h after beginning the study. After each hour of exposure, C. albicans and L. casei colonies were counted.<br><br>RESULTS: L. casei had a significant ability to aggregate with both fluconazole- and amphotericin B-resistant C. albicans in all designated intervals, which increased with time. In the first hour of the study, no significant difference was observed between the effects of L. casei on the two drug-resistant strains. However, as time passed, it had a more significant antifungal effect on fluconazole, compared to amphotericin B resistant species (p Value<0.001). Cell counts showed that the number of fungal cells decreased significantly as time passed (p< 0.001).<br><br>CONCLUSION: L. casei had a significant ability to aggregate with both drug-resistant C. albicans species and showed higher antifungal activity on fluconazole-resistant than amphotericin B-resistant species.}, }
@article {pmid38143860, year = {2023}, author = {Peng, C and May, A and Abeel, T}, title = {Unveiling microbial biomarkers of ruminant methane emission through machine learning.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1308363}, pmid = {38143860}, issn = {1664-302X}, abstract = {BACKGROUND: Enteric methane from cow burps, which results from microbial fermentation of high-fiber feed in the rumen, is a significant contributor to greenhouse gas emissions. A promising strategy to address this problem is microbiome-based precision feed, which involves identifying key microorganisms for methane production. While machine learning algorithms have shown success in associating human gut microbiome with various human diseases, there have been limited efforts to employ these algorithms to establish microbial biomarkers for methane emissions in ruminants.<br><br>METHODS: In this study, we aim to identify potential methane biomarkers for methane emission from ruminants by employing regression algorithms commonly used in human microbiome studies, coupled with different feature selection methods. To achieve this, we analyzed the microbiome compositions and identified possible confounding metadata variables in two large public datasets of Holstein cows. Using both the microbiome features and identified metadata variables, we trained different regressors to predict methane emission. With the optimized models, permutation tests were used to determine feature importance to find informative microbial features.<br><br>RESULTS: Among the regression algorithms tested, random forest regression outperformed others and allowed the identification of several crucial microbial taxa for methane emission as members of the native rumen microbiome, including the genera Piromyces, Succinivibrionaceae UCG-002, and Acetobacter. Additionally, our results revealed that certain herd locations and feed composition markers, such as the lipid intake and neutral-detergent fiber intake, are also predictive features for methane emissions.<br><br>CONCLUSION: We demonstrated that machine learning, particularly regression algorithms, can effectively predict cow methane emissions and identify relevant rumen microorganisms. Our findings offer valuable insights for the development of microbiome-based precision feed strategies aiming at reducing methane emissions.}, }
@article {pmid38138045, year = {2023}, author = {Bosch, B and Hartikainen, A and Ronkainen, A and Scheperjans, F and Arkkila, P and Satokari, R}, title = {Development of a Protocol for Anaerobic Preparation and Banking of Fecal Microbiota Transplantation Material: Evaluation of Bacterial Richness in the Cultivated Fraction.}, journal = {Microorganisms}, volume = {11}, number = {12}, pages = {}, pmid = {38138045}, issn = {2076-2607}, support = {6600A-C1012//Finnish National Agency for Education/ ; 323156//Academy of Finland/ ; TYH2019204//The Hospital District of Helsinki and Uusimaa/ ; }, abstract = {Fecal microbiota transplantation (FMT) has shown highly variable results in indications beyond recurrent Clostridioides difficile infection. Microbiota dysbiosis in many diseases is characterized by the depletion of strictly anaerobic bacteria, which may be crucial for FMT efficacy. We developed a protocol to ensure anaerobic conditions during the entire transplant preparation and banking process, from material collection to administration. The protocol necessitates an anaerobic cabinet, i.e., a non-standard laboratory equipment. We analyzed the population of viable anaerobes by combining cultivation and 16S rRNA gene profiling during the transplant preparation, and after 4, 8, and 12 months of anaerobic or aerobic storage at -80 °C, 78% of fecal species were captured via cultivation. Our findings suggest that strictly anaerobic transplant preparation and storage may preserve species richness better than oxic conditions, but the overall difference was not significant. However, specific anaerobes such as Neglecta and Anaerotruncus were affected by the oxygen exposure. A storage time of up to 12 months did not affect the presence of cultivated taxa. Noteworthy, our analysis focused on the richness of cultivated anaerobes rather than their abundance, which may have been affected. The benefits of the developed anaerobic protocol in FMT for specific indications remain to be demonstrated in clinical trials.}, }
@article {pmid38135286, year = {2023}, author = {Angkananard, T}, title = {The Human Microbiome and Atherosclerotic Coronary Heart Disease.}, journal = {European journal of preventive cardiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/eurjpc/zwad401}, pmid = {38135286}, issn = {2047-4881}, }
@article {pmid38132866, year = {2023}, author = {Cheddadi, R and Yeramilli, V and Martin, C}, title = {From Mother to Infant, from Placenta to Gut: Understanding Varied Microbiome Profiles in Neonates.}, journal = {Metabolites}, volume = {13}, number = {12}, pages = {}, pmid = {38132866}, issn = {2218-1989}, abstract = {The field of human microbiome and gut microbial diversity research has witnessed a profound transformation, driven by advances in omics technologies. These advancements have unveiled essential connections between microbiome alterations and severe conditions, prompting the development of new frameworks through epidemiological studies. Traditionally, it was believed that each individual harbored unique microbial communities acquired early in life, evolving over the course of their lifetime, with little acknowledgment of any prenatal microbial development, but recent research challenges this belief. The neonatal microbiome's onset, influenced by factors like delivery mode and maternal health, remains a subject of intense debate, hinting at potential intrauterine microbial processes. In-depth research reveals associations between microbiome profiles and specific health outcomes, ranging from obesity to neurodevelopmental disorders. Understanding these diverse microbiome profiles is essential for unraveling the intricate relationships between the microbiome and health outcomes.}, }
@article {pmid38132864, year = {2023}, author = {Bartsch, M and Hahn, A and Berkemeyer, S}, title = {Bridging the Gap from Enterotypes to Personalized Dietary Recommendations: A Metabolomics Perspective on Microbiome Research.}, journal = {Metabolites}, volume = {13}, number = {12}, pages = {}, pmid = {38132864}, issn = {2218-1989}, abstract = {Advances in high-throughput DNA sequencing have propelled research into the human microbiome and its link to metabolic health. We explore microbiome analysis methods, specifically emphasizing metabolomics, how dietary choices impact the production of microbial metabolites, providing an overview of studies examining the connection between enterotypes and diet, and thus, improvement of personalized dietary recommendations. Acetate, propionate, and butyrate constitute more than 95% of the collective pool of short-chain fatty acids. Conflicting data on acetate's effects may result from its dynamic signaling, which can vary depending on physiological conditions and metabolic phenotypes. Human studies suggest that propionate has overall anti-obesity effects due to its well-documented chemistry, cellular signaling mechanisms, and various clinical benefits. Butyrate, similar to propionate, has the ability to reduce obesity by stimulating the release of appetite-suppressing hormones and promoting the synthesis of leptin. Tryptophan affects systemic hormone secretion, with indole stimulating the release of GLP-1, which impacts insulin secretion, appetite suppression, and gastric emptying. Bile acids, synthesized from cholesterol in the liver and subsequently modified by gut bacteria, play an essential role in the digestion and absorption of dietary fats and fat-soluble vitamins, but they also interact directly with intestinal microbiota and their metabolites. One study using statistical methods identified primarily two groupings of enterotypes Bacteroides and Ruminococcus. The Prevotella-dominated enterotype, P-type, in humans correlates with vegetarians, high-fiber and carbohydrate-rich diets, and traditional diets. Conversely, individuals who consume diets rich in animal fats and proteins, typical in Western-style diets, often exhibit the Bacteroides-dominated, B-type, enterotype. The P-type showcases efficient hydrolytic enzymes for plant fiber degradation but has limited lipid and protein fermentation capacity. Conversely, the B-type features specialized enzymes tailored for the degradation of animal-derived carbohydrates and proteins, showcasing an enhanced saccharolytic and proteolytic potential. Generally, models excel at predictions but often struggle to fully elucidate why certain substances yield varied responses. These studies provide valuable insights into the potential for personalized dietary recommendations based on enterotypes.}, }
@article {pmid38132480, year = {2023}, author = {Kim, MJ and Ko, H and Kim, JY and Kim, HJ and Kim, HY and Cho, HE and Cho, HD and Seo, WS and Kang, HC}, title = {Improvement in Yield of Extracellular Vesicles Derived from Edelweiss Callus Treated with LED Light and Enhancement of Skin Anti-Aging Indicators.}, journal = {Current issues in molecular biology}, volume = {45}, number = {12}, pages = {10159-10178}, pmid = {38132480}, issn = {1467-3045}, abstract = {The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs' efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.}, }
@article {pmid38127919, year = {2023}, author = {L'Heureux, JE and van der Giezen, M and Winyard, PG and Jones, AM and Vanhatalo, A}, title = {Localisation of nitrate-reducing and highly abundant microbial communities in the oral cavity.}, journal = {PloS one}, volume = {18}, number = {12}, pages = {e0295058}, pmid = {38127919}, issn = {1932-6203}, mesh = {Humans ; *Nitrates/metabolism ; Nitrogen Dioxide ; Mouth/microbiology ; Bacteria ; Saliva/metabolism ; *Microbiota ; Streptococcus ; }, abstract = {The nitrate (NO3-) reducing bacteria resident in the oral cavity have been implicated as key mediators of nitric oxide (NO) homeostasis and human health. NO3--reducing oral bacteria reduce inorganic dietary NO3- to nitrite (NO2-) via the NO3--NO2--NO pathway. Studies of oral NO3--reducing bacteria have typically sampled from either the tongue surface or saliva. The aim of this study was to assess whether other areas in the mouth could contain a physiologically relevant abundance of NO3- reducing bacteria, which may be important for sampling in clinical studies. The bacterial composition of seven oral sample types from 300 individuals were compared using a meta-analysis of the Human Microbiome Project data. This analysis revealed significant differences in the proportions of 20 well-established oral bacteria and highly abundant NO3--reducing bacteria across each oral site. The genera included Actinomyces, Brevibacillus, Campylobacter, Capnocytophaga, Corynebacterium, Eikenella, Fusobacterium, Granulicatella, Haemophilus, Leptotrichia, Microbacterium, Neisseria, Porphyromonas, Prevotella, Propionibacterium, Rothia, Selenomonas, Staphylococcus, Streptococcus and Veillonella. The highest proportion of NO3--reducing bacteria was observed in saliva, where eight of the bacterial genera were found in higher proportion than on the tongue dorsum, whilst the lowest proportions were found in the hard oral surfaces. Saliva also demonstrated higher intra-individual variability and bacterial diversity. This study provides new information on where samples should be taken in the oral cavity to assess the abundance of NO3--reducing bacteria. Taking saliva samples may benefit physiological studies, as saliva contained the highest abundance of NO3- reducing bacteria and is less invasive than other sampling methods. These results inform future studies coupling oral NO3--reducing bacteria research with physiological outcomes affecting human health.}, }
@article {pmid38126017, year = {2023}, author = {Gätjens-Boniche, O and Jiménez-Madrigal, JP and Whetten, RW and Valenzuela-Diaz, S and Alemán-Gutiérrez, A and Hanson, PE and Pinto-Tomás, AA}, title = {Microbiome and plant cell transformation trigger insect gall induction in cassava.}, journal = {Frontiers in plant science}, volume = {14}, number = {}, pages = {1237966}, pmid = {38126017}, issn = {1664-462X}, abstract = {Several specialised insects can manipulate normal plant development to induce a highly organised structure known as a gall, which represents one of the most complex interactions between insects and plants. Thus far, the mechanism for insect-induced plant galls has remained elusive. To study the induction mechanism of insect galls, we selected the gall induced by Iatrophobia brasiliensis (Diptera: Cecidomyiidae) in cassava (Euphorbiaceae: Manihot esculenta Crantz) as our model. PCR-based molecular markers and deep metagenomic sequencing data were employed to analyse the gall microbiome and to test the hypothesis that gall cells are genetically transformed by insect vectored bacteria. A shotgun sequencing discrimination approach was implemented to selectively discriminate between foreign DNA and the reference host plant genome. Several known candidate insertion sequences were identified, the most significant being DNA sequences found in bacterial genes related to the transcription regulatory factor CadR, cadmium-transporting ATPase encoded by the cadA gene, nitrate transport permease protein (nrtB gene), and arsenical pump ATPase (arsA gene). In addition, a DNA fragment associated with ubiquitin-like gene E2 was identified as a potential accessory genetic element involved in gall induction mechanism. Furthermore, our results suggest that the increased quality and rapid development of gall tissue are mostly driven by microbiome enrichment and the acquisition of critical endophytes. An initial gall-like structure was experimentally obtained in M. esculenta cultured tissues through inoculation assays using a Rhodococcus bacterial strain that originated from the inducing insect, which we related to the gall induction process. We provide evidence that the modification of the endophytic microbiome and the genetic transformation of plant cells in M. esculenta are two essential requirements for insect-induced gall formation. Based on these findings and having observed the same potential DNA marker in galls from other plant species (ubiquitin-like gene E2), we speculate that bacterially mediated genetic transformation of plant cells may represent a more widespread gall induction mechanism found in nature.}, }
@article {pmid38123504, year = {2024}, author = {Patjas, A and Martelius, A and Ollgren, J and Kantele, A}, title = {International travel increases risk of urinary tract infection caused by extended-spectrum beta-lactamase-producing Enterobacterales-three-arm case-control study.}, journal = {Journal of travel medicine}, volume = {31}, number = {1}, pages = {}, doi = {10.1093/jtm/taad155}, pmid = {38123504}, issn = {1708-8305}, support = {//Sigrid Juselius Foundation/ ; TYH2021314//Finnish Governmental Subsidy for Health Science Research/ ; //University of Helsinki Doctoral School/ ; }, mesh = {Female ; Humans ; Male ; Anti-Bacterial Agents/therapeutic use ; beta-Lactamases ; Case-Control Studies ; Escherichia coli ; *Escherichia coli Infections/drug therapy ; Risk Factors ; *Urinary Tract Infections/drug therapy/epidemiology ; }, abstract = {BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) have worldwide become increasingly prevalent as pathogens causing urinary tract infections (UTIs), posing challenges in their treatment. Of particular concern are travellers to low- and middle-income countries (LMICs), a substantial proportion of whom become colonized by ESBL-PE, with UTIs as the most common clinical manifestation. Seeking tools for preventing ESBL-PE UTI, we explored factors associated with (i) any UTI (versus control), (ii) ESBL-PE UTI (versus control) and (iii) ESBL-PE versus non-ESBL-PE UTI.<br><br>METHODS: During 2015-20, we recruited patients with recent ESBL-PE or non-ESBL-PE UTIs, and controls with no UTI to fill in questionnaires covering potential (ESBL-PE-)UTI risk factors.<br><br>RESULTS: Of our 430 participants, 130 had ESBL-PE UTI and 187 non-ESBL-PE UTI; 113 were controls. Our three comparisons showed several risk factors as exemplified for any UTI versus controls by female sex, lower education, age, diabetes, antibiotic use, diarrhoea; for ESBL-PE UTI versus controls by travel to LMICs, antibiotic use, swimming; and ESBL-PE versus non-ESBL-PE UTI by male sex, higher education, LMIC travel (participant/household member), pets and antibiotic use. Weekly fish meals appeared protective against both UTI and ESBL-PE UTI.<br><br>CONCLUSIONS: Of the numerous factors predisposing to UTI and/or ESBL-PE UTI, our study highlights antibiotic use and LMIC travel. Household members' LMIC travel appears to pose a risk of ESBL-PE UTI, pointing to household transmission of travel-acquired uropathogens. As predisposing factors to multidrug-resistant UTI, international travel and antibiotic use constitute practical targets for prevention efforts.}, }
@article {pmid38116074, year = {2024}, author = {Sheng, Y and Wang, J and Gao, Y and Peng, Y and Li, X and Huang, W and Zhou, H and Liu, R and Zhang, W}, title = {Combined analysis of cross-population healthy adult human microbiome reveals consistent differences in gut microbial characteristics between Western and non-Western countries.}, journal = {Computational and structural biotechnology journal}, volume = {23}, number = {}, pages = {87-95}, pmid = {38116074}, issn = {2001-0370}, abstract = {Despite extensive research on the gut microbiome of healthy individuals from a single country, there are still a limited number of population-level comparative studies. Moreover, the sequencing approach used in most related studies involves 16 S ribosomal RNA (rRNA) sequencing with a limited resolution, which cannot provide detailed functional profiles. In the present study, we applied a combined analysis approach to analyze whole metagenomic shotgun sequencing data from 2035 healthy adult samples from six countries across four continents. Analysis of core species revealed that 13 species were present in more than 90 % of all investigated individuals, the majority of which produced short-chain fatty acids (SCFA)-producing bacteria. Our analysis revealed consistently significant differences in gut microbial species and pathways between Western and non-Western countries, such as Escherichia coli and the relation of MetaCyc pathways to the TCA cycle. Specific changes in microbial species and pathways are potentially related to lifestyle and diet. Furthermore, we identified several noteworthy microbial species and pathways that exhibit distinct characteristics specific to China. Interestingly, we observed that China (CHN) was more similar to the United States (USA) and United Kingdom (GBR) in terms of the taxonomic and functional composition of the gut microbiome than India (IND) and Madagascar (MDG), which were more similar to the China (CHN) diet. The current study identified consistent microbial features associated with population and geography, which will inspire further clinical translations that consider paying attention to differences in microbiota backgrounds and confounding factors.}, }
@article {pmid38111603, year = {2023}, author = {Rowley, CE and Lodge, S and Egan, S and Itsiopoulos, C and Christophersen, CT and Silva, D and Kicic-Starcevich, E and O'Sullivan, TA and Wist, J and Nicholson, J and Frost, G and Holmes, E and D'Vaz, N}, title = {Altered dietary behaviour during pregnancy impacts systemic metabolic phenotypes.}, journal = {Frontiers in nutrition}, volume = {10}, number = {}, pages = {1230480}, pmid = {38111603}, issn = {2296-861X}, abstract = {RATIONALE: Evidence suggests consumption of a Mediterranean diet (MD) can positively impact both maternal and offspring health, potentially mediated by a beneficial effect on inflammatory pathways. We aimed to apply metabolic profiling of serum and urine samples to assess differences between women who were stratified into high and low alignment to a MD throughout pregnancy and investigate the relationship of the diet to inflammatory markers.<br><br>METHODS: From the ORIGINS cohort, 51 pregnant women were stratified for persistent high and low alignment to a MD, based on validated MD questionnaires. [1]H Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the urine and serum metabolite profiles of these women at 36&#x2009;weeks of pregnancy. The relationship between diet, metabolite profile and inflammatory status was investigated.<br><br>RESULTS: There were clear differences in both the food choice and metabolic profiles of women who self-reported concordance to a high (HMDA) and low (LMDA) Mediterranean diet, indicating that alignment with the MD was associated with a specific metabolic phenotype during pregnancy. Reduced meat intake and higher vegetable intake in the HMDA group was supported by increased levels of urinary hippurate (p&#x2009;=&#x2009;0.044) and lower creatine (p&#x2009;=&#x2009;0.047) levels. Serum concentrations of the NMR spectroscopic inflammatory biomarkers GlycA (p&#x2009;=&#x2009;0.020) and GlycB (p&#x2009;=&#x2009;0.016) were significantly lower in the HDMA group and were negatively associated with serum acetate, histidine and isoleucine (p&#x2009;<&#x2009;0.05) suggesting a greater level of plant-based nutrients in the diet. Serum branched chain and aromatic amino acids were positively associated with the HMDA group while both urinary and serum creatine, urine creatinine and dimethylamine were positively associated with the LMDA group.<br><br>CONCLUSION: Metabolic phenotypes of pregnant women who had a high alignment with the MD were significantly different from pregnant women who had a poor alignment with the MD. The metabolite profiles aligned with reported food intake. Differences were most significant biomarkers of systemic inflammation and selected gut-microbial metabolites. This research expands our understanding of the mechanisms driving health outcomes during the perinatal period and provides additional biomarkers for investigation in pregnant women to assess potential health risks.}, }
@article {pmid38108668, year = {2024}, author = {Ye, H-L and Zhi, M-F and Chen, B-Y and Lin, W-Z and Li, Y-L and Huang, S-J and Zhou, L-J and Xu, S and Zhang, J and Zhang, W-C and Feng, Q and Duan, S-Z}, title = {Alterations of oral and gut viromes in hypertension and/or periodontitis.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0116923}, pmid = {38108668}, issn = {2379-5077}, support = {81991503 81725003 81921002//MOST | National Natural Science Foundation of China (NSFC)/ ; SHSMU-ZDCX20212500//Innovative Research Team of High-level Local University in Shanghai (Innovative Research Team of High-level Local Universities in Shanghai)/ ; }, mesh = {Humans ; Virome ; *Viruses/genetics ; *Microbiota/genetics ; *Periodontitis ; *Hypertension ; }, abstract = {The microbiota plays an important role in both hypertension (HTN) and periodontitis (PD), and PD exacerbates the development of HTN by oral and gut microbiota. Previous studies have focused on exploring the importance of the bacteriome in HTN and PD but overlooked the impact of the virome, which is also a member of the microbiota. We collected 180 samples of subgingival plaques, saliva, and feces from a cohort of healthy subjects (nHTNnPD), subjects with HTN (HTNnPD) or PD (PDnHTN), and subjects with both HTN and PD (HTNPD). We performed metagenomic sequencing to assess the roles of the oral and gut viromes in HTN and PD. The HTNnPD, PDnHTN, and HTNPD groups all showed significantly distinct beta diversity from the nHTNnPD group in saliva. We analyzed alterations in oral and gut viral composition in HTN and/or PD and identified significantly changed viruses in each group. Many viruses across three sites were significantly associated with blood pressure and other clinical parameters. Combined with these clinical associations, we found that Gillianvirus in subgingival plaques was negatively associated with HTN and that Torbevirus in saliva was positively associated with HTN. We found that Pepyhexavirus from subgingival plaques was indicated to be transferred to the gut. We finally evaluated viral-bacterial transkingdom interactions and found that viruses and bacteria may cooperate to affect HTN and PD. Correspondingly, HTN and PD may synergize to improve communications between viruses and bacteria.IMPORTANCEPeriodontitis (PD) and hypertension (HTN) are both highly prevalent worldwide and cause serious adverse outcomes. Increasing studies have shown that PD exacerbates HTN by oral and gut microbiota. Previous studies have focused on exploring the importance of the bacteriome in HTN and PD but overlooked the impact of the virome, even though viruses are common inhabitants in humans. Alterations in oral and gut viral diversity and composition contribute to diseases. The present study, for the first time, profiled the oral and gut viromes in HTN and/or PD. We identified key indicator viruses and their clinical implications in HTN and/or PD. We also investigated interactions between viruses and bacteria. This work improved the overall understanding of the viromes in HTN and PD, providing vital insights into the role of the virome in the development of HTN and PD.}, }
@article {pmid38107520, year = {2023}, author = {Fenneman, AC and van der Spek, AH and Hartstra, A and Havik, S and Salonen, A and de Vos, WM and Soeters, MR and Saeed, P and Nieuwdorp, M and Rampanelli, E}, title = {Intestinal permeability is associated with aggravated inflammation and myofibroblast accumulation in Graves' orbitopathy: the MicroGO study.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1173481}, pmid = {38107520}, issn = {1664-2392}, mesh = {Humans ; *Graves Ophthalmopathy/metabolism ; Myofibroblasts ; Receptors, Thyrotropin ; Intestinal Barrier Function ; Toll-Like Receptor 5/metabolism ; Toll-Like Receptor 9/metabolism ; *Graves Disease/metabolism ; Inflammation ; }, abstract = {BACKGROUND: Graves' disease (GD) and Graves' orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability. This study hypothesizes that enhanced intestinal permeability may aggravate orbital inflammation and, thus, increase myofibroblast differentiation and the degree of fibrosis.<br><br>METHODS: Two distinct cohorts of GO patients were studied, one of which was a unique cohort consisting of blood, fecal, and retro-orbital tissue samples. Intestinal permeability was assessed by measuring serum lipopolysaccharide-binding protein (LBP), zonulin, TLR5, and TLR9 ligands. The influx of macrophages and accumulation of T-cells and myofibroblast were quantified in orbital connective tissue. The NanoString immune-oncology RNA targets panel was used to determine the transcriptional profile of active fibrotic areas within orbital sections.<br><br>RESULTS: GO patients displayed significantly higher LBP serum concentrations than healthy controls. Within the MicroGO cohort, patients with high serum LBP levels also showed higher levels of zonulin and TLR5 and TLR9 ligands in their circulation. The increased intestinal permeability was accompanied by augmented expression of genes marking immune cell infiltration and encoding key proteins for immune cell adhesion, antigen presentation, and cytokine signaling in the orbital tissue. Macrophage influx was positively linked to the extent of T cell influx and fibroblast activation within GO-affected orbital tissues. Moreover, serum LBP levels significantly correlated with the abundance of specific Gram-negative gut bacteria, linking the gut to local orbital inflammation.<br><br>CONCLUSION: These results indicate that GO patients have enhanced intestinal permeability. The subsequent translocation of bacterial compounds to the systemic circulation may aggravate inflammatory processes within the orbital tissue and, as a consequence, augment the proportion of activated myofibroblasts, which actively secrete extracellular matrix leading to retro-orbital tissue expansion. These findings warrant further exploration to assess the correlation between specific inflammatory pathways in the orbital tissue and the gut microbiota composition and may pave the way for new microbiota-targeting therapies.}, }
@article {pmid38101449, year = {2023}, author = {Vanstokstraeten, R and Demuyser, T and Piérard, D and Wybo, I and Blockeel, C and Mackens, S}, title = {Culturomics in Unraveling the Upper Female Reproductive Tract Microbiota.}, journal = {Seminars in reproductive medicine}, volume = {41}, number = {5}, pages = {151-159}, doi = {10.1055/s-0043-1777758}, pmid = {38101449}, issn = {1526-4564}, mesh = {Female ; Humans ; *Genitalia, Female ; *Microbiota ; Endometrium ; Embryo Implantation ; }, abstract = {In recent years, the study of the human microbiome has surged, shedding light on potential connections between microbiome composition and various diseases. One specific area of intense interest within this research is the female reproductive tract, as it holds the potential to influence the process of embryo implantation. Advanced sequencing technologies have delivered unprecedented insights into the microbial communities, also known as microbiota, residing in the female reproductive tract. However, their efficacy encounters significant challenges when analyzing low-biomass microbiota, such as those present in the endometrium. These molecular techniques are susceptible to contamination from laboratory reagents and extraction kits, leading to sequencing bias that can significantly alter the perceived taxonomy of a sample. Consequently, investigating the microbiota of the upper female reproductive tract necessitates the exploration of alternative methods. In this context, the current review delves into the application of culturomics in unraveling the upper female reproductive tract microbiota. While culturomics holds value in research, its transition to routine clinical practice appears remote, at least in the foreseeable future.}, }
@article {pmid38099679, year = {2024}, author = {Souza, CE and Jacobson, NE and An, MA and Droit, L and Vega, AA and Rosales, M and Mihindukulasuriya, KA and Pastrana, K and Handley, SA and Parkes, M and Rimmer, J and Wang, D and Dinsdale, EA and A Edwards, R and Segall, AM}, title = {Draft genomes of 12 Bifidobacterium isolates from human IBD fecal samples.}, journal = {Microbiology resource announcements}, volume = {13}, number = {1}, pages = {e0013023}, pmid = {38099679}, issn = {2576-098X}, support = {RC2 DK116713/DK/NIDDK NIH HHS/United States ; }, abstract = {Twelve Bifidobacterium strains were isolated from fecal samples of inflammatory bowel disease patients and matched "household control" individuals. These include the species Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium breve, Bifidobacterium catenulatum, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum.}, }
@article {pmid38098667, year = {2023}, author = {Chung, Y and Kang, SB and Son, D and Lee, JY and Chung, MJ and Lim, S}, title = {Characterization of the probiotic properties of Lacticaseibacillus rhamnosus LR6 isolated from the vaginas of healthy Korean women against vaginal pathogens.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1308293}, pmid = {38098667}, issn = {1664-302X}, abstract = {The human microbiome exhibits intricate populations across the body, with the vaginal tract serving as an ecosystem characterized by the prevalence of the genus Lactobacillus. Disruptions in the vaginal microbiota, which are frequently linked to variables such as sexual activity, hormonal fluctuations, and excessive use of antibiotics, can result in vaginal dysbiosis and the development of diseases such as bacterial vaginosis (BV) and candidiasis. Lactobacillus species, owing to their capacity to create an acidic environment through the production of lactic acid, have a key function within this complex microbial community: they inhibit the growth of harmful microorganisms. This study aimed to investigate the genomic characteristics of L. rhamnosus LR6, a newly discovered strain isolated from the vaginal microbiota of 20 healthy women to assess its potential as a vaginal probiotic. We performed a comparative investigation of the genetic traits of L. rhamnosus using 45 publicly available genomes from various sources. We evaluated the genetic characteristics related to carbohydrate utilization, adhesion to host cells, and the presence of bacteriocin clusters. A comprehensive study was conducted by integrating in silico evaluations with experimental techniques to authenticate the physiological characteristics of strain LR6. We further used a rat model to assess the impact of L. rhamnosus LR6 administration on the changes in the gastrointestinal tract and the vaginal microbiome. The assessments revealed a significantly high inhibitory activity against pathogens, enhanced adherence to host cells, and high lactic acid production. Rat experiments revealed changes in both the fecal and vaginal microbiota; in treated rats, Firmicutes increased in both; Lactobacillaceae increased in the fecal samples; and Enterobacteriaceae decreased but Enterococcaceae, Streptococcaceae, and Morganellaceae increased in the vaginal samples. The study results provide evidence of the genetic characteristics and probiotic properties of LR6, and suggest that oral administration of L. rhamnosus LR6 can alter both gut and vaginal microbiome. Collectively, these findings establish L. rhamnosus LR6 as a highly promising candidate for improving vaginal health.}, }
@article {pmid38097930, year = {2023}, author = {Lu, S and Liang, Y and Li, L and Miao, R and Liao, S and Zou, Y and Yang, C and Ouyang, D}, title = {Predicting potential microbe-disease associations based on auto-encoder and graph convolution network.}, journal = {BMC bioinformatics}, volume = {24}, number = {1}, pages = {476}, pmid = {38097930}, issn = {1471-2105}, support = {No.2022KY0608//Young and Middle aged Teachers Research Basic Ability Improvement Project of Guangxi Universities/ ; No.0056/2020/AFJ//Macau Science and Technology Development Funds Grant No.0056/2020/AFJ from the Macau Special Administrative Region of the People's Republic of China/ ; }, mesh = {Humans ; *Algorithms ; Computational Biology/methods ; *Neoplasms ; }, abstract = {The increasing body of research has consistently demonstrated the intricate correlation between the human microbiome and human well-being. Microbes can impact the efficacy and toxicity of drugs through various pathways, as well as influence the occurrence and metastasis of tumors. In clinical practice, it is crucial to elucidate the association between microbes and diseases. Although traditional biological experiments accurately identify this association, they are time-consuming, expensive, and susceptible to experimental conditions. Consequently, conducting extensive biological experiments to screen potential microbe-disease associations becomes challenging. The computational methods can solve the above problems well, but the previous computational methods still have the problems of low utilization of node features and the prediction accuracy needs to be improved. To address this issue, we propose the DAEGCNDF model predicting potential associations between microbes and diseases. Our model calculates four similar features for each microbe and disease. These features are fused to obtain a comprehensive feature matrix representing microbes and diseases. Our model first uses the graph convolutional network module to extract low-rank features with graph information of microbes and diseases, and then uses a deep sparse Auto-Encoder to extract high-rank features of microbe-disease pairs, after which the low-rank and high-rank features are spliced to improve the utilization of node features. Finally, Deep Forest was used for microbe-disease potential relationship prediction. The experimental results show that combining low-rank and high-rank features helps to improve the model performance and Deep Forest has better classification performance than the baseline model.}, }
@article {pmid38095449, year = {2024}, author = {Arehart, CH and Sterrett, JD and Garris, RL and Quispe-Pilco, RE and Gignoux, CR and Evans, LM and Stanislawski, MA}, title = {Poly-omic risk scores predict inflammatory bowel disease diagnosis.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0067723}, pmid = {38095449}, issn = {2379-5077}, support = {K01 HL157658/HL/NHLBI NIH HHS/United States ; P30 DK048520/DK/NIDDK NIH HHS/United States ; T32 MH016880/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/diagnosis ; Metagenomics/methods ; Phenotype ; *Microbiota ; Risk Factors ; }, abstract = {Inflammatory bowel disease (IBD) is characterized by complex etiology and a disrupted colonic ecosystem. We provide a framework for the analysis of multi-omic data, which we apply to study the gut ecosystem in IBD. Specifically, we train and validate models using data on the metagenome, metatranscriptome, virome, and metabolome from the Human Microbiome Project 2 IBD multi-omic database, with 1,785 repeated samples from 130 individuals (103 cases and 27 controls). After splitting the participants into training and testing groups, we used mixed-effects least absolute shrinkage and selection operator regression to select features for each omic. These features, with demographic covariates, were used to generate separate single-omic prediction scores. All four single-omic scores were then combined into a final regression to assess the relative importance of the individual omics and the predictive benefits when considered together. We identified several species, pathways, and metabolites known to be associated with IBD risk, and we explored the connections between data sets. Individually, metabolomic and viromic scores were more predictive than metagenomics or metatranscriptomics, and when all four scores were combined, we predicted disease diagnosis with a Nagelkerke's R[2] of 0.46 and an area under the curve of 0.80 (95% confidence interval: 0.63, 0.98). Our work supports that some single-omic models for complex traits are more predictive than others, that incorporating multiple omic data sets may improve prediction, and that each omic data type provides a combination of unique and redundant information. This modeling framework can be extended to other complex traits and multi-omic data sets.IMPORTANCEComplex traits are characterized by many biological and environmental factors, such that multi-omic data sets are well-positioned to help us understand their underlying etiologies. We applied a prediction framework across multiple omics (metagenomics, metatranscriptomics, metabolomics, and viromics) from the gut ecosystem to predict inflammatory bowel disease (IBD) diagnosis. The predicted scores from our models highlighted key features and allowed us to compare the relative utility of each omic data set in single-omic versus multi-omic models. Our results emphasized the importance of metabolomics and viromics over metagenomics and metatranscriptomics for predicting IBD status. The greater predictive capability of metabolomics and viromics is likely because these omics serve as markers of lifestyle factors such as diet. This study provides a modeling framework for multi-omic data, and our results show the utility of combining multiple omic data types to disentangle complex disease etiologies and biological signatures.}, }
@article {pmid38094244, year = {2023}, author = {Wijdeveld, M and Schrantee, A and Hagemeijer, A and Nederveen, AJ and Scheithauer, TPM and Levels, JHM and Prodan, A and de Vos, WM and Nieuwdorp, M and Ijzerman, RG}, title = {Intestinal acetate and butyrate availability is associated with glucose metabolism in healthy individuals.}, journal = {iScience}, volume = {26}, number = {12}, pages = {108478}, pmid = {38094244}, issn = {2589-0042}, abstract = {Animal studies suggest that short-chain fatty acids acetate and butyrate are key players in the gut-brain axis and may affect insulin sensitivity. We investigated the association of intestinal acetate and butyrate availability (measured by butyryl-coenzyme A transferase (ButCoA) gene amount) with insulin sensitivity and secretion in healthy subjects from the HELIUS cohort study from the highest 15% (N = 30) and the lowest 15% (N = 30) intestinal ButCoA gene amount. The groups did not differ in insulin sensitivity or secretion. However, the high ButCoA group showed lower glucose and insulin peaks during the first 60 min after a meal and a higher nadir during the second 60 min (p < 0.01), suggesting delayed glucose adsorption from the small intestine. Our data suggest that chronically increased acetate and butyrate availability may improve glucose metabolism by delaying gastric emptying and intestinal adsorption. Future studies should further investigate the effect of acetate and butyrate interventions.}, }
@article {pmid38088868, year = {2024}, author = {Zhao, Z and Sun, X and Cao, L and Zhu, C and He, K and Hu, X and Liu, C and Feng, Q and Qin, Y}, title = {Salivary Proteome and Intact N-Glycopeptides Analysis Reveal Specific Signatures in Periodontitis.}, journal = {Journal of proteome research}, volume = {23}, number = {1}, pages = {25-39}, doi = {10.1021/acs.jproteome.3c00253}, pmid = {38088868}, issn = {1535-3907}, mesh = {Humans ; Proteome/genetics/metabolism ; *Diabetes Mellitus, Type 2/metabolism ; Glycopeptides/metabolism ; Tandem Mass Spectrometry ; *Periodontitis ; Biomarkers/metabolism ; Hypoglycemic Agents ; Saliva/metabolism ; }, abstract = {Periodontitis is a prevalent oral inflammatory disease that can result in tooth loss and is closely linked to type 2 diabetes (T2D). In this study, we analyzed the salivary proteome and intact N-glycopeptides (IGPs) of individuals with mild-moderate, severe, aggressive periodontitis, and periodontitis with T2D, including those treated with antidiabetic drugs, to identify specific signatures associated with the disease. Our results revealed that salivary proteins and glycoproteins were altered in all periodontitis groups (PRIDE ID: 1-20230612-72345), with fucose- and sialic acid-containing N-glycans showing the greatest increase. Additionally, differentially expressed proteins were classified into 9 clusters, including those that were increased in all periodontitis groups and those that were only altered in certain types of periodontitis. Interestingly, treatment with antidiabetic drugs reversed many of the changes observed in the salivary proteome and IGPs in T2D-related periodontitis, suggesting a potential therapeutic approach for managing periodontitis in patients with T2D. Consistent with MS/MS results, the expression of salivary IGHA2 and Fucα1-3/6GlcNAc (AAL) was significantly increased in MP. These findings provide new insights into the pathogenesis of periodontitis and highlight the potential of salivary biomarkers for diagnosis, prognosis, and monitoring of disease progression and treatment response.}, }
@article {pmid38088552, year = {2024}, author = {Konstanti, P and Ligthart, K and Fryganas, C and Constantinos, P and Smidt, H and de Vos, WM and Belzer, C}, title = {Physiology of γ-aminobutyric acid production by Akkermansia muciniphila.}, journal = {Applied and environmental microbiology}, volume = {90}, number = {1}, pages = {e0112123}, pmid = {38088552}, issn = {1098-5336}, support = {024.00.002//Soehngen Institute of Anaerobic Microbiology (SIAM)/ ; Union's Horizon 2020 grant//Eat2beNICE/ ; }, mesh = {Animals ; Humans ; *Proteomics ; *Verrucomicrobia/metabolism ; Neurotransmitter Agents/metabolism ; gamma-Aminobutyric Acid/metabolism ; Akkermansia ; }, abstract = {Gut bacteria hold the potential to produce a broad range of metabolites that can modulate human functions, including molecules with neuroactive potential. One such molecule is γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter of the central nervous system in animals. Metagenomic analyses suggest that the genomes of many gut bacteria encode glutamate decarboxylase (GAD), the enzyme that catalyzes GABA production. The genome of Akkermansia muciniphila, a mucin specialist and potential next-generation probiotic from the human gut, is predicted to encode GAD, suggesting a contributing role in GABA production in the human gut. In this study, A. muciniphila was grown in batch cultures with and without pH control. In both experiments, A. muciniphila was found to produce GABA as a response to acid (pH <5.5), although only when GABA precursors, either glutamate or glutamine, were present in the medium. Proteomic analysis comparing A. muciniphila grown with and without precursors at pH 4 did not show a difference in GAD expression, suggesting that it is expressed regardless of the presence of GABA precursors. To further investigate the function of A. muciniphila GAD, we heterologously expressed the gad gene (encoded by locus tag Amuc_0372) with a His tag in Escherichia coli and purified the GAD protein. Enzyme assays showed GAD activity in a pH range between 4 and 6, with the highest specific activity at pH 5 of 144 ± 16 µM GABA/min/mg. Overall, our results demonstrate the ability of A. muciniphila to produce GABA as an acid response and unravel the conditions under which GABA production in A. muciniphila occurs.IMPORTANCEAkkermansia muciniphila is considered to be a beneficial bacterium from the human gut, but the exact mechanisms by which A. muciniphila influences its host are not yet fully understood. To this end, it is important to identify which metabolites are produced and consumed by A. muciniphila that may contribute to a healthy gut. In the present study, we demonstrate the ability of A. muciniphila to produce γ-aminobutyric acid (GABA) when grown in an acidic environment, which often occurs in the gut. GABA is the major inhibitory neurotransmitter in the central nervous system and is present in the human gut. For this reason, it is considered an important bacterial metabolite. Our finding that A. muciniphila produces GABA in acidic environments adds to the growing body of understanding of its relationship with host health and provides an explanation on how it can survive acid stress in the human gut.}, }
@article {pmid38085102, year = {2024}, author = {Blake, KS and Schwartz, DJ and Paruthiyil, S and Wang, B and Ning, J and Isidean, SD and Burns, DS and Whiteson, H and Lalani, T and Fraser, JA and Connor, P and Troth, T and Porter, CK and Tribble, DR and Riddle, MS and Gutiérrez, RL and Simons, MP and Dantas, G}, title = {Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.}, journal = {mBio}, volume = {15}, number = {1}, pages = {e0279023}, pmid = {38085102}, issn = {2150-7511}, support = {T32 DK077653/DK/NIDDK NIH HHS/United States ; T32 DK007130/DK/NIDDK NIH HHS/United States ; 2021081/DDCF/Doris Duke Charitable Foundation/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; U01 AI123394/AI/NIAID NIH HHS/United States ; K08 AI159384/AI/NIAID NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; Y01 AI005072/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Diarrhea/prevention &amp; control ; *Gastrointestinal Microbiome ; Travel ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Drug Resistance, Microbial ; }, abstract = {The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.}, }
@article {pmid38078749, year = {2024}, author = {Park, H and Joachimiak, MP and Jungbluth, SP and Yang, Z and Riehl, WJ and Canon, RS and Arkin, AP and Dehal, PS}, title = {A bacterial sensor taxonomy across earth ecosystems for machine learning applications.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0002623}, pmid = {38078749}, issn = {2379-5077}, support = {//DOE | NNSA | LDRD | Lawrence Berkeley National Laboratory (LBNL)/ ; }, mesh = {Humans ; *Metagenomics ; *Microbiota ; Metagenome ; Machine Learning ; Earth, Planet ; }, abstract = {Microbial communities have evolved to colonize all ecosystems of the planet, from the deep sea to the human gut. Microbes survive by sensing, responding, and adapting to immediate environmental cues. This process is driven by signal transduction proteins such as histidine kinases, which use their sensing domains to bind or otherwise detect environmental cues and "transduce" signals to adjust internal processes. We hypothesized that an ecosystem's unique stimuli leave a sensor "fingerprint," able to identify and shed insight on ecosystem conditions. To test this, we collected 20,712 publicly available metagenomes from Host-associated, Environmental, and Engineered ecosystems across the globe. We extracted and clustered the collection's nearly 18M unique sensory domains into 113,712 similar groupings with MMseqs2. We built gradient-boosted decision tree machine learning models and found we could classify the ecosystem type (accuracy: 87%) and predict the levels of different physical parameters (R2 score: 83%) using the sensor cluster abundance as features. Feature importance enables identification of the most predictive sensors to differentiate between ecosystems which can lead to mechanistic interpretations if the sensor domains are well annotated. To demonstrate this, a machine learning model was trained to predict patient's disease state and used to identify domains related to oxygen sensing present in a healthy gut but missing in patients with abnormal conditions. Moreover, since 98.7% of identified sensor domains are uncharacterized, importance ranking can be used to prioritize sensors to determine what ecosystem function they may be sensing. Furthermore, these new predictive sensors can function as targets for novel sensor engineering with applications in biotechnology, ecosystem maintenance, and medicine.IMPORTANCEMicrobes infect, colonize, and proliferate due to their ability to sense and respond quickly to their surroundings. In this research, we extract the sensory proteins from a diverse range of environmental, engineered, and host-associated metagenomes. We trained machine learning classifiers using sensors as features such that it is possible to predict the ecosystem for a metagenome from its sensor profile. We use the optimized model's feature importance to identify the most impactful and predictive sensors in different environments. We next use the sensor profile from human gut metagenomes to classify their disease states and explore which sensors can explain differences between diseases. The sensors most predictive of environmental labels here, most of which correspond to uncharacterized proteins, are a useful starting point for the discovery of important environment signals and the development of possible diagnostic interventions.}, }
@article {pmid38075911, year = {2023}, author = {Bakir-Gungor, B and Temiz, M and Jabeer, A and Wu, D and Yousef, M}, title = {microBiomeGSM: the identification of taxonomic biomarkers from metagenomic data using grouping, scoring and modeling (G-S-M) approach.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1264941}, pmid = {38075911}, issn = {1664-302X}, abstract = {Numerous biological environments have been characterized with the advent of metagenomic sequencing using next generation sequencing which lays out the relative abundance values of microbial taxa. Modeling the human microbiome using machine learning models has the potential to identify microbial biomarkers and aid in the diagnosis of a variety of diseases such as inflammatory bowel disease, diabetes, colorectal cancer, and many others. The goal of this study is to develop an effective classification model for the analysis of metagenomic datasets associated with different diseases. In this way, we aim to identify taxonomic biomarkers associated with these diseases and facilitate disease diagnosis. The microBiomeGSM tool presented in this work incorporates the pre-existing taxonomy information into a machine learning approach and challenges to solve the classification problem in metagenomics disease-associated datasets. Based on the G-S-M (Grouping-Scoring-Modeling) approach, species level information is used as features and classified by relating their taxonomic features at different levels, including genus, family, and order. Using four different disease associated metagenomics datasets, the performance of microBiomeGSM is comparatively evaluated with other feature selection methods such as Fast Correlation Based Filter (FCBF), Select K Best (SKB), Extreme Gradient Boosting (XGB), Conditional Mutual Information Maximization (CMIM), Maximum Likelihood and Minimum Redundancy (MRMR) and Information Gain (IG), also with other classifiers such as AdaBoost, Decision Tree, LogitBoost and Random Forest. microBiomeGSM achieved the highest results with an Area under the curve (AUC) value of 0.98% at the order taxonomic level for IBDMD dataset. Another significant output of microBiomeGSM is the list of taxonomic groups that are identified as important for the disease under study and the names of the species within these groups. The association between the detected species and the disease under investigation is confirmed by previous studies in the literature. The microBiomeGSM tool and other supplementary files are publicly available at: https://github.com/malikyousef/microBiomeGSM.}, }
@article {pmid38075858, year = {2023}, author = {Marcos-Zambrano, LJ and López-Molina, VM and Bakir-Gungor, B and Frohme, M and Karaduzovic-Hadziabdic, K and Klammsteiner, T and Ibrahimi, E and Lahti, L and Loncar-Turukalo, T and Dhamo, X and Simeon, A and Nechyporenko, A and Pio, G and Przymus, P and Sampri, A and Trajkovik, V and Lacruz-Pleguezuelos, B and Aasmets, O and Araujo, R and Anagnostopoulos, I and Aydemir, &#xd6; and Berland, M and Calle, ML and Ceci, M and Duman, H and Gündoğdu, A and Havulinna, AS and Kaka Bra, KHN and Kalluci, E and Karav, S and Lode, D and Lopes, MB and May, P and Nap, B and Nedyalkova, M and Paciência, I and Pasic, L and Pujolassos, M and Shigdel, R and Susín, A and Thiele, I and Truică, CO and Wilmes, P and Yilmaz, E and Yousef, M and Claesson, MJ and Truu, J and Carrillo de Santa Pau, E}, title = {A toolbox of machine learning software to support microbiome analysis.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1250806}, pmid = {38075858}, issn = {1664-302X}, abstract = {The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis.}, }
@article {pmid38069593, year = {2023}, author = {Tiwari, S and Han, Z}, title = {Immunotherapy: Advancing glioblastoma treatment-A narrative review of scientific studies.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {7}, number = {2}, pages = {e1947}, pmid = {38069593}, issn = {2573-8348}, abstract = {BACKGROUND: Glioblastoma (GB) is an aggressive and deadly brain tumor with a poor prognosis despite the current standard of care, including surgery, radiation, and chemotherapy.<br><br>RECENT FINDINGS: In recent years, there has been increasing interest in the potential of immunotherapies, seen to be effective in treating other cancers, in the treatment of GB. This comprehensive review presents an in-depth analysis of the remarkable progress of immunotherapy in GB treatment, focusing on human clinical studies. It also analyzes the current findings, challenges, and limitations that underscore the transformative potential of immunotherapy in managing GB. Of particular significance, it delves into the intriguing interaction of the human microbiome with immunotherapy as a novel avenue for enhancing treatment outcomes of GB.<br><br>CONCLUSION: This study sheds light on the complex GB therapy landscape and the cutting-edge strategies that show promise for enhancing patient prognosis.}, }
@article {pmid38065982, year = {2023}, author = {Roslan, MAM and Omar, MN and Sharif, NAM and Raston, NHA and Arzmi, MH and Neoh, HM and Ramzi, AB}, title = {Recent advances in single-cell engineered live biotherapeutic products research for skin repair and disease treatment.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {95}, pmid = {38065982}, issn = {2055-5008}, mesh = {Humans ; *Anti-Bacterial Agents ; Skin ; *Microbiota ; }, abstract = {The human microbiome has emerged as a key player in maintaining skin health, and dysbiosis has been linked to various skin disorders. Amidst growing concerns regarding the side effects of antibiotic treatments, the potential of live biotherapeutic products (LBPs) in restoring a healthy microbiome has garnered significant attention. This review aims to evaluate the current state of the art of the genetically or metabolically engineered LBPs, termed single-cell engineered LBPs (eLBPs), for skin repair and disease treatment. While some studies demonstrate promising outcomes, the translation of eLBPs into clinical applications remains a significant hurdle. Substantial concerns arise regarding the practical implementation and scalability of eLBPs, despite the evident potential they hold in targeting specific cells and delivering therapeutic agents. This review underscores the need for further research, robust clinical trials, and the exploration of current advances in eLBP-based bioengineered bacterial chassis and new outlooks to substantiate the viability and effectiveness of eLBPs as a transformative approach in skin repair and disease intervention.}, }
@article {pmid38063388, year = {2024}, author = {Song, L and Rauf, F and Hou, C-W and Qiu, J and Murugan, V and Chung, Y and Lai, H and Adam, D and Magee, DM and Trivino Soto, G and Peterson, M and Anderson, KS and Rice, SG and Readhead, B and Park, JG and LaBaer, J}, title = {Quantitative assessment of multiple pathogen exposure and immune dynamics at scale.}, journal = {Microbiology spectrum}, volume = {12}, number = {1}, pages = {e0239923}, pmid = {38063388}, issn = {2165-0497}, support = {75N91019D00024/CA/NCI NIH HHS/United States ; R21 CA196442/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Public Health ; *Immune System ; *Serology/methods ; }, abstract = {Serology reveals exposure to pathogens, as well as the state of autoimmune and other clinical conditions. It is used to evaluate individuals and their histories and as a public health tool to track epidemics. Employing a variety of formats, studies nearly always perform serology by testing response to only one or a few antigens. However, clinical outcomes of new infections also depend on which previous infections may have occurred. We developed a high-throughput serology method that evaluates responses to hundreds of antigens simultaneously. It can be used to evaluate thousands of samples at a time and provide a quantitative readout. This tool will enable doctors to monitor which pathogens an individual has been exposed to and how that changes in the future. Moreover, public health officials could track populations and look for infectious trends among large populations. Testing many potential antigens at a time may also aid in vaccine development.}, }
@article {pmid38058765, year = {2023}, author = {Ponsero, AJ and Miller, M and Hurwitz, BL}, title = {Comparison of k-mer-based de novo comparative metagenomic tools and approaches.}, journal = {Microbiome research reports}, volume = {2}, number = {4}, pages = {27}, pmid = {38058765}, issn = {2771-5965}, abstract = {Aim: Comparative metagenomic analysis requires measuring a pairwise similarity between metagenomes in the dataset. Reference-based methods that compute a beta-diversity distance between two metagenomes are highly dependent on the quality and completeness of the reference database, and their application on less studied microbiota can be challenging. On the other hand, de-novo comparative metagenomic methods only rely on the sequence composition of metagenomes to compare datasets. While each one of these approaches has its strengths and limitations, their comparison is currently limited. Methods: We developed sets of simulated short-reads metagenomes to (1) compare k-mer-based and taxonomy-based distances and evaluate the impact of technical and biological variables on these metrics and (2) evaluate the effect of k-mer sketching and filtering. We used a real-world metagenomic dataset to provide an overview of the currently available tools for de novo metagenomic comparative analysis. Results: Using simulated metagenomes of known composition and controlled error rate, we showed that k-mer-based distance metrics were well correlated to the taxonomic distance metric for quantitative Beta-diversity metrics, but the correlation was low for presence/absence distances. The community complexity in terms of taxa richness and the sequencing depth significantly affected the quality of the k-mer-based distances, while the impact of low amounts of sequence contamination and sequencing error was limited. Finally, we benchmarked currently available de-novo comparative metagenomic tools and compared their output on two datasets of fecal metagenomes and showed that most k-mer-based tools were able to recapitulate the data structure observed using taxonomic approaches. Conclusion: This study expands our understanding of the strength and limitations of k-mer-based de novo comparative metagenomic approaches and aims to provide concrete guidelines for researchers interested in applying these approaches to their metagenomic datasets.}, }
@article {pmid38053859, year = {2023}, author = {Sharma, S and Bakht, A and Jahanzaib, M and Kim, M and Lee, H and Park, C and Park, D}, title = {Characterization of bacterial species and antibiotic resistance observed in Seoul, South Korea's popular Gangnam-gu area.}, journal = {Heliyon}, volume = {9}, number = {11}, pages = {e21751}, pmid = {38053859}, issn = {2405-8440}, abstract = {Public transportation facilities, especially road crossings, which raise the pathogenic potential of urban environments, are the most conducive places for the transfer of germs between people and the environment. It is necessary to study the variety of the microbiome and describe its unique characteristics to comprehend these relationships. In this investigation, we used 16 S rRNA gene sample sequencing to examine the biological constituents and inhalable, thoracic, and alveolar particles in aerosol samples collected from busy areas in the Gangnam-gu district of the Seoul metropolitan area using a mobile vehicle. We also conducted a comparison analysis of these findings with the previously published data and tested for antibiotic resistance to determine the distribution of bacteria related to the human microbiome and the environment. Actinobacteria, Cyanobacteria, Bacteriodetes, Proteobacteria, and Firmicutes were the top five phyla in the bacterial 16 S rRNA libraries, accounting for >90 % of all readings across all examined locations. The most prevalent classes among the 12 found bacterial classes were Bacilli (45.812 %), Gammaproteobacteria (25.238 %), Tissierellia (13.078 %), Clostridia (5.697 %), and Alphaproteobacteria (5.142 %). The data acquired offer useful information on the variety of bacterial communities and their resistance to antibiotic drugs on the streets of Gangnam-gu, one of the most significant social centers in the Seoul metropolitan area. This work emphasizes the relevance of biological particles and particulate matter in the air, and it suggests more research is needed to perform biological characterization of the ambient particulate matter.}, }
@article {pmid38051964, year = {2023}, author = {Lavoie, T and Appaneal, HJ and LaPlante, KL}, title = {Advancements in Novel Live Biotherapeutic Products for Clostridioides difficile Infection Prevention.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {Suppl 6}, pages = {S447-S454}, doi = {10.1093/cid/ciad639}, pmid = {38051964}, issn = {1537-6591}, support = {//Seres and Ferring/ ; }, mesh = {Humans ; Dysbiosis/therapy ; *Clostridioides difficile ; Fecal Microbiota Transplantation ; *Clostridium Infections/prevention &amp; control/drug therapy ; Feces/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {The profound impact of the human microbiome on health and disease has captivated the interest of clinical and scientific communities. The human body hosts a vast array of microorganisms collectively forming the human microbiome, which significantly influences various physiological processes and profoundly shapes overall well-being. Notably, the gut stands out as an exceptional reservoir, harboring the most significant concentration of microorganisms, akin to an organ in itself. The gut microbiome's composition and function are influenced by genetics, environment, age, underlying conditions, and antibiotic usage, leading to dysbiosis and pathogenesis, such as Clostridioides difficile infection (CDI). Conventional CDI treatment, involving antibiotics like oral vancomycin and fidaxomicin, fails to address dysbiosis and may further disrupt gut microbial communities. Consequently, emerging therapeutic strategies are focused on targeting dysbiosis and restoring gut microbiota to advance CDI therapeutics. Fecal microbiota transplantation (FMT) has demonstrated remarkable efficacy in treating recurrent CDI by transferring processed stool from a healthy donor to a recipient, restoring gut dysbiosis and enhancing bacterial diversity. Moreover, 2 newer Food and Drug Administration (FDA)-approved live biotherapeutic products (LBP), namely, Fecal Microbiota Live-JSLM and Fecal Microbiota Spores Live-BRPK, have shown promise in preventing CDI recurrence. This review explores the role of the gut microbiota in preventing and treating CDI, with an emphasis on gut-based interventions like FMT and fecal microbiota-based products that hold potential for gut restoration and prevention of CDI recurrence. Understanding the microbiome's impact on CDI prevention and treatment offers valuable insights for advancing future CDI therapeutics.}, }
@article {pmid38049273, year = {2024}, author = {Mantegazza, G and Duncan, R and Telesca, N and Gargari, G and Perotti, S and Riso, P and Guglielmetti, S}, title = {Lactic acid bacteria naturally associated with ready-to-eat rocket salad can survive the human gastrointestinal transit.}, journal = {Food microbiology}, volume = {118}, number = {}, pages = {104418}, doi = {10.1016/j.fm.2023.104418}, pmid = {38049273}, issn = {1095-9998}, mesh = {Humans ; *Lactobacillales ; *Salads ; Food Microbiology ; Gastrointestinal Transit ; Vegetables/microbiology ; Bacteria ; Leuconostoc ; }, abstract = {It was theorized that modernization and the decline in harmless microbial populations associated with food have altered the gut microbiota, impacting host metabolism and immunity. Western dietary patterns, characterized by processed foods and preservation methods, may significantly reduce the microbial population associated with food. To mitigate the consequences of bacterial deprivation, the integration of these diets with fermented foods is commonly proposed. Nonetheless, non-fermented food consumed raw may also be an important source of viable microbial cells for the human microbiome. This study investigates whether salad-associated LAB can survive the gastrointestinal transit (GIT) and contribute to the gut microbiota. LAB strains were quantified and isolated from rocket salad (Eruca vesicaria subsp. sativa), and their survival through GIT was assessed via intervention trials in healthy adults and in vitro. Moreover, bacterial communities in fecal samples were analyzed after three days of rocket salad consumption. Washing with a sodium hypochlorite solution drastically reduced total bacterial load and eliminated viable LAB. The quantity of LAB introduced through salads did not significantly alter the gut microbiota composition. Rocket salads harbored Weissella and Leuconostoc species. A significant increase in Weissella spp. but not in Leuconostoc spp. was observed after the consumption of rocket salad. Simulated GIT experiments suggested that the food matrix and the initial number of ingested viable bacteria may have been important in determining survival. These findings propose that plant products could serve as sources of live LAB for the human gut. Further research with diverse vegetables and longer interventions is needed, encouraging studies on raw, non-fermented foods and their impact on the human intestinal microbiome.}, }
@article {pmid38048079, year = {2023}, author = {Fu, P and Wu, Y and Zhang, Z and Qiu, Y and Wang, Y and Peng, Y}, title = {VIGA: a one-stop tool for eukaryotic virus identification and genome assembly from next-generation-sequencing data.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {1}, pages = {}, pmid = {38048079}, issn = {1477-4054}, support = {32370700//National Natural Science Foundation of China/ ; 2022YFC2303802//National Key Plan for Scientific Research and Development of China/ ; }, mesh = {Humans ; High-Throughput Nucleotide Sequencing ; *Colitis, Ulcerative ; *Crohn Disease ; Genome, Viral ; Metagenome ; }, abstract = {Identification of viruses and further assembly of viral genomes from the next-generation-sequencing data are essential steps in virome studies. This study presented a one-stop tool named VIGA (available at https://github.com/viralInformatics/VIGA) for eukaryotic virus identification and genome assembly from NGS data. It was composed of four modules, namely, identification, taxonomic annotation, assembly and novel virus discovery, which integrated several third-party tools such as BLAST, Trinity, MetaCompass and RagTag. Evaluation on multiple simulated and real virome datasets showed that VIGA assembled more complete virus genomes than its competitors on both the metatranscriptomic and metagenomic data and performed well in assembling virus genomes at the strain level. Finally, VIGA was used to investigate the virome in metatranscriptomic data from the Human Microbiome Project and revealed different composition and positive rate of viromes in diseases of prediabetes, Crohn's disease and ulcerative colitis. Overall, VIGA would help much in identification and characterization of viromes, especially the known viruses, in future studies.}, }
@article {pmid38047279, year = {2023}, author = {Candeliere, F and Musmeci, E and Amaretti, A and Sola, L and Raimondi, S and Rossi, M}, title = {Profiling of the intestinal community of Clostridia: taxonomy and evolutionary analysis.}, journal = {Microbiome research reports}, volume = {2}, number = {2}, pages = {13}, pmid = {38047279}, issn = {2771-5965}, abstract = {Aim: Clostridia are relevant commensals of the human gut due to their major presence and correlations to the host. In this study, we investigated intestinal Clostridia of 51 healthy subjects and reconstructed their taxonomy and phylogeny. The relatively small number of intestinal Clostridia allowed a systematic whole genome approach based on average amino acid identity (AAI) and core genome with the aim of revising the current classification into genera and determining evolutionary relationships. Methods: 51 healthy subjects' metagenomes were retrieved from public databases. After the dataset's validation through comparison with Human Microbiome Project (HMP) samples, the metagenomes were profiled using MetaPhlAn3 to identify the population ascribed to the class Clostridia. Intestinal Clostridia genomes were retrieved and subjected to AAI analysis and core genome identification. Phylogeny investigation was conducted with RAxML and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) algorithms, and SplitsTree for split decomposition. Results: 225 out of 406 bacterial taxonomic units were ascribed to Bacillota [Firmicutes], among which 124 were assigned to the class Clostridia. 77 out of the 124 taxonomic units were referred to a species, altogether covering 87.7% of Clostridia abundance. According to the lowest AAI genus boundary set at 55%, 15 putative genera encompassing more than one species (G1 to G15) were identified, while 19 species did not cluster with any other one and each appeared to belong to a diverse genus. Phylogenetic investigations highlighted that most of the species clustered into three main evolutive clades. Conclusion: This study shed light on the species of Clostridia colonizing the gut of healthy adults and pinpointed several gaps in knowledge regarding the taxonomy and the phylogeny of Clostridia.}, }
@article {pmid38045923, year = {2023}, author = {Al, KF and Allen, L and Bedell, S and Burton, JP and de Vrijer, B}, title = {Assessing the impact of pregnancy and birth factors on the maternal and infant microbiota.}, journal = {Microbiome research reports}, volume = {2}, number = {4}, pages = {29}, pmid = {38045923}, issn = {2771-5965}, abstract = {Background: The microbiota acquired at birth is known to play an intimate role in later life health and disease and has been shown to be affected by the mode of birth. There has been recent interest in microbiota correction by maternal vaginal seeding in Cesarean section-born infants; however, the safety of this practice has been debated. The aim of this study was to assess how other factors, such as timing of sampling, maternal obesity, vaginal Group B Streptococcus colonization (GBS), and antibiotic exposure, affect the maternal and infant microbiota. Methods: Maternal vaginal and saliva samples were collected at three time periods: 35-37 weeks gestation (prenatal), within 24-36 hours after birth (birth), and at ~6 weeks postpartum. Infant saliva and stool samples were collected at ~6 weeks postpartum. 16S rRNA amplicon sequencing was utilized to assess the taxonomic and inferred functional compositions of the bacterial communities from both mothers and infants. Results: Samples from 36 mothers and 32 infants were obtained. Gestational age, breastfeeding, mode of birth, and gravidity were associated with taxonomic alterations in the infant samples, while obesity, antibiotic use, and GBS status were not. Maternal samples were predominantly affected by time, whereby significant alterations including increased microbial diversity were seen at birth and persisted to 6 weeks postpartum. Conclusion: This study provides information on the relationship between health and delivery factors and changes in vaginal and infant microbiota. These results may better direct clinicians and mothers in optimizing the infant microbiota towards health during infancy and later life.}, }
@article {pmid38045612, year = {2023}, author = {Brüssow, H}, title = {The human microbiome project at ten years - some critical comments and reflections on "our third genome", the human virome.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {7}, pmid = {38045612}, issn = {2771-5965}, abstract = {The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch's postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease - in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.}, }
@article {pmid38045610, year = {2023}, author = {Reid, G}, title = {Perspective: microbial interventions in the urinary tract.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {3}, pmid = {38045610}, issn = {2771-5965}, abstract = {Despite multiple advances in medicine, the management of urinary tract infections (UTIs) in women has remained stalled for decades. To prevent the development of symptomatic recurrences, low-dose antibiotics are the mainstay, while alternative approaches have been attempted with limited success. The use of probiotics was first considered forty years ago, and while some promising studies have been published, additional evidence in larger patient groups is needed to recommend specific strains as a primary preventive regimen. Overall, the role of beneficial microbes in reducing the risk of UTI and other urological diseases, such as urolithiasis, remains a target for researchers. The aim of this perspective is to offer a viewpoint on the status of this approach and recommendations for how to develop novel probiotic therapies.}, }
@article {pmid38045608, year = {2023}, author = {Segers, A and de Vos, WM}, title = {Mode of action of Akkermansia muciniphila in the intestinal dialogue: role of extracellular proteins, metabolites and cell envelope components.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {6}, pmid = {38045608}, issn = {2771-5965}, abstract = {Akkermansia muciniphila is a promising next-generation beneficial microbe due to its natural presence in the mucus layer of the gut, its symbiotic ability to degrade mucus, and its capacity to improve the intestinal barrier function. A. muciniphila is able to counteract weight gain and immuno-metabolic disturbances in several animal models. Many of these disorders, including obesity and auto-immune diseases, have been associated with decreased gut barrier function and consequent increased inflammation. Since A. muciniphila was found to normalize these changes and strengthen the gut barrier function, it is hypothesized that other beneficial effects of A. muciniphila might be caused by this restoration. In search for A. muciniphila's mode of action in enhancing the gut barrier function and promoting health, we reasoned that secreted components or cell envelope components of A. muciniphila are interesting candidates as they can potentially reach and interact with the epithelial barrier. In this review, we focus on the potential mechanisms through which A. muciniphila can exert its beneficial effects on the host by the production of extracellular and secreted proteins, metabolites and cell envelope components. These products have been studied in isolation for their structure, signaling capacity, and in some cases, also for their effects in preclinical models. This includes the protein known as Amuc_1100, which we here rename as pilus-associated signaling (PAS) protein , the P9 protein encoded by Amuc_1631, the short-chain fatty acids acetate and propionate, and cell envelope components, such as phosphatidylethanolamine and peptidoglycan.}, }
@article {pmid38045399, year = {2023}, author = {Olm, MR and Spencer, SP and Silva, EL and Sonnenburg, JL}, title = {Metagenomic Immunoglobulin Sequencing (MIG-Seq) Exposes Patterns of IgA Antibody Binding in the Healthy Human Gut Microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38045399}, issn = {2692-8205}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; K08 DK134856/DK/NIDDK NIH HHS/United States ; S10 OD026929/OD/NIH HHS/United States ; S10 OD026831/OD/NIH HHS/United States ; F32 DK128865/DK/NIDDK NIH HHS/United States ; }, abstract = {IgA, the most highly produced human antibody, is continually secreted into the gut to shape the intestinal microbiota. Methodological limitations have critically hindered defining which microbial strains are targeted by IgA and why. Here, we develop a new technique, Metagenomic Immunoglobulin Sequencing (MIG-Seq), and use it to determine IgA coating levels for thousands of gut microbiome strains in healthy humans. We find that microbes associated with both health and disease have higher levels of coating, and that microbial genes are highly predictive of IgA binding levels, with mucus degradation genes especially correlated with high binding. We find a significant reduction in replication rates among microbes bound by IgA, and demonstrate that IgA binding is more correlated with host immune status than traditional microbial abundance measures. This study introduces a powerful technique for assessing strain-level IgA binding in human stool, paving the way for deeper understanding of IgA-based host microbe interactions.}, }
@article {pmid38041504, year = {2023}, author = {Fujimoto, A and Fujii, K and Suido, H and Fukuike, H and Miyake, N and Suzuki, H and Eguchi, T and Tobata, H}, title = {Changes in oral microflora following 0.3% cetylpyridinium chloride-containing mouth spray intervention in adult volunteers after professional oral care: Randomized clinical study.}, journal = {Clinical and experimental dental research}, volume = {9}, number = {6}, pages = {1034-1043}, pmid = {38041504}, issn = {2057-4347}, support = {//Sunstar Inc./ ; }, mesh = {Adult ; Humans ; Cetylpyridinium ; *Anti-Infective Agents, Local ; Mouthwashes ; *Dental Plaque/microbiology ; Tongue/microbiology ; Double-Blind Method ; Volunteers ; }, abstract = {OBJECTIVES: This study explored the changes in bacterial flora composition and total bacterial count in the saliva and tongue coating, along with the change in the tongue coating index (TCI) following an intervention with 0.3% cetylpyridinium chloride (CPC) mouth spray after professional oral care.<br><br>MATERIALS AND METHODS: Fifty-two adult volunteers aged 30-60 years were equally divided into CPC spray (n&#x2009;=&#x2009;26) and control (n&#x2009;=&#x2009;26) groups. All subjects underwent scaling and polishing. The CPC spray group was administered four puffs of CPC spray to the tongue dorsum four times a day for 3 weeks. The control group performed only routine daily oral care (brushing) and did not use any other spray. Bacteriological evaluation of saliva and tongue coating was performed using 16S ribosomal RNA&#xa0;gene sequencing and quantitative polymerase chain reaction. The tongue coating was evaluated to calculate the TCI. A per-protocol analysis was conducted for 44 subjects (CPC spray group, n&#x2009;=&#x2009;23; control group, n&#x2009;=&#x2009;21).<br><br>RESULTS: At 1 and 3 weeks after CPC spray use, the flora of the saliva and tongue coating changed; the genus Haemophilus was dominant in the CPC spray group, whereas the genus Saccharibacteria was dominant in the control group. The sampling time differed among individual participants, which may have affected the bacterial counts. There was no significant intragroup change in TCI in either group.<br><br>CONCLUSIONS: CPC spray affected the bacterial flora in the saliva and tongue coating, particularly with respect to an increase in the abundance of Haemophilus. However, CPC spray did not change the TCI. These results suggest that it may be optimal to combine CPC spray with a physical cleaning method such as using a tongue brush or scraper.&#xa0;Clinical Trial Registration:&#xa0;University Hospital Medical Information Network UMIN000041140.}, }
@article {pmid38032644, year = {2023}, author = {Landry, MJ and Ward, CP and Cunanan, KM and Durand, LR and Perelman, D and Robinson, JL and Hennings, T and Koh, L and Dant, C and Zeitlin, A and Ebel, ER and Sonnenburg, ED and Sonnenburg, JL and Gardner, CD}, title = {Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {6}, number = {11}, pages = {e2344457}, pmid = {38032644}, issn = {2574-3805}, support = {UL1 TR003142/TR/NCATS NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; T32 HL161270/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; Body Weight ; *Cardiovascular Diseases/prevention &amp; control ; Cholesterol, LDL ; *Diet, Vegan ; Insulins ; Twins, Monozygotic ; Vegetables ; Middle Aged ; Diet, Healthy ; }, abstract = {IMPORTANCE: Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds).<br><br>OBJECTIVE: To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention.<br><br>This single-center, population-based randomized clinical trial of 22 pairs of twins (N&#x2009;=&#x2009;44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data.<br><br>INTERVENTION: Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks.<br><br>MAIN OUTCOMES AND MEASURES: The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being.<br><br>RESULTS: A total of 22 pairs (N&#x2009;=&#x2009;44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] &#x3bc;IU/mL; 95% CI, -5.3 to -0.4 &#x3bc;IU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg).<br><br>CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05297825.}, }
@article {pmid38029237, year = {2023}, author = {Rinaldi, F and Chirico, R and Trink, A and Pinto, D}, title = {Resistance and Pseudo-resistance to permethrin: the importance of controlling scabies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1297337}, pmid = {38029237}, issn = {2235-2988}, mesh = {Humans ; *Scabies/drug therapy ; Permethrin/pharmacology ; *Insecticides/pharmacology ; Ivermectin ; }, }
@article {pmid38022690, year = {2023}, author = {Meng, D and Ai, S and Spanos, M and Shi, X and Li, G and Cretoiu, D and Zhou, Q and Xiao, J}, title = {Exercise and microbiome: From big data to therapy.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {5434-5445}, pmid = {38022690}, issn = {2001-0370}, abstract = {Exercise is a vital component in maintaining optimal health and serves as a prospective therapeutic intervention for various diseases. The human microbiome, comprised of trillions of microorganisms, plays a crucial role in overall health. Given the advancements in microbiome research, substantial databases have been created to decipher the functionality and mechanisms of the microbiome in health and disease contexts. This review presents an initial overview of microbiomics development and related databases, followed by an in-depth description of the multi-omics technologies for microbiome. It subsequently synthesizes the research pertaining to exercise-induced modifications of the microbiome and diseases that impact the microbiome. Finally, it highlights the potential therapeutic implications of an exercise-modulated microbiome in intestinal disease, obesity and diabetes, cardiovascular disease, and immune/inflammation-related diseases.}, }
@article {pmid38022043, year = {2023}, author = {Kaliamoorthy, S and Priya Sayeeram, S and SundarRaj, S and Balakrishnan, J and Nagarajan, M and Samidorai, A}, title = {Investigating the Association Between Fusobacterium nucleatum and Oral Squamous Cell Carcinoma: A Pilot Case-Control Study on Tissue Samples.}, journal = {Cureus}, volume = {15}, number = {10}, pages = {e47238}, pmid = {38022043}, issn = {2168-8184}, abstract = {Background Fusobacterium nucleatum (F. nucleatum) has been increasingly linked to oral squamous cell carcinoma (OSCC), prompting this study to explore its presence using polymerase chain reaction (PCR) and evaluate its clinical significance. Methods In this pilot case-control study, 12 OSCC tissue samples and 12 non-cancerous oral mucosal tissue samples were analyzed. Total RNA extraction and complementary DNA (cDNA) synthesis were performed using Trizol-based methods, followed by PCR amplification and gel electrophoresis. The clinical characteristics of participants and PCR results were recorded. Results Among the OSCC tissue samples, three out of 12 tested positive for F. nucleatum, while none of the control samples showed its presence. The detection rate of F. nucleatum in OSCC was 25%. Gel analysis confirmed specific amplicon amplification, and ImageJ software enabled copy number quantification. Discussion Our findings support previous research indicating a potential association between F. nucleatum and OSCC. Understanding the etiological significance of F. nucleatum in OSCC has clinical implications, including early detection, risk stratification, and prognostication. However, the limited sample size and the need for further research to elucidate underlying mechanisms are acknowledged. Conclusion This pilot study provides initial evidence of F. nucleatum's presence in a subset of OSCC samples, supporting its potential association with oral cancer. Detecting F. nucleatum in OSCC tissues holds promise for future research and clinical applications as a diagnostic and prognostic biomarker. Understanding its role in oral carcinogenesis will facilitate the development of targeted therapeutic strategies. Larger studies are warranted to validate these findings and investigate the precise mechanisms involved.}, }
@article {pmid38018964, year = {2024}, author = {Nguyen, VH and Sharon, BM and Shipman, BM and Zimmern, PE and De Nisco, NJ}, title = {Complete genomes of Limosilactobacillus portuensis and Limosilactobacillus vaginalis isolated from the urine of postmenopausal women.}, journal = {Microbiology resource announcements}, volume = {13}, number = {1}, pages = {e0088323}, pmid = {38018964}, issn = {2576-098X}, support = {R01 DK131267/DK/NIDDK NIH HHS/United States ; }, abstract = {There is frequent evidence that Limosilactobacillus vaginalis colonizes female genitourinary tracts but few reports of Limosilactobacillus portuensis. Their role in urinary tract infection (UTI) is unclear. We present the first complete genome of L. portuensis and a complete genome of L. vaginalis isolated from postmenopausal women with varying UTI histories.}, }
@article {pmid38011708, year = {2023}, author = {Moody, M and Sawyer, R}, title = {Is There a Community Microbial Community? A Comparison of Pathogens Between Two Hospital Surgical Intensive Care Units in a Single City.}, journal = {Surgical infections}, volume = {24}, number = {10}, pages = {897-902}, doi = {10.1089/sur.2023.069}, pmid = {38011708}, issn = {1557-8674}, mesh = {Humans ; *Intensive Care Units ; Bacteria ; *Cross Infection/epidemiology/microbiology ; Hospitals ; Critical Care ; }, abstract = {Background: Nosocomial and health-care-associated infections drive increased healthcare costs and negatively affect patient outcomes. The human microbiome has been heavily explored in recent years with incomplete data regarding hospital-specific and community-specific microbial communities. Although bacterial species differ between intensive care units in the same hospital, it is unclear if they differ between similar units in similar hospitals in the same community. Our hypothesis is that pathogens in surgical intensive care units (SICUs) are distinct between hospitals, even in the same community. Methods: From 2017 to 2021, data were collected prospectively from the SICUs of two 400-bed hospitals located three miles apart in the same city (Hospital A and Hospital B). Infections defined using U.S. Centers for Disease Control and Prevention (CDC) criteria were recorded for trauma and general surgery patients, as well as patient demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and causative organism. Results: Overall, Escherichia coli was the most commonly isolated pathogen in Hospital A, whereas Staphylococcus aureus was most commonly isolated at Hospital B. Enterococci were more common in Hospital A, and Haemophilus influenzae and Enterobacter spp. were more common in Hospital B. After stratification between trauma and non-trauma patients, however, these differences disappeared, with the exception of more overall gram-positive organisms and fewer gram-negative organisms among Hospital A trauma patients compared to Hospital B. There were no differences in rates of isolation of either fungi or resistant bacteria between hospitals. Conclusions: At a species level, admission diagnosis appears to be a greater determinant of pathogen isolation than hospital when comparing similar intensive care units (ICUs) in the same geographic area, but a larger body of data is needed to flesh out a distinct microbial map of the organisms occupying a certain geographic region. Further areas for investigation include comparison between hospital units, specific anatomic sites, and ICU versus floor patients.}, }
@article {pmid38007438, year = {2023}, author = {Al, KF and Joris, BR and Daisley, BA and Chmiel, JA and Bjazevic, J and Reid, G and Gloor, GB and Denstedt, JD and Razvi, H and Burton, JP}, title = {Multi-site microbiota alteration is a hallmark of kidney stone formation.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {263}, pmid = {38007438}, issn = {2049-2618}, mesh = {Humans ; *Kidney Calculi ; *Microbiota/genetics ; Oxalates/metabolism ; Metagenome ; Bacteria ; }, abstract = {BACKGROUND: Inquiry of microbiota involvement in kidney stone disease (KSD) has largely focussed on potential oxalate handling abilities by gut bacteria and the increased association with antibiotic exposure. By systematically comparing the gut, urinary, and oral microbiota of 83 stone formers (SF) and 30 healthy controls (HC), we provide a unified assessment of the bacterial contribution to KSD.<br><br>RESULTS: Amplicon and shotgun metagenomic sequencing approaches were consistent in identifying multi-site microbiota disturbances in SF relative to HC. Biomarker taxa, reduced taxonomic and functional diversity, functional replacement of core bioenergetic pathways with virulence-associated gene markers, and community network collapse defined SF, but differences between cohorts did not extend to oxalate metabolism.<br><br>CONCLUSIONS: We conclude that multi-site microbiota alteration is a hallmark of SF, and KSD treatment should consider microbial functional restoration and the avoidance of aberrant modulators such as poor diet and antibiotics where applicable to prevent stone recurrence. Video Abstract.}, }
@article {pmid38006744, year = {2023}, author = {Elgart, M and Zhang, Y and Zhang, Y and Yu, B and Kim, Y and Zee, PC and Gellman, MD and Boerwinkle, E and Daviglus, ML and Cai, J and Redline, S and Burk, RD and Kaplan, R and Sofer, T}, title = {Anaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion.}, journal = {EBioMedicine}, volume = {98}, number = {}, pages = {104891}, pmid = {38006744}, issn = {2352-3964}, support = {HHSN268201300004C/HL/NHLBI NIH HHS/United States ; R21 HL145425/HL/NHLBI NIH HHS/United States ; N01 HC065233/HL/NHLBI NIH HHS/United States ; N01 HC065236/HL/NHLBI NIH HHS/United States ; N01 HC065235/HL/NHLBI NIH HHS/United States ; R01 HL161012/HL/NHLBI NIH HHS/United States ; R35 HL135818/HL/NHLBI NIH HHS/United States ; HHSN268201300003C/HG/NHGRI NIH HHS/United States ; N01 HC065237/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Amino Acids ; Anaerobiosis ; Cohort Studies ; Prospective Studies ; *Sleep Apnea, Obstructive/complications ; }, abstract = {BACKGROUND: The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).<br><br>METHODS: Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA.<br><br>FINDINGS: Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids.<br><br>INTERPRETATION: We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation.<br><br>FUNDING: Described in methods.}, }
@article {pmid38004827, year = {2023}, author = {Kim, J and Koh, H}, title = {MiTree: A Unified Web Cloud Analytic Platform for User-Friendly and Interpretable Microbiome Data Mining Using Tree-Based Methods.}, journal = {Microorganisms}, volume = {11}, number = {11}, pages = {}, pmid = {38004827}, issn = {2076-2607}, support = {2021R1C1C1013861//National Research Foundation of Korea/ ; }, abstract = {The advent of next-generation sequencing has greatly accelerated the field of human microbiome studies. Currently, investigators are seeking, struggling and competing to find new ways to diagnose, treat and prevent human diseases through the human microbiome. Machine learning is a promising approach to help such an effort, especially due to the high complexity of microbiome data. However, many of the current machine learning algorithms are in a "black box", i.e., they are difficult to understand and interpret. In addition, clinicians, public health practitioners and biologists are not usually skilled at computer programming, and they do not always have high-end computing devices. Thus, in this study, we introduce a unified web cloud analytic platform, named MiTree, for user-friendly and interpretable microbiome data mining. MiTree employs tree-based learning methods, including decision tree, random forest and gradient boosting, that are well understood and suited to human microbiome studies. We also stress that MiTree can address both classification and regression problems through covariate-adjusted or unadjusted analysis. MiTree should serve as an easy-to-use and interpretable data mining tool for microbiome-based disease prediction modeling, and should provide new insights into microbiome-based diagnostics, treatment and prevention. MiTree is an open-source software that is available on our web server.}, }
@article {pmid38003692, year = {2023}, author = {Maslennikov, R and Poluektova, E and Zolnikova, O and Sedova, A and Kurbatova, A and Shulpekova, Y and Dzhakhaya, N and Kardasheva, S and Nadinskaia, M and Bueverova, E and Nechaev, V and Karchevskaya, A and Ivashkin, V}, title = {Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis.}, journal = {International journal of molecular sciences}, volume = {24}, number = {22}, pages = {}, pmid = {38003692}, issn = {1422-0067}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Bacterial Translocation ; Liver Cirrhosis/pathology ; Liver/pathology ; *Liver Diseases/pathology ; Dysbiosis/microbiology ; }, abstract = {Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.}, }
@article {pmid38003359, year = {2023}, author = {Siebieszuk, A and Sejbuk, M and Witkowska, AM}, title = {Studying the Human Microbiota: Advances in Understanding the Fundamentals, Origin, and Evolution of Biological Timekeeping.}, journal = {International journal of molecular sciences}, volume = {24}, number = {22}, pages = {}, pmid = {38003359}, issn = {1422-0067}, mesh = {Humans ; Oxidation-Reduction ; Circadian Rhythm/physiology ; *Circadian Clocks/genetics ; Protein Processing, Post-Translational ; *Microbiota ; }, abstract = {The recently observed circadian oscillations of the intestinal microbiota underscore the profound nature of the human-microbiome relationship and its importance for health. Together with the discovery of circadian clocks in non-photosynthetic gut bacteria and circadian rhythms in anucleated cells, these findings have indicated the possibility that virtually all microorganisms may possess functional biological clocks. However, they have also raised many essential questions concerning the fundamentals of biological timekeeping, its evolution, and its origin. This narrative review provides a comprehensive overview of the recent literature in molecular chronobiology, aiming to bring together the latest evidence on the structure and mechanisms driving microbial biological clocks while pointing to potential applications of this knowledge in medicine. Moreover, it discusses the latest hypotheses regarding the evolution of timing mechanisms and describes the functions of peroxiredoxins in cells and their contribution to the cellular clockwork. The diversity of biological clocks among various human-associated microorganisms and the role of transcriptional and post-translational timekeeping mechanisms are also addressed. Finally, recent evidence on metabolic oscillators and host-microbiome communication is presented.}, }
@article {pmid38002043, year = {2023}, author = {Rinaldi, F and Trink, A and Mondadori, G and Giuliani, G and Pinto, D}, title = {The Menopausal Transition: Is the Hair Follicle "Going through Menopause"?.}, journal = {Biomedicines}, volume = {11}, number = {11}, pages = {}, pmid = {38002043}, issn = {2227-9059}, abstract = {This article explores the link between menopause and changes in the hair follicle (HF) lifecycle, focusing on hormonal and metabolic dynamics. During menopause, hormonal fluctuations and aging can impact the HF, leading to phenomena such as thinning, loss of volume, and changes in hair texture. These changes are primarily attributed to a decrease in estrogen levels. However, not all women experience significant hair changes during menopause, and the extent of transformations can vary considerably from person to person, influenced by genetic factors, stress, diet, and other elements. Furthermore, menopause mirrors the aging process, affecting metabolism and blood flow to the HFs, influencing the availability of vital nutrients. The article also discusses the key role of energy metabolism in the HF lifecycle and the effect of hormones, particularly estrogens, on metabolic efficiency. The concept of a possible "menopause" clinically independent of menopause is introduced, related to changes in HF metabolism, emphasizing the importance of individual factors such as estrogen receptor responses, genetics, and last but not least, the microbiota in determining these dynamics.}, }
@article {pmid37998819, year = {2023}, author = {DuPont, HL and Salge, MMH}, title = {The Importance of a Healthy Microbiome in Pregnancy and Infancy and Microbiota Treatment to Reverse Dysbiosis for Improved Health.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37998819}, issn = {2079-6382}, abstract = {BACKGROUND: The microbiome of newborn infants during the first 1000 days, influenced early on by their mothers' microbiome health, mode of delivery and breast feeding, orchestrates the education and programming of the infant's immune system and determines in large part the general health of the infant for years.<br><br>METHODS: PubMed was reviewed for maternal infant microbiome health and microbiota therapy in this setting with prebiotics, probiotics, vaginal seeding and fecal microbiota transplantation (FMT).<br><br>RESULTS: A healthy nonobese mother, vaginal delivery and strict breast feeding contribute to microbiome health in a newborn and young infant. With reduced microbiome diversity (dysbiosis) during pregnancy, cesarean delivery, prematurity, and formula feeding contribute to dysbiosis in the newborn. Microbiota therapy is an important approach to repair dysbiosis in pregnant women and their infants. Currently available probiotics can have favorable metabolic effects on mothers and infants, but these effects are variable. In research settings, reversal of infant dysbiosis can be achieved via vaginal seeding or FMT. Next generation probiotics in development should replace current probiotics and FMT.<br><br>CONCLUSIONS: The most critical phase of human microbiome development is in the first 2-3 years of life. Preventing and treating dysbiosis during pregnancy and early life can have a profound effect on an infant's later health.}, }
@article {pmid37998794, year = {2023}, author = {Akomoneh, EA and Gestels, Z and Abdellati, S and Vereecken, K and Bartholomeeusen, K and Van den Bossche, D and Kenyon, C and Manoharan-Basil, SS}, title = {Genome Mining Uncovers NRPS and PKS Clusters in Rothia dentocariosa with Inhibitory Activity against Neisseria Species.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {11}, pages = {}, pmid = {37998794}, issn = {2079-6382}, support = {2021//SOFI 2021 grant/ ; }, abstract = {The growing global threat of antimicrobial resistance is reaching a crisis point as common bacterial infections, including those caused by pathogenic Neisseria species, are becoming increasingly untreatable. This is compelling the scientific community to search for new antimicrobial agents, taking advantage of computational mining and using whole genome sequences to discover natural products from the human microbiome with antibiotic effects. In this study, we investigated the crude extract from a Rothia dentocariosa strain with demonstrated antimicrobial activity against pathogenic Neisseria spp. by spot-on-lawn assay. The genomic DNA of the R. dentocariosa strain was sequenced, and bioinformatic evaluation was performed using antiSMASH and PRISM to search for biosynthetic gene clusters (BGCs). The crude extract with potential antimicrobial activity was run on Tricine-SDS-PAGE, and the putative peptides were characterised using liquid chromatography-tandem mass spectrometry (LC-MS). The crude extract inhibited the growth of the pathogenic Neisseria spp. Six BGCs were identified corresponding to non-ribosomal peptide synthases (NRPSs), polyketide synthases (PKSs), and ribosomally synthesised and post-translationally modified peptides. Three peptides were also identified corresponding to Actinorhodin polyketide putative beta-ketoacyl synthase 1. These findings serve as a useful reference to facilitate the research and development of NRPS and PKS as antimicrobial products against multidrug-resistant N. gonorrhoeae.}, }
@article {pmid37997816, year = {2024}, author = {Kumavath, R and Pavithran, H and Paul, S and Anju, VT and Busi, S and Dyavaiah, M}, title = {Effects of gut microbiome and obesity on the development, progression and prevention of cancer (Review).}, journal = {International journal of oncology}, volume = {64}, number = {1}, pages = {}, doi = {10.3892/ijo.2023.5592}, pmid = {37997816}, issn = {1791-2423}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; Obesity/complications ; Carcinogenesis ; *Colorectal Neoplasms/metabolism ; *Liver Neoplasms ; }, abstract = {Cancer is one of the leading causes of death worldwide and it is estimated that the mortality rate of cancer will increase in the coming years. The etiology of the development and progression of cancer is multifactorial. Insights have been gained on the association between the human microbiome and tumor cell malignancy. A number of commensal microbe species are present in the human gut. They serve pivotal roles in maintaining several health and disease conditions, such as inflammatory bowel disease, irritable bowel syndrome, obesity and diabetes. Known major factors involved in cancer development include age, hormone levels, alcohol consumption, diet, being overweight, obesity, and infections, regardless of the type of cancer. Therefore, the present review aims to discuss the relationship between the gut microbiome and obesity‑associated malignancies, including colorectal, gastric and liver cancer. Obesity has been reported to contribute to the development of numerous types of cancer primarily caused by high fatty food intake. In addition, obesity‑associated microbiome alterations can lead to cancer and its progression. Dysbiosis of the gut microbiota can alter the metabolite profile, whilst increasing the levels of toxins, such as Bacteroides fragilis toxin and colibactin and cytolethal distending toxin, which are responsible for oncogenesis. The present review provides insights into the impact of gut microbiome dysbiosis on the progression of different types of cancers associated with obesity. It also discusses possible strategies for preserving a healthy gut microbiome. Different pre‑clinical and clinical models are available for studying cancer development downstream of gut microbiome dysbiosis. Furthermore, the role of metabolites or drugs employed in colorectal, gastric and liver cancer therapy would be discussed.}, }
@article {pmid37997472, year = {2023}, author = {Akbari, E and Milani, A and Seyedinkhorasani, M and Bolhassani, A}, title = {HPV co-infections with other pathogens in cancer development: A comprehensive review.}, journal = {Journal of medical virology}, volume = {95}, number = {11}, pages = {e29236}, doi = {10.1002/jmv.29236}, pmid = {37997472}, issn = {1096-9071}, mesh = {Female ; Humans ; *Papillomavirus Infections/complications ; *Coinfection ; *Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; *Neoplasms/complications ; Papillomaviridae ; }, abstract = {High-risk human papillomaviruses (HR-HPVs) cause various malignancies in the anogenital and oropharyngeal regions. About 70% of cervical and oropharyngeal cancers are caused by HPV types 16 and 18. Notably, some viruses including herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus along with various bacteria often interact with HPV, potentially impacting its replication, persistence, and cancer progression. Thus, HPV infection can be significantly influenced by co-infecting agents that influence infection dynamics and disease progression. Bacterial co-infections (e.g., Chlamydia trachomatis) along with bacterial vaginosis-related species also interact with HPV in genital tract leading to viral persistence and disease outcomes. Co-infections involving HPV and diverse infectious agents have significant implications for disease transmission and clinical progression. This review explores multiple facets of HPV infection encompassing the co-infection dynamics with other pathogens, interaction with the human microbiome, and its role in disease development.}, }
@article {pmid37995844, year = {2023}, author = {Bonnici, V and Mengoni, C and Mangoni, M and Franco, G and Giugno, R}, title = {PanDelos-frags: A methodology for discovering pangenomic content of incomplete microbial assemblies.}, journal = {Journal of biomedical informatics}, volume = {148}, number = {}, pages = {104552}, doi = {10.1016/j.jbi.2023.104552}, pmid = {37995844}, issn = {1532-0480}, mesh = {Humans ; Ecosystem ; Genome ; *Genomics/methods ; Metagenomics/methods ; Software ; *Microbiota/genetics ; }, abstract = {Pangenomics was originally defined as the problem of comparing the composition of genes into gene families within a set of bacterial isolates belonging to the same species. The problem requires the calculation of sequence homology among such genes. When combined with metagenomics, namely for human microbiome composition analysis, gene-oriented pangenome detection becomes a promising method to decipher ecosystem functions and population-level evolution. Established computational tools are able to investigate the genetic content of isolates for which a complete genomic sequence is available. However, there is a plethora of incomplete genomes that are available on public resources, which only a few tools may analyze. Incomplete means that the process for reconstructing their genomic sequence is not complete, and only fragments of their sequence are currently available. However, the information contained in these fragments may play an essential role in the analyses. Here, we present PanDelos-frags, a computational tool which exploits and extends previous results in analyzing complete genomes. It provides a new methodology for inferring missing genetic information and thus for managing incomplete genomes. PanDelos-frags outperforms state-of-the-art approaches in reconstructing gene families in synthetic benchmarks and in a real use case of metagenomics. PanDelos-frags is publicly available at https://github.com/InfOmics/PanDelos-frags.}, }
@article {pmid37994755, year = {2023}, author = {Donato, K and Donato, K and Bonetti, G and Cristoni, S and Connelly, ST and Bertelli, M}, title = {Exploring the Impact of Tobacco Usage on Microbiome Dysbiosis and Associated Health Risks: A Comprehensive Review of Recent Advancements and Future Directions.}, journal = {La Clinica terapeutica}, volume = {174}, number = {Suppl 2(6)}, pages = {119-125}, doi = {10.7417/CT.2023.2478}, pmid = {37994755}, issn = {1972-6007}, mesh = {Humans ; Dysbiosis/microbiology ; *Microbiota ; *Colitis, Ulcerative ; *Crohn Disease ; }, abstract = {All over the world, tobacco usage is quickly expanding. Though it presents a major health risk and is anticipated to have long-lasting impacts on the public and economic health of the country, its consumers are increasing with every passing day. Tobacco is being used in a variety of ways, with cigarettes being the most popular. Smoking affects the healthy oral, intestinal, and pulmonary microbiomes, often altering the dynamic equilibrium of the diverse bacteria that make up the human microbiome, or "dysbiosis". Smoking-induced dysbiosis can lead to developing conditions like asthma, chronic obstructive pul-monary disease, Crohn's disease, ulcerative colitis, and periodontitis. The purpose of the following article is to provide a better and more comprehensive overview of the key areas that the tobacco industry needs to investigate, such as microbiome manipulation, to provide a complete picture of recent advancements in tobacco research while also keeping public safety in mind, and the various diseases linked to tobacco use.}, }
@article {pmid37994699, year = {2024}, author = {Hirsch, P and Tagirdzhanov, A and Kushnareva, A and Olkhovskii, I and Graf, S and Schmartz, GP and Hegemann, JD and Bozhüyük, KAJ and Müller, R and Keller, A and Gurevich, A}, title = {ABC-HuMi: the Atlas of Biosynthetic Gene Clusters in the Human Microbiome.}, journal = {Nucleic acids research}, volume = {52}, number = {D1}, pages = {D579-D585}, pmid = {37994699}, issn = {1362-4962}, support = {//Saarland University/ ; 466168626//DFG/ ; }, mesh = {Humans ; *Biosynthetic Pathways/genetics ; Computational Biology/instrumentation ; *Databases, Genetic ; Internet ; *Microbiota/genetics ; *Multigene Family/genetics ; Metagenome/genetics ; }, abstract = {The human microbiome has emerged as a rich source of diverse and bioactive natural products, harboring immense potential for therapeutic applications. To facilitate systematic exploration and analysis of its biosynthetic landscape, we present ABC-HuMi: the Atlas of Biosynthetic Gene Clusters (BGCs) in the Human Microbiome. ABC-HuMi integrates data from major human microbiome sequence databases and provides an expansive repository of BGCs compared to the limited coverage offered by existing resources. Employing state-of-the-art BGC prediction and analysis tools, our database ensures accurate annotation and enhanced prediction capabilities. ABC-HuMi empowers researchers with advanced browsing, filtering, and search functionality, enabling efficient exploration of the resource. At present, ABC-HuMi boasts a catalog of 19 218 representative BGCs derived from the human gut, oral, skin, respiratory and urogenital systems. By capturing the intricate biosynthetic potential across diverse human body sites, our database fosters profound insights into the molecular repertoire encoded within the human microbiome and offers a comprehensive resource for the discovery and characterization of novel bioactive compounds. The database is freely accessible at https://www.ccb.uni-saarland.de/abc_humi/.}, }
@article {pmid37986834, year = {2023}, author = {Wang, SH and Zheng, T and Fawzi, NL}, title = {Structure and position-specific interactions of prion-like domains in transcription factor Efg1 phase separation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37986834}, issn = {2692-8205}, support = {R01 GM147677/GM/NIGMS NIH HHS/United States ; }, abstract = {Candida albicans, a prominent member of the human microbiome, can make an opportunistic switch from commensal coexistence to pathogenicity accompanied by an epigenetic shift between the white and opaque cell states. This transcriptional switch is under precise regulation by a set of transcription factors (TFs), with Enhanced Filamentous Growth Protein 1 (Efg1) playing a central role. Previous research has emphasized the importance of Egf1's prion-like domain (PrLD) and the protein's ability to undergo phase separation for the white-to-opaque transition of C. albicans. However, the underlying molecular mechanisms of Efg1 phase separation have remained underexplored. In this study, we delved into the biophysical basis of Efg1 phase separation, revealing the significant contribution of both N-terminal (N) and C-terminal (C) PrLDs. Through NMR structural analysis, we found that Efg1 N-PrLD and C-PrLD are mostly disordered though have prominent partial α-helical secondary structures in both domains. NMR titration experiments suggest that the partially helical structures in N-PrLD act as hubs for self-interaction as well as Efg1 interaction with RNA. Using condensed-phase NMR spectroscopy, we uncovered diverse amino acid interactions underlying Efg1 phase separation. Particularly, we highlight the indispensable role of tyrosine residues within the transient α-helical structures of PrLDs particularly in the N-PrLD compared to the C-PrLD in stabilizing phase separation. Our study provides evidence that the transient α-helical structure is present in the phase separated state and highlights the particular importance of aromatic residues within these structures for phase separation. Together, these results enhance the understanding of C. albicans TF interactions that lead to virulence and provide a crucial foundation for potential antifungal therapies targeting the transcriptional switch.}, }
@article {pmid37978888, year = {2024}, author = {Cohen, DG and Wingert, RA}, title = {Forever young by Alpha(diversity)ville: restricting intestinal microbiome maturation stunts immune system development and increases susceptibility to infection.}, journal = {Tissue barriers}, volume = {12}, number = {3}, pages = {2281209}, pmid = {37978888}, issn = {2168-8370}, mesh = {Humans ; Disease Susceptibility ; *Gastrointestinal Microbiome/immunology/physiology ; Immune System/microbiology ; }, abstract = {The microbiome is a keystone of adult gastrointestinal (GI) tract health, where it facilitates digestion, wards off pathogen colonization, and exerts a powerful influence on the physiological health of organs ranging from the brain to the kidneys. From its establishment at birth and through the initial years of childhood, the human microbiome is particularly dynamic, shifting in its composition and alpha (species) diversity to an adult profile as dietary sustenance transitions from milk-based sources to others such as solid food. An innovative study has now demonstrated how microbiome maturation is requisite both for the progression of immune system development and for long-term gut barrier function. These insights have significant ramifications for designing pediatric approaches to cultivate immune cell ontogeny in the formative stages of human infancy.}, }
@article {pmid37978428, year = {2023}, author = {Garba, Z and Bonkoungou, IOJ and Millogo, NO and Natama, HM and Vokouma, PAP and Bonko, MDA and Karama, I and Tiendrebeogo, LAW and Haukka, K and Tinto, H and Sangaré, L and Barro, N}, title = {Wastewater from healthcare centers in Burkina Faso is a source of ESBL, AmpC-β-lactamase and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {351}, pmid = {37978428}, issn = {1471-2180}, mesh = {Humans ; Animals ; Escherichia coli ; Klebsiella pneumoniae ; Wastewater ; Burkina Faso ; Microbial Sensitivity Tests ; beta-Lactamases ; Bacterial Proteins ; Anti-Bacterial Agents/pharmacology ; *Escherichia coli Infections/microbiology ; Bacteria ; *Carbapenem-Resistant Enterobacteriaceae ; }, abstract = {BACKGROUND: Extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC-β-lactamase and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae have spread into the environment worldwide posing a potential public health threat. However, the prevalence data for low- and middle-income countries are still scarce. The aim of this study was to evaluate the presence of ESBL, AmpC-β-lactamase and carbapenemase-producing and multidrug-resistant E. coli and K. pneumoniae in wastewaters from healthcare centers in Burkina Faso.<br><br>RESULTS: Eighty-four (84) wastewater samples were collected from five healthcare centers and plated on selective ESBL ChromAgar. E. coli and Klebsiella pneumoniae isolates were identified using API20E. ESBL-producing bacteria were detected in 97.6% of the samples and their average concentration per hospital ranged from 1.10&#x2009;&#xd7;&#x2009;10[5] to 5.23&#x2009;&#xd7;&#x2009;10[6]&#xa0;CFU/mL. Out of 170 putative ESBL-producing isolates (64% of them were E. coli) and 51 putative AmpC-&#x3b2;-lactamase-producing isolates, 95% and 45% were confirmed, respectively. Carbapenemase production was detected in 10 isolates, of which 6 were NDM producers, 3 were OXA-48 producers and 1 was NDM and OXA-48 producer. All isolates were multidrug resistant and, moreover, all of them were resistant to all tested &#x3b2;-lactams. Resistance to ESBL inhibitors was also common, up to 66% in E. coli and 62% in K. pneumoniae. Amikacin, fosfomycin and nitrofurantoin were the antibiotics to which the least resistance was detected.<br><br>CONCLUSIONS: This study showed that wastewater from healthcare centers constitutes a reservoir of multidrug-resistant bacteria in Burkina Faso, including carbapenemase producers. Untreated healthcare wastewater entering the environment exposes people and animals to infections caused by these multi-resistant bacteria, which are difficult to treat, especially in the resource-poor settings.}, }
@article {pmid37975292, year = {2024}, author = {Chmiel, JA and Stuivenberg, GA and Wong, JFW and Nott, L and Burton, JP and Razvi, H and Bjazevic, J}, title = {Predictive Modeling of Urinary Stone Composition Using Machine Learning and Clinical Data: Implications for Treatment Strategies and Pathophysiological Insights.}, journal = {Journal of endourology}, volume = {38}, number = {8}, pages = {778-787}, doi = {10.1089/end.2023.0446}, pmid = {37975292}, issn = {1557-900X}, mesh = {Humans ; *Machine Learning ; Male ; Female ; Middle Aged ; *Urinary Calculi/chemistry ; Calcium Oxalate ; Adult ; Calcium Phosphates ; Aged ; Uric Acid/urine ; Calcium/urine/blood ; Models, Biological ; }, abstract = {Purpose: Preventative strategies and surgical treatments for urolithiasis depend on stone composition. However, stone composition is often unknown until the stone is passed or surgically managed. Given that stone composition likely reflects the physiological parameters during its formation, we used clinical data from stone formers to predict stone composition. Materials and Methods: Data on stone composition, 24-hour urine, serum biochemistry, patient demographics, and medical history were prospectively collected from 777 kidney stone patients. Data were used to train gradient boosted machine and logistic regression models to distinguish calcium vs noncalcium, calcium oxalate monohydrate vs dihydrate, and calcium oxalate vs calcium phosphate vs uric acid stone types. Model performance was evaluated using the kappa score, and the influence of each predictor variable was assessed. Results: The calcium vs noncalcium model differentiated stone types with a kappa of 0.5231. The most influential predictors were 24-hour urine calcium, blood urate, and phosphate. The calcium oxalate monohydrate vs dihydrate model is the first of its kind and could discriminate stone types with a kappa of 0.2042. The key predictors were 24-hour urine urea, calcium, and oxalate. The multiclass model had a kappa of 0.3023 and the top predictors were age and 24-hour urine calcium and creatinine. Conclusions: Clinical data can be leveraged with machine learning algorithms to predict stone composition, which may help urologists determine stone type and guide their management plan before stone treatment. Investigating the most influential predictors of each classifier may improve the understanding of key clinical features of urolithiasis and shed light on pathophysiology.}, }
@article {pmid37973865, year = {2023}, author = {King, AM and Zhang, Z and Glassey, E and Siuti, P and Clardy, J and Voigt, CA}, title = {Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra.}, journal = {Nature microbiology}, volume = {8}, number = {12}, pages = {2420-2434}, pmid = {37973865}, issn = {2058-5276}, support = {HR0011-15-C-0084//United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)/ ; }, mesh = {Humans ; Antimicrobial Peptides ; *Methicillin-Resistant Staphylococcus aureus ; Escherichia coli ; Peptides/genetics/pharmacology/chemistry ; Bacteria/genetics ; *Microbiota/genetics ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Human-associated bacteria secrete modified peptides to control host physiology and remodel the microbiota species composition. Here we scanned 2,229 Human Microbiome Project genomes of species colonizing skin, gastrointestinal tract, urogenital tract, mouth and trachea for gene clusters encoding RiPPs (ribosomally synthesized and post-translationally modified peptides). We found 218 lanthipeptides and 25 lasso peptides, 70 of which were synthesized and expressed in E. coli and 23 could be purified and functionally characterized. They were tested for activity against bacteria associated with healthy human flora and pathogens. New antibiotics were identified against strains implicated in skin, nasal and vaginal dysbiosis as well as from oral strains selectively targeting those in the gut. Extended- and narrow-spectrum antibiotics were found against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Mining natural products produced by human-associated microbes will enable the elucidation of ecological relationships and may be a rich resource for antimicrobial discovery.}, }
@article {pmid37969883, year = {2023}, author = {Azamfirei, L}, title = {The Human Microbiome in Intensive Care - A Journey Forward?.}, journal = {Journal of critical care medicine (Universitatea de Medicina si Farmacie din Targu-Mures)}, volume = {9}, number = {4}, pages = {205-207}, pmid = {37969883}, issn = {2393-1809}, }
@article {pmid37968359, year = {2024}, author = {Asnicar, F and Thomas, AM and Passerini, A and Waldron, L and Segata, N}, title = {Machine learning for microbiologists.}, journal = {Nature reviews. Microbiology}, volume = {22}, number = {4}, pages = {191-205}, pmid = {37968359}, issn = {1740-1534}, support = {R01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Machine Learning ; *Microbiota ; }, abstract = {Machine learning is increasingly important in microbiology where it is used for tasks such as predicting antibiotic resistance and associating human microbiome features with complex host diseases. The applications in microbiology are quickly expanding and the machine learning tools frequently used in basic and clinical research range from classification and regression to clustering and dimensionality reduction. In this Review, we examine the main machine learning concepts, tasks and applications that are relevant for experimental and clinical microbiologists. We provide the minimal toolbox for a microbiologist to be able to understand, interpret and use machine learning in their experimental and translational activities.}, }
@article {pmid37965266, year = {2023}, author = {Piazzesi, A and Pane, S and Russo, A and Del Chierico, F and Francalanci, P and Cotugno, N and Rossi, P and Locatelli, F and Palma, P and Putignani, L}, title = {Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1281440}, pmid = {37965266}, issn = {2235-2988}, mesh = {Animals ; Humans ; Child ; Child, Preschool ; *Cryptosporidiosis/complications/parasitology ; CD40 Ligand ; *Gastrointestinal Microbiome ; *Cryptosporidium/genetics ; Intestines/microbiology ; *Immunologic Deficiency Syndromes/complications ; *Parasites ; *Cryptosporidium parvum ; Bacteria/genetics ; Propionibacterium acnes ; }, abstract = {Cryptosporidium parvum is a protozoan parasite and one of the leading causes of gastroenteritis in the world, primarily affecting very young children and immunocompromised patients. While infection is usually self-limiting, it can become chronic and even lethal in these vulnerable populations, in whom Cryptosporidium treatments are generally ineffective, due to their acting in concert with a functioning immune system. Here, we describe a case of chronic cryptosporidiosis in a European child with severe CD40L immunodeficiency infected with Cryptosporidium parvum of the IIa20G1 subgenotype, a lineage which has thus far only ever been described in the Middle East. After years of on-off treatment with conventional and non-conventional anti-parasitic drugs failed to clear parasitosis, we performed targeted metagenomics to observe the bacterial composition of the patient's gut microbiota (GM), and to evaluate fecal microbiota transplantation (FMT) as a potential treatment option. We found that C. parvum infection led to significant shifts in GM bacterial composition in our patient, with consequent shifts in predicted intestinal functional signatures consistent with a state of persistent inflammation. This, combined with the patient's poor prognosis and increasing parasitic burden despite many rounds of anti-parasitic drug treatments, made the patient a potential candidate for an experimental FMT procedure. Unfortunately, given the many comorbidities that were precipitated by the patient's immunodeficiency and chronic C. parvum infection, FMT was postponed in favor of more urgently necessary liver and bone marrow transplants. Tragically, after the first liver transplant failed, the patient lost his life before undergoing FMT and a second liver transplant. With this case report, we present the first description of how cryptosporidiosis can shape the gut microbiota of a pediatric patient with severe immunodeficiency. Finally, we discuss how both our results and the current scientific literature suggest that GM modulations, either by probiotics or FMT, can become novel treatment options for chronic Cryptosporidium infection and its consequent complications, especially in those patients who do not respond to the currently available anti-parasitic therapies.}, }
@article {pmid37963399, year = {2024}, author = {Jennings, SAV and Clavel, T}, title = {Synthetic Communities of Gut Microbes for Basic Research and Translational Approaches in Animal Health and Nutrition.}, journal = {Annual review of animal biosciences}, volume = {12}, number = {}, pages = {283-300}, doi = {10.1146/annurev-animal-021022-025552}, pmid = {37963399}, issn = {2165-8110}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome ; Reproducibility of Results ; Nutritional Status ; }, abstract = {Microbes and animals have a symbiotic relationship that greatly influences nutrient uptake and animal health. This relationship can be studied using selections of microbes termed synthetic communities, or SynComs. SynComs are used in many different animal hosts, including agricultural animals, to investigate microbial interactions with nutrients and how these affect animal health. The most common host focuses for SynComs are currently mouse and human, from basic mechanistic research through to translational disease models and live biotherapeutic products (LBPs) as treatments. We discuss SynComs used in basic research models and findings that relate to human and animal health and nutrition. Translational use cases of SynComs are discussed, followed by LBPs, especially within the context of agriculture. SynComs still face challenges, such as standardization for reproducibility and contamination risks. However, the future of SynComs is hopeful, especially in the areas of genome-guided SynCom design and custom SynCom-based treatments.}, }
@article {pmid37961318, year = {2023}, author = {Walker, AC and Bhargava, R and Bucher, M and Brust, AS and Czy, DM}, title = {Identification of proteotoxic and proteoprotective bacteria that non-specifically affect proteins associated with neurodegenerative diseases.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37961318}, issn = {2692-8205}, support = {P40 OD010440/OD/NIH HHS/United States ; R03 AG070580/AG/NIA NIH HHS/United States ; }, abstract = {Neurodegenerative protein conformational diseases (PCDs), such as Alzheimer's, Parkinson's, and Huntington's, are a leading cause of death and disability worldwide and have no known cures or effective treatments. Emerging evidence suggests a role for the gut microbiota in the pathogenesis of neurodegenerative PCDs; however, the influence of specific bacteria on the culprit proteins associated with each of these diseases remains elusive, primarily due to the complexity of the microbiota. In the present study, we employed a single-strain screening approach to identify human bacterial isolates that enhance or suppress the aggregation of culprit proteins and the associated toxicity in Caenorhabditis elegans expressing Aβ1-42, α-synuclein, and polyglutamine tracts. Here, we reveal the first comprehensive analysis of the human microbiome for its effect on proteins associated with neurodegenerative diseases. Our results suggest that bacteria affect the aggregation of metastable proteins by modulating host proteostasis rather than selectively targeting specific disease-associated proteins. These results reveal bacteria that potentially influence the pathogenesis of PCDs and open new promising prevention and treatment opportunities by altering the abundance of beneficial and detrimental microbes.}, }
@article {pmid37958613, year = {2023}, author = {Mäenpää, K and Ilves, M and Zhao, L and Alenius, H and Sinkko, H and Karisola, P}, title = {Effects of Superficial Scratching and Engineered Nanomaterials on Skin Gene Profiles and Microbiota in SKH-1 Mice.}, journal = {International journal of molecular sciences}, volume = {24}, number = {21}, pages = {}, pmid = {37958613}, issn = {1422-0067}, support = {307768//Academy of Finland/ ; 1333178//Academy of Finland/ ; Personal funding//Finnish Cultural Foundation/ ; }, mesh = {Mice ; Animals ; *Skin/metabolism ; Wound Healing ; Administration, Cutaneous ; *Microbiota ; Neutrophils ; }, abstract = {Scratching damages upper layers of the skin, breaks this first line of immune defence, and leads to inflammation response, which often also modifies the microbiota of the skin. Although the healing of incision wounds is well-described, there are fewer studies on superficial wounds. We used a simulated model of skin scratching to study changes in the host transcriptome, skin microbiota, and their relationship. Additionally, we examined the effect of nanosized ZnO, TiO2, and Ag on both intact and damaged skin. At 24 h after exposure, the number of neutrophils was increased, 396 genes were differentially expressed, and microbiota compositions changed between scratched and intact control skin. At 7 d, the skin was still colonised by gut-associated microbes, including Lachnospiraceae, present in the cage environment, while the transcriptomic responses decreased. To sum up, the nanomaterial exposures reduced the relative abundance of cutaneous microbes on healthy skin, but the effect of scratching was more significant for the transcriptome than the nanomaterial exposure both at 24 h and 7 d. We conclude that superficial skin scratching induces inflammatory cell accumulation and changes in gene expression especially at 24 h, while the changes in the microbiota last at least 7 days.}, }
@article {pmid37950262, year = {2023}, author = {Smajdor, J and Jedlińska, K and Porada, R and Górska-Ratusznik, A and Policht, A and Śróttek, M and Więcek, G and Baś, B and Strus, M}, title = {The impact of gut bacteria producing long chain homologs of vitamin K2 on colorectal carcinogenesis.}, journal = {Cancer cell international}, volume = {23}, number = {1}, pages = {268}, pmid = {37950262}, issn = {1475-2867}, support = {2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; 2018/31/B/NZ6/02472//Narodowym Centrum Nauki/ ; }, abstract = {Colorectal cancer (CRC) is one of the foremost causes of cancer-related deaths. Lately, a close connection between the course of CRC and the intestinal microbiota has been revealed. Vitamin K2 (VK2) is a bacterially derived compound that plays a crucial role in the human body. Its significant anti-cancer properties may result, inter alia, from a quinone ring possessing a specific chemical structure found in many chemotherapeutics. VK2 can be supplied to our body exogenously, i.e., through dietary supplements or fermented food (e.g., yellow cheese, fermented soybeans -Natto), and endogenously, i.e., through the production of bacteria that constantly colonize the human microbiome of the large intestine.This paper focuses on endogenous K2 synthesized by the most active members of the human gut microbiome. This analysis tested 86 intestinally derived bacterial strains, among which the largest VK2 producers (Lactobacillus, Bifidobacterium, Bacillus) were selected. Moreover, based on the chosen VK2-MK4 homolog, the potential of VK2 penetration into Caco-2 cells in an aqueous environment without the coexistence of fats, pancreatic enzymes, or bile salts has been displayed. The influence of three VK2 homologs: VK2-MK4, VK2-MK7 and VK2-MK9 on apoptosis and necrosis of Caco-2 cells was tested proving the lack of their harmful effects on the tested cells. Moreover, the unique role of long-chain homologs (VK2-MK9 and VK2-MK7) in inhibiting the secretion of pro-inflammatory cytokines such as IL-8 (for Caco-2 tissue) and IL-6 and TNFα (for RAW 264.7) has been documented.}, }
@article {pmid37950236, year = {2023}, author = {Zhou, X and You, L and Xin, Z and Su, H and Zhou, J and Ma, Y}, title = {Leveraging circulating microbiome signatures to predict tumor immune microenvironment and prognosis of patients with non-small cell lung cancer.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {800}, pmid = {37950236}, issn = {1479-5876}, mesh = {Humans ; *Carcinoma, Non-Small-Cell Lung ; Tumor Microenvironment ; *Lung Neoplasms ; Prognosis ; *Microbiota ; }, abstract = {BACKGROUND: Accumulating evidence supports the significant role of human microbiome in development and therapeutic response of tumors. Circulating microbial DNA is non-invasive and could show a general view of the microbiome of host, making it a promising biomarker for cancers. However, whether circulating microbiome is associated with prognosis of non-small cell lung cancer (NSCLC) and its potential mechanisms on tumor immune microenvironment still remains unknown.<br><br>METHODS: The blood microbiome data and matching tumor RNA-seq data of TCGA NSCLC patients were obtained from Poore's study and UCSC Xena. Univariate and multivariate Cox regression analysis were used to identify circulating microbiome signatures associated with overall survival (OS) and construct the circulating microbial abundance prognostic scoring (MAPS) model. Nomograms integrating clinical characteristics and circulating MAPS scores were established to predict OS rate of NSCLC patients. Joint analysis of blood microbiome data and matching tumor RNA-seq data was used to deciphered the tumor microenvironment landscape of patients in circulating MAPS-high and MAPS-low groups. Finally, the predictive value of circulating MAPS on the efficacy of immunotherapy and chemotherapy were assessed.<br><br>RESULTS: A circulating MAPS prediction model consisting of 14 circulating microbes was constructed and had an independent prognostic value for NSCLC. The integration of circulating MAPS into nomograms may improve the prognosis predictive power. Joint analysis revealed potential interactions between prognostic circulating microbiome and tumor immune microenvironment. Especially, intratumor plasma cells and humoral immune response were enriched in circulating MAPS-low group, while intratumor CD4&#x2009;+&#x2009;Th2 cells and proliferative related pathways were enriched in MAPS-high group. Finally, drug sensitivity analysis indicated the potential of circulating MAPS as a predictor of chemotherapy efficacy.<br><br>CONCLUSION: A circulating MAPS prediction model was constructed successfully and showed great prognostic value for NSCLC. Our study provides new insights of interactions between microbes, tumors and immunity, and may further contribute to precision medicine for NSCLC.}, }
@article {pmid37941395, year = {2022}, author = {Blumberg, K and Miller, M and Ponsero, A and Hurwitz, B}, title = {Ontology-driven analysis of marine metagenomics: what more can we learn from our data?.}, journal = {GigaScience}, volume = {12}, number = {}, pages = {}, pmid = {37941395}, issn = {2047-217X}, mesh = {*Ecology ; *Microbiota/genetics ; Metagenome ; Metagenomics ; }, abstract = {BACKGROUND: The proliferation of metagenomic sequencing technologies has enabled novel insights into the functional genomic potentials and taxonomic structure of microbial communities. However, cyberinfrastructure efforts to manage and enable the reproducible analysis of sequence data have not kept pace. Thus, there is increasing recognition of the need to make metagenomic data discoverable within machine-searchable frameworks compliant with the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles for data stewardship. Although a variety of metagenomic web services exist, none currently leverage the hierarchically structured terminology encoded within common life science ontologies to programmatically discover data.<br><br>RESULTS: Here, we integrate large-scale marine metagenomic datasets with community-driven life science ontologies into a novel FAIR web service. This approach enables the retrieval of data discovered by intersecting the knowledge represented within ontologies against the functional genomic potential and taxonomic structure computed from marine sequencing data. Our findings highlight various microbial functional and taxonomic patterns relevant to the ecology of prokaryotes in various aquatic environments.<br><br>CONCLUSIONS: In this work, we present and evaluate a novel Semantic Web architecture that can be used to ask novel biological questions of existing marine metagenomic datasets. Finally, the FAIR ontology searchable data products provided by our API can be leveraged by future research efforts.}, }
@article {pmid37929823, year = {2024}, author = {Yi, X and Lu, H and Liu, X and He, J and Li, B and Wang, Z and Zhao, Y and Zhang, X and Yu, X}, title = {Unravelling the enigma of the human microbiome: Evolution and selection of sequencing technologies.}, journal = {Microbial biotechnology}, volume = {17}, number = {1}, pages = {e14364}, pmid = {37929823}, issn = {1751-7915}, support = {82202569//National Natural Science Foundation of China/ ; 20210302124635//Shanxi Province Basic Research Program Project/ ; }, mesh = {Humans ; *Microbiota ; Metagenome ; High-Throughput Nucleotide Sequencing/methods ; Metagenomics ; Technology ; }, abstract = {The human microbiome plays a crucial role in maintaining health, with advances in high-throughput sequencing technology and reduced sequencing costs triggering a surge in microbiome research. Microbiome studies generally incorporate five key phases: design, sampling, sequencing, analysis, and reporting, with sequencing strategy being a crucial step offering numerous options. Present mainstream sequencing strategies include Amplicon sequencing, Metagenomic Next-Generation Sequencing (mNGS), and Targeted Next-Generation Sequencing (tNGS). Two innovative technologies recently emerged, namely MobiMicrobe high-throughput microbial single-cell genome sequencing technology and 2bRAD-M simplified metagenomic sequencing technology, compensate for the limitations of mainstream technologies, each boasting unique core strengths. This paper reviews the basic principles and processes of these three mainstream and two novel microbiological technologies, aiding readers in understanding the benefits and drawbacks of different technologies, thereby guiding the selection of the most suitable method for their research endeavours.}, }
@article {pmid37923896, year = {2023}, author = {Marzano, V and Levi Mortera, S and Vernocchi, P and Del Chierico, F and Marangelo, C and Guarrasi, V and Gardini, S and Dentici, ML and Capolino, R and Digilio, MC and Di Donato, M and Spasari, I and Abreu, MT and Dallapiccola, B and Putignani, L}, title = {Williams-Beuren syndrome shapes the gut microbiota metaproteome.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {18963}, pmid = {37923896}, issn = {2045-2322}, mesh = {Humans ; *Williams Syndrome ; *Gastrointestinal Microbiome ; Bacteria/genetics ; Firmicutes ; Gastrointestinal Tract ; }, abstract = {Williams-Beuren syndrome (WBS) is a rare genetic neurodevelopmental disorder with multi-systemic manifestations. The evidence that most subjects with WBS face gastrointestinal (GI) comorbidities, have prompted us to carry out a metaproteomic investigation of their gut microbiota (GM) profile compared to age-matched healthy subjects (CTRLs). Metaproteomic analysis was carried out on fecal samples collected from 41 individuals with WBS, and compared with samples from 45 CTRLs. Stool were extracted for high yield in bacterial protein group (PG) content, trypsin-digested and analysed by nanoLiquid Chromatography-Mass Spectrometry. Label free quantification, taxonomic assignment by the lowest common ancestor (LCA) algorithm and functional annotations by COG and KEGG databases were performed. Data were statistically interpreted by multivariate and univariate analyses. A WBS GM functional dissimilarity respect to CTRLs, regardless age distribution, was reported. The alterations in function of WBSs GM was primarily based on bacterial pathways linked to carbohydrate transport and metabolism and energy production. Influence of diet, obesity, and GI symptoms was assessed, highlighting changes in GM biochemical patterns, according to WBS subsets' stratification. The LCA-derived ecology unveiled WBS-related functionally active bacterial signatures: Bacteroidetes related to over-expressed PGs, and Firmicutes, specifically the specie Faecalibacterium prausnitzii, linked to under-expressed PGs, suggesting a depletion of beneficial bacteria. These new evidences on WBS gut dysbiosis may offer novel targets for tailored interventions.}, }
@article {pmid37923839, year = {2024}, author = {Routy, B and Lenehan, JG and Miller, WH and Jamal, R and Messaoudene, M and Daisley, BA and Hes, C and Al, KF and Martinez-Gili, L and Punčochář, M and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Richard, C and Ninkov, M and Piccinno, G and Armanini, F and Pinto, F and Krishnamoorthy, M and Figueredo, R and Thebault, P and Takis, P and Magrill, J and Ramsay, L and Derosa, L and Marchesi, JR and Parvathy, SN and Elkrief, A and Watson, IR and Lapointe, R and Segata, N and Haeryfar, SMM and Mullish, BH and Silverman, MS and Burton, JP and Maleki Vareki, S}, title = {Author Correction: Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.}, journal = {Nature medicine}, volume = {30}, number = {2}, pages = {604}, doi = {10.1038/s41591-023-02650-8}, pmid = {37923839}, issn = {1546-170X}, }
@article {pmid37921025, year = {2024}, author = {Qiao, X and He, H and Sun, L and Bai, S and Ye, P}, title = {Testing latent classes in gut microbiome data using generalized Poisson regression models.}, journal = {Statistics in medicine}, volume = {43}, number = {1}, pages = {102-124}, doi = {10.1002/sim.9944}, pmid = {37921025}, issn = {1097-0258}, support = {P20GM109036/GF/NIH HHS/United States ; }, mesh = {Humans ; Models, Statistical ; *Gastrointestinal Microbiome ; Computer Simulation ; *Microbiota ; Longitudinal Studies ; Poisson Distribution ; }, abstract = {Human microbiome research has gained increasing importance due to its critical roles in comprehending human health and disease. Within the realm of microbiome research, the data generated often involves operational taxonomic unit counts, which can frequently present challenges such as over-dispersion and zero-inflation. To address dispersion-related concerns, the generalized Poisson model offers a flexible solution, effectively handling data characterized by over-dispersion, equi-dispersion, and under-dispersion. Furthermore, the realm of zero-inflated generalized Poisson models provides a strategic avenue to simultaneously tackle both over-dispersion and zero-inflation. The phenomenon of zero-inflation frequently stems from the heterogeneous nature of study populations. It emerges when specific microbial taxa fail to thrive in the microbial community of certain subjects, consequently resulting in a consistent count of zeros for these individuals. This subset of subjects represents a latent class, where their zeros originate from the genuine absence of the microbial taxa. In this paper, we introduce a novel testing methodology designed to uncover such latent classes within generalized Poisson regression models. We establish a closed-form test statistic and deduce its asymptotic distribution based on estimating equations. To assess its efficacy, we conduct an extensive array of simulation studies, and further apply the test to detect latent classes in human gut microbiome data from the Bogalusa Heart Study.}, }
@article {pmid37918889, year = {2023}, author = {Thomas, SC and Miller, G and Li, X and Saxena, D}, title = {Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs.}, journal = {Gut}, volume = {73}, number = {1}, pages = {175-185}, pmid = {37918889}, issn = {1468-3288}, support = {R01 CA206105/CA/NCI NIH HHS/United States ; R01 DE027074/DE/NIDCR NIH HHS/United States ; R41 CA250892/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; *Mycobiome ; Virome ; *Neoplasms/etiology ; }, abstract = {The gastrointestinal ecosystem has received the most attention when examining the contributions of the human microbiome to health and disease. This concentration of effort is logical due to the overwhelming abundance of microbes in the gut coupled with the relative ease of sampling compared with other organs. However, the intestines are intimately connected to multiple extraintestinal organs, providing an opportunity for homeostatic microbial colonisation and pathogenesis in organs traditionally thought to be sterile or only transiently harbouring microbiota. These habitats are challenging to sample, and their low microbial biomass among large amounts of host tissue can make study challenging. Nevertheless, recent findings have shown that many extraintestinal organs that are intimately linked to the gut harbour stable microbiomes, which are colonised from the gut in selective manners and have highlighted not just the influence of the bacteriome but that of the mycobiome and virome on oncogenesis and health.}, }
@article {pmid37908308, year = {2023}, author = {Celoria, V and Rosset, F and Pala, V and Dapavo, P and Ribero, S and Quaglino, P and Mastorino, L}, title = {The Skin Microbiome and Its Role in Psoriasis: A Review.}, journal = {Psoriasis (Auckland, N.Z.)}, volume = {13}, number = {}, pages = {71-78}, pmid = {37908308}, issn = {2230-326X}, abstract = {The skin microbiome is made of various microorganisms, most of which have the function of protecting individuals from harmful pathogens, and they are involved in innate and adaptive immune responses. The skin acts as a physical and immunological barrier against external stimuli, including pathogens and physical damage. Changes in the composition of the skin microbiome can trigger inflammatory processes leading to inflammatory skin diseases in susceptible individuals. Psoriasis (PsO) is a chronic inflammatory disease with a multifactorial etiology, where breakdown of immune tolerance to cutaneous microorganisms is implicated in its pathogenesis. Dysregulation of the microbiome due to genetic and environmental factors plays a significant role in the development of psoriatic disease. Dermatologic conditions such as atopic dermatitis, acne, psoriasis, and rosacea have been associated with intestinal dysbiosis. The skin microbiota composition is crucial for the development of appropriate immune responses, and alterations in the skin microbiome can contribute to changes in physiology and susceptibility to skin diseases or inflammatory conditions. Understanding the microbial settlement of the skin and the network of interactions that occur throughout life is essential for comprehending the pathogenesis of skin diseases and developing innovative treatments. With this article we tried to explore the relationship between the human microbiome and psoriatic disease, shedding light on the functions of the microbiome and the inflammatory disease processes to identify additional therapeutic targets. This review aims to highlight the relationship between skin and gut microbiome functions and inflammatory processes in skin psoriasis and psoriatic arthritis (PsA). The goal is to facilitate future studies on the skin microbiome to identify potential novel therapies for patients with psoriatic disease.}, }
@article {pmid37906201, year = {2024}, author = {Hussein, N and Rajasuriar, R and Khan, AM and Lim, YA and Gan, GG}, title = {The Role of the Gut Microbiome in Hematological Cancers.}, journal = {Molecular cancer research : MCR}, volume = {22}, number = {1}, pages = {7-20}, doi = {10.1158/1541-7786.MCR-23-0080}, pmid = {37906201}, issn = {1557-3125}, support = {FRGS/1/2019/SKK06/UM/01/2//Ministry of Higher Education, Malaysia (MOHE)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology/therapy ; *Microbiota ; Inflammation ; *Hematologic Neoplasms ; }, abstract = {Humans are in a complex symbiotic relationship with a wide range of microbial organisms, including bacteria, viruses, and fungi. The evolution and composition of the human microbiome can be an indicator of how it may affect human health and susceptibility to diseases. Microbiome alteration, termed as dysbiosis, has been linked to the pathogenesis and progression of hematological cancers. A variety of mechanisms, including epithelial barrier disruption, local chronic inflammation response trigger, antigen dis-sequestration, and molecular mimicry, have been proposed to be associated with gut microbiota. Dysbiosis may be induced or worsened by cancer therapies (such as chemotherapy and/or hematopoietic stem cell transplantation) or infection. The use of antibiotics during treatment may also promote dysbiosis, with possible long-term consequences. The aim of this review is to provide a succinct summary of the current knowledge describing the role of the microbiome in hematological cancers, as well as its influence on their therapies. Modulation of the gut microbiome, involving modifying the composition of the beneficial microorganisms in the management and treatment of hematological cancers is also discussed. Additionally discussed are the latest developments in modeling approaches and tools used for computational analyses, interpretation and better understanding of the gut microbiome data.}, }
@article {pmid37904958, year = {2023}, author = {Mishra, AK and Mahmud, I and Lorenzi, PL and Jenq, RR and Wargo, JA and Ajami, NJ and Peterson, CB}, title = {TARO: tree-aggregated factor regression for microbiome data integration.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.10.17.562792}, pmid = {37904958}, issn = {2692-8205}, support = {R01 CA244845/CA/NCI NIH HHS/United States ; }, abstract = {MOTIVATION: Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns.<br><br>RESULTS: We propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information on the phylogenetic tree structure to flexibly aggregate rare features. We demonstrate through simulation studies that TARO accurately recovers a low-rank coefficient matrix and identifies relevant features. We applied TARO to microbiome and metabolomic profiles gathered from subjects being screened for colorectal cancer to understand how gut microrganisms shape intestinal metabolite abundances.<br><br>The R package TARO implementing the proposed methods is available online at https://github.com/amishra-stats/taro-package .}, }
@article {pmid37895330, year = {2023}, author = {Vata, D and Tarcau, BM and Popescu, IA and Halip, IA and Patrascu, AI and Gheuca Solovastru, DF and Mocanu, M and Chiriac, PC and Gheuca Solovastru, L}, title = {Update on Obesity in Psoriasis Patients.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {37895330}, issn = {2075-1729}, abstract = {Psoriasis is a chronic inflammatory skin condition, with genetic, epigenetic, environmental, and lifestyle factors contributing to its onset and recurrence. Severe psoriasis has a great impact on quality of life, which is similar to that of insulin-dependent diabetes, depression, and ischemic heart disease, but with a lower mortality. There is an overlap between the rising incidences of autoimmune diseases and obesity. In recent years, research has shown that there is an association between psoriasis and obesity. Psoriasis is linked to obesity in a two-way manner, as each can precipitate the development of the other. Several adipose tissue-secreted adipokines were shown to be elevated in obese psoriasis patients, exhibiting similar mechanisms of action to those underlying the pathogenesis of psoriasis. Excess body weight can influence not only the treatment response in psoriasis, but also the adverse events, leading to decreased patient compliance. Specific human microbiome patterns have been identified for obesity and psoriasis and could represent a future therapeutic target in selected individuals.}, }
@article {pmid37895286, year = {2023}, author = {Aboushaala, K and Wong, AYL and Barajas, JN and Lim, P and Al-Harthi, L and Chee, A and Forsyth, CB and Oh, CD and Toro, SJ and Williams, FMK and An, HS and Samartzis, D}, title = {The Human Microbiome and Its Role in Musculoskeletal Disorders.}, journal = {Genes}, volume = {14}, number = {10}, pages = {}, pmid = {37895286}, issn = {2073-4425}, support = {R21 AR079679/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Bacteria ; *Musculoskeletal Diseases ; Oxygen ; }, abstract = {Musculoskeletal diseases (MSDs) are characterized as injuries and illnesses that affect the musculoskeletal system. MSDs affect every population worldwide and are associated with substantial global burden. Variations in the makeup of the gut microbiota may be related to chronic MSDs. There is growing interest in exploring potential connections between chronic MSDs and variations in the composition of gut microbiota. The human microbiota is a complex community consisting of viruses, archaea, bacteria, and eukaryotes, both inside and outside of the human body. These microorganisms play crucial roles in influencing human physiology, impacting metabolic and immunological systems in health and disease. Different body areas host specific types of microorganisms, with facultative anaerobes dominating the gastrointestinal tract (able to thrive with or without oxygen), while strict aerobes prevail in the nasal cavity, respiratory tract, and skin surfaces (requiring oxygen for development). Together with the immune system, these bacteria have coevolved throughout time, forming complex biological relationships. Changes in the microbial ecology of the gut may have a big impact on health and can help illnesses develop. These changes are frequently impacted by lifestyle choices and underlying medical disorders. The potential for safety, expenses, and efficacy of microbiota-based medicines, even with occasional delivery, has attracted interest. They are, therefore, a desirable candidate for treating MSDs that are chronic and that may have variable progression patterns. As such, the following is a narrative review to address the role of the human microbiome as it relates to MSDs.}, }
@article {pmid37894256, year = {2023}, author = {Ye, C and Dong, C and Lin, Y and Shi, H and Zhou, W}, title = {Interplay between the Human Microbiome and Biliary Tract Cancer: Implications for Pathogenesis and Therapy.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894256}, issn = {2076-2607}, support = {82260555//the National Natural Science Foundation of China/ ; ldyyyn2021-78//the First Hospital of Lanzhou University Intra-Hospital Fund Youth Fund/ ; 2022B-027//the Education Department of Gansu Province: Innovation Fund Project/ ; }, abstract = {Biliary tract cancer, encompassing intrahepatic and extrahepatic cholangiocarcinoma as well as gallbladder carcinoma, stands as a prevalent malignancy characterized by escalating incidence rates and unfavorable prognoses. The onset of cholangiocarcinoma involves a multitude of risk factors and could potentially be influenced by microbial exposure. The human microbiome, encompassing the entirety of human microbial genetic information, assumes a pivotal role in regulating key aspects such as host digestion, absorption, immune responses, and metabolism. The widespread application of next-generation sequencing technology has notably propelled investigations into the intricate relationship between the microbiome and diseases. An accumulating body of evidence strongly suggests a profound interconnection between biliary tract cancer and the human microbiome. This article critically appraises the existing evidence pertaining to the microbiome milieu within patients afflicted by biliary tract cancer. Furthermore, it delves into potential mechanisms through which dysregulation of the human microbiome could contribute to the advancement of biliary tract cancer. Additionally, the article expounds on its role in the context of chemotherapy and immunotherapy for biliary tract cancer.}, }
@article {pmid37894194, year = {2023}, author = {Lopetuso, LR and Laterza, L and Petito, V and Pecere, S and Quaranta, G and Del Chierico, F and Puca, P and Schiavoni, E and Napolitano, D and Poscia, A and Ianiro, G and Pugliese, D and Putignani, L and Sanguinetti, M and Armuzzi, A and Masucci, L and Gasbarrini, A and Cammarota, G and Scaldaferri, F}, title = {Serial Fecal Microbiota Infusions via Colonoscopy for Active Ulcerative Colitis: A Feasibility, Safety, and Translational Monocentric Italian Study.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894194}, issn = {2076-2607}, abstract = {The effectiveness of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study aimed to investigate the feasibility and effectiveness of serial fecal infusions via colonoscopy in patients with active UC. Subjects with mild-to-moderate UC received three consecutive fecal infusions via colonoscopy. A control population with the same baseline features receiving Infliximab treatment was enrolled. Adverse events and clinical, endoscopic, and microbial outcomes were investigated. Nineteen patients with mildly-to-moderately active UC were enrolled. Clinical response was obtained in six patients at week 2, in eight at week 6, and in nine at week 12. Clinical response was maintained in eight patients at week 24. Endoscopic remission at week 12 was reached in six patients. In the control population, 13/19 patients achieved clinical response at week 6, and 10/19 patients maintained clinical response after 6 months. Microbiota richness was higher in responders compared with the non-responders. Peptostreptococcus, Lactobacillus, and Veillonella were higher in non-responders, while Parabacteroides, Bacteroides, Faecalibacterium, and Akkermansia were higher in responders at all timepoints. Serial FMT infusions appear to be feasible, safe, and effective in UC patients, with a potential role in inducing and maintaining clinical response. Specific bacteria predict the response to FMT.}, }
@article {pmid37894167, year = {2023}, author = {Cláudia-Ferreira, A and Barbosa, DJ and Saegeman, V and Fernández-Rodríguez, A and Dinis-Oliveira, RJ and Freitas, AR and On Behalf Of The Escmid Study Group Of Forensic And Post-Mortem Microbiology Esgfor, }, title = {The Future Is Now: Unraveling the Expanding Potential of Human (Necro)Microbiome in Forensic Investigations.}, journal = {Microorganisms}, volume = {11}, number = {10}, pages = {}, pmid = {37894167}, issn = {2076-2607}, abstract = {The relevance of postmortem microbiological examinations has been controversial for decades, but the boom in advanced sequencing techniques over the last decade is increasingly demonstrating their usefulness, namely for the estimation of the postmortem interval. This comprehensive review aims to present the current knowledge about the human postmortem microbiome (the necrobiome), highlighting the main factors influencing this complex process and discussing the principal applications in the field of forensic sciences. Several limitations still hindering the implementation of forensic microbiology, such as small-scale studies, the lack of a universal/harmonized workflow for DNA extraction and sequencing technology, variability in the human microbiome, and limited access to human cadavers, are discussed. Future research in the field should focus on identifying stable biomarkers within the dominant Bacillota and Pseudomonadota phyla, which are prevalent during postmortem periods and for which standardization, method consolidation, and establishment of a forensic microbial bank are crucial for consistency and comparability. Given the complexity of identifying unique postmortem microbial signatures for robust databases, a promising future approach may involve deepening our understanding of specific bacterial species/strains that can serve as reliable postmortem interval indicators during the process of body decomposition. Microorganisms might have the potential to complement routine forensic tests in judicial processes, requiring robust investigations and machine-learning models to bridge knowledge gaps and adhere to Locard's principle of trace evidence.}, }
@article {pmid37884870, year = {2023}, author = {Mukherjee, P and Paul, S and Dutta, T and Nath, S and Ghosh, B and Chatterjee, D and Mukhopadhyay, S and Mukherjee, S}, title = {Nasal MRSA carriage is a risk factor for development of antibiotic resistance in diabetic foot ulcers and is significantly higher than diabetic and non-diabetic individuals without foot ulcer.}, journal = {BMC infectious diseases}, volume = {23}, number = {1}, pages = {729}, pmid = {37884870}, issn = {1471-2334}, support = {63 (Sanc.)-BT (Estt.)-RD-20/2016//Department of Biotechnology, Government of West Bengal/ ; 63 (Sanc.)-BT (Estt.)-RD-20/2016//Department of Biotechnology, Government of West Bengal/ ; }, mesh = {Humans ; *Diabetic Foot/drug therapy ; *Methicillin-Resistant Staphylococcus aureus ; Methicillin Resistance ; Staphylococcus aureus ; Risk Factors ; *Staphylococcal Infections/complications/drug therapy/microbiology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Multiplex Polymerase Chain Reaction ; *Diabetes Mellitus/drug therapy ; }, abstract = {BACKGROUND: Diabetic foot ulcer (DFU) is a major complication of diabetes often impacted by polymicrobial infection in the wound site. Diabetic patients are immunocompromised in nature and hence vulnerable to infection once the skin barrier is breached. Microbiological culture-based methods show that Staphylococcus aureus (SA) is the most frequently isolated bacteria from the DFU wounds. SA and its most clinically important antibiotic resistant variant methicillin-resistant S. aureus (MRSA) are commonly found in the nasal vestibule and colonization of SA as well as MRSA in any wound site can aggravate the condition. We hypothesize that the presence of nasal MRSA carriage can serve as a potential risk factor contributing to the emergence of antibiotic resistance in diabetic foot ulcer wounds.<br><br>METHODS: In the present study, we have compared the carriage of SA and MRSA in nasal cavity and foot skin among DFU patients (D+F+, n&#x2009;=&#x2009;50), diabetic patients without any ulcer (D+F-, n&#x2009;=&#x2009;50), and healthy controls (D-F-, n&#x2009;=&#x2009;40) by using bacterial culture and PCR based methods. The D+F+, D+F- and D-F-individuals were further categorized based on the presence or absence of MRSA and clinical parameters were compared between MRSA+&#x2009;ve and MRSA-ve individuals in each of the three groups mentioned above.<br><br>RESULTS: Our results show that, (a) nasal MRSA carriage is significantly higher (p&#x2009;<&#x2009;0.05) in D+F+&#x2009;group than the D+F- and D-F- and significantly associated with wound MRSA carriage in D+&#x2009;F+&#x2009;individuals (O.R.&#x2009;=&#x2009;4.09; 95% C.I.&#x2009;=&#x2009;1.12-15.05) and (b) the HbA1C level is significantly higher (p&#x2009;<&#x2009;0.02) in wound MRSA positive, compared to MRSA negative D+F+&#x2009;patients. Interestingly more than half of the MRSA (64%) isolated from DFU wound were identified to be multidrug resistant.<br><br>CONCLUSION: These findings strongly suggest that nasal MRSA carriage can act as a risk factor for development of antibiotic resistance in diabetic foot ulcers and it is therefore important to screen nasal and wound sites of these patients regularly. We have also developed a rapid multiplex PCR assay to detect MRSA from clinical isolates or microbial DNA isolated from clinical samples in the hospital settings.}, }
@article {pmid37884078, year = {2024}, author = {Steinbach, E and Masi, D and Ribeiro, A and Serradas, P and Le Roy, T and Clément, K}, title = {Upper small intestine microbiome in obesity and related metabolic disorders: A new field of investigation.}, journal = {Metabolism: clinical and experimental}, volume = {150}, number = {}, pages = {155712}, doi = {10.1016/j.metabol.2023.155712}, pmid = {37884078}, issn = {1532-8600}, mesh = {Humans ; *Diabetes Mellitus, Type 2 ; *Microbiota ; *Metabolic Diseases/metabolism ; Obesity/therapy ; Intestine, Small/metabolism ; }, abstract = {The study of the gut microbiome holds great promise for understanding and treating metabolic diseases, as its functions and derived metabolites can influence the metabolic status of the host. While research on the fecal microbiome has provided valuable insights, it tells us only part of the story. This limitation arises from the substantial variations in microorganism distribution throughout the gastrointestinal tract due to changes in physicochemical conditions. Thus, relying solely on the fecal microbiome may not be sufficient to draw comprehensive conclusions about metabolic diseases. The proximal part of the small intestine, particularly the jejunum, indeed, serves as the crucial site for digestion and absorption of nutrients, suggesting a potential role of its microbiome in metabolic regulation. Unfortunately, it remains relatively underexplored due to limited accessibility. This review presents current evidence regarding the relationships between the microbiome in the upper small intestine and various phenotypes, focusing on obesity and type 2 diabetes, in both humans and rodents. Research on humans is still limited with variability in the population and methods used. Accordingly, to better understand the role of the whole gut microbiome in metabolic diseases, studies exploring the human microbiome in different niches are needed.}, }
@article {pmid37883976, year = {2023}, author = {Blanco-Míguez, A and Gálvez, EJC and Pasolli, E and De Filippis, F and Amend, L and Huang, KD and Manghi, P and Lesker, TR and Riedel, T and Cova, L and Punčochář, M and Thomas, AM and Valles-Colomer, M and Schober, I and Hitch, TCA and Clavel, T and Berry, SE and Davies, R and Wolf, J and Spector, TD and Overmann, J and Tett, A and Ercolini, D and Segata, N and Strowig, T}, title = {Extension of the Segatella copri complex to 13 species with distinct large extrachromosomal elements and associations with host conditions.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {11}, pages = {1804-1819.e9}, pmid = {37883976}, issn = {1934-6069}, support = {U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; *Gastrointestinal Microbiome/genetics ; Metagenome ; *Microbiota ; Phylogeny ; Prevotella ; Female ; }, abstract = {The Segatella copri (formerly Prevotella copri) complex (ScC) comprises taxa that are key members of the human gut microbiome. It was previously described to contain four distinct phylogenetic clades. Combining targeted isolation with large-scale metagenomic analysis, we defined 13 distinct Segatella copri-related species, expanding the ScC complex beyond four clades. Complete genome reconstruction of thirteen strains from seven species unveiled the presence of genetically diverse large circular extrachromosomal elements. These elements are consistently present in most ScC species, contributing to intra- and inter-species diversities. The nine species-level clades present in humans display striking differences in prevalence and intra-species genetic makeup across human populations. Based on a meta-analysis, we found reproducible associations between members of ScC and the male sex and positive correlations with lower visceral fat and favorable markers of cardiometabolic health. Our work uncovers genomic diversity within ScC, facilitating a better characterization of the human microbiome.}, }
@article {pmid37882845, year = {2023}, author = {Om, H and Chand, U and Kushawaha, PK}, title = {Human anaerobic microbiome: a promising and innovative tool in cancer prevention and treatment by targeting pyruvate metabolism.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {72}, number = {12}, pages = {3919-3930}, pmid = {37882845}, issn = {1432-0851}, mesh = {Humans ; Anaerobiosis ; *Microbiota ; *Neoplasms/prevention &amp; control ; Pyruvates ; Bacteria, Anaerobic ; }, abstract = {INTRODUCTION: Even in present-day times, cancer is one of the most fatal diseases. People are overwhelmed by pricey chemotherapy, immunotherapy, and other costly cancer therapies in poor and middle-income countries. Cancer cells grow under anaerobic and hypoxic conditions. Pyruvate is the final product of the anaerobic glycolysis pathway, and many cancer cells utilize pyruvate for their growth and development. The anaerobic microbiome produces many anti-cancer substances that can act as anti-tumor agents and are both feasible and of low cost. There are different mechanisms of action of the anaerobic microbiome, such as the production of short-chain fatty acids (SCFAs), and competition for the anaerobic environment includes the metabolic product pyruvate to form lactic acid for energy.<br><br>KEY FINDINGS: In this review, we have summarized the role of the metabolic approach of the anaerobic human microbiome in cancer prevention and treatment by interfering with cancer metabolite pyruvate. SCFAs possess decisive outcomes in condoning almost all the hallmarks of cancer and helping the spread of cancer to other body parts. Studies have demonstrated the impact and significance of using SCFA, which results from anaerobic bacteria, as an anti-cancer agent. Anaerobic bacteria-based cancer therapy has become a promising approach to treat cancer using obligate and facultative anaerobic bacteria because of their ability to penetrate and increase in an acidic hypoxic environment.<br><br>SIGNIFICANCE: This review attempts to provide the interconnection of cancer metabolism and anaerobic microbiome metabolism with a focus on pyruvate metabolism to understand and design unique anaerobic microbiota-based therapy for cancer patients.}, }
@article {pmid37882794, year = {2023}, author = {Väinämö, S and Saqib, S and Kalliala, I and Kervinen, K and Luiro, K and Niinimäki, M and Halttunen-Nieminen, M and Virtanen, S and Nieminen, P and Salonen, A and Holster, T}, title = {Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy.}, journal = {Microbiology spectrum}, volume = {11}, number = {6}, pages = {e0165023}, pmid = {37882794}, issn = {2165-0497}, support = {814102//EC | H2020 | PRIORITY 'Excellent science' | H2020 Marie Sk&#x142;odowska-Curie Actions (MSCA)/ ; TYH2020401//Department of Obstetrics and Gynaecology, Helsinki University Hospital/ ; //Suomen L&#xe4;&#xe4;ketieteen S&#xe4;&#xe4;ti&#xf6; (Finnish Medical Foundation)/ ; //Academy of Finland (AKA)/ ; }, mesh = {Pregnancy ; Female ; Humans ; Embryo Transfer ; Fertilization in Vitro ; *Infertility/therapy ; Vagina ; *Microbiota ; }, abstract = {Infertility is a global public health issue which leads many couples to seek fertility treatments, of which in vitro fertilization (IVF) is considered to be the most effective. Still, only about one-third of the women achieve live birth after the first IVF embryo transfer (IVF-ET). Factors affecting embryo implantation are poorly known, but the female reproductive tract microbiota may play a key role. Our study confirms the beneficial role of vaginal lactobacilli, especially Lactobacillus crispatus, in the probability of achieving clinical pregnancy and live birth following IVF-ET. Our findings regarding the intra-individual shift of vaginal microbiota between non-pregnancy and pregnancy states are novel and provide new information about the dynamics of microbiota in the early steps of human reproduction. These findings may help clinicians in their attempts to optimize the conditions for ET by microbiota screening or modulation and timing the ET when the microbiota is the most favorable.}, }
@article {pmid37881747, year = {2023}, author = {Sampaio, S and Araujo, R and Merino-Riba, A and Lelouvier, B and Servant, F and Quelhas-Santos, J and Pestana, M and Sampaio-Maia, B}, title = {Blood, Gut, and Oral Microbiome in Kidney Transplant Recipients.}, journal = {Indian journal of nephrology}, volume = {33}, number = {5}, pages = {366-370}, pmid = {37881747}, issn = {0971-4065}, abstract = {BACKGROUND AND OBJECTIVE: Recent reports describe the existence of a blood microbiome profile not associated with an infection state. Given the high impact that the dysbiotic human microbiome appears to have in chronic kidney disease and, in particular, in the outcome of kidney transplant recipients (KTRs), we aimed to explore the variations and correlations of the gut, oral, and blood microbiome of recipients, 3 months after kidney transplantation.<br><br>MATERIALS AND METHODS: We conducted a cross-sectional study where the microbiome of stool, saliva, and blood collected from recipients 3 months after kidney transplantation (N = 6) was analyzed by polymerase chain reaction (PCR) amplification and sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene using MiSeq Illumina[&#xae;] technology.<br><br>RESULTS: Blood of KTRs harbors a distinct low-abundance microbiome dominated by Proteobacteria and Firmicutes. Gut and oral microbiome of KTRs also present distinct profiles. The existence of a proportion of shared operational taxonomic units among the different body sites is reported, mainly classified as Proteobacteria and Firmicutes.<br><br>CONCLUSIONS: This study provides evidence of existence a blood microbiome in KTRs, different from the gut and the oral microbiome profiles, with a small number of operational taxonomic units representing a shared microbiome. The clinical relevance of this observation should be further explored in these patients.}, }
@article {pmid37875417, year = {2024}, author = {Li, J and Yang, Z and Yuan, W and Bao, Z and Li, MD}, title = {Heme Metabolism Mediates the Effects of Smoking on Gut Microbiome.}, journal = {Nicotine &amp; tobacco research : official journal of the Society for Research on Nicotine and Tobacco}, volume = {26}, number = {6}, pages = {742-751}, doi = {10.1093/ntr/ntad209}, pmid = {37875417}, issn = {1469-994X}, support = {2016YFC0906300//China Precision Medicine Initiative/ ; 2021539200340045//Joint Research Institute of Tobacco and Health of China/ ; //Research Center for Air Pollution and Health of Zhejiang University/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Heme/metabolism ; Transcriptome ; Male ; Female ; Metagenome ; Adult ; Smoking/adverse effects ; Bacteroides/genetics ; }, abstract = {INTRODUCTION: The number of smokers worldwide increased greatly during the past decades and reached 1.14 billion in 2019, becoming a leading risk factor for human health. Tobacco smoking has wide effects on human genetics, epigenetics, transcriptome, and gut microbiome. Although many studies have revealed effects of smoking on host transcriptome, research on the relationship between smoking, host gene expression, and the gut microbiome is limited.<br><br>AIMS AND METHODS: We first explored transcriptome and metagenome profile differences between smokers and nonsmokers. To evaluate the relationship between host gene expression and gut microbiome, we then applied bidirectional mediation analysis to infer causal relationships between smoking, gene expression, and gut microbes.<br><br>RESULTS: Metagenome and transcriptome analyses revealed 71 differential species and 324 differential expressed genes between smokers and nonsmokers. With smoking as an exposure variable, we identified 272 significant causal relationships between gene expression and gut microbes, among which there were 247 genes that mediate the effect of smoking on gut microbes. Pathway-based enrichment analysis showed that these genes were significantly enriched in heme metabolic pathway, which mainly mediated the changes of Bacteroides finegoldii and Lachnospiraceae bacterium 9_1_43BFAA. Additionally, by performing metabolome data analysis in the Integrated Human Microbiome Project (iHMP) database, we verified the correlation between the intermediate products of the heme metabolism pathway (porphobilinogen, bilirubin, and biliverdin) and gut microbiome.<br><br>CONCLUSIONS: By investigating the bidirectional interaction between smoking-related host gene expression and gut microbes, this study provided evidence for the mediation of smoking on gut microbes through co-involvement or interaction of heme metabolism.<br><br>IMPLICATIONS: By comparing the metagenome and transcriptome sequencing profiles between 34 smokers and 33 age- and gender-matched nonsmokers, we are the first to reveal causal relationships among tobacco smoking, host gene expression, and gut microbes. These findings offer insight into how smoking affects gut microbes through host gene expression and metabolism, which highlights the importance of heme metabolism in modulating the effects of smoking on gut microbiome.}, }
@article {pmid37874156, year = {2023}, author = {Vänni, P and Tejesvi, MV and Paalanne, N and Aagaard, K and Ackermann, G and Camargo, CA and Eggesbø, M and Hasegawa, K and Hoen, AG and Karagas, MR and Kolho, K-L and Laursen, MF and Ludvigsson, J and Madan, J and Ownby, D and Stanton, C and Stokholm, J and Tapiainen, T}, title = {Machine-learning analysis of cross-study samples according to the gut microbiome in 12 infant cohorts.}, journal = {mSystems}, volume = {8}, number = {6}, pages = {e0036423}, pmid = {37874156}, issn = {2379-5077}, support = {UH3 OD023275/OD/NIH HHS/United States ; UH3 OD023253/OD/NIH HHS/United States ; UG3 OD023275/OD/NIH HHS/United States ; UG3 OD023253/OD/NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; R01 DK089201/DK/NIDDK NIH HHS/United States ; }, mesh = {Infant ; Humans ; *Gastrointestinal Microbiome/genetics ; Feces ; *Microbiota ; Machine Learning ; RNA, Ribosomal, 16S/genetics ; }, abstract = {There are challenges in merging microbiome data from diverse research groups due to the intricate and multifaceted nature of such data. To address this, we utilized a combination of machine-learning (ML) models to analyze 16S sequencing data from a substantial set of gut microbiome samples, sourced from 12 distinct infant cohorts that were gathered prospectively. Our initial focus was on the mode of delivery due to its prior association with changes in infant gut microbiomes. Through ML analysis, we demonstrated the effective merging and comparison of various gut microbiome data sets, facilitating the identification of robust microbiome biomarkers applicable across varied study populations.}, }
@article {pmid37873416, year = {2023}, author = {Abdill, RJ and Graham, SP and Rubinetti, V and Albert, FW and Greene, CS and Davis, S and Blekhman, R}, title = {Integration of 168,000 samples reveals global patterns of the human gut microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37873416}, issn = {2692-8205}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 LM013863/LM/NLM NIH HHS/United States ; }, abstract = {Understanding the factors that shape variation in the human microbiome is a major goal of research in biology. While other genomics fields have used large, pre-compiled compendia to extract systematic insights requiring otherwise impractical sample sizes, there has been no comparable resource for the 16S rRNA sequencing data commonly used to quantify microbiome composition. To help close this gap, we have assembled a set of 168,484 publicly available human gut microbiome samples, processed with a single pipeline and combined into the largest unified microbiome dataset to date. We use this resource, which is freely available at microbiomap.org, to shed light on global variation in the human gut microbiome. We find that Firmicutes, particularly Bacilli and Clostridia, are almost universally present in the human gut. At the same time, the relative abundance of the 65 most common microbial genera differ between at least two world regions. We also show that gut microbiomes in undersampled world regions, such as Central and Southern Asia, differ significantly from the more thoroughly characterized microbiomes of Europe and Northern America. Moreover, humans in these overlooked regions likely harbor hundreds of taxa that have not yet been discovered due to this undersampling, highlighting the need for diversity in microbiome studies. We anticipate that this new compendium can serve the community and enable advanced applied and methodological research.}, }
@article {pmid37873282, year = {2023}, author = {Anderson, DM and Logan, MG and Patty, SS and Kendall, AJ and Borland, CZ and Pfeifer, CS and Kreth, J and Merritt, JL}, title = {Microbiome imaging goes à la carte: Incorporating click chemistry into the fluorescence-activating and absorption-shifting tag (FAST) imaging platform.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37873282}, issn = {2692-8205}, support = {R01 DE029492/DE/NIDCR NIH HHS/United States ; R21 DE029612/DE/NIDCR NIH HHS/United States ; R35 DE028252/DE/NIDCR NIH HHS/United States ; R35 DE029083/DE/NIDCR NIH HHS/United States ; }, abstract = {The human microbiome is predominantly composed of facultative and obligate anaerobic bacteria that live in hypoxic/anoxic polymicrobial biofilm communities. Given the oxidative sensitivity of large fractions of the human microbiota, green fluorescent protein (GFP) and related genetically-encoded fluorophores only offer limited utility for live cell imaging due the oxygen requirement for chromophore maturation. Consequently, new fluorescent imaging modalities are needed to study polymicrobial interactions and microbiome-host interactions within anaerobic environments. The fluorescence-activating and absorption shifting tag (FAST) is a rapidly developing genetically-encoded fluorescent imaging technology that exhibits tremendous potential to address this need. In the FAST system, fluorescence only occurs when the FAST protein is complexed with one of a suite of cognate small molecule fluorogens. To expand the utility of FAST imaging, we sought to develop a modular platform (Click-FAST) to democratize fluorogen engineering for personalized use cases. Using Click-FAST, investigators can quickly and affordably sample a vast chemical space of compounds, potentially imparting a broad range of desired functionalities to the parental fluorogen. In this work, we demonstrate the utility of the Click-FAST platform using a novel fluorogen, [PL]Blaze-alkyne, which incorporates the widely available small molecule ethylvanillin as the hydroxybenzylidine head group. Different azido reagents were clicked onto [PL]Blaze-alkyne and shown to impart useful characteristics to the fluorogen, such as selective bacterial labeling in mixed populations as well as fluorescent signal enhancement. Conjugation of an 80 Å PEG molecule to [PL]Blaze-alkyne illustrates the broad size range of functional fluorogen chimeras that can be employed. This PEGylated fluorogen also functions as an exquisitely selective membrane permeability marker capable of outperforming propidium iodide as a fluorescent marker of cell viability.}, }
@article {pmid37870467, year = {2024}, author = {Wang, M and Liu, G and Liu, M and Tai, C and Deng, Z and Song, J and Ou, HY}, title = {ICEberg 3.0: functional categorization and analysis of the integrative and conjugative elements in bacteria.}, journal = {Nucleic acids research}, volume = {52}, number = {D1}, pages = {D732-D737}, pmid = {37870467}, issn = {1362-4962}, support = {32070572//National Natural Science Foundation of China/ ; 19JC1413000//Science and Technology Commission of Shanghai Municipality/ ; }, mesh = {Humans ; *Bacteria/genetics ; *Conjugation, Genetic ; Databases, Factual ; *Databases, Genetic ; DNA Transposable Elements ; Microbiota ; }, abstract = {ICEberg 3.0 (https://tool2-mml.sjtu.edu.cn/ICEberg3/) is an upgraded database that provides comprehensive insights into bacterial integrative and conjugative elements (ICEs). In comparison to the previous version, three key enhancements were introduced: First, through text mining and manual curation, it now encompasses details of 2065 ICEs, 607 IMEs and 275 CIMEs, including 430 with experimental support. Secondly, ICEberg 3.0 systematically categorizes cargo gene functions of ICEs into six groups based on literature curation and predictive analysis, providing a profound understanding of ICEs'diverse biological traits. The cargo gene prediction pipeline is integrated into the online tool ICEfinder 2.0. Finally, ICEberg 3.0 aids the analysis and exploration of ICEs from the human microbiome. Extracted and manually curated from 2405 distinct human microbiome samples, the database comprises 1386 putative ICEs, offering insights into the complex dynamics of Bacteria-ICE-Cargo networks within the human microbiome. With the recent updates, ICEberg 3.0 enhances its capability to unravel the intricacies of ICE biology, particularly in the characterization and understanding of cargo gene functions and ICE interactions within the microbiome. This enhancement may facilitate the investigation of the dynamic landscape of ICE biology and its implications for microbial communities.}, }
@article {pmid37869650, year = {2023}, author = {Ibrahimi, E and Lopes, MB and Dhamo, X and Simeon, A and Shigdel, R and Hron, K and Stres, B and D'Elia, D and Berland, M and Marcos-Zambrano, LJ}, title = {Overview of data preprocessing for machine learning applications in human microbiome research.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1250909}, pmid = {37869650}, issn = {1664-302X}, abstract = {Although metagenomic sequencing is now the preferred technique to study microbiome-host interactions, analyzing and interpreting microbiome sequencing data presents challenges primarily attributed to the statistical specificities of the data (e.g., sparse, over-dispersed, compositional, inter-variable dependency). This mini review explores preprocessing and transformation methods applied in recent human microbiome studies to address microbiome data analysis challenges. Our results indicate a limited adoption of transformation methods targeting the statistical characteristics of microbiome sequencing data. Instead, there is a prevalent usage of relative and normalization-based transformations that do not specifically account for the specific attributes of microbiome data. The information on preprocessing and transformations applied to the data before analysis was incomplete or missing in many publications, leading to reproducibility concerns, comparability issues, and questionable results. We hope this mini review will provide researchers and newcomers to the field of human microbiome research with an up-to-date point of reference for various data transformation tools and assist them in choosing the most suitable transformation method based on their research questions, objectives, and data characteristics.}, }
@article {pmid39808466, year = {2023}, author = {Kolář, M}, title = {[Selected aspects of the human microbiome].}, journal = {Klinicka mikrobiologie a infekcni lekarstvi}, volume = {29}, number = {2}, pages = {46-51}, pmid = {39808466}, issn = {1211-264X}, abstract = {This review briefly defines the term microbiome and characterizes its importance in health and disease.}, }
@article {pmid39076604, year = {2022}, author = {Qian, J and Wu, Z and Zhu, Y and Liu, C}, title = {One Health: a holistic approach for food safety in livestock.}, journal = {Science in One Health}, volume = {1}, number = {}, pages = {100015}, pmid = {39076604}, issn = {2949-7043}, abstract = {The food safety of livestock is a critical issue between animals and humans due to their complex interactions. Pathogens have the potential to spread at every stage of the animal food handling process, including breeding, processing, packaging, storage, transportation, marketing and consumption. In addition, application of the antibiotic usage in domestic animals is a controversial issue because, while they can combat food-borne zoonotic pathogens and promote animal growth and productivity, they can also lead to the transmission of antibiotic-resistant microorganisms and antibiotic-resistant genes across species and habitats. Coevolution of microbiomes may occur in humans and animals as well which may alter the structure of the human microbiome through animal food consumption. One Health is a holistic approach to systematically understand the complex relationships among humans, animals and environments which may provide effective countermeasures to solve food safety problems aforementioned. This paper depicts the main pathogen spectrum of livestock and animal products, summarizes the flow of antibiotic-resistant bacteria and genes between humans and livestock along the food-chain production, and the correlation of their microbiome is reviewed as well to advocate for deeper interdisciplinary communication and collaboration among researchers in medicine, epidemiology, veterinary medicine and ecology to promote One Health approaches to address the global food safety challenges.}, }
@article {pmid39295904, year = {2023}, author = {Ruxton, CHS and Kajita, C and Rocca, P and Pot, B}, title = {Microbiota and probiotics: chances and challenges - a symposium report.}, journal = {Gut microbiome (Cambridge, England)}, volume = {4}, number = {}, pages = {e6}, pmid = {39295904}, issn = {2632-2897}, abstract = {The 10th International Yakult Symposium was held in Milan, Italy, on 13-14 October 2022. Two keynote lectures covered the crewed journey to space and its implications for the human microbiome, and how current regulatory systems can be adapted and updated to ensure the safety of microorganisms used as probiotics or food processing ingredients. The remaining lectures were split into sections entitled "Chances" and "Challenges." The "Chances" section explored opportunities for the science of probiotics and fermented foods to contribute to diverse areas of health such as irritable bowel syndrome, major depression, Parkinson's disease, immune dysfunction, infant colic, intensive care, respiratory infections, and promoting healthy longevity. The "Challenges" section included selecting appropriate clinical trial participants and methodologies to minimise heterogeneity in responses, how to view probiotics in the context of One Health, adapting regulatory frameworks, and understanding how substances of bacterial origin can cross the blood-brain barrier. The symposium provided evidence from cutting-edge research that gut eubiosis is vital for human health and, like space, the microbiota deserves further exploration of its vast potential.}, }
@article {pmid39295911, year = {2023}, author = {Panwar, S and Kumari, S and Verma, J and Bakshi, S and Narendrakumar, L and Paul, D and Das, B}, title = {Toxin-linked mobile genetic elements in major enteric bacterial pathogens.}, journal = {Gut microbiome (Cambridge, England)}, volume = {4}, number = {}, pages = {e5}, pmid = {39295911}, issn = {2632-2897}, abstract = {One of the fascinating outcomes of human microbiome studies adopting multi-omics technology is its ability to decipher millions of microbial encoded functions in the most complex and crowded microbial ecosystem, including the human gastrointestinal (GI) tract without cultivating the microbes. It is well established that several functions that modulate the human metabolism, nutrient assimilation, immunity, infections, disease severity and therapeutic efficacy of drugs are mostly of microbial origins. In addition, these microbial functions are dynamic and can disseminate between microbial taxa residing in the same ecosystem or other microbial ecosystems through horizontal gene transfer. For clinicians and researchers alike, understanding the toxins, virulence factors and drug resistance traits encoded by the microbes associated with the human body is of utmost importance. Nevertheless, when such traits are genetically linked with mobile genetic elements (MGEs) that make them transmissible, it creates an additional burden to public health. This review mainly focuses on the functions of gut commensals and the dynamics and crosstalk between commensal and pathogenic bacteria in the gut. Also, the review summarises the plethora of MGEs linked with virulence genes present in the genomes of various enteric bacterial pathogens, which are transmissible among other pathogens and commensals.}, }
@article {pmid38550941, year = {2023}, author = {Ellinghaus, D}, title = {COVID-19 host genetics and ABO blood group susceptibility.}, journal = {Cambridge prisms. Precision medicine}, volume = {1}, number = {}, pages = {e10}, pmid = {38550941}, issn = {2752-6143}, abstract = {Twenty-five susceptibility loci for SARS-CoV-2 infection and/or COVID-19 disease severity have been identified in the human genome by genome-wide association studies, and the most frequently replicated genetic findings for susceptibility are genetic variants at the ABO gene locus on chromosome 9q34.2, which is supported by the association between ABO blood group distribution and COVID-19. The ABO blood group effect appears to influence a variety of disease conditions and pathophysiological mechanisms associated with COVID-19. Transmission models for SARS-CoV-2 combined with observational public health and genome-wide data from patients and controls, as well as receptor binding experiments in cell lines and human samples, indicate that there may be a reduction or slowing of infection events by up to 60% in certain ABO blood group constellations of index and contact person in the early phase of a SARS-CoV-2 outbreak. The strength of the ABO blood group effect on reducing infection rates further depends on the distribution of the ABO blood groups in the respective population and the proportion of blood group O in that population. To understand in detail the effect of ABO blood groups on COVID-19, further studies are needed in relation to different demographic characteristics, but also in relation to recent data on reinfection with new viral variants and in the context of the human microbiome.}, }
@article {pmid38867907, year = {2022}, author = {Ma, Y and Ke, D and Li, D and Zhang, Q}, title = {Donors' experiences and attitudes of fecal microbiota transplantation: An empirical bioethics study from China.}, journal = {iMeta}, volume = {1}, number = {4}, pages = {e62}, pmid = {38867907}, issn = {2770-596X}, abstract = {Donor participation is a critical part of ensuring the development of human microbiome research and the clinical application of fecal microbiota transplantation (FMT). Most FMT donors are still not sufficiently aware of the risks associated with the act of donating gut microbiota, especially the risk of data privacy disclosure. Enhanced awareness of the moral responsibility of the researchers and ethical oversight by ethics committees are needed.}, }
@article {pmid39628703, year = {2022}, author = {Liu, D and Siguenza, NE and Zarrinpar, A and Ding, Y}, title = {Methods of DNA introduction for the engineering of commensal microbes.}, journal = {Engineering microbiology}, volume = {2}, number = {4}, pages = {100048}, pmid = {39628703}, issn = {2667-3703}, support = {R01 EB030134/EB/NIBIB NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; U01 CA265719/CA/NCI NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, abstract = {The microbiome is an essential component of ecological systems and is comprised of a diverse array of microbes. Over the past decades, the accumulated observational evidence reveals a close correlation between the microbiome and human health and disease. Many groups are now manipulating individual microbial strains, species and the community as a whole to gain a mechanistic understanding of the functions of the microbiome. Here, we discuss three major approaches for introducing DNA to engineer model bacteria and isolated undomesticated bacteria, including transformation, transduction, and conjugation. We provide an overview of these approaches and describe the advantages and limitations of each method. In addition, we highlight examples of human microbiome engineering using these approaches. Finally, we provide perspectives for the future of microbiome engineering.}, }
@article {pmid38046357, year = {2022}, author = {Aguanno, D and Metwaly, A and Coleman, OI and Haller, D}, title = {Modeling microbiota-associated human diseases: from minimal models to complex systems.}, journal = {Microbiome research reports}, volume = {1}, number = {3}, pages = {17}, pmid = {38046357}, issn = {2771-5965}, abstract = {Alterations in the intestinal microbiota are associated with various human diseases of the digestive system, including obesity and its associated metabolic diseases, inflammatory bowel diseases (IBD), and colorectal cancer (CRC). All three diseases are characterized by modifications of the richness, composition, and metabolic functions of the human intestinal microbiota. Despite being multi-factorial diseases, studies in germ-free animal models have unarguably identified the intestinal microbiota as a causal driver of disease pathogenesis. However, for an increased mechanistic understanding of microbial signatures in human diseases, models require detailed refinement to closely mimic the human microbiota and reflect the complexity and range of dysbiosis observed in patients. The transplantation of human fecal microbiota into animal models represents a powerful tool for studying the causal and functional role of the dysbiotic human microbiome in a pathological context. While human microbiota-associated models were initially employed to study obesity, an increasing number of studies have applied this approach in the context of IBD and CRC over the past decade. In this review, we discuss different approaches that allow the functional validation of the bacterial contribution to human diseases, with emphasis on obesity and its associated metabolic diseases, IBD, and CRC. We discuss the utility of simple models, such as in vitro fermentation systems of the human microbiota and ex vivo intestinal organoids, as well as more complex whole organism models. Our focus here lies on human microbiota-associated mouse models in the context of all three diseases, as well as highlighting the advantages and limitations of this approach.}, }
@article {pmid39295776, year = {2022}, author = {Puhlmann, ML and Jokela, R and van Dongen, KCW and Bui, TPN and van Hangelbroek, RWJ and Smidt, H and de Vos, WM and Feskens, EJM}, title = {Dried chicory root improves bowel function, benefits intestinal microbial trophic chains and increases faecal and circulating short chain fatty acids in subjects at risk for type 2 diabetes.}, journal = {Gut microbiome (Cambridge, England)}, volume = {3}, number = {}, pages = {e4}, pmid = {39295776}, issn = {2632-2897}, abstract = {We investigated the impact of dried chicory root in a randomised, placebo-controlled trial with 55 subjects at risk for type 2 diabetes on bowel function, gut microbiota and its products, and glucose homeostasis. The treatment increased stool softness (+1.1 ± 0.3 units; p = 0.034) and frequency (+0.6 ± 0.2 defecations/day; p < 0.001), strongly modulated gut microbiota composition (7 % variation; p = 0.001), and dramatically increased relative levels (3-4-fold) of Anaerostipes and Bifidobacterium spp., in a dose-dependent, reversible manner. A synthetic community, including selected members of these genera and a Bacteroides strain, generated a butyrogenic trophic chain from the product. Faecal acetate, propionate and butyrate increased by 25.8 % (+13.0 ± 6.3 mmol/kg; p = 0.023) as did their fasting circulating levels by 15.7 % (+7.7 ± 3.9 μM; p = 0.057). In the treatment group the glycaemic coefficient of variation decreased from 21.3 ± 0.94 to 18.3 ± 0.84 % (p = 0.004), whereas fasting glucose and HOMA-ir decreased in subjects with low baseline Blautia levels (-0.3 ± 0.1 mmol/L fasting glucose; p = 0.0187; -0.14 ± 0.1 HOMA-ir; p = 0.045). Dried chicory root intake rapidly and reversibly affects bowel function, benefits butyrogenic trophic chains, and promotes glycaemic control.}, }
@article {pmid37938295, year = {2022}, author = {Sanchez-Cid, C and Guironnet, A and Keuschnig, C and Wiest, L and Vulliet, E and Vogel, TM}, title = {Gentamicin at sub-inhibitory concentrations selects for antibiotic resistance in the environment.}, journal = {ISME communications}, volume = {2}, number = {1}, pages = {29}, pmid = {37938295}, issn = {2730-6151}, abstract = {Antibiotics released into the environment at low (sub-inhibitory) concentrations could select for antibiotic resistance that might disseminate to the human microbiome. In this case, low-level anthropogenic sources of antibiotics would have a significant impact on human health risk. In order to provide data necessary for the evaluation of this risk, we implemented river water microcosms at both sub-inhibitory and inhibitory concentrations of gentamicin as determined previously based on bacterial growth in enriched media. Using metagenomic sequencing and qPCR/RT-qPCR, we assessed the effects of gentamicin on water bacterial communities and their resistome. A change in the composition of total and active communities, as well as a gentamicin resistance gene selection identified via mobile genetic elements, was observed during a two-day exposure. We demonstrated the effects of sub-inhibitory concentrations of gentamicin on bacterial communities and their associated resistome in microcosms (simulating in situ conditions). In addition, we established relationships between antibiotic dose and the magnitude of the community response in the environment. The scope of resistance selection under sub-inhibitory concentrations of antibiotics and the mechanisms underlying this process might provide the basis for understanding resistance dispersion and associated risks in relatively low impacted ecosystems.}, }
@article {pmid38993286, year = {2022}, author = {Reynoso-García, J and Miranda-Santiago, AE and Meléndez-Vázquez, NM and Acosta-Pagán, K and Sánchez-Rosado, M and Díaz-Rivera, J and Rosado-Quiñones, AM and Acevedo-Márquez, L and Cruz-Roldán, L and Tosado-Rodríguez, EL and Figueroa-Gispert, MDM and Godoy-Vitorino, F}, title = {A complete guide to human microbiomes: Body niches, transmission, development, dysbiosis, and restoration.}, journal = {Frontiers in systems biology}, volume = {2}, number = {}, pages = {}, pmid = {38993286}, issn = {2674-0702}, support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; U54 CA096297/CA/NCI NIH HHS/United States ; R25 GM061838/GM/NIGMS NIH HHS/United States ; U54 MD007587/MD/NIMHD NIH HHS/United States ; S21 MD001830/MD/NIMHD NIH HHS/United States ; R25 GM061151/GM/NIGMS NIH HHS/United States ; }, abstract = {Humans are supra-organisms co-evolved with microbial communities (Prokaryotic and Eukaryotic), named the microbiome. These microbiomes supply essential ecosystem services that play critical roles in human health. A loss of indigenous microbes through modern lifestyles leads to microbial extinctions, associated with many diseases and epidemics. This narrative review conforms a complete guide to the human holobiont-comprising the host and all its symbiont populations- summarizes the latest and most significant research findings in human microbiome. It pretends to be a comprehensive resource in the field, describing all human body niches and their dominant microbial taxa while discussing common perturbations on microbial homeostasis, impacts of urbanization and restoration and humanitarian efforts to preserve good microbes from extinction.}, }
@article {pmid37938646, year = {2021}, author = {Mayerhofer, MM and Eigemann, F and Lackner, C and Hoffmann, J and Hellweger, FL}, title = {Dynamic carbon flux network of a diverse marine microbial community.}, journal = {ISME communications}, volume = {1}, number = {1}, pages = {50}, pmid = {37938646}, issn = {2730-6151}, abstract = {The functioning of microbial ecosystems has important consequences from global climate to human health, but quantitative mechanistic understanding remains elusive. The components of microbial ecosystems can now be observed at high resolution, but interactions still have to be inferred e.g., a time-series may show a bloom of bacteria X followed by virus Y suggesting they interact. Existing inference approaches are mostly empirical, like correlation networks, which are not mechanistically constrained and do not provide quantitative mass fluxes, and thus have limited utility. We developed an inference method, where a mechanistic model with hundreds of species and thousands of parameters is calibrated to time series data. The large scale, nonlinearity and feedbacks pose a challenging optimization problem, which is overcome using a novel procedure that mimics natural speciation or diversification e.g., stepwise increase of bacteria species. The method allows for curation using species-level information from e.g., physiological experiments or genome sequences. The product is a mass-balancing, mechanistically-constrained, quantitative representation of the ecosystem. We apply the method to characterize phytoplankton-heterotrophic bacteria interactions via dissolved organic matter in a marine system. The resulting model predicts quantitative fluxes for each interaction and time point (e.g., 0.16 µmolC/L/d of chrysolaminarin to Polaribacter on April 16, 2009). At the system level, the flux network shows a strong correlation between the abundance of bacteria species and their carbon flux during blooms, with copiotrophs being relatively more important than oligotrophs. However, oligotrophs, like SAR11, are unexpectedly high carbon processors for weeks into blooms, due to their higher biomass. The fraction of exudates (vs. grazing/death products) in the DOM pool decreases during blooms, and they are preferentially consumed by oligotrophs. In addition, functional similarity of phytoplankton i.e., what they produce, decouples their association with heterotrophs. The methodology is applicable to other microbial ecosystems, like human microbiome or wastewater treatment plants.}, }
@article {pmid39296724, year = {2020}, author = {Hill, C}, title = {You have the microbiome you deserve.}, journal = {Gut microbiome (Cambridge, England)}, volume = {1}, number = {}, pages = {e3}, pmid = {39296724}, issn = {2632-2897}, abstract = {The human microbiome is one of the most exciting areas of microbiology. From a starting point of tens of papers annually a couple of decades ago, there are now thousands of papers published every year on the microbiome. Huge strides have been made in terms of defining the individual members of complex human microbiomes from different body sites. The individuality and diversity of the human microbiome almost surpasses our ability to comprehend it. Advances in metagenomics and computational sciences have increased the complexity of the field, while at the same time we have moved from regarding the human microbiome as a benign passenger to a situation where it has been linked to almost every chronic disease, including obesity, cancer and infectious disease. The microbiome tantalizes us with the promise of novel therapeutic molecules and modalities for a range of intractable diseases. And yet, very few microbiome-based therapies have made it to the clinic or the pharmacy and we still cannot really define a healthy microbiome. We are entering the most exciting phase of microbiome research, as we develop effective, evidence-based interventions to preserve and restore human health. But we need rigour and numeracy if we are to realize this vision.}, }
@article {pmid40084234, year = {2019}, author = {Werlang, C and Cárcarmo-Oyarce, G and Ribbeck, K}, title = {Engineering mucus to study and influence the microbiome.}, journal = {Nature reviews. Materials}, volume = {4}, number = {2}, pages = {134-145}, pmid = {40084234}, issn = {2058-8437}, support = {R01 EB017755/EB/NIBIB NIH HHS/United States ; }, abstract = {Mucus is a 3D hydrogel that houses the majority of the human microbiome. The mucous environment plays an important role in the differentiation and behaviour of microbial phenotypes and enables the creation of spatial distributions. Dysregulation of mucus is further associated with various diseases. Therefore, mucus is the key ingredient to study the behaviour of commensal and pathogenic microbiota in vitro. Indeed, microorganisms cultured in mucus exhibit phenotypes substantially different from those exhibited in standard laboratory media. In this Review, we discuss the impact of mucus on the microbiome and examine the structure and glycosylation of mucins - the main building blocks of mucus. We investigate the impact of glycans on mucin function and highlight different approaches for the engineering of synthetic mucins, including synthesis of the backbone, the design of mucin-mimetic hydrogels and the engineering of glycans. Finally, mucin mimetics for 3D in vitro cell culture and for modulating microbial community structure and function are discussed.}, }
@article {pmid37864136, year = {2023}, author = {Tan, A and Murugapiran, S and Mikalauskas, A and Koble, J and Kennedy, D and Hyde, F and Ruotti, V and Law, E and Jensen, J and Schroth, GP and Macklaim, JM and Kuersten, S and LeFrançois, B and Gohl, DM}, title = {Rational probe design for efficient rRNA depletion and improved metatranscriptomic analysis of human microbiomes.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {299}, pmid = {37864136}, issn = {1471-2180}, mesh = {Humans ; RNA, Ribosomal/genetics ; Bacteria/genetics ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; }, abstract = {The microbiota that colonize the human gut and other tissues are dynamic, varying both in composition and functional state between individuals and over time. Gene expression measurements can provide insights into microbiome composition and function. However, efficient and unbiased removal of microbial ribosomal RNA (rRNA) presents a barrier to acquiring metatranscriptomic data. Here we describe a probe set that achieves efficient enzymatic rRNA removal of complex human-associated microbial communities. We demonstrate that the custom probe set can be further refined through an iterative design process to efficiently deplete rRNA from a range of human microbiome samples. Using synthetic nucleic acid spike-ins, we show that the rRNA depletion process does not introduce substantial quantitative error in gene expression profiles. Successful rRNA depletion allows for efficient characterization of taxonomic and functional profiles, including during the development of the human gut microbiome. The pan-human microbiome enzymatic rRNA depletion probes described here provide a powerful tool for studying the transcriptional dynamics and function of the human microbiome.}, }
@article {pmid37863831, year = {2024}, author = {Budzinski, L and von Goetze, V and Chang, HD}, title = {Single-cell phenotyping of bacteria combined with deep sequencing for improved contextualization of microbiome analyses.}, journal = {European journal of immunology}, volume = {54}, number = {1}, pages = {e2250337}, doi = {10.1002/eji.202250337}, pmid = {37863831}, issn = {1521-4141}, support = {375876048 TRR241 B03//Deutsche Forschungsgemeinschaft/ ; CH938/4-1//Deutsche Forschungsgemeinschaft/ ; 1.6./01: "BacFlow - Analyse bakterieller Gemeinschaften durch Mikrobiota-Zytometrie."//EFRE-Projekt/ ; }, mesh = {Humans ; Cross-Sectional Studies ; *Microbiota ; Bacteria/genetics ; Flow Cytometry ; High-Throughput Nucleotide Sequencing ; }, abstract = {Great effort was made to characterize the bacterial communities inhabiting the human body as a factor in disease, resulting in the realization that a wide spectrum of diseases is associated with an altered composition of the microbiome. However, the identification of disease-relevant bacteria has been hindered by the high cross-sectional diversity of individual microbiomes, and in most cases, it remains unclear whether the observed alterations are cause or consequence of disease. Hence, innovative analysis approaches are required that enable inquiries of the microbiome beyond mere taxonomic cataloging. This review highlights the utility of microbiota flow cytometry, a single-cell analysis platform to directly interrogate cellular interactions, cell conditions, and crosstalk with the host's immune system within the microbiome to take into consideration the role of microbes as critical interaction partners of the host and the spectrum of microbiome alterations, beyond compositional changes. In conjunction with advanced sequencing approaches it could reveal the genetic potential of target bacteria and advance our understanding of taxonomic diversity and gene usage in the context of the microenvironment. Single-cell bacterial phenotyping has the potential to change our perspective on the human microbiome and empower microbiome research for the development of microbiome-based therapy approaches and personalized medicine.}, }
@article {pmid37851822, year = {2023}, author = {Farias Amorim, C and Lovins, VM and Singh, TP and Novais, FO and Harris, JC and Lago, AS and Carvalho, LP and Carvalho, EM and Beiting, DP and Scott, P and Grice, EA}, title = {Multiomic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity.}, journal = {Science translational medicine}, volume = {15}, number = {718}, pages = {eadh1469}, pmid = {37851822}, issn = {1946-6242}, support = {F31 AR079845/AR/NIAMS NIH HHS/United States ; P50 AI030639/AI/NIAID NIH HHS/United States ; P30 AR069589/AR/NIAMS NIH HHS/United States ; R01 NR015639/NR/NINR NIH HHS/United States ; T32 AR007465/AR/NIAMS NIH HHS/United States ; F31 AR079901/AR/NIAMS NIH HHS/United States ; R01 AI162711/AI/NIAID NIH HHS/United States ; R01 AI143790/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; Staphylococcus aureus ; Multiomics ; *Leishmaniasis, Cutaneous ; Inflammation ; Bacteria ; *Microbiota ; Patient Acuity ; }, abstract = {Leishmania braziliensis is a parasitic infection that can result in inflammation and skin injury with highly variable and unpredictable clinical outcomes. Here, we investigated the potential impact of microbiota on infection-induced inflammatory responses and disease resolution by conducting an integrated analysis of the skin microbiome and host transcriptome on a cohort of 62 patients infected with L. braziliensis. We found that overall bacterial burden and microbiome configurations dominated with Staphylococcus spp. were associated with delayed healing and enhanced inflammatory responses, especially by IL-1 family members. Quantification of host and bacterial transcripts on human lesions revealed that high lesional S. aureus transcript abundance was associated with delayed healing and increased expression of IL-1β. This cytokine was critical for modulating disease outcomes in L. braziliensis-infected mice colonized with S. aureus, given that its neutralization reduced pathology and inflammation. These results highlight how the human microbiome can shape disease outcomes in cutaneous leishmaniasis and suggest pathways toward host-directed therapies to mitigate the inflammatory consequences.}, }
@article {pmid37847418, year = {2023}, author = {Refisch, A and Walter, M}, title = {[The importance of the human microbiome for mental health].}, journal = {Der Nervenarzt}, volume = {94}, number = {11}, pages = {1001-1009}, pmid = {37847418}, issn = {1433-0407}, mesh = {Humans ; Mental Health ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Mental Disorders/therapy ; Brain ; }, abstract = {Many common diseases including psychiatric disorders show characteristic alterations in the microbiome. Preclinical studies have uncovered important mechanisms by which the microbiome interacts bidirectionally with neural functions. Dysregulation of the complex interplay between the microbiome, immune system, stress response, and energy homeostasis, particularly in the early stages of life, can predispose to the development of psychiatric symptoms later in life. Although few clinical studies are available to date, the broad influence of the microbiome on neural and mental functions as well as its high plasticity, have generated great interest in its therapeutic potential for common psychiatric disorders.}, }
@article {pmid37846925, year = {2023}, author = {Sun, L and Wang, Q and Wang, H and Huang, J and Yu, Z}, title = {A cross-sectional cohort study on the skin microbiota in patients with different acne durations.}, journal = {Experimental dermatology}, volume = {32}, number = {12}, pages = {2102-2111}, doi = {10.1111/exd.14951}, pmid = {37846925}, issn = {1600-0625}, support = {32000054//National Natural Science Foundation of China/ ; 32170071//National Natural Science Foundation of China/ ; }, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; *Acne Vulgaris/microbiology ; Skin/microbiology ; *Microbiota/genetics ; Cohort Studies ; }, abstract = {Acne is a chronic disease that often persists for years. Skin microbial communities play an essential role in the development of acne. However, limited information is available about the dynamic patterns of skin microbiota in acne. This study aimed to characterize microbial community changes in skin pores and surfaces of acne patients with varying disease time. In this study, a total of 70 skin samples from 22 subjects were collected and sequenced using 16S rRNA amplicon sequencing. Although microbial compositions in skin pores were similar over time, significant differences in microbial structure were observed on the skin surface, with the dominance of Cutibacterium in the first 3 years and replacement by Staphylococcus in 4-6 years. Lactobacillus and Acinetobacter were more abundant in the normal group and continuingly decreased with disease time on the skin surface. Microbial networks further revealed substantial increases in microbial interactions in the 4-6 years group in both skin surfaces and pores. These results demonstrate that the skin microbiota alters with the disease duration and may provide a potential guide in redirecting skin microbiota towards healthy states.}, }
@article {pmid37843778, year = {2024}, author = {Shad, NS and Shaikh, NI and Cunningham, SA}, title = {Migration Spurs Changes in the Human Microbiome: a Review.}, journal = {Journal of racial and ethnic health disparities}, volume = {11}, number = {6}, pages = {3618-3632}, pmid = {37843778}, issn = {2196-8837}, support = {R25DK078381/DK/NIDDK NIH HHS/United States ; R25DK078381/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Emigration and Immigration/statistics &amp; numerical data ; Emigrants and Immigrants/statistics &amp; numerical data ; }, abstract = {International migration often results in major changes in living environments and lifestyles, and these changes may lead to the observed increases in obesity and diabetes among foreign-born people after resettling in higher-income countries. A possible mechanism linking changes in living environments to the onset of health conditions may be changes in the microbiome. Previous research has shown that unfavorable changes in the composition of the microbiome can increase disposition to diseases such as diabetes, obesity, kidney disease, and inflammatory bowel disease. We investigated the relationship between human migration and microbiome composition through a review using microbiome- and migration-related search terms in PubMed and Web of Science. We included articles examining the gut, oral, or oropharyngeal microbiome in people who migrated internationally. Nine articles met eligibility criteria. All but one examined migration from a non-Western to a Western country. Four of these found a difference in the microbiome of migrants compared with non-migrating residents of their country of birth, seven found differences in the microbiome of migrants compared with the native-born population in the country of resettlement, and five found microbiome differences associated with duration of stay in the country of resettlement. Microbiome composition varies with country of birth, age at migration, time since immigration, and country of resettlement. The results suggest that migration may lead to changes in the microbiome; thus, microbiome characteristics are a plausible pathway to examine changes in health after resettlement in a new country.}, }
@article {pmid37843744, year = {2024}, author = {Moitas, B and Caldas, IM and Sampaio-Maia, B}, title = {Microbiology and postmortem interval: a systematic review.}, journal = {Forensic science, medicine, and pathology}, volume = {20}, number = {2}, pages = {696-715}, pmid = {37843744}, issn = {1556-2891}, support = {(UIDB/04004/2020)//Minist&#xe9;rio da Ci&#xea;ncia, Tecnologia e Ensino Superior/ ; }, mesh = {Humans ; *Postmortem Changes ; *Microbiota ; }, abstract = {This systematic review aims to learn if and how it is possible to use the human microbiome to indicate the time elapsed after death. Articles were searched on the PubMed database using predefined data fields and keywords; reviews, systematic reviews, and meta-analyses were excluded. The final selection included 14 papers (out of 144). The results indicated that the microorganisms present in the cadaveric island succeed predictably over time, with markers between the stages of decomposition constituting a potential innovative tool for postmortem interval (PMI) estimation. The human microbiome has the potential to be used for PMI estimation and may present advantages as microbes are present in all seasons, in all habitats, including the most extreme ones, and because microbial communities respond predictably to environmental changes.}, }
@article {pmid37841330, year = {2023}, author = {Zhou, R and Ng, SK and Sung, JJY and Goh, WWB and Wong, SH}, title = {Data pre-processing for analyzing microbiome data - A mini review.}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {4804-4815}, pmid = {37841330}, issn = {2001-0370}, abstract = {The human microbiome is an emerging research frontier due to its profound impacts on health. High-throughput microbiome sequencing enables studying microbial communities but suffers from analytical challenges. In particular, the lack of dedicated preprocessing methods to improve data quality impedes effective minimization of biases prior to downstream analysis. This review aims to address this gap by providing a comprehensive overview of preprocessing techniques relevant to microbiome research. We outline a typical workflow for microbiome data analysis. Preprocessing methods discussed include quality filtering, batch effect correction, imputation of missing values, normalization, and data transformation. We highlight strengths and limitations of each technique to serve as a practical guide for researchers and identify areas needing further methodological development. Establishing robust, standardized preprocessing will be essential for drawing valid biological conclusions from microbiome studies.}, }
@article {pmid37840574, year = {2023}, author = {Jang, H and Park, S and Koh, H}, title = {Comprehensive microbiome causal mediation analysis using MiMed on user-friendly web interfaces.}, journal = {Biology methods &amp; protocols}, volume = {8}, number = {1}, pages = {bpad023}, pmid = {37840574}, issn = {2396-8923}, abstract = {It is a central goal of human microbiome studies to see the roles of the microbiome as a mediator that transmits environmental, behavioral, or medical exposures to health or disease outcomes. Yet, mediation analysis is not used as much as it should be. One reason is because of the lack of carefully planned routines, compilers, and automated computing systems for microbiome mediation analysis (MiMed) to perform a series of data processing, diversity calculation, data normalization, downstream data analysis, and visualizations. Many researchers in various disciplines (e.g. clinicians, public health practitioners, and biologists) are not also familiar with related statistical methods and programming languages on command-line interfaces. Thus, in this article, we introduce a web cloud computing platform, named as MiMed, that enables comprehensive MiMed on user-friendly web interfaces. The main features of MiMed are as follows. First, MiMed can survey the microbiome in various spheres (i) as a whole microbial ecosystem using different ecological measures (e.g. alpha- and beta-diversity indices) or (ii) as individual microbial taxa (e.g. phyla, classes, orders, families, genera, and species) using different data normalization methods. Second, MiMed enables covariate-adjusted analysis to control for potential confounding factors (e.g. age and gender), which is essential to enhance the causality of the results, especially for observational studies. Third, MiMed enables a breadth of statistical inferences in both mediation effect estimation and significance testing. Fourth, MiMed provides flexible and easy-to-use data processing and analytic modules and creates nice graphical representations. Finally, MiMed employs ChatGPT to search for what has been known about the microbial taxa that are found significantly as mediators using artificial intelligence technologies. For demonstration purposes, we applied MiMed to the study on the mediating roles of oral microbiome in subgingival niches between e-cigarette smoking and gingival inflammation. MiMed is freely available on our web server (http://mimed.micloud.kr).}, }
@article {pmid37839408, year = {2023}, author = {Frey-Furtado, L and Magalhães, I and Sampaio-Maia, B and Azevedo, MJ}, title = {Oral microbiome characterization in oral mucositis patients-A systematic review.}, journal = {Journal of oral pathology &amp; medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology}, volume = {52}, number = {10}, pages = {911-918}, doi = {10.1111/jop.13492}, pmid = {37839408}, issn = {1600-0714}, support = {SFRH/BD/144982/2019//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e a Tecnologia/ ; }, mesh = {Humans ; *Stomatitis ; *Microbiota ; *Drug-Related Side Effects and Adverse Reactions ; Candida ; Disease Progression ; }, abstract = {BACKGROUND: Oral mucositis (OM) is a severe and common adverse effect of cancer treatment. The oral microbiome appears to play a role on the onset and severity of OM. Therefore, this systematic review aims to characterize the oral dysbiosis associated with OM.<br><br>METHODS: The PRISMA checklist was followed and PubMed, Web of Science, and Scopus were screened for clinical studies characterizing the oral microbiome alterations in patients with OM.<br><br>RESULTS: From a total of 2500 articles retrieved, we included nine articles in this systematic review. Certain types of bacteria, as Fusobacterium, were recognized as predictors of the onset of OM. In addition, it was reported that patients with severe OM presented a reduction in alpha-diversity, an increase in beta-diversity. The abundance of some taxa significantly changed with OM severity, with Bacillota phylum and genera Leptotrichia, Actinomyces, and Prevotella decreasing and Treponema increasing with disease progression. Additionally, during cancer treatment, changes in the oral microbiome have been observed in OM patients, with an increase in Candida and nosocomial pathogens, including Staphylococcus species.<br><br>CONCLUSION: Our review indicates that cancer treatment can significantly alter the oral microbiome, with more pronounced changes observed in patients with severe OM in all relevant oral phyla, but more pronounced in Bacillota phylum.}, }
@article {pmid37835899, year = {2023}, author = {Man, MA and Ungur, RA and Motoc, NS and Pop, LA and Berindan-Neagoe, I and Ruta, VM}, title = {Lung Microbiota in Idiopathic Pulmonary Fibrosis, Hypersensitivity Pneumonitis, and Unclassified Interstitial Lung Diseases: A Preliminary Pilot Study.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {19}, pages = {}, pmid = {37835899}, issn = {2075-4418}, abstract = {(1) Introduction: Although historically, the lung has been considered a sterile organ, recent studies through 16S rRNA gene sequencing have identified a substantial number of microorganisms. The human microbiome has been considered an "essential organ," carrying about 150 times more information (genes) than are found in the entire human genome. The purpose of the present study is to characterize and compare the microbiome in three different interstitial lung diseases: idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, and nondifferential interstitial lung disease. (2) Material and methods: This was a prospective cohort study where the DNA of 28 patients with ILD was extracted from the lavage and then processed using the standard technique of 16S RNA gene sequencing. In a tertiary teaching hospital in the northern, western part of Romania, samples were collected through bronchoscopy and then processed. (3) Results: The same four species were found in all the patients but in different quantities and compositions: Firmicutes, Actinobacteria, Proteobacteria and Bacteroides. Streptococcus was the most prevalent genus, followed by Staphylococcus and Prevotella. Statistically significant differences in the OUT count for the ten most abundant taxa were found for the genus: Gemella, Actinobacteria, Prevotella, Neisseria, Haemophilus, and Bifidobacterium. The comparative analysis showed a richer microbiota in patients with IPF, as shown by the alpha diversity index. (4) Conclusions: In interstitial lung diseases, the microorganisms normally found in the lung are reduced to a restricted flora dominated by the Firmicutes family. These changes significantly disrupt the continuity of the observed bacterial pattern from the oropharynx to the bronchial tree and lung, possibly impacting the evolution and severity of interstitial lung diseases.}, }
@article {pmid37834423, year = {2023}, author = {Mascellino, MT}, title = {Molecular Research in Human Microbiome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {19}, pages = {}, pmid = {37834423}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; Intestines ; Inflammation ; }, abstract = {Recent evidence has shown that the human microbiome is associated with a wide range of diseases, from non-neoplastic to tumourigenesis, including cancer, inflammation, intestinal damage, etc [...].}, }
@article {pmid37833788, year = {2023}, author = {Ma, C and Yang, C and Peng, A and Sun, T and Ji, X and Mi, J and Wei, L and Shen, S and Feng, Q}, title = {Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment.}, journal = {Molecular cancer}, volume = {22}, number = {1}, pages = {170}, pmid = {37833788}, issn = {1476-4598}, mesh = {Humans ; *Cancer-Associated Fibroblasts/metabolism ; Tumor Microenvironment ; *Carcinoma/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Single-Cell Analysis ; Fibroblasts ; }, abstract = {Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population that plays a crucial role in remodeling the tumor microenvironment (TME). Here, through the integrated analysis of spatial and single-cell transcriptomics data across six common cancer types, we identified four distinct functional subgroups of CAFs and described their spatial distribution characteristics. Additionally, the analysis of single-cell RNA sequencing (scRNA-seq) data from three additional common cancer types and two newly generated scRNA-seq datasets of rare cancer types, namely epithelial-myoepithelial carcinoma (EMC) and mucoepidermoid carcinoma (MEC), expanded our understanding of CAF heterogeneity. Cell-cell interaction analysis conducted within the spatial context highlighted the pivotal roles of matrix CAFs (mCAFs) in tumor angiogenesis and inflammatory CAFs (iCAFs) in shaping the immunosuppressive microenvironment. In patients with breast cancer (BRCA) undergoing anti-PD-1 immunotherapy, iCAFs demonstrated heightened capacity in facilitating cancer cell proliferation, promoting epithelial-mesenchymal transition (EMT), and contributing to the establishment of an immunosuppressive microenvironment. Furthermore, a scoring system based on iCAFs showed a significant correlation with immune therapy response in melanoma patients. Lastly, we provided a web interface (https://chenxisd.shinyapps.io/pancaf/) for the research community to investigate CAFs in the context of pan-cancer.}, }
@article {pmid37831574, year = {2023}, author = {Koh, H}, title = {Subgroup Identification Using Virtual Twins for Human Microbiome Studies.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {20}, number = {6}, pages = {3800-3808}, doi = {10.1109/TCBB.2023.3324139}, pmid = {37831574}, issn = {1557-9964}, mesh = {Humans ; *Microbiota/genetics ; Precision Medicine ; Machine Learning ; }, abstract = {Even when the same treatment is employed, some patients are cured, while others are not. The patients that are cured may have beneficial microbes in their body that can boost treatment effects, but it is vice versa for the patients that are not cured. That is, treatment effects can vary depending on the patient's microbiome. If the effects of candidate treatments are well-predicted based on the patient's microbiome, we can select a treatment that is suited to the patient's microbiome or alter the patient's microbiome to improve treatment effects. Here, I introduce a streamlined analytic method, microbiome virtual twins (MiVT), to probe for the interplay between microbiome and treatment. MiVT employs a new prediction method, distance-based machine learning (dML), to improve prediction accuracy in microbiome studies and a new significance test, bootstrap-based test for regression tree (BoRT), to test if each subgroup's treatment effect is the same with the overall treatment effect. MiVT will serve as a useful guideline in microbiome-based personalized medicine to select the therapy that is most suited to the patient's microbiome or to tune the patient's microbiome to be suited to the treatment.}, }
@article {pmid37820693, year = {2023}, author = {Legakis, I and Chrousos, GP and Chatzipanagiotou, S}, title = {Thyroid Diseases and Intestinal Microbiome.}, journal = {Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme}, volume = {55}, number = {12}, pages = {813-818}, doi = {10.1055/a-2190-3847}, pmid = {37820693}, issn = {1439-4286}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Thyroid Diseases ; *Hashimoto Disease ; *Autoimmune Diseases ; *Thyroid Neoplasms ; }, abstract = {The human microbiome plays an integral role in health. In particular, it is important for the development, differentiation, and maturation of the immune system, 70% of which resides in the intestinal mucosa. Microbiome studies conducted to date have revealed an association between disturbances in the microbiota (dysbiosis) and various pathological disorders, including changes in host immune status. Autoimmune thyroid diseases are one of the most common organ-specific autoimmune disorders, with a worldwide prevalence higher than 5%. The predominant autoimmune thyroid diseases are Hashimoto's thyroiditis and Grave's disease. Several factors, such as genetic and environmental ones, have been studied. In accordance with recent studies, it is assumed that the gut microbiome might play a significant role in triggering autoimmune diseases of the thyroid gland. However, the exact etiology has not yet been elucidated. The present review aims to describe the work carried out so far regarding the role of gut microflora in the pathogenesis of autoimmune thyroid diseases and its involvement in the appearance of benign nodules and papillary thyroid cancer. It appears that future work is needed to elucidate more precisely the mechanism for gut microbiota involvement in the development of autoimmune thyroid diseases.}, }
@article {pmid37819042, year = {2024}, author = {Zhou, T and Xiao, L and Zuo, Z and Zhao, F}, title = {MAMI: a comprehensive database of mother-infant microbiome and probiotic resources.}, journal = {Nucleic acids research}, volume = {52}, number = {D1}, pages = {D738-D746}, pmid = {37819042}, issn = {1362-4962}, support = {2022YFA1303900//National Key R&amp;D Program of China/ ; 32001082//National Natural Science Foundation of China/ ; }, mesh = {Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; *Microbiota ; Probiotics ; Maternal-Fetal Exchange ; }, abstract = {Extensive evidence has demonstrated that the human microbiome and probiotics confer great impacts on human health, particularly during critical developmental stages such as pregnancy and infancy when microbial communities undergo remarkable changes and maturation. However, a major challenge in understanding the microbial community structure and interactions between mothers and infants lies in the current lack of comprehensive microbiome databases specifically focused on maternal and infant health. To address this gap, we have developed an extensive database called MAMI (Microbiome Atlas of Mothers and Infants) that archives data on the maternal and neonatal microbiome, as well as abundant resources on edible probiotic strains. By leveraging this resource, we can gain profound insights into the dynamics of microbial communities, contributing to lifelong wellness for both mothers and infants through precise modulation of the developing microbiota. The functionalities incorporated into MAMI provide a unique perspective on the study of the mother-infant microbiome, which not only advance microbiome-based scientific research but also enhance clinical practice. MAMI is publicly available at https://bioinfo.biols.ac.cn/mami/.}, }
@article {pmid37815708, year = {2024}, author = {Higashi, DL and Zou, Z and Qin, H and Kreth, J and Merritt, J}, title = {Employing Cloning-Independent Mutagenesis of Parvimonas micra for the Study of Cell Wall Biogenesis.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2727}, number = {}, pages = {57-67}, pmid = {37815708}, issn = {1940-6029}, support = {R01 DE029492/DE/NIDCR NIH HHS/United States ; R21 DE029612/DE/NIDCR NIH HHS/United States ; R35 DE028252/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Firmicutes/genetics ; *Microbiota ; Mutagenesis ; Cloning, Molecular ; }, abstract = {The cell wall plays an important structural role for bacteria and is intimately tied to a variety of critical processes ranging from growth and differentiation to pathogenesis. Our understanding of cell wall biogenesis is primarily derived from a relatively small number of heavily studied model organisms. Consequently, these processes can only be inferred for the vast majority of prokaryotes, especially among groups of uncharacterized and/or genetically intractable organisms. Recently, we developed the first tractable genetic system for Parvimonas micra, which is a ubiquitous Gram-positive pathobiont of the human microbiome involved in numerous types of inflammatory infections as well as a variety of malignant tumors. P. micra is also the first, and currently only, member of the entire Tissierellia class of the Bacillota phylum in which targeted genetic manipulation has been demonstrated. Thus, it is now possible to study cell wall biogenesis mechanisms within a member of the Tissierellia, which may also reveal novel aspects of P. micra pathobiology. Herein, we describe a procedure for cloning-independent genetic manipulation of P. micra, including allelic replacement mutagenesis and genetic complementation. The described techniques are also similarly applicable for the study of other aspects of P. micra pathobiology and physiology.}, }
@article {pmid37811798, year = {2023}, author = {Lohse, MB and Ziv, N and Johnson, AD}, title = {Variation in transcription regulator expression underlies differences in white-opaque switching between the SC5314 reference strain and the majority of Candida albicans clinical isolates.}, journal = {Genetics}, volume = {225}, number = {3}, pages = {}, pmid = {37811798}, issn = {1943-2631}, support = {P30 CA082103/CA/NCI NIH HHS/United States ; R01 AI049187/AI/NIAID NIH HHS/United States ; R01 AI175080/AI/NIAID NIH HHS/United States ; R01 GM037049/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Candida albicans/metabolism ; *Fungal Proteins/genetics/metabolism ; Genes, Mating Type, Fungal ; Phenotype ; Cell Communication ; Gene Expression Regulation, Fungal ; }, abstract = {Candida albicans, a normal member of the human microbiome and an opportunistic fungal pathogen, undergoes several morphological transitions. One of these transitions is white-opaque switching, where C. albicans alternates between 2 stable cell types with distinct cellular and colony morphologies, metabolic preferences, mating abilities, and interactions with the innate immune system. White-to-opaque switching is regulated by mating type; it is repressed by the a1/α2 heterodimer in a/α cells, but this repression is lifted in a/a and α/α mating type cells (each of which are missing half of the repressor). The widely used C. albicans reference strain, SC5314, is unusual in that white-opaque switching is completely blocked when the cells are a/α; in contrast, most other C. albicans a/α strains can undergo white-opaque switching at an observable level. In this paper, we uncover the reason for this difference. We show that, in addition to repression by the a1/α2 heterodimer, SC5314 contains a second block to white-opaque switching: 4 transcription regulators of filamentous growth are upregulated in this strain and collectively suppress white-opaque switching. This second block is missing in the majority of clinical strains, and, although they still contain the a1/α2 heterodimer repressor, they exhibit a/α white-opaque switching at an observable level. When both blocks are absent, white-opaque switching occurs at very high levels. This work shows that white-opaque switching remains intact across a broad group of clinical strains, but the precise way it is regulated and therefore the frequency at which it occurs varies from strain to strain.}, }
@article {pmid37808321, year = {2023}, author = {D'Elia, D and Truu, J and Lahti, L and Berland, M and Papoutsoglou, G and Ceci, M and Zomer, A and Lopes, MB and Ibrahimi, E and Gruca, A and Nechyporenko, A and Frohme, M and Klammsteiner, T and Pau, ECS and Marcos-Zambrano, LJ and Hron, K and Pio, G and Simeon, A and Suharoschi, R and Moreno-Indias, I and Temko, A and Nedyalkova, M and Apostol, ES and Truică, CO and Shigdel, R and Telalović, JH and Bongcam-Rudloff, E and Przymus, P and Jordamović, NB and Falquet, L and Tarazona, S and Sampri, A and Isola, G and Pérez-Serrano, D and Trajkovik, V and Klucar, L and Loncar-Turukalo, T and Havulinna, AS and Jansen, C and Bertelsen, RJ and Claesson, MJ}, title = {Advancing microbiome research with machine learning: key findings from the ML4Microbiome COST action.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1257002}, pmid = {37808321}, issn = {1664-302X}, abstract = {The rapid development of machine learning (ML) techniques has opened up the data-dense field of microbiome research for novel therapeutic, diagnostic, and prognostic applications targeting a wide range of disorders, which could substantially improve healthcare practices in the era of precision medicine. However, several challenges must be addressed to exploit the benefits of ML in this field fully. In particular, there is a need to establish "gold standard" protocols for conducting ML analysis experiments and improve interactions between microbiome researchers and ML experts. The Machine Learning Techniques in Human Microbiome Studies (ML4Microbiome) COST Action CA18131 is a European network established in 2019 to promote collaboration between discovery-oriented microbiome researchers and data-driven ML experts to optimize and standardize ML approaches for microbiome analysis. This perspective paper presents the key achievements of ML4Microbiome, which include identifying predictive and discriminatory 'omics' features, improving repeatability and comparability, developing automation procedures, and defining priority areas for the novel development of ML methods targeting the microbiome. The insights gained from ML4Microbiome will help to maximize the potential of ML in microbiome research and pave the way for new and improved healthcare practices.}, }
@article {pmid37806533, year = {2024}, author = {McGuinness, AJ and Stinson, LF and Snelson, M and Loughman, A and Stringer, A and Hannan, AJ and Cowan, CSM and Jama, HA and Caparros-Martin, JA and West, ML and Wardill, HR and , }, title = {From hype to hope: Considerations in conducting robust microbiome science.}, journal = {Brain, behavior, and immunity}, volume = {115}, number = {}, pages = {120-130}, doi = {10.1016/j.bbi.2023.09.022}, pmid = {37806533}, issn = {1090-2139}, mesh = {Humans ; Reproducibility of Results ; *Microbiota ; Machine Learning ; }, abstract = {Microbiome science has been one of the most exciting and rapidly evolving research fields in the past two decades. Breakthroughs in technologies including DNA sequencing have meant that the trillions of microbes (particularly bacteria) inhabiting human biological niches (particularly the gut) can be profiled and analysed in exquisite detail. This microbiome profiling has profound impacts across many fields of research, especially biomedical science, with implications for how we understand and ultimately treat a wide range of human disorders. However, like many great scientific frontiers in human history, the pioneering nature of microbiome research comes with a multitude of challenges and potential pitfalls. These include the reproducibility and robustness of microbiome science, especially in its applications to human health outcomes. In this article, we address the enormous promise of microbiome science and its many challenges, proposing constructive solutions to enhance the reproducibility and robustness of research in this nascent field. The optimisation of microbiome science spans research design, implementation and analysis, and we discuss specific aspects such as the importance of ecological principals and functionality, challenges with microbiome-modulating therapies and the consideration of confounding, alternative options for microbiome sequencing, and the potential of machine learning and computational science to advance the field. The power of microbiome science promises to revolutionise our understanding of many diseases and provide new approaches to prevention, early diagnosis, and treatment.}, }
@article {pmid37800929, year = {2023}, author = {Hisatomi, A and Tourlousse, DM and Hamajima, M and Ohkuma, M and Sekiguchi, Y and Sakamoto, M}, title = {Complete genome sequences of Ruminococcus torques strains JCM 36208 and JCM 36209, isolated from the feces of a healthy Japanese male.}, journal = {Microbiology resource announcements}, volume = {12}, number = {11}, pages = {e0063223}, pmid = {37800929}, issn = {2576-098X}, support = {JP22ae0121035//Japan Agency for Medical Research and Development (AMED)/ ; }, abstract = {Here, we report the complete genome sequences of two Ruminococcus torques strains (JCM 36208 and JCM 36209) that were newly isolated from the feces of a healthy Japanese male. Both genomes consist of a single circular chromosome with a length of ~2.8 Mbp and a G+C content of 41.8%.}, }
@article {pmid37797477, year = {2023}, author = {Ückert, AK and Rütschlin, S and Gutbier, S and Wörz, NC and Miah, MR and Martins, AC and Hauer, I and Holzer, AK and Meyburg, B and Mix, AK and Hauck, C and Aschner, M and Böttcher, T and Leist, M}, title = {Identification of the bacterial metabolite aerugine as potential trigger of human dopaminergic neurodegeneration.}, journal = {Environment international}, volume = {180}, number = {}, pages = {108229}, pmid = {37797477}, issn = {1873-6750}, support = {R01 ES007331/ES/NIEHS NIH HHS/United States ; R01 ES010563/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Caenorhabditis elegans/metabolism ; Animals, Genetically Modified ; *Parkinson Disease ; Antioxidants/metabolism ; Neurons ; }, abstract = {The causes of nigrostriatal cell death in idiopathic Parkinson's disease are unknown, but exposure to toxic chemicals may play some role. We followed up here on suggestions that bacterial secondary metabolites might be selectively cytotoxic to dopaminergic neurons. Extracts from Streptomyces venezuelae were found to kill human dopaminergic neurons (LUHMES cells). Utilizing this model system as a bioassay, we identified a bacterial metabolite known as aerugine (C10H11NO2S; 2-[4-(hydroxymethyl)-4,5-dihydro-1,3-thiazol-2-yl]phenol) and confirmed this finding by chemical re-synthesis. This 2-hydroxyphenyl-thiazoline compound was previously shown to be a product of a wide-spread biosynthetic cluster also found in the human microbiome and in several pathogens. Aerugine triggered half-maximal dopaminergic neurotoxicity at 3-4 µM. It was less toxic for other neurons (10-20 µM), and non-toxic (at <100 µM) for common human cell lines. Neurotoxicity was completely prevented by several iron chelators, by distinct anti-oxidants and by a caspase inhibitor. In the Caenorhabditis elegans model organism, general survival was not affected by aerugine concentrations up to 100 µM. When transgenic worms, expressing green fluorescent protein only in their dopamine neurons, were exposed to aerugine, specific neurodegeneration was observed. The toxicant also exerted functional dopaminergic toxicity in nematodes as determined by the "basal slowing response" assay. Thus, our research has unveiled a bacterial metabolite with a remarkably selective toxicity toward human dopaminergic neurons in vitro and for the dopaminergic nervous system of Caenorhabditis elegans in vivo. These findings suggest that microbe-derived environmental chemicals should be further investigated for their role in the pathogenesis of Parkinson's disease.}, }
@article {pmid37792894, year = {2023}, author = {Pompei, S and Bella, E and Weitz, JS and Grilli, J and Lagomarsino, MC}, title = {Metacommunity structure preserves genome diversity in the presence of gene-specific selective sweeps under moderate rates of horizontal gene transfer.}, journal = {PLoS computational biology}, volume = {19}, number = {10}, pages = {e1011532}, pmid = {37792894}, issn = {1553-7358}, mesh = {Humans ; *Gene Transfer, Horizontal/genetics ; *Bacteria/genetics ; Biological Evolution ; Genome ; }, abstract = {The horizontal transfer of genes is fundamental for the eco-evolutionary dynamics of microbial communities, such as oceanic plankton, soil, and the human microbiome. In the case of an acquired beneficial gene, classic population genetics would predict a genome-wide selective sweep, whereby the genome spreads clonally within the community and together with the beneficial gene, removing genome diversity. Instead, several sources of metagenomic data show the existence of "gene-specific sweeps", whereby a beneficial gene spreads across a bacterial community, maintaining genome diversity. Several hypotheses have been proposed to explain this process, including the decreasing gene flow between ecologically distant populations, frequency-dependent selection from linked deleterious allelles, and very high rates of horizontal gene transfer. Here, we propose an additional possible scenario grounded in eco-evolutionary principles. Specifically, we show by a mathematical model and simulations that a metacommunity where species can occupy multiple patches, acting together with a realistic (moderate) HGT rate, helps maintain genome diversity. Assuming a scenario of patches dominated by single species, our model predicts that diversity only decreases moderately upon the arrival of a new beneficial gene, and that losses in diversity can be quickly restored. We explore the generic behaviour of diversity as a function of three key parameters, frequency of insertion of new beneficial genes, migration rates and horizontal transfer rates.Our results provides a testable explanation for how diversity can be maintained by gene-specific sweeps even in the absence of high horizontal gene transfer rates.}, }
@article {pmid37791672, year = {2023}, author = {Shittu, AR and Iwaloye, OF and Ojewole, AE and Rabiu, AG and Amechi, MO and Herve, OF}, title = {The effects of per- and polyfluoroalkyl substances on environmental and human microorganisms and their potential for bioremediation.}, journal = {Arhiv za higijenu rada i toksikologiju}, volume = {74}, number = {3}, pages = {167-178}, pmid = {37791672}, issn = {1848-6312}, mesh = {Humans ; Biodegradation, Environmental ; *Drug Contamination ; Escherichia coli ; Soil ; *Fluorocarbons/toxicity ; }, abstract = {Utilised in a variety of consumer products, per- and polyfluoroalkyl substances (PFAS) are major environmental contaminants that accumulate in living organisms due to their highly hydrophobic, lipophobic, heat-resistant, and non-biodegradable properties. This review summarizes their effects on microbial populations in soils, aquatic and biogeochemical systems, and the human microbiome. Specific microbes are insensitive to and even thrive with PFAS contamination, such as Escherichia coli and the Proteobacteria in soil and aquatic environments, while some bacterial species, such as Actinobacteria and Chloroflexi, are sensitive and drop in population. Some bacterial species, in turn, have shown success in PFAS bioremediation, such as Acidimicrobium sp. and Pseudomonas parafulva.}, }
@article {pmid37790536, year = {2023}, author = {Wakade, RS and Krysan, DJ}, title = {Comparative dynamics of gene expression during in vitro and in vivo Candida albicans filamentation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37790536}, issn = {2692-8205}, support = {R01 AI133409/AI/NIAID NIH HHS/United States ; }, abstract = {Candida albicans is one of them most common causes of fungal disease in humans and is a commensal member of the human microbiome. The ability of C. albicans to cause disease is tightly correlated with its ability to undergo a morphological transition from budding yeast to a filamentous form (hyphae and pseudohyphae). This morphological transition is accompanied by the induction of a set of well characterized hyphae-associated genes and transcriptional regulators. To date, the vast majority of data regarding this process has been based on in vitro studies of filamentation using a range of inducing conditions. Recently, we developed an in vivo imaging approach that allows the direct characterization of morphological transition during mammalian infection. Here, we couple this imaging assay with in vivo expression profiling to characterize the time course of in vivo filamentation and the accompanying changes in gene expression. We also compare in vivo observations to in vitro filamentation using a medium (RPMI 1640 tissue culture medium with 10% bovine calf serum) widely used to mimic host conditions. From these data, we make the following conclusions regarding in vivo and in vitro filamentation. First, the transcriptional programs regulating filamentation are rapidly induced in vitro and in vivo. Second, the tempo of filamentation in vivo is prolonged relative to in vitro filamentation and the period of high expression of genes associated with that process is also prolonged. Third, hyphae are adapting to changing infection environments after filamentation has reached steady-state.}, }
@article {pmid37786407, year = {2023}, author = {Pietilä, JP and Häkkinen, TA and Pakarinen, L and Ollgren, J and Kantele, A}, title = {Treatment of Dientamoeba fragilis: A retrospective Finnish analysis of faecal clearance and clinical cure comparing four antiprotozoal drugs.}, journal = {New microbes and new infections}, volume = {54}, number = {}, pages = {101179}, pmid = {37786407}, issn = {2052-2975}, abstract = {BACKGROUND: Dientamoeba fragilis (DF), the most common intestinal protozoal pathogen in affluent countries, causes asymptomatic or symptomatic infections with severity ranging from mild to disabling. Currently, many studies of treatment options only have small sample sizes and report results that are partly contradictory.<br><br>METHODS: Investigating data retrieved from Helsinki University Hospital and Helsinki City patient records, we searched for the most effective antiprotozoal in treating DF infections. To study microbiological clearance of DF, we collected laboratory results of control samples from patients given one of four commonly used antiprotozoals: doxycycline, metronidazole, paromomycin, or secnidazole. For patients symptomatic prior to antiprotozoal treatment, we also retrieved data on clinical outcomes. Furthermore, we explored factors associated with faecal clearance and clinical cure.<br><br>RESULTS: A total of 369 patients (median age 38) and 492 treatment episodes were included. Paromomycin (n&#xa0;&#x200b;=&#xa0;&#x200b;297) proved effective (clearance rate 83%), showing strong association with faecal clearance (aOR 18.08 [7.24-45.16], p&#xa0;&#x200b;<&#xa0;&#x200b;0.001). For metronidazole the rate was 42% (n&#xa0;&#x200b;=&#xa0;&#x200b;84), for secnidazole 37% (n&#xa0;&#x200b;=&#xa0;&#x200b;79), and doxycycline 22% (n&#xa0;&#x200b;=&#xa0;&#x200b;32). In pairwise comparisons, paromomycin outdid the three other regimens (p&#xa0;&#x200b;<&#xa0;&#x200b;0.001, &#x3c7;[2] test). Faecal clearance was associated with clinical cure (aOR 5.85 [3.02-11.32], p&#xa0;&#x200b;<&#xa0;&#x200b;0.001).<br><br>CONCLUSIONS: Faecal clearance, strongly associated with clinical cure, is most effectively achieved with a course of paromomycin, followed by metronidazole, secnidazole and doxycycline. Our findings will be useful in devising treatment guidelines for adults with symptomatic D.&#xa0;fragilis infection.}, }
@article {pmid37781374, year = {2023}, author = {Zhang, J and Deng, J and Li, J and Su, Y and Hu, J and Lin, D and Su, M and Chen, Y and Liao, S and Bai, X and Lv, M and Xu, T and Zhong, Q and Guo, X}, title = {Changes of gut microbiota under different nutritional methods in elderly patients with severe COVID-19 and their relationship with prognosis.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1260112}, pmid = {37781374}, issn = {1664-3224}, mesh = {Humans ; Aged ; *Gastrointestinal Microbiome ; *COVID-19/therapy ; SARS-CoV-2 ; Prognosis ; Parenteral Nutrition/methods ; }, abstract = {BACKGROUND: The clinical progression of individuals afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits significant heterogeneity, particularly affecting the elderly population to a greater extent. Consequently, the association between nutrition and microbiota has garnered considerable interest. Hence, the objective of this study was to gather clinical data pertaining to the influence of diverse nutritional support interventions on the prognosis of geriatric patients with COVID-19, while additionally examining the fecal microbiota of these individuals to assess the repercussions of microecological alterations on their prognostic outcomes.<br><br>RESULTS: A total of 71 elderly patients diagnosed with severe COVID-19 were included in this study. These patients were subsequently divided into two groups, namely the enteral nutrition (EN) group and the parenteral nutrition (PN) group, based on the type of nutritional support therapy they received after admission. The occurrence of complications was observed in 10.4% of patients in the EN group, whereas it was significantly higher at 69.6% in the PN group (P<0.001). Furthermore, the 60-day mortality rate was 2.1% (1/48) in the EN group, while it was notably higher at 30.4% (7/23) in the PN group (P=0.001). To identify the independent predictors of 60-day mortality, stepwise logistic regression analysis was employed. Among different bacterial groups, Enterococcus_faecium (18.19%) and Pseudomonas_aeruginosa (1.91%) had higher average relative abundance in the PN group (P<0.05). However, the relative abundance of Ruminococcus was higher in the EN group. Further Spearman correlation analysis showed that Enterococcus_faecium was positively correlated with poor clinical prognosis, while Ruminococcus was negatively correlated with poor clinical prognosis.<br><br>CONCLUSIONS: This study shows that the changes in the composition of intestinal flora in elderly COVID-19 patients receiving different nutritional support strategies may be related to different clinical outcomes. The abundance of Enterococcus_faecium in elderly COVID-19 patients receiving PN is significantly increased and is closely related to poor clinical outcomes. It highlights the potential of microbiome-centric interventions to mitigate and manage COVID-19 in older adults with different nutritional support options.}, }
@article {pmid37776987, year = {2023}, author = {Liu, S and Zhang, S and Guo, M and Lei, Q and He, L and Li, Z}, title = {Acoustic stimulation during sleep improves cognition and ameliorates Alzheimer's disease pathology in APP/PS1 mice.}, journal = {Experimental gerontology}, volume = {182}, number = {}, pages = {112299}, doi = {10.1016/j.exger.2023.112299}, pmid = {37776987}, issn = {1873-6815}, abstract = {Nonpharmacological therapies for Alzheimer's disease (AD) have become a popular research topic, and acoustic stimulation during sleep is one such promising strategy for the clinical treatment of AD. Some animal experiments have illustrated that acoustic stimulation at a specific frequency can ameliorate AD-related pathology or improve cognition in mice, but these studies did not explore the effective time window of auditory stimulation. Here, we explored the effects of acoustic stimulation during wakefulness and acoustic stimulation during sleep on cognition and AD-related pathology in APP/PS1 mice and the underlying mechanisms. In this study, forty APP/PS1 mice were equally divided into the following 4 groups and treated for 28 days: the chronic sleep deprivation (CSD) group (exposed to sleep deprivation from zeitgeber time [ZT] 0 to ZT 12 each day), the normal sleep and stress exposure (NSS) group (exposed to a stressor from ZT 0 to ZT 12 each day), the acoustic stimulation during wakefulness (ASW) group (exposed to sleep deprivation and 40 Hz acoustic stimulation from ZT 0 to ZT 12 each day) and the acoustic stimulation during sleep (ASS) group (exposed to sleep deprivation from ZT 0 to ZT 12 and 40 Hz acoustic stimulation from ZT 12 to ZT 24 each day). After the intervention, cognition was assessed by behavioural experiments. The amyloid-β burden was analysed by Western blotting, immunofluorescence and enzyme-linked immunosorbent assay. Tau pathology was assessed by Western blotting. Mitochondrial function was evaluated by transmission electron microscopy, Western blotting and fluorescence intensity measurement. We found that the NSS and ASS groups had better cognitive functions than the CSD and ASW groups. The Aβ burden and tau phosphorylation were lower in the NSS and ASS groups than in the CSD and ASW groups. Mitochondrial function was better in the NSS and ASS groups than in the CSD and ASW groups. However, the differences in these parameters between the NSS and ASS groups and between the CSD and ASW groups were not significant. Our findings suggest that acoustic stimulation at a specific frequency during sleep, but not during wakefulness, reduces the amyloid-β burden by inhibiting amyloid beta precursor protein-binding protein 2, hinders tau phosphorylation by blocking glycogen synthase kinase 3 beta, and restores mitochondrial function by elevating mitophagy and promoting mitochondrial biogenesis.}, }
@article {pmid37770743, year = {2023}, author = {Bader, AC and Van Zuylen, EM and Handsley-Davis, M and Alegado, RA and Benezra, A and Pollet, RM and Ehau-Taumaunu, H and Weyrich, LS and Anderson, MZ}, title = {A relational framework for microbiome research with Indigenous communities.}, journal = {Nature microbiology}, volume = {8}, number = {10}, pages = {1768-1776}, pmid = {37770743}, issn = {2058-5276}, mesh = {Humans ; *Population Groups ; *Microbiota ; }, abstract = {Ethical practices in human microbiome research have failed to keep pace with scientific advances in the field. Researchers seeking to 'preserve' microbial species associated with Indigenous groups, but absent from industrialized populations, have largely failed to include Indigenous people in knowledge co-production or benefit, perpetuating a legacy of intellectual and material extraction. We propose a framework centred on relationality among Indigenous peoples, researchers and microbes, to guide ethical microbiome research. Our framework centres accountability to flatten historical power imbalances that favour researcher perspectives and interests to provide space for Indigenous worldviews in pursuit of Indigenous research sovereignty. Ethical inclusion of Indigenous communities in microbiome research can provide health benefits for all populations and reinforce mutually beneficial partnerships between researchers and the public.}, }
@article {pmid37764046, year = {2023}, author = {Efremova, I and Maslennikov, R and Poluektova, E and Zharkova, M and Kudryavtseva, A and Krasnov, G and Fedorova, M and Shirokova, E and Kozlov, E and Levshina, A and Ivashkin, V}, title = {Gut Dysbiosis and Hemodynamic Changes as Links of the Pathogenesis of Complications of Cirrhosis.}, journal = {Microorganisms}, volume = {11}, number = {9}, pages = {}, pmid = {37764046}, issn = {2076-2607}, support = {National Research Grant Russia 2019//Biocodex (France)/ ; }, abstract = {The aim was to evaluate the relationship between gut dysbiosis and hemodynamic changes (hyperdynamic circulation) in cirrhosis, and between hemodynamic changes and complications of this disease. This study included 47 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Echocardiography with a simultaneous assessment of blood pressure and heart rate was performed to assess systemic hemodynamics. Patients with hyperdynamic circulation had more severe cirrhosis, lower albumin, sodium and prothrombin levels, higher C-reactive protein, aspartate aminotransferase and total bilirubin levels, and higher incidences of portopulmonary hypertension, ascites, overt hepatic encephalopathy, hypoalbuminemia, hypoprothrombinemia, systemic inflammation, and severe hyperbilirubinemia than patients with normodynamic circulation. Patients with hyperdynamic circulation compared with those with normodynamic circulation had increased abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Fusobacteria, Micrococcaceae, Intestinobacter, Clostridium sensu stricto, Proteus and Rumicoccus, and decreased abundance of Bacteroidetes, Bacteroidaceae, Holdemanella, and Butyrivibrio. The systemic vascular resistance and cardiac output values correlated with the abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Micrococcaceae, and Fusobacteria. Heart rate and cardiac output value were negatively correlated with the abundance of Bacteroidetes. The mean pulmonary artery pressure value was positively correlated with the abundance of Proteobacteria and Micrococcaceae, and negatively with the abundance of Holdemanella.}, }
@article {pmid37763004, year = {2023}, author = {Kovaleva, A and Poluektova, E and Maslennikov, R and Karchevskaya, A and Shifrin, O and Kiryukhin, A and Tertychnyy, A and Kovalev, L and Kovaleva, M and Lobanova, O and Kudryavtseva, A and Krasnov, G and Fedorova, M and Ivashkin, V}, title = {Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial.}, journal = {Journal of clinical medicine}, volume = {12}, number = {18}, pages = {}, pmid = {37763004}, issn = {2077-0383}, abstract = {Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine.}, }
@article {pmid37762089, year = {2023}, author = {Mousa, WK and Mousa, S and Ghemrawi, R and Obaid, D and Sarfraz, M and Chehadeh, F and Husband, S}, title = {Probiotics Modulate Host Immune Response and Interact with the Gut Microbiota: Shaping Their Composition and Mediating Antibiotic Resistance.}, journal = {International journal of molecular sciences}, volume = {24}, number = {18}, pages = {}, pmid = {37762089}, issn = {1422-0067}, support = {Ph2022-3-100//Al Ain University of Science and Technology/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Caco-2 Cells ; Drug Resistance, Microbial ; Anti-Bacterial Agents/pharmacology ; Immunity ; }, abstract = {The consortium of microbes inhabiting the human body, together with their encoded genes and secreted metabolites, is referred to as the "human microbiome." Several studies have established a link between the composition of the microbiome and its impact on human health. This impact spans local gastrointestinal inflammation to systemic autoimmune disorders and neurodegenerative diseases such as Alzheimer's and Autism. Some of these links have been validated by rigorous experiments that identify specific strains as mediators or drivers of a particular condition. Consequently, the development of probiotics to compensate for a missing beneficial microbe(s) has advanced and become popular, especially in the treatment of irritable bowel diseases and to restore disrupted gut flora after antibiotic administration. The widespread use of probiotics is often advocated as a natural ecological therapy. However, this perception is not always accurate, as there is a potential for unexpected interactions when administering live microbial cultures. Here, we designed this research to explore the intricate interactions among probiotics, the host, and microbes through a series of experiments. Our objectives included assessing their immunomodulatory effects, response to oral medications, impact on microbial population dynamics, and mediation of antibiotic resistance. To achieve these goals, we employed diverse experimental protocols, including cell-based enzyme -linked immunosorbent assay (ELISA), antibiotic susceptibility testing, antimicrobial activity assays, computational prediction of probiotic genes responsible for antibiotic resistance, polymerase chain reaction (PCR)-based validation of predicted genes, and survival assays of probiotics in the presence of selected oral medications. Our findings highlight that more than half of the tested probiotics trigger an inflammatory response in the Caco-2 cell line, are influenced by oral medications, exhibit antibacterial activity, and possess genes encoding antimicrobial resistance. These results underscore the necessity for a reevaluation of probiotic usage and emphasize the importance of establishing regulations to govern probiotic testing, approval, and administration.}, }
@article {pmid37757827, year = {2023}, author = {Blaustein, RA and Shen, Z and Kashaf, SS and Lee-Lin, S and Conlan, S and ,  and Bosticardo, M and Delmonte, OM and Holmes, CJ and Taylor, ME and Banania, G and Nagao, K and Dimitrova, D and Kanakry, JA and Su, H and Holland, SM and Bergerson, JRE and Freeman, AF and Notarangelo, LD and Kong, HH and Segre, JA}, title = {Expanded microbiome niches of RAG-deficient patients.}, journal = {Cell reports. Medicine}, volume = {4}, number = {10}, pages = {101205}, pmid = {37757827}, issn = {2666-3791}, support = {T32 HD007009/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Skin ; Metagenome ; }, abstract = {The complex interplay between microbiota and immunity is important to human health. To explore how altered adaptive immunity influences the microbiome, we characterize skin, nares, and gut microbiota of patients with recombination-activating gene (RAG) deficiency-a rare genetically defined inborn error of immunity (IEI) that results in a broad spectrum of clinical phenotypes. Integrating de novo assembly of metagenomes from RAG-deficient patients with reference genome catalogs provides an expansive multi-kingdom view of microbial diversity. RAG-deficient patient microbiomes exhibit inter-individual variation, including expansion of opportunistic pathogens (e.g., Corynebacterium bovis, Haemophilus influenzae), and a relative loss of body site specificity. We identify 35 and 27 bacterial species derived from skin/nares and gut microbiomes, respectively, which are distinct to RAG-deficient patients compared to healthy individuals. Underscoring IEI patients as potential reservoirs for viral persistence and evolution, we further characterize the colonization of eukaryotic RNA viruses (e.g., Coronavirus 229E, Norovirus GII) in this patient population.}, }
@article {pmid37754546, year = {2023}, author = {Walker, JN and Hanson, BM and Hunter, T and Simar, SR and Duran Ramirez, JM and Obernuefemann, CLP and Parikh, RP and Tenenbaum, MM and Margenthaler, JA and Hultgren, SJ and Myckatyn, TM}, title = {A prospective randomized clinical trial to assess antibiotic pocket irrigation on tissue expander breast reconstruction.}, journal = {Microbiology spectrum}, volume = {11}, number = {5}, pages = {e0143023}, pmid = {37754546}, issn = {2165-0497}, support = {R01 DK051406/DK/NIDDK NIH HHS/United States ; }, abstract = {Bacterial infection is the most common complication following staged post-mastectomy breast reconstruction initiated with a tissue expander (TE). To limit bacterial infection, antibiotic irrigation of the surgical site is commonly performed despite little high-quality data to support this practice. We performed a prospective randomized control trial to compare the impact of saline irrigation alone to a triple antibiotic irrigation regimen (1 g cefazolin, 80 mg gentamicin, and 50,000 units of bacitracin in 500 mL of saline) for breast implant surgery. The microbiome in breasts with cancer (n = 16) was compared to those without (n = 16), as all patients (n = 16) had unilateral cancers but bilateral mastectomies (n = 32). Biologic and prosthetic specimens procured both at the time of mastectomy and during TE removal months later were analyzed for longitudinal comparison. Outcomes included clinical infection, bacterial abundance, and relative microbiome composition. No patient in either group suffered a reconstructive failure or developed an infection. Triple antibiotic irrigation administered at the time of immediate TE reconstruction did not reduce bacterial abundance or impact microbial diversity relative to saline irrigation at the time of planned exchange. Implanted prosthetic material adopted the microbial composition of the surrounding host tissue. In cancer-naïve breasts, relative to saline, antibiotic irrigation increased bacterial abundance on periprosthetic capsules (P = 0.03) and acellular dermal matrices (P = 0.04) and altered the microbiota on both. These data show that, relative to saline only, the use of triple antibiotic irrigation in TE breast reconstruction does impact the bacterial abundance and diversity of certain biomaterials from cancer-naïve breasts. IMPORTANCE The lifetime risk of breast cancer is ~13% in women and is treated with a mastectomy in ~50% of cases. The majority are reconstructed, usually starting with a tissue expander to help restore the volume for a subsequent permanent breast implant or the women's own tissues. The biopsychosocial benefits of breast reconstruction, though, can be tempered by a high complication rate of at least 7% but over 30% in some women. Bacterial infection is the most common complication, and can lead to treatment delays, patient physical and emotional distress and escalating health care cost. To limit this risk, plastic surgeons have tried a variety of strategies to limit bacterial infection including irrigating the pocket created after removing the breast implant with antibiotic solutions, but good-quality data are scarce. Herein, we study the value of antibiotics in pocket irrigation using a robust randomized clinical trial design and molecular microbiology approaches.}, }
@article {pmid37753524, year = {2023}, author = {Ejtahed, HS and Parsa, M and Larijani, B}, title = {Ethical challenges in conducting and the clinical application of human microbiome research.}, journal = {Journal of medical ethics and history of medicine}, volume = {16}, number = {}, pages = {5}, pmid = {37753524}, issn = {2008-0387}, }
@article {pmid37751622, year = {2023}, author = {Hyvönen, S and Tapiainen, T and Pokka, T and Solasaari, T and Korpela, K and de Vos, WM and Salonen, A and Kolho, KL}, title = {Perinatal and Other Risk Factors for Common Infections in Infancy: A Prospective Cohort Study.}, journal = {The Pediatric infectious disease journal}, volume = {42}, number = {12}, pages = {e447-e453}, pmid = {37751622}, issn = {1532-0987}, mesh = {Child ; Infant ; Pregnancy ; Male ; Humans ; Female ; *Cesarean Section/adverse effects ; Cohort Studies ; Prospective Studies ; Risk Factors ; Anti-Bacterial Agents/therapeutic use ; *Urinary Tract Infections/epidemiology/etiology ; }, abstract = {OBJECTIVE: Limited data from prospective cohort studies in high-income countries are available on the perinatal risk factors for common infections in children. Our hypothesis was that perinatal factors may be risk factors for infectious episodes during the first year of life.<br><br>METHODS: In this prospective Health and Early Life Microbiota birth cohort study of full-term infants (n = 1052) born in 2016-2018, the number and duration of infection episodes were collected online at weekly to monthly intervals. In a multivariate regression model, the main exposures were perinatal factors such as mode of delivery and intrapartum antibiotics. Environmental factors were additional exposures. The outcomes were the number and duration of infectious episodes in the first year of life.<br><br>RESULTS: The mean number of infection episodes was 4.2 (2.9 SD). The mean duration of infection symptoms was 44 days (40 SD). Upper respiratory infections accounted for 83% of the episodes (3674/4455). Perinatal factors were not associated with the number nor the duration of infection episodes, but cesarean section was associated with an increased occurrence of urinary tract infections in infancy [adjusted odds ratio (aOR): 3.6; 95% confidence interval (CI): 1.13-11.1]. Of the additional exposures male sex (aOR: 1.1; 95% CI: 1.0-1.2) and the presence of siblings (aOR: 1.3; 95% CI: 1.2-1.4) were associated with the number of infection episodes.<br><br>CONCLUSIONS: This prospective cohort study showed that perinatal factors, mode of delivery and intrapartum antibiotics were not associated with the risk of common infections in infancy, but cesarean delivery was associated with a risk of urinary tract infections.}, }
@article {pmid37750731, year = {2023}, author = {Roche, CE and Montague, MJ and Wang, J and Dickey, AN and Ruiz-Lambides, A and Brent, LJN and Platt, ML and Horvath, JE}, title = {Yearly variation coupled with social interactions shape the skin microbiome in free-ranging rhesus macaques.}, journal = {Microbiology spectrum}, volume = {11}, number = {5}, pages = {e0297423}, pmid = {37750731}, issn = {2165-0497}, support = {R01 MH089484/MH/NIMH NIH HHS/United States ; R01 MH118203/MH/NIMH NIH HHS/United States ; P40 OD012217/OD/NIH HHS/United States ; C06 OD026690/OD/NIH HHS/United States ; R01 MH096875/MH/NIMH NIH HHS/United States ; }, abstract = {While skin microbes are known to mediate human health and disease, there has been minimal research on the interactions between skin microbiota, social behavior, and year-to-year effects in non-human primates-important animal models for translational biomedical research. To examine these relationships, we analyzed skin microbes from 78 rhesus macaques living on Cayo Santiago Island, Puerto Rico. We considered age, sex, and social group membership, and characterized social behavior by assessing dominance rank and patterns of grooming as compared to nonsocial behaviors. To measure the effects of a shifting environment, we sampled skin microbiota (based on sequence analysis of the 16S rRNA V4 region) and assessed weather across sampling periods between 2013 and 2015. We hypothesized that, first, monkeys with similar social behavior and/or in the same social group would possess similar skin microbial composition due, in part, to physical contact, and, second, microbial diversity would differ across sampling periods. We found significant phylum-level differences between social groups in the core microbiome as well as an association between total grooming rates and alpha diversity in the complete microbiome, but no association between microbial diversity and measures of rank or other nonsocial behaviors. We also identified alpha and beta diversity differences in microbiota and differential taxa abundance across two sampling periods. Our findings indicate that social dynamics interact with yearly environmental changes to shape the skin microbiota in rhesus macaques, with potential implications for understanding the factors affecting the microbiome in humans, which share many biological and social characteristics with these animals. IMPORTANCE Primate studies are valuable for translational and evolutionary insights into the human microbiome. The majority of primate microbiome studies focus on the gut, so less is known about the factors impacting the microbes on skin and how their links affect health and behavior. Here, we probe the impact of social interactions and the yearly environmental changes on food-provisioned, free-ranging monkeys living on a small island. We expected animals that lived together and groomed each other would have more similar microbes on their skin, but surprisingly found that the external environment was a stronger influence on skin microbiome composition. These findings have implications for our understanding of the human skin microbiome, including potential manipulations to improve health and treat disease.}, }
@article {pmid37746792, year = {2023}, author = {Fiocchi, A and Monaci, L and De Angelis, E and Calandrelli, V and Dahdah, L and Valluzzi, R and Urbani, S and Mazzuca, C and Arasi, S and Cafarotti, A and Riccardi, C and Artesani, MC and Putignani, L and Pecora, V and Marzano, V and Fierro, V}, title = {Reactivity to allergenic food contaminants: A study on products on the market.}, journal = {Clinical and translational allergy}, volume = {13}, number = {9}, pages = {e12301}, pmid = {37746792}, issn = {2045-7022}, support = {n.a.//Soremartec Italia S.R.L., Alba, Italy/ ; n.a.//Allegria ONLUS, Milan, Italy/ ; }, abstract = {BACKGROUND: The frequency and severity of reactions in food-allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre-packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%-5% of the population could react (ED01-ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen-free pre-packaged products by children affected by severe allergies to milk and hazelnuts.<br><br>METHODS: Oral Food Challenges with commercially available hazelnut-free wafer biscuits and milk-free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry.<br><br>RESULTS: No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35&#xa0;mg total protein/kg food. In our dose model, these amounts exceeded 1.5-10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation.<br><br>CONCLUSIONS: Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses.}, }
@article {pmid37741805, year = {2023}, author = {Wicaksono, WA and Cernava, T and Wassermann, B and Abdelfattah, A and Soto-Giron, MJ and Toledo, GV and Virtanen, SM and Knip, M and Hyöty, H and Berg, G}, title = {The edible plant microbiome: evidence for the occurrence of fruit and vegetable bacteria in the human gut.}, journal = {Gut microbes}, volume = {15}, number = {2}, pages = {2258565}, pmid = {37741805}, issn = {1949-0984}, mesh = {Humans ; Vegetables ; Plants, Edible ; Fruit ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Bacteria/genetics ; }, abstract = {Diversity of the gut microbiota is crucial for human health. However, whether fruit and vegetable associated bacteria contribute to overall gut bacterial diversity is still unknown. We reconstructed metagenome-assembled genomes from 156 fruit and vegetable metagenomes to investigate the prevalence of associated bacteria in 2,426 publicly available gut metagenomes. The microbiomes of fresh fruits and vegetables and the human gut are represented by members in common such as Enterobacterales, Burkholderiales, and Lactobacillales. Exposure to bacteria via fruit and vegetable consumption potentially has a beneficial impact on the functional diversity of gut microbiota particularly due to the presence of putative health-promoting genes for the production of vitamin and short-chain fatty acids. In the human gut, they were consistently present, although at a low abundance, approx. 2.2%. Host age, vegetable consumption frequency, and the diversity of plants consumed were drivers favoring a higher proportion. Overall, these results provide one of the primary links between the human microbiome and the environmental microbiome. This study revealed evidence that fruit and vegetable-derived microbes could be found in the human gut and contribute to gut microbiome diversity.}, }
@article {pmid37738402, year = {2023}, author = {Cho, H and Qu, Y and Liu, C and Tang, B and Lyu, R and Lin, BM and Roach, J and Azcarate-Peril, MA and Aguiar Ribeiro, A and Love, MI and Divaris, K and Wu, D}, title = {Comprehensive evaluation of methods for differential expression analysis of metatranscriptomics data.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {5}, pages = {}, pmid = {37738402}, issn = {1477-4054}, support = {R01 HG009937/HG/NHGRI NIH HHS/United States ; U01 DE025046/DE/NIDCR NIH HHS/United States ; R03 DE028983/DE/NIDCR NIH HHS/United States ; }, mesh = {Child ; Humans ; Child, Preschool ; *Benchmarking ; Biofilms ; Computer Simulation ; Lactic Acid ; *Stomatognathic Diseases ; }, abstract = {Understanding the function of the human microbiome is important but the development of statistical methods specifically for the microbial gene expression (i.e. metatranscriptomics) is in its infancy. Many currently employed differential expression analysis methods have been designed for different data types and have not been evaluated in metatranscriptomics settings. To address this gap, we undertook a comprehensive evaluation and benchmarking of 10 differential analysis methods for metatranscriptomics data. We used a combination of real and simulated data to evaluate performance (i.e. type I error, false discovery rate and sensitivity) of the following methods: log-normal (LN), logistic-beta (LB), MAST, DESeq2, metagenomeSeq, ANCOM-BC, LEfSe, ALDEx2, Kruskal-Wallis and two-part Kruskal-Wallis. The simulation was informed by supragingival biofilm microbiome data from 300 preschool-age children enrolled in a study of childhood dental disease (early childhood caries, ECC), whereas validations were sought in two additional datasets from the ECC study and an inflammatory bowel disease study. The LB test showed the highest sensitivity in both small and large samples and reasonably controlled type I error. Contrarily, MAST was hampered by inflated type I error. Upon application of the LN and LB tests in the ECC study, we found that genes C8PHV7 and C8PEV7, harbored by the lactate-producing Campylobacter gracilis, had the strongest association with childhood dental disease. This comprehensive model evaluation offers practical guidance for selection of appropriate methods for rigorous analyses of differential expression in metatranscriptomics. Selection of an optimal method increases the possibility of detecting true signals while minimizing the chance of claiming false ones.}, }
@article {pmid37736390, year = {2023}, author = {Dweh, TJ and Pattnaik, S and Sahoo, JP}, title = {Assessing the impact of meta-genomic tools on current cutting-edge genome engineering and technology.}, journal = {International journal of biochemistry and molecular biology}, volume = {14}, number = {4}, pages = {62-75}, pmid = {37736390}, issn = {2152-4114}, abstract = {Metagenomics is defined as the study of the genome of the total microbiota found in nature and is often referred to as microbial environmental genomics because it entails the examination of a group of genetic components (genomes) from a diverse community of organisms in a particular setting. It is a sub-branch of omics technology that encompasses Deoxyribonucleic Acid (DNA), Ribonucleic acid (DNA), proteins, and various components associated with comprehensive analysis of all aspects of biological molecules in a system-wide manner. Clustered regularly interspaced palindromic repeats and its endonuclease, CRISPR-associated protein which forms a complex called CRISPR-cas9 technology, though it is a different technique used to make precise changes to the genome of an organism, it can be used in conjunction with metagenomic approaches to give a better, rapid, and more accurate description of genomes and sequence reads. There have been ongoing improvements in sequencing that have deepened our understanding of microbial genomes forever. From the time when only a small amount of gene could be sequenced using traditional methods (e.g., "the plus and minus" method developed by Allan and Sanger and the "chemical cleavage" method that is known for its use in the sequencing the phiX174 bacteriophage genome via radio-labeled DNA polymerase-primer in a polymerization reaction aided by polyacrylamide gel) to the era of total genomes sequencing which includes "sequencing-by-ligation" and the "sequencing-by-synthesis" that detects hydrogen ions when new DNA is synthesized (Second Generation) and then Next Generation Sequencing technologies (NGS). With these technologies, the Human Genome Project (HGP) was made possible. The study looks at recent advancements in metagenomics in plants and animals by examining findings from randomly selected research papers. All selected case studies examined the functional and taxonomical analysis of different microbial communities using high-throughput sequencing to generate different sequence reads. In animals, five studies indicated how Zebrafish, Livestock, Poultry, cattle, niches, and the human microbiome were exploited using environmental samples, such as soil and water, to identify microbial communities and their functions. It has also been used to study the microbiome of humans and other organisms, including gut microbiomes. Recent studies demonstrated how these technologies have allowed for faster and more accurate identification of pathogens, leading to improved disease diagnostics. They have also enabled the development of personalized medicine by allowing for the identification of genetic variations that can impact drug efficacy and toxicity. Continued advancements in sequencing techniques and the refinement of CRISPR-Cas9 tools offer even greater potential for transformative breakthroughs in scientific research and applications. On the other hand, metagenomic data are always large and uneasy to handle. The complexity of taxonomical profiling, functional annotation, and mechanisms of complex interaction still needs better bioinformatics tools. Current review focuses on better (e.g., AI-driven algorithms) tools that can predict metabolic pathways and interactions, and manipulate complex data to address potential bias for accurate interpretation.}, }
@article {pmid37731926, year = {2023}, author = {Dikareva, E and Matharu, D and Lahtinen, E and Kolho, KL and De Vos, WM and Salonen, A and Ponsero, AJ}, title = {An extended catalog of integrated prophages in the infant and adult fecal microbiome shows high prevalence of lysogeny.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1254535}, pmid = {37731926}, issn = {1664-302X}, abstract = {BACKGROUND AND AIMS: The acquisition and gradual maturation of gut microbial communities during early childhood is central to an individual's healthy development. Bacteriophages have the potential to shape the gut bacterial communities. However, the complex ecological interactions between phages and their bacterial host are still poorly characterized. In this study, we investigated the abundance and diversity of integrated prophages in infant and adult gut bacteria by detecting integrated prophages in metagenome assembled genomes (MAGs) of commensal bacteria.<br><br>METHODS: Our study included 88 infants sampled at 3&#x2009;weeks, 3&#x2009;months, 6&#x2009;months, and 12&#x2009;months (n&#x2009;=&#x2009;323 total samples), and their parents around delivery time (n&#x2009;=&#x2009;138 total samples). Fecal DNA was extracted and characterized by using shotgun metagenomic sequencing, and a collection of prokaryotic MAGs was generated. The MAG collection was screened for the presence of integrated bacteriophage sequences, allowing their taxonomic and functional characterization.<br><br>RESULTS: A large collection of 6,186 MAGs from infant and adult gut microbiota was obtained and screened for integrated prophages, allowing the identification of 7,165 prophage sequences longer than 10&#x2009;kb. Strikingly, more than 70% of the near-complete MAGs were identified as lysogens. The prevalence of prophages in MAGs varied across bacterial families, with a lower prevalence observed among Coriobacteriaceae, Eggerthellaceae, Veillonellaceae and Burkholderiaceae, while a very high prevalence of lysogen MAGs were observed in Oscillospiraceae, Enterococcaceae, and Enterobacteriaceae. Interestingly for several bacterial families such as Bifidobacteriaceae and Bacteroidaceae, the prevalence of prophages in MAGs was higher in early infant time point (3&#x2009;weeks and 3&#x2009;months) than in later sampling points (6 and 12&#x2009;months) and in adults. The prophage sequences were clustered into 5,616 species-like vOTUs, 77% of which were novel. Finally, we explored the functional repertoire of the potential auxiliary metabolic genes carried by these prophages, encoding functions involved in carbohydrate metabolism and degradation, amino acid metabolism and carbon metabolism.<br><br>CONCLUSION: Our study provides an enhanced understanding of the diversity and prevalence of lysogens in infant and adult gut microbiota and suggests a complex interplay between prophages and their bacterial hosts.}, }
@article {pmid37730417, year = {2023}, author = {Li, YQ and Peng, X and Ren, B and Yan, FH and Pan, YP and Chen, F and Du, WB and Liu, JG and Feng, Q and Yang, DQ and Huang, XJ and Pan, YH and Huang, ZZ and Ding, PH and Zhang, KK and Liu, HX and Zhou, XD}, title = {[Standardized nomenclature of oral microorganisms in Chinese: the 2023 update].}, journal = {Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology}, volume = {58}, number = {10}, pages = {1051-1061}, doi = {10.3760/cma.j.cn112144-20230816-00079}, pmid = {37730417}, issn = {1002-0098}, abstract = {Oral microbial community, as an important part of human microbial community, is closely related to oral and general health. Oral microbiological research has become the forefront of international microbiological research. Standardized and unified nomenclature for oral microorganisms in Chinese is of great significance to support the development of oral medicine research. Standardized translation of microbial names is the basis for writing canonical and authoritative professional textbooks and reference books, which helps students to accurately acquire the characteristics and classifications of oral microbes. Unified translation of oral microorganisms is also conducive to academic communication and cooperation, and plays an important role in oral health education and science popularization, which enables oral microbiology knowledge to be accurately disseminated to the public. Therefore, in order to standardize the words in scientific research, funding application, publications, academic exchanges and science popularization within the field of oral medicine, we have fully discussed and revised the Chinese names of oral microorganisms in 2017 edition and ones of newly discovered oral microbes, finally reaching a consensus to form the 2023 edition of Chinese names of oral microorganisms.}, }
@article {pmid37722774, year = {2023}, author = {Wang, Y and Jian, C}, title = {Novel plant-based meat alternatives: Implications and opportunities for consumer nutrition and health.}, journal = {Advances in food and nutrition research}, volume = {106}, number = {}, pages = {241-274}, doi = {10.1016/bs.afnr.2023.03.006}, pmid = {37722774}, issn = {1043-4526}, mesh = {Animals ; Humans ; *Nutritional Status ; Meat ; Food Additives ; *Meat Products ; Nutrients ; }, abstract = {Against the backdrop of the global protein transition needed to remain within planetary boundaries, there is an influx of plant-based meat alternatives that seek to approximate the texture, flavor and/or nutrient profiles of conventional animal meat. These novel plant-based meat alternatives, enabled by advances in food technology, can be fundamentally different from the whole-plant foods from which they are derived. One of the reasons is the necessity to use food additives on various occasions, since consumers' acceptance of plant-based meat products primarily depends on the organoleptic properties. Consequently, a high degree of heterogeneity in formulation and nutritional profiles exists both within and between product categories of plant-based meat alternatives with unknown effects on several aspects of human health. This is further complicated by the differences in digestibility and bioavailability between proteins from animal and plant sources, which have a profound impact on colonic fermentation, nutritional adequacy and potential health effects. On the other hand, emerging strategies provide opportunities to develop affordable, delicious and nutritious plant-based meat alternatives that align with consumer interests.}, }
@article {pmid37705730, year = {2023}, author = {Saglam, D and Colak, GA and Sahin, E and Ekren, BY and Sezerman, U and Bas, M}, title = {Effects of Ramadan intermittent fasting on gut microbiome: is the diet key?.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1203205}, pmid = {37705730}, issn = {1664-302X}, abstract = {Much research has been conducted regarding the impact of diet on the gut microbiota. However, the effects of dietary habits such as intermittent fasting are unclear. This study aimed to investigate the effect of intermittent fasting during Ramadan on the gut microbiota. The study was conducted on 12 healthy adult individuals who practiced fasting 17 h per day for 29 consecutive days during the month of Ramadan. To determine the dietary intake of individuals, a 3-day dietary record was kept at the beginning and end of the study. Reads that passed quality filtering were clustered, and custom-prepared 16S rRNA gene regions of bacteria associated with the human microbiome were used as a reference. Consensus sequences were created, and genus-level taxonomic annotations were determined using a sequence identity threshold of 95%. The correlations between the dietary intake measurements of the participants and the respective relative abundance of bacterial genera were investigated. The results showed that Firmicutes were higher in abundance in the gut microbiota before fasting among participants, while they were significantly lower in abundance at the end of Ramadan fasting (p < 0.05). Proteobacteria were significantly higher in abundance at the end of the month of Ramadan (p < 0.05). Fasting was associated with a significant decrease in levels of seven genera: Blautia, Coprococcus, Dorea, Faecalicatena, Fusicatenibacter, Lachnoclostridium, and Mediterraneibacter. Conversely, the abundances of two bacterial genera were enhanced at the end of the fasting month: Escherichia and Shigella. The results of the dietary intake analysis showed that a negative correlation was detected for three comparisons: Ihubacter and protein (rho = -0.54, p = 0.0068), Fusicatenibacter and vegetables (rho = -0.54, p = 0.0042), and Intestinibacter and nuts (rho = -0.54, p-value = 0.0065). The results suggest that even when the fasting period during Ramadan is consistent, the types of food consumed by individuals can affect the gut microbiota.}, }
@article {pmid37705353, year = {2024}, author = {Kobyliak, N and Khomenko, M and Falalyeyeva, T and Fedchenko, A and Savchuk, O and Tseyslyer, Y and Ostapchenko, L}, title = {Probiotics for pancreatic β-cell function: from possible mechanism of action to assessment of effectiveness.}, journal = {Critical reviews in microbiology}, volume = {50}, number = {5}, pages = {663-683}, doi = {10.1080/1040841X.2023.2257776}, pmid = {37705353}, issn = {1549-7828}, mesh = {*Probiotics/pharmacology/therapeutic use ; Humans ; *Insulin-Secreting Cells/metabolism ; *Diabetes Mellitus, Type 2/microbiology ; Animals ; *Gastrointestinal Microbiome ; }, abstract = {Type 2 diabetes (T2D) is a metabolic disease characterized by chronic hyperglycemia because of insulin resistance (IR) and\or pancreatic β-cell dysfunction. Last century research showed that gut microbiota has a direct effect on metabolism and metabolic diseases. New studies into the human microbiome and its connection with the host is making it possible to develop new therapies for a wide variety of diseases. Inflammation is a well-known precursor to metabolic syndrome, which increases the risk of hypertension, visceral obesity, and dyslipidemia, which can lead to T2D through the damage of pancreatic β-cell and reduce insulin secretion. Current understanding for beneficial effects of probiotics in T2D strictly rely on both animal and clinical data, which mostly focused on their impact on IR, anthropometric parameters, glycemic control and markers of chronic systemic inflammation. From the other hand, there is a lack of evidence-based probiotic efficacy on pancreatic β-cell function in terms of T2D and related metabolic disorders. Therefore, current review will focus on the efficacy of probiotics for the protection of β-cells damage and it`s mechanism in patients with T2D.}, }
@article {pmid37700048, year = {2023}, author = {Zuo, T}, title = {Gut bacteriophages ignite mammalian immunity.}, journal = {Nature reviews. Microbiology}, volume = {21}, number = {10}, pages = {634}, pmid = {37700048}, issn = {1740-1534}, }
@article {pmid37699408, year = {2023}, author = {Carvalho, MR and Yan, LP and Li, B and Zhang, CH and He, YL and Reis, RL and Oliveira, JM}, title = {Gastrointestinal organs and organoids-on-a-chip: advances and translation into the clinics.}, journal = {Biofabrication}, volume = {15}, number = {4}, pages = {}, doi = {10.1088/1758-5090/acf8fb}, pmid = {37699408}, issn = {1758-5090}, mesh = {United States ; Humans ; *Microphysiological Systems ; *Gastrointestinal Tract ; Stomach ; Liver ; Organoids ; }, abstract = {Microfluidic organs and organoids-on-a-chip models of human gastrointestinal systems have been established to recreate adequate microenvironments to study physiology and pathophysiology. In the effort to find more emulating systems and less costly models for drugs screening or fundamental studies, gastrointestinal system organoids-on-a-chip have arisen as promising pre-clinicalin vitromodel. This progress has been built on the latest developments of several technologies such as bioprinting, microfluidics, and organoid research. In this review, we will focus on healthy and disease models of: human microbiome-on-a-chip and its rising correlation with gastro pathophysiology; stomach-on-a-chip; liver-on-a-chip; pancreas-on-a-chip; inflammation models, small intestine, colon and colorectal cancer organoids-on-a-chip and multi-organoids-on-a-chip. The current developments related to the design, ability to hold one or more 'organs' and its challenges, microfluidic features, cell sources and whether they are used to test drugs are overviewed herein. Importantly, their contribution in terms of drug development and eminent clinical translation in precision medicine field, Food and Drug Administration approved models, and the impact of organoid-on-chip technology in terms of pharmaceutical research and development costs are also discussed by the authors.}, }
@article {pmid37698033, year = {2023}, author = {Zuo, T and Liang, G and Huang, Z and Cao, Z and Bai, F and Zhou, Y and Wu, X and Wu, X and Chen, YQ and Balati, M and Maimaitiyiming, M and ,  and Lan, P}, title = {Baseline gut microbiome features prior to SARS-CoV-2 infection are associated with host symptoms in and post COVID-19.}, journal = {Journal of medical virology}, volume = {95}, number = {9}, pages = {e29083}, doi = {10.1002/jmv.29083}, pmid = {37698033}, issn = {1096-9071}, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; SARS-CoV-2 ; *Microbiota ; China/epidemiology ; }, abstract = {The human gut microbiome varies substantially across individuals and populations and differentially tames our immunity at steady-state. Hence, we hypothesize that the large heterogeneity of gut microbiomes at steady-state may shape our baseline immunity differentially, and then mediate discrepant immune responses and symptoms when one encounters a viral infection, such as SARS-CoV-2 infection. To validate this hypothesis, we conducted an exploratory, longitudinal microbiome-COVID-19 study involving homogenous young participants from two geographically different regions in China. Subjects were recruited and sampled of fecal specimens before the 3-week surge window of COVID-19 (between December 11 and December 31, 2022) in China, and then were followed up for assessment of COVID-19 and post-COVID-19 manifestations. Our data showed that the baseline gut microbiome composition was intricately associated with different COVID-19 manifestations, particularly gastrointestinal involvement and post-COVID-19 lingering symptoms, in both an individual- and population-dependent manner. Our study intriguingly for the first time highlight that the gut microbiome at steady-state may prepare us differentially for weathering a respiratory viral infection.}, }
@article {pmid37697153, year = {2024}, author = {}, title = {BugSigDB - a database for identifying unusual abundance patterns in human microbiome studies.}, journal = {Nature biotechnology}, volume = {42}, number = {5}, pages = {708-709}, pmid = {37697153}, issn = {1546-1696}, mesh = {Humans ; *Microbiota/genetics ; Databases, Genetic ; Databases, Factual ; }, }
@article {pmid37696680, year = {2024}, author = {Del Chierico, F and Cardile, S and Baldelli, V and Alterio, T and Reddel, S and Bramuzzo, M and Knafelz, D and Lega, S and Bracci, F and Torre, G and Maggiore, G and Putignani, L}, title = {Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {4}, pages = {529-537}, pmid = {37696680}, issn = {1536-4844}, support = {//Italian Ministry of Health/ ; }, mesh = {Humans ; Child ; *Colitis, Ulcerative/complications ; *Gastrointestinal Microbiome ; *Cholangitis, Sclerosing/complications ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; Bacteroidetes ; Italy ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis.<br><br>METHODS: By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs).<br><br>RESULTS: Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients.<br><br>CONCLUSIONS: We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.}, }
@article {pmid37690584, year = {2024}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {An updated overview on the relationship between human gut microbiome dysbiosis and psychiatric and psychological disorders.}, journal = {Progress in neuro-psychopharmacology &amp; biological psychiatry}, volume = {128}, number = {}, pages = {110861}, doi = {10.1016/j.pnpbp.2023.110861}, pmid = {37690584}, issn = {1878-4216}, abstract = {There is a lot of evidence establishing that nervous system development is related to the composition and functions of the gut microbiome. In addition, the central nervous system (CNS) controls the imbalance of the intestinal microbiota, constituting a bidirectional communication system. At present, various gut-brain crosstalk routes have been described, including immune, endocrine and neural circuits via the vagal pathway. Several empirical data have associated gut microbiota alterations (dysbiosis) with neuropsychiatric diseases, such as Alzheimer's disease, autism and Parkinson's disease, and with other psychological disorders, like anxiety and depression. Fecal microbiota transplantation (FMT) therapy has shown that the gut microbiota can transfer behavioral features to recipient animals, which provides strong evidence to establish a causal-effect relationship. Interventions, based on prebiotics, probiotics or synbiotics, have demonstrated an important influence of microbiota on neurological disorders by the synthesis of neuroactive compounds that interact with the nervous system and by the regulation of inflammatory and endocrine processes. Further research is needed to demonstrate the influence of gut microbiota dysbiosis on psychiatric and psychological disorders, and how microbiota-based interventions may be used as potential therapeutic tools.}, }
@article {pmid37686314, year = {2023}, author = {Santos, FP and Carvalhos, CA and Figueiredo-Dias, M}, title = {New Insights into Photobiomodulation of the Vaginal Microbiome-A Critical Review.}, journal = {International journal of molecular sciences}, volume = {24}, number = {17}, pages = {}, pmid = {37686314}, issn = {1422-0067}, mesh = {Female ; Humans ; Autoimmunity ; Dysbiosis ; *Microbiota ; *Vagina/microbiology ; Low-Level Light Therapy ; }, abstract = {The development of new technologies such as sequencing has greatly enhanced our understanding of the human microbiome. The interactions between the human microbiome and the development of several diseases have been the subject of recent research. In-depth knowledge about the vaginal microbiome (VMB) has shown that dysbiosis is closely related to the development of gynecologic and obstetric disorders. To date, the progress in treating or modulating the VMB has lagged far behind research efforts. Photobiomodulation (PBM) uses low levels of light, usually red or near-infrared, to treat a diversity of conditions. Several studies have demonstrated that PBM can control the microbiome and improve the activity of the immune system. In recent years, increasing attention has been paid to the microbiome, mostly to the gut microbiome and its connections with many diseases, such as metabolic disorders, obesity, cardiovascular disorders, autoimmunity, and neurological disorders. The applicability of PBM therapeutics to treat gut dysbiosis has been studied, with promising results. The possible cellular and molecular effects of PBM on the vaginal microbiome constitute a theoretical and promising field that is starting to take its first steps. In this review, we will discuss the potential mechanisms and effects of photobiomodulation in the VMB.}, }
@article {pmid37685376, year = {2023}, author = {Unal, M and Bostanci, E and Ozkul, C and Acici, K and Asuroglu, T and Guzel, MS}, title = {Crohn's Disease Prediction Using Sequence Based Machine Learning Analysis of Human Microbiome.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {13}, number = {17}, pages = {}, pmid = {37685376}, issn = {2075-4418}, abstract = {Human microbiota refers to the trillions of microorganisms that inhabit our bodies and have been discovered to have a substantial impact on human health and disease. By sampling the microbiota, it is possible to generate massive quantities of data for analysis using Machine Learning algorithms. In this study, we employed several modern Machine Learning techniques to predict Inflammatory Bowel Disease using raw sequence data. The dataset was obtained from NCBI preprocessed graph representations and converted into a structured form. Seven well-known Machine Learning frameworks, including Random Forest, Support Vector Machines, Extreme Gradient Boosting, Light Gradient Boosting Machine, Gaussian Naïve Bayes, Logistic Regression, and k-Nearest Neighbor, were used. Grid Search was employed for hyperparameter optimization. The performance of the Machine Learning models was evaluated using various metrics such as accuracy, precision, fscore, kappa, and area under the receiver operating characteristic curve. Additionally, Mc Nemar's test was conducted to assess the statistical significance of the experiment. The data was constructed using k-mer lengths of 3, 4 and 5. The Light Gradient Boosting Machine model overperformed over other models with 67.24%, 74.63% and 76.47% accuracy for k-mer lengths of 3, 4 and 5, respectively. The LightGBM model also demonstrated the best performance in each metric. The study showed promising results predicting disease from raw sequence data. Finally, Mc Nemar's test results found statistically significant differences between different Machine Learning approaches.}, }
@article {pmid37682568, year = {2023}, author = {Moir, J and Hyman, M and Wang, J and Flores, A and Skondra, D}, title = {The Association of Antibiotic Use and the Odds of a New-Onset ICD Code Diagnosis of Age-Related Macular Degeneration: A Large National Case-Control Study.}, journal = {Investigative ophthalmology &amp; visual science}, volume = {64}, number = {12}, pages = {14}, pmid = {37682568}, issn = {1552-5783}, mesh = {Humans ; *Anti-Bacterial Agents/adverse effects ; International Classification of Diseases ; Case-Control Studies ; Prospective Studies ; Aminoglycosides ; Fluoroquinolones ; *Macular Degeneration/diagnosis/epidemiology ; }, abstract = {PURPOSE: The widespread use of antibiotics has many well-documented impacts on the human microbiome, which may be associated with the development of various inflammatory diseases. Despite age-related macular degeneration (AMD) featuring an inflammatory pathogenesis, the relationship between antibiotics and AMD has remained unexplored. We conducted the first study to determine the association between antibiotic exposure and a new-onset International Classification of Diseases (ICD) diagnosis of AMD.<br><br>METHODS: We performed a case-control analysis of patients aged 55 and older with new-onset AMD between 2008 and 2017 from a nationwide commercial health insurance claims database. Exposure to antibiotics in the two years before the index date was determined for cases and controls matched one-to-one by age, year, region, anemia, hypertension, and a comorbidity index. Conditional multivariable logistic regression, adjusted for AMD risk factors, was performed to calculate odd ratios (OR) and 95% confidence intervals (CI).<br><br>RESULTS: Among the antibiotic classes, exposure to aminoglycosides (OR = 1.24; 95% CI, 1.22-1.26) and fluoroquinolones (OR = 1.13; 95% CI, 1.12-1.14) was associated with the greatest odds of a new-onset ICD code diagnosis of AMD. Broad-spectrum antibiotics were associated with nearly three times greater odds of a new-onset ICD code diagnosis of AMD (OR = 1.15; 95% CI, 1.13-1.16) compared to narrow-spectrum antibiotics (OR = 1.05; 95% CI, 1.03-1.07). We also identified a frequency- and duration-dependent association, with a greater cumulative number of antibiotic prescriptions or day supply of antibiotics conferring increased odds of a new-onset ICD code diagnosis of AMD.<br><br>CONCLUSIONS: Greater cumulative exposure to antibiotics, particularly fluoroquinolones, aminoglycosides, and those with broader-spectrum coverage, may be associated with the development of AMD, a finding that requires further investigation using prospective studies.}, }
@article {pmid37671026, year = {2023}, author = {Pietiäinen, V and Polso, M and Migh, E and Guckelsberger, C and Harmati, M and Diosdi, A and Turunen, L and Hassinen, A and Potdar, S and Koponen, A and Sebestyen, EG and Kovacs, F and Kriston, A and Hollandi, R and Burian, K and Terhes, G and Visnyovszki, A and Fodor, E and Lacza, Z and Kantele, A and Kolehmainen, P and Kakkola, L and Strandin, T and Levanov, L and Kallioniemi, O and Kemeny, L and Julkunen, I and Vapalahti, O and Buzas, K and Paavolainen, L and Horvath, P and Hepojoki, J}, title = {Image-based and machine learning-guided multiplexed serology test for SARS-CoV-2.}, journal = {Cell reports methods}, volume = {3}, number = {8}, pages = {100565}, pmid = {37671026}, issn = {2667-2375}, mesh = {Humans ; *SARS-CoV-2 ; *COVID-19 ; COVID-19 Testing ; Acclimatization ; Machine Learning ; }, abstract = {We present a miniaturized immunofluorescence assay (mini-IFA) for measuring antibody response in patient blood samples. The method utilizes machine learning-guided image analysis and enables simultaneous measurement of immunoglobulin M (IgM), IgA, and IgG responses against different viral antigens in an automated and high-throughput manner. The assay relies on antigens expressed through transfection, enabling use at a low biosafety level and fast adaptation to emerging pathogens. Using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as the model pathogen, we demonstrate that this method allows differentiation between vaccine-induced and infection-induced antibody responses. Additionally, we established a dedicated web page for quantitative visualization of sample-specific results and their distribution, comparing them with controls and other samples. Our results provide a proof of concept for the approach, demonstrating fast and accurate measurement of antibody responses in a research setup with prospects for clinical diagnostics.}, }
@article {pmid37669300, year = {2023}, author = {Casulli, A and Pane, S and Randi, F and Scaramozzino, P and Carvelli, A and Marras, CE and Carai, A and Santoro, A and Santolamazza, F and Tamarozzi, F and Putignani, L}, title = {Primary cerebral cystic echinococcosis in a child from Roman countryside: Source attribution and scoping review of cases from the literature.}, journal = {PLoS neglected tropical diseases}, volume = {17}, number = {9}, pages = {e0011612}, pmid = {37669300}, issn = {1935-2735}, mesh = {Humans ; Child ; Animals ; Sheep ; Young Adult ; Adult ; *Echinococcosis ; *Cysticercosis ; *Central Nervous System Parasitic Infections ; Zoonoses ; *Cysts ; Larva ; }, abstract = {BACKGROUND: Human cystic echinococcosis (CE) is a zoonotic parasitic infection caused by the larval stage of the species belonging to the Echinococcus granulosus sensu lato (s.l.) complex. Parasitic cysts causing human CE are mainly localized in the liver and in the lungs. In a smaller number of cases, larvae may establish in any organ or tissue, including the central nervous system (CNS). Cerebral CE (CCE) is rare but poses serious clinical challenges.<br><br>METHODS: This study presents a case of CCE in a child living in the countryside near Rome (Italy), along with a comparative molecular analysis of the isolated cyst specimens from the patient and sheep of local farms. We also systematically searched the literature to summarize the most relevant epidemiological and clinical aspects of this uncommon localization.<br><br>FINDINGS: The comparative molecular analysis confirmed that the infection was caused by E. granulosus sensu stricto (s.s.) (G3 genotype), and most likely acquired in the family farm. The literature search identified 2,238 cases of CCE. In 80.51% of cases, brain was the only localization and single CCE cysts were present in 84.07% of cases. Mean patients' age was 20 years and 70.46% were children. Cyst rupture was reported in 12.96% and recurrence of CCE after treatment in 9.61% of cases. Permanent disability was reported in 7.86% of cases, while death occurred in 6.21%. In case series reporting all CE localization, CCE represented 1.5% of all CE cases. In the few reports that identified at molecular level the CCE cyst, E. granulosus s.s. was found in 40% and E. canadensis in 60% of cases.<br><br>CONCLUSIONS: We report a rare case of CCE and evidenced the probable local origin of infection. The proportions of CE cases with uncommon localizations and with high impact on patients' lives have been globally neglected and should be included in the computation of the global burden of CE.}, }
@article {pmid37657351, year = {2023}, author = {Toyomane, K and Akutsu, T and Watanabe, K and Yamagishi, T and Kubota, S}, title = {Potential application of Staphylococcus species detection in the specific identification of saliva.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {65}, number = {}, pages = {102320}, doi = {10.1016/j.legalmed.2023.102320}, pmid = {37657351}, issn = {1873-4162}, mesh = {Humans ; *Saliva ; *Staphylococcus/genetics ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; Polymerase Chain Reaction ; }, abstract = {When found at crime scenes, saliva constitutes forensically relevant evidence. Although several tests have been developed to effectively identify saliva in such circumstances, most cannot discriminate between saliva and nasal secretion. Recently, studies have developed saliva tests involving oral bacteria as salivary markers. Although the specificity of such tests has been evaluated on most biological specimens, their specificity for nasal secretion samples remains to be tested. Herein, to improve the specificity of the saliva detection tests for nasal secretion samples, we reanalyzed a public microbiome dataset and conducted inhouse 16S rRNA sequencing to identify a new marker to distinguish between saliva and nasal secretions. The sequencing data indicated the existence of oral bacteria such as Streptococcus in nasal secretion samples, which may be responsible for the false positives in the saliva tests. Furthermore, we found that including the 16S rRNA gene of the genus Staphylococcus as a nasal secretion marker may improve the specificity of PCR-based saliva tests for nasal secretion samples. In addition, we assessed the specificity of previously developed salivary bacteria detection tests for nasal secretion samples and oral bacterial markers were detected in two of eight nasal secretion samples, which led to the false positive results for saliva detection. Thus, the specificity of such tests can be improved by adding Staphylococcus as a nasal marker, as revealed by our sequencing analysis.}, }
@article {pmid37656392, year = {2023}, author = {Rahman, SO and Bariguian, F and Mobasheri, A}, title = {The Potential Role of Probiotics in the Management of Osteoarthritis Pain: Current Status and Future Prospects.}, journal = {Current rheumatology reports}, volume = {25}, number = {12}, pages = {307-326}, pmid = {37656392}, issn = {1534-6307}, mesh = {Humans ; Lipopolysaccharides ; *Osteoarthritis/complications/therapy ; Pain ; *Probiotics/therapeutic use ; Arthralgia ; }, abstract = {PURPOSE OF REVIEW: This narrative review article comprehensively explains the pathophysiology of osteoarthritis (OA) pain perception, how the gut microbiota is correlated with it, possible molecular pathways involved in probiotics-mediated OA pain reduction, limitations in the current research approaches, and future perspectives.<br><br>RECENT FINDINGS: The initiation and progression of OA, including the development of chronic pain, is intricately associated with activation of the innate immune system and subsequent inflammatory responses. Trauma, lifestyle (e.g., obesity and metabolic disease), and chronic antibiotic treatment can disrupt commensal homeostasis of the human microbiome, thereby affecting intestinal integrity and promoting leakage of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into circulation. Increased level of LPS is associated with knee osteophyte severity and joint pain. Both preclinical and clinical studies strongly suggest that probiotics may benefit patients with OA pain through positive gut microbiota modulation and attenuating low-grade inflammation via multiple pathways. Patent data also suggests increased interest in the development of new innovations that involve probiotic use for reducing OA and joint pain. Recent data suggest that probiotics are attracting more and more attention for OA pain management. The advancement of knowledge in this area may pave the way for developing different probiotic strains that can be used to support joint health, improve treatment outcomes in OA, and reduce the huge impact of the disease on healthcare systems worldwide.}, }
@article {pmid37655878, year = {2023}, author = {Cauwenberghs, E and Oerlemans, E and Wittouck, S and Allonsius, CN and Gehrmann, T and Ahannach, S and De Boeck, I and Spacova, I and Bron, PA and Donders, G and Verhoeven, V and Lebeer, S}, title = {Salivary microbiome of healthy women of reproductive age.}, journal = {mBio}, volume = {14}, number = {5}, pages = {e0030023}, pmid = {37655878}, issn = {2150-7511}, support = {//Interuniversitair Bijzonder Onderzoeksfonds/ ; 26850//EC | European Research Council (ERC)/ ; 12S4222N, 1277222N//Fonds Wetenschappelijk Onderzoek (FWO)/ ; 37054//Interuniversitair Bijzonder Onderzoeksfonds/ ; }, mesh = {Humans ; Female ; *Reproduction ; Saliva ; Sexual Partners ; *Microbiota ; Health Status ; RNA, Ribosomal, 16S ; }, abstract = {The salivary microbiome has been proven to play a crucial role in local and systemic diseases. Moreover, the effects of biological and lifestyle factors such as oral hygiene and smoking on this microbial community have already been explored. However, what was not yet well understood was the natural variation of the saliva microbiome in healthy women and how this is associated with specific use of hormonal contraception and with the number of different sexual partners with whom microbiome exchange is expected regularly. In this paper, we characterized the salivary microbiome of 255 healthy women of reproductive age using an in-depth questionnaire and self-sampling kits. Using the large metadata set, we were able to investigate the associations of several host-related and lifestyle variables with the salivary microbiome profiles. Our study shows a high preservation between individuals.}, }
@article {pmid37650878, year = {2023}, author = {Lahtinen, MH and Kynkäänniemi, E and Jian, C and Salonen, A and Pajari, AM and Mikkonen, KS}, title = {Metabolic Fate of Lignin in Birch Glucuronoxylan Extracts as Dietary Fiber Studied in a Rat Model.}, journal = {Molecular nutrition &amp; food research}, volume = {67}, number = {20}, pages = {e2300201}, doi = {10.1002/mnfr.202300201}, pmid = {37650878}, issn = {1613-4133}, mesh = {Rats ; Animals ; *Lignin/chemistry/metabolism ; *Betula/metabolism ; Dietary Fiber ; Xylans ; }, abstract = {SCOPE: While previously considered inert, recent studies suggest lignin metabolism with unknown metabolic fates is occurring in the gastrointestinal tract of several animal models. This study focuses on analyzing the potential metabolites of lignin.<br><br>METHODS AND RESULTS: The diets of rats include relatively pure birch glucuronoxylan (pureGX) with residual lignin or lignin-rich GX (GXpoly) in their diet. Nuclear magnetic spectroscopy of the lignin isolated from the GXpoly-fed rats fecal sample shows high alteration in chemical structure, whereas lignin-carbohydrate complexes (LCCs) are enriched in fecal samples from the pureGX group. Moreover, the increased syringyl-to-guaiacyl (S/G) ratio suggests that lignin G-units are predominantly metabolized based on pyrolysis gas chromatography-mass spectrometry (pyr-GC/MS). The presence of small phenolic metabolites identified in urine samples of the GXpoly group, for example, ferulic and sinapic acids, their sulfate and glucuronide derivatives, and 4-sulfobenzylalcohol, suggests that the small fragmented lignin metabolites in the large intestine enter the plasma, and are further processed in the liver. Finally, the relative abundances of polyphenol-degrading Enterorhabdus and Akkermansia in the gut microbiota are associated with lignin metabolism.<br><br>CONCLUSION: These findings give further evidence to lignin metabolism in the gut of nonruminants and provide insight to the potential microbes and metabolic routes.}, }
@article {pmid37644161, year = {2023}, author = {Koo, H and Morrow, CD}, title = {Identification of donor Bacteroides vulgatus genes encoding proteins that correlate with early colonization following fecal transplant of patients with recurrent Clostridium difficile.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14112}, pmid = {37644161}, issn = {2045-2322}, mesh = {Child ; Humans ; Animals ; Mice ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/genetics ; Tissue Donors ; Bacteroides/genetics ; }, abstract = {Due to suppressive antibiotics, patients with recurrent Clostridium difficile have gut microbial communities that are devoid of most commensal microbes. Studies have shown that most of the failures using fecal microbe transplantation (FMT) for recurrent C. difficile occur during the first 4 weeks following transplantation. To identify features of donor Bacteroides vulgatus that lead to early colonization, we used two data sets that collected fecal samples from recipients at early times points post FMT. The first analysis used the shotgun metagenomic DNA sequencing data set from Aggarwala et al. consisting of 7 FMT donors and 13 patients with recurrent C. difficile with fecal samples taken as early as 24 h post FMT. We identified 2 FMT donors in which colonization of recipients by donor B. vulgatus was detected as early as 24 h post FMT. We examined a second data set from Hourigan et al. that collected fecal samples from C. difficile infected children and identified 1 of 3 FMT that also had early colonization of the donor B. vulgatus. We found 19 genes out of 4911 encoding proteins were unique to the 3 donors that had early colonization. A gene encoding a putative chitobiase was identified that was in a gene complex that had been previously identified to enhance colonization in mice. A gene encoding a unique fimbrillin (i.e., pili) family protein and 17 genes encoding hypothetical proteins were also specific for early colonizing donors. Most of the genes encoding hypothetical proteins had neighboring genes that encoded proteins involved in mobilization or transposition. Finally, analysis of 42 paired fecal samples from the human microbiome project (HMP) found no individuals had all 19 genes while 2 individuals had none of the 19 genes. Based on the results from our study, consideration should be given to the screening of FMT donors for these B. vulgatus genes found to enhance early colonization that would be of benefit to promote colonization following FMT.}, }
@article {pmid37642431, year = {2023}, author = {Farmer, N and Maki, KA and Barb, JJ and Jones, KK and Yang, L and Baumer, Y and Powell-Wiley, TM and Wallen, GR}, title = {Geographic social vulnerability is associated with the alpha diversity of the human microbiome.}, journal = {mSystems}, volume = {8}, number = {5}, pages = {e0130822}, pmid = {37642431}, issn = {2379-5077}, mesh = {Humans ; *Social Vulnerability ; *Microbiota/genetics ; Geography ; Risk Factors ; Public Health ; }, abstract = {As a risk factor for conditions related to the microbiome, understanding the role of SVI on microbiome diversity may assist in identifying public health implications for microbiome research. Here we found, using a sub-sample of the Human Microbiome Project phase 1 cohort, that SVI was linked to microbiome diversity across body sites and that SVI may influence race/ethnicity-based differences in diversity. Our findings, build on the current knowledge regarding the role of human geography in microbiome research, suggest that measures of geographic social vulnerability be considered as additional contextual factors when exploring microbiome alpha diversity.}, }
@article {pmid37630623, year = {2023}, author = {Cho, YJ and Shin, B and Lee, SH and Park, S and Kim, YK and Kim, JJ and Kim, E}, title = {Altered Urine Microbiome in Male Children and Adolescents with Attention-Deficit Hyperactivity Disorder.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630623}, issn = {2076-2607}, support = {6-2019-0174//Yonsei University, College of Medicine/ ; }, abstract = {While interest in developing the human microbiome as a biomarker for attention-deficit hyperactivity disorder (ADHD) is increasing, there has been limited exploration in utilizing urine samples. In this study, we analysed urine microbiome profiles by extracting 16S ribosomal DNA from purified bacteria-derived extracellular membrane vesicles obtained from urine samples. Sequencing libraries were constructed by amplifying V3-V4 hypervariable regions sequenced using Illumina MiSeq. Profiles of male Korean children and adolescents with ADHD (n = 33) were compared with healthy sex-matched controls (n = 39). Statistically controlling for age, we found decreased alpha diversity in the urine bacteria of the ADHD group, as evidenced by reduced Shannon and Simpson indices (p < 0.05), and significant differences in beta diversity between the two groups (p < 0.001). The phyla Firmicutes and Actinobacteriota, as well as the genera Ralstonia and Afipia, were relatively more abundant in the ADHD group. The phylum Proteobacteria and the genera Corynebacterium and Peptoniphilus were more abundant in the control group. Notably, the genus Afipia exhibited significant correlations with the Child Behavior Checklist Attention Problems score and DSM-oriented ADHD subscale. This study is the first to propose the urine microbiome as a potential biomarker for pediatric ADHD.}, }
@article {pmid37627516, year = {2023}, author = {Torreggiani, A and Demarinis, C and Pinto, D and Papale, A and Difonzo, G and Caponio, F and Pontonio, E and Verni, M and Rizzello, CG}, title = {Up-Cycling Grape Pomace through Sourdough Fermentation: Characterization of Phenolic Compounds, Antioxidant Activity, and Anti-Inflammatory Potential.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {37627516}, issn = {2076-3921}, abstract = {Despite its appealing composition, because it is rich in fibers and polyphenols, grape pomace, the major by-product of the wine industry, is still discarded or used for feed. This study aimed at exploiting grape pomace functional potential through fermentation with lactic acid bacteria (LAB). A systematic approach, including the progressively optimization of the grape pomace substrate, was used, evaluating pomace percentage, pH, and supplementation of nitrogen and carbon sources. When grape pomace was used at 10%, especially without pH correction, LAB cell viability decreased up to 2 log cycles. Hence, the percentage was lowered to 5 or 2.5% and supplementations with carbon and nitrogen sources, which are crucial for LAB metabolism, were considered aiming at obtaining a proper fermentation of the substrate. The optimization of the substrate enabled the comparison of strains performances and allowed the selection of the best performing strain (Lactiplantibacillus plantarum T0A10). A sourdough, containing 5% of grape pomace and fermented with the selected strain, showed high antioxidant activity on DPPH and ABTS radicals and anti-inflammatory potential on Caco2 cells. The anthocyanins profile of the grape pomace sourdough was also characterized, showing qualitative and quantitative differences before and after fermentation. Overall, the grape pomace sourdough showed promising applications as a functional ingredient in bread making.}, }
@article {pmid37627114, year = {2023}, author = {Miya, TV and Marima, R and Damane, BP and Ledet, EM and Dlamini, Z}, title = {Dissecting Microbiome-Derived SCFAs in Prostate Cancer: Analyzing Gut Microbiota, Racial Disparities, and Epigenetic Mechanisms.}, journal = {Cancers}, volume = {15}, number = {16}, pages = {}, pmid = {37627114}, issn = {2072-6694}, support = {23108//South African Medical Research Council/ ; 138139//National Research Foundation/ ; }, abstract = {Prostate cancer (PCa) continues to be the most diagnosed cancer and the second primary cause of fatalities in men globally. There is an abundance of scientific evidence suggesting that the human microbiome, together with its metabolites, plays a crucial role in carcinogenesis and has a significant impact on the efficacy of anticancer interventions in solid and hematological cancers. These anticancer interventions include chemotherapy, immune checkpoint inhibitors, and targeted therapies. Furthermore, the microbiome can influence systemic and local immune responses using numerous metabolites such as short-chain fatty acids (SCFAs). Despite the lack of scientific data in terms of the role of SCFAs in PCa pathogenesis, recent studies show that SCFAs have a profound impact on PCa progression. Several studies have reported racial/ethnic disparities in terms of bacterial content in the gut microbiome and SCFA composition. These studies explored microbiome and SCFA racial/ethnic disparities in cancers such as colorectal, colon, cervical, breast, and endometrial cancer. Notably, there are currently no published studies exploring microbiome/SCFA composition racial disparities and their role in PCa carcinogenesis. This review discusses the potential role of the microbiome in PCa development and progression. The involvement of microbiome-derived SCFAs in facilitating PCa carcinogenesis and their effect on PCa therapeutic response, particularly immunotherapy, are discussed. Racial/ethnic differences in microbiome composition and SCFA content in various cancers are also discussed. Lastly, the effects of SCFAs on PCa progression via epigenetic modifications is also discussed.}, }
@article {pmid37619924, year = {2023}, author = {Golovko, G and Khanipov, K and Reyes, V and Pinchuk, I and Fofanov, Y}, title = {Identification of multivariable Boolean patterns in microbiome and microbial gene composition data.}, journal = {Bio Systems}, volume = {233}, number = {}, pages = {105007}, doi = {10.1016/j.biosystems.2023.105007}, pmid = {37619924}, issn = {1872-8324}, abstract = {Virtually every biological system is governed by complex relations among its components. Identifying such relations requires a rigorous or heuristics-based search for patterns among variables/features of a system. Various algorithms have been developed to identify two-dimensional (involving two variables) patterns employing correlation, covariation, mutual information, etc. It seems obvious, however, that comprehensive descriptions of complex biological systems need also to include more complicated multivariable relations, which can only be described using patterns that simultaneously embrace 3, 4, and more variables. The goal of this manuscript is to (a) introduce a novel type of associations (multivariable Boolean patterns) that can be manifested between features of complex systems but cannot be identified (described) by traditional pair-vise metrics; (b) propose patterns classification method, and (c) provide a novel definition of the pattern's strength (pattern's score) able to accommodate heterogeneous multi-omics data. To demonstrate the presence of such patterns, we performed a search for all possible 2-, 3-, and 4-dimensional patterns in historical data from the Human Microbiome Project (15 body sites) and collection of H. pylori genomes associated with gastric ulcers, gastritis, and duodenal ulcers. In all datasets under consideration, we were able to identify hundreds of statistically significant multivariable patterns. These results suggest that such patterns can be common in microbial genomics/microbiomics systems.}, }
@article {pmid37609252, year = {2023}, author = {Hsu, TY and Nzabarushimana, E and Wong, D and Luo, C and Beiko, RG and Langille, M and Huttenhower, C and Nguyen, LH and Franzosa, EA}, title = {Profiling novel lateral gene transfer events in the human microbiome.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37609252}, issn = {2692-8205}, support = {K23 DK125838/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; T32 CA009001/CA/NCI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, abstract = {Lateral gene transfer (LGT) is an important mechanism for genome diversification in microbial populations, including the human microbiome. While prior work has surveyed LGT events in human-associated microbial isolate genomes, the scope and dynamics of novel LGT events arising in personal microbiomes are not well understood, as there are no widely adopted computational methods to detect, quantify, and characterize LGT from complex microbial communities. We addressed this by developing, benchmarking, and experimentally validating a computational method (WAAFLE) to profile novel LGT events from assembled metagenomes. Applying WAAFLE to >2K human metagenomes from diverse body sites, we identified >100K putative high-confidence but previously uncharacterized LGT events (~2 per assembled microbial genome-equivalent). These events were enriched for mobile elements (as expected), as well as restriction-modification and transport functions typically associated with the destruction of foreign DNA. LGT frequency was quantifiably influenced by biogeography, the phylogenetic similarity of the involved taxa, and the ecological abundance of the donor taxon. These forces manifest as LGT networks in which hub species abundant in a community type donate unequally with their close phylogenetic neighbors. Our findings suggest that LGT may be a more ubiquitous process in the human microbiome than previously described. The open-source WAAFLE implementation, documentation, and data from this work are available at http://huttenhower.sph.harvard.edu/waafle.}, }
@article {pmid37607643, year = {2023}, author = {Kloepfer, KM and Kennedy, JL}, title = {Childhood respiratory viral infections and the microbiome.}, journal = {The Journal of allergy and clinical immunology}, volume = {152}, number = {4}, pages = {827-834}, pmid = {37607643}, issn = {1097-6825}, support = {U19 AI070535/AI/NIAID NIH HHS/United States ; U01 AI143514/AI/NIAID NIH HHS/United States ; R21 AI154127/AI/NIAID NIH HHS/United States ; U01 AI126614/AI/NIAID NIH HHS/United States ; R21 AI156446/AI/NIAID NIH HHS/United States ; P01 HL158507/HL/NHLBI NIH HHS/United States ; U01 AI179563/AI/NIAID NIH HHS/United States ; P01 HL114471/HL/NHLBI NIH HHS/United States ; R01 HL137192/HL/NHLBI NIH HHS/United States ; }, mesh = {Child ; Humans ; *Microbiota ; *Virus Diseases ; *Asthma ; Lung/microbiology ; Bacteria ; *Viruses ; }, abstract = {The human microbiome associated with the respiratory tract is diverse, heterogeneous, and dynamic. The diversity and complexity of the microbiome and the interactions between microorganisms, host cells, and the host immune system are complex and multifactorial. Furthermore, the lymphatics provide a direct highway, the gut-lung axis, for the gut microbiome to affect outcomes related to respiratory disease and the host immune response. Viral infections in the airways can also alter the presence or absence of bacterial species, which might increase the risks for allergies and asthma. Viruses infect the airway epithelium and interact with the host to promote inflammatory responses that can trigger a wheezing illness. This immune response may alter the host's immune response to microbes and allergens, leading to T2 inflammation. However, exposure to specific bacteria may also tailor the host's response long before the virus has infected the airway. The frequency of viral infections, age at infection, sampling season, geographic location, population differences, and preexisting composition of the microbiota have all been linked to changes in microbiota diversity and stability. This review aims to evaluate the current reported evidence for microbiome interactions and the influences that viral infection may have on respiratory and gut microbiota, affecting respiratory outcomes in children.}, }
@article {pmid37607064, year = {2023}, author = {Wan, KH and Park, S and Booth, BW and Brydon, EC and Eichenberger, J and Inman, JL and Mao, JH and Snijders, AM and Celniker, SE}, title = {Complete genome sequence of the Microbacterium sp. strain BDGP8.}, journal = {Microbiology resource announcements}, volume = {12}, number = {9}, pages = {e0038423}, pmid = {37607064}, issn = {2576-098X}, support = {U.S. Department of Energy Contract No. DE-AC02-05CH11231//DNI | Intelligence Advanced Research Projects Activity (IARPA)/ ; }, abstract = {Microbacterium sp. BDGP8 is a species of facultative anaerobic gram-positive bacterium of the family Microbacteriaceae. The complete genome consists of a single circular chromosome of 3,293,567 bp with a G + C content of 69.84% and two plasmids of 49,365 bp and 32,884 bp.}, }
@article {pmid37603700, year = {2023}, author = {Singh, A and Amod, A and Mulpuru, V and Mishra, N and Sahoo, AK and Samanta, SK}, title = {Finding Novel AMPs Secreted from the Human Microbiome as Potent Antibacterial and Antibiofilm Agents and Studying Their Synergistic Activity with Ag NCs.}, journal = {ACS applied bio materials}, volume = {6}, number = {9}, pages = {3674-3682}, doi = {10.1021/acsabm.3c00302}, pmid = {37603700}, issn = {2576-6422}, mesh = {Humans ; *Antimicrobial Peptides ; Biological Transport ; Anti-Bacterial Agents/pharmacology ; *Microbiota ; Biofilms ; }, abstract = {Due to the enhanced resistance of bacteria to antibiotics, researchers always try to find effective alternatives to treat drug-resistant bacterial infections. In this context, we have explored antimicrobial peptides (AMPs), which are a broad class of small peptide molecules, and investigated their efficacy as potent antibacterial and antibiofilm agents. AMPs can cause cell death either through disruption of the cell membrane or by inhibiting vital intracellular functions, by binding to RNA, DNA, or intracellular components upon transversion through the cell membrane. We attempted to find potent intracellular cationic AMPs that can demonstrate antibacterial activity through interaction with DNA. As a source of AMPs, we have utilized those that are secreted from the human microbiome with the anticipation that these will be non-toxic in nature. Out of the total 1087 AMPs, 27 were screened on the basis of amino acid length and efficacy to cross the cell membrane barrier. From the list of 27 peptides, 4 candidates were selected through the docking score of these peptides with the DNA binding domain of H2A proteins. Further, the molecular dynamics simulation analysis demonstrated that 2 AMPs, i.e., peptides 7 and 25, are having considerable membrane permeation and DNA binding ability. Further, the in vitro analysis indicated that both peptides 7 and 25 could exhibit potent antibacterial and antibiofilm activities. In order to further enhance the antibiofilm potency, the above AMPs were used as supplements to silver nanoclusters (Ag NCs) to get synergistic activity. The synergistic activity of Ag NCs was found to be significantly increased with both the above AMPs.}, }
@article {pmid37603579, year = {2023}, author = {Liu, Y and Zhang, YZ and Imoto, S}, title = {Microbial Gene Ontology informed deep neural network for microbe functionality discovery in human diseases.}, journal = {PloS one}, volume = {18}, number = {8}, pages = {e0290307}, pmid = {37603579}, issn = {1932-6203}, mesh = {Humans ; *Genes, Microbial ; Benchmarking ; Gene Ontology ; *Inflammatory Bowel Diseases/genetics ; Neural Networks, Computer ; }, abstract = {The human microbiome plays a crucial role in human health and is associated with a number of human diseases. Determining microbiome functional roles in human diseases remains a biological challenge due to the high dimensionality of metagenome gene features. However, existing models were limited in providing biological interpretability, where the functional role of microbes in human diseases is unexplored. Here we propose to utilize a neural network-based model incorporating Gene Ontology (GO) relationship network to discover the microbe functionality in human diseases. We use four benchmark datasets, including diabetes, liver cirrhosis, inflammatory bowel disease, and colorectal cancer, to explore the microbe functionality in the human diseases. Our model discovered and visualized the novel candidates' important microbiome genes and their functions by calculating the important score of each gene and GO term in the network. Furthermore, we demonstrate that our model achieves a competitive performance in predicting the disease by comparison with other non-Gene Ontology informed models. The discovered candidates' important microbiome genes and their functions provide novel insights into microbe functional contribution.}, }
@article {pmid37602324, year = {2023}, author = {Suryavanshi, M and Agudelo, J and Miller, A}, title = {Rare phylotypes in stone, stool, and urine microbiomes are associated with urinary stone disease.}, journal = {Frontiers in molecular biosciences}, volume = {10}, number = {}, pages = {1210225}, pmid = {37602324}, issn = {2296-889X}, abstract = {Introduction: In complex microbial communities, the importance of microbial species at very low abundance levels and their prevalence for overall community structure and function is increasingly being recognized. Clinical microbiome studies on urinary stone disease (USD) have indicated that both the gut and urinary tract microbiota are associated with the onset of the disease and that kidney stones them-selves harbor a complex, yet consistent and viable, microbiome. However, how rare phylotypes contribute to this association remains unclear. Delineating the contribution of rare and common phylotypes to urinary stone disease is important for the development of bacteriotherapies to promote urologic health. Methods: The objectives of the current report were to conduct a metaanalysis of 16S rRNA datasets derived from the kidney stone, stool, and urine samples of participants with or without urinary stone disease. To delineate the impact of rare and common phylotypes, metaanalyses were conducted by first separating rare and common taxa determined by both the frequency and abundance of amplicon sequence variants. Results: Consistent with previous analyses, we found that gut, upper urinary, and lower urinary tract microbiomes were all unique. Rare phylotypes comprised the majority of species observed in all sample types, with kidney stones exhibiting the greatest bias toward rarity, followed by urine and stool. Both rare and common fractions contributed significantly to the differences observed between sample types and health disparity. Furthermore, the rare and common fractions were taxonomically unique across all sample types. A total of 222 and 320 unique rare phylotypes from urine and stool samples were found to be significantly associated with USD. A co-occurrence correlation analysis revealed that rare phylotypes are most important for microbiome structure in stones, followed by urine and stool. Discussion: Collectively, the results indicate that rare phylotypes may be important for the pathophysiology of USD, particularly in the kidney stone matrix, which is inherently a very low microbial biomass niche that can have implications for the diagnosis and treatment of kidney stones. Further studies are needed to investigate the functional significance of rare phylotypes in kidney stone pathogenesis.}, }
@article {pmid37602232, year = {2023}, author = {Guo, C and Yi, B and Wu, J and Lu, J}, title = {The microbiome in post-acute infection syndrome (PAIS).}, journal = {Computational and structural biotechnology journal}, volume = {21}, number = {}, pages = {3904-3911}, pmid = {37602232}, issn = {2001-0370}, abstract = {Post-Acute Infection Syndrome (PAIS) is a relatively new medical terminology that represents prolonged sequelae symptoms after acute infection by numerous pathogenic agents. Imposing a substantial public health burden worldwide, PASC (post-acute sequelae of COVID-19 infection) and ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome) are two of the most recognized and prevalent PAIS conditions. The presences of prior infections and similar symptom profiles in PAIS reflect a plausible common etiopathogenesis. The human microbiome is known to play an essential role in health and disease. In this review, we reviewed and summarized available research on oral and gut microbiota alterations in patients with different infections or PAIS conditions. We discussed key theories about the associations between microbiome dysbiosis and PAIS disease development, aiming to explore the mechanistic roles and potential functions the microbiome may have in the process. Additionally, we discuss the areas of knowledge gaps and propose the potential clinical applications of the microbiome for prevention and treatment of PAIS conditions.}, }
@article {pmid37600938, year = {2023}, author = {Reuben, RC and Beugnon, R and Jurburg, SD}, title = {COVID-19 alters human microbiomes: a meta-analysis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1211348}, pmid = {37600938}, issn = {2235-2988}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected a substantial portion of the world's population, and novel consequences of COVID-19 on the human body are continuously being uncovered. The human microbiome plays an essential role in host health and well-being, and multiple studies targeting specific populations have reported altered microbiomes in patients infected with SARS-CoV-2. Given the global scale and massive incidence of COVID on the global population, determining whether the effects of COVID-19 on the human microbiome are consistent and generalizable across populations is essential.<br><br>METHODS: We performed a synthesis of human microbiome responses to COVID-19. We collected 16S rRNA gene amplicon sequence data from 11 studies sampling the oral and nasopharyngeal or gut microbiome of COVID-19-infected and uninfected subjects. Our synthesis included 1,159 respiratory (oral and nasopharyngeal) microbiome samples and 267 gut microbiome samples from patients in 11 cities across four countries.<br><br>RESULTS: Our reanalyses revealed communitywide alterations in the respiratory and gut microbiomes across human populations. We found significant overall reductions in the gut microbial diversity of COVID-19-infected patients, but not in the respiratory microbiome. Furthermore, we found more consistent community shifts in the gut microbiomes of infected patients than in the respiratory microbiomes, although the microbiomes in both sites exhibited higher host-to-host variation in infected patients. In respiratory microbiomes, COVID-19 infection resulted in an increase in the relative abundance of potentially pathogenic bacteria, including Mycoplasma.<br><br>DISCUSSION: Our findings shed light on the impact of COVID-19 on the human-associated microbiome across populations, and highlight the need for further research into the relationship between long-term effects of COVID-19 and altered microbiota.}, }
@article {pmid37596619, year = {2023}, author = {Li, F and Ling, X and Chakraborty, S and Fountzilas, C and Wang, J and Jamroze, A and Liu, X and Kalinski, P and Tang, DG}, title = {Role of the DEAD-box RNA helicase DDX5 (p68) in cancer DNA repair, immune suppression, cancer metabolic control, virus infection promotion, and human microbiome (microbiota) negative influence.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {42}, number = {1}, pages = {213}, pmid = {37596619}, issn = {1756-9966}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; R01 CA237027/CA/NCI NIH HHS/United States ; 20-65-FENG/PCAN/Pancreatic Cancer Action Network/United States ; R01 CA240290/CA/NCI NIH HHS/United States ; R44 CA176937/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Cell Transformation, Neoplastic ; *DEAD-box RNA Helicases/genetics ; DNA Repair ; *Microbiota ; Prostatic Neoplasms ; Signal Transduction ; Immunosuppression Therapy ; }, abstract = {There is increasing evidence indicating the significant role of DDX5 (also called p68), acting as a master regulator and a potential biomarker and target, in tumorigenesis, proliferation, metastasis and treatment resistance for cancer therapy. However, DDX5 has also been reported to act as an oncosuppressor. These seemingly contradictory observations can be reconciled by DDX5's role in DNA repair. This is because cancer cell apoptosis and malignant transformation can represent the two possible outcomes of a single process regulated by DDX5, reflecting different intensity of DNA damage. Thus, targeting DDX5 could potentially shift cancer cells from a growth-arrested state (necessary for DNA repair) to apoptosis and cell killing. In addition to the increasingly recognized role of DDX5 in global genome stability surveillance and DNA damage repair, DDX5 has been implicated in multiple oncogenic signaling pathways. DDX5 appears to utilize distinct signaling cascades via interactions with unique proteins in different types of tissues/cells to elicit opposing roles (e.g., smooth muscle cells versus cancer cells). Such unique features make DDX5 an intriguing therapeutic target for the treatment of human cancers, with limited low toxicity to normal tissues. In this review, we discuss the multifaceted functions of DDX5 in DNA repair in cancer, immune suppression, oncogenic metabolic rewiring, virus infection promotion, and negative impact on the human microbiome (microbiota). We also provide new data showing that FL118, a molecular glue DDX5 degrader, selectively works against current treatment-resistant prostate cancer organoids/cells. Altogether, current studies demonstrate that DDX5 may represent a unique oncotarget for effectively conquering cancer with minimal toxicity to normal tissues.}, }
@article {pmid37592350, year = {2023}, author = {Zhou, J and Boyd, JA and Nyeverecz, B and Vivian, C and Angel, N and Wood, DLA and Hugenholtz, P and Tyson, GW and Krause, L and Ó Cuív, P}, title = {Draft genome sequence of two "Candidatus Intestinicoccus colisanans" strains isolated from faeces of healthy humans.}, journal = {BMC research notes}, volume = {16}, number = {1}, pages = {174}, pmid = {37592350}, issn = {1756-0500}, mesh = {Humans ; Feces ; *Gastrointestinal Microbiome/genetics ; Health Status ; Phylogeny ; Tissue Donors ; }, abstract = {OBJECTIVES: In order to provide a better insight into the functional capacity of the human gut microbiome, we isolated a novel bacterium, "Candidatus Intestinicoccus colisanans" gen. nov. sp. nov., and performed whole genome sequencing. This study will provide new insights into the functional potential of this bacterium and its role in modulating host health and well-being. We expect that this data resource will be useful in providing additional insight into the diversity and functional potential of the human microbiome.<br><br>DATA DESCRIPTION: Here, we report the first draft genome sequences of "Candidatus Intestinicoccus colisanans" strains MH27-1 and MH27-2, recovered from faeces collected from healthy human donors. The genomes were sequenced using short-read Illumina technology and whole-genome-based comparisons and phylogenomics reconstruction indicate that "Candidatus Intestinicoccus colisanans" represents a novel genus and species within the family Acutalibacteraceae. Both genomes were estimated to be >&#x2009;98% completed and to range in size from 2.9 to 3.3&#xa0;Mb with a G&#x2009;+&#x2009;C content of approximately 51%. The gene repertoire of "Candidatus Intestinicoccus colisanans" indicate it is likely a saccharolytic gut bacterium.}, }
@article {pmid37590208, year = {2023}, author = {Mallott, EK and Sitarik, AR and Leve, LD and Cioffi, C and Camargo, CA and Hasegawa, K and Bordenstein, SR}, title = {Human microbiome variation associated with race and ethnicity emerges as early as 3 months of age.}, journal = {PLoS biology}, volume = {21}, number = {8}, pages = {e3002230}, pmid = {37590208}, issn = {1545-7885}, support = {UH3 OD023389/OD/NIH HHS/United States ; P50 DA048756/DA/NIDA NIH HHS/United States ; R01 DA035062/DA/NIDA NIH HHS/United States ; UH3 OD023253/OD/NIH HHS/United States ; UG3 OD023253/OD/NIH HHS/United States ; }, mesh = {Adult ; Child ; Humans ; Ethnicity/genetics ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Knowledge ; Machine Learning ; }, abstract = {Human microbiome variation is linked to the incidence, prevalence, and mortality of many diseases and associates with race and ethnicity in the United States. However, the age at which microbiome variability emerges between these groups remains a central gap in knowledge. Here, we identify that gut microbiome variation associated with race and ethnicity arises after 3 months of age and persists through childhood. One-third of the bacterial taxa that vary across caregiver-identified racial categories in children are taxa reported to also vary between adults. Machine learning modeling of childhood microbiomes from 8 cohort studies (2,756 samples from 729 children) distinguishes racial and ethnic categories with 87% accuracy. Importantly, predictive genera are also among the top 30 most important taxa when childhood microbiomes are used to predict adult self-identified race and ethnicity. Our results highlight a critical developmental window at or shortly after 3 months of age when social and environmental factors drive race and ethnicity-associated microbiome variation and may contribute to adult health and health disparities.}, }
@article {pmid37587941, year = {2023}, author = {Dobon, B and Musciotto, F and Mira, A and Greenacre, M and Schlaepfer, R and Aguileta, G and Astete, LH and Ngales, M and Latora, V and Battiston, F and Vinicius, L and Migliano, AB and Bertranpetit, J}, title = {The making of the oral microbiome in Agta hunter-gatherers.}, journal = {Evolutionary human sciences}, volume = {5}, number = {}, pages = {e13}, pmid = {37587941}, issn = {2513-843X}, abstract = {Ecological and genetic factors have influenced the composition of the human microbiome during our evolutionary history. We analysed the oral microbiota of the Agta, a hunter-gatherer population where some members have adopted an agricultural diet. We show that age is the strongest factor modulating the microbiome, probably through immunosenescence since we identified an increase in the number of species classified as pathogens with age. We also characterised biological and cultural processes generating sexual dimorphism in the oral microbiome. A small subset of oral bacteria is influenced by the host genome, linking host collagen genes to bacterial biofilm formation. Our data also suggest that shifting from a fish/meat diet to a rice-rich diet transforms their microbiome, mirroring the Neolithic transition. All of these factors have implications in the epidemiology of oral diseases. Thus, the human oral microbiome is multifactorial and shaped by various ecological and social factors that modify the oral environment.}, }
@article {pmid37577371, year = {2023}, author = {Naud, S and Valles, C and Abdillah, A and Abou Chacra, L and Mekhalif, FZ and Ibrahim, A and Caputo, A and Baudoin, JP and Gouriet, F and Bittar, F and Lagier, JC and Ranque, S and Fenollar, F and Tidjani Alou, M and Raoult, D}, title = {Preliminary landscape of Candidatus Saccharibacteria in the human microbiome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1195679}, pmid = {37577371}, issn = {2235-2988}, mesh = {Female ; Humans ; Prospective Studies ; Retrospective Studies ; *Bacteria/genetics ; *Microbiota ; Real-Time Polymerase Chain Reaction ; }, abstract = {INTRODUCTION: Candidate Phyla Radiation (CPR) and more specifically Candidatus Saccharibacteria (TM7) have now been established as ubiquitous members of the human oral microbiota. Additionally, CPR have been reported in the gastrointestinal and urogenital tracts. However, the exploration of new human niches has been limited to date.<br><br>METHODS: In this study, we performed a prospective and retrospective screening of TM7 in human samples using standard PCR, real-time PCR, scanning electron microscopy (SEM) and shotgun metagenomics.<br><br>RESULTS: Using Real-time PCR and standard PCR, oral samples presented the highest TM7 prevalence followed by fecal samples, breast milk samples, vaginal samples and urine samples. Surprisingly, TM7 were also detected in infectious samples, namely cardiac valves and blood cultures at a low prevalence (under 3%). Moreover, we observed CPR-like structures using SEM in all sample types except cardiac valves. The reconstruction of TM7 genomes in oral and fecal samples from shotgun metagenomics reads further confirmed their high prevalence in some samples.<br><br>CONCLUSION: This study confirmed, through their detection in multiple human samples, that TM7 are human commensals that can also be found in clinical settings. Their detection in clinical samples warrants further studies to explore their role in a pathological setting.}, }
@article {pmid37574509, year = {2023}, author = {Kolsi, A and Haukka, K and Dougnon, V and Agbankpè, AJ and Fabiyi, K and Virta, M and Skurnik, M and Kantele, A and Kiljunen, S}, title = {Isolation and characterization of three novel Acinetobacter baumannii phages from Beninese hospital wastewater.}, journal = {Archives of virology}, volume = {168}, number = {9}, pages = {228}, pmid = {37574509}, issn = {1432-8798}, mesh = {Humans ; *Bacteriophages/genetics ; *Acinetobacter baumannii ; Wastewater ; Phylogeny ; Host Specificity ; Anti-Bacterial Agents ; }, abstract = {Acinetobacter baumannii is an opportunistic pathogen that is mostly associated with hospital-acquired infections. The rapid emergence of multi- and pan-drug-resistant Acinetobacter strains poses an increasing challenge in hospitals. Phage therapy offers one treatment option for infections caused by A. baumannii. We isolated three phages from Beninese hospital wastewater - fBenAci001, fBenAci002, and fBenAci003 - that infected clinical A. baumannii strains from Finnish patients. Phylogenetic analysis showed that these phages resemble phages of the genus Friunavirus, family Autographiviridae. The isolated phages meet the requirements set for phages used for phage therapy. However, they were found to have a narrow host range, which may limit their therapeutic use.}, }
@article {pmid37572831, year = {2023}, author = {Riekkinen, M and Pakkanen, SH and Hutse, V and Roukaerts, I and Ollgren, J and Käyhty, H and Herzog, C and Rombo, L and Kantele, A}, title = {Coadministered pneumococcal conjugate vaccine decreases immune response to hepatitis A vaccine: a randomized controlled trial.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {29}, number = {12}, pages = {1553-1560}, doi = {10.1016/j.cmi.2023.08.006}, pmid = {37572831}, issn = {1469-0691}, mesh = {Humans ; Adolescent ; Adult ; Hepatitis A Vaccines/adverse effects ; Vaccines, Conjugate ; *Hepatitis A/prevention &amp; control ; Hepatitis A Antibodies ; Antibodies, Bacterial ; Pneumococcal Vaccines ; Streptococcus pneumoniae ; Immunity ; Immunoglobulin G ; *Pneumococcal Infections/prevention &amp; control ; Double-Blind Method ; }, abstract = {OBJECTIVES: We explored the influence of coadministration on safety and immunogenicity of the most common travellers' vaccine hepatitis A (HepA) and the pneumococcal conjugate vaccine (PCV) increasingly used both at home and before travel.<br><br>METHODS: Volunteers aged &#x2265;18&#xa0;years (n&#xa0;=&#xa0;305) were randomly assigned 1:1:1 into three groups receiving: 13-valent PCV (PCV13)&#xa0;+&#xa0;HepA, PCV13, or HepA. Anti-pneumococcal IgG concentrations, opsonophagocytic activity (OPA) titres, and total hepatitis A antibody (anti-HAV) concentrations were measured before and 28&#xa0;&#xb1;&#xa0;3&#xa0;days after vaccination. Adverse events (AEs) were recorded over 4&#xa0;weeks.<br><br>RESULTS: After vaccination, the anti-HAV geometric mean concentration was significantly lower in the PCV13+HepA than the HepA group: 34.47 mIU/mL (95% CI: 26.42-44.97 mIU/mL) versus 72.94 mIU/mL (95% CI: 55.01-96.72 mIU/mL), p&#xa0;<&#xa0;0.001. Anti-HAV &#x2265;10 mIU/mL considered protective was reached by 71 of 85 (83.5%) in the PCV13+HepA group versus 76 of 79 (96.2%) in the HepA group, p 0.008. The increases in anti-pneumococcal IgG and OPA levels were comparable in the PCV13+HepA and PCV13 groups, apart from a bigger rise in the PCV13+HepA group for serotype 3 (one-way ANOVA: serotype 3 IgG p 0.010, OPA p 0.002). AEs proved more frequent among those receiving PCV13 than HepA, but simultaneous administration did not increase the rates: &#x2265;one AE was reported by 45 of 56 (80.4%) PCV13, 43 of 54 (79.6%) PCV13+HepA, and 25 of 53 (47.2%) HepA recipients providing structured AE data.<br><br>DISCUSSION: Coadministration of HepA and PCV13 did not cause safety concerns, nor did it impact the patients' response to PCV13, apart from serotype 3. However, coadministered PCV13 significantly impaired antibody responses to HepA.}, }
@article {pmid37571295, year = {2023}, author = {Lupu, VV and Butnariu, LI and Fotea, S and Morariu, ID and Badescu, MC and Starcea, IM and Salaru, DL and Popp, A and Dragan, F and Lupu, A and Mocanu, A and Chisnoiu, T and Pantazi, AC and Jechel, E}, title = {The Disease with a Thousand Faces and the Human Microbiome-A Physiopathogenic Intercorrelation in Pediatric Practice.}, journal = {Nutrients}, volume = {15}, number = {15}, pages = {}, pmid = {37571295}, issn = {2072-6643}, mesh = {Humans ; Child ; *Gastrointestinal Microbiome ; Quality of Life ; *Microbiota ; *Lupus Erythematosus, Systemic/etiology ; Heart ; }, abstract = {Numerous interrelationships are known in the literature that have the final effect of unmasking or influencing various pathologies. Among these, the present article aims to discuss the connection between systemic lupus erythematosus (SLE) and the human microbiome. The main purpose of this work is to popularize information about the impact of dysbiosis on the pathogenesis and evolutionary course of pediatric patients with SLE. Added to this is the interest in knowledge and awareness of adjunctive therapeutic means that has the ultimate goal of increasing the quality of life. The means by which this can be achieved can be briefly divided into prophylactic or curative, depending on the phase of the condition in which the patient is. We thus reiterate the importance of the clinician acquiring an overview of SLE and the human microbiome, doubled by in-depth knowledge of the physio-pathogenic interactions between the two (in part achieved through the much-studied gut-target organ axes-brain, heart, lung, skin), with the target objective being that of obtaining individualized, multimodal and efficient management for each individual patient.}, }
@article {pmid37562360, year = {2023}, author = {Huang, Z and Zuo, T}, title = {The gut microbiome: Bridging medications and clinical outcomes post stem cell transplantation.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {8}, pages = {1257-1259}, doi = {10.1016/j.chom.2023.06.012}, pmid = {37562360}, issn = {1934-6069}, mesh = {*Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; }, abstract = {Anti-cancer therapies are usually intertwined with prolonged use of drugs, which may lead to different clinical outcomes. Recently in Cell and Cell Host &amp; Microbe, Nguyen et al. and Vallet et al., respectively, deconvolute the drug effects on gut microbiome dynamics underpinning clinical outcomes after allogeneic hematopoietic stem cell transplantation.}, }
@article {pmid37560521, year = {2023}, author = {Xiao, Y and Wu, K and Batool, SS and Wang, Q and Chen, H and Zhai, X and Yu, Z and Huang, J}, title = {Enzymatic properties of alcohol dehydrogenase PedE_M.s. derived from Methylopila sp. M107 and its broad metal selectivity.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1191436}, pmid = {37560521}, issn = {1664-302X}, abstract = {As an important metabolic enzyme in methylotrophs, pyrroloquinoline quinone (PQQ)-dependent alcohol dehydrogenases play significant roles in the global carbon and nitrogen cycles. In this article, a calcium (Ca[2+])-dependent alcohol dehydrogenase PedE_M.s., derived from the methylotroph Methylopila sp. M107 was inserted into the modified vector pCM80 and heterologously expressed in the host Methylorubrum extorquens AM1. Based on sequence analysis, PedE_M.s., a PQQ-dependent dehydrogenase belonging to a methanol/ethanol family, was successfully extracted and purified. Showing by biochemical results, its enzymatic activity was detected as 0.72 U/mg while the Km value was 0.028 mM while employing ethanol as optimal substrate. The activity of PedE_M.s. could be enhanced by the presence of potassium (K[+]) and calcium (Ca[2+]), while acetonitrile and certain common detergents have been found to decrease the activity of PedE_M.s.. In addition, its optimum temperature and pH were 30°C and pH 9.0, respectively. Chiefly, as a type of Ca[2+]-dependent alcohol dehydrogenase, PedE_M.s. maintained 60-80% activity in the presence of 10 mM lanthanides and displayed high affinity for ethanol compared to other PedE-type enzymes. The 3D structure of PedE_M.s. was predicted by AlphaFold, and it had an 8-bladed propeller-like super-barrel. Meanwhile, we could speculate that PedE_M.s. contained the conserved residues Glu213, Asn300, and Asp350 through multiple sequence alignment by Clustal and ESpript. The analysis of enzymatic properties of PedE_M.s. enriches our knowledge of the methanol/ethanol family PQQ-dependent dehydrogenase. This study provides new ideas to broaden the application of alcohol dehydrogenase in alcohol concentration calculation, biosensor preparation, and other industries.}, }
@article {pmid37554313, year = {2023}, author = {Chowdhry, A and Kapoor, P and Bhargava, D and Bagga, DK}, title = {Exploring the oral microbiome: an updated multidisciplinary oral healthcare perspective.}, journal = {Discoveries (Craiova, Romania)}, volume = {11}, number = {2}, pages = {e165}, pmid = {37554313}, issn = {2359-7232}, abstract = {The oral cavity is home to diverse microbial content, collectively called as the oral microbiome. The latest technological advancements have unraveled the intricacies of the oral microbiome. It can be of great importance for oral health care givers to know the fundamentals and latest developments in the field of the oral microbiome, as oral dysbiosis is associated with many common diseases frequently seen and managed by them. These diseases include dental caries, periodontitis, mucosal diseases (such as oral leukoplakia, oral lichen planus, and systemic lupus erythematosus), oral cancers, and even co-infections related to the current COVID-19 pandemic. The emergence of new genomic and molecular biology methodologies has been pivotal for understanding the role of the human microbiome in health and disease. The current review compiles oral microbiome in health and disease with a multidisciplinary dental approach. The insight into the oral microbiome, which is provided dental specialty wise in the current article will initiate and guide researchers of various disciplines in developing microbiome-based therapeutic or prophylactic management strategies, managing public health challenges by microbiome-based boarder interventions and divert resources for preserving and achieving a balanced oral microbiome.}, }
@article {pmid37552810, year = {2023}, author = {Bahuguna, A and Dubey, SK}, title = {Overview of the Mechanistic Potential of Probiotics and Prebiotics in Cancer Chemoprevention.}, journal = {Molecular nutrition &amp; food research}, volume = {67}, number = {19}, pages = {e2300221}, doi = {10.1002/mnfr.202300221}, pmid = {37552810}, issn = {1613-4133}, abstract = {Despite of strides in modern cancer therapeutic strategies, there has not been a successful cure for it until now and prognostic side effects and substantial toxicity to chemotherapy and subsequent homeostatic imbalance remains a major concern for professionals in this field. The significance of the human microbiome in the pathogenesis of cancer is being recognized, documented, and established worldwide. Probiotics and prebiotics are some of the most extensively researched approaches to modulate the microbiota for therapeutic purposes, and research on their potential to prevent and treat cancer has sparked an immense amount of interest. The characteristics of probiotics and prebiotics allow for an array of efficient applications in cancer preventive measures. Probiotics can also be administered coupled with chemotherapy and surgery to alleviate their side effects and help promote the effectiveness of chemotherapeutic drugs. Besides showing promising results they are accompanied by potential risks and controversies that may eventually result in clinical repercussions. This review emphasizes the mechanistic potential and oncosuppressive effects of probiotic and prebiotics through maintenance of intestinal barrier function, modifying innate immune system, immunomodulation, intestinal microbiota metabolism, inhibition of host cell proliferation, preventing pathogen colonization, and exerting selective cytotoxicity against tumor cells.}, }
@article {pmid37548476, year = {2023}, author = {Bucci, V and Ward, DV and Bhattarai, S and Rojas-Correa, M and Purkayastha, A and Holler, D and Qu, MD and Mitchell, WG and Yang, J and Fountain, S and Zeamer, A and Forconi, CS and Fujimori, G and Odwar, B and Cawley, C and Moormann, AM and Wessolossky, M and Maldonado-Contreras, A}, title = {The intestinal microbiota predicts COVID-19 severity and fatality regardless of hospital feeding method.}, journal = {mSystems}, volume = {8}, number = {4}, pages = {e0031023}, pmid = {37548476}, issn = {2379-5077}, support = {U01 CA261276/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *COVID-19 ; SARS-CoV-2 ; Feeding Methods ; Hospitals ; }, abstract = {SARS-CoV-2-positive patients exhibit gut and oral microbiome dysbiosis, which is associated with various aspects of COVID-19 disease (1-4). Here, we aim to identify gut and oral microbiome markers that predict COVID-19 severity in hospitalized patients, specifically severely ill patients compared to moderately ill ones. Moreover, we investigate whether hospital feeding (solid versus enteral), an important cofounder, influences the microbial composition of hospitalized COVID-19 patients. We used random forest classification machine learning models with interpretable secondary analyses. The gut, but not the oral microbiota, was a robust predictor of both COVID-19-related fatality and severity of hospitalized patients, with a higher predictive value than most clinical variables. In addition, perturbations of the gut microbiota due to enteral feeding did not associate with species that were predictive of COVID-19 severity. IMPORTANCE SARS-CoV-2 infection leads to wide-ranging, systemic symptoms with sometimes unpredictable morbidity and mortality. It is increasingly clear that the human microbiome plays an important role in how individuals respond to viral infections. Our study adds to important literature about the associations of gut microbiota and severe COVID-19 illness during the early phase of the pandemic before the availability of vaccines. Increased understanding of the interplay between microbiota and SARS-CoV-2 may lead to innovations in diagnostics, therapies, and clinical predictions.}, }
@article {pmid37545638, year = {2023}, author = {Maslennikov, R and Alieva, A and Poluektova, E and Zharikov, Y and Suslov, A and Letyagina, Y and Vasileva, E and Levshina, A and Kozlov, E and Ivashkin, V}, title = {Sarcopenia in cirrhosis: Prospects for therapy targeted to gut microbiota.}, journal = {World journal of gastroenterology}, volume = {29}, number = {27}, pages = {4236-4251}, pmid = {37545638}, issn = {2219-2840}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; *Sarcopenia/etiology/therapy ; Liver Cirrhosis/complications/therapy/microbiology ; }, abstract = {Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.}, }
@article {pmid37539732, year = {2023}, author = {Jotshi, A and Sukla, KK and Haque, MM and Bose, C and Varma, B and Koppiker, CB and Joshi, S and Mishra, R}, title = {Exploring the human microbiome - A step forward for precision medicine in breast cancer.}, journal = {Cancer reports (Hoboken, N.J.)}, volume = {6}, number = {11}, pages = {e1877}, pmid = {37539732}, issn = {2573-8348}, mesh = {Female ; Humans ; *Breast Neoplasms/genetics/therapy ; Precision Medicine ; Dysbiosis ; Artificial Intelligence ; *Microbiota/genetics ; }, abstract = {BACKGROUND: The second most frequent cancer in the world and the most common malignancy in women is breast cancer. Breast cancer is a significant health concern in India with a high mortality-to-incidence ratio and presentation at a younger age.<br><br>RECENT FINDINGS: Recent studies have identified gut microbiota as a significant factor that can have an influence on the development, treatment, and prognosis of breast cancer. This review article aims to describe the influence of microbial dysbiosis on breast cancer occurrence and the possible interactions between oncobiome and specific breast cancer molecular subtypes. The review further also discusses the role of epigenetics and diet/nutrition in the regulation of the gut and breast microbiome and its association with breast cancer prevention, therapy, and recurrence. Additionally, the recent technological advances in microbiome research, including next-generation sequencing (NGS) technologies, genome sequencing, single-cell sequencing, and microbial metabolomics along with recent advances in artificial intelligence (AI) have also been reviewed. This is an attempt to present a comprehensive status of the microbiome as a key cancer biomarker.<br><br>CONCLUSION: We believe that correlating microbiome and carcinogenesis is important as it can provide insights into the mechanisms by which microbial dysbiosis can influence cancer development and progression, leading to the potential use of the microbiome as a tool for prognostication and personalized therapy.}, }
@article {pmid37533117, year = {2023}, author = {Pantoja-Feliciano De Goodfellow, IG and Agans, R and Barbato, R and Colston, S and Goodson, MS and Hammamieh, R and Hentchel, K and Jones, R and Karl, JP and Kokoska, R and Leary, DH and Mauzy, C and Racicot, K and Stamps, BW and Varaljay, V and Soares, JW}, title = {Meeting report of the sixth annual tri-service microbiome consortium symposium.}, journal = {Environmental microbiome}, volume = {18}, number = {1}, pages = {66}, pmid = {37533117}, issn = {2524-6372}, abstract = {The Tri-Service Microbiome Consortium (TSMC) was founded to enhance collaboration, coordination, and communication of microbiome research among DoD organizations and to facilitate resource, material and information sharing amongst consortium members, which includes collaborators in academia and industry. The 6th Annual TSMC Symposium was a hybrid meeting held in Fairlee, Vermont on 27-28 September 2022 with presentations and discussions centered on microbiome-related topics within seven broad thematic areas: (1) Human Microbiomes: Stress Response; (2) Microbiome Analysis &amp; Surveillance; (3) Human Microbiomes Enablers &amp; Engineering; (4) Human Microbiomes: Countermeasures; (5) Human Microbiomes Discovery - Earth &amp; Space; (6) Environmental Micro &amp; Myco-biome; and (7) Environmental Microbiome Analysis &amp; Engineering. Collectively, the symposium provided an update on the scope of current DoD microbiome research efforts, highlighted innovative research being done in academia and industry that can be leveraged by the DoD, and fostered collaborative opportunities. This report summarizes the activities and outcomes from the 6th annual TSMC symposium.}, }
@article {pmid37532819, year = {2023}, author = {Fletcher, AA and Kelly, MS and Eckhoff, AM and Allen, PJ}, title = {Revisiting the intrinsic mycobiome in pancreatic cancer.}, journal = {Nature}, volume = {620}, number = {7972}, pages = {E1-E6}, pmid = {37532819}, issn = {1476-4687}, support = {K23 AI135090/AI/NIAID NIH HHS/United States ; T32 CA093245/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Mycobiome ; *Pancreatic Neoplasms/genetics ; Pancreas ; Carcinogenesis ; }, abstract = {A growing body of literature suggests that alterations in the human microbiome are causative of disease initiation and progression. Aykut et al. present data supporting the argument that alterations in the gut fungal microbiome (the “mycobiome”), along with the presence of fungal elements within pancreatic tissue (specifically those of the genus Malassezia), are associated with pancreatic oncogenesis. Upon analyzing the human sequencing data presented in the original manuscript, we found few fungal reads in pancreatic tissue samples and did not identify differences in pancreatic or gut mycobiome composition between healthy and pancreatic ductal adenocarcinoma (PDAC) patients. Our re-analysis of these data does not support an association between an intrinsic pancreatic mycobiome and the development of human PDAC, and illustrates the challenges in analyzing microbiome sequencing data from low biomass samples.}, }
@article {pmid37528343, year = {2023}, author = {Chopyk, J and Cobián Güemes, AG and Ramirez-Sanchez, C and Attai, H and Ly, M and Jones, MB and Liu, R and Liu, C and Yang, K and Tu, XM and Abeles, SR and Nelson, K and Pride, DT}, title = {Common antibiotics, azithromycin and amoxicillin, affect gut metagenomics within a household.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {206}, pmid = {37528343}, issn = {1471-2180}, support = {T32 AI007036/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology ; *Amoxicillin/pharmacology ; Azithromycin/pharmacology ; Metagenomics ; Macrolides/pharmacology ; Drug Resistance, Bacterial ; }, abstract = {BACKGROUND: The microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.<br><br>RESULTS: We characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.<br><br>CONCLUSIONS: As we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.}, }
@article {pmid37527009, year = {2023}, author = {Yang, C and Mai, J and Cao, X and Burberry, A and Cominelli, F and Zhang, L}, title = {ggpicrust2: an R package for PICRUSt2 predicted functional profile analysis and visualization.}, journal = {Bioinformatics (Oxford, England)}, volume = {39}, number = {8}, pages = {}, pmid = {37527009}, issn = {1367-4811}, support = {P30 DK097948/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; P30 AG072959/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Software ; RNA, Ribosomal, 16S/genetics ; Phylogeny ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {SUMMARY: Microbiome research is now moving beyond the compositional analysis of microbial taxa in a sample. Increasing evidence from large human microbiome studies suggests that functional consequences of changes in the intestinal microbiome may provide more power for studying their impact on inflammation and immune responses. Although 16S rRNA analysis is one of the most popular and a cost-effective method to profile the microbial compositions, marker-gene sequencing cannot provide direct information about the functional genes that are present in the genomes of community members. Bioinformatic tools have been developed to predict microbiome function with 16S rRNA gene data. Among them, PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) has become one of the most popular functional profile prediction tools, which generates community-wide pathway abundances. However, no state-of-art inference tools are available to test the differences in pathway abundances between comparison groups. We have developed ggpicrust2, an R package, for analyzing functional profiles derived from 16S rRNA sequencing. This powerful tool enables researchers to conduct extensive differential abundance analyses and generate visually appealing visualizations that effectively highlight functional signals. With ggpicrust2, users can obtain publishable results and gain deeper insights into the functional composition of their microbial communities.<br><br>The package is open-source under the MIT and file license and is available at CRAN and https://github.com/cafferychen777/ggpicrust2. Its shiny web is available at https://a95dps-caffery-chen.shinyapps.io/ggpicrust2_shiny/.}, }
@article {pmid37524974, year = {2023}, author = {Walker, AW and Hoyles, L}, title = {Human microbiome myths and misconceptions.}, journal = {Nature microbiology}, volume = {8}, number = {8}, pages = {1392-1396}, pmid = {37524974}, issn = {2058-5276}, mesh = {Humans ; *Communication ; }, abstract = {Over the past two decades, interest in human microbiome research has increased exponentially. Regrettably, this increased activity has brought with it a degree of hype and misinformation, which can undermine progress and public confidence in the research. Here we highlight selected human microbiome myths and misconceptions that lack a solid evidence base. By presenting these examples, we hope to draw increased attention to the implications of inaccurate dogma becoming embedded in the literature, and the importance of acknowledging nuance when describing the complex human microbiome.}, }
@article {pmid37524139, year = {2023}, author = {Lane, JM and Wright, RO and Eggers, S}, title = {The interconnection between obesity and executive function in adolescence: The role of the gut microbiome.}, journal = {Neuroscience and biobehavioral reviews}, volume = {153}, number = {}, pages = {105337}, pmid = {37524139}, issn = {1873-7528}, support = {R00 ES032884/ES/NIEHS NIH HHS/United States ; K99 ES032884/ES/NIEHS NIH HHS/United States ; R01 ES013744/ES/NIEHS NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Humans ; *Gastrointestinal Microbiome/physiology ; Executive Function ; *Pediatric Obesity/complications ; *Microbiota ; Brain/metabolism ; }, abstract = {In the United States, adolescent obesity is a growing epidemic associated with maladaptive executive functioning. Likewise, data link the microbiome to obesity. Emerging microbiome research has demonstrated an interconnection between the gut microbiome and the brain, indicating a bidirectional communication system within the gut-microbiome-brain axis in the pathophysiology of obesity. This narrative review identifies and summarizes relevant research connecting adolescent obesity as it relates to three core domains of executive functioning and the contribution of the gut microbiome in the relationship between obesity and executive functions in adolescence. The review suggests that (1) the interconnection between obesity, executive function, and the gut microbiome is a bidirectional connection, and (2) the gut microbiome may mediate the neurobiological pathways between obesity and executive function deficits. The findings of this review provide valuable insights into obesity-associated executive function deficits and elucidate the possible mediation role of the gut microbiome.}, }
@article {pmid37523293, year = {2023}, author = {Maigoro, AY and Muhammad, M and Bello, B and Useh, U and Lee, S}, title = {Exploration of Gut Microbiome Research in Africa: A Scoping Review.}, journal = {Journal of medicinal food}, volume = {26}, number = {9}, pages = {616-623}, doi = {10.1089/jmf.2023.K.0005}, pmid = {37523293}, issn = {1557-7600}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; Africa ; Dietary Supplements ; }, abstract = {The crucial role of the gut microbiome in various diseases has led to increased interest in interventions and therapeutics targeting the human microbiome. Accordingly, the current scoping review analyzed the diseases and interventions involved in gut microbiome research in Africa. The electronic databases of PubMed, Google Scholar, and Scopus were searched from inception to October 2021. This study identified 48 studies involving 7073 study participants. Of the 48 studies, 20 (42%) used interventions to modulate gut microbiota, whereas the remaining 28 (58%) did not. Out of the total African countries, only 13% were involved in intervention-based gut microbiome research, whereas a larger proportion of 67% were not involved in any gut microbiome research. The interventions used in gut microbiome research in Africa include supplements, natural products, educational approaches, associated pathogens, albendazole, fresh daily yogurt, iron-containing lipid-based nutrient supplements, fecal microbiota transplant, and prophylactic cotrimoxazole. This scoping review highlights the current state of gut microbiome research in Africa. The findings of this review can inform the design of future studies and interventions aimed at improving gut health in African populations.}, }
@article {pmid37516837, year = {2023}, author = {Salonen, T and Jokinen, E and Satokari, R and Lahtinen, P}, title = {Randomized, double-blinded, placebo-controlled pilot study: efficacy of faecal microbiota transplantation on chronic fatigue syndrome.}, journal = {Journal of translational medicine}, volume = {21}, number = {1}, pages = {513}, pmid = {37516837}, issn = {1479-5876}, mesh = {Humans ; Female ; Male ; Adult ; *Fatigue Syndrome, Chronic/therapy ; Fecal Microbiota Transplantation ; Pilot Projects ; Quality of Life ; Double-Blind Method ; }, abstract = {BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transplantation (FMT) on fatigue severity and health-related quality of life (HRQOL) in patients with CFS was evaluated.<br><br>METHODS: Randomized, placebo-controlled pilot trial. Patients and researchers were blinded to treatment assignment. 11 patients with CFS (10 female and 1 male, mean age 42.2&#xa0;years and mean duration of CFS 6.3&#xa0;years) were randomly assigned to receive either FMT from a universal donor (n&#x2009;=&#x2009;5) or autologous FMT (n&#x2009;=&#x2009;6) via colonoscopy. Patients' HRQOL was assessed by using visual analog scale (VAS) and self-reporting questionnaires Modified Fatigue Impact Scale (MFIS), 15D and EQ-5D-3L. Patients' HRQOL was evaluated at baseline, and 1 and 6&#xa0;months after the FMT.<br><br>RESULTS: The baseline VAS scores in the FMT and placebo groups were 62.4 and 76.0 (p&#x2009;=&#x2009;0.29). 1-month scores were 60.0 and 73.7 and 6-months scores 72.8 and 69.5, respectively. Total MFIS scores in the FMT and placebo groups were 59.6 and 61.0 at the baseline (p&#x2009;=&#x2009;0.80), 53.5 and 62.0 at 1&#xa0;month and 58.6 and 56.2 at 6&#xa0;months. Compared to the baseline scores, differences at 1 and 6&#xa0;months were statistically insignificant both in VAS and in MFIS. The 15D and EQ-5D-3L profiles did not change after the FMT or placebo. FMT-related adverse events were not reported.<br><br>CONCLUSION: FMT was safe but did not relieve symptoms or improve the HRQOL of patients with CFS. Small number of study subjects limits the generalizability of these results. Trial Registration ClinicalTrials.gov Identifier NCT04158427, https://register.<br><br>CLINICALTRIALS: gov , date of registration 08/08/2019.}, }
@article {pmid37513952, year = {2023}, author = {Aslan, I and Tarhan Celebi, L and Kayhan, H and Kizilay, E and Gulbahar, MY and Kurt, H and Cakici, B}, title = {Probiotic Formulations Containing Fixed and Essential Oils Ameliorates SIBO-Induced Gut Dysbiosis in Rats.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {16}, number = {7}, pages = {}, pmid = {37513952}, issn = {1424-8247}, abstract = {Dysbiosis of the gut microbiota is associated with the pathogenesis of intestinal diseases such as inflammatory bowel disease, irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), and metabolic disease states such as allergies, cardiovascular diseases, obesity, and diabetes. SIBO is a condition characterized by an increased number (>1 × 10[3] CFU) of abnormal bacterial species in the small intestine. Interest in SIBO has gained importance due to increased awareness of the human microbiome and its potential relationships with human health and disease, which has encouraged new work in this area. In recent years, standard antibiotic regimens (rifaximin and metronidazole) have been used to treat SIBO, but solo antibiotics or their derivatives are insufficient. In this study, the therapeutic effects of the probiotic form, which contains coconut oil and traces of peppermint-lemon-patchouli essential oil, were evaluated on the Dysbiosis-Based Rat SIBO Model. There are significant differences between sick and healthy rats (p = 0.014), between sick rats and rats treated with the oil mix plus probiotic mix protocol (p = 0.026), and between rats treated with only the probiotic and only oil protocols (p = 0.030) in the evaluation of TNF-α levels. Histologically, villi distortion and loss of crypts, epithelial shedding and necrotic changes in the apical regions of the villi, and inflammatory cell infiltrations extending to the lamina propria and submucosa were observed in sick rats. Mitotic figures in villus epithelium and crypts were observed in rats treated with 9.2 × 10[9] CFU/1000 mg/coconut oil + trace amounts of peppermint-lemon-patchouli essential oil and a probiotic mixture (oil + probiotic mix protocol). A regression of inflammatory reactions and an increase in goblet cells were observed. A decrease was observed in inflammation markers in sick rats. On the other hand, the oil plus probiotic mix protocol recovered digestive system defects in the animals caused by dysbiosis. In the future, these treatment approaches can be effective in the treatment of SIBO.}, }
@article {pmid37512565, year = {2023}, author = {Cao, X and Zolnikova, O and Maslennikov, R and Reshetova, M and Poluektova, E and Bogacheva, A and Zharkova, M and Ivashkin, V}, title = {Differences in Fecal Short-Chain Fatty Acids between Alcoholic Fatty Liver-Induced Cirrhosis and Non-alcoholic (Metabolic-Associated) Fatty Liver-Induced Cirrhosis.}, journal = {Metabolites}, volume = {13}, number = {7}, pages = {}, pmid = {37512565}, issn = {2218-1989}, abstract = {The objective of this study was to investigate the metabolic activity of the gut microbiota in cirrhosis due to different variants of fatty liver disease (alcoholic vs. non-alcoholic [metabolic-associated] one [AFLD and MAFLD]). The present study included 24 patients with alcoholic liver cirrhosis, 16 patients with MAFLD-related cirrhosis, and 20 healthy controls. The level and spectrum of short-chain fatty acids (SCFAs) were determined via gas-liquid chromatography. All patients with cirrhosis showed a decrease in the total content of SCFAs (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), butyrate (p < 0.001), and isovalerate (p < 0.001). In MAFLD cirrhosis, the metabolic activity of the microbiota was significantly altered compared to patients with alcoholic cirrhosis, as evidenced by a lower total SCFA content (p < 0.001) and absolute content of acetate (p < 0.001), propionate (p < 0.001), and butyrate (p < 0.001); a higher relative content of isovalerate (p < 0.001); and a higher IsoCn/Cn ratio (p < 0.001). Various clinical and laboratory parameters correlate differently with fecal SCFAs and their fractions in cirrhosis due to AFLD and MAFLD. SCFA-producing metabolic activity is reduced more in MAFLD cirrhosis than in alcoholic cirrhosis. According to the etiological factors of cirrhosis, disorders of this metabolic activity may be involved in different pathogenetic pathways.}, }
@article {pmid37511612, year = {2023}, author = {Mendes, I and Vale, N}, title = {How Can the Microbiome Induce Carcinogenesis and Modulate Drug Resistance in Cancer Therapy?.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511612}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome ; Carcinogenesis ; *Microbiota/genetics ; *Neoplasms/drug therapy/genetics ; Drug Resistance ; }, abstract = {Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted therapies or immunotherapies. Drug resistance in cancer is one of the limiting factors contributing to unsuccessful therapies; therefore, understanding how cancer cells acquire this resistance is essential to help cure individuals affected by cancer. Recently, the altered microbiome was observed to be an important hallmark of cancer and therefore it represents a promising topic of cancer research. Our review aims to provide a global perspective of some cancer hallmarks, for instance how genetic and epigenetic modifications may be caused by an altered human microbiome. We also provide information on how an altered human microbiome can lead to cancer development as well as how the microbiome can influence drug resistance and ultimately targeted therapies. This may be useful to develop alternatives for cancer treatment, i.e., future personalized medicine that can help in cases where traditional cancer treatment is unsuccessful.}, }
@article {pmid37511022, year = {2023}, author = {Neidhöfer, C and Bagniceva, M and Wetzig, N and Sieber, MA and Thiele, R and Parčina, M}, title = {Pragmatic Considerations When Extracting DNA for Metagenomics Analyses of Clinical Samples.}, journal = {International journal of molecular sciences}, volume = {24}, number = {14}, pages = {}, pmid = {37511022}, issn = {1422-0067}, mesh = {DNA, Bacterial/genetics ; *Metagenomics/methods ; Sequence Analysis, DNA/methods ; RNA, Ribosomal, 16S/genetics ; *DNA ; }, abstract = {Microbiome analyses are essential for understanding microorganism composition and diversity, but interpretation is often challenging due to biological and technical variables. DNA extraction is a critical step that can significantly bias results, particularly in samples containing a high abundance of challenging-to-lyse microorganisms. Taking into consideration the distinctive microenvironments observed in different bodily locations, our study sought to assess the extent of bias introduced by suboptimal bead-beating during DNA extraction across diverse clinical sample types. The question was whether complex targeted extraction methods are always necessary for reliable taxonomic abundance estimation through amplicon sequencing or if simpler alternatives are effective for some sample types. Hence, for four different clinical sample types (stool, cervical swab, skin swab, and hospital surface swab samples), we compared the results achieved from extracting targeted manual protocols routinely used in our research lab for each sample type with automated protocols specifically not designed for that purpose. Unsurprisingly, we found that for the stool samples, manual extraction protocols with vigorous bead-beating were necessary in order to avoid erroneous taxa proportions on all investigated taxonomic levels and, in particular, false under- or overrepresentation of important genera such as Blautia, Faecalibacterium, and Parabacteroides. However, interestingly, we found that the skin and cervical swab samples had similar results with all tested protocols. Our results suggest that the level of practical automation largely depends on the expected microenvironment, with skin and cervical swabs being much easier to process than stool samples. Prudent consideration is necessary when extending the conclusions of this study to applications beyond rough estimations of taxonomic abundance.}, }
@article {pmid37509225, year = {2023}, author = {Pandey, A and Lieu, CH and Kim, SS}, title = {The Local Microbiome in Esophageal Cancer and Treatment Response: A Review of Emerging Data and Future Directions.}, journal = {Cancers}, volume = {15}, number = {14}, pages = {}, pmid = {37509225}, issn = {2072-6694}, abstract = {UNLABELLED: The incidence of esophageal cancer is increasing worldwide, with established risk factors explaining only a small fraction of cases. Currently, there are no established screening protocols in most countries, and treatment options are limited. The human microbiome has been implicated in carcinogenesis and the cancer treatment response. The advent of nucleic acid sequencing technologies has enabled more comprehensive, culture-independent bacterial identification. Across several tumor types, studies of tissue-specific microbiomes have shown associations between the overall microbiome composition, the relative abundance of specific bacteria, and tumorigenesis. Furthermore, in the era of cancer immunotherapy, several studies have demonstrated that the microbiome and specific bacteria may modify treatment responses and the risk of immune-related adverse events.<br><br>DESIGN: peer-reviewed, published studies describing the role of local, gastrointestinal-specific microbiota or the role of the gut microbiome in treatment responses were reviewed. PubMed was searched from 1 September 2022 to 1 November 2022, using the following terms in combination: "microbiome", "tumor microbiome", "esophageal cancer", "cancer", "cancer treatment", and "immunotherapy". Original research articles were considered, and other reviews or editorials were discarded. In total, approximately 250 articles were considered.<br><br>RESULTS: over 70 studies describing microbiome research in either gastrointestinal carcinogenesis or the systemic treatment response were identified and reviewed.<br><br>CONCLUSIONS: a growing body of evidence supports the role of the esophageal microbiome in both esophageal tumorigenesis and the immune checkpoint inhibitor response. More well-designed, comprehensive studies are required to collect the appropriate clinical, microbial, and immunophenotype data that are needed to clarify the precise role of the microbiome in esophageal carcinogenesis and treatment.}, }
@article {pmid37508310, year = {2023}, author = {Nyhamar, E and Webber, P and Liong, O and Yilmaz, &#xd6; and Pajunen, M and Skurnik, M and Wan, X}, title = {Discovery of Bactericidal Proteins from Staphylococcus Phage Stab21 Using a High-Throughput Screening Method.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {37508310}, issn = {2079-6382}, support = {288701//Academy of Finland/ ; 200050//Jane and Aatos Erkko Foundation/ ; Decision 2016//Jane and Aatos Erkko Foundation/ ; }, abstract = {In the escalating battle against antimicrobial resistance, there is an urgent need to discover and investigate new antibiotic strategies. Bacteriophages are untapped reservoirs of such potential antimicrobials. This study focused on Hypothetical Proteins of Unknown Function (HPUFs) from a Staphylococcus phage Stab21. We examined its HPUFs for bactericidal activity against E. coli using a Next Generation Sequencing (NGS)-based approach. Among the 96 HPUFs examined, 5 demonstrated cross-species toxicity towards E. coli, suggesting the presence of shared molecular targets between E. coli and S. aureus. One toxic antibacterial HPUF (toxHPUF) was found to share homology with a homing endonuclease. The implications of these findings are profound, particularly given the potential broad applicability of these bactericidal agents. This study confirms the efficacy of NGS in streamlining the screening process of toxHPUFs, contributes significantly to the ongoing exploration of phage biology, and offers promises in the search for potent antimicrobial agents.}, }
@article {pmid37501991, year = {2023}, author = {Abot, A and Brochot, A and Pomié, N and Astre, G and Druart, C and de Vos, WM and Knauf, C and Cani, PD}, title = {Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release.}, journal = {Heliyon}, volume = {9}, number = {7}, pages = {e18196}, pmid = {37501991}, issn = {2405-8440}, abstract = {BACKGROUND AND OBJECTIVE: Pasteurized Akkermansia muciniphila cells have shown anti-diabetic effects in rodents and human. Although, its primary site of action consists in maintaining the gut barrier function, there are no study exploring if A. muciniphila controls glycemia via a gut to brain axis. Targeting the gut motility represents an alternative pathway to treat hyperglycemia. Here, we tested the impact of pasteurized A. muciniphila on gut motility, gut-brain axis and glucose metabolism.<br><br>METHODS: We used mice fed a 45% high-fat (HFD) treated or not with pasteurized A. muciniphila Muc[T] during 12 weeks. We measured the effects of the treatment on body weight gain, glucose metabolism (insulin, glycemia, glucose tolerance), gut contraction and enteric neurotransmitter release, and hypothalamic nitric oxide (NO) release.<br><br>RESULTS: We show that pasteurized A. muciniphila exerts positive effects on different metabolic parameters such as body weight, fat mass, insulin, glycemia and glucose tolerance. This could be explained by the ability of pasteurized A. muciniphila supplementation to decrease duodenal contraction and to increase hypothalamic NO release in HFD mice.<br><br>CONCLUSION: We demonstrate a novel mode of action of pasteurized A. muciniphila explaining its beneficial impact on the control of glycemia in a preclinical model of type 2 diabetes via gut-brain axis signaling.}, }
@article {pmid37498052, year = {2023}, author = {Huang, Z and Li, Y and Park, H and Ho, M and Bhardwaj, K and Sugimura, N and Lee, HW and Meng, H and Ebert, MP and Chao, K and Burgermeister, E and Bhatt, AP and Shetty, SA and Li, K and Wen, W and Zuo, T}, title = {Unveiling and harnessing the human gut microbiome in the rising burden of non-communicable diseases during urbanization.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2237645}, pmid = {37498052}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Urbanization ; *Noncommunicable Diseases/therapy/drug therapy ; *Microbiota ; *Probiotics ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/drug therapy ; Prebiotics ; }, abstract = {The world is witnessing a global increase in the urban population, particularly in developing Asian and African countries. Concomitantly, the global burden of non-communicable diseases (NCDs) is rising, markedly associated with the changing landscape of lifestyle and environment during urbanization. Accumulating studies have revealed the role of the gut microbiome in regulating the immune and metabolic homeostasis of the host, which potentially bridges external factors to the host (patho-)physiology. In this review, we discuss the rising incidences of NCDs during urbanization and their links to the compositional and functional dysbiosis of the gut microbiome. In particular, we elucidate the effects of urbanization-associated factors (hygiene/pollution, urbanized diet, lifestyles, the use of antibiotics, and early life exposure) on the gut microbiome underlying the pathogenesis of NCDs. We also discuss the potential and feasibility of microbiome-inspired and microbiome-targeted approaches as novel avenues to counteract NCDs, including fecal microbiota transplantation, diet modulation, probiotics, postbiotics, synbiotics, celobiotics, and precision antibiotics.}, }
@article {pmid37498047, year = {2023}, author = {Kandalai, S and Li, H and Zhang, N and Peng, H and Zheng, Q}, title = {The human microbiome and cancer: a diagnostic and therapeutic perspective.}, journal = {Cancer biology &amp; therapy}, volume = {24}, number = {1}, pages = {2240084}, pmid = {37498047}, issn = {1555-8576}, mesh = {Humans ; *Microbiota ; *Neoplasms/diagnosis/therapy ; Immunotherapy ; }, abstract = {Recent evidence has shown that the human microbiome is associated with various diseases, including cancer. The salivary microbiome, fecal microbiome, and circulating microbial DNA in blood plasma have all been used experimentally as diagnostic biomarkers for many types of cancer. The microbiomes present within local tissue, other regions, and tumors themselves have been shown to promote and restrict the development and progression of cancer, most often by affecting cancer cells or the host immune system. These microbes have also been shown to impact the efficacy of various cancer therapies, including radiation, chemotherapy, and immunotherapy. Here, we review the research advances focused on how microbes impact these different facets and why they are important to the clinical care of cancer. It is only by better understanding the roles these microbes play in the diagnosis, development, progression, and treatment of cancer, that we will be able to catch and treat cancer early.}, }
@article {pmid37484251, year = {2023}, author = {Bappy, MNI and Robin, TB and Prome, AA and Patil, RB and Moin, AT and Akter, R and Laskar, FS and Roy, A and Akter, H and Zinnah, KMA}, title = {Subtractive proteomics analysis to uncover the potent drug targets for distinctive drug design of Candidaauris.}, journal = {Heliyon}, volume = {9}, number = {6}, pages = {e17026}, pmid = {37484251}, issn = {2405-8440}, abstract = {Candida auris is a serious health concern of the current world that possesses a serious global health threat and is emerging at a high rate. Available antifungal drugs are failing to combat this pathogen as they are growing resistant to those drugs and some strains have already shown resistance to all three available antifungal drugs in the market. Hence, finding alternative therapies is essential for saving lives from this enemy. To make the development of new treatments easier, we conducted some in silico study of this pathogen to discover possible targets for drug design and also recommended some possible metabolites to test in vivo circumstances. The complete proteome of the representative strain was retrieved, and the duplicate, non-essential, human homologous, non-metabolic, and druggable proteins were then eliminated. As a result, out of a total of 5441 C. auris proteins, we were able to isolate three proteins (XP 028890156.1, XP 028891672.1, and XP 028891858.1) that are crucial for the pathogen's survival as well as host-non-homolog, metabolic, and unrelated proteins to the human microbiome. Their subcellular locations and interactions with a large number of proteins (10 proteins) further point to them being good candidates for therapeutic targets. Following in silico docking of 29 putative antifungals of plant origin against the three proteins we chose, Caledonixanthone E, Viniferin, Glaucine, and Jatrorrhizine were discovered to be the most effective means of inhibiting those proteins since they displayed higher binding affinities (ranging from -28.97 kcal/mol to -51.99 kcal/mol) than the control fluconazole (which ranged between -28.84 kcal/mol and -41.15 kcal/mol). According to the results of MD simulations and MM-PBSA calculations, Viniferin and Caledonixanthone E are the most effective ligands for the proteins XP 028890156.1, XP 028891672.1, and XP 028891858.1. Furthermore, they were predicted to be safe and also showed proper ADME properties.}, }
@article {pmid37480129, year = {2023}, author = {Coccolini, F and Sartelli, M and Sawyer, R and Rasa, K and Viaggi, B and Abu-Zidan, F and Soreide, K and Hardcastle, T and Gupta, D and Bendinelli, C and Ceresoli, M and Shelat, VG and Broek, RT and Baiocchi, GL and Moore, EE and Sall, I and Podda, M and Bonavina, L and Kryvoruchko, IA and Stahel, P and Inaba, K and Montravers, P and Sakakushev, B and Sganga, G and Ballestracci, P and Malbrain, MLNG and Vincent, JL and Pikoulis, M and Beka, SG and Doklestic, K and Chiarugi, M and Falcone, M and Bignami, E and Reva, V and Demetrashvili, Z and Di Saverio, S and Tolonen, M and Navsaria, P and Bala, M and Balogh, Z and Litvin, A and Hecker, A and Wani, I and Fette, A and De Simone, B and Ivatury, R and Picetti, E and Khokha, V and Tan, E and Ball, C and Tascini, C and Cui, Y and Coimbra, R and Kelly, M and Martino, C and Agnoletti, V and Boermeester, MA and De'Angelis, N and Chirica, M and Biffl, WL and Ansaloni, L and Kluger, Y and Catena, F and Kirkpatrick, AW}, title = {Source control in emergency general surgery: WSES, GAIS, SIS-E, SIS-A guidelines.}, journal = {World journal of emergency surgery : WJES}, volume = {18}, number = {1}, pages = {41}, pmid = {37480129}, issn = {1749-7922}, mesh = {Female ; Humans ; Male ; *Surgeons ; *Abdominal Cavity ; *Intraabdominal Infections ; }, abstract = {Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections.}, }
@article {pmid37479864, year = {2023}, author = {Freitas, P and Silva, F and Sousa, JV and Ferreira, RM and Figueiredo, C and Pereira, T and Oliveira, HP}, title = {Machine learning-based approaches for cancer prediction using microbiome data.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11821}, pmid = {37479864}, issn = {2045-2322}, mesh = {Humans ; *Colonic Neoplasms/diagnosis ; *Rectal Neoplasms ; *Stomach Neoplasms/diagnosis ; Machine Learning ; *Microbiota/genetics ; }, abstract = {Emerging evidence of the relationship between the microbiome composition and the development of numerous diseases, including cancer, has led to an increasing interest in the study of the human microbiome. Technological breakthroughs regarding DNA sequencing methods propelled microbiome studies with a large number of samples, which called for the necessity of more sophisticated data-analytical tools to analyze this complex relationship. The aim of this work was to develop a machine learning-based approach to distinguish the type of cancer based on the analysis of the tissue-specific microbial information, assessing the human microbiome as valuable predictive information for cancer identification. For this purpose, Random Forest algorithms were trained for the classification of five types of cancer-head and neck, esophageal, stomach, colon, and rectum cancers-with samples provided by The Cancer Microbiome Atlas database. One versus all and multi-class classification studies were conducted to evaluate the discriminative capability of the microbial data across increasing levels of cancer site specificity, with results showing a progressive rise in difficulty for accurate sample classification. Random Forest models achieved promising performances when predicting head and neck, stomach, and colon cancer cases, with the latter returning accuracy scores above 90% across the different studies conducted. However, there was also an increased difficulty when discriminating esophageal and rectum cancers, failing to differentiate with adequate results rectum from colon cancer cases, and esophageal from head and neck and stomach cancers. These results point to the fact that anatomically adjacent cancers can be more complex to identify due to microbial similarities. Despite the limitations, microbiome data analysis using machine learning may advance novel strategies to improve cancer detection and prevention, and decrease disease burden.}, }
@article {pmid37479852, year = {2023}, author = {Ren, Q and Hill, JE}, title = {Rapid and accurate taxonomic classification of cpn60 amplicon sequence variants.}, journal = {ISME communications}, volume = {3}, number = {1}, pages = {77}, pmid = {37479852}, issn = {2730-6151}, abstract = {The "universal target" region of the gene encoding the 60 kDa chaperonin protein (cpn60, also known as groEL or hsp60) is a proven sequence barcode for bacteria and a useful target for marker gene amplicon-based studies of complex microbial communities. To date, identification of cpn60 sequence variants from microbiome studies has been accomplished by alignment of queries to a reference database. Naïve Bayesian classifiers offer an alternative identification method that provides variable rank classification and shorter analysis times. We curated a set of cpn60 barcode sequences to train the RDP classifier and tested its performance on data from previous human microbiome studies. Results showed that sequences accounting for 79%, 86% and 92% of the observations (read counts) in saliva, vagina and infant stool microbiome data sets were classified to the species rank. We also trained the QIIME 2 q2-feature-classifier on cpn60 sequence data and demonstrated that it gives results consistent with the standalone RDP classifier. Successful implementation of a naïve Bayesian classifier for cpn60 sequences will facilitate future microbiome studies and open opportunities to integrate cpn60 amplicon sequence identification into existing analysis pipelines.}, }
@article {pmid37479064, year = {2023}, author = {Bosch, B and Moutaharrik, S and Gazzaniga, A and Hiippala, K and Santos, HA and Maroni, A and Satokari, R}, title = {Development of a time-dependent oral colon delivery system of anaerobic Odoribacter splanchnicus for bacteriotherapy.}, journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V}, volume = {190}, number = {}, pages = {73-80}, doi = {10.1016/j.ejpb.2023.07.010}, pmid = {37479064}, issn = {1873-3441}, mesh = {*Inflammatory Bowel Diseases/metabolism ; Anaerobiosis ; Drug Delivery Systems ; Tablets/metabolism ; Anti-Inflammatory Agents/metabolism ; Humans ; Bacteroidetes ; Hydrogen-Ion Concentration ; *Colon/metabolism ; }, abstract = {Odoribacter (O.) splanchnicus is an anaerobic member of the human intestinal microbiota. Its decrease in abundance has been associated with inflammatory bowel disease (IBD), non-alcoholic fatty liver, and cystic fibrosis. Considering the anti-inflammatory properties of O. splanchnicus and its possible use for IBD, intestinal isolate O. splanchnicus 57 was here formulated for oral colonic release based on a time-dependent strategy. Freeze-drying protocol was determined to ensure O. splanchnicus 57 viability during the process. Disintegrating tablets, containing the freeze-dried O. splanchnicus 57, were manufactured by direct compression and coated by powder-layering technique with hydroxypropyl methylcellulose (Methocel™ E50) in a tangential-spray fluid bed. Eudragit® L was then applied by spray-coating in a top-spray fluid bed. Double-coated tablets were tested for release, showing gastric resistance properties and, as desired, lag phases of reproducible duration prior to release in phosphate buffer pH 6.8. The cell viability and anti-inflammatory activity of the strain were assessed after the main manufacturing steps. While freeze-drying did not affect bacterial viability, the tableting and coating processes were more stressful. Nonetheless, O. splanchnicus 57 cells survived manufacturing and the final formulations had 10[6]-10[7] CFU/g of viable cells. The strain kept its anti-inflammatory properties after tableting and coating, reducing Escherichia coli lipopolysaccharide-induced interleukin-8 cytokine release from HT-29 cells. Overall, O. splanchnicus 57 strain was formulated successfully for oral colon delivery, opening new ways to formulate pure cultures of single anaerobic strains or mixtures for oral delivery.}, }
@article {pmid37474544, year = {2023}, author = {Castellini, G and Cassioli, E and Vitali, F and Rossi, E and Dani, C and Melani, G and Flaccomio, D and D'Andria, M and Mejia Monroy, M and Galli, A and Cavalieri, D and Ricca, V and Bartolucci, GL and De Filippo, C}, title = {Gut microbiota metabolites mediate the interplay between childhood maltreatment and psychopathology in patients with eating disorders.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {11753}, pmid = {37474544}, issn = {2045-2322}, mesh = {Humans ; Child ; Adolescent ; Young Adult ; *Gastrointestinal Microbiome ; *Feeding and Eating Disorders ; *Anorexia Nervosa/psychology ; Butyrates ; *Child Abuse ; }, abstract = {Eating disorders (EDs) are syndromes with a multifactorial etiopathogenesis, involving childhood traumatic experiences, as well as biological factors. Human microbiome has been hypothesised to play a fundamental role, impacting on emotion regulation, as well as with eating behaviours through its metabolites such as short chain fatty acids (SCFAs). The present study investigated the interactions between psychopathology of EDs, the gut microbiome and SCFAs resulting from bacterial community metabolic activities in a population of 47 patients with Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder and in healthy controls (HCs). Bacterial gut microbiota composition differences were found between subjects with EDs and HCs, especially in association with different pathological behaviours (binge-purge vs restricting). A mediation model of early trauma and ED-specific psychopathology linked reduction of microbial diversity to a typical microbiota-derived metabolite such as butyric acid. A possible interpretation for this model might be that childhood trauma represents a risk factor for gut dysbiosis and for a stable modification of mechanisms responsible for SCFAs production, and that this dysfunctional community is inherited in the passage from childhood to adulthood. These findings might open the way to novel interventions of butyric acid-like compounds as well as faecal transplant.}, }
@article {pmid37469430, year = {2023}, author = {Fernandez-Cantos, MV and Garcia-Morena, D and Yi, Y and Liang, L and Gómez-Vázquez, E and Kuipers, OP}, title = {Bioinformatic mining for RiPP biosynthetic gene clusters in Bacteroidales reveals possible new subfamily architectures and novel natural products.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1219272}, pmid = {37469430}, issn = {1664-302X}, abstract = {The Bacteroidales order, widely distributed among diverse human populations, constitutes a key component of the human microbiota. Members of this Gram-negative order have been shown to modulate the host immune system, play a fundamental role in the gut's microbial food webs, or be involved in pathogenesis. Bacteria inhabiting such a complex environment as the human microbiome are expected to display social behaviors and, hence, possess factors that mediate cooperative and competitive interactions. Different types of molecules can mediate interference competition, including non-ribosomal peptides (NRPs), polyketides, and bacteriocins. The present study investigates the potential of Bacteroidales bacteria to biosynthesize class I bacteriocins, which are ribosomally synthesized and post-translationally modified peptides (RiPPs). For this purpose, 1,136 genome-sequenced strains from this order were mined using BAGEL4. A total of 1,340 areas of interest (AOIs) were detected. The most commonly identified enzymes involved in RiPP biosynthesis were radical S-adenosylmethionine (rSAM), either alone or in combination with other biosynthetic enzymes such as YcaO. A more comprehensive analysis of a subset of 9 biosynthetic gene clusters (BGCs) revealed a consistent association in Bacteroidales BGCs between peptidase-containing ATP-binding transporters (PCATs) and precursor peptides with GG-motifs. This finding suggests a possibly shared mechanism for leader peptide cleavage and transport of mature products. Notably, human metagenomic studies showed a high prevalence and abundance of the RiPP BGCs from Phocaeicola vulgatus and Porphyromonas gulae. The mature product of P. gulae BGC is hypothesized to display γ-thioether linkages and a C-terminal backbone amidine, a potential new combination of post-translational modifications (PTM). All these findings highlight the RiPP biosynthetic potential of Bacteroidales bacteria, as a rich source of novel peptide structures of possible relevance in the human microbiome context.}, }
@article {pmid37466413, year = {2024}, author = {Revankar, NA and Negi, PS}, title = {Biotics: An emerging food supplement for health improvement in the era of immune modulation.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {39}, number = {2}, pages = {311-329}, doi = {10.1002/ncp.11036}, pmid = {37466413}, issn = {1941-2452}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; Immunity ; }, abstract = {The involvement of the commensal microbiota in immune function is a multifold process. Biotics, such as probiotics, prebiotics, synbiotics, and paraprobiotics, have been subjected to animal and human trials demonstrating the association between gut microbes and immunity biomarkers leading to improvement in overall health. In recent years, studies on human microbiome interaction have established the multifarious role of biotics in maintaining overall health. The consumption of biotics has been extensively reported to help in maintaining microbial diversity, enhancing gut-associated mucosal immune homeostasis, and providing protection against a wide range of lifestyle disorders. However, the establishment of biotics as an alternative therapy for a range of health conditions is yet to be ascertained. Despite the fact that scientific literature has demonstrated the correlation between biotics and immune modulation, most in vivo and in vitro reports are inconclusive on the dosage required. This review provides valuable insights into the immunomodulatory effects of biotics consumption based on evidence obtained from animal models and clinical trials. Furthermore, we highlight the optimal dosages of biotics that have been reported to deliver maximum health benefits. By identifying critical research gaps, we have suggested a roadmap for future investigations to advance our understanding of the intricate crosstalk between biotics and immune homeostasis.}, }
@article {pmid37460001, year = {2023}, author = {Boopathi, S and Priya, PS and Haridevamuthu, B and Nayak, SPRR and Chandrasekar, M and Arockiaraj, J and Jia, AQ}, title = {Expanding germ-organ theory: Understanding non-communicable diseases through enterobacterial translocation.}, journal = {Pharmacological research}, volume = {194}, number = {}, pages = {106856}, doi = {10.1016/j.phrs.2023.106856}, pmid = {37460001}, issn = {1096-1186}, mesh = {Humans ; Enterobacteriaceae ; *Noncommunicable Diseases ; *Gastrointestinal Microbiome ; Inflammation/microbiology ; *Microbiota ; }, abstract = {Diverse microbial communities colonize different habitats of the human body, including gut, oral cavity, nasal cavity and tissues. These microbial communities are known as human microbiome, plays a vital role in maintaining the health. However, changes in the composition and functions of human microbiome can result in chronic low-grade inflammation, which can damage the epithelial cells and allows pathogens and their toxic metabolites to translocate into other organs such as the liver, heart, and kidneys, causing metabolic inflammation. This dysbiosis of human microbiome has been directly linked to the onset of several non-communicable diseases. Recent metabolomics studies have revealed that pathogens produce several uraemic toxins. These metabolites can serve as inter-kingdom signals, entering the circulatory system and altering host metabolism, thereby aggravating a variety of diseases. Interestingly, Enterobacteriaceae, a critical member of Proteobacteria, has been commonly associated with several non-communicable diseases, and the abundance of this family has been positively correlated with uraemic toxin production. Hence, this review provides a comprehensive overview of Enterobacterial translocation and their metabolites role in non-communicable diseases. This understanding may lead to the identification of novel biomarkers for each metabolic disease as well as the development of novel therapeutic drugs.}, }
@article {pmid37457960, year = {2023}, author = {Dame-Teixeira, N and Do, T}, title = {Editorial: Rising stars in bacteria and host: 2022.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1240952}, pmid = {37457960}, issn = {2235-2988}, mesh = {*Bacteria ; *Microbiota ; }, }
@article {pmid37445613, year = {2023}, author = {Satala, D and Bednarek, A and Kozik, A and Rapala-Kozik, M and Karkowska-Kuleta, J}, title = {The Recruitment and Activation of Plasminogen by Bacteria-The Involvement in Chronic Infection Development.}, journal = {International journal of molecular sciences}, volume = {24}, number = {13}, pages = {}, pmid = {37445613}, issn = {1422-0067}, mesh = {Humans ; *Plasminogen/metabolism ; *Persistent Infection ; Bacteria/metabolism ; Fibrinolysin/metabolism ; Fibrinolysis ; }, abstract = {The development of infections caused by pathogenic bacteria is largely related to the specific properties of the bacterial cell surface and extracellular hydrolytic activity. Furthermore, a significant role of hijacking of host proteolytic cascades by pathogens during invasion should not be disregarded during consideration of the mechanisms of bacterial virulence. This is the key factor for the pathogen evasion of the host immune response, tissue damage, and pathogen invasiveness at secondary infection sites after initial penetration through tissue barriers. In this review, the mechanisms of bacterial impact on host plasminogen-the precursor of the important plasma serine proteinase, plasmin-are characterized, principally focusing on cell surface exposition of various proteins, responsible for binding of this host (pro)enzyme and its activators or inhibitors, as well as the fibrinolytic system activation tactics exploited by different bacterial species, not only pathogenic, but also selected harmless residents of the human microbiome. Additionally, the involvement of bacterial factors that modulate the process of plasminogen activation and fibrinolysis during periodontitis is also described, providing a remarkable example of a dual use of this host system in the development of chronic diseases.}, }
@article {pmid37437419, year = {2023}, author = {Gundogdu, A and Nalbantoglu, OU}, title = {The role of the Mediterranean diet in modulating the gut microbiome: A review of current evidence.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {114}, number = {}, pages = {112118}, doi = {10.1016/j.nut.2023.112118}, pmid = {37437419}, issn = {1873-1244}, mesh = {Humans ; *Diet, Mediterranean ; *Gastrointestinal Microbiome ; Nutrients ; Nutritional Status ; Micronutrients ; }, abstract = {The Mediterranean diet (MedDiet) is recognized as one of the United Nations Educational, Scientific and Cultural Organization Intangible Cultural Heritage assets associated with lower rates of cardiometabolic diseases; lower prevalence of cancer, Alzheimer's disease, depression, and onset of inflammatory bowel disease; and more generally low-grade inflammation and mortality risks. Beyond being an input source of beneficial micronutrients, it recently has been discovered that the MedDiet plays a role in a more complex human microbiome-mediated mechanism. An interesting hypothesis suggests a bidirectional relationship between the MedDiet and the gut microbiome, where gut microbiota assembly and biosynthetic capacity are responsive to the diet; in return, the microbiome-reachable nutrients shape and modulate the microbiome toward a characteristic probiotic state. It can be speculated that that primary health benefits of the MedDiet exerted via the gut microbiome are mediated by the bioactive compounds transformed by the microbiome. Furthermore, it is possible that additional probiotic properties of the organisms promoted by diet adherence have secondary benefits. As more detailed omic-based studies take place, more evidence on the MedDiet as a core generic probiotic microbiome modulation strategy surface. However, individual-specific microbiome compositions might impose personal variations on the diet outcome. Therefore, a prospective strategy of a fine-tuned precision nutrition approach might deliver optimized benefits of the MedDiet.}, }
@article {pmid37437088, year = {2023}, author = {Robben, M and Nasr, MS and Das, A and Veerla, JP and Huber, M and Jaworski, J and Weidanz, J and Luber, J}, title = {Comparison of the Strengths and Weaknesses of Machine Learning Algorithms and Feature Selection on KEGG Database Microbial Gene Pathway Annotation and Its Effects on Reconstructed Network Topology.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {30}, number = {7}, pages = {766-782}, doi = {10.1089/cmb.2022.0370}, pmid = {37437088}, issn = {1557-8666}, mesh = {Humans ; Molecular Sequence Annotation ; *Algorithms ; *Genes, Microbial ; Neural Networks, Computer ; Machine Learning ; }, abstract = {The development of tools for the annotation of genes from newly sequenced species has not evolved much from homologous alignment to prior annotated species. While the quality of gene annotations continues to decline as we sequence and assemble more evolutionary distant gut microbiome species, machine learning presents a high quality alternative to traditional techniques. In this study, we investigate the relative performance of common classical and nonclassical machine learning algorithms in the problem of gene annotation using human microbiome-associated species genes from the KEGG database. The majority of the ensemble, clustering, and deep learning algorithms that we investigated showed higher prediction accuracy than CD-Hit in predicting partial KEGG function. Motif-based, machine-learning methods of annotation in new species were faster and had higher precision-recall than methods of homologous alignment or orthologous gene clustering. Gradient boosted ensemble methods and neural networks also predicted higher connectivity in reconstructed KEGG pathways, finding twice as many new pathway interactions than blast alignment. The use of motif-based, machine-learning algorithms in annotation software will allow researchers to develop powerful tools to interact with bacterial microbiomes in ways previously unachievable through homologous sequence alignment alone.}, }
@article {pmid37429848, year = {2023}, author = {Sadhu, S and Dalal, R and Dandotiya, J and Binayke, A and Singh, V and Tripathy, MR and Das, V and Goswami, S and Kumar, S and Rizvi, ZA and Awasthi, A}, title = {IL-9 aggravates SARS-CoV-2 infection and exacerbates associated airway inflammation.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {4060}, pmid = {37429848}, issn = {2041-1723}, mesh = {Inflammation ; SARS-CoV-2 ; Thymus Gland/abnormalities ; Immunologic Deficiency Syndromes ; Angiotensin-Converting Enzyme 2 ; *Interleukin-9/genetics ; Animals ; Mice ; *COVID-19 ; }, abstract = {SARS-CoV-2 infection is known for causing broncho-alveolar inflammation. Interleukin 9 (IL-9) induces airway inflammation and bronchial hyper responsiveness in respiratory viral illnesses and allergic inflammation, however, IL-9 has not been assigned a pathologic role in COVID-19. Here we show, in a K18-hACE2 transgenic (ACE2.Tg) mouse model, that IL-9 contributes to and exacerbates viral spread and airway inflammation caused by SARS-CoV-2 infection. ACE2.Tg mice with CD4[+] T cell-specific deficiency of the transcription factor Forkhead Box Protein O1 (Foxo1) produce significantly less IL-9 upon SARS-CoV-2 infection than the wild type controls and they are resistant to the severe inflammatory disease that characterises the control mice. Exogenous IL-9 increases airway inflammation in Foxo1-deficient mice, while IL-9 blockade reduces and suppresses airway inflammation in SARS-CoV-2 infection, providing further evidence for a Foxo1-Il-9 mediated Th cell-specific pathway playing a role in COVID-19. Collectively, our study provides mechanistic insight into an important inflammatory pathway in SARS-CoV-2 infection, and thus represents proof of principle for the development of host-directed therapeutics to mitigate disease severity.}, }
@article {pmid37426026, year = {2023}, author = {Eggers, S and Midya, V and Bixby, M and Gennings, C and Torres-Olascoaga, LA and Walker, RW and Wright, RO and Arora, M and Téllez-Rojo, MM}, title = {Prenatal lead exposure is negatively associated with the gut microbiome in childhood.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1193919}, pmid = {37426026}, issn = {1664-302X}, support = {U2C ES026555/ES/NIEHS NIH HHS/United States ; R00 ES032884/ES/NIEHS NIH HHS/United States ; K99 ES032884/ES/NIEHS NIH HHS/United States ; R01 ES013744/ES/NIEHS NIH HHS/United States ; UL1 TR004419/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Metal exposures are associated with gut microbiome (GM) composition and function, and exposures early in development may be particularly important. Considering the role of the GM in association with many adverse health outcomes, understanding the relationship between prenatal metal exposures and the GM is critically important. However, there is sparse knowledge of the association between prenatal metal exposure and GM later in childhood.<br><br>OBJECTIVES: This analysis aims to identify associations between prenatal lead (Pb) exposure and GM composition and function in children 9-11 years old.<br><br>METHODS: Data come from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort based in Mexico City, Mexico. Prenatal metal concentrations were measured in maternal whole blood drawn during the second and third trimesters of pregnancy. Stool samples collected at 9-11 years old underwent metagenomic sequencing to assess the GM. This analysis uses multiple statistical modeling approaches, including linear regression, permutational analysis of variance, weighted quantile sum regression (WQS), and individual taxa regressions, to estimate the association between maternal blood Pb during pregnancy and multiple aspects of the child GM at 9-11 years old, adjusting for relevant confounders.<br><br>RESULTS: Of the 123 child participants in this pilot data analysis, 74 were male and 49 were female. Mean prenatal maternal blood Pb was 33.6 (SE&#x2009;=&#x2009;2.1) ug/L and 34.9 (SE&#x2009;=&#x2009;2.1) ug/L at second and third trimesters, respectively. Analysis suggests a consistent negative relationship between prenatal maternal blood Pb and the GM at age 9-11, including measures of alpha and beta diversity, microbiome mixture analysis, and individual taxa. The WQS analysis showed a negative association between prenatal Pb exposure and the gut microbiome, for both second and third trimester exposures (2T&#x3b2;&#x2009;=&#x2009;-0.17, 95%CI&#x2009;=&#x2009;[-0.46,0.11]; 3T&#x3b2;&#x2009;=&#x2009;-0.17, 95%CI&#x2009;=&#x2009;[-0.44,0.10]). Ruminococcus gnavus, Bifidobacterium longum, Alistipes indistinctus, Bacteroides caccae, and Bifidobacterium bifidum all had weights above the importance threshold from 80% or more of the WQS repeated holdouts in association with both second and third trimester Pb exposure.<br><br>DISCUSSION: Pilot data analysis suggests a negative association between prenatal Pb exposure and the gut microbiome later in childhood; however, additional investigation is needed.}, }
@article {pmid37414899, year = {2023}, author = {Routy, B and Lenehan, JG and Miller, WH and Jamal, R and Messaoudene, M and Daisley, BA and Hes, C and Al, KF and Martinez-Gili, L and Punčochář, M and Ernst, S and Logan, D and Belanger, K and Esfahani, K and Richard, C and Ninkov, M and Piccinno, G and Armanini, F and Pinto, F and Krishnamoorthy, M and Figueredo, R and Thebault, P and Takis, P and Magrill, J and Ramsay, L and Derosa, L and Marchesi, JR and Parvathy, SN and Elkrief, A and Watson, IR and Lapointe, R and Segata, N and Haeryfar, SMM and Mullish, BH and Silverman, MS and Burton, JP and Maleki Vareki, S}, title = {Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial.}, journal = {Nature medicine}, volume = {29}, number = {8}, pages = {2121-2132}, pmid = {37414899}, issn = {1546-170X}, support = {MC_PC_12025/MRC_/Medical Research Council/United Kingdom ; PJT &#x2013; 156295//CIHR/Canada ; MOP 389137//CIHR/Canada ; PJT-178341//CIHR/Canada ; }, mesh = {Animals ; Mice ; *Fecal Microbiota Transplantation/methods ; Immune Checkpoint Inhibitors ; Feces/microbiology ; *Melanoma/therapy ; Immunotherapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) represents a potential strategy to overcome resistance to immune checkpoint inhibitors in patients with refractory melanoma; however, the role of FMT in first-line treatment settings has not been evaluated. We conducted a multicenter phase I trial combining healthy donor FMT with the PD-1 inhibitors nivolumab or pembrolizumab in 20 previously untreated patients with advanced melanoma. The primary end point was safety. No grade 3 adverse events were reported from FMT alone. Five patients (25%) experienced grade 3 immune-related adverse events from combination therapy. Key secondary end points were objective response rate, changes in gut microbiome composition and systemic immune and metabolomics analyses. The objective response rate was 65% (13 of 20), including four (20%) complete responses. Longitudinal microbiome profiling revealed that all patients engrafted strains from their respective donors; however, the acquired similarity between donor and patient microbiomes only increased over time in responders. Responders experienced an enrichment of immunogenic and a loss of deleterious bacteria following FMT. Avatar mouse models confirmed the role of healthy donor feces in increasing anti-PD-1 efficacy. Our results show that FMT from healthy donors is safe in the first-line setting and warrants further investigation in combination with immune checkpoint inhibitors. ClinicalTrials.gov identifier NCT03772899 .}, }
@article {pmid37409975, year = {2023}, author = {Pratap Singh, R and Kumari, N and Gupta, S and Jaiswal, R and Mehrotra, D and Singh, S and Mukherjee, S and Kumar, R}, title = {Intratumoral Microbiota Changes with Tumor Stage and Influences the Immune Signature of Oral Squamous Cell Carcinoma.}, journal = {Microbiology spectrum}, volume = {11}, number = {4}, pages = {e0459622}, pmid = {37409975}, issn = {2165-0497}, mesh = {Humans ; *Carcinoma, Squamous Cell/pathology ; Squamous Cell Carcinoma of Head and Neck ; *Mouth Neoplasms ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; *Head and Neck Neoplasms ; Tumor Microenvironment ; }, abstract = {Characterization of the oral microbiota profile through various studies has shown an association between the microbiome and oral cancer; however, stage-specific determinants of dynamic changes in microbial communities of oral cancer remain elusive. Additionally, the influence of the intratumoral microbiota on the intratumoral immune system remains largely unexplored. Therefore, this study aims to stratify microbial abundance in the early-onset and subsequent stages of oral cancer and analyze their influence on clinical-pathological and immunological features. The microbiome composition of tissue biopsy samples was identified using 16S rRNA amplicon sequencing, while intratumoral and systemic immune profiling was done with flow cytometry and immunohistochemistry-based analysis. The bacterial composition differed significantly among precancer, early cancer, and late cancer stages with the enrichment of genera Capnocytophaga, Fusobacterium, and Treponema in the cancer group, while Streptococcus and Rothia were enriched in the precancer group. Late cancer stages were significantly associated with Capnocytophaga with high predicting accuracy, while Fusobacterium was associated with early stages of cancer. A dense intermicrobial and microbiome-immune network was observed in the precancer group. At the cellular level, intratumoral immune cell infiltration of B cells and T cells (CD4[+] and CD8[+]) was observed with enrichment of the effector memory phenotype. Naive and effector subsets of tumor-infiltrating lymphocytes (TILs) and related gene expression were found to be distinctly associated with bacterial communities; most importantly, highly abundant bacterial genera of the tumor microenvironment were either negatively correlated or not associated with the effector lymphocytes, which led to the conclusion that the tumor microenvironment favors an immunosuppressive and nonimmunogenic microbiota. IMPORTANCE The gut microbiome has been explored extensively for its importance in the modulation of systemic inflammation and immune response; in contrast, the intratumoral microbiome is less studied for its influence on immunity in cancer. Given the established correlation between intratumoral lymphocyte infiltration and patient survival in cases of solid tumors, it was pertinent to explore the extrinsic factor influencing immune cell infiltration in the tumor. Modulation of intratumoral microbiota could have a beneficial effect on the antitumor immune response. This study stratifies the microbial profile of oral squamous cell carcinoma starting from precancer to late-stage cancer and provides evidence for their immunomodulatory role in the tumor microenvironment. Our results suggest combining microbiome study with immunological signatures of tumors for their prognostic and diagnostic application.}, }
@article {pmid37409956, year = {2023}, author = {Montelongo Hernandez, C and Putonti, C and Wolfe, AJ}, title = {Urinary Plasmids Reduce Permissivity to Coliphage Infection.}, journal = {Microbiology spectrum}, volume = {11}, number = {4}, pages = {e0130923}, pmid = {37409956}, issn = {2165-0497}, mesh = {Humans ; Escherichia coli/genetics ; Plasmids/genetics ; Coliphages/genetics ; *Bacteriophages/genetics ; *Escherichia coli Infections/microbiology ; *Urinary Tract ; Bacteria/genetics ; Anti-Bacterial Agents ; }, abstract = {The microbial community of the urinary tract (urinary microbiota or urobiota) has been associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacterial dynamics. While urinary Escherichia coli strains associated with urinary tract infection (UTI) and their phages have been catalogued for the urobiome, bacterium-plasmid-phage interactions have yet to be explored. In this study, we characterized urinary E. coli plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Putative F plasmids were predicted in 47 of 67 urinary E. coli isolates, and most of these plasmids carried genes that encode toxin-antitoxin (TA) modules, antibiotic resistance, and/or virulence. Urinary E. coli plasmids, from urinary microbiota strains UMB0928 and UMB1284, were conjugated into E. coli K-12 strains. These transconjugants included genes for antibiotic resistance and virulence, and they decreased permissivity to coliphage infection by the laboratory phage P1vir and the urinary phages Greed and Lust. Plasmids in one transconjugant were maintained in E. coli K-12 for up to 10 days in the absence of antibiotic resistance selection; this included the maintenance of the antibiotic resistance phenotype and decreased permissivity to phage. Finally, we discuss how F plasmids present in urinary E. coli strains could play a role in coliphage dynamics and the maintenance of antibiotic resistance in urinary E. coli. IMPORTANCE The urinary tract contains a resident microbial community called the urinary microbiota or urobiota. Evidence exists that it is associated with human health. Bacteriophages (phages) and plasmids present in the urinary tract, like in other niches, may shape urinary bacterial dynamics. Bacterium-plasmid-phage interactions have been studied primarily in laboratory settings and are yet to be thoroughly tested in complex communities. This is especially true of the urinary tract, where the bacterial genetic determinants of phage infection are not well understood. In this study, we characterized urinary E. coli plasmids and their ability to decrease permissivity to E. coli phage (coliphage) infection. Urinary E. coli plasmids, encoding antibiotic resistance and transferred by conjugation into naive laboratory E. coli K-12 strains, decreased permissivity to coliphage infection. We propose a model by which urinary plasmids present in urinary E. coli strains could help to decrease phage infection susceptibility and maintain the antibiotic resistance of urinary E. coli. This has consequences for phage therapy, which could inadvertently select for plasmids that encode antibiotic resistance.}, }
@article {pmid37404032, year = {2023}, author = {Deschênes, T and Tohoundjona, FWE and Plante, PL and Di Marzo, V and Raymond, F}, title = {Gene-based microbiome representation enhances host phenotype classification.}, journal = {mSystems}, volume = {8}, number = {4}, pages = {e0053123}, pmid = {37404032}, issn = {2379-5077}, mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics ; *Microbiota/genetics ; Metagenome ; *Gastrointestinal Microbiome/genetics ; Phenotype ; }, abstract = {With the concomitant advances in both the microbiome and machine learning fields, the gut microbiome has become of great interest for the potential discovery of biomarkers to be used in the classification of the host health status. Shotgun metagenomics data derived from the human microbiome is composed of a high-dimensional set of microbial features. The use of such complex data for the modeling of host-microbiome interactions remains a challenge as retaining de novo content yields a highly granular set of microbial features. In this study, we compared the prediction performances of machine learning approaches according to different types of data representations derived from shotgun metagenomics. These representations include commonly used taxonomic and functional profiles and the more granular gene cluster approach. For the five case-control datasets used in this study (Type 2 diabetes, obesity, liver cirrhosis, colorectal cancer, and inflammatory bowel disease), gene-based approaches, whether used alone or in combination with reference-based data types, allowed improved or similar classification performances as the taxonomic and functional profiles. In addition, we show that using subsets of gene families from specific functional categories of genes highlight the importance of these functions on the host phenotype. This study demonstrates that both reference-free microbiome representations and curated metagenomic annotations can provide relevant representations for machine learning based on metagenomic data. IMPORTANCE Data representation is an essential part of machine learning performance when using metagenomic data. In this work, we show that different microbiome representations provide varied host phenotype classification performance depending on the dataset. In classification tasks, untargeted microbiome gene content can provide similar or improved classification compared to taxonomical profiling. Feature selection based on biological function also improves classification performance for some pathologies. Function-based feature selection combined with interpretable machine learning algorithms can generate new hypotheses that can potentially be assayed mechanistically. This work thus proposes new approaches to represent microbiome data for machine learning that can potentiate the findings associated with metagenomic data.}, }
@article {pmid37401755, year = {2023}, author = {Ronkainen, A and Khan, I and Krzyżewska-Dudek, E and Hiippala, K and Freitag, TL and Satokari, R}, title = {In vitro adhesion, pilus expression, and in vivo amelioration of antibiotic-induced microbiota disturbance by Bifidobacterium spp. strains from fecal donors.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2229944}, pmid = {37401755}, issn = {1949-0984}, mesh = {Animals ; Mice ; Anti-Bacterial Agents/pharmacology ; Bifidobacterium ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; *Clostridioides difficile ; Mice, Inbred C57BL ; Feces/microbiology ; Fecal Microbiota Transplantation ; *Microbiota ; *Clostridium Infections/microbiology ; }, abstract = {Fecal microbiota transplantation (FMT) is used routinely to treat recurrent Clostridioides difficile infection (rCDI) and investigated as a treatment for numerous conditions associated with gut microbiota alterations. Metagenomic analyses have indicated that recipient colonization by donor bacteria may be associated with favorable clinical outcomes. Bifidobacteria are abundant gut commensals associated with health. We have previously demonstrated that Bifidobacterium strains transferred in FMT can colonize recipients in long term, at least for a year, and recovered such strains by cultivation. This study addressed in vitro adhesion and pilus gene expression of long-term colonizing Bifidobacterium strains from FMT donors as well as in vivo colonization and capability to ameliorate antibiotic-induced microbiota disturbance. RNA-Seq differential gene expression analysis showed that the strongly adherent B. longum strains DY_pv11 and DX_pv23 expressed tight adherence and sortase-dependent pilus genes, respectively. Two B. longum strains, adherent DX_pv23 and poorly adhering DX_pv18, were selected to address in vivo colonization and efficacy to restore antibiotic-disturbed microbiota in C57BL/6 murine model. DX_pv23 colonized mice transiently with a rate comparable to that of the B. animalis BB-12 used as a reference. Although long-term colonization was not observed with any of the three strains, 16S rRNA gene profiling revealed that oral administration of DX_pv23 enhanced the recovery of antibiotic-disturbed microbiota to the original configuration significantly better than the other strains. The findings suggest that selected strains from FMT donors, such as DX_pv23 in this study, may have therapeutic potential by in vitro expression of colonization factors and boosting endogenous gut microbiota.}, }
@article {pmid37401478, year = {2023}, author = {Riekkinen, M and Kajova, M and Eriksson, M and Luukkainen, A and Holmberg, V and Aro, T and Pakkanen, SH and Miettinen, S and Montonen, R and Smura, T and Lääveri, T and Kantele, A}, title = {Superspreading of SARS-CoV-2 Omicron BA.2.23 among vaccinated Finnish adults: symptomatic COVID-19 only contracted by those without recent infection.}, journal = {Epidemiology and infection}, volume = {151}, number = {}, pages = {e113}, pmid = {37401478}, issn = {1469-4409}, mesh = {Humans ; *COVID-19/prevention &amp; control ; SARS-CoV-2/genetics ; Finland/epidemiology ; Disease Outbreaks ; Fever ; }, abstract = {An outbreak of SARS-CoV-2 was confirmed after an academic party in Helsinki, Finland, in 2022. All 70 guests were requested to fill in follow-up questionnaires; serologic analyses and whole-genome sequencing (WGS) were conducted when possible.Of those participating - all but one with ≥3 vaccine doses - 21/53 (40%) had test-confirmed symptomatic COVID-19: 7% of those with earlier episodes and 76% of those without. Half (11/21) were febrile, but none needed hospitalisation. WGS revealed subvariant BA.2.23.Compared to vaccination alone, our data suggest remarkable protection by hybrid immunity against symptomatic infection, particularly in instances of recent infections with homologous variants.}, }
@article {pmid37400581, year = {2023}, author = {El Tekle, G and Garrett, WS}, title = {Bacteria in cancer initiation, promotion and progression.}, journal = {Nature reviews. Cancer}, volume = {23}, number = {9}, pages = {600-618}, pmid = {37400581}, issn = {1474-1768}, support = {C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Humans ; *Neoplasms/etiology ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria ; Immune System ; Tumor Microenvironment ; }, abstract = {Cancer cells originate from a series of acquired genetic mutations that can drive their uncontrolled cell proliferation and immune evasion. Environmental factors, including the microorganisms that colonize the human body, can shift the metabolism, growth pattern and function of neoplastic cells and shape the tumour microenvironment. Dysbiosis of the gut microbiome is now recognized as a hallmark of cancer by the scientific community. However, only a few microorganisms have been identified that directly initiate tumorigenesis or skew the immune system to generate a tumour-permissive milieu. Over the past two decades, research on the human microbiome and its functionalities within and across individuals has revealed microbiota-focused strategies for health and disease. Here, we review the evolving understanding of the mechanisms by which the microbiota acts in cancer initiation, promotion and progression. We explore the roles of bacteria in gastrointestinal tract malignancies and cancers of the lung, breast and prostate. Finally, we discuss the promises and limitations of targeting or harnessing bacteria in personalized cancer prevention, diagnostics and treatment.}, }
@article {pmid37399600, year = {2023}, author = {Jokela, R and Ponsero, AJ and Dikareva, E and Wei, X and Kolho, KL and Korpela, K and de Vos, WM and Salonen, A}, title = {Sources of gut microbiota variation in a large longitudinal Finnish infant cohort.}, journal = {EBioMedicine}, volume = {94}, number = {}, pages = {104695}, pmid = {37399600}, issn = {2352-3964}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Infant ; Finland ; Female ; *RNA, Ribosomal, 16S/genetics ; Longitudinal Studies ; Male ; *Feces/microbiology ; Infant, Newborn ; Bacteria/genetics/classification/isolation &amp; purification ; Biodiversity ; }, abstract = {BACKGROUND: Although the infant gut microbiota has been extensively studied, comprehensive assessment on the microbiota determinants including technical variables has not been performed in large infant cohorts.<br><br>METHODS: We studied the effect of 109 variables on the 16S rRNA gene amplicon-based gut microbiota profiles of infants sampled longitudinally from three weeks to two years of life in the Finnish HELMi birth cohort. Spot faecal samples from both parents were included for intra-family analyses, totalling to 7657 samples from 985 families that were evaluated for beta-diversity patterns using permutational multivariate analysis on Bray-Curtis distances, and differential abundance testing and alpha-diversity for variables of interest. We also assessed the effect of different taxonomic levels and distance methods.<br><br>FINDINGS: In time point-specific models, the largest share of variation explained, up to 2-6%, were seen in decreasing order for the DNA extraction batch, delivery mode and related perinatal exposures, defecation frequency and parity/siblings. Variables describing the infant gastrointestinal function were continuously important during the first two years, reflecting changes in e.g., feeding habits. The effect of parity/siblings on infant microbiota was modified by birth mode and exposure to intrapartum antibiotics, exemplifying the tight interlinkage of perinatal factors relevant for infant microbiota research. In total, up to 19% of the biological microbiota variation in the infant gut could be explained. Our results highlight the need to interpret variance partitioning results in the context of each cohort's characteristics and microbiota processing.<br><br>INTERPRETATION: Our study provides a comprehensive report of key factors associated with infant gut microbiota composition across the two first years of life in a homogenous cohort. The study highlights possible important future research areas and confounding factors to be considered.<br><br>FUNDING: This research was supported by Business Finland, Academy of Finland, Foundation for Nutrition Research and the Doctoral Program in Microbiology and Biotechnology, University of Helsinki, Finland.}, }
@article {pmid37397017, year = {2023}, author = {You, Y and Yin, M and Zheng, X and Liang, Q and Zhang, H and Wu, BL and Xu, W}, title = {Saccharibacteria (TM7), but not other bacterial taxa, are associated with childhood caries regardless of age in a South China population.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15605}, pmid = {37397017}, issn = {2167-8359}, mesh = {Child ; Humans ; Child, Preschool ; Male ; Female ; RNA, Ribosomal, 16S/genetics ; *Dental Caries/epidemiology ; Dental Caries Susceptibility ; Bacteria/genetics ; Firmicutes/genetics ; China/epidemiology ; }, abstract = {BACKGROUND: Human microbiome dysbiosis is related to various human diseases, and identifying robust and consistent biomarkers that apply in different populations is a key challenge. This challenge arises when identifying key microbial markers of childhood caries.<br><br>METHODS: We analyzed unstimulated saliva and supragingival plaque samples from children of different ages and sexes, performed 16S rRNA gene sequencing, and sought to identify whether consistent markers exist among subpopulations by using a multivariate linear regression model.<br><br>RESULTS: We found that Acinetobacter and Clostridiales bacterial taxa were associated with caries in plaque and saliva, respectively, while Firmicutes and Clostridia were found in plaque isolated from children of different ages in preschool and school. These identified bacterial markers largely differ between different populations, leaving only Saccharibacteria as a significant caries-associated phylum in children. Saccharibacteria is a newly identified phylum, and our taxonomic assignment database could not be used to identify its specific genus.<br><br>CONCLUSION: Our data indicated that, in a South China population, oral microbial signatures for dental caries show age and sex differences, but Saccharibacteria might be a consistent signal and worth further investigation, considering the lack of research on this microbe.}, }
@article {pmid37389570, year = {2023}, author = {Acosta, EM and Little, KA and Bratton, BP and Lopez, JG and Mao, X and Payne, AS and Donia, M and Devenport, D and Gitai, Z}, title = {Bacterial DNA on the skin surface overrepresents the viable skin microbiome.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {37389570}, issn = {2050-084X}, support = {P30 AR069589/AR/NIAMS NIH HHS/United States ; DP1 AI124669/AI/NIAID NIH HHS/United States ; TL1TR003019/TR/NCATS NIH HHS/United States ; TL1 TR003019/TR/NCATS NIH HHS/United States ; T32 GM007388/GM/NIGMS NIH HHS/United States ; GM007388/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Animals ; Mice ; DNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; *Skin ; Aggression ; *Microbiota ; }, abstract = {The skin microbiome provides vital contributions to human health. However, the spatial organization and viability of its bacterial components remain unclear. Here, we apply culturing, imaging, and molecular approaches to human and mouse skin samples, and find that the skin surface is colonized by fewer viable bacteria than predicted by bacterial DNA levels. Instead, viable skin-associated bacteria are predominantly located in hair follicles and other cutaneous invaginations. Furthermore, we show that the skin microbiome has a uniquely low fraction of viable bacteria compared to other human microbiome sites, indicating that most bacterial DNA on the skin surface is not associated with viable cells Additionally, a small number of bacterial families dominate each skin site and traditional sequencing methods overestimate both the richness and diversity of the skin microbiome. Finally, we performed an in vivo skin microbiome perturbation-recovery study using human volunteers. Bacterial 16S rRNA gene sequencing revealed that, while the skin microbiome is remarkably stable even in the wake of aggressive perturbation, repopulation of the skin surface is driven by the underlying viable population. Our findings help explain the dynamics of skin microbiome perturbation as bacterial DNA on the skin surface can be transiently perturbed but is replenished by a stable underlying viable population. These results address multiple outstanding questions in skin microbiome biology with significant implications for future efforts to study and manipulate it.}, }
@article {pmid37389338, year = {2023}, author = {Loyola Irizarry, HG and Brito, IL}, title = {Characterizing conjugative plasmids from an antibiotic-resistant dataset for use as broad-host delivery vectors.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1199640}, pmid = {37389338}, issn = {1664-302X}, abstract = {Human microbiome engineering is increasingly proposed as a way to modulate health outcomes. However, one of the current limitations to engineering microbial communities in situ is delivery of a genetic payload for introducing or modifying genes. Indeed, there is a need to identify novel broad-host delivery vectors for microbiome engineering. Therefore, in this study, we characterized conjugative plasmids from a publicly available dataset of antibiotic-resistant isolate genomes in order to identify potential broad-host vectors for further applications. From the 199 closed genomes available in the CDC &amp; FDA AR Isolate Bank, we identified 439 plasmids, of which 126 were predicted to be mobilizable and 206 conjugative. Various characteristics of the conjugative plasmids, such as size, replication origin, conjugation machinery, host defense mechanisms, and plasmid stability proteins, were analyzed to determine these plasmids' potential host-range. Following this analysis, we clustered plasmid sequences and chose 22 unique, broad-host range plasmids that would be suitable for use as delivery vectors. This novel set of plasmids will provide a valuable resource for engineering microbial communities.}, }
@article {pmid37389240, year = {2023}, author = {Efremova, I and Maslennikov, R and Poluektova, E and Vasilieva, E and Zharikov, Y and Suslov, A and Letyagina, Y and Kozlov, E and Levshina, A and Ivashkin, V}, title = {Epidemiology of small intestinal bacterial overgrowth.}, journal = {World journal of gastroenterology}, volume = {29}, number = {22}, pages = {3400-3421}, pmid = {37389240}, issn = {2219-2840}, mesh = {Humans ; *Diabetic Neuropathies ; Liver Cirrhosis ; Risk Factors ; Abdominal Pain ; Autonomic Nervous System ; }, abstract = {Small intestinal bacterial overgrowth (SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms. SIBO is significantly associated with functional dyspepsia, irritable bowel syndrome, functional abdominal bloating, functional constipation, functional diarrhea, short bowel syndrome, chronic intestinal pseudo-obstruction, lactase deficiency, diverticular and celiac diseases, ulcerative colitis, Crohn's disease, cirrhosis, metabolic-associated fatty liver disease (MAFLD), primary biliary cholangitis, gastroparesis, pancreatitis, cystic fibrosis, gallstone disease, diabetes, hypothyroidism, hyperlipidemia, acromegaly, multiple sclerosis, autism, Parkinson's disease, systemic sclerosis, spondylarthropathy, fibromyalgia, asthma, heart failure, and other diseases. The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine. The slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut, autonomic diabetic polyneuropathy, and portal hypertension, or a decrease in the motor-stimulating influence of thyroid hormones. In a number of diseases, including cirrhosis, MAFLD, diabetes, and pancreatitis, an association was found between disease severity and the presence of SIBO. Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.}, }
@article {pmid37386089, year = {2023}, author = {Kadyan, S and Park, G and Wang, B and Singh, P and Arjmandi, B and Nagpal, R}, title = {Resistant starches from dietary pulses modulate the gut metabolome in association with microbiome in a humanized murine model of ageing.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {10566}, pmid = {37386089}, issn = {2045-2322}, mesh = {Humans ; Animals ; Mice ; Aged ; Resistant Starch ; Disease Models, Animal ; Metabolome ; *Microbiota ; Diet, Western ; *Lens Plant ; Aging ; Bacteroidetes ; }, abstract = {Emerging evidence suggests that plant-based fiber-rich diets improve ageing-associated health by fostering a healthier gut microbiome and microbial metabolites. However, such effects and mechanisms of resistant starches from dietary pulses remain underexplored. Herein, we examine the prebiotic effects of dietary pulses-derived resistant starch (RS) on gut metabolome in older (60-week old) mice carrying a human microbiome. Gut metabolome and its association with microbiome are examined after 20-weeks feeding of a western-style diet (control; CTL) fortified (5% w/w) with RS from pinto beans (PTB), black-eyed-peas (BEP), lentils (LEN), chickpeas (CKP), or inulin (INU; reference control). NMR spectroscopy-based untargeted metabolomic analysis yield differential abundance linking phenotypic differences in specific metabolites among different RS groups. LEN and CKP increase butyrate, while INU promotes propionate. Conversely, bile acids and cholesterol are reduced in prebiotic groups along with suppressed choline-to-trimethylamine conversion by LEN and CKP, whereas amino acid metabolism is positively altered. Multi-omics microbiome-metabolome interactions reveal an association of beneficial metabolites with the Lactobacilli group, Bacteroides, Dubosiella, Parasutterella, and Parabacteroides, while harmful metabolites correlate with Butyricimonas, Faecalibaculum, Colidextribacter, Enterococcus, Akkermansia, Odoribacter, and Bilophila. These findings demonstrate the functional effects of pulses-derived RS on gut microbial metabolism and their beneficial physiologic responses in an aged host.}, }
@article {pmid37382539, year = {2023}, author = {Botin, T and Ramirez-Chamorro, L and Vidic, J and Langella, P and Martin-Verstraete, I and Chatel, JM and Auger, S}, title = {The Tolerance of Gut Commensal Faecalibacterium to Oxidative Stress Is Strain Dependent and Relies on Detoxifying Enzymes.}, journal = {Applied and environmental microbiology}, volume = {89}, number = {7}, pages = {e0060623}, pmid = {37382539}, issn = {1098-5336}, mesh = {Humans ; Reactive Oxygen Species/metabolism ; Faecalibacterium/metabolism ; *Hydrogen Peroxide/metabolism ; *Oxidative Stress ; Proteins/metabolism ; Bacteria/metabolism ; }, abstract = {Obligate anaerobic bacteria in genus Faecalibacterium are among the most dominant taxa in the colon of healthy individuals and contribute to intestinal homeostasis. A decline in the abundance of this genus is associated with the occurrence of various gastrointestinal disorders, including inflammatory bowel diseases. In the colon, these diseases are accompanied by an imbalance between the generation and elimination of reactive oxygen species (ROS), and oxidative stress is closely linked to disruptions in anaerobiosis. In this work, we explored the impact of oxidative stress on several strains of faecalibacteria. An in silico analysis of complete genomes of faecalibacteria revealed the presence of genes encoding O2- and/or ROS-detoxifying enzymes, including flavodiiron proteins, rubrerythrins, reverse rubrerythrins, superoxide reductases, and alkyl peroxidase. However, the presence and the number of these detoxification systems varied greatly among faecalibacteria. These results were confirmed by O2 stress survival tests, in which we found that strains differed widely in their sensitivity. We showed the protective role of cysteine, which limited the production of extracellular O2[•-] and improved the survival of Faecalibacterium longum L2-6 under high O2 tension. In the strain F. longum L2-6, we observed that the expression of genes encoding detoxifying enzymes was upregulated in the response to O2 or H2O2 stress but with different patterns of regulation. Based on these results, we propose a first model of the gene regulatory network involved in the response to oxidative stress in F. longum L2-6. IMPORTANCE Commensal bacteria in the genus Faecalibacterium have been proposed for use as next-generation probiotics, but efforts to cultivate and exploit the potential of these strains have been limited by their sensitivity to O2. More broadly, little is known about how commensal and health-associated bacterial species in the human microbiome respond to the oxidative stress that occurs as a result of inflammation in the colon. In this work, we provide insights regarding the genes that encode potential mechanisms of protection against O2 or ROS stress in faecalibacteria, which may facilitate future advances in work with these important bacteria.}, }
@article {pmid37379671, year = {2023}, author = {Steininger, H and Moltzau-Anderson, J and Lynch, SV}, title = {Contributions of the early-life microbiome to childhood atopy and asthma development.}, journal = {Seminars in immunology}, volume = {69}, number = {}, pages = {101795}, pmid = {37379671}, issn = {1096-3618}, support = {P01 AI089473/AI/NIAID NIH HHS/United States ; P01 AI148104/AI/NIAID NIH HHS/United States ; UG3 OD023282/OD/NIH HHS/United States ; }, mesh = {Humans ; *Asthma ; *Hypersensitivity ; *Microbiota ; }, abstract = {The rapid rise in atopy and asthma in industrialized nations has led to the identification of early life environmental factors that promote these conditions and spurred research into how such exposures may mediate the trajectory to childhood disease development. Over the past decade, the human microbiome has emerged as a key determinant of human health. This is largely due to the increasing appreciation for the myriad of non-mutually exclusive mechanisms by which microbes tune and train host immunity. Microbiomes, particularly those in early life, are shaped by extrinsic and intrinsic factors, including many of the exposures known to influence allergy and asthma risk. This has led to the over-arching hypothesis that such exposures mediate their effect on childhood atopy and asthma by altering the functions and metabolic productivity of microbiomes that shape immune function during this critical developmental period. The capacity to study microbiomes at the genetic and molecular level in humans from the pre-natal period into childhood with well-defined clinical outcomes, offers an unprecedented opportunity to identify early-life and inter-generational determinants of atopy and asthma outcomes. Moreover, such studies provide an integrative microbiome research framework that can be applied to other chronic inflammatory conditions. This review attempts to capture key studies in the field that offer insights into the developmental origins of childhood atopy and asthma, providing novel insights into microbial mediators of maladaptive immunity and chronic inflammatory disease in childhood.}, }
@article {pmid37378284, year = {2023}, author = {Chmiel, JA and Carr, C and Stuivenberg, GA and Venema, R and Chanyi, RM and Al, KF and Giguere, D and Say, H and Akouris, PP and Domínguez Romero, SA and Kwong, A and Tai, V and Koval, SF and Razvi, H and Bjazevic, J and Burton, JP}, title = {Corrigendum: New perspectives on an old grouping: the genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1231746}, pmid = {37378284}, issn = {1664-302X}, abstract = {[This corrects the article DOI: 10.3389/fmicb.2022.1011102.].}, }
@article {pmid37374978, year = {2023}, author = {Talapko, J and Meštrović, T and Dmitrović, B and Juzbašić, M and Matijević, T and Bekić, S and Erić, S and Flam, J and Belić, D and Petek Erić, A and Milostić Srb, A and Škrlec, I}, title = {A Putative Role of Candida albicans in Promoting Cancer Development: A Current State of Evidence and Proposed Mechanisms.}, journal = {Microorganisms}, volume = {11}, number = {6}, pages = {}, pmid = {37374978}, issn = {2076-2607}, abstract = {Candida albicans is a commensal fungal species that commonly colonizes the human body, but it is also a pervasive opportunistic pathogen in patients with malignant diseases. A growing body of evidence suggests that this fungus is not only coincidental in oncology patients, but may also play an active role in the development of cancer. More specifically, several studies have investigated the potential association between C. albicans and various types of cancer, including oral, esophageal, and colorectal cancer, with a possible role of this species in skin cancer as well. The proposed mechanisms include the production of carcinogenic metabolites, modulation of the immune response, changes in cell morphology, microbiome alterations, biofilm production, the activation of oncogenic signaling pathways, and the induction of chronic inflammation. These mechanisms may act together or independently to promote cancer development. Although more research is needed to fully grasp the potential role of C. albicans in carcinogenesis, the available evidence suggests that this species may be an active contributor and underscores the importance of considering the impact of the human microbiome on cancer pathogenesis. In this narrative review, we aimed to summarize the current state of evidence and offer some insights into proposed mechanisms.}, }
@article {pmid37373701, year = {2023}, author = {Villarejo-Campos, P and García-Arranz, M and Qian, S and Jiménez de Los Galanes, S and Domínguez-Prieto, V and Vélez-Pinto, JF and Guijo Castellano, I and Jiménez-Fuertes, M and Guadalajara, H and García-Olmo, D}, title = {Under the Hood: Understanding the Features of Mucin in Pseudomyxoma Peritonei.}, journal = {Journal of clinical medicine}, volume = {12}, number = {12}, pages = {}, pmid = {37373701}, issn = {2077-0383}, support = {PI20/01052 and DTS22/00048).//ISCIII-FEDER (Instituto de Salud Carlos III-Fondo Europeo de Desarrollo Regional), Spanish Ministry of Health/ ; }, abstract = {Pseudomyxoma peritonei (PMP) is a rare malignant growth characterized by the production of mucin and the potential for peritoneal relapse. This study aimed to investigate the immunohistochemical and biological characteristics of mucin in patients with cellular and acellular PMP. We prospectively analyzed mucin specimens obtained from our patient cohort and described the composition and type of mucin present in each sample. A metagenomic analysis of the samples was performed to investigate the bacterial composition of the PMP microbiome. Secreted mucins 2 and 5AC and membrane-associated mucin-1 were the primary components of mucin in both cellular and acellular tumor specimens. The metagenomic study revealed a predominance of the phylum Proteobacteria and the genus Pseudomonas. Notably, Pseudomonas plecoglossicida, a species not previously reported in the human microbiome, was found to be the most abundant organism in the mucin of pseudomyxoma peritonei. Our findings suggest that the presence of MUC-2 and mucin colonization by Pseudomonas are characteristic features of both cellular and acellular disease. These results may have significant implications for the diagnosis and treatment of this rare entity.}, }
@article {pmid37361341, year = {2023}, author = {Magill, RG and MacDonald, SM}, title = {Male infertility and the human microbiome.}, journal = {Frontiers in reproductive health}, volume = {5}, number = {}, pages = {1166201}, pmid = {37361341}, issn = {2673-3153}, abstract = {The historical belief in urology was that the genitourinary system should be sterile in a normal, healthy, asymptomatic adult. This idea was perpetuated for decades until research revealed a diverse microbiota existing in human anatomical niches that contributed to both human health and disease processes. In recent years, the search for an etiology and modifiable risk factors in infertility has turned to the human microbiome as well. Changes in the human gut microbiome have been associated with changes in systemic sex hormones and spermatogenesis. Certain microbial species are associated with higher levels of oxidative stress, which may contribute to an environment higher in oxidative reactive potential. Studies have demonstrated a link between increased oxidative reactive potential and abnormal semen parameters in infertile men. It has also been hypothesized that antioxidant probiotics may be able to correct an imbalance in the oxidative environment and improve male fertility, with promising results in small studies. Further, the sexual partner's microbiome may play a role as well; studies have demonstrated an overlap in the genitourinary microbiomes in sexually active couples that become more similar after intercourse. While the potential applications of the microbiome to male fertility is exciting, there is a need for larger studies with uniform microbial sequencing procedures to further expand this topic.}, }
@article {pmid37349675, year = {2023}, author = {Theorell, A and Stelling, J}, title = {Assumptions on decision making and environment can yield multiple steady states in microbial community models.}, journal = {BMC bioinformatics}, volume = {24}, number = {Suppl 1}, pages = {262}, pmid = {37349675}, issn = {1471-2105}, support = {177164//Schweizerischer Nationalfonds zur F&#xf6;rderung der Wissenschaftlichen Forschung/ ; }, mesh = {Humans ; *Models, Biological ; Computer Simulation ; *Microbiota ; Genome ; Decision Making ; }, abstract = {BACKGROUND: Microbial community simulations using genome scale metabolic networks (GSMs) are relevant for many application areas, such as the analysis of the human microbiome. Such simulations rely on assumptions about the culturing environment, affecting if the culture may reach a metabolically stationary state with constant microbial concentrations. They also require assumptions on decision making by the microbes: metabolic strategies can be in the interest of individual community members or of the whole community. However, the impact of such common assumptions on community simulation results has not been investigated systematically.<br><br>RESULTS: Here, we investigate four combinations of assumptions, elucidate how they are applied in literature, provide novel mathematical formulations for their simulation, and show how the resulting predictions differ qualitatively. Our results stress that different assumption combinations give qualitatively different predictions on microbial coexistence by differential substrate utilization. This fundamental mechanism is critically under explored in the steady state GSM literature with its strong focus on coexistence states due to crossfeeding (division of labor). Furthermore, investigating a realistic synthetic community, where the two involved strains exhibit no growth in isolation, but grow as a community, we predict multiple modes of cooperation, even without an explicit cooperation mechanism.<br><br>CONCLUSIONS: Steady state GSM modelling of microbial communities relies both on assumed decision making principles and environmental assumptions. In principle, dynamic flux balance analysis addresses both. In practice, our methods that address the steady state directly may be preferable, especially if the community is expected to display multiple steady states.}, }
@article {pmid37349525, year = {2023}, author = {Selma-Royo, M and Segata, N and Ricci, L}, title = {Human microbiome cultivation expands with AI.}, journal = {Nature biotechnology}, volume = {41}, number = {10}, pages = {1389-1391}, pmid = {37349525}, issn = {1546-1696}, mesh = {Humans ; *Microbiota ; Phylogeny ; }, }
@article {pmid37348522, year = {2023}, author = {Morton, SU and Hehnly, C and Burgoine, K and Ssentongo, P and Ericson, JE and Kumar, MS and Hagmann, C and Fronterre, C and Smith, J and Movassagh, M and Streck, N and Bebell, LM and Bazira, J and Kumbakumba, E and Bajunirwe, F and Mulondo, R and Mbabazi-Kabachelor, E and Nsubuga, BK and Natukwatsa, D and Nalule, E and Magombe, J and Erickson, T and Ngonzi, J and Ochora, M and Olupot-Olupot, P and Onen, J and Ssenyonga, P and Mugamba, J and Warf, BC and Kulkarni, AV and Lane, J and Whalen, AJ and Zhang, L and Sheldon, K and Meier, FA and Kiwanuka, J and Broach, JR and Paulson, JN and Schiff, SJ}, title = {Paenibacillus spp infection among infants with postinfectious hydrocephalus in Uganda: an observational case-control study.}, journal = {The Lancet. Microbe}, volume = {4}, number = {8}, pages = {e601-e611}, pmid = {37348522}, issn = {2666-5247}, support = {DP1 HD086071/HD/NICHD NIH HHS/United States ; R01 AI145057/AI/NIAID NIH HHS/United States ; }, mesh = {United States ; Infant, Newborn ; Child ; Humans ; Infant ; Female ; Pregnancy ; Uganda/epidemiology ; *Neonatal Sepsis/complications ; Placenta ; *Paenibacillus/genetics ; *Sepsis/complications/microbiology ; *Meningitis/complications ; *Hydrocephalus/epidemiology/etiology ; Case-Control Studies ; }, abstract = {BACKGROUND: Paenibacillus thiaminolyticus is a cause of postinfectious hydrocephalus among Ugandan infants. To determine whether Paenibacillus spp is a pathogen in neonatal sepsis, meningitis, and postinfectious hydrocephalus, we aimed to complete three separate studies of Ugandan infants. The first study was on peripartum prevalence of Paenibacillus in mother-newborn pairs. The second study assessed Paenibacillus in blood and cerebrospinal fluid (CSF) from neonates with sepsis. The third study assessed Paenibacillus in CSF from infants with hydrocephalus.<br><br>METHODS: In this observational study, we recruited mother-newborn pairs with and without maternal fever (mother-newborn cohort), neonates (aged &#x2264;28 days) with sepsis (sepsis cohort), and infants (aged &#x2264;90 days) with hydrocephalus with and without a history of neonatal sepsis and meningitis (hydrocephalus cohort) from three hospitals in Uganda between Jan 13, 2016 and Oct 2, 2019. We collected maternal blood, vaginal swabs, and placental samples and the cord from the mother-newborn pairs, and blood and CSF from neonates and infants. Bacterial content of infant CSF was characterised by 16S rDNA sequencing. We analysed all samples using quantitative PCR (qPCR) targeting either the Paenibacillus genus or Paenibacillus thiaminolyticus spp. We collected cranial ultrasound and computed tomography images in the subset of participants represented in more than one cohort.<br><br>FINDINGS: No Paenibacillus spp were detected in vaginal, maternal blood, placental, or cord blood specimens from the mother-newborn cohort by qPCR. Paenibacillus spp was detected in 6% (37 of 631 neonates) in the sepsis cohort and, of these, 14% (5 of 37 neonates) developed postinfectious hydrocephalus. Paenibacillus was the most enriched bacterial genera in postinfectious hydrocephalus CSF (91 [44%] of 209 patients) from the hydrocephalus cohort, with 16S showing 94% accuracy when validated by qPCR. Imaging showed progression from Paenibacillus spp-related meningitis to postinfectious hydrocephalus over 1-3 months. Patients with postinfectious hydrocephalus with Paenibacillus spp infections were geographically clustered.<br><br>INTERPRETATION: Paenibacillus spp causes neonatal sepsis and meningitis in Uganda and is the dominant cause of subsequent postinfectious hydrocephalus. There was no evidence of transplacental transmission, and geographical evidence was consistent with an environmental source of neonatal infection. Further work is needed to identify routes of infection and optimise treatment of neonatal Paenibacillus spp infection to lessen the burden of morbidity and mortality.<br><br>FUNDING: National Institutes of Health and Boston Children's Hospital Office of Faculty Development.}, }
@article {pmid37348505, year = {2023}, author = {Carter, MM and Olm, MR and Merrill, BD and Dahan, D and Tripathi, S and Spencer, SP and Yu, FB and Jain, S and Neff, N and Jha, AR and Sonnenburg, ED and Sonnenburg, JL}, title = {Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes.}, journal = {Cell}, volume = {186}, number = {14}, pages = {3111-3124.e13}, pmid = {37348505}, issn = {1097-4172}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; F32 DK128865/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; K08 DK134856/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Metagenome ; Eukaryota ; High-Throughput Nucleotide Sequencing ; Metagenomics ; }, abstract = {The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers of Tanzania and comparative populations in Nepal and California. We recovered 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource, expands our understanding of microbes capable of colonizing the human gut, and clarifies the extensive perturbation induced by the industrialized lifestyle.}, }
@article {pmid37345281, year = {2023}, author = {Launonen, H and Luiskari, L and Linden, J and Siltari, A and Salmenkari, H and Korpela, R and Vapaatalo, H}, title = {Adverse effects of an aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286), on inflamed rat colon.}, journal = {Basic &amp; clinical pharmacology &amp; toxicology}, volume = {133}, number = {3}, pages = {211-225}, doi = {10.1111/bcpt.13918}, pmid = {37345281}, issn = {1742-7843}, support = {//Finska L&#xe4;kares&#xe4;llskapet/ ; //Mary and Georg C. Ehrnrooth's Foundation/ ; //Maud Kuistila Memory Foundation/ ; //Paulo Foundation/ ; //Finnish Cultural Foundation (Kymenlaakso regional fund, Olavi and Alli Pietik&#xe4;inen fund)/ ; }, mesh = {Rats ; Animals ; Mice ; *Cytochrome P-450 CYP11B2 ; *Fadrozole/toxicity ; Aldosterone ; Rats, Sprague-Dawley ; Iatrogenic Disease ; Inflammation/chemically induced ; Colon ; }, abstract = {Recently, we described local aldosterone production in the murine large intestine. Upregulated local aldosterone synthesis in different tissues has been linked with inflammatory conditions, which have been attenuated by the aldosterone synthase (CYP11B2) inhibitor, fadrozole (FAD286). Therefore, we investigated the effect of inhibition of intestinal aldosterone synthesis on the development of intestinal inflammation. Sprague-Dawley rats were administered 5% (v/w) dextran sodium sulphate (DSS) for 7 days with or without daily FAD286 (30 mg/kg/d) subcutaneous injections on 3 days before, during and one day after DSS. Tissue aldosterone concentrations were evaluated by ELISA, CYP11B2 by Western blot and RT-qPCR. FAD286 halved adrenal aldosterone production but, intriguingly, increased the colonic aldosterone concentration. The lack of inhibitory effect of FAD286 in the colon might have been affected by the smaller size of colonic vs. adrenal CYP11B2, as seen in Western blot. When combined with DSS, FAD286 aggravated the macroscopic and histological signs of intestinal inflammation, lowered the animals' body weight gain and increased the incidence of gastrointestinal bleeding and the permeability to iohexol in comparison to DSS-animals. To conclude, FAD286 exerted harmful effects during intestinal inflammation. Local intestinal aldosterone did not seem to play any role in the inflammatory pathogenesis occurring in the intestine.}, }
@article {pmid37343497, year = {2023}, author = {Ogilvie, CE and Czekster, CM}, title = {Cyclic dipeptides and the human microbiome: Opportunities and challenges.}, journal = {Bioorganic &amp; medicinal chemistry}, volume = {90}, number = {}, pages = {117372}, doi = {10.1016/j.bmc.2023.117372}, pmid = {37343497}, issn = {1464-3391}, support = {210486/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; 204821/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Dipeptides/pharmacology/chemistry ; Health Promotion ; *Microbiota ; }, abstract = {Research into the human microbiome has implicated its constituents in a variety of non-communicable diseases, with certain microbes found to promote health and others leading to dysbiosis and pathogenesis.Microbes communicate and coordinate their behaviour through the secretion of small molecules, such as cyclic dipeptides (CDPs), into their surrounding environment. CDPs are ubiquitous signalling molecules thatexhibit a wide range of biological activities, with particular relevance to human health due to their potential to act as microbiome modulators.}, }
@article {pmid37338299, year = {2023}, author = {Hurst, JH and Kelly, MS}, title = {Leveraging the human microbiota to target bacterial respiratory pathogens: new paths toward an expanded antimicrobial armamentarium.}, journal = {mBio}, volume = {14}, number = {4}, pages = {e0085423}, pmid = {37338299}, issn = {2150-7511}, support = {K01 AI173398/AI/NIAID NIH HHS/United States ; }, mesh = {Child ; Humans ; Moraxella catarrhalis/drug effects ; *Anti-Infective Agents ; *Respiratory Tract Infections/drug therapy/microbiology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; }, abstract = {Acute respiratory infections are the most frequent infections across the lifespan and are the leading infectious cause of death among children globally. Bacterial respiratory infections are routinely treated with antibiotics, nearly all of which are derived from microbial natural products. Unfortunately, antibiotic-resistant bacteria are an increasingly frequent cause of respiratory infections, and there are few new antibiotics in development that target these pathogens. In the article by Stubbendieck et al., the authors identified Rothia species that demonstrate in vitro and ex vivo growth inhibition of the respiratory pathobiont Moraxella catarrhalis. The authors present experiments suggesting that this activity is mediated at least in part through the secretion of a novel peptidoglycan endopeptidase that targets the M. catarrhalis cell wall. In this commentary, we discuss these findings in the context of the urgent threat of antimicrobial resistance and highlight the promise of the human respiratory microbiota as a source of novel biotherapeutics.}, }
@article {pmid37333098, year = {2023}, author = {Grodner, B and Shi, H and Farchione, O and Vill, AC and Ntekas, I and Diebold, PJ and Zipfel, WR and Brito, IL and Vlaminck, I}, title = {Spatial Mapping of Mobile Genetic Elements and their Cognate Hosts in Complex Microbiomes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37333098}, issn = {2692-8205}, support = {DP2 AI138242/AI/NIAID NIH HHS/United States ; R33 CA235302/CA/NCI NIH HHS/United States ; S10 OD018516/OD/NIH HHS/United States ; }, abstract = {The frequent exchange of mobile genetic elements (MGEs) between bacteria accelerates the spread of functional traits, including antimicrobial resistance, within the human microbiome. Yet, progress in understanding these intricate processes has been hindered by the lack of tools to map the spatial spread of MGEs in complex microbial communities, and to associate MGEs to their bacterial hosts. To overcome this challenge, we present an imaging approach that pairs single molecule DNA Fluorescence In Situ Hybridization (FISH) with multiplexed ribosomal RNA FISH, thereby enabling the simultaneous visualization of both MGEs and host bacterial taxa. We used this methodology to spatially map bacteriophage and antimicrobial resistance (AMR) plasmids in human oral biofilms, and we studied the heterogeneity in their spatial distributions and demonstrated the ability to identify their host taxa. Our data revealed distinct clusters of both AMR plasmids and prophage, coinciding with densely packed regions of host bacteria in the biofilm. These results suggest the existence of specialized niches that maintain MGEs within the community, possibly acting as local hotspots for horizontal gene transfer. The methods introduced here can help advance the study of MGE ecology and address pressing questions regarding antimicrobial resistance and phage therapy.}, }
@article {pmid37331612, year = {2023}, author = {Adelfio, M and Bonzanni, M and Callen, GE and Paster, BJ and Hasturk, H and Ghezzi, CE}, title = {A physiologically relevant culture platform for long-term studies of in vitro gingival tissue.}, journal = {Acta biomaterialia}, volume = {167}, number = {}, pages = {321-334}, pmid = {37331612}, issn = {1878-7568}, support = {R03 DE030224/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Gingiva/pathology ; *Periodontitis/microbiology/pathology ; Epithelium ; Bacteria ; Biomarkers ; Porphyromonas gingivalis ; }, abstract = {There is a clinical need to understand the etiologies of periodontitis, considering the growing socio-economic impact of the disease. Despite recent advances in oral tissue engineering, experimental approaches have failed to develop a physiologically relevant gingival model that combines tissue organization with salivary flow dynamics and stimulation of the shedding and non-shedding oral surfaces. Herein, we develop a dynamic gingival tissue model composed of a silk scaffold, replicating the cyto-architecture and oxygen profile of the human gingiva, along with a saliva-mimicking medium that reflected the ionic composition, viscosity, and non-Newtonian behavior of human saliva. The construct was cultured in a custom designed bioreactor, in which force profiles on the gingival epithelium were modulated through analysis of inlet position, velocity and vorticity to replicate the physiological shear stress of salivary flow. The gingival bioreactor supported the long-term in vivo features of the gingiva and improved the integrity of the epithelial barrier, critical against the invasion of pathogenic bacteria. Furthermore, the challenge of the gingival tissue with P. gingivalis lipopolysaccharide, as an in vitro surrogate for microbial interactions, indicated a greater stability of the dynamic model in maintaining tissue homeostasis and, thus, its applicability in long-term studies. The model will be integrated into future studies with the human subgingival microbiome to investigate host-pathogen and host-commensal interactions. STATEMENT OF SIGNIFICANCE: The major societal impact of human microbiome had reverberated up to the establishment of the Common Fund's Human Microbiome Project, that has the intent of studying the role of microbial communities in human health and diseases, including periodontitis, atopic dermatitis, or asthma and inflammatory bowel disease. In addition, these chronic diseases are emergent drivers of global socioeconomic status. Not only common oral diseases have been shown to be directly correlated with several systemic conditions, but they are differentially impacting some racial/ethnic and socioeconomic groups. To address this growing social disparity, the development of in vitro gingival model would provide a time and cost-effective experimental platform, able to mimic the spectrum of periodontal disease presentation, for the identification of predictive biomarkers for early-stage diagnosis.}, }
@article {pmid37330560, year = {2023}, author = {Algavi, YM and Borenstein, E}, title = {A data-driven approach for predicting the impact of drugs on the human microbiome.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3614}, pmid = {37330560}, issn = {2041-1723}, support = {U19 AG057377/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Microbiota ; *Gastrointestinal Microbiome ; *Drug-Related Side Effects and Adverse Reactions ; Genomics ; Dysbiosis ; }, abstract = {Many medications can negatively impact the bacteria residing in our gut, depleting beneficial species, and causing adverse effects. To guide personalized pharmaceutical treatment, a comprehensive understanding of the impact of various drugs on the gut microbiome is needed, yet, to date, experimentally challenging to obtain. Towards this end, we develop a data-driven approach, integrating information about the chemical properties of each drug and the genomic content of each microbe, to systematically predict drug-microbiome interactions. We show that this framework successfully predicts outcomes of in-vitro pairwise drug-microbe experiments, as well as drug-induced microbiome dysbiosis in both animal models and clinical trials. Applying this methodology, we systematically map a large array of interactions between pharmaceuticals and human gut bacteria and demonstrate that medications' anti-microbial properties are tightly linked to their adverse effects. This computational framework has the potential to unlock the development of personalized medicine and microbiome-based therapeutic approaches, improving outcomes and minimizing side effects.}, }
@article {pmid37328672, year = {2023}, author = {O'Toole, PW and Paoli, M}, title = {The human microbiome, global health and the Sustainable Development Goals: opportunities and challenges.}, journal = {Nature reviews. Microbiology}, volume = {21}, number = {10}, pages = {624-625}, pmid = {37328672}, issn = {1740-1534}, mesh = {Humans ; *Global Health ; Sustainable Development ; Public Health ; *Microbiota ; }, }
@article {pmid37328513, year = {2023}, author = {Del Chierico, F and Marzano, V and Scanu, M and Reddel, S and Dentici, ML and Capolino, R and Di Donato, M and Spasari, I and Fiscarelli, EV and Digilio, MC and Abreu, MT and Dallapiccola, B and Putignani, L}, title = {Analysis of gut microbiota in patients with Williams-Beuren Syndrome reveals dysbiosis linked to clinical manifestations.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {9797}, pmid = {37328513}, issn = {2045-2322}, mesh = {Humans ; *Williams Syndrome/genetics/diagnosis ; Dysbiosis/microbiology ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Quality of Life ; *Gastrointestinal Diseases/complications ; }, abstract = {Williams-Beuren syndrome (WBS) is a multisystem genetic disease caused by the deletion of a region of 1.5-1.8 Mb on chromosome 7q11.23. The elastin gene seems to account for several comorbidities and distinct clinical features such including cardiovascular disease, connective tissue abnormalities, growth retardation, and gastrointestinal (GI) symptoms. Increasing evidence points to alterations in gut microbiota composition as a primary or secondary cause of some GI or extra-intestinal characteristics. In this study, we performed the first exploratory analysis of gut microbiota in WBS patients compared to healthy subjects (CTRLs) using 16S rRNA amplicon sequencing, by investigating the gut dysbiosis in relation to diseases and comorbidities. We found that patients with WBS have significant dysbiosis compared to age-matched CTRLs, characterized by an increase in proinflammatory bacteria such as Pseudomonas, Gluconacetobacter and Eggerthella, and a reduction of anti-inflammatory bacteria including Akkermansia and Bifidobacterium. Microbial biomarkers associated with weight gain, GI symptoms and hypertension were identified. Gut microbiota profiling could represent a new tool that characterise intestinal dysbiosis to complement the clinical management of these patients. In particular, the administration of microbial-based treatments, alongside traditional therapies, could help in reducing or preventing the burden of these symptoms and improve the quality of life of these patients.}, }
@article {pmid37325707, year = {2023}, author = {Wang, Y and Zhang, R and Pu, Y and Wang, D and Wang, Y and Wu, X and Pan, Y and Luo, C and Zhao, G and Quan, Z and Zheng, Y}, title = {Sample Collection, DNA Extraction, and Library Construction Protocols of the Human Microbiome Studies in the International Human Phenome Project.}, journal = {Phenomics (Cham, Switzerland)}, volume = {3}, number = {3}, pages = {300-308}, pmid = {37325707}, issn = {2730-5848}, abstract = {UNLABELLED: The human microbiome plays a crucial role in human health. In the past decade, advances in high-throughput sequencing technologies and analytical software have significantly improved our knowledge of the human microbiome. However, most studies concerning the human microbiome did not provide repeatable protocols to guide the sample collection, handling, and processing procedures, which impedes obtaining valid and timely microbial taxonomic and functional results. This protocol provides detailed operation methods of human microbial sample collection, DNA extraction, and library construction for both the amplicon sequencing-based measurements of the microbial samples from the human nasal cavity, oral cavity, and skin, as well as the shotgun metagenomic sequencing-based measurements of the human stool samples among adult participants. This study intends to develop practical procedure standards to improve the reproducibility of microbiota profiling of human samples.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-023-00097-y.}, }
@article {pmid37324782, year = {2023}, author = {Campbell, CD and Gleeson, M and Sulaiman, I}, title = {The role of the respiratory microbiome in asthma.}, journal = {Frontiers in allergy}, volume = {4}, number = {}, pages = {1120999}, pmid = {37324782}, issn = {2673-6101}, abstract = {Asthma is a common airways disease and the human microbiome plays an increasingly recognised role in asthma pathogenesis. Furthermore, the respiratory microbiome varies with asthma phenotype, endotype and disease severity. Consequently, asthma therapies have a direct effect on the respiratory microbiome. Newer biological therapies have led to a significant paradigm shift in how we treat refractory Type 2 high asthma. While airway inflammation is the generally accepted mechanism of action of all asthma therapies, including both inhaled and systemic therapies, there is evidence to suggest that they may also alter the microbiome to create a more functionally balanced airway microenvironment while also influencing airway inflammation directly. This downregulated inflammatory cascade seen biochemically, and reflected in improved clinical outcomes, supports the hypothesis that biological therapies may in fact affect the microbiome-host immune system dynamic and thus represent a therapeutic target for exacerbations and disease control.}, }
@article {pmid37323911, year = {2023}, author = {Nowicki, C and Ray, L and Engen, P and Madrigrano, A and Witt, T and Lad, T and Cobleigh, M and Mutlu, EA}, title = {Comparison of gut microbiome composition in colonic biopsies, endoscopically-collected and at-home-collected stool samples.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1148097}, pmid = {37323911}, issn = {1664-302X}, support = {R21 TR003105/TR/NCATS NIH HHS/United States ; }, abstract = {AIM: The goal of this study is to compare microbiome composition in three different sample types in women, namely stool brought from home vs. solid stool samples obtained at the time of an unprepped sigmoidoscopy vs. biopsies of the colonic mucosa at the time of an unprepped sigmoidoscopy, using alpha- and beta-diversity metrics following bacterial 16S rRNA sequencing. The findings may have relevance to health and disease states in which bacterial metabolism has a significant impact on molecules/metabolites that are recirculated between the gut lumen and mucosa and systemic circulation, such as estrogens (as in breast cancer) or bile acids.<br><br>METHODS: Concomitant at-home-collected stool, endoscopically-collected stool, and colonic biopsy samples were collected from 48 subjects (24 breast cancer, 24 control.) After 16S rRNA sequencing, an amplicon sequence variant (ASV) based approach was used to analyze the data. Alpha diversity metrics (Chao1, Pielou's Evenness, Faith PD, Shannon, and Simpson) and beta diversity metrics (Bray-Curtis, Weighted and Unweighted Unifrac) were calculated. LEfSe was used to analyze differences in the abundance of various taxa between sample types.<br><br>RESULTS: Alpha and beta diversity metrics were significantly different between the three sample types. Biopsy samples were different than stool samples in all metrics. The highest variation in microbiome diversity was noted in the colonic biopsy samples. At-home and endoscopically-collected stool showed more similarities in count-based and weighted beta diversity metrics. There were significant differences in rare taxa and phylogenetically-diverse taxa between the two types of stool samples. Generally, there were higher levels of Proteobacteria in biopsy samples, with significantly more Actinobacteria and Firmicutes in stool (all p <&#x2009;0.001, q-value < 0.05). Overall, there was a significantly higher relative abundance of Lachnospiraceae and Ruminococcaceae in stool samples (at-home collected and endoscopically-collected) and higher abundances of Tisserellaceae in biopsy samples (all p <&#x2009;0.001, q-value < 0.05).<br><br>CONCLUSION: Our data shows that different sampling methods can impact results when looking at the composition of the gut microbiome using ASV-based approaches.}, }
@article {pmid37321219, year = {2023}, author = {Chen, H and Rosen, CE and González-Hernández, JA and Song, D and Potempa, J and Ring, AM and Palm, NW}, title = {Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions.}, journal = {Cell}, volume = {186}, number = {14}, pages = {3095-3110.e19}, pmid = {37321219}, issn = {1097-4172}, support = {R21 AI137935/AI/NIAID NIH HHS/United States ; R01 DE030939/DE/NIDCR NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; RM1 GM141649/GM/NIGMS NIH HHS/United States ; DP2 DK125119/DK/NIDDK NIH HHS/United States ; R01 DE022597/DE/NIDCR NIH HHS/United States ; R01 AG068863/AG/NIA NIH HHS/United States ; K22 AI123477/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Receptors, G-Protein-Coupled/metabolism ; *Microbiota ; Metabolome ; Mammals/metabolism ; }, abstract = {The human body contains thousands of metabolites derived from mammalian cells, the microbiota, food, and medical drugs. Many bioactive metabolites act through the engagement of G-protein-coupled receptors (GPCRs); however, technological limitations constrain current explorations of metabolite-GPCR interactions. Here, we developed a highly multiplexed screening technology called PRESTO-Salsa that enables simultaneous assessment of nearly all conventional GPCRs (>300 receptors) in a single well of a 96-well plate. Using PRESTO-Salsa, we screened 1,041 human-associated metabolites against the GPCRome and uncovered previously unreported endogenous, exogenous, and microbial GPCR agonists. Next, we leveraged PRESTO-Salsa to generate an atlas of microbiome-GPCR interactions across 435 human microbiome strains from multiple body sites, revealing conserved patterns of cross-tissue GPCR engagement and activation of CD97/ADGRE5 by the Porphyromonas gingivalis protease gingipain K. These studies thus establish a highly multiplexed bioactivity screening technology and expose a diverse landscape of human, diet, drug, and microbiota metabolome-GPCRome interactions.}, }
@article {pmid37320892, year = {2023}, author = {Santosh Kumar, BY and Mohan Kumar, GC and Shahapurkar, K and Tirth, V and Algahtani, A and Al-Mughanam, T and Alghtani, AH and Ananda Murthy, HC}, title = {Processing and characterization of egg shell derived nano-hydroxyapatite synthetic bone for Orthopaedic and Arthroscopy implants and substitutes in dentistry.}, journal = {Journal of the mechanical behavior of biomedical materials}, volume = {144}, number = {}, pages = {105963}, doi = {10.1016/j.jmbbm.2023.105963}, pmid = {37320892}, issn = {1878-0180}, mesh = {Animals ; Humans ; *Durapatite/chemistry ; Egg Shell ; *Orthopedics ; Arthroscopy ; Bone and Bones ; Tissue Engineering/methods ; X-Ray Diffraction ; Dentistry ; Spectroscopy, Fourier Transform Infrared ; Tissue Scaffolds/chemistry ; }, abstract = {The present work is focused on the nano-Hydroxyapatite (nHAp) synthesis with two different Indian breed Aseel and Kadaknath eggshells. The alloplast implants were developed through the foam replica method with polyurethane 45-PPI as a porous template. The synthesized nHAp was characterized by Field Emission Scanning Electron Microscopy (FE-SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The FE-SEM images of the nHAp showed the one dimensional clustered nanoparticles and the X-ray diffraction spectrum confirms that the major phase was hydroxyapatite with a small trace of β-tricalcium phosphate. The maximum compression strength of the sample was 5.49 ± 0.12 MPa which is in the range of the compression strength of human trabecular bone. The thermal and degradability studies results confirmed that these are highly stable and provides necessary a resorption needed for new bone tissue formation. Besides, the antimicrobial activity against tested human microbiome are satisfactory and the cell viability towards MG 63 human osteoblast-like cells provides a potential pathway for developing the nHAp implants for bone tissue engineering.}, }
@article {pmid37317139, year = {2023}, author = {Clarke, TH and Greco, C and Brinkac, L and Nelson, KE and Singh, H}, title = {MPrESS: An R-Package for Accurately Predicting Power for Comparisons of 16S rRNA Microbiome Taxa Distributions including Simulation by Dirichlet Mixture Modeling.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317139}, issn = {2076-2607}, support = {2015-R2-CX-K036//National Institute of Justice/ ; }, abstract = {Deep sequencing has revealed that the 16S rRNA gene composition of the human microbiome can vary between populations. However, when existing data are insufficient to address the desired study questions due to limited sample sizes, Dirichlet mixture modeling (DMM) can simulate 16S rRNA gene predictions from experimental microbiome data. We examined the extent to which simulated 16S rRNA gene microbiome data can accurately reflect the diversity within that identified from experimental data and calculate the power. Even when experimental and simulated datasets differed by less than 10%, simulation by DMM consistently overestimates power, except when using only highly discriminating taxa. Admixtures of DMM with experimental data performed poorly compared to pure simulation and did not show the same correlation with experimental data p-value and power values. While multiple replications of random sampling remain the favored method of determining the power, when the estimated sample size required to achieve a certain power exceeds the sample number, then simulated samples based on DMM can be used. We introduce an R-Package, MPrESS, to assist in power calculation and sample size estimation for a 16S rRNA gene microbiome dataset to detect a difference between populations. MPrESS can be downloaded from GitHub.}, }
@article {pmid37317128, year = {2023}, author = {Bar, K and Litera-Bar, M and Sozańska, B}, title = {Bacterial Microbiota of Asthmatic Children and Preschool Wheezers' Airways-What Do We Know?.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317128}, issn = {2076-2607}, abstract = {Asthma is the most chronic pulmonary disease in pediatric population, and its etiopathology still remains unclear. Both viruses and bacteria are suspected factors of disease development and are responsible for its exacerbation. Since the launch of The Human Microbiome Project, there has been an explosion of research on microbiota and its connection with various diseases. In our review, we have collected recent data about both upper- and lower-airway bacterial microbiota of asthmatic children. We have also included studies regarding preschool wheezers, since asthma diagnosis in children under 5 years of age remains challenging due to the lack of an objective tool. This paper indicates the need for further studies of microbiome and asthma, as in today's knowledge, there is no particular bacterium that discriminates the asthmatics from the healthy peers and can be used as a potential biological factor in the disease prevalence and treatment.}, }
@article {pmid37312410, year = {2023}, author = {Liu, C and Gong, J and Zhang, Q and Chen, G and Yin, S and Luo, Z and Zeng, W and Yu, J and Lan, P and He, Z}, title = {Dietary iron modulates gut microbiota and induces SLPI secretion to promote colorectal tumorigenesis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2221978}, pmid = {37312410}, issn = {1949-0984}, mesh = {Animals ; Mice ; *Gastrointestinal Microbiome ; Iron, Dietary ; Secretory Leukocyte Peptidase Inhibitor ; Carcinogenesis ; Iron ; *Colorectal Neoplasms ; }, abstract = {Dietary iron intake is closely related to the incidence of colorectal cancer. However, the interactions among dietary iron, gut microbiota, and epithelial cells in promoting tumorigenesis have rarely been discussed. Here, we report that gut microbiota plays a crucial role in promoting colorectal tumorigenesis in multiple mice models under excessive dietary iron intake. Gut microbiota modulated by excessive dietary iron are pathogenic, irritating the permeability of the gut barrier and causing leakage of lumen bacteria. Mechanistically, epithelial cells released more secretory leukocyte protease inhibitor (SLPI) to combat the leaked bacteria and limit inflammation. The upregulated SLPI acted as a pro-tumorigenic factor and promoted colorectal tumorigenesis by activating the MAPK signaling pathway. Moreover, excessive dietary iron significantly depleted Akkermansiaceae in the gut microbiota; while supplementation with Akkermansia muciniphila could successfully attenuate the tumorigenic effect from excessive dietary iron. Overall, excessive dietary iron perturbs diet - microbiome-epithelium interactions, which contributes to intestinal tumor initiation.}, }
@article {pmid37310633, year = {2023}, author = {Shin, W and Kim, HJ}, title = {In Vitro Morphogenesis and Differentiation of Human Intestinal Epithelium in a Gut-on-a-Chip.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2650}, number = {}, pages = {197-206}, pmid = {37310633}, issn = {1940-6029}, support = {K00 CA245801/CA/NCI NIH HHS/United States ; R21 CA236690/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Caco-2 Cells ; *Intestinal Mucosa ; Cell Differentiation ; Morphogenesis ; *Lab-On-A-Chip Devices ; }, abstract = {The establishment of a three-dimensional (3D) epithelial structure and cytodifferentiation in vitro is necessary to recapitulate in vivo-relevant structure and function of the human intestine. Here, we describe an experimental protocol to build an organomimetic gut-on-a-chip microdevice that allows inducing 3D morphogenesis of human intestinal epithelium using Caco-2 cells or intestinal organoid cells. Under physiological flow and physical motions, intestinal epithelium spontaneously recreates 3D epithelial morphology in a gut-on-a-chip that offers enhanced mucus production, epithelial barrier, and longitudinal host-microbe co-culture. This protocol may provide implementable strategies to advance traditional in vitro static cultures, human microbiome studies, and pharmacological testing.}, }
@article {pmid37305030, year = {2023}, author = {Wang, Y and Salonen, A and Jian, C}, title = {Can prebiotics help tackle the childhood obesity epidemic?.}, journal = {Frontiers in endocrinology}, volume = {14}, number = {}, pages = {1178155}, pmid = {37305030}, issn = {1664-2392}, mesh = {Child ; Adolescent ; Adult ; Humans ; *Pediatric Obesity/epidemiology/prevention &amp; control ; Prebiotics ; Overweight ; Adiposity ; Dysbiosis/epidemiology/prevention &amp; control ; }, abstract = {Globally, excess weight during childhood and adolescence has become a public health crisis with limited treatment options. Emerging evidence suggesting the involvement of gut microbial dysbiosis in obesity instills hope that targeting the gut microbiota could help prevent or treat obesity. In pre-clinical models and adults, prebiotic consumption has been shown to reduce adiposity partially via restoring symbiosis. However, there is a dearth of clinical research into its potential metabolic benefits in the pediatric population. Here, we provide a succinct overview of the common characteristics of the gut microbiota in childhood obesity and mechanisms of action of prebiotics conferring metabolic benefits. We then summarize available clinical trials in children with overweight or obesity investigating the effects of prebiotics on weight management. This review highlights several controversial aspects in the microbiota-dependent mechanisms by which prebiotics are thought to affect host metabolism that warrant future investigation in order to design efficacious interventions for pediatric obesity.}, }
@article {pmid37301875, year = {2023}, author = {Li, L and Wang, T and Ning, Z and Zhang, X and Butcher, J and Serrana, JM and Simopoulos, CMA and Mayne, J and Stintzi, A and Mack, DR and Liu, YY and Figeys, D}, title = {Revealing proteome-level functional redundancy in the human gut microbiome using ultra-deep metaproteomics.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {3428}, pmid = {37301875}, issn = {2041-1723}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; RF1 AG067744/AG/NIA NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Proteome ; Proteomics ; Xenobiotics ; Feces ; *Microbiota ; }, abstract = {Functional redundancy is a key ecosystem property representing the fact that different taxa contribute to an ecosystem in similar ways through the expression of redundant functions. The redundancy of potential functions (or genome-level functional redundancy [Formula: see text]) of human microbiomes has been recently quantified using metagenomics data. Yet, the redundancy of expressed functions in the human microbiome has never been quantitatively explored. Here, we present an approach to quantify the proteome-level functional redundancy [Formula: see text] in the human gut microbiome using metaproteomics. Ultra-deep metaproteomics reveals high proteome-level functional redundancy and high nestedness in the human gut proteomic content networks (i.e., the bipartite graphs connecting taxa to functions). We find that the nested topology of proteomic content networks and relatively small functional distances between proteomes of certain pairs of taxa together contribute to high [Formula: see text] in the human gut microbiome. As a metric comprehensively incorporating the factors of presence/absence of each function, protein abundances of each function and biomass of each taxon, [Formula: see text] outcompetes diversity indices in detecting significant microbiome responses to environmental factors, including individuality, biogeography, xenobiotics, and disease. We show that gut inflammation and exposure to specific xenobiotics can significantly diminish the [Formula: see text] with no significant change in taxonomic diversity.}, }
@article {pmid37301199, year = {2023}, author = {Stražar, M and Park, J and Abelin, JG and Taylor, HB and Pedersen, TK and Plichta, DR and Brown, EM and Eraslan, B and Hung, YM and Ortiz, K and Clauser, KR and Carr, SA and Xavier, RJ and Graham, DB}, title = {HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.}, journal = {Immunity}, volume = {56}, number = {7}, pages = {1681-1698.e13}, pmid = {37301199}, issn = {1097-4180}, support = {U19 AI110495/AI/NIAID NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; RC2 DK114784/DK/NIDDK NIH HHS/United States ; U24 CA271075/CA/NCI NIH HHS/United States ; U24 CA270823/CA/NCI NIH HHS/United States ; P01 CA206978/CA/NCI NIH HHS/United States ; U24 CA210979/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Captan ; *Deep Learning ; *COVID-19 ; SARS-CoV-2 ; HLA Antigens ; Epitopes, T-Lymphocyte ; Peptides ; }, abstract = {CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies.}, }
@article {pmid37299414, year = {2023}, author = {Hughes, RL and Frankenfeld, CL and Gohl, DM and Huttenhower, C and Jackson, SA and Vandeputte, D and Vogtmann, E and Comstock, SS and Kable, ME}, title = {Methods in Nutrition &amp; Gut Microbiome Research: An American Society for Nutrition Satellite Session [13 October 2022].}, journal = {Nutrients}, volume = {15}, number = {11}, pages = {}, pmid = {37299414}, issn = {2072-6643}, support = {IAFNS-HUGESRILEY-20221026//Institute for the Advancement of Food and Nutrition Sciences/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Nutritional Status ; *Microbiota ; Research ; *Nutrition Therapy ; }, abstract = {The microbial cells colonizing the human body form an ecosystem that is integral to the regulation and maintenance of human health. Elucidation of specific associations between the human microbiome and health outcomes is facilitating the development of microbiome-targeted recommendations and treatments (e.g., fecal microbiota transplant; pre-, pro-, and post-biotics) to help prevent and treat disease. However, the potential of such recommendations and treatments to improve human health has yet to be fully realized. Technological advances have led to the development and proliferation of a wide range of tools and methods to collect, store, sequence, and analyze microbiome samples. However, differences in methodology at each step in these analytic processes can lead to variability in results due to the unique biases and limitations of each component. This technical variability hampers the detection and validation of associations with small to medium effect sizes. Therefore, the American Society for Nutrition (ASN) Nutritional Microbiology Group Engaging Members (GEM), sponsored by the Institute for the Advancement of Food and Nutrition Sciences (IAFNS), hosted a satellite session on methods in nutrition and gut microbiome research to review currently available methods for microbiome research, best practices, as well as tools and standards to aid in comparability of methods and results. This manuscript summarizes the topics and research discussed at the session. Consideration of the guidelines and principles reviewed in this session will increase the accuracy, precision, and comparability of microbiome research and ultimately the understanding of the associations between the human microbiome and health.}, }
@article {pmid37299395, year = {2023}, author = {Policastro, V and Righelli, D and Ravà, L and Vernocchi, P and Bianchi, M and Vallone, C and Signore, F and Manco, M}, title = {Dietary Fatty Acids Contribute to Maintaining the Balance between Pro-Inflammatory and Anti-Inflammatory Responses during Pregnancy.}, journal = {Nutrients}, volume = {15}, number = {11}, pages = {}, pmid = {37299395}, issn = {2072-6643}, support = {GR-2010-2304957//Ministero della Salute/ ; }, mesh = {Female ; Humans ; Pregnancy ; *Leptin ; Intercellular Adhesion Molecule-1 ; *Diabetes, Gestational ; Adiponectin ; Fatty Acids ; Cytokines ; }, abstract = {BACKGROUND: During pregnancy, the balance between pro-inflammatory and anti-inflammatory responses is essential for ensuring healthy outcomes. Dietary Fatty acids may modulate inflammation.<br><br>METHODS: We investigated the association between dietary fatty acids as profiled on red blood cells membranes and a few pro- and anti-inflammatory cytokines, including the adipokines leptin and adiponectin at ~38 weeks in 250 healthy women.<br><br>RESULTS: We found a number of associations, including, but not limited to those of adiponectin with C22:3/C22:4 (coeff -1.44; p = 0.008), C18:1 c13/c14 (coeff 1.4; p = 0.02); endotoxin with C20:1 (coeff -0.9; p = 0.03), C22:0 (coeff -0.4; p = 0.05); MCP-1 with C16:0 (coeff 0.8; p = 0.04); and ICAM-1 with C14:0 (coeff -86.8; p = 0.045). Several cytokines including leptin were associated with maternal body weight (coeff 0.9; p = 2.31 &#xd7; 10[-5]), smoking habits (i.e., ICAM-1 coeff 133.3; p = 0.09), or gestational diabetes (i.e., ICAM-1 coeff 688; p = 0.06).<br><br>CONCLUSIONS: In a general cohort of pregnant women, the intake of fatty acids influenced the balance between pro- and anti-inflammatory molecules together with weight gain, smoking habits, and gestational diabetes.}, }
@article {pmid37298483, year = {2023}, author = {Park, S and Zhang, T and Kang, S}, title = {Fecal Microbiota Composition, Their Interactions, and Metagenome Function in US Adults with Type 2 Diabetes According to Enterotypes.}, journal = {International journal of molecular sciences}, volume = {24}, number = {11}, pages = {}, pmid = {37298483}, issn = {1422-0067}, support = {RS-2023-00208567//National Research Foundation of Korea/ ; }, mesh = {Adult ; Humans ; Metagenome ; *Diabetes Mellitus, Type 2/genetics ; *Microbiota ; *Gastrointestinal Microbiome/genetics ; Feces/microbiology ; Bacteria/genetics ; }, abstract = {T2DM etiology differs among Asians and Caucasians and may be associated with gut microbiota influenced by different diet patterns. However, the association between fecal bacterial composition, enterotypes, and T2DM susceptibility remained controversial. We investigated the fecal bacterial composition, co-abundance network, and metagenome function in US adults with T2DM compared to healthy adults based on enterotypes. We analyzed 1911 fecal bacterial files of 1039 T2DM and 872 healthy US adults from the Human Microbiome Projects. Operational taxonomic units were obtained after filtering and cleaning the files using Qiime2 tools. Machine learning and network analysis identified primary bacteria and their interactions influencing T2DM incidence, clustered into enterotypes, Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), and Prevotellaceae (ET-P). ET-B showed higher T2DM incidence. Alpha-diversity was significantly lower in T2DM in ET-L and ET-P (p < 0.0001), but not in ET-B. Beta-diversity revealed a distinct separation between T2DM and healthy groups across all enterotypes (p < 0.0001). The XGBoost model exhibited high accuracy and sensitivity. Enterocloster bolteae, Facalicatena fissicatena, Clostridium symbiosum, and Facalibacterium prausnitizii were more abundant in the T2DM group than in the healthy group. Bacteroides koreensis, Oscillibacter ruminantium, Bacteroides uniformis, and Blautia wexlerae were lower in the T2DM than in the healthy group regardless of the enterotypes in the XGBoost model (p < 0.0001). However, the patterns of microbial interactions varied among different enterotypes affecting T2DM risk. The interaction between fecal bacteria was more tightly regulated in the ET-L than in the ET-B and ET-P groups (p < 0.001). Metagenomic analysis revealed an inverse association between bacteria abundance in T2DM, energy utility, butanoate and propanoate metabolism, and the insulin signaling pathway (p < 0.0001). In conclusion, fecal bacteria play a role in T2DM pathogenesis, particularly within different enterotypes, providing valuable insights into the link between gut microbiota and T2DM in the US population.}, }
@article {pmid37293045, year = {2023}, author = {Zhao, L and Cunningham, CM and Andruska, AM and Schimmel, K and Ali, MK and Kim, D and Gu, S and Chang, JL and Spiekerkoetter, E and Nicolls, MR}, title = {Rat microbial biogeography and age-dependent lactic acid bacteria in healthy lungs.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.05.19.541527}, pmid = {37293045}, issn = {2692-8205}, abstract = {The laboratory rat emerges as a useful tool for studying the interaction between the host and its microbiome. To advance principles relevant to the human microbiome, we systematically investigated and defined a multi-tissue full lifespan microbial biogeography for healthy Fischer 344 rats. Microbial community profiling data was extracted and integrated with host transcriptomic data from the Sequencing Quality Control (SEQC) consortium. Unsupervised machine learning, Spearman's correlation, taxonomic diversity, and abundance analyses were performed to determine and characterize the rat microbial biogeography and the identification of four inter-tissue microbial heterogeneity patterns (P1-P4). The 11 body habitats harbor a greater diversity of microbes than previously suspected. Lactic acid bacteria (LAB) abundances progressively declined in lungs from breastfeed newborn to adolescence/adult and was below detectable levels in elderly rats. LAB's presence and levels in lungs were further evaluated by PCR in the two validation datasets. The lung, testes, thymus, kidney, adrenal, and muscle niches were found to have age-dependent alterations in microbial abundance. P1 is dominated by lung samples. P2 contains the largest sample size and is enriched for environmental species. Liver and muscle samples were mostly classified into P3. Archaea species were exclusively enriched in P4. The 357 pattern-specific microbial signatures were positively correlated with host genes in cell migration and proliferation (P1), DNA damage repair and synaptic transmissions (P2), as well as DNA transcription and cell cycle in P3. Our study established a link between metabolic properties of LAB with lung microbiota maturation and development. Breastfeeding and environmental exposure influence microbiome composition and host health and longevity. The inferred rat microbial biogeography and pattern-specific microbial signatures would be useful for microbiome therapeutic approaches to human health and good quality of life.}, }
@article {pmid37287813, year = {2023}, author = {Koizumi, Y and Maruyama, F}, title = {Editorial: Ecology, environment, and human microbiome interaction with infection.}, journal = {Frontiers in public health}, volume = {11}, number = {}, pages = {1217927}, doi = {10.3389/fpubh.2023.1217927}, pmid = {37287813}, issn = {2296-2565}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; }, }
@article {pmid37280117, year = {2023}, author = {Scaldaferri, F and D'Onofrio, AM and Calia, R and Di Vincenzo, F and Ferrajoli, GF and Petito, V and Maggio, E and Pafundi, PC and Napolitano, D and Masi, L and Schiavoni, E and Fanali, C and Puca, P and Turchini, L and Lopetuso, LR and Del Chierico, F and Putignani, L and Gasbarrini, A and Camardese, AG}, title = {Gut Microbiota Signatures Are Associated With Psychopathological Profiles in Patients With Ulcerative Colitis: Results From an Italian Tertiary IBD Center.}, journal = {Inflammatory bowel diseases}, volume = {29}, number = {11}, pages = {1805-1818}, pmid = {37280117}, issn = {1536-4844}, mesh = {Humans ; *Colitis, Ulcerative/pathology ; *Gastrointestinal Microbiome ; Longitudinal Studies ; *Depressive Disorder, Major/complications ; Prospective Studies ; Quality of Life ; Bacteria ; }, abstract = {BACKGROUND: Several patients with ulcerative colitis (UC) suffer from psychiatric disorders, such as major depressive disorder, anxiety, or bipolar disorder, and show specific personality traits. Despite this, there are few data about personality profiles' characterization in UC patients and about correlation of their psychopathological profile with their intestinal microbiota.The aim of our study is to analyze the psychopathological and personality profile of UC patients and correlate it with specific signatures of their gut microbiota.<br><br>METHODS: This is a prospective interventional longitudinal cohort study. We enrolled consecutive patients affected by UC attending to the IBD Unit of Center for Digestive Disease of "A. Gemelli" IRCCS Hospital in Rome and a group of healthy subjects, matched for specific characteristics. Each patient was evaluated by a gastroenterologist and a psychiatrist. Moreover, all participants underwent psychological tests and a collection of stool samples.<br><br>RESULTS: We recruited 39 UC patients and 37 healthy subjects. Most patients showed high level of alexithymia, anxiety symptoms, depressive symptoms, as well as neuroticism and hypochondria, with obsessive-compulsive features at the behavioral level, which significantly impaired their quality of life and abilities at work. Gut microbiota analysis in UC patients demonstrated an increase in actinobacteria, Proteobacteria and Saccharibacteria (TM7), with a reduction in verrucomicrobia, euryarchaeota and tenericutes.<br><br>CONCLUSIONS: Our study confirmed the presence of high levels of psycho-emotional distress in UC patients, alongside alterations of the intestinal microbiota, and highlighted some families and genera of bacteria (Enterobacteriaceae, Streptococcus, Veillonella, Klebsiella, and Clostridiaceae) as potential markers of an altered gut-brain axis in these patients.}, }
@article {pmid37279589, year = {2023}, author = {Ericson, JE and Burgoine, K and Kumbakumba, E and Ochora, M and Hehnly, C and Bajunirwe, F and Bazira, J and Fronterre, C and Hagmann, C and Kulkarni, AV and Kumar, MS and Magombe, J and Mbabazi-Kabachelor, E and Morton, SU and Movassagh, M and Mugamba, J and Mulondo, R and Natukwatsa, D and Kaaya, BN and Olupot-Olupot, P and Onen, J and Sheldon, K and Smith, J and Ssentongo, P and Ssenyonga, P and Warf, B and Wegoye, E and Zhang, L and Kiwanuka, J and Paulson, JN and Broach, JR and Schiff, SJ}, title = {Neonatal Paenibacilliosis: Paenibacillus Infection as a Novel Cause of Sepsis in Term Neonates With High Risk of Sequelae in Uganda.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {77}, number = {5}, pages = {768-775}, pmid = {37279589}, issn = {1537-6591}, support = {DP1 HD086071/HD/NICHD NIH HHS/United States ; KL2 TR002015/TR/NCATS NIH HHS/United States ; R01 AI145057/AI/NIAID NIH HHS/United States ; }, mesh = {Infant, Newborn ; Humans ; Female ; Pregnancy ; *Neonatal Sepsis ; Uganda/epidemiology ; *Sepsis/complications/epidemiology/drug therapy ; Anti-Bacterial Agents/therapeutic use ; *Hydrocephalus ; Disease Progression ; *Paenibacillus ; }, abstract = {BACKGROUND: Paenibacillus thiaminolyticus may be an underdiagnosed cause of neonatal sepsis.<br><br>METHODS: We prospectively enrolled a cohort of 800 full-term neonates presenting with a clinical diagnosis of sepsis at 2 Ugandan hospitals. Quantitative polymerase chain reaction specific to P. thiaminolyticus and to the Paenibacillus genus were performed on the blood and cerebrospinal fluid (CSF) of 631 neonates who had both specimen types available. Neonates with Paenibacillus genus or species detected in either specimen type were considered to potentially have paenibacilliosis, (37/631, 6%). We described antenatal, perinatal, and neonatal characteristics, presenting signs, and 12-month developmental outcomes for neonates with paenibacilliosis versus clinical sepsis due to other causes.<br><br>RESULTS: Median age at presentation was 3 days (interquartile range 1, 7). Fever (92%), irritability (84%), and clinical signs of seizures (51%) were common. Eleven (30%) had an adverse outcome: 5 (14%) neonates died during the first year of life; 5 of 32 (16%) survivors developed postinfectious hydrocephalus (PIH) and 1 (3%) additional survivor had neurodevelopmental impairment without hydrocephalus.<br><br>CONCLUSIONS: Paenibacillus species was identified in 6% of neonates with signs of sepsis who presented to 2 Ugandan referral hospitals; 70% were P. thiaminolyticus. Improved diagnostics for neonatal sepsis are urgently needed. Optimal antibiotic treatment for this infection is unknown but ampicillin and vancomycin will be ineffective in many cases. These results highlight the need to consider local pathogen prevalence and the possibility of unusual pathogens when determining antibiotic choice for neonatal sepsis.}, }
@article {pmid37265934, year = {2023}, author = {Kedia, S and Ahuja, V}, title = {Human gut microbiome: A primer for the clinician.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {7}, number = {5}, pages = {337-350}, pmid = {37265934}, issn = {2397-9070}, abstract = {The human host gets tremendously influenced by a genetically and phenotypically distinct and heterogeneous constellation of microbial species-the human microbiome-the gut being one of the most densely populated and characterized site for these organisms. Microbiome science has advanced rapidly, technically with respect to the analytical methods and biologically with respect to its mechanistic influence in health and disease states. A clinician conducting a microbiome study should be aware of the nuances related to microbiome research, especially with respect to the technical and biological factors that can influence the interpretation of research outcomes. Hence, this review is an attempt to detail these aspects of the human gut microbiome, with emphasis on its determinants in a healthy state.}, }
@article {pmid37265494, year = {2023}, author = {Chen, H and Sun, R and Wang, J and Yao, S and Batool, SS and Yu, Z and Huang, S and Huang, J}, title = {Bacillus amyloliquefaciens alleviates the pathological injuries in mice infected with Schistosoma japonicum by modulating intestinal microbiome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1172298}, pmid = {37265494}, issn = {2235-2988}, mesh = {Animals ; Mice ; *Schistosoma japonicum ; Liver Cirrhosis/pathology ; *Bacillus amyloliquefaciens ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Liver/pathology ; Mammals ; }, abstract = {Schistosoma japonicum causes serious pathological organ damage and alteration of the intestinal microbiome in the mammalian host, threatening the health of millions of people in China. Bacillus amyloliquefaciens has been reported to be able to alleviate the damage to the gut and liver and maintain the homeostasis of the intestinal microenvironment. However, it was unclear whether B. amyloliquefaciens could alleviate the hepatic and intestinal symptoms caused by S. japonicum. In this study, the intragastric administration of B. amyloliquefaciens was performed to treat S. japonicum-infected mice during the acute phase. Histopathological analysis and 16S rRNA gene sequencing were used to evaluate the pathological damage and changes in the intestinal microbiome. The results of the study showed that B. amyloliquefaciens treatment significantly reduced the degree of granuloma and fibrosis in infected mice. Additionally, recovery of diversity in the intestinal microbiome, decrease in the relative abundance of potential pathogenic bacteria such as Escherichia-Shigella, and reshaping of the interactive network between genera in the intestine were also observed after treatment with B. amyloliquefaciens. Our findings indicated that treatment with B. amyloliquefaciens effectively alleviated the pathological injuries of the liver and intestine in mice infected with S. japonicum by modulating the intestinal microbiome, implying that this probiotic can function as an effective therapeutic agent against schistosomiasis. We hope our study will provide auxiliary strategies and methods for the early prevention of schistosomiasis japonica.}, }
@article {pmid37257272, year = {2023}, author = {Li, F and Lai, J and Ma, F and Cai, Y and Li, S and Feng, Z and Lu, Z and Liu, X and Ke, Q and Hao, H and Xiao, X}, title = {Maternal melatonin supplementation shapes gut microbiota and protects against inflammation in early life.}, journal = {International immunopharmacology}, volume = {120}, number = {}, pages = {110359}, doi = {10.1016/j.intimp.2023.110359}, pmid = {37257272}, issn = {1878-1705}, mesh = {Female ; Mice ; Animals ; *Melatonin/pharmacology/therapeutic use ; Butyric Acid/pharmacology ; Lipopolysaccharides/pharmacology ; *Gastrointestinal Microbiome ; Inflammation/drug therapy ; Fatty Acids, Volatile ; *Intestinal Diseases ; Dietary Supplements ; }, abstract = {BACKGROUND: Gut microbiota colonization is critical for immune education and nutrient metabolism. Research shows that melatonin has beneficial effects as a therapy for many diseases via modulating gut dysbiosis. However, it is unclear whether melatonin alters gut microbiota colonization in early life.<br><br>METHODS: In the experimental group (Mel), mice were intraperitoneally injected with melatonin at 10&#xa0;mg/kg body weight for embryonic days 14-16 and received drinking water containing 0.4&#xa0;mg/mL melatonin until 28&#xa0;days postpartum. In the control group (Ctrl), mice were injected with the same volume of 2.5% ethanol in saline and provided with standard water. Two more groups were created by treating neonatal mice with 20&#xa0;mg/kg lipopolysaccharide (LPS) to induce inflammation, resulting in the groups Ctrl&#xa0;+&#xa0;LPS and Mel&#xa0;+&#xa0;LPS, respectively. We examined the gut microbiota of the neonatal mice in the Ctrl and Mel group on Days 7, 14, 21, and 28 post-birth. On Day 14, melatonin and short-chain fatty acids (SCFAs) concentrations were measured in the Ctrl and Mel group and the mice were treated with LPS to be evaluated for intestinal injury and inflammatory response 15&#xa0;h post treatment. According to the result of the SCFAs concentrations, some neonatal mice were intraperitoneally injected with 500&#xa0;mg/kg sodium butyrate (SB) from Days 11-13, intraperitoneally injected with 20&#xa0;mg/kg LPS on Day 14, and then euthanized by carbon dioxide inhalation the next morning. Intestinal injury and inflammatory responses were evaluated in the Ctrl&#xa0;+&#xa0;LPS and SB&#xa0;+&#xa0;LPS groups, respectively.<br><br>RESULTS: By Day 14, it was evident that maternal melatonin supplementation significantly increased the relative abundance of Firmicutes in the ileal [61.03 (35.35 - 76.18) % vs. 98.02 (86.61 - 99.01) %, P&#xa0;=&#xa0;0.003] and colonic [73.88 (69.77 - 85.99) % vs. 96.16 (94.57 - 96.34) %, P&#xa0;=&#xa0;0.04] microbiota, the concentration of melatonin (0.79&#xa0;&#xb1;&#xa0;0.49&#xa0;ng/ml vs. 6.11&#xa0;&#xb1;&#xa0;3.48&#xa0;ng/ml, P&#xa0;=&#xa0;0.008) in the gut lumen, and the fecal butyric acid (12.91&#xa0;&#xb1;&#xa0;5.74&#xa0;&#x3bc;g/g vs. 23.58&#xa0;&#xb1;&#xa0;10.71&#xa0;&#x3bc;g/g, P&#xa0;=&#xa0;0.026) concentration of neonatal mice. Melatonin supplementation, and sodium butyrate treatment markedly alleviated intestinal injury and decreased inflammatory factors in neonatal mice.<br><br>CONCLUSION: This study suggests that maternal melatonin supplementation can shape the gut microbiota and metabolism of offspring under normal physiological conditions and protect them against LPS-induced inflammation in early life.}, }
@article {pmid37251147, year = {2023}, author = {Nurxat, N and Wang, L and Wang, Q and Li, S and Jin, C and Shi, Y and Wulamu, A and Zhao, N and Wang, Y and Wang, H and Li, M and Liu, Q}, title = {Commensal Staphylococcus epidermidis Defends against Staphylococcus aureus through SaeRS Two-Component System.}, journal = {ACS omega}, volume = {8}, number = {20}, pages = {17712-17718}, pmid = {37251147}, issn = {2470-1343}, abstract = {Staphylococcus aureus is a high-virulent Gram-positive pathogen that is responsible for a serious of diseases. The emergence of antibiotic-resistant S. aureus poses a significant challenge in terms of treatment. The recent research on the human microbiome suggested that the application of commensal bacteria is a new strategy for combating pathogenic infections. Staphylococcus epidermidis, one of the most abundant species in the nasal microbiome, is able to inhibit the colonization of S. aureus. However, during bacterial competition, S. aureus undergoes evolutionary changes to adapt to the diverse environment. Our study has demonstrated that the nasal colonized S. epidermidis possesses the ability to inhibit the hemolytic activity of S. aureus. Moreover, we deciphered another layer of mechanism to inhibit S. aureus colonization by S. epidermidis. The active component present in the cell-free culture of S. epidermidis was found to significantly reduce the hemolytic activity of S. aureus in SaeRS- and Agr-dependent manner. Specifically, the hemolytic inhibition on the S. aureus Agr-I type by S. epidermidis is primarily dependent on the SaeRS two-component system. The active component is characterized as a small molecule that is heat sensitive and protease resistant. Critically, S. epidermidis significantly inhibit the virulence of S. aureus in a mouse skin abscess model, suggesting that the active compound could potentially be used as a therapeutic agent for managing S. aureus infections.}, }
@article {pmid37249060, year = {2023}, author = {Wolf, M and Schallert, K and Knipper, L and Sickmann, A and Sczyrba, A and Benndorf, D and Heyer, R}, title = {Advances in the clinical use of metaproteomics.}, journal = {Expert review of proteomics}, volume = {20}, number = {4-6}, pages = {71-86}, doi = {10.1080/14789450.2023.2215440}, pmid = {37249060}, issn = {1744-8387}, mesh = {Humans ; *Proteomics/methods ; *Microbiota/genetics ; Bacterial Proteins/metabolism ; Computational Biology/methods ; Obesity ; }, abstract = {INTRODUCTION: Investigating the taxonomic and functional composition of human microbiomes can aid in the understanding of disease etiologies, diagnosis, and therapy monitoring for several diseases, including inflammatory bowel disease or obesity. One method for microbiome monitoring is metaproteomics, which assesses human and microbial proteins and thus enables the study of host-microbiome interactions. This advantage led to increased interest in metaproteome analyses and significant developments to introduce this method into a clinical context.<br><br>AREAS COVERED: This review summarizes the recent progress from a technical side and an application-related point of view.<br><br>EXPERT OPINION: Numerous publications imply the massive potential of metaproteomics to impact human health care. However, the key challenges of standardization and validation of experimental and bioinformatic workflows and accurate quantification methods must be overcome.}, }
@article {pmid37244386, year = {2023}, author = {Zhang, Y and Chen, T and Hao, X and Hu, Y and Chen, M and Zhang, D and Cai, H and Luo, J and Kong, L and Huang, S and Huang, Y and Yang, N and Liu, R and Li, Q and Yuan, C and Wang, C and Zhou, H and Huang, W and Zhang, W}, title = {Mapping the regulatory effects of herbal organic compounds on gut bacteria.}, journal = {Pharmacological research}, volume = {193}, number = {}, pages = {106804}, doi = {10.1016/j.phrs.2023.106804}, pmid = {37244386}, issn = {1096-1186}, mesh = {Humans ; Mice ; Animals ; Bacteria ; *Plants, Medicinal ; Terpenes ; *Alkaloids ; Flavonoids/pharmacology ; Phenols ; }, abstract = {Herbal organic compounds (HOCs) are bioactive natural products from medicinal plants and some traditional Chinese medicines (TCMs). Recently, ingestion of a few HOCs with low bioavailability has been associated with alterations in gut microbiota, but the extent of this phenomenon remains unclear. Here, we systematically screened 481 HOCs against 47 representative gut bacterial strains in vitro and found that almost one-third of the HOCs exhibited unique anticommensal activity. Quinones showed a potent anticommensal activity, while saturated fatty acids exhibited stronger inhibition of the Lactobacillus genus. Flavonoids, phenylpropanoids, terpenoids, triterpenoids, alkaloids and phenols displayed weaker anticommensal activity, but steroids, saccharides and glycosides had hardly any effect on strain growth. Notably, S-configuration HOCs demonstrated stronger anticommensal activity than R-configuration HOCs. The strict screening conditions ensured high accuracy (95%) through benchmarking validation. Additionally, the effects of HOCs on human fecal microbiota profiling were positively correlated with their anticommensal activity against bacterial strains. Molecular and chemical features such as AATS3i and XLogP3 were correlated with the anticommensal activity of the HOCs in the random forest classifier. Finally, we validated that curcumin, a polyhydric phenol with anticommensal activity, improved insulin resistance in HFD mice by modulating the composition and metabolic function of gut microbiota. Our results systematically mapped the profile of HOCs directly affecting human gut bacterial strains, offering a resource for future research on HOC-microbiota interaction, and broadening our understanding of natural product utilization through gut microbiota modulation.}, }
@article {pmid37240974, year = {2023}, author = {Karakasidis, E and Kotsiou, OS and Gourgoulianis, KI}, title = {Lung and Gut Microbiome in COPD.}, journal = {Journal of personalized medicine}, volume = {13}, number = {5}, pages = {}, pmid = {37240974}, issn = {2075-4426}, abstract = {Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. The association between lung and gut microbiomes in the pathogenesis of COPD has been recently uncovered. The goal of this study was to discuss the role of the lung and gut microbiomes in COPD pathophysiology. A systematic search of the PubMed database for relevant articles submitted up to June 2022 was performed. We examined the association between the lung and gut microbiome dysbiosis, reflected in bronchoalveolar lavage (BAL), lung tissue, sputum, and feces samples, and the pathogenesis and progression of COPD. It is evident that the lung and gut microbiomes affect each other and both play a vital role in the pathogenesis of COPD. However, more research needs to be carried out to find the exact associations between microbiome diversity and COPD pathophysiology and exacerbation genesis. Another field that research should focus on is the impact of treatment interventions targeting the human microbiome in preventing COPD genesis and progression.}, }
@article {pmid37239856, year = {2023}, author = {Csader, S and Ismaiah, MJ and Kuningas, T and Heinäniemi, M and Suhonen, J and Männistö, V and Pentikäinen, H and Savonen, K and Tauriainen, MM and Galano, JM and Lee, JC and Rintamäki, R and Karisola, P and El-Nezami, H and Schwab, U}, title = {Twelve Weeks of High-Intensity Interval Training Alters Adipose Tissue Gene Expression but Not Oxylipin Levels in People with Non-Alcoholic Fatty Liver Disease.}, journal = {International journal of molecular sciences}, volume = {24}, number = {10}, pages = {}, pmid = {37239856}, issn = {1422-0067}, support = {813781//European Union's Horizon 2020 research and innovation program under the Marie Sk&#x142;odowska-Curie/ ; }, mesh = {Humans ; Female ; *Non-alcoholic Fatty Liver Disease/genetics/therapy/complications ; *High-Intensity Interval Training ; Adipose Tissue/metabolism ; Weight Loss ; Gene Expression ; Liver/metabolism ; }, abstract = {Lifestyle modifications, including increased physical activity and exercise, are recommended for non-alcoholic fatty liver disease (NAFLD). Inflamed adipose tissue (AT) contributes to the progression and development of NAFLD and oxylipins such as hydroxyeicosatetraenoic acids (HETE), hydroxydocosahexanenoic acids (HDHA), prostaglandins (PEG2), and isoprostanoids (IsoP), which all may play a role in AT homeostasis and inflammation. To investigate the role of exercise without weight loss on AT and plasma oxylipin concentrations in NAFLD subjects, we conducted a 12-week randomized controlled exercise intervention. Plasma samples from 39 subjects and abdominal subcutaneous AT biopsy samples from 19 subjects were collected both at the beginning and the end of the exercise intervention. In the AT of women, a significant reduction of gene expression of hemoglobin subunits (HBB, HBA1, HBA2) was observed within the intervention group during the 12-week intervention. Their expression levels were negatively associated with VO2max and maxW. In addition, pathways involved in adipocyte morphology alterations significantly increased, whereas pathways in fat metabolism, branched-chain amino acids degradation, and oxidative phosphorylation were suppressed in the intervention group (p < 0.05). Compared to the control group, in the intervention group, the ribosome pathway was activated, but lysosome, oxidative phosphorylation, and pathways of AT modification were suppressed (p < 0.05). Most of the oxylipins (HETE, HDHA, PEG2, and IsoP) in plasma did not change during the intervention compared to the control group. 15-F2t-IsoP significantly increased in the intervention group compared to the control group (p = 0.014). However, this oxylipin could not be detected in all samples. Exercise intervention without weight loss may influence the AT morphology and fat metabolism at the gene expression level in female NAFLD subjects.}, }
@article {pmid37237407, year = {2023}, author = {Schamarek, I and Anders, L and Chakaroun, RM and Kovacs, P and Rohde-Zimmermann, K}, title = {The role of the oral microbiome in obesity and metabolic disease: potential systemic implications and effects on taste perception.}, journal = {Nutrition journal}, volume = {22}, number = {1}, pages = {28}, pmid = {37237407}, issn = {1475-2891}, mesh = {Humans ; Taste Perception ; Obesity/complications ; *Metabolic Diseases ; Inflammation/complications ; *Gastrointestinal Microbiome ; }, abstract = {Obesity and its metabolic sequelae still comprise a challenge when it comes to understanding mechanisms, which drive these pandemic diseases. The human microbiome as a potential key player has attracted the attention of broader research for the past decade. Most of it focused on the gut microbiome while the oral microbiome has received less attention. As the second largest niche, the oral microbiome is associated with a multitude of mechanisms, which are potentially involved in the complex etiology of obesity and associated metabolic diseases. These mechanisms include local effects of oral bacteria on taste perception and subsequent food preference as well as systemic effects on adipose tissue function, the gut microbiome and systemic inflammation. This review summarizes a growing body of research, pointing towards a more prominent role of the oral microbiome in obesity and associated metabolic diseases than expected. Ultimately, our knowledge on the oral microbiome may support the development of new patient oriented therapeutic approaches inevitable to relieve the health burden of metabolic diseases and to reach long-term benefits in patients´ lives.}, }
@article {pmid37228387, year = {2023}, author = {Fung, DLX and Li, X and Leung, CK and Hu, P}, title = {A self-knowledge distillation-driven CNN-LSTM model for predicting disease outcomes using longitudinal microbiome data.}, journal = {Bioinformatics advances}, volume = {3}, number = {1}, pages = {vbad059}, pmid = {37228387}, issn = {2635-0041}, abstract = {MOTIVATION: Human microbiome is complex and highly dynamic in nature. Dynamic patterns of the microbiome can capture more information than single point inference as it contains the temporal changes information. However, dynamic information of the human microbiome can be hard to be captured due to the complexity of obtaining the longitudinal data with a large volume of missing data that in conjunction with heterogeneity may provide a challenge for the data analysis.<br><br>RESULTS: We propose using an efficient hybrid deep learning architecture convolutional neural network-long short-term memory, which combines with self-knowledge distillation to create highly accurate models to analyze the longitudinal microbiome profiles to predict disease outcomes. Using our proposed models, we analyzed the datasets from Predicting Response to Standardized Pediatric Colitis Therapy (PROTECT) study and DIABIMMUNE study. We showed the significant improvement in the area under the receiver operating characteristic curve scores, achieving 0.889 and 0.798 on PROTECT study and DIABIMMUNE study, respectively, compared with state-of-the-art temporal deep learning models. Our findings provide an effective artificial intelligence-based tool to predict disease outcomes using longitudinal microbiome profiles from collected patients.<br><br>The data and source code can be accessed at https://github.com/darylfung96/UC-disease-TL.}, }
@article {pmid37228370, year = {2023}, author = {Thijssen, M and Tacke, F and Van Espen, L and Cassiman, D and Naser Aldine, M and Nevens, F and Van Ranst, M and Matthijnssens, J and Pourkarim, MR}, title = {Plasma virome dynamics in chronic hepatitis B virus infected patients.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1172574}, pmid = {37228370}, issn = {1664-302X}, abstract = {The virome remains an understudied domain of the human microbiome. The role of commensal viruses on the outcome of infections with known pathogens is not well characterized. In this study we aimed to characterize the longitudinal plasma virome dynamics in chronic hepatitis B virus (HBV) infected patients. Eighty-five longitudinal plasma samples were collected from 12 chronic HBV infected individuals that were classified in the four stages of HBV infection. The virome was characterized with an optimized viral extraction protocol and deep-sequenced on a NextSeq 2500 platform. The plasma virome was primarily composed of members of the Anello- Flavi-, and Hepadnaviridae (HBV) families. The virome structure and dynamics did not correlate with the different stages of chronic HBV infection nor with the administration of antiviral therapy. We observed a higher intrapersonal similarity of viral contigs. Genomic analysis of viruses observed in multiple timepoint demonstrated the presence of a dynamic community. This study comprehensively assessed the blood virome structure in chronic HBV infected individuals and provided insights in the longitudinal development of this viral community.}, }
@article {pmid37224760, year = {2023}, author = {Dixon, R and Egan, S and Hughes, S and Chapman, B}, title = {The Sexome - A proof of concept study into microbial transfer between heterosexual couples after sexual intercourse.}, journal = {Forensic science international}, volume = {348}, number = {}, pages = {111711}, doi = {10.1016/j.forsciint.2023.111711}, pmid = {37224760}, issn = {1872-6283}, mesh = {Humans ; Male ; Female ; *Coitus ; *Heterosexuality ; Proof of Concept Study ; RNA, Ribosomal, 16S/genetics ; DNA ; DNA Fingerprinting/methods ; Bacteria/genetics ; Microsatellite Repeats ; High-Throughput Nucleotide Sequencing ; }, abstract = {The detection and recovery of male DNA post-assault is important in sexual assault investigations, particularly where an offender is unknown to the victim. The collection of DNA evidence often occurs when the female victim undergoes a forensic medical assessment. Analysis regularly results in mixed autosomal DNA profiles with both victim and perpetrator DNA, often making it difficult to interpret a male profile suitable for DNA database searching. While short tandem repeat (STR) profiling of the male Y-chromosome is often used to overcome this challenge, successful identification of an individual can be hindered by the paternal inheritance pattern of Y-STRs and small Y-STR databases. Human microbiome research has suggested that a person's microbial diversity is unique. Therefore microbiome analysis using Massively Parallel Sequencing (MPS) could serve as a useful adjunct method of perpetrator identification. This study aimed to identify bacteria taxa that were unique to each participant and compare the bacterial communities found on their genitals both pre- and post-coitus. Samples were collected from six male-female sexual partner pairs. Volunteers were asked to self-collect low vaginal (females) and penis shaft and glans (males) samples before and after intercourse. Samples were extracted using the PureLink™ Microbiome DNA Purification Kit. Extracted DNA underwent library preparation using primers targeting the V3-V4 hypervariable regions of the bacterial 16S rRNA gene (∼450 bp). Libraries were sequenced on the Illumina MiSeq® platform. From the sequence data derived, statistical analysis was performed to investigate if bacteria sequences could be used to infer contact between each male-female pairing. Unique bacterial signatures were detected in low frequencies (<1%) in male and female participants pre-coitus. The data indicated a significant disruption to microbial diversity post-coitus in all samples. A transfer of the female microbiome during intercourse was most significant. As expected, one couple who did not use a barrier contraceptive yielded the most microbial transfer and disruption to diversity demonstrating a proof-of-concept in the utility of microbiome interrogation for sexual assault cases. Further genomic analysis is needed to confirm species and subspecies classification of bacteria that may produce a unique microbial profile that could then be used to identify a specific individual.}, }
@article {pmid37218407, year = {2023}, author = {Renardy, M and Prokopienko, AJ and Maxwell, JR and Flusberg, DA and Makaryan, S and Selimkhanov, J and Vakilynejad, M and Subramanian, K and Wille, L}, title = {A Quantitative Systems Pharmacology Model Describing the Cellular Kinetic-Pharmacodynamic Relationship for a Live Biotherapeutic Product to Support Microbiome Drug Development.}, journal = {Clinical pharmacology and therapeutics}, volume = {114}, number = {3}, pages = {633-643}, doi = {10.1002/cpt.2952}, pmid = {37218407}, issn = {1532-6535}, mesh = {Humans ; *Vancomycin ; Kinetics ; Network Pharmacology ; Drug Development ; *Microbiota ; }, abstract = {Live biotherapeutic products (LBPs) are human microbiome therapies showing promise in the clinic for a range of diseases and conditions. Describing the kinetics and behavior of LBPs poses a unique modeling challenge because, unlike traditional therapies, LBPs can expand, contract, and colonize the host digestive tract. Here, we present a novel cellular kinetic-pharmacodynamic quantitative systems pharmacology model of an LBP. The model describes bacterial growth and competition, vancomycin effects, binding and unbinding to the epithelial surface, and production and clearance of butyrate as a therapeutic metabolite. The model is calibrated and validated to published data from healthy volunteers. Using the model, we simulate the impact of treatment dose, frequency, and duration as well as vancomycin pretreatment on butyrate production. This model enables model-informed drug development and can be used for future microbiome therapies to inform decision making around antibiotic pretreatment, dose selection, loading dose, and dosing duration.}, }
@article {pmid37216534, year = {2023}, author = {Barbour, A and Smith, L and Oveisi, M and Williams, M and Huang, RC and Marks, C and Fine, N and Sun, C and Younesi, F and Zargaran, S and Orugunty, R and Horvath, TD and Haidacher, SJ and Haag, AM and Sabharwal, A and Hinz, B and Glogauer, M}, title = {Discovery of phosphorylated lantibiotics with proimmune activity that regulate the oral microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {120}, number = {22}, pages = {e2219392120}, pmid = {37216534}, issn = {1091-6490}, mesh = {Humans ; *Bacteriocins/pharmacology/chemistry ; Bacteria ; Anti-Bacterial Agents/pharmacology/chemistry ; Peptides ; }, abstract = {Lantibiotics are ribosomally synthesized and posttranslationally modified peptides (RiPPs) that are produced by bacteria. Interest in this group of natural products is increasing rapidly as alternatives to conventional antibiotics. Some human microbiome-derived commensals produce lantibiotics to impair pathogens' colonization and promote healthy microbiomes. Streptococcus salivarius is one of the first commensal microbes to colonize the human oral cavity and gastrointestinal tract, and its biosynthesis of RiPPs, called salivaricins, has been shown to inhibit the growth of oral pathogens. Herein, we report on a phosphorylated class of three related RiPPs, collectively referred to as salivaricin 10, that exhibit proimmune activity and targeted antimicrobial properties against known oral pathogens and multispecies biofilms. Strikingly, the immunomodulatory activities observed include upregulation of neutrophil-mediated phagocytosis, promotion of antiinflammatory M2 macrophage polarization, and stimulation of neutrophil chemotaxis-these activities have been attributed to the phosphorylation site identified on the N-terminal region of the peptides. Salivaricin 10 peptides were determined to be produced by S. salivarius strains found in healthy human subjects, and their dual bactericidal/antibiofilm and immunoregulatory activity may provide new means to effectively target infectious pathogens while maintaining important oral microbiota.}, }
@article {pmid37215849, year = {2023}, author = {Zhao, Z and Lin, J and Chen, S and Wang, X and Wang, H and Xu, G and Wang, J and Zhou, R and Huang, Z and Li, Y and Zhang, Y and Liu, X and Wang, P and Huang, M and Luo, Y and Yu, H}, title = {Clinical atlas of rectal cancer highlights the barriers and insufficient interventions underlying the unfavorable outcomes in older patients.}, journal = {Heliyon}, volume = {9}, number = {5}, pages = {e15966}, pmid = {37215849}, issn = {2405-8440}, abstract = {BACKGROUND: Aging confers an increased risk of developing cancer, and the global burden of cancer is cumulating as human longevity increases. Providing adequate care for old patients with rectal cancer is challenging and complex.<br><br>METHOD: A total of 428 and 44,788 patients diagnosed with non-metastatic rectal cancer from a referral tertiary care center (SYSU cohort) and the Surveillance Epidemiology and End Results database (SEER cohort) were included. Patients were categorized into old (over 65 years) and young (aged 50-65 years) groups. An age-specific clinical atlas of rectal cancer was generated, including the demographic and clinicopathological features, molecular profiles, treatment strategies, and clinical outcomes.<br><br>RESULTS: Old and young patients were similar in clinicopathological risk factors and molecular features, including TNM stage, tumor location, tumor differentiation, tumor morphology, lymphovascular invasion, and perineural invasion. However, old patients had significantly worse nutritional status and more comorbidities than young patients. In addition, old age was independently associated with less systemic cancer treatment (adjusted odds ratio 0.294 [95% CI 0.184-0.463, P&#xa0;<&#xa0;0.001]). We found that old patients had significantly worse overall survival (OS) outcomes in both SYSU (P&#xa0;<&#xa0;0.001) and SEER (P&#xa0;<&#xa0;0.001) cohorts. Moreover, the death and recurrence risk of old patients in the subgroup not receiving chemo/radiotherapy (P&#xa0;<&#xa0;0.001 for OS, and P&#xa0;=&#xa0;0.046 for time to recurrence [TTR]) reverted into no significant risk in the subgroup receiving chemo/radiotherapy.<br><br>CONCLUSIONS: Although old patients had similar tumor features to young patients, they had unfavorable survival outcomes associated with insufficient cancer care from old age. Specific trials with comprehensive geriatric assessment for old patients are needed to identify the optimal treatment regimens and improve unmet cancer care.<br><br>STUDY REGISTRATION: The study was registered on the research registry with the identifier of researchregistry 7635.}, }
@article {pmid37213403, year = {2023}, author = {Lahtinen, P and Jalanka, J and Mattila, E and Tillonen, J and Bergman, P and Satokari, R and Arkkila, P}, title = {Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis: A randomized controlled trial.}, journal = {World journal of gastroenterology}, volume = {29}, number = {17}, pages = {2666-2678}, pmid = {37213403}, issn = {2219-2840}, mesh = {Humans ; *Fecal Microbiota Transplantation/adverse effects/methods ; *Colitis, Ulcerative/diagnosis/therapy/etiology ; Quality of Life ; Remission Induction ; Feces ; Leukocyte L1 Antigen Complex ; }, abstract = {BACKGROUND: Fecal microbial transplantation (FMT) is a promising new method for treating active ulcerative colitis (UC), but knowledge regarding FMT for quiescent UC is scarce.<br><br>AIM: To investigate FMT for the maintenance of remission in UC patients.<br><br>METHODS: Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy. The primary endpoint was set to the maintenance of remission, a fecal calprotectin level below 200 &#x3bc;g/g, and a clinical Mayo score below three throughout the 12-mo follow-up. As secondary endpoints, we recorded the patient's quality of life, fecal calprotectin, blood chemistry, and endoscopic findings at 12 mo.<br><br>RESULTS: The main endpoint was achieved by 13 out of 24 (54%) patients in the FMT group and by 10 out of 24 (41%) patients in the placebo group (log-rank test, P = 0.660). Four months after FMT, the quality-of-life scores decreased in the FMT group compared to the placebo group (P = 0.017). In addition, the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point (P = 0.003). There were no differences in blood chemistry, fecal calprotectin, or endoscopic findings among the study groups at 12 mo. The adverse events were infrequent, mild, and distributed equally between the groups.<br><br>CONCLUSION: There were no differences in the number of relapses between the study groups at the 12-mo follow-up. Thus, our results do not support the use of a single-dose FMT for the maintenance of remission in UC.}, }
@article {pmid37211280, year = {2023}, author = {Chow, EWL and Pang, LM and Wang, Y}, title = {Impact of the host microbiota on fungal infections: New possibilities for intervention?.}, journal = {Advanced drug delivery reviews}, volume = {198}, number = {}, pages = {114896}, doi = {10.1016/j.addr.2023.114896}, pmid = {37211280}, issn = {1872-8294}, mesh = {Humans ; Antifungal Agents/pharmacology/therapeutic use ; *Mycoses/drug therapy ; Fungi ; *Microbiota ; Bacteria ; }, abstract = {Many human fungal pathogens are opportunistic. They are primarily benign residents of the human body and only become infectious when the host's immunity and microbiome are compromised. Bacteria dominate the human microbiome, playing an essential role in keeping fungi harmless and acting as the first line of defense against fungal infection. The Human Microbiome Project, launched by NIH in 2007, has stimulated extensive investigation and significantly advanced our understanding of the molecular mechanisms governing the interaction between bacteria and fungi, providing valuable insights for developing future antifungal strategies by exploiting the interaction. This review summarizes recent progress in this field and discusses new possibilities and challenges. We must seize the opportunities presented by researching bacterial-fungal interplay in the human microbiome to address the global spread of drug-resistant fungal pathogens and the drying pipelines of effective antifungal drugs.}, }
@article {pmid37208436, year = {2023}, author = {Winders, TM and Holman, DB and Schmidt, KN and Luecke, SM and Smith, DJ and Neville, BW and Dahlen, CR and Swanson, KC and Amat, S}, title = {Feeding hempseed cake alters the bovine gut, respiratory and reproductive microbiota.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8121}, pmid = {37208436}, issn = {2045-2322}, mesh = {Humans ; Cattle ; Animals ; Female ; Infant ; *Animal Feed/analysis ; RNA, Ribosomal, 16S/genetics ; *Diet/veterinary ; Silage/analysis ; Reproduction ; Zea mays/chemistry ; Rumen ; }, abstract = {A growing number of studies have investigated the feasibility of utilizing hemp by-products as livestock feedstuffs; however, their impact on livestock microbiomes remains unexplored. Here, we evaluated the effects of feeding hempseed cake on the gastrointestinal, respiratory, and reproductive microbiota in beef heifers. Angus-crossbred heifers (19-months old, initial body weight = 494 ± 10 kg [SE]) were fed a corn-based finishing diet containing 20% hempseed cake as a substitute for 20% corn dried distillers' grains with solubles (DM basis; Control; n = 16/group) for 111 days until slaughter. Ruminal fluid and deep nasopharyngeal swabs (days 0, 7, 42, 70 and 98), and vaginal and uterine swabs (at slaughter) were collected, and the microbiota assessed using 16S rRNA gene sequencing. Diet affected the community structure of the ruminal (d 7-98; 0.06 ≤ R[2] ≤ 0.12; P < 0.05), nasopharyngeal (d 98; R[2] = 0.18; P < 0.001), and vaginal (R[2] = 0.06; P < 0.01) microbiota. Heifers fed hempseed cake had increased microbial diversity in the rumen, reduced microbial richness in the vagina, and greater microbial diversity and richness in the uterus. In addition to the distinct microbial communities in the rumen, nasopharynx, vagina and uterus, we identified 28 core taxa that were shared (≥ 60% of all samples) across these sampling locations. Feeding hempseed cake appeared to alter the bovine gut, respiratory and reproductive microbiota. Our results suggest that future research aiming to evaluate the use of hemp by-products in livestock diet should consider their impact on animal microbiome and microbiome mediated animal health and reproductive efficiency. Our findings also highlight the need for research evaluating the impact of hemp-associated food and personal care products on the human microbiome.}, }
@article {pmid37205434, year = {2023}, author = {Inglis, LK and Roach, MJ and Edwards, RA}, title = {Prophage rates in the human microbiome vary by body site and host health.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {37205434}, issn = {2692-8205}, abstract = {Phages integrated into a bacterial genome-called prophages-continuously monitor the health of the host bacteria to determine when to escape the genome, protect their host from other phage infections, and may provide genes that promote bacterial growth. Prophages are essential to almost all microbiomes, including the human microbiome. However, most human microbiome studies focus on bacteria, ignoring free and integrated phages, so we know little about how these prophages affect the human microbiome. We compared the prophages identified in 11,513 bacterial genomes isolated from human body sites to characterise prophage DNA in the human microbiome. Here, we show that prophage DNA comprised an average of 1-5% of each bacterial genome. The prophage content per genome varies with the isolation site on the human body, the health of the human, and whether the disease was symptomatic. The presence of prophages promotes bacterial growth and sculpts the microbiome. However, the disparities caused by prophages vary throughout the body.}, }
@article {pmid37204436, year = {2023}, author = {Kodila, A and Franko, N and Sollner Dolenc, M}, title = {A review on immunomodulatory effects of BPA analogues.}, journal = {Archives of toxicology}, volume = {97}, number = {7}, pages = {1831-1846}, pmid = {37204436}, issn = {1432-0738}, support = {P1-0208//Javna Agencija za Raziskovalno Dejavnost RS/ ; Young Researcher grant//Javna Agencija za Raziskovalno Dejavnost RS/ ; Grant Agreement No 101057014//European Union's Horizon Europe research and innovation programme/ ; }, mesh = {Humans ; *Receptors, Cytoplasmic and Nuclear ; Phenols/toxicity ; Benzhydryl Compounds/toxicity ; Body Weight ; *Endocrine Disruptors/toxicity ; }, abstract = {Bisphenol A (BPA) is a known endocrine disruptor found in many consumer products that humans come into contact with on a daily basis. Due to increasing concerns about the safety of BPA and the introduction of new legislation restricting its use, industry has responded by adopting new, less studied BPA analogues that have similar polymer-forming properties. Some BPA analogues have already been shown to exhibit effects similar to BPA, for example, contributing to endocrine disruption through agonistic or antagonistic behaviour at various nuclear receptors such as estrogen (ER), androgen (AR), glucocorticoid (GR), aryl hydrocarbon (AhR), and pregnane X receptor (PXR). Since the European Food Safety Authority (EFSA) issued a draft re-evaluation of BPA and drastically reduced the temporary tolerable daily intake (t-TDI) of BPA from 4 mg/kg body weight/day to 0.2 ng/kg body weight/day due to increasing concern about the toxic properties of BPA, including its potential to disrupt immune system processes, we conducted a comprehensive review of the immunomodulatory activity of environmentally abundant BPA analogues. The results of the review suggest that BPA analogues may affect both the innate and acquired immune systems and can contribute to various immune-mediated conditions such as hypersensitivity reactions, allergies, and disruption of the human microbiome.}, }
@article {pmid37202853, year = {2023}, author = {Velsko, IM and Gallois, S and Stahl, R and Henry, AG and Warinner, C}, title = {High conservation of the dental plaque microbiome across populations with differing subsistence strategies and levels of market integration.}, journal = {Molecular ecology}, volume = {32}, number = {14}, pages = {3872-3891}, doi = {10.1111/mec.16988}, pmid = {37202853}, issn = {1365-294X}, mesh = {Humans ; *Dental Plaque ; *Microbiota/genetics ; Mouth ; Diet ; North America ; }, abstract = {Industrialization-including urbanization, participation in the global food chain and consumption of heavily processed foods-is thought to drive substantial shifts in the human microbiome. While diet strongly influences stool microbiome composition, the influence of diet on the oral microbiome is largely speculative. Multiple ecologically distinct surfaces in the mouth, each harbouring a unique microbial community, pose a challenge to assessing changes in the oral microbiome in the context of industrialization, as the results depend on the oral site under study. Here, we investigated whether microbial communities of dental plaque, the dense biofilm on non-shedding tooth surfaces, are distinctly different across populations with dissimilar subsistence strategies and degree of industrialized market integration. Using a metagenomic approach, we compared the dental plaque microbiomes of Baka foragers and Nzime subsistence agriculturalists in Cameroon (n = 46) with the dental plaque and calculus microbiomes of highly industrialized populations in North America and Europe (n = 38). We found that differences in microbial taxonomic composition between populations were minimal, with high conservation of abundant microbial taxa and no significant differences in microbial diversity related to dietary practices. Instead, we find that the major source of variation in dental plaque microbial species composition is related to tooth location and oxygen availability, which may be influenced by toothbrushing or other dental hygiene measures. Our results support that dental plaque, in contrast to the stool microbiome, maintains an inherent stability against ecological perturbations in the oral environment.}, }
@article {pmid37198426, year = {2023}, author = {Benincà, E and Pinto, S and Cazelles, B and Fuentes, S and Shetty, S and Bogaards, JA}, title = {Wavelet clustering analysis as a tool for characterizing community structure in the human microbiome.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {8042}, pmid = {37198426}, issn = {2045-2322}, mesh = {Humans ; *Microbiota ; Wavelet Analysis ; *Gastrointestinal Microbiome ; Microbial Consortia ; Cluster Analysis ; }, abstract = {Human microbiome research is helped by the characterization of microbial networks, as these may reveal key microbes that can be targeted for beneficial health effects. Prevailing methods of microbial network characterization are based on measures of association, often applied to limited sampling points in time. Here, we demonstrate the potential of wavelet clustering, a technique that clusters time series based on similarities in their spectral characteristics. We illustrate this technique with synthetic time series and apply wavelet clustering to densely sampled human gut microbiome time series. We compare our results with hierarchical clustering based on temporal correlations in abundance, within and across individuals, and show that the cluster trees obtained by using either method are significantly different in terms of elements clustered together, branching structure and total branch length. By capitalizing on the dynamic nature of the human microbiome, wavelet clustering reveals community structures that remain obscured in correlation-based methods.}, }
@article {pmid37191901, year = {2023}, author = {Seidel, J and Magzamen, S and Wang, YH and Neujahr, V and Schaeffer, JW}, title = {Lessons from Dairy Farmers for Occupational Allergy and Respiratory Disease.}, journal = {Current allergy and asthma reports}, volume = {23}, number = {6}, pages = {325-339}, pmid = {37191901}, issn = {1534-6315}, support = {U54 OH008085/OH/NIOSH CDC HHS/United States ; R01 OH012046/OH/NIOSH CDC HHS/United States ; }, mesh = {Humans ; *Occupational Exposure/adverse effects ; Farmers ; *Respiration Disorders ; *Respiratory Tract Diseases/epidemiology/etiology ; *Hypersensitivity ; }, abstract = {PURPOSE OF REVIEW: Exposure to bioaerosols at dairies has long been associated with allergy, respiratory disease, and decreases in lung function. Recent advancements in exposure assessments have aided our understanding on the size distribution and composition of these bioaerosols, but investigations focusing solely on exposures may overlook important intrinsic factors impacting worker's susceptibility to disease.<br><br>RECENT FINDINGS: In our review, we discuss the most recent studies examining the exposures and genetic factors that contribute to occupational disease in dairy work. We also review more recent concerns in livestock work associated with zoonotic pathogens, antimicrobial resistant genes, and the role of the human microbiome. The studies highlighted in this review demonstrate the need for further research to better understand bioaerosol exposure-response relationships in the context of extrinsic and intrinsic factors, antibiotic-resistant genes, viral pathogens, and the human microbiome to help inform effective interventions that improve respiratory health among dairy farmers.}, }
@article {pmid37190067, year = {2023}, author = {Lupu, VV and Adam Raileanu, A and Mihai, CM and Morariu, ID and Lupu, A and Starcea, IM and Frasinariu, OE and Mocanu, A and Dragan, F and Fotea, S}, title = {The Implication of the Gut Microbiome in Heart Failure.}, journal = {Cells}, volume = {12}, number = {8}, pages = {}, pmid = {37190067}, issn = {2073-4409}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis/microbiology ; *Heart Failure ; *Microbiota ; Risk Factors ; }, abstract = {Heart failure is a worldwide health problem with important consequences for the overall wellbeing of affected individuals as well as for the healthcare system. Over recent decades, numerous pieces of evidence have demonstrated that the associated gut microbiota represent an important component of human physiology and metabolic homeostasis, and can affect one's state of health or disease directly, or through their derived metabolites. The recent advances in human microbiome studies shed light on the relationship between the gut microbiota and the cardiovascular system, revealing its contribution to the development of heart failure-associated dysbiosis. HF has been linked to gut dysbiosis, low bacterial diversity, intestinal overgrowth of potentially pathogenic bacteria and a decrease in short chain fatty acids-producing bacteria. An increased intestinal permeability allowing microbial translocation and the passage of bacterial-derived metabolites into the bloodstream is associated with HF progression. A more insightful understanding of the interactions between the human gut microbiome, HF and the associated risk factors is mandatory for optimizing therapeutic strategies based on microbiota modulation and offering individualized treatment. The purpose of this review is to summarize the available data regarding the influence of gut bacterial communities and their derived metabolites on HF, in order to obtain a better understanding of this multi-layered complex relationship.}, }
@article {pmid37189783, year = {2023}, author = {Monticolo, M and Mucha, K and Foroncewicz, B}, title = {Lupus Nephritis and Dysbiosis.}, journal = {Biomedicines}, volume = {11}, number = {4}, pages = {}, pmid = {37189783}, issn = {2227-9059}, abstract = {Lupus nephritis (LN) is one of the most common and serious complications of systemic lupus erythematosus (SLE). The risk factors for developing LN by SLE patients are not fully understood. They are considered to be a mix of genetic and environmental variables, one of them being dysbiosis, proposed recently to interfere with autoimmunity. As of yet, the relations between the human microbiome, its genetic determinants, individual variability and clinical consequences remain to be established. One of the major obstacles in studying them is the magnitude of confounders, such as diet, drugs, infections or antibiotics use. They also make comparison between the studies extremely complicated. We reviewed the available evidence for the interplay between microbiome, dysbiosis and mechanisms triggering the autoimmune responses and potentially contributing to LN development. One such mechanism is the stimulation of autoimmune responses by bacterial metabolites that can mimic autoantigens and cause antibody production. These mimicking microbial antigens seem to be a promising target for future interventions.}, }
@article {pmid37180436, year = {2023}, author = {Che, Y and Wang, N and Ma, Q and Liu, J and Xu, Z and Li, Q and Wang, J and Sun, Y}, title = {Microbial characterization of the nasal cavity in patients with allergic rhinitis and non-allergic rhinitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1166389}, pmid = {37180436}, issn = {2235-2988}, mesh = {Humans ; Male ; Female ; Young Adult ; Adult ; *Rhinitis, Allergic/microbiology ; *Rhinitis/microbiology ; *Nasal Cavity/microbiology ; Metagenome ; Biodiversity ; *Microbiota ; RNA, Ribosomal, 16S/analysis ; *Bacteria/classification/genetics/isolation &amp; purification ; }, abstract = {INTRODUCTION: Although recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis.<br><br>METHOD: From February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora.<br><br>RESULTS: The microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans.<br><br>CONCLUSION: In conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.}, }
@article {pmid37178069, year = {2023}, author = {Bracaglia, C and Marucci, G and Del Chierico, F and Russo, A and Pardeo, M and Pires Marafon, D and Quagliariello, A and Caiello, I and Rea, F and Fingerhutova, S and Insalaco, A and Prencipe, G and Dolezalova, P and De Benedetti, F and Putignani, L}, title = {Microbiota transplant to control inflammation in a patient with NLRC4 gain-of-function-induced disease.}, journal = {The Journal of allergy and clinical immunology}, volume = {152}, number = {1}, pages = {302-303}, doi = {10.1016/j.jaci.2023.03.031}, pmid = {37178069}, issn = {1097-6825}, mesh = {Humans ; *Gain of Function Mutation ; *Inflammation ; CARD Signaling Adaptor Proteins/genetics ; Calcium-Binding Proteins/genetics ; Inflammasomes ; }, }
@article {pmid37174009, year = {2023}, author = {Munteanu, R and Feder, RI and Onaciu, A and Munteanu, VC and Iuga, CA and Gulei, D}, title = {Insights into the Human Microbiome and Its Connections with Prostate Cancer.}, journal = {Cancers}, volume = {15}, number = {9}, pages = {}, pmid = {37174009}, issn = {2072-6694}, abstract = {The human microbiome represents the diversity of microorganisms that live together at different organ sites, influencing various physiological processes and leading to pathological conditions, even carcinogenesis, in case of a chronic imbalance. Additionally, the link between organ-specific microbiota and cancer has attracted the interest of numerous studies and projects. In this review article, we address the important aspects regarding the role of gut, prostate, urinary and reproductive system, skin, and oral cavity colonizing microorganisms in prostate cancer development. Various bacteria, fungi, virus species, and other relevant agents with major implications in cancer occurrence and progression are also described. Some of them are assessed based on their values of prognostic or diagnostic biomarkers, while others are presented for their anti-cancer properties.}, }
@article {pmid37173453, year = {2023}, author = {Baba, Y and Hara, Y and Toihata, T and Kosumi, K and Iwatsuki, M and Iwagami, S and Miyamoto, Y and Yoshida, N and Komohara, Y and Baba, H}, title = {Relationship between gut microbiome Fusobacterium nucleatum and LINE-1 methylation level in esophageal cancer.}, journal = {Esophagus : official journal of the Japan Esophageal Society}, volume = {20}, number = {4}, pages = {704-712}, pmid = {37173453}, issn = {1612-9067}, mesh = {Humans ; Fusobacterium nucleatum/genetics ; Methylation ; *Gastrointestinal Microbiome/genetics ; *Colorectal Neoplasms/genetics/microbiology/pathology ; *Esophageal Neoplasms/genetics/pathology ; }, abstract = {BACKGROUND: We previously demonstrated the relationship of human microbiome Fusobacterium nucleatum with unfavorable clinical outcomes and inferior chemotherapeutic responses in esophageal cancer. Global DNA methylation is associated with the occurrence and development of various cancers. In our previous study, LINE-1 hypomethylation (i.e., global DNA hypomethylation) was associated with a poor prognosis in esophageal cancer. As the gut microbiota may play crucial roles in the DNA methylation of host cells, we hypothesized that F. nucleatum might influence LINE-1 methylation levels in esophageal cancer.<br><br>METHODS: We qualified the F. nucleatum DNA using a quantitative PCR assay and LINE-1 methylation via a pyrosequencing assay using formalin-fixed paraffin-embedded specimens from 306 esophageal cancer patients.<br><br>RESULTS: Intratumoral F. nucleatum DNA was detected in 65 cases (21.2%). The LINE-1 methylation scores ranged from 26.9 to 91.8 (median&#x2009;=&#x2009;64.8) in tumors. F. nucleatum DNA was related to the LINE-1 hypomethylation of tumor lesions in esophageal cancer (P&#x2009;<&#x2009;0.0001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.71 for F. nucleatum positivity. Finally, we found that the impact of F. nucleatum on clinical outcomes was not modified by LINE-1 hypomethylation (P for interaction&#x2009;=&#x2009;0.34).<br><br>CONCLUSIONS: F. nucleatum alters genome-wide methylation levels in cancer cells, which may be one of the mechanisms by which F. nucleatum affects the malignant behavior of esophageal cancer.}, }
@article {pmid37173385, year = {2023}, author = {Dave, A and Beyoğlu, D and Park, EJ and Idle, JR and Pezzuto, JM}, title = {Influence of grape consumption on the human microbiome.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {7706}, pmid = {37173385}, issn = {2045-2322}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; *Vitis/metabolism ; Diet ; *Microbiota ; Plasma ; Metabolomics ; }, abstract = {Over the years, a substantial body of information has accumulated suggesting dietary consumption of grapes may have a positive influence on human health. Here, we investigate the potential of grapes to modulate the human microbiome. Microbiome composition as well as urinary and plasma metabolites were sequentially assessed in 29 healthy free-living male (age 24-55 years) and female subjects (age 29-53 years) following two-weeks of a restricted diet (Day 15), two-weeks of a restricted diet with grape consumption (equivalent to three servings per day) (Day 30), and four-weeks of restricted diet without grape consumption (Day 60). Based on alpha-diversity indices, grape consumption did not alter the overall composition of the microbial community, other than with the female subset based on the Chao index. Similarly, based on beta-diversity analyses, the diversity of species was not significantly altered at the three time points of the study. However, following 2 weeks of grape consumption, taxonomic abundance was altered (e.g., decreased Holdemania spp. and increased Streptococcus thermophiles), as were various enzyme levels and KEGG pathways. Further, taxonomic, enzyme and pathway shifts were observed 30 days following the termination of grape consumption, some of which returned to baseline and some of which suggest a delayed effect of grape consumption. Metabolomic analyses supported the functional significance of these alterations wherein, for example, 2'-deoxyribonic acid, glutaconic acid, and 3-hydroxyphenylacetic acid were elevated following grape consumption and returned to baseline following the washout period. Inter-individual variation was observed and exemplified by analysis of a subgroup of the study population showing unique patterns of taxonomic distribution over the study period. The biological ramifications of these dynamics remain to be defined. However, while it seems clear that grape consumption does not perturb the eubiotic state of the microbiome with normal, healthy human subjects, it is likely that shifts in the intricate interactive networks that result from grape consumption have physiological significance of relevance to grape action.}, }
@article {pmid37171860, year = {2023}, author = {Snaith, AE and Dunn, SJ and Moran, RA and Newton, PN and Dance, DAB and Davong, V and Kuenzli, E and Kantele, A and Corander, J and McNally, A}, title = {The highly diverse plasmid population found in Escherichia coli colonizing travellers to Laos and its role in antimicrobial resistance gene carriage.}, journal = {Microbial genomics}, volume = {9}, number = {5}, pages = {}, pmid = {37171860}, issn = {2057-5858}, support = {MRS0136601/MRC_/Medical Research Council/United Kingdom ; BBR0062611/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; MR/S013660/1/MRC_/Medical Research Council/United Kingdom ; 106698/Z/14/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Escherichia coli ; Anti-Bacterial Agents/pharmacology ; *Escherichia coli Infections/epidemiology ; Laos ; beta-Lactamases/genetics ; Drug Resistance, Bacterial/genetics ; Plasmids/genetics ; }, abstract = {Increased colonization by antimicrobial-resistant organisms is closely associated with international travel. This study investigated the diversity of mobile genetic elements involved with antimicrobial resistance (AMR) gene carriage in extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli that colonized travellers to Laos. Long-read sequencing was used to reconstruct complete plasmid sequences from 48 isolates obtained from the daily stool samples of 23 travellers over a 3 week period. This method revealed a collection of 105 distinct plasmids, 38.1 % (n=40) of which carried AMR genes. The plasmids in this population were diverse, mostly unreported and included 38 replicon types, with F-type plasmids (n=23) the most prevalent amongst those carrying AMR genes. Fine-scale analysis of all plasmids identified numerous AMR gene contexts and emphasized the importance of IS elements, specifically members of the IS6/IS26 family, in the evolution of complex multidrug resistance regions. We found a concerning convergence of ESBL and colistin resistance determinants, with three plasmids from two different F-type lineages carrying bla CTX-M and mcr genes. The extensive diversity seen here highlights the worrying probability that stable new vehicles for AMR will evolve in E. coli populations that can disseminate internationally through travel networks.}, }
@article {pmid37171266, year = {2023}, author = {Nagarajan, G and Govindan, R and Poomarimuthu, M and Andiappan, R and Elango, S and Maruthamuthu, S and Mariakuttikan, J and Kadiam, S}, title = {The microbiome and rheumatic heart disease: current knowledge and future perspectives.}, journal = {Acta cardiologica}, volume = {78}, number = {5}, pages = {525-533}, doi = {10.1080/00015385.2023.2207933}, pmid = {37171266}, issn = {1784-973X}, mesh = {Child ; Humans ; *Rheumatic Heart Disease ; Dysbiosis/complications ; *Streptococcal Infections ; Inflammation ; *Microbiota ; }, abstract = {Rheumatic heart disease (RHD) is a cardiovascular disease caused by an autoimmune response to group A Streptococcus (GAS) infection resulting in the damage of heart valves. RHD is the most commonly acquired heart disease among children and young adults with a global burden of over 40 million cases accounting for 306,000 deaths annually. Inflammation in the heart valves caused due to molecular mimicry between the GAS antigens and host cardiac proteins is facilitated by cytokines, cross-reactive antibodies and CD4[+] T cells. The complex interaction between genetic and environmental factors linked with erratic events leads to the loss of immunological tolerance and autoimmunity in RHD. Despite extensive research on the etiopathogenesis of RHD, the precise mechanism underpinning the initiation of acute rheumatic fever (ARF) to the progression of RHD still remains elusive. Mounting evidences support the contribution of the human microbiome in the development of several immune-mediated diseases including rheumatoid arthritis, juvenile idiopathic arthritis, Kawasaki disease, inflammatory bowel disease and type 1 diabetes. The microbiome and their metabolites could play a crucial role in the integrity of the epithelial barrier, development of the immune system, inflammation and differentiation of T cell subsets. Consequently, microbiome dysbiosis might result in autoimmunity by molecular mimicry, epitope spreading and bystander activation. This review discusses various aspects of the interaction between the microbiome and the immune system in order to reveal causative links relating dysbiosis and autoimmune diseases with special emphasis on RHD.}, }
@article {pmid37165188, year = {2023}, author = {Shalon, D and Culver, RN and Grembi, JA and Folz, J and Treit, PV and Shi, H and Rosenberger, FA and Dethlefsen, L and Meng, X and Yaffe, E and Aranda-Díaz, A and Geyer, PE and Mueller-Reif, JB and Spencer, S and Patterson, AD and Triadafilopoulos, G and Holmes, SP and Mann, M and Fiehn, O and Relman, DA and Huang, KC}, title = {Profiling the human intestinal environment under physiological conditions.}, journal = {Nature}, volume = {617}, number = {7961}, pages = {581-591}, pmid = {37165188}, issn = {1476-4687}, support = {R01 AI147023/AI/NIAID NIH HHS/United States ; RM1 GM135102/GM/NIGMS NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Bile Acids and Salts/metabolism ; *Gastrointestinal Microbiome/physiology ; *Metabolome ; *Proteome/metabolism ; Bacteria/classification/isolation &amp; purification ; Bacteriophages/isolation &amp; purification/physiology ; Feces/chemistry/microbiology/virology ; *Intestines/chemistry/metabolism/microbiology/physiology/virology ; Digestion/physiology ; }, abstract = {The spatiotemporal structure of the human microbiome[1,2], proteome[3] and metabolome[4,5] reflects and determines regional intestinal physiology and may have implications for disease[6]. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals[7]. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.}, }
@article {pmid37163788, year = {2023}, author = {Seyedsayamdost, MR and Clardy, J}, title = {Discovering functional small molecules in the gut microbiome.}, journal = {Current opinion in chemical biology}, volume = {75}, number = {}, pages = {102309}, pmid = {37163788}, issn = {1879-0402}, support = {R01 AI172147/AI/NIAID NIH HHS/United States ; R01 AT009708/AT/NCCIH NIH HHS/United States ; R01 GM140034/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Bacteria/metabolism ; }, abstract = {The human microbiome has emerged as a source of bacterially produced, functional small molecules that help regulate health and disease, and their discovery and annotation has become a popular research topic. Identifying these molecules provides an essential step in unraveling the molecular mechanisms underlying biological outcomes. The relevance of specific bacterial members of the microbiome has been demonstrated in a variety of correlative studies, and there are many possible paths from these correlations to the responsible metabolites. Herein, we summarize two studies that have recently identified gut microbiome metabolites that modulate immune responses or promote physical activity. Aside from the deep insights gained, these studies provide blueprints for successfully uncovering the molecules and mechanisms that control important physiological pathways.}, }
@article {pmid37161031, year = {2023}, author = {Chmiel, JA and Stuivenberg, GA and Al, KF and Akouris, PP and Razvi, H and Burton, JP and Bjazevic, J}, title = {Vitamins as regulators of calcium-containing kidney stones - new perspectives on the role of the gut microbiome.}, journal = {Nature reviews. Urology}, volume = {20}, number = {10}, pages = {615-637}, pmid = {37161031}, issn = {1759-4820}, mesh = {Humans ; Vitamins/therapeutic use ; Calcium ; *Gastrointestinal Microbiome ; *Kidney Calculi ; *Urolithiasis ; Vitamin A ; Vitamin K ; }, abstract = {Calcium-based kidney stone disease is a highly prevalent and morbid condition, with an often complicated and multifactorial aetiology. An abundance of research on the role of specific vitamins (B6, C and D) in stone formation exists, but no consensus has been reached on how these vitamins influence stone disease. As a consequence of emerging research on the role of the gut microbiota in urolithiasis, previous notions on the contribution of these vitamins to urolithiasis are being reconsidered in the field, and investigation into previously overlooked vitamins (A, E and K) was expanded. Understanding how the microbiota influences host vitamin regulation could help to determine the role of vitamins in stone disease.}, }
@article {pmid37159872, year = {2023}, author = {Golob, JL}, title = {Human Microbiomes and Disease for the Biomedical Data Scientist.}, journal = {Annual review of biomedical data science}, volume = {6}, number = {}, pages = {259-273}, doi = {10.1146/annurev-biodatasci-020722-043017}, pmid = {37159872}, issn = {2574-3414}, mesh = {Humans ; *Microbiota ; Precision Medicine ; High-Throughput Nucleotide Sequencing/methods ; }, abstract = {The human microbiome is complex, variable from person to person, essential for health, and related to both the risk for disease and the efficacy of our treatments. There are robust techniques to describe microbiota with high-throughput sequencing, and there are hundreds of thousands of already-sequenced specimens in public archives. The promise remains to use the microbiome both as a prognostic factor and as a target for precision medicine. However, when used as an input in biomedical data science modeling, the microbiome presents unique challenges. Here, we review the most common techniques used to describe microbial communities, explore these unique challenges, and discuss the more successful approaches for biomedical data scientists seeking to use the microbiome as an input in their studies.}, }
@article {pmid37155564, year = {2023}, author = {Chernyaeva, L and Ratti, G and Teirilä, L and Fudo, S and Rankka, U and Pelkonen, A and Korhonen, P and Leskinen, K and Keskitalo, S and Salokas, K and Gkolfinopoulou, C and Crompton, KE and Javanainen, M and Happonen, L and Varjosalo, M and Malm, T and Leinonen, V and Chroni, A and Saavalainen, P and Meri, S and Kajander, T and Wollman, AJ and Nissilä, E and Haapasalo, K}, title = {Reduced binding of apoE4 to complement factor H promotes amyloid-β oligomerization and neuroinflammation.}, journal = {EMBO reports}, volume = {24}, number = {7}, pages = {e56467}, pmid = {37155564}, issn = {1469-3178}, support = {331108//Academy of Finland (AKA)/ ; 338160//Academy of Finland (AKA)/ ; 25022019//Jane and Aatos Erkko Foundation/ ; }, mesh = {Humans ; *Apolipoprotein E4/genetics/metabolism ; Complement Factor H/genetics ; *Alzheimer Disease/genetics/metabolism ; Neuroinflammatory Diseases ; Apolipoproteins E/chemistry/genetics/metabolism ; Amyloid beta-Peptides/metabolism ; Protein Isoforms/genetics/metabolism ; }, abstract = {The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset Alzheimer's disease (AD). ApoE interacts with complement regulator factor H (FH), but the role of this interaction in AD pathogenesis is unknown. Here we elucidate the mechanism by which isoform-specific binding of apoE to FH alters Aβ1-42-mediated neurotoxicity and clearance. Flow cytometry and transcriptomic analysis reveal that apoE and FH reduce binding of Aβ1-42 to complement receptor 3 (CR3) and subsequent phagocytosis by microglia which alters expression of genes involved in AD. Moreover, FH forms complement-resistant oligomers with apoE/Aβ1-42 complexes and the formation of these complexes is isoform specific with apoE2 and apoE3 showing higher affinity to FH than apoE4. These FH/apoE complexes reduce Aβ1-42 oligomerization and toxicity, and colocalize with complement activator C1q deposited on Aβ plaques in the brain. These findings provide an important mechanistic insight into AD pathogenesis and explain how the strongest genetic risk factor for AD predisposes for neuroinflammation in the early stages of the disease pathology.}, }
@article {pmid37154305, year = {2023}, author = {Zou, D and Dong, Y and Chen, J}, title = {[Live biotherapeutic products: the forefront of innovative drug development driven by biotechnology].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {39}, number = {4}, pages = {1275-1289}, doi = {10.13345/j.cjb.220669}, pmid = {37154305}, issn = {1872-2075}, mesh = {Humans ; *Probiotics ; Dietary Supplements ; Bacteria ; Drug Development ; Biotechnology ; }, abstract = {As human microbiome research advances, a large body of evidence shows that microorganisms are closely related to human health. Probiotics were discovered and used as foods or dietary supplements with health benefits in the last century. Microorganisms have shown broader application prospects in human health since the turn of the century, owing to the rapid development of technologies such as microbiome analysis, DNA synthesis and sequencing, and gene editing. In recent years, the concept of "next-generation probiotics" has been proposed as new drugs, and microorganisms are considered as "live biotherapeutic products (LBP)". In a nutshell, LBP is a living bacterial drug that can be used to prevent or treat certain human diseases and indications. Because of its distinct advantages, LBP has risen to the forefront of drug development research and has very broad development prospects. This review introduces the varieties and research advances on LBP from a biotechnology standpoint, followed by summarizing the challenges and opportunities for LBP clinical implementations, with the aim to facilitate LBP development.}, }
@article {pmid37146137, year = {2023}, author = {Lietzan, AD and Simpson, JB and Walton, WG and Jariwala, PB and Xu, Y and Boynton, MH and Liu, J and Redinbo, MR}, title = {Microbial β-glucuronidases drive human periodontal disease etiology.}, journal = {Science advances}, volume = {9}, number = {18}, pages = {eadg3390}, pmid = {37146137}, issn = {2375-2548}, support = {R01 GM135218/GM/NIGMS NIH HHS/United States ; UM1 TR004406/TR/NCATS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; R01 GM137286/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Glucuronidase/metabolism ; *Gastrointestinal Microbiome/physiology ; *Periodontal Diseases/etiology ; *Microbiota ; *Periodontitis/microbiology ; Enzyme Inhibitors/pharmacology ; }, abstract = {Periodontitis is a chronic inflammatory disease associated with persistent oral microbial dysbiosis. The human β-glucuronidase (GUS) degrades constituents of the periodontium and is used as a biomarker for periodontitis severity. However, the human microbiome also encodes GUS enzymes, and the role of these factors in periodontal disease is poorly understood. Here, we define the 53 unique GUSs in the human oral microbiome and examine diverse GUS orthologs from periodontitis-associated pathogens. Oral bacterial GUS enzymes are more efficient polysaccharide degraders and processers of biomarker substrates than the human enzyme, particularly at pHs associated with disease progression. Using a microbial GUS-selective inhibitor, we show that GUS activity is reduced in clinical samples obtained from individuals with untreated periodontitis and that the degree of inhibition correlates with disease severity. Together, these results establish oral GUS activity as a biomarker that captures both host and microbial contributions to periodontitis, facilitating more efficient clinical monitoring and treatment paradigms for this common inflammatory disease.}, }
@article {pmid37144511, year = {2023}, author = {Xia, B and Wang, J and Zhang, D and Hu, X}, title = {The human microbiome links to prostate cancer risk and treatment (Review).}, journal = {Oncology reports}, volume = {49}, number = {6}, pages = {}, pmid = {37144511}, issn = {1791-2431}, mesh = {Male ; Humans ; *Prostatic Neoplasms/therapy ; Androgen Antagonists ; *Microbiota/physiology ; }, abstract = {Prostate cancer (Pca) is the second most common cancer type worldwide. Microorganisms colonized in different body parts may affect the development/progression and treatment of Pca through direct or indirect interactions. The composition of microorganisms in different colonization sites and their effects on Pca may differ. In recent years, several studies have focused on the differences in the microbiota of patients with Pca, and dysbiosis may affect the inflammatory status, hormone levels and microbial metabolites leading to Pca progression. However, little is known about the interaction between Pca treatment and microorganisms; for example, how androgen deprivation therapy and androgen receptor axis‑targeting therapeutics for Pca affect microbiota composition and metabolism, and how the microbiota affects treatment response in patients with Pca remain to be understood. The present review explored the current studies on the relevance of microbiota to Pca progression and treatment to provide direction for future microbiome‑Pca research. Due to the complexity of the potential interconnections between Pca and the microbiota, further investigation is critical.}, }
@article {pmid37139495, year = {2023}, author = {Gao, J and Zhao, L and Cheng, Y and Lei, W and Wang, Y and Liu, X and Zheng, N and Shao, L and Chen, X and Sun, Y and Ling, Z and Xu, W}, title = {Probiotics for the treatment of depression and its comorbidities: A systemic review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1167116}, pmid = {37139495}, issn = {2235-2988}, mesh = {Animals ; Humans ; Brain ; Depression/therapy ; Dysbiosis/therapy ; *Gastrointestinal Microbiome/physiology ; *Mental Disorders ; *Probiotics/therapeutic use ; }, abstract = {Depression is one of the most common psychiatric conditions, characterized by significant and persistent depressed mood and diminished interest, and often coexists with various comorbidities. The underlying mechanism of depression remain elusive, evidenced by the lack of an appreciate therapy. Recent abundant clinical trials and animal studies support the new notion that the gut microbiota has emerged as a novel actor in the pathophysiology of depression, which partakes in bidirectional communication between the gut and the brain through the neuroendocrine, nervous, and immune signaling pathways, collectively known as the microbiota-gut-brain (MGB) axis. Alterations in the gut microbiota can trigger the changes in neurotransmitters, neuroinflammation, and behaviors. With the transition of human microbiome research from studying associations to investigating mechanistic causality, the MGB axis has emerged as a novel therapeutic target in depression and its comorbidities. These novel insights have fueled idea that targeting on the gut microbiota may open new windows for efficient treatment of depression and its comorbidities. Probiotics, live beneficial microorganisms, can be used to modulate gut dysbiosis into a new eubiosis and modify the occurrence and development of depression and its comorbidities. In present review, we summarize recent findings regarding the MGB axis in depression and discuss the potential therapeutic effects of probiotics on depression and its comorbidities.}, }
@article {pmid37138077, year = {2023}, author = {Bayfield, OW and Shkoporov, AN and Yutin, N and Khokhlova, EV and Smith, JLR and Hawkins, DEDP and Koonin, EV and Hill, C and Antson, AA}, title = {Structural atlas of a human gut crassvirus.}, journal = {Nature}, volume = {617}, number = {7960}, pages = {409-416}, pmid = {37138077}, issn = {1476-4687}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 GM129325/GM/NIGMS NIH HHS/United States ; /LM/NLM NIH HHS/United States ; /AI/NIAID NIH HHS/United States ; }, mesh = {Bacteroides ; Capsid/chemistry/metabolism/ultrastructure ; Protein Unfolding ; Humans ; *Virion/chemistry/metabolism/ultrastructure ; *DNA Viruses/classification/chemistry/isolation &amp; purification/ultrastructure/metabolism ; *Viral Proteins/chemistry/metabolism/ultrastructure ; *Intestines/microbiology/virology ; Protein Folding ; Cryoelectron Microscopy ; Virus Assembly ; }, abstract = {CrAssphage and related viruses of the order Crassvirales (hereafter referred to as crassviruses) were originally discovered by cross-assembly of metagenomic sequences. They are the most abundant viruses in the human gut, are found in the majority of individual gut viromes, and account for up to 95% of the viral sequences in some individuals[1-4]. Crassviruses are likely to have major roles in shaping the composition and functionality of the human microbiome, but the structures and roles of most of the virally encoded proteins are unknown, with only generic predictions resulting from bioinformatic analyses[4,5]. Here we present a cryo-electron microscopy reconstruction of Bacteroides intestinalis virus ΦcrAss001[6], providing the structural basis for the functional assignment of most of its virion proteins. The muzzle protein forms an assembly about 1 MDa in size at the end of the tail and exhibits a previously unknown fold that we designate the 'crass fold', that is likely to serve as a gatekeeper that controls the ejection of cargos. In addition to packing the approximately 103 kb of virus DNA, the ΦcrAss001 virion has extensive storage space for virally encoded cargo proteins in the capsid and, unusually, within the tail. One of the cargo proteins is present in both the capsid and the tail, suggesting a general mechanism for protein ejection, which involves partial unfolding of proteins during their extrusion through the tail. These findings provide a structural basis for understanding the mechanisms of assembly and infection of these highly abundant crassviruses.}, }
@article {pmid37132117, year = {2023}, author = {Gong, J and Liu, S and Wang, S and Ruan, H and Mou, Q and Fan, P and Chen, T and Cai, W and Lu, Y and Lu, Z}, title = {Identification of fecal microbiome signatures associated with familial longevity and candidate metabolites for healthy aging.}, journal = {Aging cell}, volume = {22}, number = {6}, pages = {e13848}, pmid = {37132117}, issn = {1474-9726}, mesh = {Humans ; *Healthy Aging/genetics ; RNA, Ribosomal, 16S/genetics ; Longevity/genetics ; *Microbiota ; Aging/genetics ; Metabolomics ; }, abstract = {Gut microbiota associated with longevity plays an important role in the adaptation to damaging stimuli accumulated during the aging process. The mechanism by which the longevity-associated microbiota protects the senescent host remains unclear, while the metabolites of the gut bacteria are of particular interest. Here, an integrated analysis of untargeted metabolomics and 16S rRNA gene sequencing was used to characterize the metabolite and microbiota profiles of long-lived individuals (aged ≥90 years) in comparison to old-elderly (aged 75-89 years), young-elderly (aged 60-74 years), and young to middle-aged (aged ≤59 years) individuals. This novel study constructed both metabolite and microbiota trajectories across aging in populations from Jiaoling county (the seventh longevity town of the world) in China. We found that the long-lived group exhibited remarkably differential metabolomic signatures, highlighting the existence of metabolic heterogeneity with aging. Importantly, we also discovered that long-lived individuals from the familial longevity cohort harbored a microbiome distinguished from that of the general population. Specifically, we identified that the levels of a candidate metabolite, pinane thromboxane A2 (PTA2), which is positively associated with aging, were consistently higher in individuals with familial longevity and their younger descendants than in those of the general population. Furtherly, functional analysis revealed that PTA2 potentiated the efficiency of microglial phagocytosis of β-amyloid 40 and enhanced an anti-inflammatory phenotype, indicating a protective role of PTA2 toward host health. Collectively, our results improve the understanding of the role of the gut microbiome in longevity and may facilitate the development of strategies for healthy aging.}, }
@article {pmid37129834, year = {2023}, author = {Duarte, MJ and Tien, PC and Somsouk, M and Price, JC}, title = {The human microbiome and gut-liver axis in people living with HIV.}, journal = {Current HIV/AIDS reports}, volume = {20}, number = {3}, pages = {170-180}, pmid = {37129834}, issn = {1548-3576}, support = {U01 HL146242/NH/NIH HHS/United States ; K24 AI108516/AI/NIAID NIH HHS/United States ; K24 AI108516/NH/NIH HHS/United States ; R01DK123746/NH/NIH HHS/United States ; T32 DK060414/DK/NIDDK NIH HHS/United States ; U01 HL146242/HL/NHLBI NIH HHS/United States ; R01 DK123746/DK/NIDDK NIH HHS/United States ; T32 DK060414/NH/NIH HHS/United States ; R01 DK109823/DK/NIDDK NIH HHS/United States ; R01 DK109823/NH/NIH HHS/United States ; }, mesh = {Humans ; Dysbiosis ; *HIV Infections/complications ; Liver ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {PURPOSE OF REVIEW: Chronic liver disease is a major cause of morbidity and mortality amongst people living with HIV (PLWH). Emerging data suggests that gut microbial translocation may play a role in driving and modulating liver disease, a bi-directional relationship termed the gut-liver axis. While it is recognized that PLWH have a high degree of dysbiosis and gut microbial translocation, little is known about the gut-liver axis in PLWH.<br><br>RECENT FINDINGS: Recent studies have shown that microbial translocation can directly lead to hepatic inflammation, and have linked gut microbial signatures, dysbiosis, and translocation to liver disease in PLWH. Additionally, multiple trials have explored interventions targeting the microbiome in PLWH. Emerging research supports the interaction between the gut microbiome and liver disease in PLWH. This offers new opportunities to expand our understanding of the pathophysiology of liver disease in this population, as well as to explore possible clinical interventions.}, }
@article {pmid37127667, year = {2023}, author = {Nearing, JT and DeClercq, V and Langille, MGI}, title = {Investigating the oral microbiome in retrospective and prospective cases of prostate, colon, and breast cancer.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {23}, pmid = {37127667}, issn = {2055-5008}, mesh = {Male ; Humans ; *Breast Neoplasms ; Retrospective Studies ; Prostate ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; *Prostatic Neoplasms ; *Colonic Neoplasms ; }, abstract = {The human microbiome has been proposed as a potentially useful biomarker for several cancers. To examine this, we made use of salivary samples from the Atlantic Partnership for Tomorrow's Health (PATH) project and Alberta's Tomorrow Project (ATP). Sample selection was divided into both a retrospective and prospective case control design examining prostate, breast, and colon cancer. In total 89 retrospective and 260 prospective cancer cases were matched to non-cancer controls and saliva samples were sequenced using 16S rRNA gene sequencing. We found no significant differences in alpha diversity. All beta diversity measures were insignificant except for unweighted UniFrac profiles in retrospective breast cancer cases and weighted UniFrac, Bray-Curtis and Robust Atchinson's distances in colon cancer after testing with age and sex adjusted MiRKAT models. Differential abundance (DA) analysis showed several taxa that were associated with previous cancer in all three groupings. Only one genus (Clostridia UCG-014) in breast cancer and one ASV (Fusobacterium periodonticum) in colon cancer was identified by more than one DA tool. In prospective cases three ASVs were associated with colon cancer, one ASV with breast cancer, and one ASV with prostate cancer. Random Forest classification showed low levels of signal in both study designs in breast and prostate cancer. Contrastingly, colon cancer did show signal in our retrospective analysis (AUC: 0.737) and in one of two prospective cohorts (AUC: 0.717). Our results indicate that it is unlikely that reliable microbial oral biomarkers for breast and prostate cancer exist.. However, further research into the oral microbiome and colon cancer could be fruitful.}, }
@article {pmid37122947, year = {2023}, author = {Sinkko, H and Lehtimäki, J and Lohi, H and Ruokolainen, L and Hielm-Björkman, A}, title = {Distinct healthy and atopic canine gut microbiota is influenced by diet and antibiotics.}, journal = {Royal Society open science}, volume = {10}, number = {4}, pages = {221104}, pmid = {37122947}, issn = {2054-5703}, abstract = {The rising trend in non-communicable chronic inflammatory diseases coincides with changes in Western lifestyle. While changes in the human microbiota may play a central role in the development of chronic diseases, estimating the contribution of associated lifestyle factors remains challenging. We studied the influence of lifestyle-diet, antibiotic use, and residential environment with housing and family-on the gut microbiota of healthy and owner-reported atopic pet dogs, searching for associations between the lifestyle factors, atopy and microbiota. The results showed that atopic and healthy dogs had contrasting gut microbial composition. The gut microbiota also differed between two breeds, Labrador Retriever and Finnish Lapphund, selected for our study. Among all lifestyle factors studied, diet was most significantly associated with gut microbiota but only weakly with atopic symptoms. Thus, diet- and atopy-associated changes in the microbiota were not interrelated. Instead, the severity of symptoms was positively associated with the usage of antibiotics, which in turn was associated with the microbiota composition. Urban lifestyle was significantly associated with the increased prevalence of allergies but not with the gut microbiota. Our results from pet dogs supported previous evidence from humans, demonstrating that antibiotics, gut microbiota and atopic manifestation are interrelated. This congruence suggests that canine atopy might be a promising model for understanding the aetiology of human allergy.}, }
@article {pmid37122075, year = {2023}, author = {Simpson, JB and Sekela, JJ and Carry, BS and Beaty, V and Patel, S and Redinbo, MR}, title = {Diverse but desolate landscape of gut microbial azoreductases: A rationale for idiopathic IBD drug response.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2203963}, pmid = {37122075}, issn = {1949-0984}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; R01 GM135218/GM/NIGMS NIH HHS/United States ; R01 GM137286/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Prodrugs ; *Amlodipine Besylate, Olmesartan Medoxomil Drug Combination ; *Crohn Disease ; *Colitis, Ulcerative ; Mesalamine/therapeutic use ; *Inflammatory Bowel Diseases/drug therapy ; }, abstract = {Prodrugs reliant on microbial activation are widely used but exhibit a range of efficacies that remain poorly understood. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA), which is packaged in a variety of azo-linked prodrugs provided to most Ulcerative Colitis (UC) patients, shows confounding inter-individual variabilities in response. Such prodrugs must be activated by azo-bond reduction to form 5-ASA, a process that has been attributed to both enzymatic and non-enzymatic catalysis. Gut microbial azoreductases (AzoRs) are the first catalysts shown to activate azo-linked drugs and to metabolize toxic azo-chemicals. Here, we chart the scope of the structural and functional diversity of AzoRs in health and in patients with the inflammatory bowel diseases (IBDs) UC and Crohn's Disease (CD). Using structural metagenomics, we define the landscape of gut microbial AzoRs in 413 healthy donor and 1059 IBD patient fecal samples. Firmicutes encode a significantly higher number of unique AzoRs compared to other phyla. However, structural and biochemical analyses of distinct AzoRs from the human microbiome reveal significant differences between prevalent orthologs in the processing of toxic azo-dyes, and their generally poor activation of IBD prodrugs. Furthermore, while individuals with IBD show higher abundances of AzoR-encoding gut microbial taxa than healthy controls, the overall abundance of AzoR-encoding microbes is markedly low in both disease and health. Together, these results establish that gut microbial AzoRs are functionally diverse but sparse in both health and disease, factors that may contribute to non-optimal processing of azo-linked prodrugs and idiopathic IBD drug responses.}, }
@article {pmid37120981, year = {2023}, author = {De Alcaraz-Fossoul, J and Wang, Y and Liu, R and Mancenido, M and Marshall, PA and Núñez, C and Broatch, J and Ferry, L}, title = {Microbes in fingerprints: A source for dating crime evidence?.}, journal = {Forensic science international. Genetics}, volume = {65}, number = {}, pages = {102883}, doi = {10.1016/j.fsigen.2023.102883}, pmid = {37120981}, issn = {1878-0326}, mesh = {Humans ; Aged ; *Microbiota ; Touch ; Crime ; Forensic Sciences ; Dermatoglyphics ; }, abstract = {Interest in the human microbiome has grown in recent years because of increasing applications to biomedicine and forensic science. However, the potential for dating evidence at a crime scene based upon time-dependent changes in microbial signatures has not been established, despite a relatively straightforward scientific process for isolating the microbiome. We hypothesize that modifications in microbial diversity, abundance, and succession can provide estimates of the time a surface was touched for investigative purposes. In this proof-of-concept research, the sequencing and analysis of the 16 S rRNA gene from microbes present in fresh and aged latent fingerprints deposited by three donors with pre- and post-washed hands is reported. The stability of major microbial phyla is confirmed while the dynamics of less abundant groups is described up to 21 days post-deposition. Most importantly, a phylum is suggested as the source for possible biological markers to date fingerprints: Deinococcus-Thermus.}, }
@article {pmid37119938, year = {2023}, author = {Luqman, A}, title = {The orchestra of human bacteriome by hormones.}, journal = {Microbial pathogenesis}, volume = {180}, number = {}, pages = {106125}, doi = {10.1016/j.micpath.2023.106125}, pmid = {37119938}, issn = {1096-1208}, mesh = {Humans ; *Norepinephrine/pharmacology ; *Epinephrine/pharmacology ; Bacteria/metabolism ; Quorum Sensing ; Hormones ; }, abstract = {Human microbiome interact reciprocally with the host. Recent findings showed the capability of microorganisms to response towards host signaling molecules, such as hormones. Studies confirmed the complex response of bacteria in response to hormones exposure. These hormones impact many aspects on bacteria, such as the growth, metabolism, and virulence. The effects of each hormone seem to be species-specific. The most studied hormones are cathecolamines also known as stress hormones that consists of epinephrine, norepinephrine and dopamine. These hormones affect the growth of bacteria either inhibit or enhance by acting like a siderophore. Epinephrine and norepinephrine have also been reported to activate QseBC, a quorum sensing in Gram-negative bacteria and eventually enhances the virulence of pathogens. Other hormones were also reported to play a role in shaping human microbiome composition and affect their behavior. Considering the complex response of bacteria on hormones, it highlights the necessity to take the impact of hormones on bacteria into account in studying human health in relation to human microbiome.}, }
@article {pmid37116481, year = {2023}, author = {Manara, S and Selma-Royo, M and Huang, KD and Asnicar, F and Armanini, F and Blanco-Miguez, A and Cumbo, F and Golzato, D and Manghi, P and Pinto, F and Valles-Colomer, M and Amoroso, L and Corrias, MV and Ponzoni, M and Raffaetà, R and Cabrera-Rubio, R and Olcina, M and Pasolli, E and Collado, MC and Segata, N}, title = {Maternal and food microbial sources shape the infant microbiome of a rural Ethiopian population.}, journal = {Current biology : CB}, volume = {33}, number = {10}, pages = {1939-1950.e4}, pmid = {37116481}, issn = {1879-0445}, support = {U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Infant ; Infant, Newborn ; *Microbiota ; Bacteria ; Milk, Human/microbiology ; Mothers ; *Gastrointestinal Microbiome ; Feces/microbiology ; }, abstract = {The human microbiome seeding starts at birth, when pioneer microbes are acquired mainly from the mother. Mode of delivery, antibiotic prophylaxis, and feeding method have been studied as modulators of mother-to-infant microbiome transmission, but other key influencing factors like modern westernized lifestyles with high hygienization, high-calorie diets, and urban settings, compared with non-westernized lifestyles have not been investigated yet. In this study, we explored the mother-infant sharing of characterized and uncharacterized microbiome members via strain-resolved metagenomics in a cohort of Ethiopian mothers and infants, and we compared them with four other cohorts with different lifestyles. The westernized and non-westernized newborns' microbiomes composition overlapped during the first months of life more than later in life, likely reflecting similar initial breast-milk-based diets. Ethiopian and other non-westernized infants shared a smaller fraction of the microbiome with their mothers than did most westernized populations, despite showing a higher microbiome diversity, and uncharacterized species represented a substantial fraction of those shared in the Ethiopian cohort. Moreover, we identified uncharacterized species belonging to the Selenomonadaceae and Prevotellaceae families specifically present and shared only in the Ethiopian cohort, and we showed that a locally produced fermented food, injera, can contribute to the higher diversity observed in the Ethiopian infants' gut with bacteria that are not part of the human microbiome but are acquired through fermented food consumption. Taken together, these findings highlight the fact that lifestyle can impact the gut microbiome composition not only through differences in diet, drug consumption, and environmental factors but also through its effect on mother-infant strain-sharing patterns.}, }
@article {pmid37110440, year = {2023}, author = {Efremova, I and Maslennikov, R and Alieva, A and Poluektova, E and Ivashkin, V}, title = {Small Intestinal Bacterial Overgrowth Is Associated with Poor Prognosis in Cirrhosis.}, journal = {Microorganisms}, volume = {11}, number = {4}, pages = {}, pmid = {37110440}, issn = {2076-2607}, abstract = {BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study.<br><br>METHODS: This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years.<br><br>RESULTS: SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis.<br><br>CONCLUSIONS: SIBO is associated with poor prognosis in cirrhosis.}, }
@article {pmid37108423, year = {2023}, author = {Kunika,  and Frey, N and Rangrez, AY}, title = {Exploring the Involvement of Gut Microbiota in Cancer Therapy-Induced Cardiotoxicity.}, journal = {International journal of molecular sciences}, volume = {24}, number = {8}, pages = {}, pmid = {37108423}, issn = {1422-0067}, support = {RA 2717/4-1 and FR 1289/17-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Cardiotoxicity/etiology ; *Microbiota ; Intestines/microbiology ; *Neoplasms/drug therapy ; Bacteria ; Dysbiosis/chemically induced ; }, abstract = {Trillions of microbes in the human intestinal tract, including bacteria, viruses, fungi, and protozoa, are collectively referred to as the gut microbiome. Recent technological developments have led to a significant increase in our understanding of the human microbiome. It has been discovered that the microbiome affects both health and the progression of diseases, including cancer and heart disease. Several studies have indicated that the gut microbiota may serve as a potential target in cancer therapy modulation, by enhancing the effectiveness of chemotherapy and/or immunotherapy. Moreover, altered microbiome composition has been linked to the long-term effects of cancer therapy; for example, the deleterious effects of chemotherapy on microbial diversity can, in turn, lead to acute dysbiosis and serious gastrointestinal toxicity. Specifically, the relationship between the microbiome and cardiac diseases in cancer patients following therapy is poorly understood. In this article, we provide a summary of the role of the microbiome in cancer treatment, while also speculating on a potential connection between treatment-related microbial changes and cardiotoxicity. Through a brief review of the literature, we further explore which bacterial families or genera were differentially affected in cancer treatment and cardiac disease. A deeper understanding of the link between the gut microbiome and cardiotoxicity caused by cancer treatment may help lower the risk of this critical and potentially fatal side effect.}, }
@article {pmid37107220, year = {2023}, author = {Vacca, M and Pinto, D and Annunziato, A and Ressa, A and Calasso, M and Pontonio, E and Celano, G and De Angelis, M}, title = {Gluten-Free Bread Enriched with Artichoke Leaf Extract In Vitro Exerted Antioxidant and Anti-Inflammatory Properties.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {37107220}, issn = {2076-3921}, abstract = {Due to its high nutritional value and broad beneficial effects, the artichoke plant (Cynara cardunculus L.) is an excellent healthy food candidate. Additionally, the artichoke by-products are usually discarded even though they still contain a huge concentration of dietary fibers, phenolic acids, and other micronutrients. The present work aimed to characterize a laboratory-made gluten-free bread (B) using rice flour supplemented with a powdered extract from artichoke leaves (AEs). The AE, accounting for the 5% of titratable chlorogenic acid, was added to the experimental gluten-free bread. Accounting for different combinations, four different bread batches were prepared. To evaluate the differences, a gluten-free type-II sourdough (tII-SD) was added in two doughs (SB and SB-AE), while the related controls (YB and YB-AE) did not contain the tII-SD. Profiling the digested bread samples, SB showed the lowest glycemic index, while SB-AE showed the highest antioxidant properties. The digested samples were also fermented in fecal batches containing viable cells from fecal microbiota samples obtained from healthy donors. Based on plate counts, no clear tendencies emerged concerning the analyzed microbial patterns; by contrast, when profiling volatile organic compounds, significant differences were observed in SB-AE, exhibiting the highest scores of hydrocinnamic and cyclohexanecarboxylic acids. The fecal fermented supernatants were recovered and assayed for healthy properties on human keratinocyte cell lines against oxidative stress and for effectiveness in modulating the expression of proinflammatory cytokines in Caco-2 cells. While the first assay emphasized the contribution of AE to protect against stressor agents, the latter enlightened how the combination of SB with AE decreased the cellular TNF-α and IL1-β expression. In conclusion, this preliminary study suggests that the combination of AE with sourdough biotechnology could be a promising tool to increase the nutritional and healthy features of gluten-free bread.}, }
@article {pmid37106510, year = {2023}, author = {Luo, X and Li, H and Fan, X and Wu, X and Zhou, R and Lei, Y and Xue, D and Yang, F and Xu, Y and Wang, K}, title = {The Gut Microbiota-Brain Axis: Potential Mechanism of Drug Addiction.}, journal = {Current topics in medicinal chemistry}, volume = {23}, number = {18}, pages = {1782-1792}, doi = {10.2174/1568026623666230418114133}, pmid = {37106510}, issn = {1873-4294}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Brain-Gut Axis ; *Microbiota ; Brain/metabolism ; *Nervous System Diseases/metabolism ; *Substance-Related Disorders ; }, abstract = {As a chronic encephalopathy, drug addiction is responsible for millions of deaths per year around the world. The gut microbiome is a crucial component of the human microbiome. Through dynamic bidirectional communication along the 'gut-brain axis,' gut bacteria cooperate with their hosts to regulate the development and function of the immune, metabolic, and nervous systems. These processes may affect human health because some brain diseases are related to the composition of gut bacteria, and disruptions in microbial communities have been implicated in neurological disorders. We review the compositional and functional diversity of the gut microbiome in drug addiction. We discuss intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems and possible contributions by the gut microbiota to neurological disorders. Finally, the treatment of probiotics and fecal transplantation was summarized. This was done to further understand the role of intestinal microecology in the pathogenesis of drug addiction and to explore new methods for the treatment of drug addiction.}, }
@article {pmid37102387, year = {2023}, author = {Lukkarinen, M and Kirjavainen, PV and Backman, K and Gonzales-Inca, C and Hickman, B and Kallio, S and Karlsson, H and Karlsson, L and Keski-Nisula, L and Korhonen, LS and Korpela, K and Kuitunen, M and Kukkonen, AK and Käyhkö, N and Lagström, H and Lukkarinen, H and Peltola, V and Pentti, J and Salonen, A and Savilahti, E and Tuoresmäki, P and Täubel, M and Vahtera, J and de Vos, WM and Pekkanen, J and Karvonen, AM}, title = {Early-life environment and the risk of eczema at 2 years-Meta-analyses of six Finnish birth cohorts.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {34}, number = {4}, pages = {e13945}, doi = {10.1111/pai.13945}, pmid = {37102387}, issn = {1399-3038}, mesh = {Child ; Infant, Newborn ; Female ; Humans ; Child, Preschool ; Birth Cohort ; Finland/epidemiology ; *Eczema/epidemiology ; *Hypersensitivity/epidemiology ; Seasons ; }, abstract = {BACKGROUND: Urban-related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land cover classes and two greenness indices around homes at birth on the development of doctor-diagnosed eczema by the age of 2 years, and the influence of birth season.<br><br>METHODS: Data from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta-analyses.<br><br>RESULTS: In meta-analyses, neither greenness indices (NDVI or VCDI, 250&#x2009;m&#x2009;&#xd7;&#x2009;250&#x2009;m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2&#x2009;years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01-1.39 for the middle and 1.16; 0.98-1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02-1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98-1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65-0.91 highest vs. lowest tertile).<br><br>CONCLUSION: Greenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high-green areas.}, }
@article {pmid37101246, year = {2023}, author = {Zhang, D and Zhang, J and Kalimuthu, S and Liu, J and Song, ZM and He, BB and Cai, P and Zhong, Z and Feng, C and Neelakantan, P and Li, YX}, title = {A systematically biosynthetic investigation of lactic acid bacteria reveals diverse antagonistic bacteriocins that potentially shape the human microbiome.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {91}, pmid = {37101246}, issn = {2049-2618}, mesh = {Female ; Humans ; *Bacteriocins/genetics ; *Lactobacillales/genetics ; *Microbiota/genetics ; Metagenome ; Anti-Bacterial Agents/pharmacology ; }, abstract = {BACKGROUND: Lactic acid bacteria (LAB) produce various bioactive secondary metabolites (SMs), which endow LAB with a protective role for the host. However, the biosynthetic potentials of LAB-derived SMs remain elusive, particularly in their diversity, abundance, and distribution in the human microbiome. Thus, it is still unknown to what extent LAB-derived SMs are involved in microbiome homeostasis.<br><br>RESULTS: Here, we systematically investigate the biosynthetic potential of LAB from 31,977 LAB genomes, identifying 130,051 secondary metabolite biosynthetic gene clusters (BGCs) of 2,849 gene cluster families (GCFs). Most of these GCFs are species-specific or even strain-specific and uncharacterized yet. Analyzing 748 human-associated metagenomes, we gain an insight into the profile of LAB BGCs, which are highly diverse and niche-specific in the human microbiome. We discover that most LAB BGCs may encode bacteriocins with pervasive antagonistic activities predicted by machine learning models, potentially playing protective roles in the human microbiome. Class II bacteriocins, one of the most abundant and diverse LAB SMs, are particularly enriched and predominant in the vaginal microbiome. We utilized metagenomic and metatranscriptomic analyses to guide our discovery of functional class II bacteriocins. Our findings suggest that these antibacterial bacteriocins have the potential to regulate microbial communities in the vagina, thereby contributing to the maintenance of microbiome homeostasis.<br><br>CONCLUSIONS: Our study systematically investigates LAB biosynthetic potential and their profiles in the human microbiome, linking them to the antagonistic contributions to microbiome homeostasis via omics analysis. These discoveries of the diverse and prevalent antagonistic SMs are expected to stimulate the mechanism study of LAB's protective roles for the microbiome and host, highlighting the potential of LAB and their bacteriocins as therapeutic alternatives. Video Abstract.}, }
@article {pmid37100405, year = {2023}, author = {Jaffe, AL and Castelle, CJ and Banfield, JF}, title = {Habitat Transition in the Evolution of Bacteria and Archaea.}, journal = {Annual review of microbiology}, volume = {77}, number = {}, pages = {193-212}, doi = {10.1146/annurev-micro-041320-032304}, pmid = {37100405}, issn = {1545-3251}, mesh = {Animals ; Archaea/genetics ; Bacteria/genetics ; *Bacteriophages ; Genomics ; *Microbiota ; }, abstract = {Related groups of microbes are widely distributed across Earth's habitats, implying numerous dispersal and adaptation events over evolutionary time. However, relatively little is known about the characteristics and mechanisms of these habitat transitions, particularly for populations that reside in animal microbiomes. Here, we review the literature concerning habitat transitions among a variety of bacterial and archaeal lineages, considering the frequency of migration events, potential environmental barriers, and mechanisms of adaptation to new physicochemical conditions, including the modification of protein inventories and other genomic characteristics. Cells dependent on microbial hosts, particularly bacteria from the Candidate Phyla Radiation, have undergone repeated habitat transitions from environmental sources into animal microbiomes. We compare their trajectories to those of both free-living cells-including the Melainabacteria, Elusimicrobia, and methanogenic archaea-and cellular endosymbionts and bacteriophages, which have made similar transitions. We conclude by highlighting major related topics that may be worthy of future study.}, }
@article {pmid37100345, year = {2024}, author = {Shen, S and Sun, T and Ding, X and Gu, X and Wang, Y and Ma, X and Li, Z and Gao, H and Ge, S and Feng, Q}, title = {The exoprotein Gbp of Fusobacterium nucleatum promotes THP-1 cell lipid deposition by binding to CypA and activating PI3K-AKT/MAPK/NF-κB pathways.}, journal = {Journal of advanced research}, volume = {57}, number = {}, pages = {93-105}, pmid = {37100345}, issn = {2090-1224}, mesh = {Humans ; NF-kappa B ; Cyclophilin A ; Fusobacterium nucleatum ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; THP-1 Cells ; *Atherosclerosis ; Inflammation ; *Periodontitis ; Lipids ; *Calcium-Binding Proteins ; *Monosaccharide Transport Proteins ; *Periplasmic Binding Proteins ; }, abstract = {INTRODUCTION: Growing evidence has shown the correlation between periodontitis and atherosclerosis, while our knowledge on the pathogenesis of periodontitis-promoting atherosclerosis is far from sufficient.<br><br>OBJECTIVES: Illuminate the pathogenic effects of Fusobacterium nucleatum (F. nucleatum) on intracellular lipid deposition in THP-1-derived macrophages and elucidate the underlying pathogenic mechanism of how F. nucleatum promoting atherosclerosis.<br><br>METHODS AND RESULTS: F. nucleatum was frequently detected in different kinds of atherosclerotic plaques and its abundance was positively correlated with the proportion of macrophages. In vitro assays showed F. nucleatum could adhere to and invade THP-1 cells, and survive continuously in macrophages for 24&#xa0;h. F. nucleatum stimulation alone could significantly promote cellular inflammation, lipid uptake and inhibit lipid outflow. The dynamic gene expression of THP-1 cells demonstrated that F. nucleatum could time-serially induce the over-expression of multiple inflammatory related genes and activate NF-&#x3ba;B, MAPK and PI3K-AKT signaling pathways. The exoprotein of F. nucleatum, D-galactose-binding protein (Gbp), acted as one of the main pathogenic proteins to interact with the Cyclophilin A (CypA) of THP-1 cells and induced the activation of the NF- &#x3ba;B, MAPK and PI3K-AKT signaling pathways. Furthermore, use of six candidate drugs targeting to the key proteins in NF- &#x3ba;B, MAPK and PI3K-AKT pathways could dramatically decrease F. nucleatum induced inflammation and lipid deposition in THP-1 cells.<br><br>CONCLUSIONS: This study suggests that the periodontal pathogen F. nucleatum can activate macrophage PI3K-AKT/MAPK/NF-&#x3ba;B signal pathways, promotes inflammation, enhances cholesterol uptake, reduces lipid excretion, and promotes lipid deposition, which may be one of its main strategies promoting the development of atherosclerosis.}, }
@article {pmid37099803, year = {2023}, author = {Kantele, A and Riekkinen, M and Jokiranta, TS and Pakkanen, SH and Pietilä, JP and Patjas, A and Eriksson, M and Khawaja, T and Klemets, P and Marttinen, K and Siikamäki, H and Lundgren, A and Holmgren, J and Lissmats, A and Carlin, N and Svennerholm, AM}, title = {Safety and immunogenicity of ETVAX®, an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa.}, journal = {Journal of travel medicine}, volume = {30}, number = {7}, pages = {}, pmid = {37099803}, issn = {1708-8305}, support = {H2020-SMEInst-2016-2017//Scandinavian Biopharma/ ; 204139-101//PATH/ ; }, mesh = {Child ; Humans ; Benin ; *Enterotoxigenic Escherichia coli ; Vaccines, Inactivated ; Finland ; Lipopolysaccharides ; Africa, Western ; Diarrhea/prevention &amp; control ; Immunoglobulin A ; }, abstract = {BACKGROUND: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX®, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies.<br><br>METHODS: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65&#xa0;years were randomized 1:1 to receive ETVAX&#xae; or placebo. They visited Benin for 12&#xa0;days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence.<br><br>RESULTS: The AEs did not differ significantly between vaccine (n&#x2009;=&#x2009;374) and placebo (n&#x2009;=&#x2009;375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX&#xae; recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of &#x2265;2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX&#xae; recipients (93%) responded to either LTB or O78.<br><br>CONCLUSIONS: This Phase 2b trial is the largest on ETVAX&#xae; undertaken amongst travellers to date. ETVAX&#xae; showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.}, }
@article {pmid37099800, year = {2023}, author = {Gou, W and Miao, Z and Deng, K and Zheng, JS}, title = {Nutri-microbiome epidemiology, an emerging field to disentangle the interplay between nutrition and microbiome for human health.}, journal = {Protein &amp; cell}, volume = {14}, number = {11}, pages = {787-806}, pmid = {37099800}, issn = {1674-8018}, support = {2022YFA1303900//National Key R&amp;D Program of China/ ; 82204161//National Natural Science Foundation of China/ ; //Research Program of Westlake Laboratory of Life Sciences and Biomedicine/ ; 202208012//China Postdoctoral Science Foundation/ ; }, mesh = {Humans ; Diet ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Diet and nutrition have a substantial impact on the human microbiome, and interact with the microbiome, especially gut microbiome, to modulate various diseases and health status. Microbiome research has also guided the nutrition field to a more integrative direction, becoming an essential component of the rising area of precision nutrition. In this review, we provide a broad insight into the interplay among diet, nutrition, microbiome, and microbial metabolites for their roles in the human health. Among the microbiome epidemiological studies regarding the associations of diet and nutrition with microbiome and its derived metabolites, we summarize those most reliable findings and highlight evidence for the relationships between diet and disease-associated microbiome and its functional readout. Then, the latest advances of the microbiome-based precision nutrition research and multidisciplinary integration are described. Finally, we discuss several outstanding challenges and opportunities in the field of nutri-microbiome epidemiology.}, }
@article {pmid37099704, year = {2023}, author = {Choi, JM and Ji, M and Watson, LT and Zhang, L}, title = {DeepMicroGen: a generative adversarial network-based method for longitudinal microbiome data imputation.}, journal = {Bioinformatics (Oxford, England)}, volume = {39}, number = {5}, pages = {}, pmid = {37099704}, issn = {1367-4811}, mesh = {Humans ; Longitudinal Studies ; *Microbiota ; Neural Networks, Computer ; Sample Size ; Time Factors ; }, abstract = {MOTIVATION: The human microbiome, which is linked to various diseases by growing evidence, has a profound impact on human health. Since changes in the composition of the microbiome across time are associated with disease and clinical outcomes, microbiome analysis should be performed in a longitudinal study. However, due to limited sample sizes and differing numbers of timepoints for different subjects, a significant amount of data cannot be utilized, directly affecting the quality of analysis results. Deep generative models have been proposed to address this lack of data issue. Specifically, a generative adversarial network (GAN) has been successfully utilized for data augmentation to improve prediction tasks. Recent studies have also shown improved performance of GAN-based models for missing value imputation in a multivariate time series dataset compared with traditional imputation methods.<br><br>RESULTS: This work proposes DeepMicroGen, a bidirectional recurrent neural network-based GAN model, trained on the temporal relationship between the observations, to impute the missing microbiome samples in longitudinal studies. DeepMicroGen outperforms standard baseline imputation methods, showing the lowest mean absolute error for both simulated and real datasets. Finally, the proposed model improved the predicted clinical outcome for allergies, by providing imputation for an incomplete longitudinal dataset used to train the classifier.<br><br>DeepMicroGen is publicly available at https://github.com/joungmin-choi/DeepMicroGen.}, }
@article {pmid37099694, year = {2023}, author = {Li, B and Wang, T and Qian, M and Wang, S}, title = {MKMR: a multi-kernel machine regression model to predict health outcomes using human microbiome data.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {3}, pages = {}, doi = {10.1093/bib/bbad158}, pmid = {37099694}, issn = {1477-4054}, support = {R01 LM013061/LM/NLM NIH HHS/United States ; }, mesh = {Humans ; Phylogeny ; *Microbiota ; Computer Simulation ; Neural Networks, Computer ; Outcome Assessment, Health Care ; }, abstract = {Studies have found that human microbiome is associated with and predictive of human health and diseases. Many statistical methods developed for microbiome data focus on different distance metrics that can capture various information in microbiomes. Prediction models were also developed for microbiome data, including deep learning methods with convolutional neural networks that consider both taxa abundance profiles and taxonomic relationships among microbial taxa from a phylogenetic tree. Studies have also suggested that a health outcome could associate with multiple forms of microbiome profiles. In addition to the abundance of some taxa that are associated with a health outcome, the presence/absence of some taxa is also associated with and predictive of the same health outcome. Moreover, associated taxa may be close to each other on a phylogenetic tree or spread apart on a phylogenetic tree. No prediction models currently exist that use multiple forms of microbiome-outcome associations. To address this, we propose a multi-kernel machine regression (MKMR) method that is able to capture various types of microbiome signals when doing predictions. MKMR utilizes multiple forms of microbiome signals through multiple kernels being transformed from multiple distance metrics for microbiomes and learn an optimal conic combination of these kernels, with kernel weights helping us understand contributions of individual microbiome signal types. Simulation studies suggest a much-improved prediction performance over competing methods with mixture of microbiome signals. Real data applicants to predict multiple health outcomes using throat and gut microbiome data also suggest a better prediction of MKMR than that of competing methods.}, }
@article {pmid37097879, year = {2023}, author = {Stewart, CJ}, title = {2022 Fleming Prize Lecture: diet-microbe-host interaction in early life.}, journal = {Journal of medical microbiology}, volume = {72}, number = {4}, pages = {}, doi = {10.1099/jmm.0.001662}, pmid = {37097879}, issn = {1473-5644}, mesh = {Infant ; Female ; Infant, Newborn ; Humans ; Middle Aged ; *Infant, Premature ; Host Microbial Interactions ; Milk, Human ; *Microbiota ; Diet ; }, abstract = {The last decade has witnessed a meteoric rise in research focused on characterizing the human microbiome and identifying associations with disease risk. The advent of sequencing technology has all but eradicated gel-based fingerprinting approaches for studying microbial ecology, while at the same time traditional microbiological culture is undergoing a renaissance. Although multiplexed high-throughput sequencing is relatively new, the discoveries leading to this are nearly 50 years old, coinciding with the inaugural Microbiology Society Fleming Prize lecture. It was an honour to give the 2022 Fleming Prize lecture and this review will cover the topics from that lecture. The focus will be on the bacterial community in early life, beginning with term infants before moving on to infants delivered prematurely. The review will discuss recent work showing how human milk oligosaccharides (HMOs), an abundant but non-nutritious component of breast milk, can modulate infant microbiome and promote the growth of Bifidobacterium spp. This has important connotations for preterm infants at risk of necrotizing enterocolitis, a devastating intestinal disease representing the leading cause of death and long-term morbidity in this population. With appropriate mechanistic studies, it may be possible to harness the power of breast milk bioactive factors and infant gut microbiome to improve short- and long-term health in infants.}, }
@article {pmid37086551, year = {2023}, author = {Dmitrieva, K and Maslennikov, R and Vasilieva, E and Aliev, S and Bakhitov, V and Marcinkevich, V and Levshina, A and Kozlov, E and Ivashkin, V and Poluektova, E}, title = {Impact of vaccination against the novel coronavirus infection (COVID-19) with Sputnik V on mortality during the delta variant surge.}, journal = {Journal of infection and public health}, volume = {16}, number = {6}, pages = {922-927}, pmid = {37086551}, issn = {1876-035X}, mesh = {Humans ; *COVID-19 Vaccines ; Retrospective Studies ; SARS-CoV-2 ; *COVID-19/prevention &amp; control ; Vaccination ; }, abstract = {OBJECTIVES: The aim is to study impact of vaccination against the novel coronavirus disease (COVID-19) with Sputnik V on mortality during the period of predominance of the delta variant of SARS-CoV-2.<br><br>METHODS: This was a retrospective cohort study of individuals with state health insurance at the Moscow Ambulatory Center. The cohorts included 41,444 persons vaccinated with Sputnik V, 15,566 survivors of COVID-19, and 71,377 non-immune persons. The deaths of patients that occurred from June 1, 2021, to August 31, 2021, were analyzed.<br><br>RESULTS: Overall (0.39&#xa0;% vs. 1.92&#xa0;%; p&#xa0;<&#xa0;0.001), COVID-19-related (0.06&#xa0;% vs. 0.83&#xa0;%; p&#xa0;<&#xa0;0.001), and non-COVID mortality (0.33&#xa0;% vs. 1.09&#xa0;%; p&#xa0;<&#xa0;0.001) was lower among vaccinated individuals than among non-immune individuals. The efficacy of vaccination against death from COVID-19 was 96&#xa0;% [95&#xa0;% CI 91-98&#xa0;%] in the general population, 100&#xa0;% among those aged 18-50 years, 97&#xa0;% [95&#xa0;% CI 76-100&#xa0;%] among those aged 51-70 years, 98&#xa0;% [95&#xa0;% CI 90-100&#xa0;%] among those aged 71-85 years, and 88&#xa0;% [95&#xa0;% CI 49-97&#xa0;%] among those aged >&#xa0;85 years.<br><br>CONCLUSION: COVID-19 vaccination with Sputnik V is associated with a decrease in overall and COVID-19-related mortality and is not with increased non-COVID mortality.}, }
@article {pmid37085428, year = {2023}, author = {Jin, C and Qin, L and Liu, Z and Li, X and Gao, X and Cao, Y and Zhao, S and Wang, J and Han, T and Yan, L and Song, J and Zhang, F and Liu, F and Zhang, Y and Huang, Y and Song, Y and Liu, Y and Yao, Z and Chen, H and Zhang, Z and Zhao, S and Feng, Y and Zhang, YN and Qian, Y and Sun, T and Feng, Q and Zhao, H}, title = {Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.}, journal = {Reproductive biomedicine online}, volume = {46}, number = {6}, pages = {1005-1016}, doi = {10.1016/j.rbmo.2023.02.002}, pmid = {37085428}, issn = {1472-6491}, mesh = {Female ; Humans ; *Polycystic Ovary Syndrome ; Cross-Sectional Studies ; RNA, Ribosomal, 16S/genetics ; Anti-Mullerian Hormone ; *Microbiota ; }, abstract = {RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women?<br><br>DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n&#x202f;=&#x202f;733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated.<br><br>RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon P&#x202f;=&#x202f;0.03, Simpson P&#x202f;=&#x202f;0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR]&#x202f;=&#x202f;0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR&#x202f;=&#x202f;0.006; 1.2% versus 0.6%, FDR&#x202f;=&#x202f;0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-M&#xfc;llerian hormone (AMH), and triglyceride (P&#x202f;=&#x202f;2.01E-05, P&#x202f;=&#x202f;0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P&#x202f;=&#x202f;0.002, P&#x202f;=&#x202f;0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P&#x202f;=&#x202f;0.004, P&#x202f;=&#x202f;0.005, P&#x202f;=&#x202f;0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25).<br><br>CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.}, }
@article {pmid37081054, year = {2023}, author = {Hoisington, AJ and Stamper, CE and Bates, KL and Stanislawski, MA and Flux, MC and Postolache, TT and Lowry, CA and Brenner, LA}, title = {Human microbiome transfer in the built environment differs based on occupants, objects, and buildings.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {6446}, pmid = {37081054}, issn = {2045-2322}, support = {K01 HL157658/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Built Environment ; Skin/microbiology ; }, abstract = {Compared to microbiomes on other skin sites, the bacterial microbiome of the human hand has been found to have greater variability across time. To increase understanding regarding the longitudinal transfer of the hand microbiome to objects in the built environment, and vice versa, 22 participants provided skin microbiome samples from their dominant hands, as well as from frequently and infrequently touched objects in their office environments. Additional longitudinal samples from home environments were obtained from a subset of 11 participants. We observed stability of the microbiomes of both the hand and built environments within the office and home settings; however, differences in the microbial communities were detected across the two built environments. Occupants' frequency of touching an object correlated to that object having a higher relative abundance of human microbes, yet the percent of shared microbes was variable by participants. Finally, objects that were horizontal surfaces in the built environment had higher microbial diversity as compared to objects and the occupants' hands. This study adds to the existing knowledge of microbiomes of the built environment, enables more detailed studies of indoor microbial transfer, and contributes to future models and building interventions to reduce negative outcomes and improve health and well-being.}, }
@article {pmid37080202, year = {2023}, author = {Bedree, JK and Kerns, K and Chen, T and Lima, BP and Liu, G and Ha, P and Shi, J and Pan, HC and Kim, JK and Tran, L and Minot, SS and Hendrickson, EL and Lamont, EI and Schulte, F and Hardt, M and Stephens, D and Patel, M and Kokaras, A and Stodieck, L and Shirazi-Fard, Y and Wu, B and Kwak, JH and Ting, K and Soo, C and McLean, JS and He, X and Shi, W}, title = {Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight.}, journal = {Cell reports}, volume = {42}, number = {5}, pages = {112299}, pmid = {37080202}, issn = {2211-1247}, support = {KL2 TR002317/TR/NCATS NIH HHS/United States ; F31 DE026057/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE029353/DE/NIDCR NIH HHS/United States ; R01 AR061399/AR/NIAMS NIH HHS/United States ; R01 AR068835/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Chromatography, Liquid ; Travel ; Tandem Mass Spectrometry ; *Space Flight ; }, abstract = {Understanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled an ancillary investigation of the gut microbiome, varying exposure to microgravity (flight) relative to ground controls in the context of previously shown bone mineral density (BMD) loss that was observed in these flight groups. We demonstrate elevated abundance of Lactobacillus murinus and Dorea sp. during microgravity exposure relative to ground control through whole-genome sequencing and 16S rRNA analyses. Specific functionally assigned gene clusters of L. murinus and Dorea sp. capable of producing metabolites, lactic acid, leucine/isoleucine, and glutathione are enriched. These metabolites are elevated in the microgravity-exposed host serum as shown by liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomic analysis. Along with BMD loss, ELISA reveals increases in osteocalcin and reductions in tartrate-resistant acid phosphatase 5b signifying additional loss of bone homeostasis in flight.}, }
@article {pmid37077531, year = {2023}, author = {Liu, P and Lu, Y and Li, R and Chen, X}, title = {Use of probiotic lactobacilli in the treatment of vaginal infections: In vitro and in vivo investigations.}, journal = {Frontiers in cellular and infection microbiology}, volume = {13}, number = {}, pages = {1153894}, pmid = {37077531}, issn = {2235-2988}, mesh = {Infant, Newborn ; Female ; Humans ; Lactobacillus ; *Premature Birth ; Vagina ; *Vulvovaginitis ; *Probiotics/therapeutic use ; }, abstract = {The vaginal microbiome is a distinct component of the human microbiome that is colonized by a wide variety of microorganisms. Lactobacilli are the most frequently identified microorganisms in the healthy human vagina. These Gram-positive bacilli can acidify the vaginal microenvironment, inhibit the proliferation of other pathogenic microorganisms, and promote the maintenance of a eubiotic vaginal microbiome. However, a vaginal flora with a reduced proportion or abundance of lactobacilli is associated with various vaginal infections that have been linked to serious health consequences such as infertility, preterm birth, pelvic inflammatory disease, premature rupture of membranes, and miscarriage. Due to their "Generally Recognized as Safe" classification and critical role in vaginal health, probiotic lactobacilli have been widely used as an alternative or adjunct to traditional antibiotic therapy for the treatment of vaginal infections and restoration of the vaginal microbiome. This review focuses on the significant role of probiotic lactobacilli in the vaginal microenvironment and discusses the use of probiotic lactobacilli in the treatment of female vaginal infections in vitro and in vivo.}, }
@article {pmid37074210, year = {2023}, author = {Zhang, YG and Xia, Y and Zhang, J and Deb, S and Garrett, S and Sun, J}, title = {Intestinal vitamin D receptor protects against extraintestinal breast cancer tumorigenesis.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2202593}, pmid = {37074210}, issn = {1949-0984}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Mice ; Animals ; Female ; Receptors, Calcitriol/genetics ; *Breast Neoplasms/prevention &amp; control/metabolism ; Dysbiosis/metabolism ; *Gastrointestinal Microbiome ; Inflammation/metabolism ; Carcinogenesis/metabolism ; Cell Transformation, Neoplastic ; *Gastrointestinal Diseases/metabolism ; Bacteria/metabolism ; Intestinal Mucosa/microbiology ; }, abstract = {The microbiota plays critical roles in regulating the function and health of the intestine and extraintestinal organs. A fundamental question is whether an intestinal-microbiome-breast axis exists during the development of breast cancer. If so, what are the roles of host factors? Vitamin D receptor (VDR) involves host factors and the human microbiome. Vdr gene variation shapes the human microbiome, and VDR deficiency leads to dysbiosis. We hypothesized that intestinal VDR protects hosts against tumorigenesis in the breast. We examined a 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model in intestinal epithelial VDR knockout (VDR[ΔIEC]) mice with dysbiosis. We reported that VDR[ΔIEC] mice with dysbiosis are more susceptible to breast cancer induced by DMBA. Intestinal and breast microbiota analysis showed that VDR deficiency leads to a bacterial profile shift from normal to susceptible to carcinogenesis. We found enhanced bacterial staining within breast tumors. At the molecular and cellular levels, we identified the mechanisms by which intestinal epithelial VDR deficiency led to increased gut permeability, disrupted tight junctions, microbial translocation, and enhanced inflammation, thus increasing tumor size and number in the breast. Furthermore, treatment with the beneficial bacterial metabolite butyrate or the probiotic Lactobacillus plantarum reduced breast tumors, enhanced tight junctions, inhibited inflammation, increased butyryl-CoA transferase, and decreased levels of breast Streptococcus bacteria in VDR[ΔIEC] mice. The gut microbiome contributes to the pathogenesis of diseases not only in the intestine but also in the breast. Our study provides insights into the mechanism by which intestinal VDR dysfunction and gut dysbiosis lead to a high risk of extraintestinal tumorigenesis. Gut-tumor-microbiome interactions represent a new target in the prevention and treatment of breast cancer.}, }
@article {pmid37070603, year = {2023}, author = {Segota, I and Watrous, JD and Kantz, ED and Nallamshetty, S and Tiwari, S and Cheng, S and Jain, M and Long, T}, title = {Reconstructing the landscape of gut microbial species across 29,000 diverse individuals.}, journal = {Nucleic acids research}, volume = {51}, number = {9}, pages = {4178-4190}, pmid = {37070603}, issn = {1362-4962}, support = {R01 HL143227/HL/NHLBI NIH HHS/United States ; R01ES027595/NH/NIH HHS/United States ; COVID-19-8900-12/CX/CSRD VA/United States ; }, mesh = {Humans ; Bacteria/classification ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The human gut microbiome has been linked to health and disease. Investigation of the human microbiome has largely employed 16S amplicon sequencing, with limited ability to distinguish microbes at the species level. Herein, we describe the development of Reference-based Exact Mapping (RExMap) of microbial amplicon variants that enables mapping of microbial species from standard 16S sequencing data. RExMap analysis of 16S data captures ∼75% of microbial species identified by whole-genome shotgun sequencing, despite hundreds-fold less sequencing depth. RExMap re-analysis of existing 16S data from 29,349 individuals across 16 regions from around the world reveals a detailed landscape of gut microbial species across populations and geography. Moreover, RExMap identifies a core set of fifteen gut microbes shared by humans. Core microbes are established soon after birth and closely associate with BMI across multiple independent studies. RExMap and the human microbiome dataset are presented as resources with which to explore the role of the human microbiome.}, }
@article {pmid37065164, year = {2023}, author = {Wan, X and Takala, TM and Huynh, VA and Ahonen, SL and Paulin, L and Björkroth, J and Sironen, T and Kant, R and Saris, P}, title = {Comparative genomics of 40 Weissella paramesenteroides strains.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1128028}, pmid = {37065164}, issn = {1664-302X}, abstract = {Weissella strains are often detected in spontaneously fermented foods. Because of their abilities to produce lactic acid and functional exopolysaccharides as well as their probiotic traits, Weissella spp. improve not only the sensorial properties but also nutritional values of the fermented food products. However, some Weissella species have been associated with human and animal diseases. In the era of vast genomic sequencing, new genomic/genome data are becoming available to the public on daily pace. Detailed genomic analyses are due to provide a full understanding of individual Weissella species. In this study, the genomes of six Weissella paramesenteroides strains were de novo sequenced. The genomes of 42 W. paramesenteroides strains were compared to discover their metabolic and functional potentials in food fermentation. Comparative genomics and metabolic pathway reconstructions revealed that W. paramesenteroides is a compact group of heterofermentative bacteria with good capacity of producing secondary metabolites and vitamin Bs. Since the strains rarely harbored plasmid DNA, they did not commonly possess the genes associated with bacteriocin production. All 42 strains were shown to bear vanT gene from the glycopeptide resistance gene cluster vanG. Yet none of the strains carried virulence genes.}, }
@article {pmid37065142, year = {2023}, author = {Wang, X and Chen, D and Du, J and Cheng, K and Fang, C and Liao, X and Liu, Y and Sun, J and Lian, X and Ren, H}, title = {Occupational exposure in swine farm defines human skin and nasal microbiota.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1117866}, pmid = {37065142}, issn = {1664-302X}, abstract = {Anthropogenic environments take an active part in shaping the human microbiome. Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. By high-throughput sequencing, we showed that occupational exposure compositionally and functionally reshaped the volunteers' skin and nasal microbiota. The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion.}, }
@article {pmid37054680, year = {2023}, author = {Shen, J and Zhang, J and Mo, L and Li, Y and Li, Y and Li, C and Kuang, X and Tao, Z and Qu, Z and Wu, L and Chen, J and Liu, S and Zeng, L and He, Z and Chen, Z and Deng, Y and Zhang, T and Li, B and Dai, L and Ma, Y}, title = {Large-scale phage cultivation for commensal human gut bacteria.}, journal = {Cell host &amp; microbe}, volume = {31}, number = {4}, pages = {665-677.e7}, doi = {10.1016/j.chom.2023.03.013}, pmid = {37054680}, issn = {1934-6069}, mesh = {Humans ; *Bacteriophages ; *Gastrointestinal Microbiome/genetics ; Bacteria/genetics ; *Microbiota ; Symbiosis ; }, abstract = {Phages are highly abundant in the human gut, yet most of them remain uncultured. Here, we present a gut phage isolate collection (GPIC) containing 209 phages for 42 commensal human gut bacterial species. Genome analysis of the phages identified 34 undescribed genera. We discovered 22 phages from the Salasmaviridae family that have small genomes (∼10-20 kbp) and infect Gram-positive bacteria. Two phages from a candidate family, Paboviridae, with high prevalence in the human gut were also identified. Infection assays showed that Bacteroides and Parabacteroides phages are specific to a bacterial species, and strains of the same species also exhibit substantial variations in phage susceptibility. A cocktail of 8 phages with a broad host range for Bacteroides fragilis strains effectively reduced their abundance in complex host-derived communities in vitro. Our study expands the diversity of cultured human gut bacterial phages and provides a valuable resource for human microbiome engineering.}, }
@article {pmid37047594, year = {2023}, author = {Laterza, L and Putignani, L and Settanni, CR and Petito, V and Varca, S and De Maio, F and Macari, G and Guarrasi, V and Gremese, E and Tolusso, B and Wlderk, G and Pirro, MA and Fanali, C and Scaldaferri, F and Turchini, L and Amatucci, V and Sanguinetti, M and Gasbarrini, A}, title = {Ecology and Machine Learning-Based Classification Models of Gut Microbiota and Inflammatory Markers May Evaluate the Effects of Probiotic Supplementation in Patients Recently Recovered from COVID-19.}, journal = {International journal of molecular sciences}, volume = {24}, number = {7}, pages = {}, pmid = {37047594}, issn = {1422-0067}, support = {na//Actial Farmaceutica/ ; na//Fondazione Roma/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Citrulline ; *COVID-19 ; *Probiotics/therapeutic use/pharmacology ; Cytokines ; Bifidobacterium ; Machine Learning ; }, abstract = {Gut microbiota (GM) modulation can be investigated as possible solution to enhance recovery after COVID-19. An open-label, single-center, single-arm, pilot, interventional study was performed by enrolling twenty patients recently recovered from COVID-19 to investigate the role of a mixed probiotic, containing Lactobacilli, Bifidobacteria and Streptococcus thermophilus, on gastrointestinal symptoms, local and systemic inflammation, intestinal barrier integrity and GM profile. Gastrointestinal Symptom Rating Scale, cytokines, inflammatory, gut permeability, and integrity markers were evaluated before (T0) and after 8 weeks (T1) of probiotic supplementation. GM profiling was based on 16S-rRNA targeted-metagenomics and QIIME 2.0, LEfSe and PICRUSt computational algorithms. Multiple machine learning (ML) models were trained to classify GM at T0 and T1. A statistically significant reduction of IL-6 (p < 0.001), TNF-α (p < 0.001) and IL-12RA (p < 0.02), citrulline (p value < 0.001) was reported at T1. GM global distribution and microbial biomarkers strictly reflected probiotic composition, with a general increase in Bifidobacteria at T1. Twelve unique KEGG orthologs were associated only to T0, including tetracycline resistance cassettes. ML classified the GM at T1 with 100% score at phylum level. Bifidobacteriaceae and Bifidobacterium spp. inversely correlated to reduction of citrulline and inflammatory cytokines. Probiotic supplementation during post-COVID-19 may trigger anti-inflammatory effects though Bifidobacteria and related-metabolism enhancement.}, }
@article {pmid37046097, year = {2023}, author = {Metwaly, A and Haller, D}, title = {Elucidating the transmission landscape of the human microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {20}, number = {7}, pages = {415-416}, pmid = {37046097}, issn = {1759-5053}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; }, }
@article {pmid37042769, year = {2023}, author = {Ma, X and Sun, T and Zhou, J and Zhi, M and Shen, S and Wang, Y and Gu, X and Li, Z and Gao, H and Wang, P and Feng, Q}, title = {Pangenomic Study of Fusobacterium nucleatum Reveals the Distribution of Pathogenic Genes and Functional Clusters at the Subspecies and Strain Levels.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0518422}, pmid = {37042769}, issn = {2165-0497}, mesh = {*Fusobacterium nucleatum/genetics ; Phylogeny ; *Genomics ; Base Sequence ; Virulence Factors/genetics ; }, abstract = {Fusobacterium nucleatum is a prevalent periodontal pathogen and is associated with many systemic diseases. Our knowledge of the genomic characteristics and pathogenic effectors of different F. nucleatum strains is limited. In this study, we completed the whole genome assembly of the 4 F. nucleatum strains and carried out a comprehensive pangenomic study of 30 strains with their complete genome sequences. Phylogenetic analysis revealed that the F. nucleatum strains are mainly divided into 4 subspecies, while 1 of the sequenced strains was classified into a new subspecies. Gene composition analysis revealed that a total of 517 "core/soft-core genes" with housekeeping functions widely distributed in almost all the strains. Each subspecies had a unique gene cluster shared by strains within the subspecies. Analysis of the virulence factors revealed that many virulence factors were widely distributed across all the strains, with some present in multiple copies. Some virulence genes showed no consistent occurrence rule at the subspecies level and were specifically distributed in certain strains. The genomic islands mainly revealed strain-specific characteristics instead of subspecies level consistency, while CRISPR types and secondary metabolite biosynthetic gene clusters were identically distributed in F. nucleatum strains from the same subspecies. The variation in amino acid sites in the adhesion protein FadA did not affect the monomer and dimer 3D structures, but it may affect the binding surface and the stability of binding to host receptors. This study provides a basis for the pathogenic study of F. nucleatum at the subspecies and strain levels. IMPORTANCE We used F. nucleatum as an example to analyze the genomic characteristics of oral pathogens at the species, subspecies, and strain levels and elucidate the similarities and differences in functional genes and virulence factors among different subspecies/strains of the same oral pathogen. We believe that the unique biological characteristics of each subspecies/strain can be attributed to the differences in functional gene clusters or the presence/absence of certain virulence genes. This study showed that F. nucleatum strains from the same subspecies had similar functional gene compositions, CRISPR types, and secondary metabolite biosynthetic gene clusters, while pathogenic genes, such as virulence genes, antibiotic resistance genes, and GIs, had more strain level specificity. The findings of this study suggest that, for microbial pathogenicity studies, we should carefully consider the subspecies/strains being used, as different strains may vary greatly.}, }
@article {pmid37040017, year = {2023}, author = {Vitetta, L}, title = {Letter on "Role of gut microbiome in immune regulation and immune checkpoint therapy of colorectal cancer".}, journal = {Medical oncology (Northwood, London, England)}, volume = {40}, number = {5}, pages = {143}, pmid = {37040017}, issn = {1559-131X}, mesh = {Humans ; *Gastrointestinal Microbiome ; Immunotherapy ; *Colorectal Neoplasms ; Tumor Microenvironment ; }, abstract = {Investigations that decipher the human microbiome have reformed the way medicine is focusing on bacteria. An interesting research review recently published in the journal of Digestive Diseases and Sciences conceivably linked adjunctive commensal intestinal bacteria with the capacity to modulate the immune microenvironment towards immune checkpoint inhibitor (ICIs) efficacy of cancer immunotherapy. Evidence has emerged that the intestinal microbiome can modulate outcomes to ICIs therapies via two major mechanisms, namely mechanisms that are antigen-specific (i.e., epitopes are shared between microbial and tumour antigens that can enhance or reduce anti-tumour immune responses) and those mechanisms that are antigen-independent (i.e., modulation of responses to ICIs by engaging innate and/or adaptive immune cells).}, }
@article {pmid37039671, year = {2023}, author = {Gu, W and Koh, H and Jang, H and Lee, B and Kang, B}, title = {MiSurv: an Integrative Web Cloud Platform for User-Friendly Microbiome Data Analysis with Survival Responses.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0505922}, pmid = {37039671}, issn = {2165-0497}, mesh = {Humans ; Cloud Computing ; *Diabetes Mellitus, Type 1 ; *Gastrointestinal Microbiome ; *Microbiota ; }, abstract = {Investigators have studied the treatment effects on human health or disease, the treatment effects on human microbiome, and the roles of the microbiome on human health or disease. Especially, in a clinical trial, investigators commonly trace disease status over a lengthy period to survey the sequential disease progression for different treatment groups (e.g., treatment versus placebo, new treatment versus old treatment). Hence, disease responses are often available in the form of survival (i.e., time-to-event) responses stratified by treatment groups. While the recent web cloud platforms have enabled user-friendly microbiome data processing and analytics, there is currently no web cloud platform to analyze microbiome data with survival responses. Therefore, we introduce here an integrative web cloud platform, called MiSurv, for comprehensive microbiome data analysis with survival responses. IMPORTANCE MiSurv consists of a data processing module and its following four data analytic modules: (i) Module 1: Comparative survival analysis between treatment groups, (ii) Module 2: Comparative analysis in microbial composition between treatment groups, (iii) Module 3: Association testing between microbial composition and survival responses, (iv) Module 4: Prediction modeling using microbial taxa on survival responses. We demonstrate its use through an example trial on the effects of antibiotic use on the survival rate against type 1 diabetes (T1D) onset and gut microbiome composition, respectively, and the effects of the gut microbiome on the survival rate against T1D onset. MiSurv is freely available on our web server (http://misurv.micloud.kr) or can alternatively run on the user's local computer (https://github.com/wg99526/MiSurvGit).}, }
@article {pmid37034781, year = {2023}, author = {Boodaghidizaji, M and Jungles, T and Chen, T and Zhang, B and Landay, A and Keshavarzian, A and Hamaker, B and Ardekani, A}, title = {Machine learning based gut microbiota pattern and response to fiber as a diagnostic tool for chronic inflammatory diseases.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2023.03.27.534466}, pmid = {37034781}, issn = {2692-8205}, abstract = {Gut microbiota has been implicated in the pathogenesis of multiple gastrointestinal (GI) and systemic metabolic and inflammatory disorders where disrupted gut microbiota composition and function (dysbiosis) has been found in multiple studies. Thus, human microbiome data has a potential to be a great source of information for the diagnosis and disease characteristics (phenotypes, disease course, therapeutic response) of diseases with dysbiotic microbiota community. However, multiple attempts to leverage gut microbiota taxonomic data for diagnostic and disease characterization have failed due to significant inter-individual variability of microbiota community and overlap of disrupted microbiota communities among multiple diseases. One potential approach is to look at the microbiota community pattern and response to microbiota modifiers like dietary fiber in different disease states. This approach is now feasible by availability of machine learning that is able to identify hidden patterns in the human microbiome and predict diseases. Accordingly, the aim of our study was to test the hypothesis that application of machine learning algorithms can distinguish stool microbiota pattern and microbiota response to fiber between diseases where overlapping dysbiotic microbiota have been previously reported. Here, we have applied machine learning algorithms to distinguish between Parkinson's disease, Crohn's disease (CD), ulcerative colitis (UC), human immune deficiency virus (HIV), and healthy control (HC) subjects in the presence and absence of fiber treatments. We have shown that machine learning algorithms can classify diseases with accuracy as high as 95%. Furthermore, machine learning methods applied to the microbiome data to predict UC vs CD led to prediction accuracy as high as 90%.}, }
@article {pmid37032359, year = {2023}, author = {Spatz, M and Da Costa, G and Ventin-Holmberg, R and Planchais, J and Michaudel, C and Wang, Y and Danne, C and Lapiere, A and Michel, ML and Kolho, KL and Langella, P and Sokol, H and Richard, ML}, title = {Antibiotic treatment using amoxicillin-clavulanic acid impairs gut mycobiota development through modification of the bacterial ecosystem.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {73}, pmid = {37032359}, issn = {2049-2618}, mesh = {Humans ; Mice ; Animals ; *Amoxicillin-Potassium Clavulanate Combination/pharmacology ; Anti-Bacterial Agents/pharmacology ; Gastrointestinal Tract/microbiology ; *Microbiota ; Fungi ; Bacteria/genetics ; }, abstract = {BACKGROUND: Effects of antibiotics on gut bacteria have been widely studied, but very little is known about the consequences of such treatments on the fungal microbiota (mycobiota). It is commonly believed that fungal load increases in the gastrointestinal tract following antibiotic treatment, but better characterization is clearly needed of how antibiotics directly or indirectly affect the mycobiota and thus the entire microbiota.<br><br>DESIGN: We used samples from humans (infant cohort) and mice (conventional and human microbiota-associated mice) to study the consequences of antibiotic treatment (amoxicillin-clavulanic acid) on the intestinal microbiota. Bacterial and fungal communities were subjected to qPCR or 16S and ITS2 amplicon-based sequencing for microbiota analysis. In vitro assays further characterized bacterial-fungal interactions, with mixed cultures between specific bacteria and fungi.<br><br>RESULTS: Amoxicillin-clavulanic acid treatment triggered a decrease in the total fungal population in mouse feces, while other antibiotics had opposite effects on the fungal load. This decrease is accompanied by a total remodelling of the fungal population with the enrichment in Aspergillus, Cladosporium, and Valsa genera. In the presence of amoxicillin-clavulanic acid, microbiota analysis showed a remodeling of bacterial microbiota with an increase in specific bacteria belonging to the Enterobacteriaceae. Using in vitro assays, we isolated different Enterobacteriaceae species and explored their effect on different fungal strains. We showed that Enterobacter hormaechei was able to reduce the fungal population in vitro and in vivo through yet unknown mechanisms.<br><br>CONCLUSIONS: Bacteria and fungi have strong interactions within the microbiota; hence, the perturbation initiated by an antibiotic treatment targeting the bacterial community can have complex consequences and can induce opposite alterations of the mycobiota. Interestingly, amoxicillin-clavulanic acid treatment has a deleterious effect on the fungal community, which may have been partially due to the overgrowth of specific bacterial strains with inhibiting or competing effects on fungi. This study provides new insights into the interactions between fungi and bacteria of the intestinal microbiota and might offer new strategies to modulate gut microbiota equilibrium. Video Abstract.}, }
@article {pmid37032329, year = {2023}, author = {Bazant, W and Blevins, AS and Crouch, K and Beiting, DP}, title = {Improved eukaryotic detection compatible with large-scale automated analysis of metagenomes.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {72}, pmid = {37032329}, issn = {2049-2618}, mesh = {Humans ; *Metagenome/genetics ; Eukaryota/genetics ; *Microbiota/genetics ; Bacteria/genetics ; Archaea/genetics ; Metagenomics/methods ; }, abstract = {BACKGROUND: Eukaryotes such as fungi and protists frequently accompany bacteria and archaea in microbial communities. Unfortunately, their presence is difficult to study with "shotgun" metagenomic sequencing since prokaryotic signals dominate in most environments. Recent methods for eukaryotic detection use eukaryote-specific marker genes, but they do not incorporate strategies to handle the presence of eukaryotes that are not represented in the reference marker gene set, and they are not compatible with web-based tools for downstream analysis.<br><br>RESULTS: Here, we present CORRAL (for Clustering Of Related Reference ALignments), a tool for the identification of eukaryotes in shotgun metagenomic data based on alignments to eukaryote-specific marker genes and Markov clustering. Using a combination of simulated datasets, mock community standards, and large publicly available human microbiome studies, we demonstrate that our method is not only sensitive and accurate but is also capable of inferring the presence of eukaryotes not included in the marker gene reference, such as novel strains. Finally, we deploy CORRAL on our MicrobiomeDB.org resource, producing an atlas of eukaryotes present in various environments of the human body and linking their presence to study covariates.<br><br>CONCLUSIONS: CORRAL allows eukaryotic detection to be automated and carried out at scale. Implementation of CORRAL in MicrobiomeDB.org creates a running atlas of microbial eukaryotes in metagenomic studies. Since our approach is independent of the reference used, it may be applicable to other contexts where shotgun metagenomic reads are matched against redundant but non-exhaustive databases, such as the identification of bacterial virulence genes or taxonomic classification of viral reads. Video Abstract.}, }
@article {pmid37022232, year = {2023}, author = {Zimmerman, S and Tierney, BT and Patel, CJ and Kostic, AD}, title = {Quantifying Shared and Unique Gene Content across 17 Microbial Ecosystems.}, journal = {mSystems}, volume = {8}, number = {2}, pages = {e0011823}, pmid = {37022232}, issn = {2379-5077}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; R01 AI127250/AI/NIAID NIH HHS/United States ; R01 ES032470/ES/NIEHS NIH HHS/United States ; T32 DK110919/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/genetics ; Metagenome/genetics ; *Gastrointestinal Microbiome/genetics ; Metagenomics/methods ; Genome, Bacterial ; }, abstract = {Measuring microbial diversity is traditionally based on microbe taxonomy. Here, in contrast, we aimed to quantify heterogeneity in microbial gene content across 14,183 metagenomic samples spanning 17 ecologies, including 6 human associated, 7 nonhuman host associated, and 4 in other nonhuman host environments. In total, we identified 117,629,181 nonredundant genes. The vast majority of genes (66%) occurred in only one sample (i.e., "singletons"). In contrast, we found 1,864 sequences present in every metagenome, but not necessarily every bacterial genome. Additionally, we report data sets of other ecology-associated genes (e.g., abundant in only gut ecosystems) and simultaneously demonstrated that prior microbiome gene catalogs are both incomplete and inaccurately cluster microbial genetic life (e.g., at gene sequence identities that are too restrictive). We provide our results and the sets of environmentally differentiating genes described above at http://www.microbial-genes.bio. IMPORTANCE The amount of shared genetic elements has not been quantified between the human microbiome and other host- and non-host-associated microbiomes. Here, we made a gene catalog of 17 different microbial ecosystems and compared them. We show that most species shared between environment and human gut microbiomes are pathogens and that prior gene catalogs described as "nearly complete" are far from it. Additionally, over two-thirds of all genes only appear in a single sample, and only 1,864 genes (0.001%) are found in all types of metagenomes. These results highlight the large diversity between metagenomes and reveal a new, rare class of genes, those found in every type of metagenome, but not every microbial genome.}, }
@article {pmid37022154, year = {2023}, author = {Mahmud, MR and Jian, C and Uddin, MK and Huhtinen, M and Salonen, A and Peltoniemi, O and Venhoranta, H and Oliviero, C}, title = {Impact of Intestinal Microbiota on Growth Performance of Suckling and Weaned Piglets.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0374422}, pmid = {37022154}, issn = {2165-0497}, mesh = {Swine ; Animals ; Female ; Weaning ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; Feces/microbiology ; }, abstract = {Small-scale studies investigating the relationship between pigs' intestinal microbiota and growth performance have generated inconsistent results. We hypothesized that on farms under favorable environmental conditions (e.g., promoting sow nest-building behavior, high colostrum production, low incidence of diseases and minimal use of antimicrobials), the piglet gut microbiota may develop toward a population that promotes growth and reduces pathogenic bacteria. Using 16S rRNA gene amplicon sequencing, we sampled and profiled the fecal microbiota from 170 individual piglets throughout suckling and postweaning periods (in total 670 samples) to track gut microbiota development and its potential association with growth. During the suckling period, the dominant genera were Lactobacillus and Bacteroides, the latter being gradually replaced by Clostridium sensu scricto 1 as piglets aged. The gut microbiota during the nursery stage, not the suckling period, predicted the average daily growth (ADG) of piglets. The relative abundances of SCFA-producing genera, in particular Faecalibacterium, Megasphaera, Mitsuokella, and Subdoligranulum, significantly correlated with high ADG of weaned piglets. In addition, the succession of the gut microbiota in high-ADG piglets occurred faster and stabilized sooner upon weaning, whereas the gut microbiota of low-ADG piglets continued to mature after weaning. Overall, our findings suggest that weaning is the major driver of gut microbiota variation in piglets with different levels of overall growth performance. This calls for further research to verify if promotion of specific gut microbiota, identified here at weaning transition, is beneficial for piglet growth. IMPORTANCE The relationship between pigs' intestinal microbiota and growth performance is of great importance for improving piglets' health and reducing antimicrobial use. We found that gut microbiota variation is significantly associated with growth during weaning and the early nursery period. Importantly, transitions toward a mature gut microbiota enriched with fiber-degrading bacteria mostly complete upon weaning in piglets with better growth. Postponing the weaning age may therefore favor the development of fiber degrading gut bacteria, conferring the necessary capacity to digest and harvest solid postweaning feed. The bacterial taxa associated with piglet growth identified herein hold potential to improve piglet growth and health.}, }
@article {pmid37019665, year = {2023}, author = {Ka, Y and Ito, R and Nozu, R and Tomiyama, K and Ueno, M and Ogura, T and Takahashi, R}, title = {Establishment of a human microbiome- and immune system-reconstituted dual-humanized mouse model.}, journal = {Experimental animals}, volume = {72}, number = {3}, pages = {402-412}, pmid = {37019665}, issn = {1881-7122}, mesh = {Mice ; Animals ; Humans ; Mice, Inbred NOD ; *Immune System ; Hematopoietic Stem Cells ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Mice, SCID ; }, abstract = {Humanized mice are widely used to study the human immune system in vivo and investigate therapeutic targets for various human diseases. Immunodeficient NOD/Shi-scid-IL2rγ[null] (NOG) mice transferred with human hematopoietic stem cells are a useful model for studying human immune systems and analyzing engrafted human immune cells. The gut microbiota plays a significant role in the development and function of immune cells and the maintenance of immune homeostasis; however, there is currently no available animal model that has been reconstituted with human gut microbiota and immune systems in vivo. In this study, we established a new model of CD34[+] cell-transferred humanized germ-free NOG mice using an aseptic method. Flow cytometric analysis revealed that the germ-free humanized mice exhibited a lower level of human CD3[+] T cells than the SPF humanized mice. Additionally, we found that the human CD3[+] T cells slightly increased after transplanting human gut microbiota into the germ-free humanized mice, suggesting that the human microbiota supports T cell proliferation or maintenance in humanized mice colonized by the gut microbiota. Consequently, the dual-humanized mice may be useful for investigating the physiological role of the gut microbiota in human immunity in vivo and for application as a new humanized mouse model in cancer immunology.}, }
@article {pmid37010974, year = {2023}, author = {Reynolds, T and Noorbakhsh, S and Smith, R}, title = {Microbiome Contributions to Health.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {213-219}, pmid = {37010974}, issn = {1557-8674}, support = {T32 GM095442/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Gastrointestinal Tract/microbiology ; Lung ; Bacteria ; }, abstract = {The human microbiome is vast and is present in spaces previously thought to be sterile such as the lungs. A healthy microbiome is diverse and functions in an adaptive way to support local as well as organism health and function. Furthermore, a normal microbiome is essential for normal immune system development rendering the array of microbes that live in and on the human body key components of homeostasis. A wide array of clinical conditions and interventions including anesthesia, analgesia, and surgical intervention may derange the human microbiome in a maladaptive fashion with bacterial responses spanning decreased diversity to transformation to a pathogenic phenotype. Herein, we explore the normal microbiome of the skin, gastrointestinal tract, and the lungs as prototype sites to describe the influence of the microbiomes in each of those locations on health, and how care may derange those relations.}, }
@article {pmid37010972, year = {2023}, author = {Leonard, JM and Toro, DD}, title = {Defining the Microbiome Components (Bacteria, Viruses, Fungi) and Microbiome Geodiversity.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {208-212}, pmid = {37010972}, issn = {1557-8674}, support = {K08 GM137323/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Bacteria ; *Microbiota/genetics ; Fungi ; *Viruses ; }, abstract = {The recognition that a resident community of microbes contributes substantially to human health and disease is one of the emerging great discoveries in modern medicine. This collection of bacteria, archaea, fungi, viruses, and eukaryotes are referred to as microbiota, which together with the individual tissues they inhabit is defined as our individual microbiome. Recent advances in modern DNA sequencing technologies permit the identification, description, and characterization of these microbial communities as well as their variations within and between individuals and groups. This complex understanding of the human microbiome is supported by a rapidly expanding field of inquiry and offers the potential to significantly impact the treatment of a wide variety of disease states. This review explores the recent findings associated with the various components of the human microbiome, and the geodiversity of microbial communities between different tissue types, individuals, and clinical conditions.}, }
@article {pmid37010971, year = {2023}, author = {Godley, FA and Shogan, BD and Hyman, NH}, title = {Role of the Microbiome in Malignancy.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {271-275}, pmid = {37010971}, issn = {1557-8674}, support = {K08 CA248957/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; *Microbiota ; *Colorectal Neoplasms ; Carcinogenesis ; Inflammation ; }, abstract = {The conceptual underpinning of carcinogenesis has been strongly influenced by an expanded understanding of the human microbiome. Malignancy risks in diverse organs have been uniquely tied to aspects of the resident microbiota in different organs and systems including the colon, lungs, pancreas, ovaries, uterine cervix, and stomach; other organs are increasingly linked to maladaptive aspects of the microbiome as well. In this way, the maladaptive microbiome may be termed an oncobiome. Microbe-driven inflammation, anti-inflammation, and mucosal protection failure, as well as diet-induced microbiome derangement are all mechanisms that influence malignancy risk. Therefore, they also offer potential avenues of diagnostic and therapeutic intervention to modify malignancy risk, and to perhaps interrupt progression toward cancer in different sites. Each of these mechanisms will be explored using colorectal malignancy as a prototype condition to demonstrate the microbiome's role in carcinogenesis.}, }
@article {pmid37010968, year = {2023}, author = {Leonard, JM and Pascual, JL and Kaplan, LJ}, title = {Dysbiome and Its Role in Surgically Relevant Medical Disease.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {226-231}, pmid = {37010968}, issn = {1557-8674}, support = {K08 GM137323/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Inflammatory Bowel Diseases ; *Microbiota ; *Gastrointestinal Microbiome ; Skin ; }, abstract = {Several surgically relevant conditions are directly or indirectly influenced by the human microbiome. Different microbiomes may be found within, or along, specific organs and intra-organ variation is common. Such variations include those found along the course of the gastrointestinal tract as well as those on different regions of the skin. A variety of physiologic stressors and care interventions may derange the native microbiome. A deranged microbiome is termed a dysbiome and is characterized by decreased diversity and an increase in the proportion of potentially pathogenic organisms; the elaboration of virulence factors coupled with clinical consequences defines a pathobiome. Specific conditions such as Clostridium difficile colitis, inflammatory bowel disease, obesity, and diabetes mellitus are tightly linked to a dysbiome or pathobiome. Additionally, massive transfusion after injury appears to derange the gastrointestinal microbiome as well. This review explores what is known about these surgically relevant clinical conditions to chart how non-surgical interventions may support surgical undertakings or potentially reduce the need for operation.}, }
@article {pmid37010965, year = {2023}, author = {Creel, JP and Maves, RC}, title = {The Microbiome and Antimicrobial Stewardship in Surgical Patients.}, journal = {Surgical infections}, volume = {24}, number = {3}, pages = {220-225}, doi = {10.1089/sur.2022.422}, pmid = {37010965}, issn = {1557-8674}, mesh = {Humans ; *Antimicrobial Stewardship ; *Anti-Infective Agents ; *Microbiota ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/drug therapy ; }, abstract = {Abstract The human microbiome plays a critical role in health and disease. The microbiota of the human body undergoes disruptions in critical illness, in part due to alterations in physiology but also as the result of medical interventions, most notably antimicrobial drug administration. These alterations may lead to a significant dysbiosis, with increased risks of multi-drug-resistant organism-based secondary infections, Clostridioides difficile promotion, and other infection-related complications. Antimicrobial stewardship is a process that seeks to optimize antimicrobial drug prescription, with recent evidence emphasizing shorter courses of therapy, earlier transitions from empiric to pathogen-specific regimens, and enhanced diagnostic testing. Through a combination of prudent stewardship and wise use of diagnostic testing, clinicians can improve outcomes, reduce the risk of antimicrobial resistance, and help improve the integrity of the microbiome.}, }
@article {pmid37005490, year = {2023}, author = {Goenka, A and Khan, F and Verma, B and Sinha, P and Dmello, CC and Jogalekar, MP and Gangadaran, P and Ahn, BC}, title = {Tumor microenvironment signaling and therapeutics in cancer progression.}, journal = {Cancer communications (London, England)}, volume = {43}, number = {5}, pages = {525-561}, pmid = {37005490}, issn = {2523-3548}, mesh = {Humans ; *Tumor Microenvironment ; *Neoplasms/metabolism ; Signal Transduction ; Neoplastic Processes ; Receptors, Chemokine/therapeutic use ; Chemokines/pharmacology/therapeutic use ; }, abstract = {Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss the clinical advances in the prevalent and newly discovered signaling pathways in the TME, the immune checkpoints and immunosuppressive chemokines, and currently used inhibitors targeting these pathways. These include both intrinsic and non-autonomous tumor cell signaling pathways in the TME: protein kinase C (PKC) signaling, Notch, and transforming growth factor (TGF-β) signaling, Endoplasmic Reticulum (ER) stress response, lactate signaling, Metabolic reprogramming, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and Siglec signaling pathways. We also discuss the recent advances in Programmed Cell Death Protein 1 (PD-1), Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte Activating Gene 3 (LAG3) immune checkpoint inhibitors along with the C-C chemokine receptor 4 (CCR4)- C-C class chemokines 22 (CCL22)/ and 17 (CCL17), C-C chemokine receptor type 2 (CCR2)- chemokine (C-C motif) ligand 2 (CCL2), C-C chemokine receptor type 5 (CCR5)- chemokine (C-C motif) ligand 3 (CCL3) chemokine signaling axis in the TME. In addition, this review provides a holistic understanding of the TME as we discuss the three-dimensional and microfluidic models of the TME, which are believed to recapitulate the original characteristics of the patient tumor and hence may be used as a platform to study new mechanisms and screen for various anti-cancer therapies. We further discuss the systemic influences of gut microbiota in TME reprogramming and treatment response. Overall, this review provides a comprehensive analysis of the diverse and most critical signaling pathways in the TME, highlighting the associated newest and critical preclinical and clinical studies along with their underlying biology. We highlight the importance of the most recent technologies of microfluidics and lab-on-chip models for TME research and also present an overview of extrinsic factors, such as the inhabitant human microbiome, which have the potential to modulate TME biology and drug responses.}, }
@article {pmid37003965, year = {2023}, author = {Syama, K and Jothi, JAA and Khanna, N}, title = {Automatic disease prediction from human gut metagenomic data using boosting GraphSAGE.}, journal = {BMC bioinformatics}, volume = {24}, number = {1}, pages = {126}, pmid = {37003965}, issn = {1471-2105}, mesh = {Humans ; Metagenome ; *Microbiota/genetics ; Machine Learning ; Metagenomics/methods ; *Inflammatory Bowel Diseases/genetics ; *Colorectal Neoplasms/genetics ; }, abstract = {BACKGROUND: The human microbiome plays a critical role in maintaining human health. Due to the recent advances in high-throughput sequencing technologies, the microbiome profiles present in the human body have become publicly available. Hence, many works have been done to analyze human microbiome profiles. These works have identified that different microbiome profiles are present in healthy and sick individuals for different diseases. Recently, several computational methods have utilized the microbiome profiles to automatically diagnose and classify the host phenotype.<br><br>RESULTS: In this work, a novel deep learning framework based on boosting GraphSAGE is proposed for automatic prediction of diseases from metagenomic data. The proposed framework has two main components, (a). Metagenomic Disease graph (MD-graph) construction module, (b). Disease prediction Network (DP-Net) module. The graph construction module constructs a graph by considering each metagenomic sample as a node in the graph. The graph captures the relationship between the samples using a proximity measure. The DP-Net consists of a boosting GraphSAGE model which predicts the status of a sample as sick or healthy. The effectiveness of the proposed method is verified using real and synthetic datasets corresponding to diseases like inflammatory bowel disease and colorectal cancer. The proposed model achieved a highest AUC of 93%, Accuracy of 95%, F1-score of 95%, AUPRC of 95% for the real inflammatory bowel disease dataset and a best AUC of 90%, Accuracy of 91%, F1-score of 87% and AUPRC of 93% for the real colorectal cancer dataset.<br><br>CONCLUSION: The proposed framework outperforms other machine learning and deep learning models in terms of classification accuracy, AUC, F1-score and AUPRC for both synthetic and real metagenomic data.}, }
@article {pmid37002975, year = {2023}, author = {Stockdale, SR and Hill, C}, title = {Incorporating plasmid biology and metagenomics into a holistic model of the human gut microbiome.}, journal = {Current opinion in microbiology}, volume = {73}, number = {}, pages = {102307}, doi = {10.1016/j.mib.2023.102307}, pmid = {37002975}, issn = {1879-0364}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; Plasmids/genetics ; *Microbiota/genetics ; Bacteria/genetics ; Metagenomics ; }, abstract = {The human gut microbiome is often described as the collection of bacteria, archaea, fungi, protists, and viruses associated with an individual, with no acknowledgement of the plasmid constituents. However, like viruses, plasmids are autonomous intracellular replicating entities that can influence the genotype and phenotype of their host and mediate trans-kingdom interactions. Plasmids are frequently noted as vehicles for horizontal gene transfer and for spreading antibiotic resistance, yet their multifaceted contribution to mutualistic and antagonistic interactions within the human microbiome and impact on human health is overlooked. In this review, we highlight the importance of plasmids and their biological properties as overlooked components of microbiomes. Subsequent human microbiome studies should include dedicated analyses of plasmids, particularly as a holistic understanding of human-microbial interactions is required before effective and safe interventions can be implemented to improve human well-being.}, }
@article {pmid36998574, year = {2023}, author = {Haahtela, T and Alenius, H and Auvinen, P and Fyhrquist, N and von Hertzen, L and Jousilahti, P and Karisola, P and Laatikainen, T and Lehtimäki, J and Paalanen, L and Ruokolainen, L and Saarinen, K and Valovirta, E and Vasankari, T and Vlasoff, T and Erhola, M and Bousquet, J and Vartiainen, E and Mäkelä, MJ}, title = {A short history from Karelia study to biodiversity and public health interventions.}, journal = {Frontiers in allergy}, volume = {4}, number = {}, pages = {1152927}, pmid = {36998574}, issn = {2673-6101}, abstract = {Contact with natural environments enriches the human microbiome, promotes immune balance and protects against allergies and inflammatory disorders. In Finland, the allergy &amp; asthma epidemic became slowly visible in mid 1960s. After the World War II, Karelia was split into Finnish and Soviet Union (now Russia) territories. This led to more marked environmental and lifestyle changes in the Finnish compared with Russian Karelia. The Karelia Allergy Study 2002-2022 showed that allergic conditions were much more common on the Finnish side. The Russians had richer gene-microbe network and interaction than the Finns, which associated with better balanced immune regulatory circuits and lower allergy prevalence. In the Finnish adolescents, a biodiverse natural environment around the homes associated with lower occurrence of allergies. Overall, the plausible explanation of the allergy disparity was the prominent change in environment and lifestyle in the Finnish Karelia from 1940s to 1980s. The nationwide Finnish Allergy Programme 2008-2018 implemented the biodiversity hypothesis into practice by endorsing immune tolerance, nature contacts, and allergy health with favorable results. A regional health and environment programme, Nature Step to Health 2022-2032, has been initiated in the City of Lahti, EU Green Capital 2021. The programme integrates prevention of chronic diseases (asthma, diabetes, obesity, depression), nature loss, and climate crisis in the spirit of Planetary Health. Allergic diseases exemplify inappropriate immunological responses to natural environment. Successful management of the epidemics of allergy and other non-communicable diseases may pave the way to improve human and environmental health.}, }
@article {pmid36995244, year = {2023}, author = {Herviou, P and Balvay, A and Bellet, D and Bobet, S and Maudet, C and Staub, J and Alric, M and Leblond-Bourget, N and Delorme, C and Rabot, S and Denis, S and Payot, S}, title = {Transfer of the Integrative and Conjugative Element ICESt3 of Streptococcus thermophilus in Physiological Conditions Mimicking the Human Digestive Ecosystem.}, journal = {Microbiology spectrum}, volume = {11}, number = {3}, pages = {e0466722}, pmid = {36995244}, issn = {2165-0497}, mesh = {Animals ; Mice ; Humans ; *Streptococcus thermophilus/genetics ; Conjugation, Genetic ; Gastrointestinal Tract ; Gene Transfer, Horizontal ; *Microbiota ; }, abstract = {Metagenome analyses of the human microbiome suggest that horizontal gene transfer (HGT) is frequent in these rich and complex microbial communities. However, so far, only a few HGT studies have been conducted in vivo. In this work, three different systems mimicking the physiological conditions encountered in the human digestive tract were tested, including (i) the TNO gastro-Intestinal tract Model 1 (TIM-1) system (for the upper part of the intestine), (ii) the ARtificial COLon (ARCOL) system (to mimic the colon), and (iii) a mouse model. To increase the likelihood of transfer by conjugation of the integrative and conjugative element studied in the artificial digestive systems, bacteria were entrapped in alginate, agar, and chitosan beads before being placed in the different gut compartments. The number of transconjugants detected decreased, while the complexity of the ecosystem increased (many clones in TIM-1 but only one clone in ARCOL). No clone was obtained in a natural digestive environment (germfree mouse model). In the human gut, the richness and diversity of the bacterial community would offer more opportunities for HGT events to occur. In addition, several factors (SOS-inducing agents, microbiota-derived factors) that potentially increase in vivo HGT efficiency were not tested here. Even if HGT events are rare, expansion of the transconjugant clones can happen if ecological success is fostered by selecting conditions or by events that destabilize the microbial community. IMPORTANCE The human gut microbiota plays a key role in maintaining normal host physiology and health, but its homeostasis is fragile. During their transit in the gastrointestinal tract, bacteria conveyed by food can exchange genes with resident bacteria. New traits acquired by HGT (e.g., new catabolic properties, bacteriocins, antibiotic resistance) can impact the gut microbial composition and metabolic potential. We showed here that TIM-1, a system mimicking the upper digestive tract, is a useful tool to evaluate HGT events in conditions closer to the physiological ones. Another important fact pointed out in this work is that Enterococcus faecalis is a good candidate for foreign gene acquisition. Due to its high ability to colonize the gut and acquire mobile genetic elements, this commensal bacterium could serve as an intermediate for HGT in the human gut.}, }
@article {pmid36992511, year = {2023}, author = {Shafigh Kheljan, F and Sheikhzadeh Hesari, F and Aminifazl, MS and Skurnik, M and Goladze, S and Zarrini, G}, title = {Design of Phage-Cocktail-Containing Hydrogel for the Treatment of Pseudomonas aeruginosa-Infected Wounds.}, journal = {Viruses}, volume = {15}, number = {3}, pages = {}, pmid = {36992511}, issn = {1999-4915}, mesh = {Mice ; Animals ; *Bacteriophages ; Pseudomonas aeruginosa ; Hydrogels/pharmacology/therapeutic use ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Ciprofloxacin/pharmacology ; *Bacterial Infections/drug therapy ; Disease Models, Animal ; *Wound Infection/drug therapy ; }, abstract = {Recently, the treatment of infected wounds has become a global problem due to increased antibiotic resistance in bacteria. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa is often present in chronic skin infections, and it has become a threat to public health as it is increasingly multidrug resistant. Due to this, new measures to enable treatment of infections are necessary. Treatment of bacterial infections with bacteriophages, known as phage therapy, has been in use for a century, and has potential with its antimicrobial effect. The main purpose of this study was to create a phage-containing wound dressing with the ability to prevent bacterial infection and rapid wound healing without side effects. Several phages against P. aeruginosa were isolated from wastewater, and two polyvalent phages were used to prepare a phage cocktail. The phage cocktail was loaded in a hydrogel composed of polymers of sodium alginate (SA) and carboxymethyl cellulose (CMC). To compare the antimicrobial effects, hydrogels containing phages, ciprofloxacin, or phages plus ciprofloxacin were produced, and hydrogels without either. The antimicrobial effect of these hydrogels was investigated in vitro and in vivo using an experimental mouse wound infection model. The wound-healing process in different mouse groups showed that phage-containing hydrogels and antibiotic-containing hydrogels have almost the same antimicrobial effect. However, in terms of wound healing and pathological process, the phage-containing hydrogels performed better than the antibiotic alone. The best performance was achieved with the phage-antibiotic hydrogel, indicating a synergistic effect between the phage cocktail and the antibiotic. In conclusion, phage-containing hydrogels eliminate efficiently P. aeruginosa in wounds and may be a proper option for treating infectious wounds.}, }
@article {pmid36991500, year = {2023}, author = {Burckhardt, JC and Chong, DHY and Pett, N and Tropini, C}, title = {Gut commensal Enterocloster species host inoviruses that are secreted in vitro and in vivo.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {65}, pmid = {36991500}, issn = {2049-2618}, mesh = {Mice ; Animals ; Humans ; *Inovirus/genetics ; *Bacteriophages/genetics ; Bacteria ; Prophages/genetics ; *Gastrointestinal Microbiome ; Clostridiales ; }, abstract = {BACKGROUND: Bacteriophages in the family Inoviridae, or inoviruses, are under-characterized phages previously implicated in bacterial pathogenesis by contributing to biofilm formation, immune evasion, and toxin secretion. Unlike most bacteriophages, inoviruses do not lyse their host cells to release new progeny virions; rather, they encode a secretion system that actively pumps them out of the bacterial cell. To date, no inovirus associated with the human gut microbiome has been isolated or characterized.<br><br>RESULTS: In this study, we utilized in silico, in vitro, and in vivo methods to detect inoviruses in bacterial members of the gut microbiota. By screening a representative genome library of gut commensals, we detected inovirus prophages in Enterocloster spp.&#xa0;(formerly Clostridium spp.). We confirmed the secretion of inovirus particles in in vitro cultures of these organisms using imaging and qPCR. To assess how the gut abiotic environment, bacterial physiology, and inovirus secretion may be linked, we deployed a tripartite in vitro assay that progressively evaluated bacterial&#xa0;growth dynamics, biofilm formation, and inovirus secretion in the presence of changing osmotic environments. Counter to other inovirus-producing bacteria, inovirus production was not correlated with biofilm formation in Enterocloster spp. Instead, the Enterocloster strains had heterogeneous responses to changing osmolality levels relevant to gut physiology. Notably, increasing osmolality induced inovirus secretion in a strain-dependent manner. We confirmed inovirus secretion in a gnotobiotic mouse model inoculated with individual Enterocloster strains in vivo in unperturbed conditions. Furthermore, consistent with our in vitro observations, inovirus secretion was regulated by a changed osmotic environment in the gut due to osmotic laxatives.<br><br>CONCLUSION: In this study, we report on the detection and characterization of novel inoviruses from gut commensals in the Enterocloster genus. Together, our results demonstrate that human gut-associated bacteria can secrete inoviruses and begin to elucidate the environmental niche filled by inoviruses in commensal bacteria. Video Abstract.}, }
@article {pmid36991009, year = {2023}, author = {Liu, X and Zou, L and Nie, C and Qin, Y and Tong, X and Wang, J and Yang, H and Xu, X and Jin, X and Xiao, L and Zhang, T and Min, J and Zeng, Y and Jia, H and Hou, Y}, title = {Mendelian randomization analyses reveal causal relationships between the human microbiome and longevity.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {5127}, pmid = {36991009}, issn = {2045-2322}, support = {P01 AG031719/AG/NIA NIH HHS/United States ; }, mesh = {Aged, 80 and over ; Humans ; *Longevity/genetics ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; *Microbiota ; Lactobacillus acidophilus ; }, abstract = {Although recent studies have revealed the association between the human microbiome especially gut microbiota and longevity, their causality remains unclear. Here, we assess the causal relationships between the human microbiome (gut and oral microbiota) and longevity, by leveraging bidirectional two-sample Mendelian randomization (MR) analyses based on genome-wide association studies (GWAS) summary statistics of the gut and oral microbiome from the 4D-SZ cohort and longevity from the CLHLS cohort. We found that some disease-protected gut microbiota such as Coriobacteriaceae and Oxalobacter as well as the probiotic Lactobacillus amylovorus were related to increased odds of longevity, whereas the other gut microbiota such as colorectal cancer pathogen Fusobacterium nucleatum, Coprococcus, Streptococcus, Lactobacillus, and Neisseria were negatively associated with longevity. The reverse MR analysis further revealed genetically longevous individuals tended to have higher abundances of Prevotella and Paraprevotella but lower abundances of Bacteroides and Fusobacterium species. Few overlaps of gut microbiota-longevity interactions were identified across different populations. We also identified abundant links between the oral microbiome and longevity. The additional analysis suggested that centenarians genetically had a lower gut microbial diversity, but no difference in oral microbiota. Our findings strongly implicate these bacteria to play a role in human longevity and underscore the relocation of commensal microbes among different body sites that would need to be monitored for long and healthy life.}, }
@article {pmid36986037, year = {2023}, author = {Cappello, C and Tlais, AZA and Acin-Albiac, M and Lemos Junior, WJF and Pinto, D and Filannino, P and Rinaldi, F and Gobbetti, M and Di Cagno, R}, title = {Identification and Selection of Prospective Probiotics for Enhancing Gastrointestinal Digestion: Application in Pharmaceutical Preparations and Dietary Supplements.}, journal = {Nutrients}, volume = {15}, number = {6}, pages = {}, pmid = {36986037}, issn = {2072-6643}, mesh = {Animals ; Humans ; Prospective Studies ; *Probiotics ; *Lactobacillales ; Digestion ; Pharmaceutical Preparations ; }, abstract = {Our study investigated the effectiveness of 446 strains of lactic acid bacteria (LAB) belonging to different species and isolated from diverse sources (food, human, and animal) as potential probiotic candidates, with the perspective of producing dietary supplements or pharmacological formulations suitable for enhancing gastrointestinal digestion. The survival capability of all the isolates under harsh gastrointestinal tract conditions was evaluated, in which only 44 strains, named high-resistant, were selected for further food digestibility investigations. All 44 strains hydrolyzed raffinose and exhibited amino and iminopeptidase activities but at various extents, confirming species- and strain-specificity. After partial in vitro digestion mimicking oral and gastric digestive phases, food matrices were incubated with single strains for 24 h. Fermented partially digested matrices provided additional functional properties for some investigated strains by releasing peptides and increasing the release of highly bio-accessible free phenolic compounds. A scoring procedure was proposed as an effective tool to reduce data complexity and quantitively characterize the probiotic potential of each LAB strain, which could be more useful in the selection procedure of powerful probiotics.}, }
@article {pmid36984891, year = {2023}, author = {Qin, F and Li, J and Mao, T and Feng, S and Li, J and Lai, M}, title = {2 Hydroxybutyric Acid-Producing Bacteria in Gut Microbiome and Fusobacterium nucleatum Regulates 2 Hydroxybutyric Acid Level In Vivo.}, journal = {Metabolites}, volume = {13}, number = {3}, pages = {}, pmid = {36984891}, issn = {2218-1989}, support = {32170062//National Natural Science Foundation of China/ ; no. 2014//Jiangsu Shuang Chuang team/ ; }, abstract = {2-hydroxybutyric acid (2HB) serves as an important regulatory factor in a variety of diseases. The circulating level of 2HB in serum is significantly higher in multiple diseases, such as cancer and type 2 diabetes (T2D). However, there is currently no systematic study on 2HB-producing bacteria that demonstrates whether gut bacteria contribute to the circulating 2HB pool. To address this question, we used BLASTP to reveal the taxonomic profiling of 2HB-producing bacteria in the human microbiome, which are mainly distributed in the phylum Proteobacteria and Firmicutes. In vitro experiments showed that most gut bacteria (21/32) have at least one path to produce 2HB, which includes Aspartic acid, methionine, threonine, and 2-aminobutyric acid. Particularly, Fusobacterium nucleatum has the strongest ability to synthesize 2HB, which is sufficient to alter colon 2HB concentration in mice. Nevertheless, neither antibiotic (ABX) nor Fusobacterium nucleatum gavage significantly affected mouse serum 2HB levels during the time course of this study. Taken together, our study presents the profiles of 2HB-producing bacteria and demonstrates that gut microbiota was a major contributor to 2HB concentration in the intestinal lumen but a relatively minor contributor to serum 2HB concentration.}, }
@article {pmid36983812, year = {2023}, author = {Wazir, HU and Narang, P and Silvani, G and Mehner, C and Poole, K and Burke, C and Chou, J}, title = {Bacterial Virulence and Prevention for Human Spaceflight.}, journal = {Life (Basel, Switzerland)}, volume = {13}, number = {3}, pages = {}, pmid = {36983812}, issn = {2075-1729}, abstract = {With the advancement in reusable rocket propulsion technology, space tourist trips into outer space are now becoming a possibility at a cost-effective rate. As such, astronauts will face a host of health-related challenges, particularly on long-duration space missions where maintaining a balanced healthy microbiome is going to be vital for human survival in space exploration as well as mission success. The human microbiome involves a whole list of micro-organisms that reside in and on the human host, and plays an integral role in keeping the human host healthy. However, imbalances in the microbiome have been directly linked to many human diseases. Research findings have clearly shown that the outer space environment can directly affect the normal microbiome of astronauts when the astronaut is exposed to the microgravity environment. In this study, we show that the simulation of microgravity on earth can mimic the outer space microgravity environment. Staphylococus aureus (S. aureus) was chosen for this study as it is an opportunistic pathogen, which is part of the normal human skin microflora and the nasal passages. This study's results show that S. aureus proliferation was significantly increased under a microgravity environment compared to Earth's gravity conditions, which complements previous work performed on bacteria in the outer space environment in the International Space Station (ISS). This demonstrates that this technology can be utilised here on Earth to mimic the outer space environment and to study challenging health-related questions. This in return saves us the cost on conducting experiments in the ISS and can help advance knowledge at a faster rate and produce countermeasures to mitigate the negative side effects of the hostile outer space environment on humans.}, }
@article {pmid36983633, year = {2023}, author = {Kartti, S and Bendani, H and Boumajdi, N and Bouricha, EM and Zarrik, O and El Agouri, H and Fokar, M and Aghlallou, Y and El Jaoudi, R and Belyamani, L and Elkhannoussi, B and Ibrahimi, A}, title = {Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues.}, journal = {Journal of personalized medicine}, volume = {13}, number = {3}, pages = {}, pmid = {36983633}, issn = {2075-4426}, abstract = {Breast cancer is one of the main global priorities in terms of public health. It remains the most frequent cancer in women and is the leading cause of their death. The human microbiome plays various roles in maintaining health by ensuring a dynamic balance with the host or in the appearance of various pathologies including breast cancer. In this study, we performed an analysis of bacterial signature differences between tumor and adjacent tissues of breast cancer patients in Morocco. Using 16S rRNA gene sequencing, we observed that adjacent tissue contained a much higher percentage of the Gammaproteobacteria class (35.7%) while tumor tissue was characterized by a higher percentage of Bacilli and Actinobacteria classes, with about 18.8% and 17.2% average abundance, respectively. Analysis of tumor subtype revealed enrichment of genus Sphingomonodas in TNBC while Sphingomonodas was predominant in HER2. The LEfSe and the genus level heatmap analysis revealed a higher abundance of the Rothia genus in tumor tissues. The identified microbial communities can therefore serve as potential biomarkers for prognosis and diagnosis, while also helping to develop new strategies for the treatment of breast cancer patients.}, }
@article {pmid36982257, year = {2023}, author = {Zhao, L and Wang, S and Ilves, M and Lehtonen, S and Saikko, L and El-Nezami, H and Alenius, H and Karisola, P}, title = {Transcriptomic Profiling the Effects of Airway Exposure of Zinc Oxide and Silver Nanoparticles in Mouse Lungs.}, journal = {International journal of molecular sciences}, volume = {24}, number = {6}, pages = {}, pmid = {36982257}, issn = {1422-0067}, support = {307768//Academy of Finland/ ; Personal grant//China Scholarship Council/ ; }, mesh = {Mice ; Animals ; *Zinc Oxide/toxicity ; *Metal Nanoparticles/toxicity ; Silver/toxicity ; Transcriptome ; Lung ; *Nanoparticles ; }, abstract = {Consumers and manufacturers are exposed to nanosized zinc oxide (nZnO) and silver particles (nAg) via airways, but their biological effects are still not fully elucidated. To understand the immune effects, we exposed mice to 2, 10, or 50 μg of nZnO or nAg by oropharyngeal aspiration and analyzed the global gene expression profiles and immunopathological changes in the lungs after 1, 7, or 28 days. Our results show that the kinetics of responses varied in the lungs. Exposure to nZnO resulted in the highest accumulation of F4/80- and CD3-positive cells, and the largest number of differentially expressed genes (DEGs) were identified after day 1, while exposure to nAg caused peak responses at day 7. Additionally, nZnO mainly activated the innate immune responses leading to acute inflammation, whereas the nAg activated both innate and adaptive immune pathways, with long-lasting effects. This kinetic-profiling study provides an important data source to understand the cellular and molecular processes underlying nZnO- and nAg-induced transcriptomic changes, which lead to the characterization of the corresponding biological and toxicological effects of nZnO and nAg in the lungs. These findings could improve science-based hazard and risk assessment and the development of safe applications of engineered nanomaterials (ENMs), e.g., in biomedical applications.}, }
@article {pmid36978455, year = {2023}, author = {Brzozowska, E and Lipiński, T and Korzeniowska-Kowal, A and Filik, K and Górski, A and Gamian, A}, title = {Detection and Level Evaluation of Antibodies Specific to Environmental Bacteriophage I11mO19 and Related Coliphages in Non-Immunized Human Sera.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {36978455}, issn = {2079-6382}, abstract = {Bacteriophages (phages) are viruses infecting bacteria. They are widely present in the environment, food, and normal microflora. The human microbiome is a mutually interdependent network of bacteria, bacteriophages, and human cells. The stability of these tri-kingdom interactions may be essential for maintaining immunologic and metabolic health. Phages, as with each other's antigens, may evoke an immune response during a human's lifetime and induce specific antibody generation. In this manuscript, we labeled these antibodies as naturally generated. Naturally generated antibodies may be one of the most important factors limiting the efficacy of phage therapy. Herein, we attempted to determine the physiological level of these antibodies specific to a population bacteriophage named I11mO19 in human sera, using an ELISA-based assay. First, we purified the phage particles and assessed the immunoreactivity of phage proteins. Then, affinity chromatography was performed on columns with immobilized phage proteins to obtain a fraction of human polyclonal anti-phage antibodies. These antibodies were used as a reference to elaborate an immunoenzymatic test that was used to determine the level of natural anti-phage antibodies. We estimated the average level of anti-I11mO19 phage antibodies at 190 µg per one milliliter of human serum. However, immunoblotting revealed that cross-reactivity occurs between some proteins of I11mO19 and two other coliphages: T4 and ΦK1E. The antigens probably share common epitopes, suggesting that the determined level of anti-I11mO19 phage might be overestimated and reflects a group of antibodies reactive to a broad range of other E. coli phages. Anti-I11mO19 antibodies did not react with Pseudomonas bacteriophage F8, confirming specificity to the coliphage group. In this work, we wanted to show whether it is possible to determine the presence and level of anti-phage antibodies in nontargeted-immunized sera, using an immunoenzymatic assay. The conclusion is that it is possible, and specific antibodies can be determined. However, the specificity refers to a broader coliphage group of phages, not only the single phage strain.}, }
@article {pmid36978453, year = {2023}, author = {Dugot, M and Merzon, E and Ashkenazi, S and Vinker, S and Green, I and Golan-Cohen, A and Israel, A}, title = {The Association between Previous Antibiotic Consumption and SARS-CoV-2 Infection: A Population-Based Case-Control Study.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {36978453}, issn = {2079-6382}, abstract = {Background: The susceptibility to SARS-CoV-2 infection is complex and not yet fully elucidated, being related to many variables; these include human microbiome and immune status, which are both affected for a long period by antibiotic use. We therefore aimed to examine the association of previous antibiotic consumption and SARS-CoV-2 infection in a large-scale population-based study with control of known confounders. Methods: A matched case-control study was performed utilizing the electronic medical records of a large Health Maintenance Organization. Cases were subjects with confirmed SARS-CoV-2 infection (n = 31,260), matched individually (1:4 ratio) to controls without a positive SARS-CoV-2 test (n = 125,039). The possible association between previous antibiotic use and SARS-CoV-2 infection was determined by comparing antibiotic consumption in the previous 6 and 12 months between the cases and controls. For each antibiotic consumed we calculated the odds ratio (OR) for documented SARS-CoV-2 infection, 95% confidence interval (CI), and p-value using univariate and multivariate analyses. Results: The association between previous antibiotic consumption and SARS-CoV-2 infection was complex and bi-directional. In the multivariate analysis, phenoxymethylpenicillin was associated with increased rate of SARS-CoV-2 infection (OR 1.110, 95% CI: 1.036-1.191) while decreased rates were associated with previous consumption of trimethoprim-sulfonamides (OR 0.783, 95% CI: 0.632-0.971) and azithromycin (OR 0.882, 95% CI: 0.829-0.938). Fluroquinolones were associated with decreased rates (OR 0.923, 95% CI: 0.861-0.989) only in the univariate analysis. Previous consumption of other antibiotics had no significant association with SARS-CoV-2 infection. Conclusions: Previous consumption of certain antibiotic agents has an independent significant association with increased or decreased rates of SARS-CoV-2 infection. Plausible mechanisms, that should be further elucidated, are mainly antibiotic effects on the human microbiome and immune modulation.}, }
@article {pmid36971593, year = {2023}, author = {Liu, F and Lu, H and Dong, B and Huang, X and Cheng, H and Qu, R and Hu, Y and Zhong, L and Guo, Z and You, Y and Xu, ZZ}, title = {Systematic Evaluation of the Viable Microbiome in the Human Oral and Gut Samples with Spike-in Gram+/- Bacteria.}, journal = {mSystems}, volume = {8}, number = {2}, pages = {e0073822}, pmid = {36971593}, issn = {2379-5077}, mesh = {Humans ; *Microbiota/genetics ; DNA ; Feces/microbiology ; DNA, Bacterial/genetics ; Bacteria/genetics ; Firmicutes/genetics ; }, abstract = {PMA (propidium monoazide) is one of the few methods that are compatible with metagenomic sequencing to characterize the live/intact microbiota. However, its efficiency in complex communities such as saliva and feces is still controversial. An effective method for depleting host and dead bacterial DNA in human microbiome samples is lacking. Here, we systematically evaluate the efficiency of osmotic lysis and PMAxx treatment (lyPMAxx) in characterizing the viable microbiome with four live/dead Gram+/Gram- microbial strains in simple synthetic and spiked-in complex communities. We show that lyPMAxx-quantitative PCR (qPCR)/sequencing eliminated more than 95% of the host and heat-killed microbial DNA and had a much smaller effect on the live microbes in both simple mock and spiked-in complex communities. The overall microbial load and the alpha diversity of the salivary and fecal microbiome were decreased by lyPMAxx, and the relative abundances of the microbes were changed. The relative abundances of Actinobacteria, Fusobacteria, and Firmicutes in saliva were decreased by lyPMAxx, as was that of Firmicutes in feces. We also found that the frequently used sample storage method, freezing with glycerol, killed or injured 65% and 94% of the living microbial cells in saliva and feces, respectively, with the Proteobacteria phylum affected most in saliva and the Bacteroidetes and Firmicutes phyla affected most in feces. By comparing the absolute abundance variation of the shared species among different sample types and individuals, we found that sample habitat and personal differences affected the response of microbial species to lyPMAxx and freezing. IMPORTANCE The functions and phenotypes of microbial communities are largely defined by viable microbes. Through advanced nucleic acid sequencing technologies and downstream bioinformatic analyses, we gained an insight into the high-resolution microbial community composition of human saliva and feces, yet we know very little about whether such community DNA sequences represent viable microbes. PMA-qPCR was used to characterize the viable microbes in previous studies. However, its efficiency in complex communities such as saliva and feces is still controversial. By spiking-in four live/dead Gram+/Gram- bacterial strains, we demonstrate that lyPMAxx can effectively discriminate between live and dead microbes in the simple synthetic community and complex human microbial communities (saliva and feces). In addition, freezing storage was found to kill or injure the microbes in saliva and feces significantly, as measured with lyPMAxx-qPCR/sequencing. This method has a promising prospect in the viable/intact microbiota detection of complex human microbial communities.}, }
@article {pmid36971547, year = {2023}, author = {Etienne-Mesmin, L and Meslier, V and Uriot, O and Fournier, E and Deschamps, C and Denis, S and David, A and Jegou, S and Morabito, C and Quinquis, B and Thirion, F and Plaza Oñate, F and Le Chatelier, E and Ehrlich, SD and Blanquet-Diot, S and Almeida, M}, title = {In Vitro Modelling of Oral Microbial Invasion in the Human Colon.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0434422}, pmid = {36971547}, issn = {2165-0497}, abstract = {Recent advances in the human microbiome characterization have revealed significant oral microbial detection in stools of dysbiotic patients. However, little is known about the potential interactions of these invasive oral microorganisms with commensal intestinal microbiota and the host. In this proof-of-concept study, we proposed a new model of oral-to-gut invasion by the combined use of an in vitro model simulating both the physicochemical and microbial (lumen- and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol, and whole-metagenome shotgun sequencing. Oral invasion of the intestinal microbiota was simulated by injection of enriched saliva in the in vitro colon model inoculated with a fecal sample from the same healthy adult donor. The mucosal compartment of M-ARCOL was able to retain the highest species richness levels over time, while species richness levels decreased in the luminal compartment. This study also showed that oral microorganisms preferably colonized the mucosal microenvironment, suggesting potential oral-to-intestinal mucosal competitions. This new model of oral-to-gut invasion can provide useful mechanistic insights into the role of oral microbiome in various disease processes. IMPORTANCE Here, we propose a new model of oral-to-gut invasion by the combined use of an in vitro model simulating both the physicochemical and microbial (lumen- and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol, and whole-metagenome shotgun sequencing. Our study revealed the importance of integrating the mucus compartment, which retained higher microbial richness during fermentation, showed the preference of oral microbial invaders for the mucosal resources, and indicated potential oral-to-intestinal mucosal competitions. It also underlined promising opportunities to further understand mechanisms of oral invasion into the human gut microbiome, define microbe-microbe and mucus-microbe interactions in a compartmentalized fashion, and help to better characterize the potential of oral microbial invasion and their persistence in the gut.}, }
@article {pmid36969178, year = {2023}, author = {Ling, Z and Cheng, Y and Gao, J and Lei, W and Yan, X and Hu, X and Shao, L and Liu, X and Kang, R}, title = {Alterations of the fecal and vaginal microbiomes in patients with systemic lupus erythematosus and their associations with immunological profiles.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1135861}, pmid = {36969178}, issn = {1664-3224}, mesh = {Female ; Humans ; *Gastrointestinal Microbiome/genetics ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Bacteria/genetics ; Feces/microbiology ; *Lupus Erythematosus, Systemic/microbiology ; Vagina/microbiology ; }, abstract = {BACKGROUND: Exploring the human microbiome in multiple body niches is beneficial for clinicians to determine which microbial dysbiosis should be targeted first. We aimed to study whether both the fecal and vaginal microbiomes are disrupted in SLE patients and whether they are correlated, as well as their associations with immunological features.<br><br>METHODS: A group of 30 SLE patients and 30 BMI-age-matched healthy controls were recruited. Fecal and vaginal samples were collected, the 16S rRNA gene was sequenced to profile microbiomes, and immunological features were examined.<br><br>RESULTS: Distinct fecal and vaginal bacterial communities and decreased microbial diversity in feces compared with the vagina were found in SLE patients and controls. Altered bacterial communities were found in the feces and vaginas of patients. Compared with the controls, the SLE group had slightly lower gut bacterial diversity, which was accompanied by significantly higher bacterial diversity in their vaginas. The most predominant bacteria differed between feces and the vagina in all groups. Eleven genera differed in patients' feces; for example, Gardnerella and Lactobacillus increased, whereas Faecalibacterium decreased. Almost all the 13 genera differed in SLE patients' vaginas, showing higher abundances except for Lactobacillus. Three genera in feces and 11 genera in the vagina were biomarkers for SLE patients. The distinct immunological features were only associated with patients' vaginal microbiomes; for example, Escherichia-Shigella was negatively associated with serum C4.<br><br>CONCLUSIONS: Although SLE patients had fecal and vaginal dysbiosis, dysbiosis in the vagina was more obvious than that in feces. Additionally, only the vaginal microbiome interacted with patients' immunological features.}, }
@article {pmid36969036, year = {2023}, author = {Yang, X and An, H and He, Y and Fu, G and Jiang, Z}, title = {Comprehensive analysis of microbiota signature across 32 cancer types.}, journal = {Frontiers in oncology}, volume = {13}, number = {}, pages = {1127225}, pmid = {36969036}, issn = {2234-943X}, abstract = {Microbial communities significantly inhabit the human body. Evidence shows the interaction between the human microbiome and host cells plays a central role in multiple physiological processes and organ microenvironments. However, the majority of related studies focus on gut microbiota or specific tissues/organs, and the component signature of intratumor microbiota across various cancer types remains unclear. Here, we systematically analyzed the correlation between intratumor microbial signature with survival outcomes, genomic features, and immune profiles across 32 cancer types based on the public databases of Bacteria in Cancer (BIC) and The Cancer Genome Atlas (TCGA). Results showed the relative abundance of microbial taxa in tumors compared to normal tissues was observed as particularly noticeable. Survival analysis found that specific candidate microbial taxa were correlated with prognosis across various cancers. Then, a microbial-based scoring system (MS), which was composed of 64 candidate prognostic microbes, was established. Further analyses showed significant differences in survival status, genomic function, and immune profiles among the distinct MS subgroups. Taken together, this study reveals the diversity and complexity of microbiomes in tumors. Classifying cancer into different subtypes based on intratumor microbial signatures might reasonably reflect genomic characteristics, immune features, and survival status.}, }
@article {pmid36966280, year = {2023}, author = {Zhao, Y and Yi, J and Xiang, J and Jia, W and Chen, A and Chen, L and Zheng, L and Zhou, W and Wu, M and Yu, Z and Tang, J}, title = {Exploration of lung mycobiome in the patients with non-small-cell lung cancer.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {81}, pmid = {36966280}, issn = {1471-2180}, mesh = {Humans ; *Mycobiome ; *Carcinoma, Non-Small-Cell Lung ; Fungi/genetics ; *Lung Neoplasms ; Lung ; }, abstract = {As the Human Microbiome Project (HMP) progresses, the relationship between microbes and human health has been receiving increasing attention. A growing number of reports support the correlation between cancer and microbes. However, most studies have focused on bacteria, rather than fungal communities. In this study, we studied the alteration in lung mycobiome in patients with non-small-cell lung cancer (NSCLC) using metagenomic sequencing and qPCR. The higher fungal diversity and more complex network were observed in the patients with NSCLC. In addition, Alternaria arborescens was found as the most relevant fungus to NSCLC, and the enrichment of it in cancerous tissue was also detected. This study proposes that the changes in fungal communities may be closely related to lung cancer, and provides insights into further exploration the relationship between lung cancer and fungi.}, }
@article {pmid36963900, year = {2023}, author = {Elghannam, MT and Hassanien, MH and Ameen, YA and Turky, EA and Elattar, GM and ElRay, AA and Eltalkawy, MD}, title = {Oral microbiota and liver diseases.}, journal = {Clinical nutrition ESPEN}, volume = {54}, number = {}, pages = {68-72}, doi = {10.1016/j.clnesp.2022.12.030}, pmid = {36963900}, issn = {2405-4577}, mesh = {Humans ; *Carcinoma, Hepatocellular ; *Liver Neoplasms ; Dysbiosis ; Liver Cirrhosis ; *Microbiota ; }, abstract = {Gut microbiota plays a crucial role in our health and particularly liver diseases, including NAFLD, cirrhosis, and HCC. Oral microbiome and its role in health and disease represent an active field of research. Several lines of evidence have suggested that oral microbiota dysbiosis represents a major factor contributing to the occurrence and progression of many liver diseases. The human microbiome is valuable to the diagnosis of cancer and provides a novel strategy for targeted therapy of HCC. The most studied liver disease in relation to oral-gut-liver axis dysbiosis includes MAFLD; however, other diseases include Precancerous liver disease as viral liver diseases, liver cirrhosis, AIH and liver carcinoma (HCC). It seems that restoring populations of beneficial organisms and correcting dysbiosis appears to improve outcomes in liver disorders. We discuss the possible role of oral microbiota in these diseases.}, }
@article {pmid36963164, year = {2023}, author = {Beliaeva, MA and Wilmanns, M and Zimmermann, M}, title = {Decipher enzymes from human microbiota for drug discovery and development.}, journal = {Current opinion in structural biology}, volume = {80}, number = {}, pages = {102567}, doi = {10.1016/j.sbi.2023.102567}, pmid = {36963164}, issn = {1879-033X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; Bacteria/genetics ; Genomics ; Drug Discovery ; }, abstract = {The human microbiota plays an important role in human health and contributes to the metabolism of therapeutic drugs affecting their potency. However, the current knowledge on human gut bacterial metabolism is limited and lacks an understanding of the underlying mechanisms of observed drug biotransformations. Despite the complexity of the gut microbial community, genomic and metagenomic sequencing provides insights into the diversity of chemical reactions that can be carried out by the microbiota and poses new challenges to functionally annotate thousands of bacterial enzymes. Here, we outline methods to systematically address the structural and functional space of the human microbiome, highlighting a combination of in silico and in vitro approaches. Systematic knowledge about microbial enzymes could eventually be applied for personalized therapy, the development of prodrugs and modulators of unwanted bacterial activity, and the further discovery of new antibiotics.}, }
@article {pmid36959568, year = {2023}, author = {Ivashkin, V and Shifrin, O and Maslennikov, R and Poluektova, E and Korolev, A and Kudryavtseva, A and Krasnov, G and Benuni, N and Barbara, G}, title = {Eubiotic effect of rifaximin is associated with decreasing abdominal pain in symptomatic uncomplicated diverticular disease: results from an observational cohort study.}, journal = {BMC gastroenterology}, volume = {23}, number = {1}, pages = {82}, pmid = {36959568}, issn = {1471-230X}, mesh = {Humans ; Rifaximin/therapeutic use ; Cohort Studies ; Prospective Studies ; *Diverticular Diseases/complications/therapy ; Abdominal Pain/drug therapy/etiology ; Treatment Outcome ; }, abstract = {BACKGROUND: Rifaximin effectively treats symptomatic uncomplicated diverticular disease (SUDD) and has shown eubiotic potential (i.e., an increase in resident microbial elements with potential beneficial effects) in other diseases. This study investigated changes in the fecal microbiome of patients with SUDD after repeated monthly treatment with rifaximin and the association of these changes with the severity of abdominal pain.<br><br>METHODS: This was a single-center, prospective, observational, uncontrolled cohort study. Patients received rifaximin 400&#xa0;mg twice a day for 7 days per month for 6 months. Abdominal pain (assessed on a 4-point scale from 0 [no pain] to 3 [severe pain]) and fecal microbiome (assessed using 16&#xa0;S rRNA gene sequencing) were assessed at inclusion (baseline) and 3 and 6 months. The Spearman's rank test analyzed the relationship between changes in the gut microbiome and the severity of abdominal pain. A p-value&#x2009;&#x2264;&#x2009;0.05 was considered statistically significant.<br><br>RESULTS: Of the 23 patients enrolled, 12 patients completed the study and were included in the analysis. Baseline abdominal pain levels decreased significantly after 3 (p&#x2009;=&#x2009;0.036) and 6 (p&#x2009;=&#x2009;0.008) months of treatment with rifaximin. The abundance of Akkermansia in the fecal microbiome was significantly higher at 3 (p&#x2009;=&#x2009;0.017) and 6 (p&#x2009;=&#x2009;0.015) months versus baseline. The abundance of Ruminococcaceae (p&#x2009;=&#x2009;0.034), Veillonellaceae (p&#x2009;=&#x2009;0.028), and Dialister (p&#x2009;=&#x2009;0.036) were significantly increased at 6 months versus baseline, whereas Anaerostipes (p&#x2009;=&#x2009;0.049) was significantly decreased. The severity of abdominal pain was negatively correlated with the abundance of Akkermansia (r=-0.482; p&#x2009;=&#x2009;0.003) and Ruminococcaceae (r=-0.371; p&#x2009;=&#x2009;0.026) but not with Veillonellaceae, Dialister, or Anaerostipes. After 3 months of rifaximin, abdominal pain was significantly less in patients with Akkermansia in their fecal microbiome than in patients without Akkermansia (p&#x2009;=&#x2009;0.022).<br><br>CONCLUSION: The eubiotic effect of rifaximin was associated with decreased abdominal pain in patients with SUDD.}, }
@article {pmid36959210, year = {2023}, author = {Wu, CM and Wheeler, KM and Cárcamo-Oyarce, G and Aoki, K and McShane, A and Datta, SS and Mark Welch, JL and Tiemeyer, M and Griffen, AL and Ribbeck, K}, title = {Mucin glycans drive oral microbial community composition and function.}, journal = {NPJ biofilms and microbiomes}, volume = {9}, number = {1}, pages = {11}, pmid = {36959210}, issn = {2055-5008}, support = {P30 ES002109/ES/NIEHS NIH HHS/United States ; R01 EB017755/EB/NIBIB NIH HHS/United States ; R01-EB017755-041745302/NH/NIH HHS/United States ; }, mesh = {Humans ; *Mucins/chemistry/metabolism ; Glycosylation ; Mucus/metabolism ; *Microbiota ; Polysaccharides/metabolism ; }, abstract = {Human microbiome composition is closely tied to health, but how the host manages its microbial inhabitants remains unclear. One important, but understudied, factor is the natural host environment: mucus, which contains gel-forming glycoproteins (mucins) that display hundreds of glycan structures with potential regulatory function. Leveraging a tractable culture-based system to study how mucins influence oral microbial communities, we found that mucin glycans enable the coexistence of diverse microbes, while resisting disease-associated compositional shifts. Mucins from tissues with unique glycosylation differentially tuned microbial composition, as did isolated mucin glycan libraries, uncovering the importance of specific glycan patterns in microbiome modulation. We found that mucins shape microbial communities in several ways: serving as nutrients to support metabolic diversity, organizing spatial structure through reduced aggregation, and possibly limiting antagonism between competing taxa. Overall, this work identifies mucin glycans as a natural host mechanism and potential therapeutic intervention to maintain healthy microbial communities.}, }
@article {pmid36959041, year = {2023}, author = {Ait-Zenati, F and Djoudi, F and Mehelleb, D and Madaoui, M}, title = {Involvement of the human microbiome in frequent cancers, current knowledge and carcinogenesis mechanisms.}, journal = {Bulletin du cancer}, volume = {110}, number = {7-8}, pages = {776-789}, doi = {10.1016/j.bulcan.2023.01.022}, pmid = {36959041}, issn = {1769-6917}, mesh = {Humans ; *Helicobacter Infections/complications ; *Microbiota ; *Gastrointestinal Microbiome ; Carcinogenesis ; *Liver Neoplasms ; }, abstract = {The human body is home to a complex microbial community, living in symbiosis. However, when an imbalance occurs, known as dysbiosis, it can lead to organic diseases such as cancers. Helicobacter pylori is commonly recognized as the causative agent of gastric cancer. Numerous studies have explored the potential role of other microorganisms in cancers. For example, the role of intestinal microbiota in the hepatocellular carcinoma formation and progression, the microbiota in breast cancer and the interaction between the microbiome and TP53 in human lung carcinogenesis. In this review, we highlight the latest findings on the microbiome involved in the most common cancers and the suggested mechanisms of carcinogenesis.}, }
@article {pmid36957972, year = {2023}, author = {Chen, GY}, title = {The Human Microbiome and Cancer.}, journal = {Cancer journal (Sudbury, Mass.)}, volume = {29}, number = {2}, pages = {47-48}, doi = {10.1097/PPO.0000000000000653}, pmid = {36957972}, issn = {1540-336X}, mesh = {Humans ; *Neoplasms ; *Microbiota ; }, }
@article {pmid36945614, year = {2023}, author = {Gellman, RH and Olm, MR and Terrapon, N and Enam, F and Higginbottom, SK and Sonnenburg, JL and Sonnenburg, ED}, title = {Hadza Prevotella Require Diet-derived Microbiota Accessible Carbohydrates to Persist in Mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36945614}, issn = {2692-8205}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; K22 HG000044/HG/NHGRI NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, abstract = {Industrialization has transformed the gut microbiota, reducing the prevalence of Prevotella relative to Bacteroides. Here, we isolate Bacteroides and Prevotella strains from the microbiota of Hadza hunter-gatherers of Tanzania, a population with high levels of Prevotella. We demonstrate that plant-derived microbiota-accessible carbohydrates (MACs) are required for persistence of Prevotella copri but not Bacteroides thetaiotaomicron in vivo. Differences in carbohydrate metabolism gene content, expression, and in vitro growth reveal that Hadza Prevotella strains specialize in degrading plant carbohydrates, while Hadza Bacteroides isolates use both plant and host-derived carbohydrates, a difference mirrored in Bacteroides from non-Hadza populations. When competing directly, P. copri requires plant-derived MACs to maintain colonization in the presence of B. thetaiotaomicron, as a no MAC diet eliminates P. copri colonization. Prevotella's reliance on plant-derived MACs and Bacteroides' ability to use host mucus carbohydrates could explain the reduced prevalence of Prevotella in populations consuming a low-MAC, industrialized diet.}, }
@article {pmid36943054, year = {2023}, author = {Zhou, C and Wang, Y and Li, C and Xie, Z and Dai, L}, title = {Amelioration of Colitis by a Gut Bacterial Consortium Producing Anti-Inflammatory Secondary Bile Acids.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0333022}, pmid = {36943054}, issn = {2165-0497}, abstract = {The Integrative Human Microbiome Project and other cohort studies have indicated that inflammatory bowel disease is accompanied by dysbiosis of gut microbiota, decreased production of secondary bile acids, and increased levels of primary bile acids. Secondary bile acids, such as ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. In this study, we screened human gut bacterial strains for bile acid metabolism and designed a consortium of three species, including Clostridium AP sp000509125, Bacteroides ovatus, and Eubacterium limosum, and named it BAC (bile acid consortium). We showed that the three-strain gut bacterial consortium BAC is capable of converting conjugated primary bile acids taurochenodeoxycholic acid and glycochenodeoxycholic acid to secondary bile acids UDCA and LCA in vitro. Oral gavage treatment with BAC in mice resulted in protective effects against dextran sulfate sodium (DSS)-induced colitis, including reduced weight loss and increased colon length. Furthermore, BAC treatment increased the fecal level of bile acids, including UDCA and LCA. BAC treatment enhanced intestinal barrier function, which may be attributed to the increased activation of the bile acid receptor TGR5 by secondary bile acids. Finally, we examined the remodeling of gut microbiota by BAC treatment. Taken together, the three-strain gut bacterial consortium BAC restored the dysregulated bile acid metabolism and alleviated DSS-induced colitis. Our study provides a proof-of-concept demonstration that a rationally designed bacterial consortium can reshape the metabolism of the gut microbiome to treat diseases. IMPORTANCE Secondary bile acids have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. To address this gap, we designed a consortium of human gut bacterial strains based on their metabolic capacity to produce secondary bile acids UDCA and LCA, and we evaluated the efficacy of single bacterial strains and the bacterial consortium in treating the murine colitis model. We found that oral gavage of the bacterial consortium to mice restored secondary bile acid metabolism to increase levels of UDCA and LCA, which induced the activation of TGR5 to improve gut-barrier integrity and reduced the inflammation in murine colitis. Overall, our study demonstrates that rationally designed bacterial consortia can reshape the metabolism of the gut microbiome and provides novel insights into the application of live biotherapeutics for treating IBD.}, }
@article {pmid36930679, year = {2023}, author = {Puschhof, J and Elinav, E}, title = {Human microbiome research: Growing pains and future promises.}, journal = {PLoS biology}, volume = {21}, number = {3}, pages = {e3002053}, pmid = {36930679}, issn = {1545-7885}, mesh = {Humans ; *Microbiota ; Precision Medicine ; }, abstract = {Human microbiome research is evolving from describing associations to understanding the impact of bioactive strains on humans. Despite challenges, progress is being made to apply data-driven microbiome diagnostics and interventions, potentially leading to precision medicine breakthroughs in the next decade.}, }
@article {pmid36929933, year = {2023}, author = {Zou, H and Sun, T and Jin, B and Wang, S}, title = {sBGC-hm: an atlas of secondary metabolite biosynthetic gene clusters from the human gut microbiome.}, journal = {Bioinformatics (Oxford, England)}, volume = {39}, number = {3}, pages = {}, pmid = {36929933}, issn = {1367-4811}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Multigene Family ; Biosynthetic Pathways/genetics ; }, abstract = {SUMMARY: Microbial secondary metabolites exhibit potential medicinal value. A large number of secondary metabolite biosynthetic gene clusters (BGCs) in the human gut microbiome, which exhibit essential biological activity in microbe-microbe and microbe-host interactions, have not been adequately characterized, making it difficult to prioritize these BGCs for experimental characterization. Here, we present the sBGC-hm, an atlas of secondary metabolite BGCs allows researchers to explore the potential therapeutic benefits of these natural products. One of its key features is the ability to assist in optimizing the BGC structure by utilizing the gene co-occurrence matrix obtained from Human Microbiome Project data. Results are viewable online and can be downloaded as spreadsheets.<br><br>The database is openly available at https://www.wzubio.com/sbgc. The website is powered by Apache 2 server with PHP and MariaDB.}, }
@article {pmid36920536, year = {2023}, author = {Kazarina, A and Kuzmicka, J and Bortkevica, S and Zayakin, P and Kimsis, J and Igumnova, V and Sadovska, D and Freimane, L and Kivrane, A and Namina, A and Capligina, V and Poksane, A and Ranka, R}, title = {Oral microbiome variations related to ageing: possible implications beyond oral health.}, journal = {Archives of microbiology}, volume = {205}, number = {4}, pages = {116}, pmid = {36920536}, issn = {1432-072X}, mesh = {Humans ; *Oral Health ; *Microbiota ; Bacteria/genetics ; Aging ; Cluster Analysis ; RNA, Ribosomal, 16S ; }, abstract = {The global population is getting older due to a combination of longer life expectancy and declining birth rates. Growing evidence suggests that the oral microbiota composition and distribution may have a profound effect on how well we age. The purpose of this study was to investigate age-related oral microbiome variations of supragingival plaque and buccal mucosa samples in the general population in Latvia. Our results indicated significant difference between supragingival plaque bacterial profiles of three age groups (20-40; 40-60; 60 + years). Within supragingival plaque samples, age group 20-40 showed the highest bacterial diversity with a decline during the 40-60 age period and uprise again after the age of 60. Among other differences, the important oral commensal Neisseria had declined after the age of 40. Additionally, prevalence of two well-documented opportunistic pathogens Streptococcus anginosus and Gemella sanguinis gradually rose with age within our samples. Furthermore, supragingival plaque and buccal mucosa samples significantly differed in overall bacterial composition.}, }
@article {pmid36918089, year = {2023}, author = {Kapoor, B and Gulati, M and Gupta, R and Singla, RK}, title = {Microbiota dysbiosis and myasthenia gravis: Do all roads lead to Rome?.}, journal = {Autoimmunity reviews}, volume = {22}, number = {5}, pages = {103313}, doi = {10.1016/j.autrev.2023.103313}, pmid = {36918089}, issn = {1873-0183}, mesh = {Humans ; Dysbiosis ; Rome ; *Probiotics/therapeutic use ; *Myasthenia Gravis/therapy ; Prebiotics ; *Gastrointestinal Microbiome ; }, abstract = {Dysregulated immune system with a failure to recognize self from non-self-antigens is one of the common pathogeneses seen in autoimmune diseases. The complex interplay of genetic and environmental factors is important for the occurrence and development of the disease. Among the environmental factors, disturbed gut microbiota (gut dysbiosis) has recently attracted particular attention, especially with advancement in human microbiome research. Although the alterations in microbiota have been seen in various autoimmune diseases, including those of nervous system, there is paucity of information on neuromuscular system diseases. Myasthenia gravis (MG) is one such rare autoimmune disease of neuromuscular junction, and is caused by generation of pathogenic autoantibodies to components of the postsynaptic muscle endplate. In the recent years, accumulating evidences have endorsed the key role of host microbiota, particularly those of gut, in the pathogenesis of MG. Differential microbiota composition, characterized by increased abundance of Fusobacteria, Bacteroidetes, and Proteobacteria, and decreased abundance of Actinobacteria and Firmicutes, has been seen in MG patients in comparison to healthy subjects. Disturbance of microbiota composition, particularly reduced ratio of Firmicutes/Bacteroidetes, alter the gut permeability, subsequently triggering the immunological response. Resultant reduction in levels of short chain fatty acids (SCFAs) is another factor contributing to the immunological response in MG patients. Modulation of gut microbiota via intervention of probiotics, prebiotics, synbiotics, postbiotics (metabiotics), and fecal microbiota transplantation (FMT) is considered to be the futuristic approach for the management of MG. This review summarizes the role of gut microbiota and their metabolites (postbiotics) in the progression of MG. Also, various bacteriotherapeutic approaches involving gut microbiota are discussed for the prevention of MG progression.}, }
@article {pmid36916927, year = {2023}, author = {Du, Q and Xu, Q and Pan, F and Shi, Y and Yu, F and Zhang, T and Jiang, J and Liu, W and Pan, X and Han, D and Zhang, H}, title = {Association between Intestinal Colonization and Extraintestinal Infection with Carbapenem-Resistant Klebsiella pneumoniae in Children.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0408822}, pmid = {36916927}, issn = {2165-0497}, abstract = {Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a critical public health threat. However, the association between intestinal colonization and parenteral infection among pediatric patients has not been elucidated. We collected 8 fecal CRKP strains and 10 corresponding CRKP strains responsible for extraintestinal infection from eight patients who did not manifest infection upon admission to the hospital. Paired isolates showed identical resistance to antimicrobials and identical virulence in vitro and in vivo. wzi capsule typing, multilocus sequence typing, and whole-genome sequencing (WGS) indicated high similarity between paired colonizing and infecting isolates. Mutations between colonizing and infecting isolate pairs found by WGS had a distinctive molecular signature of a high proportion of complex structural variants. The mutated genes were involved in pathways associated with infection-related physiological and pathogenic functions, including antibiotic resistance, virulence, and response to the extracellular environment. The latter is important for bacterial infection of environmental niches. Various mutations related to antibiotic resistance, virulence, and colonization that were not associated with any particular mutational hot spot correlated with an increased risk of extraintestinal infection. Notably, novel subclone carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) KL19-ST15 exhibited hypervirulence in experimental assays that reflected the severe clinical symptoms of two patients infected with the clonal strains. Taken together, our findings indicate the association between CRKP intestinal colonization and extraintestinal infection, suggesting that active screening for colonization on admission could decrease infection risk in children. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes an increasing number of nosocomial infections, which can be life-threatening, as carbapenems are last-resort antibiotics. K. pneumoniae is part of the healthy human microbiome, and this provides a potential advantage for infection. This study demonstrated that CRKP intestinal colonization is strongly linked to extraintestinal infection, based on the evidence given by whole-genome sequencing data and phenotypic assays of antimicrobial resistance and virulence. Apart from these findings, our in-depth analysis of point mutations and chromosome structural variants in patient-specific infecting isolates compared with colonizing isolates may contribute insights into bacterial adaptation underlying CRKP infection. In addition, a novel subclone of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) was observed in the study. This finding highlights the importance of CRKP active surveillance among children, targeting in particular the novel high-risk CR-hvKP clone.}, }
@article {pmid36914394, year = {2022}, author = {Liu, Y and Xu, MM and Zhang, Y and Liu, SQ and Yuan, MQ and Jia, ZJ}, title = {Application Value and Research Progress of Human Microbiome in Sexual Assault Cases.}, journal = {Fa yi xue za zhi}, volume = {38}, number = {6}, pages = {774-782}, doi = {10.12116/j.issn.1004-5619.2021.511101}, pmid = {36914394}, issn = {1004-5619}, mesh = {Child ; Humans ; Female ; Artificial Intelligence ; Forensic Medicine/methods ; *Sex Offenses ; DNA ; *Microbiota ; *Crime Victims ; }, abstract = {In recent years, sexual assault cases have been on the rise, seriously infringing the legitimate rights and interests of women and children, causing widespread concern in society. DNA evidence has become the key evidence to prove the facts in sexual assault cases, but lack of DNA evidence or only DNA evidence in some sexual assault cases leads to unclear facts and insufficient evidence. With the emergence of high-throughput sequencing technology and the development of bioinformatics and artificial intelligence, new progress has been made in the study of human microbiome. Researchers have begun to use human microbiome for difficult sexual assault cases indentification. This paper reviews the characteristics of human microbiome, and its application value in the inferences of the body fluid stain origin, the sexual assault method, the crime time, etc. In addition, the challenges faced by the application of the human microbiome in practical case handling, the solutions and future development potential are analyzed and prospected.}, }
@article {pmid36914054, year = {2023}, author = {Meng, Y and Mao, Y and Tang, Z and Qiu, X and Bajinka, O and Tan, Y and Song, Z}, title = {Crosstalk between the lung microbiome and lung cancer.}, journal = {Microbial pathogenesis}, volume = {178}, number = {}, pages = {106062}, doi = {10.1016/j.micpath.2023.106062}, pmid = {36914054}, issn = {1096-1208}, mesh = {Humans ; Lung/microbiology ; *Lung Neoplasms ; *Pulmonary Disease, Chronic Obstructive ; *Lung Diseases/microbiology ; *Microbiota ; Dysbiosis ; }, abstract = {The human microbiome is a complex ecosystem that mediates interaction between the human host and the environment. All of the human body is colonized by microorganisms. The lung as an organ used to be considered sterile. Recently, however, there has been a growing number of reports with evidence that the lungs are also in a state of carrying bacteria. The pulmonary microbiome is associated with many lung diseases and is increasingly reported in current studies. These include; chronic obstructive pulmonary disease (COPD), asthma, acute chronic respiratory infections, and cancers. These lung diseases are associated with reduced diversity and dysbiosis. It directly or indirectly affects the occurrence and development of lung cancer. Very few microbes directly cause cancer, while many are complicit in cancer growth, usually working through the host's immune system. This review focuses on the correlation between lung microbiota and lung cancer, and investigates the mechanism of action of lung microorganisms on lung cancer, which will provide new and reliable treatments and diagnosis of lung cancer in the future.}, }
@article {pmid36913409, year = {2023}, author = {Mero, S and Lääveri, T and Ursing, J and Rombo, L and Kofoed, PE and Kantele, A}, title = {Seasonal variation of diarrhoeal pathogens among Guinea-Bissauan children under five years of age.}, journal = {PLoS neglected tropical diseases}, volume = {17}, number = {3}, pages = {e0011179}, pmid = {36913409}, issn = {1935-2735}, mesh = {Infant ; Humans ; Child ; Child, Preschool ; Seasons ; Prospective Studies ; Guinea ; *Cryptosporidiosis/complications ; *Cryptosporidium/genetics ; Diarrhea/microbiology ; *Bacteriophages ; }, abstract = {BACKGROUND: Diarrhoea remains a major cause of childhood morbidity and mortality in low-income countries (LICs). The frequency of diarrhoeal episodes may vary by season, yet few prospective cohort studies have examined seasonal variation among various diarrhoeal pathogens using multiplex qPCR to analyse bacterial, viral and parasitic pathogens.<br><br>METHODS: We combined our recent qPCR data of diarrhoeal pathogens (nine bacterial, five viral and four parasitic) among Guinea-Bissauan children under five years old with individual background data, dividing by season. The associations of season (dry winter and rainy summer) and the various pathogens were explored among infants (0-11 months) and young children (12-59 months) and those with and without diarrhoea.<br><br>RESULTS: Many bacterial pathogens, especially EAEC, ETEC and Campylobacter, and parasitic Cryptosporidium, prevailed in the rainy season, whereas many viruses, particularly the adenovirus, astrovirus and rotavirus proved common in the dry season. Noroviruses were found constantly throughout the year. Seasonal variation was observed in both age groups.<br><br>CONCLUSION: In childhood diarrhoea in a West African LIC, seasonal variation appears to favour EAEC, ETEC, and Cryptosporidium in the rainy and viral pathogens in the dry season.}, }
@article {pmid36906264, year = {2023}, author = {Carson, MD and Warner, AJ and Geiser, VL and Hathaway-Schrader, JD and Alekseyenko, AV and Marshall, J and Westwater, C and Novince, CM}, title = {Prolonged Antibiotic Exposure during Adolescence Dysregulates Liver Metabolism and Promotes Adiposity in Mice.}, journal = {The American journal of pathology}, volume = {193}, number = {6}, pages = {796-812}, pmid = {36906264}, issn = {1525-2191}, support = {T32 DE017551/DE/NIDCR NIH HHS/United States ; P30 DK123704/DK/NIDDK NIH HHS/United States ; R01 AG067510/AG/NIA NIH HHS/United States ; K08 DE025337/DE/NIDCR NIH HHS/United States ; P20 GM130457/GM/NIGMS NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; R01 DE029637/DE/NIDCR NIH HHS/United States ; UL1 TR001450/TR/NCATS NIH HHS/United States ; R01 AR081488/AR/NIAMS NIH HHS/United States ; }, mesh = {Male ; Mice ; Animals ; *Adiposity ; *Anti-Bacterial Agents/adverse effects ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism ; Liver/metabolism ; Tetracyclines/metabolism ; }, abstract = {Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear. Herein, a retrospective analysis of Medicaid claims data was performed, which indicated that tetracycline class antibiotics are commonly prescribed for the systemic treatment of adolescent acne. The purpose of this was to discern the impact of a prolonged tetracycline antibiotic exposure during adolescence on the gut microbiota, liver metabolism, and adiposity. Male C57BL/6T specific pathogen-free mice were administered a tetracycline antibiotic during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at different time points to assess immediate and sustained antibiotic treatment effects. Antibiotic exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic metabolism was linked to sustained disruption of the intestinal farnesoid X receptor-fibroblast growth factor 15 axis, a gut-liver endocrine axis that supports metabolic homeostasis. Antibiotic exposure during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly manifested following antibiotic therapy. This preclinical work highlights that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended deleterious effects on liver metabolism and adiposity.}, }
@article {pmid36904222, year = {2023}, author = {Rodrigues, A and Gonçalves, A and Morais, J and Araujo, R and Falcão-Pires, I}, title = {Diet-Induced Microbiome's Impact on Heart Failure: A Double-Edged Sword.}, journal = {Nutrients}, volume = {15}, number = {5}, pages = {}, pmid = {36904222}, issn = {2072-6643}, support = {CEECIND/01070/2018//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, mesh = {Humans ; *Heart Failure ; Quality of Life ; Stroke Volume ; Diet ; *Microbiota ; Inflammation ; Prognosis ; }, abstract = {Heart failure (HF) is a debilitating disease with a significant clinical and economic impact worldwide. Multiple factors seem to increase the risk of developing HF, such as hypertension, obesity and diabetes. Since chronic inflammation plays a significant role in HF pathophysiology and gut dysbiosis is associated with low-grade chronic inflammation, the risk of cardiovascular diseases is likely modulated by the gut microbiome (GM). Considerable progress has been made in HF management. However, there is a need to find new strategies to reduce mortality and increase the quality of life, mainly of HFpEF patients, since its prevalence continues to rise. Recent studies validate that lifestyle changes, such as diet modulation, represent a potential therapeutic approach to improve several cardiometabolic diseases, although their effects on the GM and its indirect cardiac impact still warrant further research. Hence, in this paper, we aim to clarify the link between HF and the human microbiome.}, }
@article {pmid36900377, year = {2023}, author = {Luu, M and Schütz, B and Lauth, M and Visekruna, A}, title = {The Impact of Gut Microbiota-Derived Metabolites on the Tumor Immune Microenvironment.}, journal = {Cancers}, volume = {15}, number = {5}, pages = {}, pmid = {36900377}, issn = {2072-6694}, support = {VI562/7-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Prevention of the effectiveness of anti-tumor immune responses is one of the canonical cancer hallmarks. The competition for crucial nutrients within the tumor microenvironment (TME) between cancer cells and immune cells creates a complex interplay characterized by metabolic deprivation. Extensive efforts have recently been made to understand better the dynamic interactions between cancer cells and surrounding immune cells. Paradoxically, both cancer cells and activated T cells are metabolically dependent on glycolysis, even in the presence of oxygen, a metabolic process known as the Warburg effect. The intestinal microbial community delivers various types of small molecules that can potentially augment the functional capabilities of the host immune system. Currently, several studies are trying to explore the complex functional relationship between the metabolites secreted by the human microbiome and anti-tumor immunity. Recently, it has been shown that a diverse array of commensal bacteria synthetizes bioactive molecules that enhance the efficacy of cancer immunotherapy, including immune checkpoint inhibitor (ICI) treatment and adoptive cell therapy with chimeric antigen receptor (CAR) T cells. In this review, we highlight the importance of commensal bacteria, particularly of the gut microbiota-derived metabolites that are capable of shaping metabolic, transcriptional and epigenetic processes within the TME in a therapeutically meaningful way.}, }
@article {pmid36898756, year = {2023}, author = {Farmer, N and Baginski, A and Alkhatib, J and Maki, KA and Baumer, Y and Powell-Wiley, TM and Wallen, GR}, title = {Neighbourhood environment as a risk factor for adverse health outcomes through association with the microbiome: protocol for a scoping review.}, journal = {BMJ open}, volume = {13}, number = {3}, pages = {e066913}, pmid = {36898756}, issn = {2044-6055}, mesh = {Humans ; *Neighborhood Characteristics ; *Outcome Assessment, Health Care ; Research Design ; Risk Factors ; Scoping Reviews As Topic ; }, abstract = {INTRODUCTION: The connection of the microbiome to human health intersects with the physical environment of humans. Each microbiome location can be influenced by environmental conditions that relate to specific geographical locations, which in turn are influenced by social determinants of health such as a neighbourhood. The objective of this scoping review is to explore the current evidence on the relationships between microbiome and neighbourhood to explain microbiome-related health outcomes.<br><br>METHODS AND ANALYSIS: Arksey and O'Malley's literature review framework will be employed throughout the process, as well as Page, et al's 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis updated workflow to process search results. The literature search will be completed using PubMed/Medline (NLM), Embase (Elsevier), Web of Science, Core Collection (Clarivate Analytics), Scopus (Elsevier), medRxiv preprint server and Open Science Framework server. The search will be conducted using a list of pre-identified Medical Subject Headings (MeSH) terms relating to neighbourhood, microbiome and individual characteristics. There will be no date or language restrictions used in the search. In order to be included in the study, a piece must include an evaluation of the relationship between microbiome diversity and neighbourhood (including at least one measurement of the neighbourhood and at least one human microbiome site). Excluded from the review will be those works that do not include all of these measures, literature reviews based on secondary sources and postmortem populations with no report of premortem health factors. The review itself will be an iterative process completed by two reviewers, with a third individual identified to break ties. Documents will be undergoing a risk assessment of bias in order for the authors to comment on the quality of the literature in this area. Finally, results will be discussed with identified stakeholders, including individuals connected to neighbourhoods facing structural inequity and experts in the topics of study through a community advisory board, for their feedback and knowledge transfer.<br><br>ETHICS AND DISSEMINATION: This review does not require ethical approval. Results of this search will be disseminated through peer-reviewed publications. Furthermore, this work is completed in conjunction with a community advisory board so as to ensure dissemination to multiple stakeholders.}, }
@article {pmid36896938, year = {2023}, author = {Fekete, EE and Figeys, D and Zhang, X}, title = {Microbiota-directed biotherapeutics: considerations for quality and functional assessment.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2186671}, pmid = {36896938}, issn = {1949-0984}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Microbiota ; *Neoplasms ; *Gastrointestinal Diseases ; *Metabolic Diseases ; }, abstract = {Mounting evidence points to causative or correlative roles of gut microbiome in the development of a myriad of diseases ranging from gastrointestinal diseases, metabolic diseases to neurological disorders and cancers. Consequently, efforts have been made to develop and apply therapeutics targeting the human microbiome, in particular the gut microbiota, for treating diseases and maintaining wellness. Here we summarize the current development of gut microbiota-directed therapeutics with a focus on novel biotherapeutics, elaborate the need of advanced -omics approaches for evaluating the microbiota-type biotherapeutics, and discuss the clinical and regulatory challenges. We also discuss the development and potential application of ex vivo microbiome assays and in vitro intestinal cellular models in this context. Altogether, this review aims to provide a broad view of promises and challenges of the emerging field of microbiome-directed human healthcare.}, }
@article {pmid36891192, year = {2023}, author = {Jeong, J and Ahn, K and Mun, S and Yun, K and Kim, YT and Jung, W and Lee, KE and Kim, MY and Ahn, Y and Han, K}, title = {Understanding the bacterial compositional network associations between oral and gut microbiome within healthy Koreans.}, journal = {Journal of oral microbiology}, volume = {15}, number = {1}, pages = {2186591}, pmid = {36891192}, issn = {2000-2297}, abstract = {Oral microbial ecosystem could influence intestinal diseases, but there have been insufficient studies demonstrating the association of microbial composition between the oral cavity and the intestinal system. Thus, we aimed to investigate the compositional network within the oral microbiome related to gut enterotype from saliva and stool samples collected from 112 healthy Korean subjects. Here, we performed bacterial 16S amplicon sequencing from clinical samples. Then, we determined oral microbiome type related to individual's gut enterotype for healthy Korean. The co-occurrence analysis was performed to interactivity prediction of microbiome within saliva samples. As a result, it could be classified into two Korean oral microbiome types (KO) and four oral-gut-associated microbiome types (KOGA) according to distribution and significant differences of oral microflora. The co-occurrence analysis showed various bacterial compositional networks linked around Streptococcus and Haemophilus within healthy subjects. The present study was first approach in healthy Koreans to identify the oral microbiome types related to the gut microbiome and investigate their characteristics. Hence, we suggest that our results could be potential healthy control data for identifying differences in microbial composition between healthy people and oral disease patients and studying microbial association with the gut microbial environment (oral-gut microbiome axis).}, }
@article {pmid36890166, year = {2023}, author = {Pasinetti, GM and Turroni, S and Palmieri, J and De Filippo, C}, title = {Human microbiome collection.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {3807}, pmid = {36890166}, issn = {2045-2322}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; }, }
@article {pmid36889023, year = {2023}, author = {Shanahan, F and Ghosh, TS and O'Toole, PW}, title = {Human microbiome variance is underestimated.}, journal = {Current opinion in microbiology}, volume = {73}, number = {}, pages = {102288}, doi = {10.1016/j.mib.2023.102288}, pmid = {36889023}, issn = {1879-0364}, mesh = {Humans ; *Microbiota ; Life Style ; Aging ; }, abstract = {Most of the variance in the human microbiome remains unexplained. Although an extensive list of individual lifestyles shaping the microbiome has been identified, important gaps in knowledge persist. Most human microbiome data are from individuals living in socioeconomically developed countries. This may have skewed the interpretation of microbiome variance and its relationship to health and disease. Moreover, striking under-representation of minority groups in microbiome studies is a missed opportunity to assess context, history and the changing nature of the microbiome in relation to the risk of disease. Therefore, we focus here on areas of recent progress - ageing and ethnicity - both of which contribute to microbiome variance with particular lessons for the promise of microbiome-based diagnostics and therapeutics.}, }
@article {pmid36871794, year = {2023}, author = {Moran, GP and Zgaga, L and Daly, B and Harding, M and Montgomery, T}, title = {Does fluoride exposure impact on the human microbiome?.}, journal = {Toxicology letters}, volume = {379}, number = {}, pages = {11-19}, doi = {10.1016/j.toxlet.2023.03.001}, pmid = {36871794}, issn = {1879-3169}, mesh = {Animals ; Humans ; Fluorides/toxicity ; Fluoridation/adverse effects ; Food ; *Microbiota ; *Fluorosis, Dental ; }, abstract = {Fluoride is added to drinking water in some countries to prevent tooth decay (caries). There is no conclusive evidence that community water fluoridation (CWF) at WHO recommended concentrations for caries prevention has any harmful effects. However, research is ongoing regarding potential effects of ingested fluoride on human neurodevelopment and endocrine dysfunction. Simultaneously, research has emerged highlighting the significance of the human microbiome in gastrointestinal and immune health. In this review we evaluate the literature examining the effect of fluoride exposure on the human microbiome. Unfortunately, none of the studies retrieved examined the effects of ingested fluoridated water on the human microbiome. Animal studies generally examined acute fluoride toxicity following ingestion of fluoridated food and water and conclude that fluoride exposure can detrimentally perturb the normal microbiome. These data are difficult to extrapolate to physiologically relevant human exposure dose ranges and the significance to humans living in areas with CWF requires further investigation. Conversely, evidence suggests that the use of fluoride containing oral hygiene products may have beneficial effects on the oral microbiome regarding caries prevention. Overall, while fluoride exposure does appear to impact the human and animal microbiome, the long-term consequences of this requires further study.}, }
@article {pmid36869345, year = {2023}, author = {Li, J and Jing, Q and Li, J and Hua, M and Di, L and Song, C and Huang, Y and Wang, J and Chen, C and Wu, AR}, title = {Assessment of microbiota in the gut and upper respiratory tract associated with SARS-CoV-2 infection.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {38}, pmid = {36869345}, issn = {2049-2618}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Microbiota ; *Gastrointestinal Microbiome ; Nose ; }, abstract = {BACKGROUND: The human microbiome plays an important role in modulating the host metabolism and immune system. Connections and interactions have been found between the microbiome of the gut and oral pharynx in the context of SARS-CoV-2 and other viral infections; hence, to broaden our understanding of host-viral responses in general and to deepen our knowledge of COVID-19, we performed a large-scale, systematic evaluation of the effect of SARS-CoV-2 infection on human microbiota in patients with varying disease severity.<br><br>RESULTS: We processed 521 samples from 203 COVID-19 patients with varying disease severity and 94 samples from 31 healthy donors, consisting of 213 pharyngeal swabs, 250 sputa, and 152 fecal samples, and obtained meta-transcriptomes as well as SARS-CoV-2 sequences from each sample. Detailed assessment of these samples revealed altered microbial composition and function in the upper respiratory tract (URT) and gut of COVID-19 patients, and these changes are significantly associated with disease severity. Moreover, URT and gut microbiota show different patterns of alteration, where gut microbiome seems to be more variable and in direct correlation with viral load; and microbial community in the upper respiratory tract renders a high risk of antibiotic resistance. Longitudinally, the microbial composition remains relatively stable during the study period.<br><br>CONCLUSIONS: Our study has revealed different trends and the relative sensitivity of microbiome in different body sites to SARS-CoV-2 infection. Furthermore, while the use of antibiotics is often essential for the prevention and treatment of secondary infections, our results indicate a need to evaluate potential antibiotic resistance in the management of COVID-19 patients in the ongoing pandemic. Moreover, a longitudinal follow-up to monitor the restoration of the microbiome could enhance our understanding of the long-term effects of COVID-19. Video Abstract.}, }
@article {pmid36868921, year = {2023}, author = {Bukavina, L and Isali, I and Ginwala, R and Sindhani, M and Calaway, A and Magee, D and Miron, B and Correa, A and Kutikov, A and Zibelman, M and Ghannoum, M and Retuerto, M and Ponsky, L and Markt, S and Uzzo, R and Abbosh, P}, title = {Global Meta-analysis of Urine Microbiome: Colonization of Polycyclic Aromatic Hydrocarbon-degrading Bacteria Among Bladder Cancer Patients.}, journal = {European urology oncology}, volume = {6}, number = {2}, pages = {190-203}, doi = {10.1016/j.euo.2023.02.004}, pmid = {36868921}, issn = {2588-9311}, support = {P30 CA043703/CA/NCI NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; R01 AI145289/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Humans ; Bacteria/genetics ; *Urinary Bladder Neoplasms/urine ; *Microbiota/genetics ; Motivation ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The application of next-generation sequencing techniques has enabled characterization of urinary tract microbiome. Although many studies have demonstrated associations between the human microbiome and bladder cancer (BC), these have not always reported consistent results, thereby necessitating cross-study comparisons. Thus, the fundamental questions remain how we can utilize this knowledge.<br><br>OBJECTIVE: The aim of our study was to examine the disease-associated changes in urine microbiome communities globally utilizing a machine learning algorithm.<br><br>Raw FASTQ files were downloaded for the three published studies in urinary microbiome in BC patients, in addition to our own prospectively collected cohort.<br><br>Demultiplexing and classification were performed using the QIIME 2020.8 platform. De novo operational taxonomic units were clustered using the uCLUST algorithm and defined by 97% sequence similarity and classified at the phylum level against the Silva RNA sequence database. The metadata available from the three studies included were used to evaluate the differential abundance between BC patients and controls via a random-effect meta-analysis using the metagen R function. A machine learning analysis was performed using the SIAMCAT R package.<br><br>RESULTS AND LIMITATIONS: Our study includes 129 BC urine and 60 healthy control samples across four different countries. We identified a total of 97/548 genera to be differentially abundant in the BC urine microbiome compared with that of healthy patients. Overall, while the differences in diversity metrics were clustered around the country of origin (Kruskal-Wallis, p&#xa0;<&#xa0;0.001), collection methodology was a driver of microbiome composition. When assessing dataset from China, Hungary, and Croatia, data demonstrated no discrimination capacity to distinguish between BC patients and healthy adults (area under the curve [AUC] 0.577). However, inclusion of samples with catheterized urine improved the diagnostic accuracy of prediction for BC to AUC 0.995, with precision-recall AUC&#xa0;=&#xa0;0.994. Through elimination of contaminants associated with the collection methodology among all cohorts, our study identified increased abundance of polycyclic aromatic hydrocarbon (PAH)-degrading bacteria Sphingomonas, Acinetobacter, Micrococcus, Pseudomonas, and Ralstonia to be consistently present in BC patients.<br><br>CONCLUSIONS: The microbiota of the BC population may be a reflection of PAH exposure from smoking, environmental pollutants, and ingestion. Presence of PAHs in the urine of BC patients may allow for a unique metabolic niche and provide necessary metabolic resources where other bacteria are not able to flourish. Furthermore, we found that while compositional differences are associated with geography more than with disease, many are driven by the collection methodology.<br><br>PATIENT SUMMARY: The goal of our study was to compare the urine microbiome of bladder cancer patients with that of healthy controls and evaluate any potential bacteria that may be more likely to be found in patients with bladder cancer. Our study is unique as it evaluates this across multiple countries, to find a common pattern. After we removed some of the contamination, we were able to localize several key bacteria that are more likely to be found in the urine of bladder cancer patients. These bacteria all share their ability to break down tobacco carcinogens.}, }
@article {pmid36862015, year = {2023}, author = {Meslé, MM and Gray, CR and Dlakić, M and DuBois, JL}, title = {Bacteroides thetaiotaomicron, a Model Gastrointestinal Tract Species, Prefers Heme as an Iron Source, Yields Protoporphyrin IX as a Product, and Acts as a Heme Reservoir.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0481522}, pmid = {36862015}, issn = {2165-0497}, support = {P20 GM103474/GM/NIGMS NIH HHS/United States ; R35 GM136390/GM/NIGMS NIH HHS/United States ; }, abstract = {Members of the phylum Bacteroidetes are abundant in healthy gastrointestinal (GI) tract flora. Bacteroides thetaiotaomicron is a commensal heme auxotroph and representative of this group. Bacteroidetes are sensitive to host dietary iron restriction but proliferate in heme-rich environments that are also associated with colon cancer. We hypothesized that B. thetaiotaomicron may act as a host reservoir for iron and/or heme. In this study, we defined growth-promoting quantities of iron for B. thetaiotaomicron. B. thetaiotaomicron preferentially consumed and hyperaccumulated iron in the form of heme when presented both heme and nonheme iron sources in excess of its growth needs, leading to an estimated 3.6 to 8.4 mg iron in a model GI tract microbiome consisting solely of B. thetaiotaomicron. Protoporphyrin IX was identified as an organic coproduct of heme metabolism, consistent with anaerobic removal of iron from the heme leaving the intact tetrapyrrole as the observed product. Notably, no predicted or discernible pathway for protoporphyrin IX generation exists in B. thetaiotaomicron. Heme metabolism in congeners of B. thetaiotaomicron has previously been associated with the 6-gene hmu operon, based on genetic studies. A bioinformatics survey demonstrated that the intact operon is widespread in but confined to members of the Bacteroidetes phylum and ubiquitous in healthy human GI tract flora. Anaerobic heme metabolism by commensal Bacteroidetes via hmu is likely a major contributor to human host metabolism of the heme from dietary red meat and a driver for the selective growth of these species in the GI tract consortium. IMPORTANCE Research on bacterial iron metabolism has historically focused on the host-pathogen relationship, where the host suppresses pathogen growth by cutting off access to iron. Less is known about how host iron is shared with bacterial species that live commensally in the anaerobic human GI tract, typified by members of phylum Bacteroidetes. While many facultative pathogens avidly produce and consume heme iron, most GI tract anaerobes are heme auxotrophs whose metabolic preferences we aimed to describe. Understanding iron metabolism by model microbiome species like Bacteroides thetaiotaomicron is essential for modeling the ecology of the GI tract, which serves the long-term biomedical goals of manipulating the microbiome to facilitate host metabolism of iron and remediate dysbiosis and associated pathologies (e.g., inflammation and cancer).}, }
@article {pmid36861799, year = {2023}, author = {Plotnikov, E and Pukhnyarskaya, D and Chernova, A}, title = {Lithium and Microorganisms: Biological Effects and Mechanisms.}, journal = {Current pharmaceutical biotechnology}, volume = {24}, number = {13}, pages = {1623-1629}, doi = {10.2174/1389201024666230302153849}, pmid = {36861799}, issn = {1873-4316}, mesh = {Humans ; *Lithium/pharmacology ; *Microbiota/drug effects ; Soil Microbiology ; Gastrointestinal Microbiome/drug effects ; }, abstract = {This review covers the lithium effects on microorganisms, including gut and soil bacteria. Available studies of the biological effects of lithium salts have revealed a wide range of different effects of lithium cations on various microorganisms, but so far, the study of this direction has not been summarized enough. Here we consider the confirmed and various plausible mechanisms of lithium action on microorganisms. Special emphasis is placed on assessing the effect of lithium ions under oxidative stress and adverse environmental conditions. The impact of lithium on the human microbiome is also being reviewed and discussed. Controversial effects of lithium have been shown, including the inhibitory and stimulating effects of lithium on bacterial growth.}, }
@article {pmid36841913, year = {2023}, author = {Stockdale, SR and Shkoporov, AN and Khokhlova, EV and Daly, KM and McDonnell, SA and O' Regan, O and Nolan, JA and Sutton, TDS and Clooney, AG and Ryan, FJ and Sheehan, D and Lavelle, A and Draper, LA and Shanahan, F and Ross, RP and Hill, C}, title = {Interpersonal variability of the human gut virome confounds disease signal detection in IBD.}, journal = {Communications biology}, volume = {6}, number = {1}, pages = {221}, pmid = {36841913}, issn = {2399-3642}, support = {SFI/12/RC/2273//Science Foundation Ireland (SFI)/ ; 101001684//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; SFI/14/SP APC/B3032//Science Foundation Ireland (SFI)/ ; 220646/Z/20/Z//Wellcome Trust (Wellcome)/ ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Humans ; Virome/genetics ; *Gastrointestinal Microbiome/genetics ; *Viruses/genetics ; *Colitis, Ulcerative/genetics/microbiology ; *Inflammatory Bowel Diseases/genetics ; }, abstract = {Viruses are increasingly recognised as important components of the human microbiome, fulfilling numerous ecological roles including bacterial predation, immune stimulation, genetic diversification, horizontal gene transfer, microbial interactions, and augmentation of metabolic functions. However, our current view of the human gut virome is tainted by previous sequencing requirements that necessitated the amplification of starting nucleic acids. In this study, we performed an original longitudinal analysis of 40 healthy control, 19 Crohn's disease, and 20 ulcerative colitis viromes over three time points without an amplification bias, which revealed and highlighted the interpersonal individuality of the human gut virome. In contrast to a 16 S rRNA gene analysis of matched samples, we show that α- and β-diversity metrics of unamplified viromes are not as efficient at discerning controls from patients with inflammatory bowel disease. Additionally, we explored the intrinsic properties of unamplified gut viromes and show there is considerable interpersonal variability in viral taxa, infrequent longitudinal persistence of intrapersonal viruses, and vast fluctuations in the abundance of temporal viruses. Together, these properties of unamplified faecal viromes confound the ability to discern disease associations but significantly advance toward an unbiased and accurate representation of the human gut virome.}, }
@article {pmid36841736, year = {2023}, author = {Wang, Q and Liu, Z and Ma, A and Li, Z and Liu, B and Ma, Q}, title = {Computational methods and challenges in analyzing intratumoral microbiome data.}, journal = {Trends in microbiology}, volume = {31}, number = {7}, pages = {707-722}, pmid = {36841736}, issn = {1878-4380}, support = {R01 GM131399/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Neoplasms/therapy ; Immunotherapy/methods ; Computational Biology/methods ; Forecasting ; }, abstract = {The human microbiome is intimately related to cancer biology and plays a vital role in the efficacy of cancer treatments, including immunotherapy. Extraordinary evidence has revealed that several microbes influence tumor development through interaction with the host immune system, that is, immuno-oncology-microbiome (IOM). This review focuses on the intratumoral microbiome in IOM and describes the available data and computational methods for discovering biological insights of microbial profiling from host bulk, single-cell, and spatial sequencing data. Critical challenges in data analysis and integration are discussed. Specifically, the microorganisms associated with cancer and cancer treatment in the context of IOM are collected and integrated from the literature. Lastly, we provide our perspectives for future directions in IOM research.}, }
@article {pmid36841691, year = {2023}, author = {Wright, JT}, title = {The human microbiome: The mouth and beyond.}, journal = {Journal of the American Dental Association (1939)}, volume = {154}, number = {4}, pages = {277-278}, doi = {10.1016/j.adaj.2023.02.007}, pmid = {36841691}, issn = {1943-4723}, mesh = {Humans ; *Mouth ; *Microbiota ; Face ; }, }
@article {pmid36840551, year = {2023}, author = {Tierney, BT and Van den Abbeele, P and Al-Ghalith, GA and Verstrepen, L and Ghyselinck, J and Calatayud, M and Marzorati, M and Gadir, AA and Daisley, B and Reid, G and Bron, PA and Gevers, D and Dhir, R and Simmons, SL}, title = {Capacity of a Microbial Synbiotic To Rescue the In Vitro Metabolic Activity of the Gut Microbiome following Perturbation with Alcohol or Antibiotics.}, journal = {Applied and environmental microbiology}, volume = {89}, number = {3}, pages = {e0188022}, pmid = {36840551}, issn = {1098-5336}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Synbiotics ; Anti-Bacterial Agents/pharmacology ; Ethanol ; Fatty Acids, Volatile/metabolism ; Butyrates ; }, abstract = {The human gut microbiome contributes crucial bioactive metabolites that support human health and is sensitive to perturbations from the ingestion of alcohol and antibiotics. We interrogated the response and recovery of human gut microbes after acute alcohol or broad-spectrum antibiotic administration in a gut model simulating the luminal and mucosal colonic environment with an inoculated human microbiome. Both alcohol and antibiotic treatments reduced the production of major short-chain fatty acids (SCFAs) (acetate, propionate, and butyrate), which are established modulators of human health. Treatment with a microbial synbiotic restored and enhanced gut function. Butyrate and acetate production increased by up to 29.7% and 18.6%, respectively, relative to untreated, dysbiotic samples. In parallel, treatment led to increases in the relative abundances of beneficial commensal organisms not found in the synbiotic (e.g., Faecalibacterium prausnitzii and the urolithin-producing organism Gordonibacter pamelaeae) as well as species present in the synbiotic (e.g., Bifidobacterium infantis), suggesting synergistic interactions between supplemented and native microorganisms. These results lead us to conclude that functional shifts in the microbiome, evaluated by both metabolite production and specific taxonomic compositional changes, are an appropriate metric to assess microbiome "recovery" following a dysbiosis-inducing disruption. Overall, these findings support the execution of randomized clinical studies to determine whether a microbial synbiotic can help restore microbiome function after a disruption. IMPORTANCE The human gut microbiome is sensitive to disruptions by common stressors such as alcohol consumption and antibiotic treatment. In this study, we used an in vitro system modeling the gut microbiome to investigate whether treatment with a microbial synbiotic can help restore microbiome function after stress. We find that a complex gut community treated with alcohol or antibiotics showed reduced levels of production of short-chain fatty acids, which are critical beneficial molecules produced by a healthy gut microbiota. Treatment of stressed communities with a microbial synbiotic resulted in the recovery of SCFA production as well as an increase in the abundance of beneficial commensal organisms. Our results suggest that treatment with a microbial synbiotic has the potential to restore healthy gut microbiome function after stress and merits further investigation in clinical studies.}, }
@article {pmid36838304, year = {2023}, author = {Moraes, MM and Mendes, TT and Borges, L and Marques, AL and Núñez-Espinosa, C and Gonçalves, DAP and Simões, CB and Vieira, TS and Ladeira, RVP and Lourenço, TGB and Ribeiro, DV and Hatanaka, E and Heller, D and Arantes, RME}, title = {A 7-Week Summer Camp in Antarctica Induces Fluctuations on Human Oral Microbiome, Pro-Inflammatory Markers and Metabolic Hormones Profile.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838304}, issn = {2076-2607}, support = {442645/2018-0//CNPq/MCTIC/CAPES/FNDCT/PROANTAR/ ; AEC-00017-18; CDS- PPM 000304/16; CBB- APQ-01419-14; DAPG- APQ-01268-21//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado de Minas Gerais (FAPEMIG)/ ; PRPq-UFMG//Pr&#xf3;-Reitoria de Pesquisa da Universidade Federal de Minas Gerais/ ; 311976/2021-2//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico (CNPq)/ ; 88887.321687/2019-00 88882.314890/2013-01//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior - Brasil (CAPES) - Finance Code 001/ ; }, abstract = {Antarctic camps pose psychophysiological challenges related to isolated, confined, and extreme (ICE) conditions, including meals composed of sealed food. ICE conditions can influence the microbiome and inflammatory responses. Seven expeditioners took part in a 7-week Antarctic summer camp (Nelson Island) and were evaluated at Pre-Camp (i.e., at the beginning of the ship travel), Camp-Initial (i.e., 4th and 5th day in camp), Camp-Middle (i.e., 19th-20th, and 33rd-34th days), Camp-Final (i.e., 45th-46th day), and at the Post-Camp (on the ship). At the Pre-Camp, Camp-Initial, and Camp-Final, we assessed microbiome and inflammatory markers. Catecholamines were accessed Pre- and Post-Camp. Heart rate variability (HRV), leptin, thyroid stimulating hormone (TSH), and thyroxine (T4) were accessed at all time points. Students' t-tests or repeated-measures analysis of variance (one or two-way ANOVA) followed by Student-Newman-Keuls (post hoc) were used for parametric analysis. Kruskal-Wallis test was applied for non-parametric analysis. Microbiome analysis showed a predominance of Pseudomonadota (34.01%), Bacillota (29.82%), and Bacteroidota (18.54%), followed by Actinomycetota (5.85%), and Fusobacteria (5.74%). Staying in a long-term Antarctic camp resulted in microbiome fluctuations with a reduction in Pseudomonadota-a "microbial signature" of disease. However, the pro-inflammatory marker leptin and IL-8 tended to increase, and the angiogenic factor VEGF was reduced during camp. These results suggest that distinct Antarctic natural environments and behavioral factors modulate oral microbiome and inflammation.}, }
@article {pmid36838283, year = {2023}, author = {Morrison, AG and Sarkar, S and Umar, S and Lee, STM and Thomas, SM}, title = {The Contribution of the Human Oral Microbiome to Oral Disease: A Review.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838283}, issn = {2076-2607}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; }, abstract = {The oral microbiome is an emerging field that has been a topic of discussion since the development of next generation sequencing and the implementation of the human microbiome project. This article reviews the current literature surrounding the oral microbiome, briefly highlighting most recent methods of microbiome characterization including cutting edge omics, databases for the microbiome, and areas with current gaps in knowledge. This article also describes reports on microorganisms contained in the oral microbiome which include viruses, archaea, fungi, and bacteria, and provides an in-depth analysis of their significant roles in tissue homeostasis. Finally, we detail key bacteria involved in oral disease, including oral cancer, and the current research surrounding their role in stimulation of inflammatory cytokines, the role of gingival crevicular fluid in periodontal disease, the creation of a network of interactions between microorganisms, the influence of the planktonic microbiome and cospecies biofilms, and the implications of antibiotic resistance. This paper provides a comprehensive literature analysis while also identifying gaps in knowledge to enable future studies to be conducted.}, }
@article {pmid36837548, year = {2023}, author = {Iavarone, I and Greco, PF and La Verde, M and Morlando, M and Torella, M and de Franciscis, P and Ronsini, C}, title = {Correlations between Gut Microbial Composition, Pathophysiological and Surgical Aspects in Endometriosis: A Review of the Literature.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {59}, number = {2}, pages = {}, pmid = {36837548}, issn = {1648-9144}, mesh = {Female ; Humans ; *Endometriosis/pathology ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; Uterus ; *Probiotics ; }, abstract = {Background and Objectives: Endometriosis is an estrogen-dependent, inflammatory, gynecological disorder represented by the migration of endometrial tissue outside the uterus. It can manifest through gynecological and gastrointestinal (GI) signs. Given the hormonal imbalances in endometriosis and the effect of microbiota on immune dysfunction, it has been thought that the human microbiome may play a role in its pathogenesis, acting differently before and after laparotomy. The aim of this review is to establish whether there is an interaction between endometriosis and gut microbial composition. Materials and Methods: We aimed to review available literature by systematically searching five databases: PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect. We included records describing gut microbiota in the context of endometriosis-observing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines-to recognize the presence of disease by the expression of bacterial taxa-based on 16S ribosomal RNA gene sequencing analysis. Results: Among 10 studies selected, there were four review articles and six clinical trials. The latter identified significant differences at a genus level in increased Prevotella, Blautia, and Bifidobacterium and decreased Paraprevotella, Ruminococcus, and Lachnospira (p < 0.05). In patients undergoing abdominal hysterectomy, Proteobacteria phylum increased from 34.36% before surgery to 54.04% after surgery (p < 0.05). Conclusions: Although scientific literature reports different characterizations of intestinal microbiota in endometriotic patients, further evidence is needed to develop new diagnostic-therapeutic strategies, for example, administration with probiotics before surgery.}, }
@article {pmid36835535, year = {2023}, author = {Candel, S and Tyrkalska, SD and Pérez-Sanz, F and Moreno-Docón, A and Esteban, &#xc1; and Cayuela, ML and Mulero, V}, title = {Analysis of 16S rRNA Gene Sequence of Nasopharyngeal Exudate Reveals Changes in Key Microbial Communities Associated with Aging.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835535}, issn = {1422-0067}, support = {00006/COVI/20//Fundaci&#xf3;n S&#xe9;neca - Agencia de Ciencia y Tecnolog&#xed;a de la Regi&#xf3;n de Murcia/ ; }, mesh = {Male ; Female ; Humans ; RNA, Ribosomal, 16S/genetics ; Genes, rRNA ; Nasopharynx/microbiology ; *Microbiota/genetics ; Bacteria/genetics ; Aging ; *Virus Diseases/genetics ; }, abstract = {Functional or compositional perturbations of the microbiome can occur at different sites, of the body and this dysbiosis has been linked to various diseases. Changes in the nasopharyngeal microbiome are associated to patient's susceptibility to multiple viral infections, supporting the idea that the nasopharynx may be playing an important role in health and disease. Most studies on the nasopharyngeal microbiome have focused on a specific period in the lifespan, such as infancy or the old age, or have other limitations such as low sample size. Therefore, detailed studies analyzing the age- and sex-associated changes in the nasopharyngeal microbiome of healthy people across their whole life are essential to understand the relevance of the nasopharynx in the pathogenesis of multiple diseases, particularly viral infections. One hundred twenty nasopharyngeal samples from healthy subjects of all ages and both sexes were analyzed by 16S rRNA sequencing. Nasopharyngeal bacterial alpha diversity did not vary in any case between age or sex groups. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the predominant phyla in all the age groups, with several sex-associated. Acinetobacter, Brevundimonas, Dolosigranulum, Finegoldia, Haemophilus, Leptotrichia, Moraxella, Peptoniphilus, Pseudomonas, Rothia, and Staphylococcus were the only 11 bacterial genera that presented significant age-associated differences. Other bacterial genera such as Anaerococcus, Burkholderia, Campylobacter, Delftia, Prevotella, Neisseria, Propionibacterium, Streptococcus, Ralstonia, Sphingomonas, and Corynebacterium appeared in the population with a very high frequency, suggesting that their presence might be biologically relevant. Therefore, in contrast to other anatomical areas such as the gut, bacterial diversity in the nasopharynx of healthy subjects remains stable and resistant to perturbations throughout the whole life and in both sexes. Age-associated abundance changes were observed at phylum, family, and genus levels, as well as several sex-associated changes probably due to the different levels of sex hormones present in both sexes at certain ages. Our results provide a complete and valuable dataset that will be useful for future research aiming for studying the relationship between changes in the nasopharyngeal microbiome and susceptibility to or severity of multiple diseases.}, }
@article {pmid36835341, year = {2023}, author = {Brogna, C and Costanzo, V and Brogna, B and Bisaccia, DR and Brogna, G and Giuliano, M and Montano, L and Viduto, V and Cristoni, S and Fabrowski, M and Piscopo, M}, title = {Analysis of Bacteriophage Behavior of a Human RNA Virus, SARS-CoV-2, through the Integrated Approach of Immunofluorescence Microscopy, Proteomics and D-Amino Acid Quantification.}, journal = {International journal of molecular sciences}, volume = {24}, number = {4}, pages = {}, pmid = {36835341}, issn = {1422-0067}, mesh = {Humans ; SARS-CoV-2/genetics ; *COVID-19 ; RNA ; *Bacteriophages/genetics ; Amino Acids ; Proteomics ; *Viruses/genetics ; Microscopy, Fluorescence ; }, abstract = {SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been observed in gut microbiome bacteria. Many studies emphasize the importance of surface immunity and also that the mucosal system is critical in the interaction of the pathogen with the cells of the oral, nasal, pharyngeal, and intestinal epithelium. Recent studies have shown how bacteria in the human gut microbiome produce toxins capable of altering the classical mechanisms of interaction of viruses with surface cells. This paper presents a simple approach to highlight the initial behavior of a novel pathogen, SARS-CoV-2, on the human microbiome. The immunofluorescence microscopy technique can be combined with spectral counting performed at mass spectrometry of viral peptides in bacterial cultures, along with identification of the presence of D-amino acids within viral peptides in bacterial cultures and in patients' blood. This approach makes it possible to establish the possible expression or increase of viral RNA viruses in general and SARS-CoV-2, as discussed in this study, and to determine whether or not the microbiome is involved in the pathogenetic mechanisms of the viruses. This novel combined approach can provide information more rapidly, avoiding the biases of virological diagnosis and identifying whether a virus can interact with, bind to, and infect bacteria and epithelial cells. Understanding whether some viruses have bacteriophagic behavior allows vaccine therapies to be focused either toward certain toxins produced by bacteria in the microbiome or toward finding inert or symbiotic viral mutations with the human microbiome. This new knowledge opens a scenario on a possible future vaccine: the probiotics vaccine, engineered with the right resistance to viruses that attach to both the epithelium human surface and gut microbiome bacteria.}, }
@article {pmid36817461, year = {2023}, author = {Sun, Y and Wen, M and Liu, Y and Wang, Y and Jing, P and Gu, Z and Jiang, T and Wang, W}, title = {The human microbiome: A promising target for lung cancer treatment.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1091165}, pmid = {36817461}, issn = {1664-3224}, mesh = {Humans ; Lung ; *Lung Neoplasms ; *Microbiota/physiology ; }, abstract = {Lung cancer is the leading cause of cancer-related deaths worldwide, and insights into its underlying mechanisms as well as potential therapeutic strategies are urgently needed. The microbiome plays an important role in human health, and is also responsible for the initiation and progression of lung cancer through its induction of inflammatory responses and participation in immune regulation, as well as for its role in the generation of metabolic disorders and genotoxicity. Here, the distribution of human microflora along with its biological functions, the relationship between the microbiome and clinical characteristics, and the role of the microbiome in clinical treatment of lung cancer were comprehensively reviewed. This review provides a basis for the current understanding of lung cancer mechanisms with a focus on the microbiome, and contributes to future decisions on treatment management.}, }
@article {pmid36811373, year = {2023}, author = {Mancini, VO and Brook, J and Hernandez, C and Strickland, D and Christophersen, CT and D'Vaz, N and Silva, D and Prescott, S and Callaghan, B and Downs, J and Finlay-Jones, A}, title = {Associations between the human immune system and gut microbiome with neurodevelopment in the first 5 years of life: A systematic scoping review.}, journal = {Developmental psychobiology}, volume = {65}, number = {2}, pages = {e22360}, pmid = {36811373}, issn = {1098-2302}, mesh = {Infant ; Child ; Humans ; *Gastrointestinal Microbiome ; Child Development ; Brain ; Immune System ; Biomarkers ; }, abstract = {The aim of this review was to map the literature assessing associations between maternal or infant immune or gut microbiome biomarkers and child neurodevelopmental outcomes within the first 5 years of life. We conducted a PRISMA-ScR compliant review of peer-reviewed, English-language journal articles. Studies reporting gut microbiome or immune system biomarkers and child neurodevelopmental outcomes prior to 5 years were eligible. Sixty-nine of 23,495 retrieved studies were included. Of these, 18 reported on the maternal immune system, 40 on the infant immune system, and 13 on the infant gut microbiome. No studies examined the maternal microbiome, and only one study examined biomarkers from both the immune system and the gut microbiome. Additionally, only one study included both maternal and infant biomarkers. Neurodevelopmental outcomes were assessed from 6 days to 5 years. Associations between biomarkers and neurodevelopmental outcomes were largely nonsignificant and small in effect size. While the immune system and gut microbiome are thought to have interactive impacts on the developing brain, there remains a paucity of published studies that report biomarkers from both systems and associations with child development outcomes. Heterogeneity of research designs and methodologies may also contribute to inconsistent findings. Future studies should integrate data across biological systems to generate novel insights into the biological underpinnings of early development.}, }
@article {pmid36803658, year = {2023}, author = {Wastyk, HC and Perelman, D and Topf, M and Fragiadakis, GK and Robinson, JL and Sonnenburg, JL and Gardner, CD and Sonnenburg, ED}, title = {Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet.}, journal = {Gut microbes}, volume = {15}, number = {1}, pages = {2178794}, pmid = {36803658}, issn = {1949-0984}, mesh = {Adult ; Humans ; *Metabolic Syndrome/drug therapy ; Prospective Studies ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; Diet ; Double-Blind Method ; }, abstract = {An individual's immune and metabolic status is coupled to their microbiome. Probiotics offer a promising, safe route to influence host health, possibly via the microbiome. Here, we report an 18-week, randomized prospective study that explores the effects of a probiotic vs. placebo supplement on 39 adults with elevated parameters of metabolic syndrome. We performed longitudinal sampling of stool and blood to profile the human microbiome and immune system. While we did not see changes in metabolic syndrome markers in response to the probiotic across the entire cohort, there were significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants. Conversely, the non-responders had increased blood glucose and insulin levels over time. The responders had a distinct microbiome profile at the end of the intervention relative to the non-responders and placebo arm. Importantly, diet was a key differentiating factor between responders and non-responders. Our results show participant-specific effects of a probiotic supplement on improving parameters of metabolic syndrome and suggest that dietary factors may enhance stability and efficacy of the supplement.}, }
@article {pmid36802215, year = {2023}, author = {Zangl, I and Beyer, R and Gattesco, A and Labuda, R and Pap, IJ and Strauss, J and Schüller, C}, title = {Limosilactobacillus fermentum Limits Candida glabrata Growth by Ergosterol Depletion.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0332622}, pmid = {36802215}, issn = {2165-0497}, abstract = {Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with Lactobacillus spp. in the gastrointestinal and vaginal tract. In fact, Lactobacillus species are thought to competitively prevent Candida overgrowth. We investigated the molecular aspects of this antifungal effect by analyzing the interaction of C. glabrata strains with Limosilactobacillus fermentum. From a collection of clinical C. glabrata isolates, we identified strains with different sensitivities to L. fermentum in coculture. We analyzed the variation of their expression pattern to isolate the specific response to L. fermentum. C. glabrata-L. fermentum coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. L. fermentum coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the Lactobacillus species, even in coculture with different Candida species. We found a similar ergosterol-depleting effect with other lactobacillus strains (Lactobacillus crispatus and Lactobacillus rhamosus) on Candida albicans, Candida tropicalis, and Candida krusei. The addition of ergosterol improved C. glabrata growth in the coculture. Blocking ergosterol synthesis with fluconazole increased the susceptibility against L. fermentum, which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata Δerg11 mutant, defective in ergosterol biosynthesis, was highly sensitive to L. fermentum. In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with L. fermentum. IMPORTANCE The yeast Candida glabrata, an opportunistic fungal pathogen, and the bacterium Limosilactobacillus fermentum both inhabit the human gastrointestinal and vaginal tract. Lactobacillus species, belonging to the healthy human microbiome, are thought to prevent C. glabrata infections. We investigated the antifungal effect of Limosilactobacillus fermentum on C. glabrata strains quantitively in vitro. The interaction between C. glabrata and L. fermentum evokes an upregulation of genes required for the synthesis of ergosterol, a sterol constituent of the fungal plasma membrane. We found a dramatic reduction of ergosterol in C. glabrata when it was exposed to L. fermentum. This effect extended to other Candida species and other Lactobacillus species. Furthermore, fungal growth was efficiently suppressed by a combination of L. fermentum and fluconazole, an antifungal drug which inhibits ergosterol synthesis. Thus, fungal ergosterol is a key metabolite for the suppression of C. glabrata by L. fermentum.}, }
@article {pmid36800400, year = {2023}, author = {Xing, Y and Clark, JR and Chang, JD and Chirman, DM and Green, S and Zulk, JJ and Jelinski, J and Patras, KA and Maresso, AW}, title = {Broad protective vaccination against systemic Escherichia coli with autotransporter antigens.}, journal = {PLoS pathogens}, volume = {19}, number = {2}, pages = {e1011082}, pmid = {36800400}, issn = {1553-7374}, support = {U19 AI144297/AI/NIAID NIH HHS/United States ; U19 AI157981/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Humans ; Mice ; Escherichia coli ; Type V Secretion Systems/genetics ; *Escherichia coli Infections/prevention &amp; control ; *Extraintestinal Pathogenic Escherichia coli/genetics ; Vaccination ; Virulence Factors/genetics ; Vaccines, Synthetic ; *Urinary Tract Infections/prevention &amp; control ; *Bacteremia/prevention &amp; control ; Immunoglobulin G/pharmacology ; }, abstract = {Extraintestinal pathogenic Escherichia coli (ExPEC) is the leading cause of adult life-threatening sepsis and urinary tract infections (UTI). The emergence and spread of multidrug-resistant (MDR) ExPEC strains result in a considerable amount of treatment failure and hospitalization costs, and contribute to the spread of drug resistance amongst the human microbiome. Thus, an effective vaccine against ExPEC would reduce morbidity and mortality and possibly decrease carriage in healthy or diseased populations. A comparative genomic analysis demonstrated a gene encoding an invasin-like protein, termed sinH, annotated as an autotransporter protein, shows high prevalence in various invasive ExPEC phylogroups, especially those associated with systemic bacteremia and UTI. Here, we evaluated the protective efficacy and immunogenicity of a recombinant SinH-based vaccine consisting of either domain-3 or domains-1,2, and 3 of the putative extracellular region of surface-localized SinH. Immunization of a murine host with SinH-based antigens elicited significant protection against various strains of the pandemic ExPEC sequence type 131 (ST131) as well as multiple sequence types in two distinct models of infection (colonization and bacteremia). SinH immunization also provided significant protection against ExPEC colonization in the bladder in an acute UTI model. Immunized cohorts produced significantly higher levels of vaccine-specific serum IgG and urinary IgG and IgA, findings consistent with mucosal protection. Collectively, these results demonstrate that autotransporter antigens such as SinH may constitute promising ExPEC phylogroup-specific and sequence-type effective vaccine targets that reduce E. coli colonization and virulence.}, }
@article {pmid36798240, year = {2023}, author = {Hall, B and Levy, S and Dufault-Thompson, K and Ndjite, GM and Weiss, A and Braccia, D and Jenkins, C and Yang, Y and Arp, G and Abeysinghe, S and Jermain, M and Wu, CH and Jiang, X}, title = {Discovery of the gut microbial enzyme responsible for bilirubin reduction to urobilinogen.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36798240}, issn = {2692-8205}, support = {U54 DK110858/DK/NIDDK NIH HHS/United States ; }, abstract = {The degradation of heme and the interplay of its catabolic derivative, bilirubin, between humans and their gut microbiota is an essential facet of human health. However, the hypothesized bacterial enzyme that reduces bilirubin to urobilinogen, a key step that produces the excretable waste products of this pathway, has remained unidentified. In this study, we used a combination of biochemical analyses and comparative genomics to identify a novel enzyme, BilR, that can reduce bilirubin to urobilinogen. We delineated the BilR sequences from other members of the Old Yellow Enzyme family through the identification of key residues in the active site that are critical for bilirubin reduction and found that BilR is predominantly encoded by Firmicutes in the gut microbiome. Our analysis of human gut metagenomes showed that BilR is a common feature of a healthy adult human microbiome but has a decreased prevalence in neonates and IBD patients. This discovery sheds new light on the role of the gut microbiome in bilirubin metabolism and highlights the significance of the gut-liver axis in maintaining bilirubin homeostasis.}, }
@article {pmid36796332, year = {2023}, author = {Liu, YY}, title = {Controlling the human microbiome.}, journal = {Cell systems}, volume = {14}, number = {2}, pages = {135-159}, pmid = {36796332}, issn = {2405-4720}, support = {U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; RF1 AG067744/AG/NIA NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; }, mesh = {Humans ; *Microbiota/genetics ; }, abstract = {We coexist with a vast number of microbes that live in and on our bodies. Those microbes and their genes are collectively known as the human microbiome, which plays important roles in human physiology and diseases. We have acquired extensive knowledge of the organismal compositions and metabolic functions of the human microbiome. However, the ultimate proof of our understanding of the human microbiome is reflected in our ability to manipulate it for health benefits. To facilitate the rational design of microbiome-based therapies, there are many fundamental questions to be addressed at the systems level. Indeed, we need a deep understanding of the ecological dynamics associated with such a complex ecosystem before we rationally design control strategies. In light of this, this review discusses progress from various fields, e.g., community ecology, network science, and control theory, that are helping us make progress toward the ultimate goal of controlling the human microbiome.}, }
@article {pmid36796148, year = {2023}, author = {Nami, Y and Haghshenas, B and Javanmard, A and Samari, M and Mohammadi, N and Oroojalian, F and Mokhtarzadeh, A}, title = {A critical review of the recent concept of artificial mechanical uterus design in relation to the maternal microbiome: An Update to past researches.}, journal = {Journal of reproductive immunology}, volume = {156}, number = {}, pages = {103828}, doi = {10.1016/j.jri.2023.103828}, pmid = {36796148}, issn = {1872-7603}, mesh = {Pregnancy ; Female ; Humans ; *Dysbiosis ; Infectious Disease Transmission, Vertical ; Uterus ; *Microbiota ; Vagina ; }, abstract = {The microbiome in the female reproductive tract plays an essential role in immune modulation and reproductive health. However, various microbes become established during pregnancy, the balance of which plays a crucial role in embryonic development and healthy births. The contribution of disturbances in the microbiome profile to embryo health is poorly understood. A better understanding of the relationship between reproductive outcomes and the vaginal microbiota is needed to optimize the chances of healthy births. In this regards, microbiome dysbiosis refers to conditions in which the pathways of communication and balance within the normal microbiome are imbalanced due to the intrusion of pathogenic microorganisms into the reproductive system. This review summarizes the current state of knowledge on the natural human microbiome, with a focus on the natural uterine microbiome, mother-to-child transmission, dysbiosis, and the pattern of microbial change in pregnancy and parturition, and reviews the effects of artificial uterus probiotics during pregnancy. These effects can be studied in the sterile environment of an artificial uterus, and microbes with potential probiotic activity can be studied as a possible therapeutic approach. The artificial uterus is a technological device or biobag used as an incubator, allowing extracorporeal pregnancy. Establishing beneficial microbial communities within the artificial womb using probiotic species could modulate the immune system of both the fetus and the mother. The artificial womb could be used to select the best strains of probiotic species to fight infection with specific pathogens. Questions about the interactions and stability of the most appropriate probiotics, as well as dosage and duration of treatment, need to be answered before probiotics can be a clinical treatment in human pregnancy.}, }
@article {pmid36790695, year = {2022}, author = {Rayo, E and Neukamm, J and Tomoum, N and Eppenberger, P and Breidenstein, A and Bouwman, AS and Schuenemann, VJ and Rühli, FJ}, title = {Metagenomic analysis of Ancient Egyptian canopic jars.}, journal = {American journal of biological anthropology}, volume = {179}, number = {2}, pages = {307-313}, pmid = {36790695}, issn = {2692-7691}, mesh = {Humans ; Egypt ; *DNA, Ancient ; *Mummies/pathology ; Lung ; Base Sequence ; }, abstract = {UNLABELLED: Ancient Egyptian remains have been of interest for anthropological research for decades. Despite many investigations, the ritual vessels for the internal organs removed during body preparation-liver, lungs, stomach, and intestines, of Egyptian mummies are rarely used for palaeopathological or medical investigations. These artifacts, commonly referred to as canopic jars, are the perfect combination of cultural and biological material and present an untapped resource for both Egyptological and medical fields. Nevertheless, technical challenges associated with this archeological material have prevented the application of current ancient DNA techniques for both the characterization of human and pathogenic DNA. We present shotgun-sequenced metagenomic profiles and ancient DNA degradation patterns from multiple canopic jars sampled from several European museum collections and enumerate current limitations and possible solutions for the future analysis of similar material. This is the first-ever recorded evidence of ancient human DNA found in Ancient Egyptian canopic jars and the first associated metagenomic description of bacterial taxa in these funerary artifacts.<br><br>OBJECTIVES: In this study, our objectives were to characterize the metagenomic profile of the Ancient Egyptian funerary vessels known as canopic jars to retrieve endogenous ancient human DNA, reconstruct ancient microbial communities, and identify possible pathogens that could shed light on disease states of individuals from the past.<br><br>METHODS: We applied ancient DNA techniques on 140 canopic jars to extract DNA and generate whole-genome sequencing libraries for the analysis of both human and bacterial DNA. The samples were obtained from museum collections in Berlin (DE), Burgdorf (DE), Leiden (NE), Manchester (UK), Munich (DE), St. Gallen (CH), Turin (IT), and Zagreb (HR).<br><br>RESULTS: Here we describe the first isolated DNA from the Egyptian artifacts that hold human viscera. No previous work was ever conducted on such material, which led to the first characterization of human DNA from Ancient Egyptian canopic jars and the profiling of the complex bacterial composition of this highly degraded, challenging, organic material. However, the DNA recovered was not of enough quality to confidently characterize bacterial taxa associated with infectious diseases, nor exclusive bacterial members of the human microbiome.<br><br>DISCUSSION: In summary, we present the first genomic survey of the visceral content of Ancient Egyptian funerary artifacts and demonstrate the limitations of current molecular methods to analyze canopic jars, such as the incomplete history of the objects or the presence of uncharacterized compounds that can hamper the recovery of DNA. Our work highlights the main challenges and caveats when working with such complicated archeological material - and offers sampling recommendations for similarly complex future studies, such as incrementing the amount of starting material and sampling from the less exposed parts of the jar content. This is the first-ever recorded evidence of ancient human DNA found in Ancient Egyptian canopic jars, and our results open new avenues in the study of neglected archeological artifacts.}, }
@article {pmid36778490, year = {2023}, author = {Zhu, B and Serrano, M and Buck, G}, title = {The influence of maternal factors on the neonatal microbiome and health.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {36778490}, issn = {2693-5015}, abstract = {The human microbiome plays an essential role in human health. However, the influence of maternal factors on the neonatal microbiome remains obscure. Herein, our observations suggest that the neonatal buccal microbiome is similar to the maternal buccal microbiome, but the neonatal gastrointestinal microbiome develops a unique composition at an early stage. The low complexity of the neonatal buccal microbiome is a hallmark of maternal and neonatal health, but that of the neonatal gastrointestinal microbiome is associated with maternal inflammation-related metabolites. Microbial infections in the maternal reproductive tract universally impact the complexity of the neonatal microbiomes, and the body site is most important in modulating the composition of the neonatal microbiomes. Additionally, maternal lipids attenuated the adverse influence of several maternal factors on the neonatal microbiomes. Finally, admission of neonates to the newborn intensive care unit is associated with sub-optimal states of the maternal buccal and rectal microbiomes and maternal health.}, }
@article {pmid36778319, year = {2023}, author = {Wright, ML and Podnar, J and Longoria, KD and Nguyen, TC and Lim, S and Garcia, S and Wylie, D}, title = {Comparison of commercial DNA extraction kits for whole metagenome sequencing of human oral, vaginal, and rectal microbiome samples.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36778319}, issn = {2692-8205}, support = {K01 NR017903/NR/NINR NIH HHS/United States ; }, abstract = {INTRODUCTION: Advancements in DNA extraction and sequencing technologies have been fundamental in deciphering the significance of the microbiome related to human health and pathology. Whole metagenome shotgun sequencing (WMS) is gaining popularity in use compared to its predecessor (i.e., amplicon-based approaches). However, like amplicon-based approaches, WMS is subject to bias from DNA extraction methods that can compromise the integrity of sequencing and subsequent findings. The purpose of this study was to evaluate systematic differences among four commercially available DNA extraction kits frequently used for WMS analysis of the microbiome.<br><br>METHODS: Oral, vaginal, and rectal swabs were collected in replicates of four by a healthcare provider from five participants and randomized to one of four DNA extraction kits. Two extraction blanks and three replicate mock community samples were also extracted using each extraction kit. WMS was completed with NovaSeq 6000 for all samples. Sequencing and microbial communities were analyzed using nonmetric multidimensional scaling and compositional bias analysis.<br><br>RESULTS: Extraction kits differentially biased the percentage of reads attributed to microbial taxa across samples and body sites. The PowerSoil Pro kit performed best in approximating expected proportions of mock communities. While HostZERO was biased against gram-negative bacteria, the kit outperformed other kits in extracting fungal DNA. In clinical samples, HostZERO yielded a smaller fraction of reads assigned to Homo sapiens across sites and had a higher fraction of reads assigned to bacterial taxa compared to other kits. However, HostZERO appears to bias representation of microbial communities and demonstrated the most dispersion by site, particularly for vaginal and rectal samples.<br><br>CONCLUSIONS: Systematic differences exist among four frequently referenced DNA extraction kits when used for WMS analysis of the human microbiome. Consideration of such differences in study design and data interpretation is imperative to safeguard the integrity of microbiome research and reproducibility of results.}, }
@article {pmid36776345, year = {2022}, author = {Osborne, N and Peterson, CB and Vannucci, M}, title = {Latent Network Estimation and Variable Selection for Compositional Data Via Variational EM.}, journal = {Journal of computational and graphical statistics : a joint publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America}, volume = {31}, number = {1}, pages = {163-175}, pmid = {36776345}, issn = {1061-8600}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {Network estimation and variable selection have been extensively studied in the statistical literature, but only recently have those two challenges been addressed simultaneously. In this article, we seek to develop a novel method to simultaneously estimate network interactions and associations to relevant covariates for count data, and specifically for compositional data, which have a fixed sum constraint. We use a hierarchical Bayesian model with latent layers and employ spike-and-slab priors for both edge and covariate selection. For posterior inference, we develop a novel variational inference scheme with an expectation-maximization step, to enable efficient estimation. Through simulation studies, we demonstrate that the proposed model outperforms existing methods in its accuracy of network recovery. We show the practical utility of our model via an application to microbiome data. The human microbiome has been shown to contribute too many of the functions of the human body, and also to be linked with a number of diseases. In our application, we seek to better understand the interaction between microbes and relevant covariates, as well as the interaction of microbes with each other. We call our algorithm simultaneous inference for networks and covariates and provide a Python implementation, which is available online.}, }
@article {pmid36774510, year = {2023}, author = {Cappello, C and Acin-Albiac, M and Pinto, D and Polo, A and Filannino, P and Rinaldi, F and Gobbetti, M and Di Cagno, R}, title = {Do nomadic lactobacilli fit as potential vaginal probiotics? The answer lies in a successful selective multi-step and scoring approach.}, journal = {Microbial cell factories}, volume = {22}, number = {1}, pages = {27}, pmid = {36774510}, issn = {1475-2859}, mesh = {Pregnancy ; Infant, Newborn ; Female ; Humans ; *Lactobacillus ; Bacterial Adhesion ; Vagina ; Candida albicans ; *Probiotics ; Inflammation ; }, abstract = {BACKGROUND: The goal of this study was to create a multi-strain probiotic gel that would foster a lactobacilli-dominated vaginal microbiota in pregnant women and ensure appropriate eubiosis for the newborn. Nomadic lactobacilli (95 strains), mostly isolated from food sources, were preliminarily screened for functional traits before being characterized for their capability to inhibit the two vaginal pathogens Streptococcus agalactiae and Candida albicans, which may lead to adverse pregnancy-related outcomes. Eight best-performing strains were chosen and furtherly investigated for their ability to produce biofilm. Lastly, the two selected potential probiotic candidates were analyzed in vitro for their ability to reduce the inflammation caused by C. albicans infection on the reconstituted human vaginal epithelium (HVE).<br><br>RESULTS: Lactiplantibacillus plantarum produced both isomers of lactic acid, while Lacticaseibacillus paracasei produced only L-isomer. The production of hydrogen peroxide was strain-dependent, with the highest concentrations found within Lact. paracasei strains. The auto-aggregation capacity and hydrophobicity traits were species-independent. S. agalactiae 88II3 was strongly inhibited both at pH 7.0 and 4.0, whereas the inhibition of C. albicans UNIBZ54 was less frequent. Overall, L. plantarum strains had the highest pathogen inhibition and functional scoring. L. plantarum C5 and POM1, which were selected as potential probiotic candidates also based on their ability to form biofilms, were able to counteract the inflammation process caused by C. albicans infection in the HVE model.<br><br>CONCLUSIONS: Our multi-step and cumulative scoring-based approach was proven successful in mining and highlighting the probiotic potential of two nomadic lactobacilli strains (L. plantarum C5 and POM1), being applicable to preserve and improve human vaginal health.}, }
@article {pmid36770726, year = {2023}, author = {Zhang, MN and Xie, R and Wang, HG and Wen, X and Wang, JY and He, L and Zhang, MH and Yang, XZ}, title = {Cepharanthine Alleviates DSS-Induced Ulcerative Colitis via Regulating Aconitate Decarboxylase 1 Expression and Macrophage Infiltration.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {3}, pages = {}, pmid = {36770726}, issn = {1420-3049}, mesh = {Animals ; Mice ; Humans ; *Colitis, Ulcerative/chemically induced/drug therapy/metabolism ; Macrophages ; Colon/metabolism ; *Benzylisoquinolines/pharmacology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; *Colitis/metabolism ; Mice, Inbred C57BL ; }, abstract = {Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.}, }
@article {pmid36769194, year = {2023}, author = {Campisciano, G and Zanotta, N and Quadrifoglio, M and Careri, A and Torresani, A and Cason, C and De Seta, F and Ricci, G and Comar, M and Stampalija, T}, title = {The Bacterial DNA Profiling of Chorionic Villi and Amniotic Fluids Reveals Overlaps with Maternal Oral, Vaginal, and Gut Microbiomes.}, journal = {International journal of molecular sciences}, volume = {24}, number = {3}, pages = {}, pmid = {36769194}, issn = {1422-0067}, support = {5MILLE15D5//Ministero della Salute/ ; }, mesh = {Pregnancy ; Female ; Humans ; *Amniotic Fluid ; Chorionic Villi ; *Gastrointestinal Microbiome ; DNA, Bacterial/genetics ; DNA Fingerprinting ; Bacteria/genetics ; Vagina/microbiology ; Cytokines/genetics ; }, abstract = {The in utero microbiome hypothesis has been long debated. This hypothesis will change our comprehension of the pioneer human microbiome if proved correct. In 60 uncomplicated pregnancies, we profiled the microbiome of chorionic villi (CV) and amniotic fluids (AF) in relation to maternal saliva, rectum, and vagina and the soluble cytokines cascade in the vagina, CV and AF. In our series, 12/37 (32%) AF and 10/23 (44%) CV tested positive for bacterial DNA. CV and AF harbored bacterial DNA of Streptococcus and Lactobacillus, overlapping that of the matched oral and vaginal niches, which showed a dysbiotic microbiome. In these pregnant women, the immune profiling revealed an immune hyporesponsiveness in the vagina and a high intraamniotic concentration of inflammatory cytokines. To understand the eventual role of bacterial colonization of the CV and AF and the associated immune response in the pregnancy outcome, further appropriate studies are needed. In this context, further studies should highlight if the hematogenous route could justify the spread of bacterial DNA from the oral microbiome to the placenta and if vaginal dysbiosis could favor the likelihood of identifying CV and AF positive for bacterial DNA.}, }
@article {pmid36765892, year = {2023}, author = {Piao, XM and Byun, YJ and Zheng, CM and Song, SJ and Kang, HW and Kim, WT and Yun, SJ}, title = {A New Treatment Landscape for RCC: Association of the Human Microbiome with Improved Outcomes in RCC.}, journal = {Cancers}, volume = {15}, number = {3}, pages = {}, pmid = {36765892}, issn = {2072-6694}, support = {2020R1I1A3062508//National Research Foundation of Korea/ ; 2021R1I1A1A01050891//National Research Foundation of Korea/ ; 2021RIS-001(1345341783)//National Research Foundation of Korea/ ; //MD-Phd/Medical Scientist Training Program through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &amp; Welfare, Republic of Korea./ ; }, abstract = {Microbes play different roles in metabolism, local or systemic inflammation, and immunity, and the human microbiome in tumor microenvironment (TME) is important for modulating the response to immunotherapy in cancer patients. Renal cell carcinoma (RCC) is an immunogenic tumor, and immunotherapy is the backbone of its treatment. Correlations between the microbiome and responsiveness to immune checkpoint inhibitors have been reported. This review summarizes the recent therapeutic strategies for RCC and the effects of TME on the systemic therapy of RCC. The current understanding and advances in microbiome research and the relationship between the microbiome and the response to immunotherapy for RCC are also discussed. Improving our understanding of the role of the microbiome in RCC treatment will facilitate the development of microbiome targeting therapies to modify the tumor microbiome and improve treatment outcomes.}, }
@article {pmid36760501, year = {2023}, author = {Schackart, KE and Graham, JB and Ponsero, AJ and Hurwitz, BL}, title = {Evaluation of computational phage detection tools for metagenomic datasets.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1078760}, pmid = {36760501}, issn = {1664-302X}, support = {T32 GM132008/GM/NIGMS NIH HHS/United States ; T34 GM008718/GM/NIGMS NIH HHS/United States ; }, abstract = {INTRODUCTION: As new computational tools for detecting phage in metagenomes are being rapidly developed, a critical need has emerged to develop systematic benchmarks.<br><br>METHODS: In this study, we surveyed 19 metagenomic phage detection tools, 9 of which could be installed and run at scale. Those 9 tools were assessed on several benchmark challenges. Fragmented reference genomes are used to assess the effects of fragment length, low viral content, phage taxonomy, robustness to eukaryotic contamination, and computational resource usage. Simulated metagenomes are used to assess the effects of sequencing and assembly quality on the tool performances. Finally, real human gut metagenomes and viromes are used to assess the differences and similarities in the phage communities predicted by the tools.<br><br>RESULTS: We find that the various tools yield strikingly different results. Generally, tools that use a homology approach (VirSorter, MARVEL, viralVerify, VIBRANT, and VirSorter2) demonstrate low false positive rates and robustness to eukaryotic contamination. Conversely, tools that use a sequence composition approach (VirFinder, DeepVirFinder, Seeker), and MetaPhinder, have higher sensitivity, including to phages with less representation in reference databases. These differences led to widely differing predicted phage communities in human gut metagenomes, with nearly 80% of contigs being marked as phage by at least one tool and a maximum overlap of 38.8% between any two tools. While the results were more consistent among the tools on viromes, the differences in results were still significant, with a maximum overlap of 60.65%. Discussion: Importantly, the benchmark datasets developed in this study are publicly available and reusable to enable the future comparability of new tools developed.}, }
@article {pmid36754953, year = {2023}, author = {Wang, Y and Wang, L and Sun, T and Shen, S and Li, Z and Ma, X and Gu, X and Zhang, X and Peng, A and Xu, X and Feng, Q}, title = {Study of the inflammatory activating process in the early stage of Fusobacterium nucleatum infected PDLSCs.}, journal = {International journal of oral science}, volume = {15}, number = {1}, pages = {8}, pmid = {36754953}, issn = {2049-3169}, mesh = {Humans ; *Fusobacterium nucleatum/metabolism ; NF-kappa B/metabolism ; Periodontal Ligament/metabolism ; Signal Transduction ; *Fusobacterium Infections/metabolism/microbiology/pathology ; Stem Cells/metabolism ; }, abstract = {Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.}, }
@article {pmid36744900, year = {2023}, author = {Bhandari, P and Tingley, J and Abbott, DW and Hill, JE}, title = {Glycogen-Degrading Activities of Catalytic Domains of α-Amylase and α-Amylase-Pullulanase Enzymes Conserved in Gardnerella spp. from the Vaginal Microbiome.}, journal = {Journal of bacteriology}, volume = {205}, number = {2}, pages = {e0039322}, pmid = {36744900}, issn = {1098-5530}, support = {//Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (NSERC)/ ; }, mesh = {Female ; Humans ; alpha-Amylases/metabolism ; Bacteria/metabolism ; Catalytic Domain ; Gardnerella ; Glycogen/metabolism ; Maltose ; *Microbiota ; *Premature Birth ; Vagina/microbiology ; *Vaginosis, Bacterial/microbiology ; }, abstract = {Gardnerella spp. are associated with bacterial vaginosis in which normally dominant lactobacilli are replaced with facultative and anaerobic bacteria, including Gardnerella spp. Co-occurrence of multiple species of Gardnerella is common in the vagina, and competition for nutrients such as glycogen likely contributes to the differential abundances of Gardnerella spp. Glycogen must be digested into smaller components for uptake, a process that depends on the combined action of glycogen-degrading enzymes. In this study, the ability of culture supernatants of 15 isolates of Gardnerella spp. to produce glucose, maltose, maltotriose, and maltotetraose from glycogen was demonstrated. Carbohydrate-active enzymes (CAZymes) were identified bioinformatically in Gardnerella proteomes using dbCAN2. Identified proteins included a single-domain α-amylase (EC 3.2.1.1) (encoded by all 15 isolates) and an α-amylase-pullulanase (EC 3.2.1.41) containing amylase, carbohydrate binding modules, and pullulanase domains (14/15 isolates). To verify the sequence-based functional predictions, the amylase and pullulanase domains of the α-amylase-pullulanase and the single-domain α-amylase were each produced in Escherichia coli. The α-amylase domain from the α-amylase-pullulanase released maltose, maltotriose, and maltotetraose from glycogen, and the pullulanase domain released maltotriose from pullulan and maltose from glycogen, demonstrating that the Gardnerella α-amylase-pullulanase is capable of hydrolyzing α-1,4 and α-1,6 glycosidic bonds. Similarly, the single-domain α-amylase protein also produced maltose, maltotriose, and maltotetraose from glycogen. Our findings show that Gardnerella spp. produce extracellular amylase enzymes as "public goods" that can digest glycogen into maltose, maltotriose, and maltotetraose that can be used by the vaginal microbiota. IMPORTANCE Increased abundance of Gardnerella spp. is a diagnostic characteristic of bacterial vaginosis, an imbalance in the human vaginal microbiome associated with troubling symptoms, and negative reproductive health outcomes, including increased transmission of sexually transmitted infections and preterm birth. Competition for nutrients is likely an important factor in causing dramatic shifts in the vaginal microbial community, but little is known about the contribution of bacterial enzymes to the metabolism of glycogen, a major food source available to vaginal bacteria. The significance of our research is characterizing the activity of enzymes conserved in Gardnerella species that contribute to the ability of these bacteria to utilize glycogen.}, }
@article {pmid36741465, year = {2022}, author = {Cobo-López, S and Gupta, VK and Sung, J and Guimerà, R and Sales-Pardo, M}, title = {Stochastic block models reveal a robust nested pattern in healthy human gut microbiomes.}, journal = {PNAS nexus}, volume = {1}, number = {3}, pages = {pgac055}, pmid = {36741465}, issn = {2752-6542}, abstract = {A key question in human gut microbiome research is what are the robust structural patterns underlying its taxonomic composition. Herein, we use whole metagenomic datasets from healthy human guts to show that such robust patterns do exist, albeit not in the conventional enterotype sense. We first introduce the concept of mixed-membership enterotypes using a network inference approach based on stochastic block models. We find that gut microbiomes across a group of people (hosts) display a nested structure, which has been observed in a number of ecological systems. This finding led us to designate distinct ecological roles to both microbes and hosts: generalists and specialists. Specifically, generalist hosts have microbiomes with most microbial species, while specialist hosts only have generalist microbes. Moreover, specialist microbes are only present in generalist hosts. From the nested structure of microbial taxonomies, we show that these ecological roles of microbes are generally conserved across datasets. Our results show that the taxonomic composition of healthy human gut microbiomes is associated with robustly structured combinations of generalist and specialist species.}, }
@article {pmid36736005, year = {2023}, author = {Fujiyoshi, S and Yarimizu, K and Perera, I and Abanto, M and Jorquera, M and Maruyama, F}, title = {Learning from mistakes: challenges in finding holobiont factors from environmental samples and the importance of methodological consistency.}, journal = {Current opinion in biotechnology}, volume = {80}, number = {}, pages = {102897}, doi = {10.1016/j.copbio.2023.102897}, pmid = {36736005}, issn = {1879-0429}, mesh = {Humans ; *Harmful Algal Bloom ; *Bacteria ; Environmental Monitoring ; }, abstract = {The cause of harmful algal blooms has been a mystery, but research to elucidate its mechanism has progressed over the years thanks to genetic technologies. We have monitored toxic algae and its associated bacteria as a community, the so-called 'holobiont' in Chilean coastal waters for years from the perspective of bacteria as an algal bloom driver. This review describes the challenges of holobiont monitoring, specifically with respect to standardizing and compliance with the monitoring protocols to collect reliable and sustainable data. Further, we suggest adopting the high-throughput sequencing (HTS) standard operating procedure (SOP) by the International Human Microbiome to improve the quality and consistency of holobiont monitoring in the harmful algal world.}, }
@article {pmid36728456, year = {2023}, author = {Markkanen, MA and Haukka, K and Pärnänen, KMM and Dougnon, VT and Bonkoungou, IJO and Garba, Z and Tinto, H and Sarekoski, A and Karkman, A and Kantele, A and Virta, MPJ}, title = {Metagenomic Analysis of the Abundance and Composition of Antibiotic Resistance Genes in Hospital Wastewater in Benin, Burkina Faso, and Finland.}, journal = {mSphere}, volume = {8}, number = {1}, pages = {e0053822}, pmid = {36728456}, issn = {2379-5042}, mesh = {Humans ; *Anti-Bacterial Agents/pharmacology ; *Wastewater ; Burkina Faso ; Benin ; Finland ; Drug Resistance, Microbial/genetics ; Hospitals ; }, abstract = {Antibiotic resistance is a global threat to human health, with the most severe effect in low- and middle-income countries. We explored the presence of antibiotic resistance genes (ARGs) in the hospital wastewater (HWW) of nine hospitals in Benin and Burkina Faso, two low-income countries in West Africa, with shotgun metagenomic sequencing. For comparison, we also studied six hospitals in Finland. The highest sum of the relative abundance of ARGs in the 68 HWW samples was detected in Benin and the lowest in Finland. HWW resistomes and mobilomes in Benin and Burkina Faso resembled each other more than those in Finland. Many carbapenemase genes were detected at various abundances, especially in HWW from Burkina Faso and Finland. The blaGES genes, the most widespread carbapenemase gene in the Beninese HWW, were also found in water intended for hand washing and in a puddle at a hospital yard in Benin. mcr genes were detected in the HWW of all three countries, with mcr-5 being the most common mcr gene. These and other mcr genes were observed in very high relative abundances, even in treated wastewater in Burkina Faso and a street gutter in Benin. The results highlight the importance of wastewater treatment, with particular attention to HWW. IMPORTANCE The global emergence and increased spread of antibiotic resistance threaten the effectiveness of antibiotics and, thus, the health of the entire population. Therefore, understanding the resistomes in different geographical locations is crucial in the global fight against the antibiotic resistance crisis. However, this information is scarce in many low- and middle-income countries (LMICs), such as those in West Africa. In this study, we describe the resistomes of hospital wastewater in Benin and Burkina Faso and, as a comparison, Finland. Our results help to understand the hitherto unrevealed resistance in Beninese and Burkinabe hospitals. Furthermore, the results emphasize the importance of wastewater management infrastructure design to minimize exposure events between humans, HWW, and the environment, preventing the circulation of resistant bacteria and ARGs between humans (hospitals and community) and the environment.}, }
@article {pmid36726632, year = {2022}, author = {Legba, BB and Dougnon, V and Koudokpon, H and Mero, S and Elovainio, R and Parry, M and Bankole, H and Haukka, K}, title = {Assessment of blood cultures and antibiotic susceptibility testing for bacterial sepsis diagnosis and utilization of results by clinicians in Benin: A qualitative study.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {1088590}, pmid = {36726632}, issn = {2296-2565}, mesh = {Humans ; *Blood Culture ; Benin ; Microbial Sensitivity Tests ; *Sepsis/diagnosis/drug therapy ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Escherichia coli ; }, abstract = {OBJECTIVES: We assessed the current status of blood culture and antibiotic susceptibility testing (AST) practices in clinical laboratories in Benin, and how the laboratory results are used by physicians to prescribe antibiotics.<br><br>METHODS: The qualitative study covered twenty-five clinical laboratories with a bacteriology unit and associated hospitals and pharmacies. Altogether 159 laboratory staff, physicians and pharmacists were interviewed about their perceptions of the state of laboratory diagnostics related to sepsis and the use of antibiotics. Face-to-face interviews based on structured questionnaires were supported by direct observations when visiting five laboratories in across the country.<br><br>RESULTS: Only 6 laboratories (24%) conducted blood cultures, half of them with a maximum of 10 samples per month. The most common gram-negative bacteria isolated from blood cultures were: Escherichia coli, Salmonella spp. and Salmonella enterica serovar Typhi while the most common gram-positives were Enterococcus spp. and Staphylococcus aureus. None of the laboratories listed Klebsiella pneumoniae among the three most common bacteria isolated from blood cultures, although other evidence indicates that it is the most common cause of sepsis in Benin. Due to limited testing capacity, physicians most commonly use empirical antibiotic therapy.<br><br>CONCLUSIONS: More resources are needed to develop laboratory testing capacity, technical skills in bacterial identification, AST, quality assurance, and communication of results must be strengthened.}, }
@article {pmid36725208, year = {2023}, author = {Walsh, AM and Leech, J and Huttenhower, C and Delhomme-Nguyen, H and Crispie, F and Chervaux, C and Cotter, PD}, title = {Integrated molecular approaches for fermented food microbiome research.}, journal = {FEMS microbiology reviews}, volume = {47}, number = {2}, pages = {}, pmid = {36725208}, issn = {1574-6976}, mesh = {Animals ; Humans ; *Microbiota ; Diet ; *Fermented Foods ; Fermentation ; High-Throughput Nucleotide Sequencing ; }, abstract = {Molecular technologies, including high-throughput sequencing, have expanded our perception of the microbial world. Unprecedented insights into the composition and function of microbial communities have generated large interest, with numerous landmark studies published in recent years relating the important roles of microbiomes and the environment-especially diet and nutrition-in human, animal, and global health. As such, food microbiomes represent an important cross-over between the environment and host. This is especially true of fermented food microbiomes, which actively introduce microbial metabolites and, to a lesser extent, live microbes into the human gut. Here, we discuss the history of fermented foods, and examine how molecular approaches have advanced research of these fermented foods over the past decade. We highlight how various molecular approaches have helped us to understand the ways in which microbes shape the qualities of these products, and we summarize the impacts of consuming fermented foods on the gut. Finally, we explore how advances in bioinformatics could be leveraged to enhance our understanding of fermented foods. This review highlights how integrated molecular approaches are changing our understanding of the microbial communities associated with food fermentation, the creation of unique food products, and their influences on the human microbiome and health.}, }
@article {pmid36721396, year = {2023}, author = {SeyedAlinaghi, S and Afzalian, A and Pashaei, Z and Varshochi, S and Karimi, A and Mojdeganlou, H and Mojdeganlou, P and Razi, A and Ghanadinezhad, F and Shojaei, A and Amiri, A and Dashti, M and Ghasemzadeh, A and Dadras, O and Mehraeen, E and Afsahi, AM}, title = {Gut microbiota and COVID-19: A systematic review.}, journal = {Health science reports}, volume = {6}, number = {2}, pages = {e1080}, pmid = {36721396}, issn = {2398-8835}, abstract = {BACKGROUND AND AIMS: Alteration in humans' gut microbiota was reported in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The gut and upper respiratory tract (URT) microbiota harbor a dynamic and complex population of microorganisms and have strong interaction with host immune system homeostasis. However, our knowledge about microbiota and its association with SARS-CoV-2 is still limited. We aimed to systematically review the effects of gut microbiota on the SARS-CoV-2 infection and its severity and the impact that SARS-CoV-2 could have on the gut microbiota.<br><br>METHODS: We searched the keywords in the online databases of Web of Science, Scopus, PubMed, and Cochrane on December 31, 2021. After duplicate removal, we performed the screening process in two stages; title/abstract and then full-text screening. The data of the eligible studies were extracted into a pre-designed word table. This study adhered to the PRISMA checklist and Newcastle-Ottawa Scale Bias Assessment tool.<br><br>RESULTS: Sixty-three publications were included in this review. Our study shows that among COVID-19 patients, particularly moderate to severe cases, the gut and lung microbiota was different compared to healthy individuals. In addition, the severity, and viral load of COVID-19 disease would probably also be influenced by the gut, and lung microbiota's composition.<br><br>CONCLUSION: Our study concludes that there was a significant difference in the composition of the URT, and gut microbiota in COVID-19 patients compared to the general healthy individuals, with an increase in opportunistic pathogens. Further, research is needed to investigate the probable bidirectional association of COVID-19 and human microbiome.}, }
@article {pmid36720857, year = {2023}, author = {Pruss, KM and Chen, H and Liu, Y and Van Treuren, W and Higginbottom, SK and Jarman, JB and Fischer, CR and Mak, J and Wong, B and Cowan, TM and Fischbach, MA and Sonnenburg, JL and Dodd, D}, title = {Host-microbe co-metabolism via MCAD generates circulating metabolites including hippuric acid.}, journal = {Nature communications}, volume = {14}, number = {1}, pages = {512}, pmid = {36720857}, issn = {2041-1723}, support = {R01 DK101674/DK/NIDDK NIH HHS/United States ; R01 AT011396/AT/NCCIH NIH HHS/United States ; K08 DK110335/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; R35 GM142873/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Female ; Humans ; Male ; Mice ; Acyl-CoA Dehydrogenase ; *Hippurates ; *Metabolomics ; Phenylalanine ; }, abstract = {The human gut microbiota produces dozens of small molecules that circulate in blood, accumulate to comparable levels as pharmaceutical drugs, and influence host physiology. Despite the importance of these metabolites to human health and disease, the origin of most microbially-produced molecules and their fate in the host remains largely unknown. Here, we uncover a host-microbe co-metabolic pathway for generation of hippuric acid, one of the most abundant organic acids in mammalian urine. Combining stable isotope tracing with bacterial and host genetics, we demonstrate reduction of phenylalanine to phenylpropionic acid by gut bacteria; the host re-oxidizes phenylpropionic acid involving medium-chain acyl-CoA dehydrogenase (MCAD). Generation of germ-free male and female MCAD[-/-] mice enabled gnotobiotic colonization combined with untargeted metabolomics to identify additional microbial metabolites processed by MCAD in host circulation. Our findings uncover a host-microbe pathway for the abundant, non-toxic phenylalanine metabolite hippurate and identify β-oxidation via MCAD as a novel mechanism by which mammals metabolize microbiota-derived metabolites.}, }
@article {pmid36711684, year = {2023}, author = {Wilson, NG and Hernandez-Leyva, A and Schwartz, DJ and Bacharier, LB and Kau, AL}, title = {The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36711684}, issn = {2692-8205}, support = {F30 DK127584/DK/NIDDK NIH HHS/United States ; K08 AI113184/AI/NIAID NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; }, abstract = {Asthma is a common allergic airway disease that develops in association with the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in children and adults 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. One differentially abundant ARG was a macrolide resistance marker, ermF, which significantly co-occurred with the Bacteroides fragilis toxin, suggesting a possible relationship between enterotoxigenic B. fragilis, antibiotic resistance, and asthma. Lastly, we found multiple virulence factor (VF) and ARG pairs that co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are co-selected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment.}, }
@article {pmid36702753, year = {2023}, author = {Sun, H and Wang, Y and Xiao, Z and Huang, X and Wang, H and He, T and Jiang, X}, title = {multiMiAT: an optimal microbiome-based association test for multicategory phenotypes.}, journal = {Briefings in bioinformatics}, volume = {24}, number = {2}, pages = {}, doi = {10.1093/bib/bbad012}, pmid = {36702753}, issn = {1477-4054}, mesh = {Humans ; *Microbiota/genetics ; Computer Simulation ; Phenotype ; *Gastrointestinal Microbiome ; Logistic Models ; }, abstract = {Microbes can affect the metabolism and immunity of human body incessantly, and the dysbiosis of human microbiome drives not only the occurrence but also the progression of disease (i.e. multiple statuses of disease). Recently, microbiome-based association tests have been widely developed to detect the association between the microbiome and host phenotype. However, the existing methods have not achieved satisfactory performance in testing the association between the microbiome and ordinal/nominal multicategory phenotypes (e.g. disease severity and tumor subtype). In this paper, we propose an optimal microbiome-based association test for multicategory phenotypes, namely, multiMiAT. Specifically, under the multinomial logit model framework, we first introduce a microbiome regression-based kernel association test for multicategory phenotypes (multiMiRKAT). As a data-driven optimal test, multiMiAT then integrates multiMiRKAT, score test and MiRKAT-MC to maintain excellent performance in diverse association patterns. Massive simulation experiments prove the success of our method. Furthermore, multiMiAT is also applied to real microbiome data experiments to detect the association between the gut microbiome and clinical statuses of colorectal cancer as well as for diverse statuses of Clostridium difficile infections.}, }
@article {pmid36697862, year = {2023}, author = {Kennedy, KM and de Goffau, MC and Perez-Muñoz, ME and Arrieta, MC and Bäckhed, F and Bork, P and Braun, T and Bushman, FD and Dore, J and de Vos, WM and Earl, AM and Eisen, JA and Elovitz, MA and Ganal-Vonarburg, SC and Gänzle, MG and Garrett, WS and Hall, LJ and Hornef, MW and Huttenhower, C and Konnikova, L and Lebeer, S and Macpherson, AJ and Massey, RC and McHardy, AC and Koren, O and Lawley, TD and Ley, RE and O'Mahony, L and O'Toole, PW and Pamer, EG and Parkhill, J and Raes, J and Rattei, T and Salonen, A and Segal, E and Segata, N and Shanahan, F and Sloboda, DM and Smith, GCS and Sokol, H and Spector, TD and Surette, MG and Tannock, GW and Walker, AW and Yassour, M and Walter, J}, title = {Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies.}, journal = {Nature}, volume = {613}, number = {7945}, pages = {639-649}, pmid = {36697862}, issn = {1476-4687}, support = {MR/K021133/1/MRC_/Medical Research Council/United Kingdom ; BBS/E/F/00044409/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 HD102318/HD/NICHD NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; R01 AI139240/AI/NIAID NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; 100974/C/13/Z/WT_/Wellcome Trust/United Kingdom ; 220876/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; R01 CA219871/CA/NCI NIH HHS/United States ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 NR014784/NR/NINR NIH HHS/United States ; R01 AI120489/AI/NIAID NIH HHS/United States ; R01 HD098867/HD/NICHD NIH HHS/United States ; R33 HL137063/HL/NHLBI NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Female ; Humans ; Pregnancy ; Amniotic Fluid/immunology/microbiology ; *Biomass ; Mammals ; *Microbiota/genetics ; Placenta/immunology/microbiology ; *Fetus/immunology/microbiology ; *DNA Contamination ; Reproducibility of Results ; }, abstract = {Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.}, }
@article {pmid36696240, year = {2022}, author = {Pang, Z and Korpela, R and Vapaatalo, H}, title = {Intestinal aldosterone synthase activity and aldosterone synthesis in mouse.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {73}, number = {4}, pages = {}, doi = {10.26402/jpp.2022.4.03}, pmid = {36696240}, issn = {1899-1505}, mesh = {Mice ; Animals ; *Cytochrome P-450 CYP11B2/genetics ; *Aldosterone/metabolism ; Corticosterone/metabolism ; }, abstract = {Aldosterone is the most important mineralocorticoid hormone regulating water and electrolyte absorption in the distal convoluted tubule of the kidney. Recently, we detected the presence of the whole chain of aldosterone production from the precursor corticosterone, transcription factor liver receptor homologue-1 (LRH-1), the aldosterone synthase enzyme protein (CYP11B2) as well as the gene to the final product aldosterone in murine large intestine. Here, we decided to correlate the amount of this synthase protein with its enzymatic activity in different parts of gastrointestinal tract and also with the aldosterone concentration in the respective tissue. Considering the physiological behavior of the animals in light and dark environment, we measured these variables at four time points - two in the light, the others during darkness. In vitro activity of CYP11B2 was measured as the amount of aldosterone formed from the precursor deoxycorticosterone using enzyme preparations from homogenized intestinal sections. CYP11B2 enzyme activity was higher in the large than in the small intestine. In ileum and colon, the CYP11B2 activity increased in the dark time. The highest aldosterone concentration was detected in the dark in the large intestine. In summary, enzyme activity of CYP11B2 was present in all parts of intestine; the large intestine formed more aldosterone during the darkness. No difference was seen in any of the variables between the early and late light hours.}, }
@article {pmid36681812, year = {2023}, author = {Gardemeister, S and Skogberg, K and Saisto, T and Salonen, A and de Vos, WM and Korpela, K and Kolho, KL}, title = {Cross-sectional study of the proportion of antibiotic use during childbirth in full-term deliveries in Finland.}, journal = {BMC pregnancy and childbirth}, volume = {23}, number = {1}, pages = {50}, pmid = {36681812}, issn = {1471-2393}, mesh = {Pregnancy ; Infant ; Female ; Humans ; *Anti-Bacterial Agents/therapeutic use ; Cross-Sectional Studies ; Cohort Studies ; Finland ; *Antibiotic Prophylaxis ; }, abstract = {PURPOSE: In developed countries, data on the frequency of antibiotics given to mothers during childbirth are limited beyond the overall effect of all various prophylactic indications. Also, data on the impact of such antibiotics to the well-being of term babies are scarce. We aimed to characterize the frequency of antibiotic use during childbirth of term pregnancy. Secondly, we assessed whether the use of antibiotics was associated with any symptoms in infants.<br><br>METHODS: This was a cross-sectional study of 1019 term deliveries of women participating in the prospective Health and Early Life Microbiota (HELMi) birth cohort study between March 2016 and March 2018 in the capital region of Finland. The data on antibiotic use were collected from the hospital records.<br><br>RESULTS: In total, 37% of the mothers received antibiotics during childbirth and 100% in Caesarean Sects.&#xa0;(17% of the deliveries). Less than 5% of antibiotics were non-prophylactic. In vaginal deliveries, the most common indication (18%) was prophylaxis for Group B Streptococcus. The most frequently used antibiotics were cefuroxime (22%) and benzylpenicillin (15%), and 56% received only one dose. In infants exposed to antibiotics during delivery, defecation frequency was higher during the first months (p-value&#x2009;<&#x2009;0.0001- 0.0145), and weight gain was higher at the age of three months (p-value 0.0371).<br><br>CONCLUSION: More than every third new-born in a developed country is exposed to antibiotics during birth. Our findings support the hypothesis that maternal antibiotics given during birth have an impact on the well-being of the infants. These findings should inform current policies for prophylactic antibiotics in childbirth.}, }
@article {pmid36680587, year = {2023}, author = {Kim, E and Yang, SM and Kim, HY}, title = {Weissella and the two Janus faces of the genus.}, journal = {Applied microbiology and biotechnology}, volume = {107}, number = {4}, pages = {1119-1127}, pmid = {36680587}, issn = {1432-0614}, mesh = {Animals ; Humans ; *Weissella ; *Lactobacillales ; *Probiotics ; *Oncorhynchus mykiss/microbiology ; Fermentation ; }, abstract = {The genus Weissella belongs to the lactic acid bacteria group. It occurs naturally in foods and is a component of the human microbiome. A few Weissella species are candidate probiotics due to their potential for survival under the harsh conditions present in the gastrointestinal tract of humans and animals. Various species have also shown potential for treating and preventing periodontal disease, skin pathologies, and atopic dermatitis; some are used as starters for the fermentation of foods due to their production of exopolysaccharides; and others are used as protective cultures due to their production of weissellicin, a bacteriocin. However, a few Weissella species are opportunistic pathogens, such as W. ceti, which is the etiological agent of weissellosis, a disease in rainbow trout. Additionally, most Weissella species are intrinsically vancomycin-resistant. Thus, the Weissella genus is important from both medical and industrial points of view, and the Janus faces of this genus should be considered in any expected biotechnological applications. In this review, we present an overview of the probiotic potential and pathogenic cases of the Weissella genus reported in the literature.}, }
@article {pmid36679633, year = {2023}, author = {Sánchez-Tirado, E and Agüí, L and González-Cortés, A and Campuzano, S and Yáñez-Sedeño, P and Pingarrón, JM}, title = {Electrochemical (Bio)Sensing Devices for Human-Microbiome-Related Biomarkers.}, journal = {Sensors (Basel, Switzerland)}, volume = {23}, number = {2}, pages = {}, pmid = {36679633}, issn = {1424-8220}, support = {PID2021-122457OB-I00//Spanish Ministerio de Ciencia e Innovaci&#xf3;n/ ; PID2019-103899RB-I00//Spanish Ministerio de Ciencia e Inniovaci&#xf3;n/ ; S2018/NMT-4349//Comunidad de Madrid/ ; }, mesh = {Humans ; Electrochemical Techniques/methods ; Biomarkers ; *Nanostructures ; *Biosensing Techniques/methods ; *Microbiota ; }, abstract = {The study of the human microbiome is a multidisciplinary area ranging from the field of technology to that of personalized medicine. The possibility of using microbiota biomarkers to improve the diagnosis and monitoring of diseases (e.g., cancer), health conditions (e.g., obesity) or relevant processes (e.g., aging) has raised great expectations, also in the field of bioelectroanalytical chemistry. The well-known advantages of electrochemical biosensors-high sensitivity, fast response, and the possibility of miniaturization, together with the potential for new nanomaterials to improve their design and performance-position them as unique tools to provide a better understanding of the entities of the human microbiome and raise the prospect of huge and important developments in the coming years. This review article compiles recent applications of electrochemical (bio)sensors for monitoring microbial metabolites and disease biomarkers related to different types of human microbiome, with a special focus on the gastrointestinal microbiome. Examples of electrochemical devices applied to real samples are critically discussed, as well as challenges to be faced and where future developments are expected to go.}, }
@article {pmid36675926, year = {2023}, author = {Maas, E and Penders, J and Venema, K}, title = {Modelling the Gut Fungal-Community in TIM-2 with a Microbiota from Healthy Individuals.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {9}, number = {1}, pages = {}, pmid = {36675926}, issn = {2309-608X}, abstract = {Most research on the human microbiome focuses on the bacterial component, and this has led to a lack of information about the fungal component (mycobiota) and how this can influence human health, e.g., by modulation through the diet. The validated, dynamic computer-controlled model of the colon (TIM-2) is an in vitro model to study the microbiome and how this is influenced by interventions such as diet. In this study, it was used to the study the gut fungal-community. This was done in combination with next-generation sequencing of the ITS2 region for fungi and 16S rRNA for bacteria. Different dietary interventions (control diet (SIEM), high-carbohydrate, high-protein, glucose as a carbon source) were performed, to see if diet could shape the mycobiome. The mycobiome was investigated after the adaptation period, and throughout the intervention period which lasted 72 h, and samples were taken every 24 h. The fungal community showed low diversity and a greater variability when compared to bacteria. The mycobiome was affected most in the first hours of the adaptation period. Taxonomic classification showed that at the phylum-level Ascomycota and Basidiomycota dominated, while Agaricus, Aspergillus, Candida, Penicillum, Malassezia, Saccharomyces, Aureobasidium, Mycosphaerella, Mucor and Clavispora were the most abundant genera. During the intervention period, it was shown that the change of diet could influence the diversity. Clustering of samples for different time points was analyzed using Bray−Curtis dissimilarities. Samples of t0 clustered together, and samples of all other time points clustered together. The Bray−Curtis-dissimilarity analysis also showed that for the different dietary interventions, samples treated with glucose clustered together and were different from the other groups (p < 0.05, PERMANOVA). Taxonomic classification showed that the genera Alternaria, Thanatephorus, Candida and Dekkera differentially changed for the various diet groups (p < 0.05, Kruskal−Wallis). These results show that the mycobiota could be modelled in TIM-2; however, the low diversity and high variability make studying fungal, as compared to bacterial, communities, much more challenging. Future research should focus on the optimization of the stability of the fungal community to increase the strength of the results.}, }
@article {pmid36675055, year = {2023}, author = {Kustrimovic, N and Bombelli, R and Baci, D and Mortara, L}, title = {Microbiome and Prostate Cancer: A Novel Target for Prevention and Treatment.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36675055}, issn = {1422-0067}, mesh = {Male ; Humans ; *Microbiota/physiology ; *Prostatic Neoplasms/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; Prostate/pathology ; Inflammation ; Dysbiosis ; }, abstract = {Growing evidence of the microbiome's role in human health and disease has emerged since the creation of the Human Microbiome Project. Recent studies suggest that alterations in microbiota composition (dysbiosis) may play an essential role in the occurrence, development, and prognosis of prostate cancer (PCa), which remains the second most frequent male malignancy worldwide. Current advances in biological technologies, such as high-throughput sequencing, transcriptomics, and metabolomics, have enabled research on the gut, urinary, and intra-prostate microbiome signature and the correlation with local and systemic inflammation, host immunity response, and PCa progression. Several microbial species and their metabolites facilitate PCa insurgence through genotoxin-mediated mutagenesis or by driving tumor-promoting inflammation and dysfunctional immunosurveillance. However, the impact of the microbiome on PCa development, progression, and response to treatment is complex and needs to be fully understood. This review addresses the current knowledge on the host-microbe interaction and the risk of PCa, providing novel insights into the intraprostatic, gut, and urinary microbiome mechanisms leading to PCa carcinogenesis and treatment response. In this paper, we provide a detailed overview of diet changes, gut microbiome, and emerging therapeutic approaches related to the microbiome and PCa. Further investigation on the prostate-related microbiome and large-scale clinical trials testing the efficacy of microbiota modulation approaches may improve patient outcomes while fulfilling the literature gap of microbial-immune-cancer-cell mechanistic interactions.}, }
@article {pmid36674563, year = {2023}, author = {He, S and Chakraborty, R and Ranganathan, S}, title = {Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36674563}, issn = {1422-0067}, mesh = {Humans ; Squamous Cell Carcinoma of Head and Neck ; *Carcinoma, Squamous Cell/metabolism ; *Mouth Neoplasms/pathology ; *Mycobiome ; Proteomics/methods ; *Head and Neck Neoplasms ; }, abstract = {Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40-50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting.}, }
@article {pmid36672959, year = {2023}, author = {Park, DJ and Plantinga, AM}, title = {Impact of Data and Study Characteristics on Microbiome Volatility Estimates.}, journal = {Genes}, volume = {14}, number = {1}, pages = {}, pmid = {36672959}, issn = {2073-4425}, mesh = {Female ; Humans ; *Microbiota ; Bacteria/genetics ; Longitudinal Studies ; Time Factors ; Specimen Handling ; }, abstract = {The human microbiome is a dynamic community of bacteria, viruses, fungi, and other microorganisms. Both the composition of the microbiome (the microbes that are present and their relative abundances) and the temporal variability of the microbiome (the magnitude of changes in their composition across time, called volatility) has been associated with human health. However, the effect of unbalanced sampling intervals and differential read depth on the estimates of microbiome volatility has not been thoroughly assessed. Using four publicly available gut and vaginal microbiome time series, we subsampled the datasets to several sampling intervals and read depths and then compared additive, multiplicative, centered log ratio (CLR)-based, qualitative, and distance-based measures of microbiome volatility between the conditions. We find that longer sampling intervals are associated with larger quantitative measures of change (particularly for common taxa), but not with qualitative measures of change or distance-based volatility quantification. A lower sequencing read depth is associated with smaller multiplicative, CLR-based, and qualitative measures of change (particularly for less common taxa). Strategic subsampling may serve as a useful sensitivity analysis in unbalanced longitudinal studies investigating clinical associations with microbiome volatility.}, }
@article {pmid36672595, year = {2022}, author = {Brogna, C and Cristoni, S and Brogna, B and Bisaccia, DR and Marino, G and Viduto, V and Montano, L and Piscopo, M}, title = {Toxin-like Peptides from the Bacterial Cultures Derived from Gut Microbiome Infected by SARS-CoV-2-New Data for a Possible Role in the Long COVID Pattern.}, journal = {Biomedicines}, volume = {11}, number = {1}, pages = {}, pmid = {36672595}, issn = {2227-9059}, abstract = {It has been 3 years since the beginning of the SARS-CoV-2 outbreak, however it is as yet little known how to care for the acute COVID-19 and long COVID patients. COVID-19 clinical manifestations are of both pulmonary and extra-pulmonary types. Extra-pulmonary ones include extreme tiredness (fatigue), shortness of breath, muscle aches, hyposmia, dysgeusia, and other neurological manifestations. In other autoimmune diseases, such as Parkinson's disease (PD) or Alzheimer's Disease (AD), it is well known that role of acetylcholine is crucial in olfactory dysfunction. We have already observed the presence of toxin-like peptides in plasma, urine, and faecal samples from COVID-19 patients, which are very similar to molecules known to alter acetylcholine signaling. After observing the production of these peptides in bacterial cultures, we have performed additional proteomics analyses to better understand their behavior and reported the extended data from our latest in vitro experiment. It seems that the gut microbiome continues to produce toxin-like peptides also after the decrease of RNA SARS-CoV-2 viral load at molecular tests. These toxicological interactions between the gut/human microbiome bacteria and the virus suggest a new scenario in the study of the clinical symptoms in long COVID and also in acute COVID-19 patients. It is discussed that in the bacteriophage similar behavior, the presence of toxins produced by bacteria continuously after viral aggression can be blocked using an appropriate combination of certain drugs.}, }
@article {pmid36662710, year = {2023}, author = {Brenes, LR and Johnson, AD and Lohse, MB}, title = {Farnesol and phosphorylation of the transcriptional regulator Efg1 affect Candida albicans white-opaque switching rates.}, journal = {PloS one}, volume = {18}, number = {1}, pages = {e0280233}, pmid = {36662710}, issn = {1932-6203}, support = {R01 AI049187/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Candida albicans/drug effects/genetics/metabolism ; *Farnesol/pharmacology ; *Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Genetic Techniques ; Phenotype ; Phosphorylation ; }, abstract = {Candida albicans is a normal member of the human microbiome and an opportunistic fungal pathogen. This species undergoes several morphological transitions, and here we consider white-opaque switching. In this switching program, C. albicans reversibly alternates between two cell types, named "white" and "opaque," each of which is normally stable across thousands of cell divisions. Although switching under most conditions is stochastic and rare, certain environmental signals or genetic manipulations can dramatically increase the rate of switching. Here, we report the identification of two new inputs which affect white-to-opaque switching rates. The first, exposure to sub-micromolar concentrations of (E,E)-farnesol, reduces white-to-opaque switching by ten-fold or more. The second input, an inferred PKA phosphorylation of residue T208 on the transcriptional regulator Efg1, increases white-to-opaque switching ten-fold. Combining these and other environmental inputs results in a variety of different switching rates, indicating that a given rate represents the integration of multiple inputs.}, }
@article {pmid36660365, year = {2023}, author = {Trovão, F and Correia, VG and Lourenço, FM and Ribeiro, DO and Carvalho, AL and Palma, AS and Pinheiro, BA}, title = {The structure of a Bacteroides thetaiotaomicron carbohydrate-binding module provides new insight into the recognition of complex pectic polysaccharides by the human microbiome.}, journal = {Journal of structural biology: X}, volume = {7}, number = {}, pages = {100084}, pmid = {36660365}, issn = {2590-1524}, abstract = {The Bacteroides thetaiotaomicron has developed a consortium of enzymes capable of overcoming steric constraints and degrading, in a sequential manner, the complex rhamnogalacturonan II (RG-II) polysaccharide. BT0996 protein acts in the initial stages of the RG-II depolymerisation, where its two catalytic modules remove the terminal monosaccharides from RG-II side chains A and B. BT0996 is modular and has three putative carbohydrate-binding modules (CBMs) for which the roles in the RG-II degradation are unknown. Here, we present the characterisation of the module at the C-terminal domain, which we designated BT0996-C. The high-resolution structure obtained by X-ray crystallography reveals that the protein displays a typical β-sandwich fold with structural similarity to CBMs assigned to families 6 and 35. The distinctive features are: 1) the presence of several charged residues at the BT0996-C surface creating a large, broad positive lysine-rich patch that encompasses the putative binding site; and 2) the absence of the highly conserved binding-site signatures observed in CBMs from families 6 and 35, such as region A tryptophan and region C asparagine. These findings hint at a binding mode of BT0996-C not yet observed in its homologues. In line with this, carbohydrate microarrays and microscale thermophoresis show the ability of BT0996-C to bind α1-4-linked polygalacturonic acid, and that electrostatic interactions are essential for the recognition of the anionic polysaccharide. The results support the hypothesis that BT0996-C may have evolved to potentiate the action of BT0996 catalytic modules on the complex structure of RG-II by binding to the polygalacturonic acid backbone sequence.}, }
@article {pmid36658342, year = {2023}, author = {Heinken, A and Hertel, J and Acharya, G and Ravcheev, DA and Nyga, M and Okpala, OE and Hogan, M and Magnúsdóttir, S and Martinelli, F and Nap, B and Preciat, G and Edirisinghe, JN and Henry, CS and Fleming, RMT and Thiele, I}, title = {Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine.}, journal = {Nature biotechnology}, volume = {41}, number = {9}, pages = {1320-1331}, pmid = {36658342}, issn = {1546-1696}, support = {757922/ERC_/European Research Council/International ; RF1 AG058942/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; Precision Medicine ; Genome ; Genomics ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; }, abstract = {The human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs. Designing precision medicine approaches that incorporate microbial metabolism would require strain- and molecule-resolved, scalable computational modeling. Here, we extend our previous resource of genome-scale metabolic reconstructions of human gut microorganisms with a greatly expanded version. AGORA2 (assembly of gut organisms through reconstruction and analysis, version 2) accounts for 7,302 strains, includes strain-resolved drug degradation and biotransformation capabilities for 98 drugs, and was extensively curated based on comparative genomics and literature searches. The microbial reconstructions performed very well against three independently assembled experimental datasets with an accuracy of 0.72 to 0.84, surpassing other reconstruction resources and predicted known microbial drug transformations with an accuracy of 0.81. We demonstrate that AGORA2 enables personalized, strain-resolved modeling by predicting the drug conversion potential of the gut microbiomes from 616 patients with colorectal cancer and controls, which greatly varied between individuals and correlated with age, sex, body mass index and disease stages. AGORA2 serves as a knowledge base for the human microbiome and paves the way to personalized, predictive analysis of host-microbiome metabolic interactions.}, }
@article {pmid36654471, year = {2023}, author = {Shelin, R and Meenakshi, S}, title = {Rise of Bacterial Small Proteins and Peptides in Therapeutic Applications.}, journal = {Protein and peptide letters}, volume = {30}, number = {2}, pages = {126-136}, doi = {10.2174/0929866530666230118144723}, pmid = {36654471}, issn = {1875-5305}, mesh = {*Bacterial Proteins ; *Peptides/therapeutic use/genetics ; Protein Biosynthesis ; Ribosomes ; Amino Acids ; Open Reading Frames ; }, abstract = {BACKGROUND: Polypeptides that comprise less than 100 amino acids (50 amino acids in some cases) are referred to as small proteins (SPs), however, as of date, there is no strict definition. In contrast to the small polypeptides that arise due to proteolytic activity or abrupt protein synthesis, SPs are coded by small open reading frames (sORFs) and are conventionally synthesized by ribosomes.<br><br>PURPOSE OF THE REVIEW: Although proteins that contain more than 100 amino acids have been studied exquisitely, studies on small proteins have been largely ignored, basically due to the unsuccessful detection of these SPs by traditional methodologies/techniques. Serendipitous observation of several small proteins and elucidation of their vital functions in cellular processes opened the floodgate of a new area of research on the new family of proteins called "Small proteins". Having known the significance of such SPs, several advanced techniques are being developed to precisely identify and characterize them.<br><br>CONCLUSION: Bacterial small proteins (BSPs) are being intensely investigated in recent days and that has brought the versatile role of BSPs into the limelight. In particular, identification of the fact that BSPs exhibit antimicrobial activity has further expanded its scope in the area of therapeutics. Since the microbiome plays an inevitable role in determining the outcome of personalized medicine, studies on the secretory small proteins of the microbiome are gaining momentum. This review discusses the importance of bacterial small proteins and peptides in terms of their therapeutic applications.}, }
@article {pmid36653831, year = {2023}, author = {Zyoud, SH and Shakhshir, M and Abushanab, AS and Koni, A and Shahwan, M and Jairoun, AA and Al-Jabi, SW}, title = {Mapping the output of the global literature on the links between gut microbiota and COVID-19.}, journal = {Journal of health, population, and nutrition}, volume = {42}, number = {1}, pages = {3}, pmid = {36653831}, issn = {2072-1315}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *COVID-19 ; *Probiotics/therapeutic use ; Anti-Bacterial Agents ; Databases, Factual ; }, abstract = {BACKGROUND: The term "human microbiota" refers to populations of microorganisms that live harmoniously in co-existence with humans. They contribute significantly to the host's immunological response when confronted with a respiratory viral infection. However, little is known about the relationship between the human microbiome and COVID-19. Therefore, our objective is to perform a bibliometric analysis to explore the overall structure and hotspots of research activity on the links between microbiota and COVID-19 at the global level.<br><br>METHODS: The research literature on the microbiota and COVID-19 published between 2020 and 2022 was obtained from the Scopus database. Bibliometric analysis and network visualization were performed with VOSviewer.<br><br>RESULTS: Of the 701 publications selected, the USA contributed the most (n&#x2009;=&#x2009;157, 22.40%), followed by China (n&#x2009;=&#x2009;118, 16.83%) and Italy (n&#x2009;=&#x2009;82, 11.70%). Hotspots in this field were "COVID-19 is associated with an altered upper respiratory tract microbiome," "the effect of antibiotics on the gut microbiome," as well as "patient nutrition and probiotic therapy in COVID-19."<br><br>CONCLUSIONS: The links between microbiota and COVID-19 remain an urgent concern at present, and the use of probiotics or/and antibiotics during the pandemic needs to be further improved. This landscape analysis of the links between the microbiota and COVID-19 will provide a basis for future research.}, }
@article {pmid36653448, year = {2023}, author = {Valles-Colomer, M and Blanco-Míguez, A and Manghi, P and Asnicar, F and Dubois, L and Golzato, D and Armanini, F and Cumbo, F and Huang, KD and Manara, S and Masetti, G and Pinto, F and Piperni, E and Punčochář, M and Ricci, L and Zolfo, M and Farrant, O and Goncalves, A and Selma-Royo, M and Binetti, AG and Becerra, JE and Han, B and Lusingu, J and Amuasi, J and Amoroso, L and Visconti, A and Steves, CM and Falchi, M and Filosi, M and Tett, A and Last, A and Xu, Q and Qin, N and Qin, H and May, J and Eibach, D and Corrias, MV and Ponzoni, M and Pasolli, E and Spector, TD and Domenici, E and Collado, MC and Segata, N}, title = {The person-to-person transmission landscape of the gut and oral microbiomes.}, journal = {Nature}, volume = {614}, number = {7946}, pages = {125-135}, pmid = {36653448}, issn = {1476-4687}, support = {MR/N01183X/1/MRC_/Medical Research Council/United Kingdom ; MR/S005013/1/MRC_/Medical Research Council/United Kingdom ; U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Female ; Humans ; Infant ; *Bacteria/classification/genetics/isolation &amp; purification ; *Gastrointestinal Microbiome/genetics ; Metagenome ; *Microbiota/genetics ; Mothers ; *Mouth/microbiology ; Infectious Disease Transmission, Vertical ; Family Characteristics ; Aging ; *Disease Transmission, Infectious ; Time Factors ; Microbial Viability ; *Home Environment ; }, abstract = {The human microbiome is an integral component of the human body and a co-determinant of several health conditions[1,2]. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown[3,4]. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies[5], especially those on non-infectious, microbiome-associated diseases.}, }
@article {pmid36647645, year = {2023}, author = {Liu, ZH and Zhou, XD and Zhang, LL}, title = {[Research Progress in the Correlation Between Oral Microbiota and Chronic Kidney Disease].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {54}, number = {1}, pages = {66-70}, pmid = {36647645}, issn = {1672-173X}, mesh = {Humans ; Dysbiosis/complications ; Quality of Life ; *Gastrointestinal Microbiome ; *Renal Insufficiency, Chronic/complications ; *Microbiota ; }, abstract = {Chronic kidney disease (CKD), one of the common clinical urological diseases, is increasingly more prevalent in recent years and has emerged as a major concern of public health around the globe. The continuous recurrence of CKD caused by renal function impairment leads eventually to irreversible renal failure and severe systemic complications, which causes severe negative impact on the quality of life of the patient. As an essential component of human microbiome, oral microbiota plays a major role in maintaining health, and there has been research suggesting close association between oral dysbiosis and CKD. It is therefore of great clinical significance to understand the correlation between CKD and oral microbiota. Herein, we reviewed the characteristics of oral microbiota of CKD patients, the possible mechanisms of oral microbiota's involvement in the pathogenesis and development of CKD, and the latest research findings on oral dysbiosis and CKD, with a view to finding new approaches to early prevention and control of CKD through oral microbial targets.}, }
@article {pmid36647641, year = {2023}, author = {Guan, ZW and Xu, TQ and Shen, S and Li, X and Feng, Q}, title = {[Pathways and Mechanisms of Periodontitis Contributing to Adverse Pregnancy Outcomes].}, journal = {Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition}, volume = {54}, number = {1}, pages = {39-48}, pmid = {36647641}, issn = {1672-173X}, mesh = {Animals ; Pregnancy ; Female ; Humans ; Pregnancy Outcome ; Placenta ; *Periodontitis/complications/microbiology ; *Pregnancy Complications ; Risk Factors ; }, abstract = {Periodontitis is a chronic oral inflammatory disease with a high incidence in the global population. Periodontal pathogens can colonize and infect multiple human tissues and organs through blood transmission, which is an important risk factor of many systemic diseases. Recently, the correlation between periodontitis and adverse pregnancy outcomes (APOs) has attracted growing research interest. Herein, we systematically reviewed the research progress in the relationship between periodontitis and APOs and summarized reported findings on the pathways and mechanisms by which periodontitis contributes to APOs. We also clarified that intrauterine infection caused by oral pathogens transmitted through blood is an important pathway by which periodontitis interferes with pregnancy. In addition, further research focused on the discovery of more APOs-related oral pathogenic bacteria and their virulence factors, analysis of the interaction between pathogenic bacteria and placental tissue, and pathogenic pathways of oral bacterial invasion of the fetus will promote thorough analysis of the specific molecular mechanism of how periodontitis affects APOs. Furthermore, the validation of the results of human population-based studies through animal/cell experiments and the translation into effective intervention strategies are of great clinical significance to the prevention and control of the occurrence and development of APOs.}, }
@article {pmid36647379, year = {2023}, author = {Mochochoko, BM and Pohl, CH and O'Neill, HG}, title = {Candida albicans-enteric viral interactions-The prostaglandin E2 connection and host immune responses.}, journal = {iScience}, volume = {26}, number = {1}, pages = {105870}, pmid = {36647379}, issn = {2589-0042}, abstract = {The human microbiome comprises trillions of microorganisms residing within different mucosal cavities and across the body surface. The gut microbiota modulates host susceptibility to viral infections in several ways, and microbial interkingdom interactions increase viral infectivity within the gut. Candida albicans, a frequently encountered fungal species in the gut, produces highly structured biofilms and eicosanoids such as prostaglandin E2 (PGE2), which aid in viral protection and replication. These biofilms encompass viruses and provide a shield from antiviral drugs or the immune system. PGE2 is a key modulator of active inflammation with the potential to regulate interferon signaling upon microbial invasion or viral infections. In this review, we raise the perspective of gut interkingdom interactions involving C. albicans and enteric viruses, with a special focus on biofilms, PGE2, and viral replication. Ultimately, we discuss the possible implications of C. albicans-enteric virus associations on host immune responses, particularly the interferon signaling pathway.}, }
@article {pmid36646294, year = {2023}, author = {Boopathi, S and Kumar, RMS and Priya, PS and Haridevamuthu, B and Nayak, SPRR and Chulenbayeva, L and Almagul, K and Arockiaraj, J}, title = {Gut Enterobacteriaceae and uraemic toxins - Perpetrators for ageing.}, journal = {Experimental gerontology}, volume = {173}, number = {}, pages = {112088}, doi = {10.1016/j.exger.2023.112088}, pmid = {36646294}, issn = {1873-6815}, mesh = {Aged, 80 and over ; Humans ; Aged ; *Enterobacteriaceae ; *Uremic Toxins ; Aging/physiology ; Longevity/physiology ; Liver ; }, abstract = {Ageing is a complex process that is associated with changes in the composition and functions of gut microbiota. Reduction of gut commensals is the hallmarks of ageing, which favours the expansion of pathogens even in healthy centenarians. Interestingly, gut Enterobacteriaceae have been found to be increased with age and also consistently observed in the patients with metabolic diseases. Thus, they are associated with all-cause mortality, regardless of genetic origin, lifestyle, and fatality rate. Moreover, Enterobacteriaceae are also implicated in accelerating the ageing process through telomere attrition, cellular senescence, inflammasome activation and impairing the functions of mitochondria. However, acceleration of ageing is likely to be determined by intrinsic interactions between Enterobacteriaceae and other associated gut bacteria. Several studies suggested that Enterobacteriaceae possess genes for the synthesis of uraemic toxins. In addition to intestine, Enterobacteriaceae and their toxic metabolites have also been found in other organs, such as adipose tissue and liver and that are implicated in multiorgan dysfunction and age-related diseases. Therefore, targeting Enterobacteriaceae is a nuance approach for reducing inflammaging and enhancing the longevity of older people. This review is intended to highlight the current knowledge of Enterobacteriaceae-mediated acceleration of ageing process.}, }
@article {pmid36645293, year = {2023}, author = {Huang, X and Erickson, DL and Meng, J}, title = {PhyloPlus: a Universal Tool for Phylogenetic Interrogation of Metagenomic Communities.}, journal = {mBio}, volume = {14}, number = {1}, pages = {e0345522}, pmid = {36645293}, issn = {2150-7511}, support = {U01 FD001418/FD/FDA HHS/United States ; }, mesh = {Humans ; Phylogeny ; *Metagenome ; Metagenomics ; *Microbiota/genetics ; Bacteria/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Phylogeny is a powerful tool that can be incorporated into quantitative descriptions of community diversity, yet its use has been limited largely due to the difficulty in constructing phylogenies which incorporate the wide genomic diversity of microbial communities. Here, we describe the development of a web portal, PhyloPlus, which enables users to generate customized phylogenies that may be applied to any bacterial or archaeal communities. We demonstrate the power of phylogeny by comparing metrics that employ phylogeny with those that do not when applied to data sets from two metagenomic studies (fermented food, n = 58; human microbiome, n = 60). This example shows how inclusion of all bacterial species identified by taxonomic classifiers (Kraken2 and Kaiju) made the phylogeny perfectly congruent to the corresponding classification outputs. Our phylogeny-based approach also enabled the construction of more constrained null models which (i) shed light into community structure and (ii) minimize potential inflation of type I errors. Construction of such null models allowed for the observation of under-dispersion in 44 (75.86%) food samples, with the metacommunity defined as bacteria that were found in different food matrices. We also observed that closely related species with high abundance and uneven distribution across different sites could potentially exaggerate the dissimilarity between phylogenetically similar communities if they were measured using traditional species-based metrics (Padj. = 0.003), whereas this effect was mitigated by incorporating phylogeny (Padj. = 1). In summary, our tool can provide additional insights into microbial communities of interest and facilitate the use of phylogeny-based approaches in metagenomic analyses. IMPORTANCE There has been an explosion of interest in how microbial diversity affects human health, food safety, and environmental functions among many other processes. Accurately measuring the diversity and structure of those communities is central to understanding their effects. Here, we describe the development of a freely available online tool, PhyloPlus, which allows users to generate custom phylogenies that may be applied to any data set, thereby removing a major obstacle to the application of phylogeny to metagenomic data analysis. We demonstrate that the genetic relatedness of the organisms within those communities is a critical feature of their overall diversity, and that using a phylogeny which captures and quantifies this diversity allows for much more accurate descriptions while preventing misleading conclusions based on estimates that ignore evolutionary relationships.}, }
@article {pmid36644130, year = {2023}, author = {Lo Presti, A and Del Chierico, F and Altomare, A and Zorzi, F and Monteleone, G and Putignani, L and Angeletti, S and Cicala, M and Guarino, MPL and Ciccozzi, M}, title = {Phylogenetic analysis of Prevotella copri from fecal and mucosal microbiota of IBS and IBD patients.}, journal = {Therapeutic advances in gastroenterology}, volume = {16}, number = {}, pages = {17562848221136328}, pmid = {36644130}, issn = {1756-283X}, abstract = {BACKGROUND: Prevotella copri is the most abundant member of the genus Prevotella that inhabits the human large intestines. Evidences correlated the increase in Prevotella abundance to inflammatory disorders, suggesting a pathobiont role.<br><br>OBJECTIVES: The aim of this study was to investigate the phylogenetic dynamics of P. copri in patients with irritable bowel syndrome (IBS), inflammatory bowel diseases (IBDs) and in healthy volunteers (CTRL).<br><br>DESIGN: A phylogenetic approach was used to characterize 64 P. copri 16S rRNA sequences, selected from a metagenomic database of fecal and mucosal samples from 52 patients affected by IBD, 44 by IBS and 59 healthy.<br><br>METHODS: Phylogenetic reconstructions were carried out using the maximum likelihood (ML) and Bayesian methods.<br><br>RESULTS: Maximum likelihood phylogenetic tree applied onto reference and data sets, assigned all the reads to P. copri clade, in agreement with the taxonomic classification previously obtained. The longer mean genetic distances were observed for both the couples IBD and CTRL and IBD and IBS, respect to the distance between IBS and CTRL, for fecal samples. The intra-group mean genetic distance increased going from IBS to CTRLs to IBD, indicating elevated genetic variability within IBD of P. copri sequences. None clustering based on the tissue inflammation or on the disease status was evidenced, leading to infer that the variability seemed to not be influenced by concomitant diseases, disease phenotypes or tissue inflammation. Moreover, patients with IBS appeared colonized by different strains of P. copri. In IBS, a correlation between isolates and disease grading was observed.<br><br>CONCLUSION: The characterization of P. copri phylogeny is relevant to better understand the interactions between microbiota and pathophysiology of IBD and IBS, especially for future development of therapies based on microbes (e.g. probiotics and synbiotics), to restore the microbiota in these bowel diseases.}, }
@article {pmid36629257, year = {2023}, author = {Pellegrino, GM and Browne, TS and Sharath, K and Bari, KA and Vancuren, SJ and Allen-Vercoe, E and Gloor, GB and Edgell, DR}, title = {Metabolically-targeted dCas9 expression in bacteria.}, journal = {Nucleic acids research}, volume = {51}, number = {2}, pages = {982-996}, pmid = {36629257}, issn = {1362-4962}, mesh = {Humans ; *Bacteria/genetics ; CRISPR-Cas Systems ; Escherichia coli/genetics ; Gene Expression Regulation ; *Glucuronides/metabolism ; Transcription Factors/genetics ; *CRISPR-Associated Protein 9/genetics ; *Operon ; }, abstract = {The ability to restrict gene expression to a relevant bacterial species in a complex microbiome is an unsolved problem. In the context of the human microbiome, one desirable target metabolic activity are glucuronide-utilization enzymes (GUS) that are implicated in the toxic re-activation of glucuronidated compounds in the human gastrointestinal (GI) tract, including the chemotherapeutic drug irinotecan. Here, we take advantage of the variable distribution of GUS enzymes in bacteria as a means to distinguish between bacteria with GUS activity, and re-purpose the glucuronide-responsive GusR transcription factor as a biosensor to regulate dCas9 expression in response to glucuronide inducers. We fused the Escherichia coli gusA regulatory region to the dCas9 gene to create pGreg-dCas9, and showed that dCas9 expression is induced by glucuronides, but not other carbon sources. When conjugated from E. coli to Gammaproteobacteria derived from human stool, dCas9 expression from pGreg-dCas9 was restricted to GUS-positive bacteria. dCas9-sgRNAs targeted to gusA specifically down-regulated gus operon transcription in Gammaproteobacteria, with a resulting ∼100-fold decrease in GusA activity. Our data outline a general strategy to re-purpose bacterial transcription factors responsive to exogenous metabolites for precise ligand-dependent expression of genetic tools such as dCas9 in diverse bacterial species.}, }
@article {pmid36625592, year = {2023}, author = {Swayambhu, M and Kümmerli, R and Arora, N}, title = {Microbiome-Based Stain Analyses in Crime Scenes.}, journal = {Applied and environmental microbiology}, volume = {89}, number = {1}, pages = {e0132522}, pmid = {36625592}, issn = {1098-5336}, mesh = {*Forensic Sciences/methods ; Machine Learning ; Crime ; *Microbiota ; High-Throughput Nucleotide Sequencing ; }, abstract = {Recent advances in next-generation sequencing technologies (NGS) coupled with machine learning have demonstrated the potential of microbiome-based analyses in applied areas such as clinical diagnostics and forensic sciences. Particularly in forensics, microbial markers in biological stains left at a crime scene can provide valuable information for the reconstruction of crime scene cases, as they contain information on bodily origin, the time since deposition, and donor(s) of the stain. Importantly, microbiome-based analyses provide a complementary or an alternative approach to current methods when these are limited or not feasible. Despite the promising results from recent research, microbiome-based stain analyses are not yet employed in routine casework. In this review, we highlight the two main gaps that need to be addressed before we can successfully integrate microbiome-based analyses in applied areas with a special focus on forensic casework: one is a comprehensive assessment of the method's strengths and limitations, and the other is the establishment of a standard operating procedure. For the latter, we provide a roadmap highlighting key decision steps and offering laboratory and bioinformatic workflow recommendations, while also delineating those aspects that require further testing. Our goal is to ultimately facilitate the streamlining of microbiome-based analyses within the existing forensic framework to provide alternate lines of evidence, thereby improving the quality of investigations.}, }
@article {pmid36624837, year = {2023}, author = {Fumagalli, MR and Saro, SM and Tajana, M and Zapperi, S and La Porta, CAM}, title = {Quantitative analysis of disease-related metabolic dysregulation of human microbiota.}, journal = {iScience}, volume = {26}, number = {1}, pages = {105868}, pmid = {36624837}, issn = {2589-0042}, abstract = {The metabolic activity of all the micro-organism composing the human microbiome interacts with the host metabolism contributing to human health and disease in a way that is not fully understood. Here, we introduce STELLA, a computational method to derive the spectrum of metabolites associated with the microbiome of an individual. STELLA integrates known information on metabolic pathways associated with each bacterial species and extracts from these the list of metabolic products of each singular reaction by means of automatic text analysis. By comparing the result obtained on a single subject with the metabolic profile data of a control set of healthy subjects, we are able to identify individual metabolic alterations. To illustrate the method, we present applications to autism spectrum disorder and multiple sclerosis.}, }
@article {pmid36624275, year = {2023}, author = {Tonelli, A and Lumngwena, EN and Ntusi, NAB}, title = {The oral microbiome in the pathophysiology of cardiovascular disease.}, journal = {Nature reviews. Cardiology}, volume = {20}, number = {6}, pages = {386-403}, pmid = {36624275}, issn = {1759-5010}, mesh = {Animals ; Humans ; *Cardiovascular Diseases/prevention &amp; control ; Dysbiosis/complications ; *Microbiota ; *Gastrointestinal Microbiome ; *Heart Failure/complications ; }, abstract = {Despite advances in our understanding of the pathophysiology of many cardiovascular diseases (CVDs) and expansion of available therapies, the global burden of CVD-associated morbidity and mortality remains unacceptably high. Important gaps remain in our understanding of the mechanisms of CVD and determinants of disease progression. In the past decade, much research has been conducted on the human microbiome and its potential role in modulating CVD. With the advent of high-throughput technologies and multiomics analyses, the complex and dynamic relationship between the microbiota, their 'theatre of activity' and the host is gradually being elucidated. The relationship between the gut microbiome and CVD is well established. Much less is known about the role of disruption (dysbiosis) of the oral microbiome; however, interest in the field is growing, as is the body of literature from basic science and animal and human investigations. In this Review, we examine the link between the oral microbiome and CVD, specifically coronary artery disease, stroke, peripheral artery disease, heart failure, infective endocarditis and rheumatic heart disease. We discuss the various mechanisms by which oral dysbiosis contributes to CVD pathogenesis and potential strategies for prevention and treatment.}, }
@article {pmid36620050, year = {2022}, author = {Chmiel, JA and Carr, C and Stuivenberg, GA and Venema, R and Chanyi, RM and Al, KF and Giguere, D and Say, H and Akouris, PP and Domínguez Romero, SA and Kwong, A and Tai, V and Koval, SF and Razvi, H and Bjazevic, J and Burton, JP}, title = {New perspectives on an old grouping: The genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1011102}, pmid = {36620050}, issn = {1664-302X}, abstract = {Oxalobacter formigenes is a unique bacterium with the ability to metabolize oxalate as a primary carbon source. Most kidney stones in humans are composed of calcium and oxalate. Therefore, supplementation with an oxalate-degrading bacterium may reduce stone burden in patients suffering from recurrent calcium oxalate-based urolithiasis. Strains of O. formigenes are divided into two groups: group I and group II. However, the differences between strains from each group remain unclear and elucidating these distinctions will provide a better understanding of their physiology and potential clinical applications. Here, genomes from multiple O. formigenes strains underwent whole genome sequencing followed by phylogenetic and functional analyses. Genetic differences suggest that the O. formigenes taxon should be divided into an additional three species: Oxalobacter aliiformigenes sp. nov, Oxalobacter paeniformigenes sp. nov, and Oxalobacter paraformigenes sp. nov. Despite the similarities in the oxalyl-CoA gene (oxc), which is essential for oxalate degradation, these strains have multiple unique genetic features that may be potential exploited for clinical use. Further investigation into the growth of these strains in a simulated fecal environment revealed that O. aliiformigenes strains are capable of thriving within the human gut microbiota. O. aliiformigenes may be a better therapeutic candidate than current group I strains (retaining the name O. formigenes), which have been previously tested and shown to be ineffective as an oral supplement to mitigate stone disease. By performing genomic analyses and identifying these novel characteristics, Oxalobacter strains better suited to mitigation of calcium oxalate-based urolithiasis may be identified in the future.}, }
@article {pmid36613488, year = {2022}, author = {Rodríguez-Daza, MC and de Vos, WM}, title = {Polyphenols as Drivers of a Homeostatic Gut Microecology and Immuno-Metabolic Traits of Akkermansia muciniphila: From Mouse to Man.}, journal = {International journal of molecular sciences}, volume = {24}, number = {1}, pages = {}, pmid = {36613488}, issn = {1422-0067}, support = {024.002.002//SIAM Gravitation/ ; }, mesh = {*Polyphenols/pharmacology/metabolism ; Anthocyanins/metabolism ; Verrucomicrobia/metabolism ; Humans ; *Diabetes Mellitus, Type 2 ; Akkermansia ; }, abstract = {Akkermansia muciniphila is a mucosal symbiont considered a gut microbial marker in healthy individuals, as its relative abundance is significantly reduced in subjects with gut inflammation and metabolic disturbances. Dietary polyphenols can distinctly stimulate the relative abundance of A. muciniphila, contributing to the attenuation of several diseases, including obesity, type 2 diabetes, inflammatory bowel diseases, and liver damage. However, mechanistic insight into how polyphenols stimulate A. muciniphila or its activity is limited. This review focuses on dietary interventions in rodents and humans and in vitro studies using different phenolic classes. We provide critical insights with respect to potential mechanisms explaining the effects of polyphenols affecting A. muciniphila. Anthocyanins, flavan-3-ols, flavonols, flavanones, stilbenes, and phenolic acids are shown to increase relative A. muciniphila levels in vivo, whereas lignans exert the opposite effect. Clinical trials show consistent findings, and high intervariability relying on the gut microbiota composition at the baseline and the presence of multiple polyphenol degraders appear to be cardinal determinants in inducing A. muciniphila and associated benefits by polyphenol intake. Polyphenols signal to the AhR receptor and impact the relative abundance of A. muciniphila in a direct and indirect fashion, resulting in the restoration of intestinal epithelial integrity and homeostatic crosstalk with the gut microbiota by affecting IL-22 production. Moreover, recent evidence suggests that A. muciniphila participates in the initial hydrolysis of some polyphenols but does not participate in their complete metabolism. In conclusion, the consumption of polyphenol-rich foods targeting A. muciniphila as a pivotal intermediary represents a promising precision nutritional therapy to prevent and attenuate metabolic and inflammatory diseases.}, }
@article {pmid36612415, year = {2022}, author = {Eggers, S and Bixby, M and Renzetti, S and Curtin, P and Gennings, C}, title = {Human Microbiome Mixture Analysis Using Weighted Quantile Sum Regression.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612415}, issn = {1660-4601}, support = {U2C ES026555/ES/NIEHS NIH HHS/United States ; K99 ES032884/ES/NIEHS NIH HHS/United States ; P30 ES023515/ES/NIEHS NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; U2CES026555/ES/NIEHS NIH HHS/United States ; P30ES023515/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; Feces ; *Microbiota ; *Gastrointestinal Microbiome ; Obesity ; Body Mass Index ; }, abstract = {Studies of the health effects of the microbiome often measure overall associations by using diversity metrics, and individual taxa associations in separate analyses, but do not consider the correlated relationships between taxa in the microbiome. In this study, we applied random subset weighted quantile sum regression with repeated holdouts (WQSRSRH), a mixture method successfully applied to 'omic data to account for relationships between many predictors, to processed amplicon sequencing data from the Human Microbiome Project. We simulated a binary variable associated with 20 operational taxonomic units (OTUs). WQSRSRH was used to test for the association between the microbiome and the simulated variable, adjusted for sex, and sensitivity and specificity were calculated. The WQSRSRH method was also compared to other standard methods for microbiome analysis. The method was further illustrated using real data from the Growth and Obesity Cohort in Chile to assess the association between the gut microbiome and body mass index. In the analysis with simulated data, WQSRSRH predicted the correct directionality of association between the microbiome and the simulated variable, with an average sensitivity and specificity of 75% and 70%, respectively, in identifying the 20 associated OTUs. WQSRSRH performed better than all other comparison methods. In the illustration analysis of the gut microbiome and obesity, the WQSRSRH analysis identified an inverse association between body mass index and the gut microbe mixture, identifying Bacteroides, Clostridium, Prevotella, and Ruminococcus as important genera in the negative association. The application of WQSRSRH to the microbiome allows for analysis of the mixture effect of all the taxa in the microbiome, while simultaneously identifying the most important to the mixture, and allowing for covariate adjustment. It outperformed other methods when using simulated data, and in analysis with real data found results consistent with other study findings.}, }
@article {pmid36609878, year = {2023}, author = {Grami, E and Badawy, S and Kiljunen, S and Saidi, N and Skurnik, M}, title = {Characterization and genome analysis of Escherichia phage fBC-Eco01, isolated from wastewater in Tunisia.}, journal = {Archives of virology}, volume = {168}, number = {2}, pages = {44}, pmid = {36609878}, issn = {1432-8798}, support = {LR15CERTE04//Tunisian Ministry of Higher Education and Scientific Research/ ; Decision 2016//Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Wastewater ; Tunisia ; Genome, Viral ; *Bacteriophages/genetics ; Escherichia coli/genetics ; *Siphoviridae/genetics ; }, abstract = {The rise of antibiotic resistance in bacterial strains has led to vigorous exploration for alternative treatments. To this end, phage therapy has been revisited, and it is gaining increasing attention, as it may represent an efficient alternative for treating multiresistant pathogenic bacteria. Phage therapy is considered safe, and phages do not infect eukaryotic cells. There have been many studies investigating phage-host bacteria interactions and the ability of phages to target specific hosts. Escherichia coli is the causative agent of a multitude of infections, ranging from urinary tract infections to sepsis, with growing antibiotic resistance. In this study, we characterized the Escherichia phage fBC-Eco01, which was isolated from a water sample collected at Oued, Tunis. Electron microscopy showed that fBC-Eco01 phage particles have siphovirus morphology, with an icosahedral head of 61 ± 3 nm in diameter and a non-contractile tail of 94 ± 2 nm in length and 12 ± 0.9 nm in width. The genome of fBC-Eco01 is a linear double-stranded DNA of 43.466 bp with a GC content of 50.4%. Comparison to databases allowed annotation of the functions to 39 of the 78 predicted gene products. A single-step growth curve revealed that fBC-Eco01 has a latent period of 30 minutes and a burst size of 175 plaque-forming units (PFU) per infected cell. Genomic analysis indicated that fBC-Eco01 is a member of the subfamily Guernseyvirinae. It is most closely related to a group of phages of the genus Kagunavirus that infect Enterobacter, Raoultella, and Escherichia strains.}, }
@article {pmid36602383, year = {2023}, author = {Swaney, MH and Nelsen, A and Sandstrom, S and Kalan, LR}, title = {Sweat and Sebum Preferences of the Human Skin Microbiota.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0418022}, pmid = {36602383}, issn = {2165-0497}, support = {F31 AR079846/AR/NIAMS NIH HHS/United States ; R35 GM137828/GM/NIGMS NIH HHS/United States ; T32 AI055397/AI/NIAID NIH HHS/United States ; U19 AI142720/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Sweat/chemistry ; Sebum ; Skin/microbiology ; *Microbiota ; Bacteria/genetics ; }, abstract = {The microorganisms inhabiting human skin must overcome numerous challenges that typically impede microbial growth, including low pH, osmotic pressure, and low nutrient availability. Yet the skin microbiota thrive on the skin and have adapted to these stressful conditions. The limited nutrients available for microbial use in this unique niche include those from host-derived sweat, sebum, and corneocytes. Here, we have developed physiologically relevant, synthetic skin-like growth media composed of compounds present in sweat and sebum. We find that skin-associated bacterial species exhibit unique growth profiles at different concentrations of artificial sweat and sebum. Most strains evaluated demonstrate a preference for high sweat concentrations, while the sebum preference is highly variable, suggesting that the capacity for sebum utilization may be a driver of the skin microbial community structure. In particular, the prominent skin commensal Staphylococcus epidermidis exhibits the strongest preference for sweat while growing equally well across sebum concentrations. Conversely, the growth of Corynebacterium kefirresidentii, another dominant skin microbiome member, is dependent on increasing concentrations of both sweat and sebum but only when sebum is available, suggesting a lipid requirement of this species. Furthermore, we observe that strains with similar growth profiles in the artificial media cluster by phylum, suggesting that phylogeny is a key factor in sweat and sebum use. Importantly, these findings provide an experimental rationale for why different skin microenvironments harbor distinct microbiome communities. In all, our study further emphasizes the importance of studying microorganisms in an ecologically relevant context, which is critical for our understanding of their physiology, ecology, and function on the skin. IMPORTANCE The human skin microbiome is adapted to survive and thrive in the harsh environment of the skin, which is low in nutrient availability. To study skin microorganisms in a system that mimics the natural skin environment, we developed and tested a physiologically relevant, synthetic skin-like growth medium that is composed of compounds found in the human skin secretions sweat and sebum. We find that most skin-associated bacterial species tested prefer high concentrations of artificial sweat but that artificial sebum concentration preference varies from species to species, suggesting that sebum utilization may be an important contributor to skin microbiome composition. This study demonstrates the utility of a skin-like growth medium, which can be applied to diverse microbiological systems, and underscores the importance of studying microorganisms in an ecologically relevant context.}, }
@article {pmid36596832, year = {2023}, author = {Kim, JH and Jeon, JY and Im, YJ and Ha, N and Kim, JK and Moon, SJ and Kim, MG}, title = {Long-term taxonomic and functional stability of the gut microbiome from human fecal samples.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {114}, pmid = {36596832}, issn = {2045-2322}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Specimen Handling/methods ; Feces ; *Microbiota ; }, abstract = {Appropriate storage of fecal samples is a critical step for unbiased analysis in human microbiome studies. The purpose of this study was to evaluate the stability of the fecal microbial community for up to 18 months. Ten healthy volunteers provided fecal samples at the Jeonbuk National University Hospital. Stool samples were stored under the following six conditions: four different storage temperatures (- 70 °C, - 20 °C, 4 °C, and room temperature [20-25 °C]) and two different collection tubes (OMNIgene-Gut and DNA/RNA shield-fecal collection tubes). The gut microbiome was analyzed with 16S rRNA sequencing. We compared the taxonomic composition, alpha diversity, beta diversity and inferred pathway abundance between the baseline and 18 months after storage. Samples collected in the DNA/RNA Shield-fecal collection tubes showed the best performance in preservation of the taxonomic composition at 18 months. Pairwise differences in alpha diversity metrics showed the least deviation from zero. The PERMANOVA test showed non-significant change of beta diversity metrics (Unweighted Unifrac: q-value 0.268; Weighted Unifrac: q-value 0.848). The functional stability was significantly well preserved in the DNA/RNA Shield-fecal collection tubes (adjusted p value < 0.05). Our results demonstrate the use of the DNA/RNA Shield-fecal collection tube as an alternative storage method for fecal samples to preserve the taxonomic and functional stability of the microbiome over a long term.}, }
@article {pmid36585105, year = {2023}, author = {Chen, BY and Lin, WZ and Li, YL and Bi, C and Du, LJ and Liu, Y and Zhou, LJ and Liu, T and Xu, S and Shi, CJ and Zhu, H and Wang, YL and Sun, JY and Liu, Y and Zhang, WC and Lu, HX and Wang, YH and Feng, Q and Chen, FX and Wang, CQ and Tonetti, MS and Zhu, YQ and Zhang, H and Duan, SZ}, title = {Roles of oral microbiota and oral-gut microbial transmission in hypertension.}, journal = {Journal of advanced research}, volume = {43}, number = {}, pages = {147-161}, pmid = {36585105}, issn = {2090-1224}, mesh = {Humans ; Animals ; Mice ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; Cross-Sectional Studies ; Follow-Up Studies ; Mice, Inbred C57BL ; *Microbiota ; *Hypertension ; *Periodontitis ; }, abstract = {INTRODUCTION: Considerable evidence has linked periodontitis (PD) to hypertension (HTN), but the nature behind this connection is unclear. Dysbiosis of oral microbiota leading to PD is known to aggravate different systematic diseases, but the alteration of oral microbiota in HTN and their impacts on blood pressure (BP) remains to be discovered.<br><br>OBJECTIVES: To characterize the alterations of oral and gut microbiota and their roles in HTN.<br><br>METHODS: We performed a cross-sectional (95 HTN participants and 39 controls) and a 6-month follow-up study (52 HTN participants and 26 controls) to analyze the roles of oral and gut microbiota in HTN. Saliva, subgingival plaques, and feces were collected for 16S rRNA gene sequencing or metagenomic analysis. C57BL/6J mice were pretreated with antibiotics to deplete gut microbiota, and then transplanted with human saliva by gavage to test the impacts of abnormal oral-gut microbial transmission on HTN.<br><br>RESULTS: BP in participants with PD was higher than no PD in both cross-sectional and follow-up cohort. Relative abundances of 14 salivary genera, 15 subgingival genera and 10 gut genera significantly altered in HTN and those of 7 salivary genera, 12 subgingival genera and 6 gut genera significantly correlated with BP. Sixteen species under 5 genera were identified as oral-gut transmitters, illustrating the presence of oral-gut microbial transmission in HTN. Veillonella was a frequent oral-gut transmitter stably enriched in HTN participants of both cross-sectional and follow-up cohorts. Saliva from HTN participants increased BP in hypertensive mice. Human saliva-derived Veillonella successfully colonized in mouse gut, more abundantly under HTN condition.<br><br>CONCLUSIONS: PD and oral microbiota are strongly associated with HTN, likely through oral-gut transmission of microbes. Ectopic colonization of saliva-derived Veillonella in the gut may aggravate HTN. Therefore, precise manipulations of oral microbiota and/or oral-gut microbial transmission may be useful strategies for better prevention and treatment of HTN.}, }
@article {pmid36572917, year = {2022}, author = {Mhuireach, G&#xc1; and Fahimipour, AK and Vandegrift, R and Muscarella, ME and Hickey, R and Bateman, AC and Van Den Wymelenberg, KG and Bohannan, BJM}, title = {Temporary establishment of bacteria from indoor plant leaves and soil on human skin.}, journal = {Environmental microbiome}, volume = {17}, number = {1}, pages = {61}, pmid = {36572917}, issn = {2524-6372}, support = {G-2015-14023//Alfred P. Sloan Foundation/ ; }, abstract = {BACKGROUND: Plants are found in a large percentage of indoor environments, yet the potential for bacteria associated with indoor plant leaves and soil to colonize human skin remains unclear. We report results of experiments in a controlled climate chamber to characterize bacterial communities inhabiting the substrates and leaves of five indoor plant species, and quantify microbial transfer dynamics and residence times on human skin following simulated touch contact events. Controlled bacterial propagule transfer events with soil and leaf donors were applied to the arms of human occupants and repeatedly measured over a 24-h period using 16S rRNA gene amplicon sequencing.<br><br>RESULTS: Substrate samples had greater biomass and alpha diversity compared to leaves and baseline skin bacterial communities, as well as dissimilar taxonomic compositions. Despite these differences in donor community diversity and biomass, we observed repeatable patterns in the dynamics of transfer events. Recipient human skin bacterial communities increased in alpha diversity and became more similar to donor communities, an effect which, for soil contact only, persisted for at least 24 h. Washing with soap and water effectively returned communities to their pre-perturbed state, although some abundant soil taxa resisted removal through washing.<br><br>CONCLUSIONS: This study represents an initial characterization of bacterial relationships between humans and indoor plants, which represent a potentially valuable element of biodiversity in the built environment. Although environmental microbiota are unlikely to permanently colonize skin following a single contact event, repeated or continuous exposures to indoor biodiversity may be increasingly relevant for the functioning and diversity of the human microbiome as urbanization continues.}, }
@article {pmid36569851, year = {2022}, author = {Blázquez-Bondia, C and Parera, M and Català-Moll, F and Casadellà, M and Elizalde-Torrent, A and Aguiló, M and Espadaler-Mazo, J and Santos, JR and Paredes, R and Noguera-Julian, M}, title = {Probiotic effects on immunity and microbiome in HIV-1 discordant patients.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {1066036}, pmid = {36569851}, issn = {1664-3224}, mesh = {Humans ; *HIV-1 ; Lipopolysaccharide Receptors ; *Probiotics/therapeutic use ; Prebiotics ; *Microbiota ; }, abstract = {BACKGROUND: Some HIV-1 infected patients are unable to completely recover normal CD4+ T-cell (CD4+) counts after achieving HIV-1 suppression with combined Antiretroviral Therapy (cART), hence being classified as immuno-discordant. The human microbiome plays a crucial role in maintaining immune homeostasis and is a potential target towards immune reconstitution.<br><br>SETTING: RECOVER (NCT03542786) was a double-blind placebo-controlled clinical trial designed to evaluate if the novel probiotic i3.1 (AB-Biotics, Sant Cugat del Vall&#xe8;s, Spain) was able to improve immune reconstitution in HIV-1 infected immuno-discordant patients with stable cART and CD4+ counts <500 cells/mm3. The mixture consisted of two strains of L. plantarum and one of P. acidilactici, given with or without a fiber-based prebiotic.<br><br>METHODS: 71 patients were randomized 1:2:2 to Placebo, Probiotic or probiotic + prebiotic (Synbiotic), and were followed over 6 months + 3-month washout period, in which changes on systemic immune status and gut microbiome were evaluated. Primary endpoints were safety and tolerability of the investigational product. Secondary endpoints were changes on CD4+ and CD8+ T-cell (CD8+) counts, inflammation markers and faecal microbiome structure, defined by alpha diversity (Gene Richness), beta diversity (Bray-Curtis) and functional profile. Comparisons across/within groups were performed using standard/paired Wilcoxon test, respectively.<br><br>RESULTS: Adverse event (AE) incidence was similar among groups (53%, 33%, and 55% in the Placebo, Probiotic and Synbiotic groups, respectively, the most common being grade 1 digestive AEs: flatulence, bloating and diarrhoea. Two grade 3 AEs were reported, all in the Synbiotic group: abdominal distension (possibly related) and malignant lung neoplasm (unrelated), and 1 grade 4&#xa0;AE in the Placebo: hepatocarcinoma (unrelated). Synbiotic exposure was associated with a higher increase in CD4+/CD8+ T-cell (CD4/CD8) ratio at 6 months vs baseline (median=0.76(IQR=0.51) vs 0.72(0. 45), median change= 0.04(IQR=0.19), p = 0.03). At month 9, the Synbiotic group had a significant increase in CD4/CD8 ratio (0.827(0.55) vs 0.825(0.53), median change = 0.04(IQR=0.15), p= 0.02) relative to baseline, and higher CD4+ counts (447 (157) vs. 342(73) counts/ml, p = 0.03), and lower sCD14 values (2.16(0.67) vs 3.18(0.8), p = 0.008) than Placebo. No effect in immune parameters was observed in the Probiotic arm. None of the two interventions modified microbial gene richness (alpha diversity). However, intervention as categorical variable was associated with slight but significant effect on Bray-Curtis distance variance (Adonis R2 = 0.02, p = 0.005). Additionally, at month 6, Synbiotic intervention was associated with lower pathway abundances vs Placebo of Assimilatory Sulphate Reduction (8.79&#xb7;10[-6] (1.25&#xb7;10[-5]) vs. 1.61&#xb7;10[-5] (2.77&#xb7;10[-5]), p = 0.03) and biosynthesis of methionine (2.3&#xb7;10[-5] (3.17&#xb7;10[-5]) vs. 4&#xb7;10[-5] (5.66&#xb7;10[-5]), p = 0.03) and cysteine (1.83&#xb7;10[-5] (2.56&#xb7;10[-5]) vs. 3.3&#xb7;10[-5] (4.62&#xb7;10[-5)], p = 0.03). At month 6, probiotic detection in faeces was associated with significant decreases in C Reactive Protein (CRP) vs baseline (11.1(22) vs. 19.2(66), median change= -2.7 (13.2) ug/ml, p = 0.04) and lower IL-6 values (0.58(1.13) vs. 1.17(1.59) ug/ml, p = 0.02) when compared with samples with no detectable probiotic. No detection of the probiotic was associated with higher CD4/CD8 ratio at month 6 vs baseline (0.718(0.57) vs. 0.58(0.4), median change = 0.4(0.2), p = 0.02). After washout, probiotic non-detection was also associated with a significant increase in CD4+ counts (457(153) vs. 416(142), median change = 45(75), counts/ml, p = 0.005) and CD4/CD8 ratio (0.67(0.5) vs 0.59(0.49), median change = 0.04 (0.18), p = 0.02).<br><br>CONCLUSION: A synbiotic intervention with L. plantarum and P. acidilactici was safe and led to small increases in CD4/CD8 ratio and minor reductions in sCD14 of uncertain clinical significance. A probiotic with the same composition was also safe but did not achieve any impact on immune parameters or faecal microbiome composition.}, }
@article {pmid36569196, year = {2022}, author = {Patpatia, S and Schaedig, E and Dirks, A and Paasonen, L and Skurnik, M and Kiljunen, S}, title = {Rapid hydrogel-based phage susceptibility test for pathogenic bacteria.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1032052}, pmid = {36569196}, issn = {2235-2988}, mesh = {Humans ; *Bacteriophages ; Hydrogels/pharmacology ; Gelatin/pharmacology ; Hyaluronic Acid/pharmacology ; Staphylococcus aureus ; Escherichia coli ; }, abstract = {Phage therapy is one alternative to cure infections caused by antibiotic resistant bacteria. Due to the narrow host range of phages, hundreds to thousands of phages are required to cover the diversity of bacterial pathogens. In personalized phage therapy, fast selection of the phages for individual patients is essential for successful therapy. The aims of this study were to set up a rapid hydrogel-based liquid phage susceptibility assay (PST) for the selection of phages for therapeutic use and to establish a "ready-to-screen" plate concept, where phages are readily stored in hydrogel as small droplets in microtiter plate wells. We first tested four commercially available hydrogels (GrowDex, Askina, Purilon, and Intrasite) for their suitability as phage matrices in PSTs with four phages, two of which infecting Escherichia coli and two Staphylococcus aureus. Of these four hydrogels, GrowDex was the best matrix for PST, as it did not inhibit bacterial growth, released phages quickly when mixed with bacterial culture, and maintained phage viability well. We then optimized the assay for both optical density and microscopy readers using GrowDex as matrix with 23 bacterial strains representing 10 different species and 23 phages possessing different morphologies and genome sizes. When the bacterial growth was monitored by microscopy reader, the PST was executed in just 3 hours, and there was no need for overnight culturing bacterial cells prior to the assay, whereas using optical density reader, bacteria had to be pre-cultured overnight, and the assay time was five hours. Finally, we evaluated the effect of three different chemical stabilizers (trehalose, hyaluronic acid, and gelatin) in a six-month stability assay with six model phages. These phages assay behaved very differently in respect to the chemical stabilizers, and there was not a single stabilizer suitable for all phages. However, when gelatin (0.01%) or hyaluronic acid (0.2 mg/ml) was used as stabilizer, all tested phages were still considered as positives in PST after a six-month storage in 1 ml volume. In "ready-to-screen" plates, the differences in phage stabilities were even more profound, varying from two to six months for the most and least stable phages, respectively.}, }
@article {pmid36567346, year = {2023}, author = {Leão, I and de Carvalho, TB and Henriques, V and Ferreira, C and Sampaio-Maia, B and Manaia, CM}, title = {Pseudomonadota in the oral cavity: a glimpse into the environment-human nexus.}, journal = {Applied microbiology and biotechnology}, volume = {107}, number = {2-3}, pages = {517-534}, pmid = {36567346}, issn = {1432-0614}, support = {PTDC/CTA-AMB/28196/2017//European Regional Development Fund/ ; PTDC/MEC-MCI/29777/2017//European Regional Development Fund/ ; }, mesh = {Humans ; *Mouth/microbiology ; Bacteria/genetics ; *Microbiota ; Anti-Bacterial Agents ; Klebsiella ; }, abstract = {The phylum Pseudomonadota is amongst the most represented in the environment, with a comparatively lower prevalence in the human oral cavity. The ubiquity of Pseudomonadota and the fact that the oral cavity is the most likely entry portal of bacteria from external sources underlie the need to better understand its occurrence in the interface environment-humans. Yet, the relevance oral Pseudomonadota is largely underexplored in the scientific literature, a gap that this review aims at addressing by making, for the first time, an overview of the diversity and ecology of Pseudomonadota in the oral cavity. The screening of scientific literature and human microbiome databases unveiled 1328 reports of Pseudomonadota in the oral cavity. Most of these belonged to the classes Beta- and Gammaproteobacteria, mainly to the families Neisseriaceae, Campylobacteriaceae, and Pasteurelaceae. Others also regularly reported include genera such as Enterobacter, Klebsiella, Acinetobacter, Escherichia, Burkholderia, or Citrobacter, whose members have high potential to acquire virulence and antibiotic resistance genes. This review provides evidence that clinically relevant environmental Pseudomonadota may colonize humans via oral cavity. The need for further investigation about Pseudomonadota at the environment-oral cavity interface and their role as vectors potentially involved in virulence and antibiotic resistance transmission is demonstrated. KEY POINTS: • Neisseriaceae, Campylobacteriaceae, and Pasteurelaceae are part of the core oral microbiome • Enterobacteriaceae, Acinetobacter, or Burkholderia are frequent in the oral microbiome • Gut dysbiosis may be associated with colonization by ubiquitous oral Pseudomonadota.}, }
@article {pmid36566203, year = {2022}, author = {Dang, T and Kumaishi, K and Usui, E and Kobori, S and Sato, T and Toda, Y and Yamasaki, Y and Tsujimoto, H and Ichihashi, Y and Iwata, H}, title = {Stochastic variational variable selection for high-dimensional microbiome data.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {236}, pmid = {36566203}, issn = {2049-2618}, mesh = {Humans ; Bayes Theorem ; Algorithms ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Metagenomics ; }, abstract = {BACKGROUND: The rapid and accurate identification of a minimal-size core set of representative microbial species plays an important role in the clustering of microbial community data and interpretation of clustering results. However, the huge dimensionality of microbial metagenomics datasets is a major challenge for the existing methods such as Dirichlet multinomial mixture (DMM) models. In the approach of the existing methods, the computational burden of identifying a small number of representative species from a large number of observed species remains a challenge.<br><br>RESULTS: We propose a novel approach to improve the performance of the widely used DMM approach by combining three ideas: (i) we propose an indicator variable to identify representative operational taxonomic units that substantially contribute to the differentiation among clusters; (ii) to address the computational burden of high-dimensional microbiome data, we propose a stochastic variational inference, which approximates the posterior distribution using a controllable distribution called variational distribution, and stochastic optimization algorithms for fast computation; and (iii) we extend the finite DMM model to an infinite case by considering Dirichlet process mixtures and estimating the number of clusters as a variational parameter. Using the proposed method, stochastic variational variable selection (SVVS), we analyzed the root microbiome data collected in our soybean field experiment, the human gut microbiome data from three published datasets of large-scale case-control studies and the healthy human microbiome data from the Human Microbiome Project.<br><br>CONCLUSIONS: SVVS demonstrates a better performance and significantly faster computation than those of the existing methods in all cases of testing datasets. In particular, SVVS is the only method that can analyze massive high-dimensional microbial data with more than 50,000 microbial species and 1000 samples. Furthermore, a core set of representative microbial species is identified using SVVS that can improve the interpretability of Bayesian mixture models for a wide range of microbiome studies. Video Abstract.}, }
@article {pmid36566175, year = {2022}, author = {Zhang, J and Ma, C and Qin, H and Wang, Z and Zhu, C and Liu, X and Hao, X and Liu, J and Li, L and Cai, Z}, title = {Construction and validation of a metabolic-related genes prognostic model for oral squamous cell carcinoma based on bioinformatics.}, journal = {BMC medical genomics}, volume = {15}, number = {1}, pages = {269}, pmid = {36566175}, issn = {1755-8794}, support = {ZR2021MH033//the Science and Technology Foundation of Shandong Province/ ; 2018M632679//China Postdoctoral Science Foundation/ ; 2021M024//Traditional Chinese Medicine Science and Technology Project of Shandong Province/ ; }, mesh = {Humans ; *Carcinoma, Squamous Cell/genetics ; Squamous Cell Carcinoma of Head and Neck ; Prognosis ; *Mouth Neoplasms/genetics ; Computational Biology ; *Head and Neck Neoplasms ; }, abstract = {BACKGROUND: Oral squamous cell carcinoma (OSCC) accounts for a frequently-occurring head and neck cancer, which is characterized by high rates of morbidity and mortality. Metabolism-related genes (MRGs) show close association with OSCC development, metastasis and progression, so we constructed an MRGs-based OSCC prognosis model for evaluating OSCC prognostic outcome.<br><br>METHODS: This work obtained gene expression profile as well as the relevant clinical information from the The Cancer Genome Atlas (TCGA) database, determined the MRGs related to OSCC by difference analysis, screened the prognosis-related MRGs by performing univariate Cox analysis, and used such identified MRGs for constructing the OSCC prognosis prediction model through Lasso-Cox regression. Besides, we validated the model with the GSE41613 dataset based on Gene Expression Omnibus (GEO) database.<br><br>RESULTS: The present work screened 317 differentially expressed MRGs from the database, identified 12 OSCC prognostic MRGs through univariate Cox regression, and then established a clinical prognostic model composed of 11 MRGs by Lasso-Cox analysis. Based on the optimal risk score threshold, cases were classified as low- or high-risk group. As suggested by Kaplan-Meier (KM) analysis, survival rate was obviously different between the two groups in the TCGA training set (P&#x2009;<&#x2009;0.001). According to subsequent univariate and multivariate Cox regression, risk score served as the factor to predict prognosis relative to additional clinical features (P&#x2009;<&#x2009;0.001). Besides, area under ROC curve (AUC) values for patient survival at 1, 3 and 5&#xa0;years were determined as 0.63, 0.70, and 0.76, separately, indicating that the prognostic model has good predictive accuracy. Then, we validated this clinical prognostic model using GSE41613. To enhance our model prediction accuracy, age, gender, risk score together with TNM stage were incorporated in a nomogram. As indicated by results of ROC curve and calibration curve analyses, the as-constructed nomogram had enhanced prediction accuracy compared with clinicopathological features alone, besides, combining clinicopathological characteristics with risk score contributed to predicting patient prognosis and guiding clinical decision-making.<br><br>CONCLUSION: In this study, 11 MRGs prognostic models based on TCGA database showed superior predictive performance and had a certain clinical application prospect in guiding individualized.}, }
@article {pmid36566099, year = {2023}, author = {Mishra, K and Isali, I and Sindhani, M and Prunty, M and Bell, S and Mahran, A and Damiani, G and Ghannoum, M and Retuerto, M and Kutikov, A and Ross, J and Woo, LL and Abbosh, PH and Bukavina, L}, title = {Characterization of Changes in Penile Microbiome Following Pediatric Circumcision.}, journal = {European urology focus}, volume = {9}, number = {4}, pages = {669-680}, doi = {10.1016/j.euf.2022.12.007}, pmid = {36566099}, issn = {2405-4569}, mesh = {United States ; Male ; Infant ; Humans ; Child ; Phylogeny ; *Gastrointestinal Microbiome ; *Microbiota/genetics ; *Mycobiome ; Inflammation ; }, abstract = {BACKGROUND: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome.<br><br>OBJECTIVE: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism.<br><br>We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project.<br><br>We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes-Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles.<br><br>RESULTS AND LIMITATIONS: Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p&#xa0;<&#xa0;0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p&#xa0;<&#xa0;0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision CONCLUSIONS: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis.<br><br>PATIENT SUMMARY: Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.}, }
@article {pmid36564884, year = {2022}, author = {Lunjani, N and Walsh, LJ and Venter, C and Power, M and MacSharry, J and Murphy, DM and O'Mahony, L}, title = {Environmental influences on childhood asthma-The effect of diet and microbiome on asthma.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {33}, number = {12}, pages = {e13892}, pmid = {36564884}, issn = {1399-3038}, mesh = {Child ; Humans ; *Asthma/etiology ; *Microbiota ; Diet ; *Gastrointestinal Microbiome ; Immune System ; }, abstract = {Early life dietary patterns and timely maturation of mucosa-associated microbial communities are important factors influencing immune development and for establishing robust immune tolerance networks. Microbial fermentation of dietary components in vivo generates a vast array of molecules, some of which are integral components of the molecular circuitry that regulates immune and metabolic functions. These in turn protect against aberrant inflammatory processes and promote effector immune responses that quickly eliminate pathogens. Multiple studies suggest that changes in dietary habits, altered microbiome composition, and microbial metabolism are associated with asthma risk and disease severity. While it remains unclear whether these microbiome alterations are a cause or consequence of dysregulated immune responses, there is significant potential for using diet in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health. In this article, we will summarize our knowledge to date on the role of dietary patterns and microbiome activities on immune responses within the airways. Given the malleability of the human microbiome, its integration into the immune system, and its responsiveness to diet, this makes it a highly attractive target for therapeutic and nutritional intervention in children with asthma.}, }
@article {pmid36561630, year = {2023}, author = {Raudoniute, J and Bironaite, D and Bagdonas, E and Kulvinskiene, I and Jonaityte, B and Danila, E and Aldonyte, R}, title = {Human airway and lung microbiome at the crossroad of health and disease (Review).}, journal = {Experimental and therapeutic medicine}, volume = {25}, number = {1}, pages = {18}, pmid = {36561630}, issn = {1792-1015}, abstract = {The evolving field of the microbiome and microbiota has become a popular research topic. The human microbiome is defined as a new organ and is considered a living community of commensal, symbiotic and pathogenic microorganisms within a certain body space. The term 'microbiome' is used to define the entire genome of the microbiota. Bacteria, archaea, fungi, algae and small protists are all members of the microbiota, followed by phages, viruses, plasmids and mobile genetic elements. The composition, heterogeneity and dynamics of microbiomes in time and space, their stability and resistance, essential characteristics and key participants, as well as interactions within the microbiome and with the host, are crucial lines of investigation for the development of successful future diagnostics and therapies. Standardization of microbiome studies and harmonized comparable methodologies are required for the transfer of knowledge from fundamental science into the clinic. Human health is dependent on microbiomes and achieved by nurturing beneficial resident microorganisms and their interplay with the host. The present study reviewed scientific knowledge on the major components of the human respiratory microbiome, i.e. bacteria, viruses and fungi, their symbiotic and parasitic roles, and, also, major diseases of the human respiratory tract and their microbial etiology. Bidirectional relationships regulate microbial ecosystems and host susceptibility. Moreover, environmental insults render host tissues and microbiota disease-prone. The human respiratory microbiome reflects the ambient air microbiome. By understanding the human respiratory microbiome, potential therapeutic strategies may be proposed.}, }
@article {pmid36560636, year = {2022}, author = {Ács, N and Holohan, R and Dunne, LJ and Fernandes, AR and Clooney, AG and Draper, LA and Ross, RP and Hill, C}, title = {Comparing In Vitro Faecal Fermentation Methods as Surrogates for Phage Therapy Application.}, journal = {Viruses}, volume = {14}, number = {12}, pages = {}, pmid = {36560636}, issn = {1999-4915}, mesh = {Humans ; Fermentation ; *Phage Therapy ; Feces ; Gastrointestinal Tract ; *Bacteriophages/genetics ; }, abstract = {The human microbiome and its importance in health and disease have been the subject of numerous research articles. Most microbes reside in the digestive tract, with up to 10[12] cells per gram of faecal material found in the colon. In terms of gene number, it has been estimated that the gut microbiome harbours >100 times more genes than the human genome. Several human intestinal diseases are strongly associated with disruptions in gut microbiome composition. Less studied components of the gut microbiome are the bacterial viruses called bacteriophages that may be present in numbers equal to or greater than the prokaryotes. Their potential to lyse their bacterial hosts, or to act as agents of horizontal gene transfer makes them important research targets. In this study in vitro faecal fermentation systems were developed and compared for their ability to act as surrogates for the human colon. Changes in bacterial and viral composition occurred after introducing a high-titre single phage preparation both with and without a known bacterial host during the 24 h-long fermentation. We also show that during this timeframe 50 mL plastic tubes can provide data similar to that generated in a sophisticated faecal fermenter system. This knowledge can guide us to a better understanding of the short-term impact of bacteriophage transplants on the bacteriomes and viromes of human recipients.}, }
@article {pmid36557565, year = {2022}, author = {Gonçalves, MFM and Fernandes, &#xc2;R and Rodrigues, AG and Lisboa, C}, title = {Microbiome in Male Genital Mucosa (Prepuce, Glans, and Coronal Sulcus): A Systematic Review.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557565}, issn = {2076-2607}, support = {NORTE-01-0145-FEDER-000057//Horizon Europe programme and Norte 2020/ ; }, abstract = {The human body represents a complex and diverse reservoir of microorganisms. Although the human microbiome remains poorly characterized and understood, it should not be underestimated, since recent studies have highlighted its importance in health. This is especially evident when considering microbiota in the male reproductive system, responsible for men’s fertility and sexual behavior. Therefore, the aim of this systematic review is to provide an overview of the microbial communities of the healthy male genital mucosa and its role in disease. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to the English language and studies published until August 2022 that included culture-independent techniques for microbiome characterization in male genital mucosa. Ten articles were included. The bacterial composition of the male genital mucosa consists of several genera including Prevotella, Finegoldia, Peptoniphilus, Staphylococcus, Corynebacterium, and Anaerococcus, suggesting that the male genital microbiome composition shows similarities with the adjacent anatomical sites and is related with sexual intercourse. Moreover, male circumcision appears to influence the penile microbiome. Despite the lack of knowledge on the male genital mucosa microbiome in disease, it was reported that Staphylococcus warneri and Prevotella bivia were associated with balanoposthitis, whereas Enterobacteriaceae, Prevotella, and Fusobacterium were more abundant in male genital lichen sclerosus. The limited data and paucity of prospective controlled studies highlight the need for additional studies and established criteria for sampling methods and the microbiome assay procedure. Such a consensus would foster the knowledge about the composition of the genital microbiome of healthy males and its role in disease.}, }
@article {pmid36555624, year = {2022}, author = {Levi Mortera, S and Marzano, V and Vernocchi, P and Matteoli, MC and Guarrasi, V and Gardini, S and Del Chierico, F and Rapini, N and Deodati, A and Fierabracci, A and Cianfarani, S and Putignani, L}, title = {Functional and Taxonomic Traits of the Gut Microbiota in Type 1 Diabetes Children at the Onset: A Metaproteomic Study.}, journal = {International journal of molecular sciences}, volume = {23}, number = {24}, pages = {}, pmid = {36555624}, issn = {1422-0067}, mesh = {Adolescent ; Humans ; Child ; Aged ; *Diabetes Mellitus, Type 1 ; *Gastrointestinal Microbiome/physiology ; RNA, Ribosomal, 16S/genetics ; *Insulin-Secreting Cells ; Insulin, Regular, Human ; Insulin ; }, abstract = {Type 1 diabetes (T1D) is a chronic autoimmune metabolic disorder with onset in pediatric/adolescent age, characterized by insufficient insulin production, due to a progressive destruction of pancreatic β-cells. Evidence on the correlation between the human gut microbiota (GM) composition and T1D insurgence has been recently reported. In particular, 16S rRNA-based metagenomics has been intensively employed in the last decade in a number of investigations focused on GM representation in relation to a pre-disease state or to a response to clinical treatments. On the other hand, few works have been published using alternative functional omics, which is more suitable to provide a different interpretation of such a relationship. In this work, we pursued a comprehensive metaproteomic investigation on T1D children compared with a group of siblings (SIBL) and a reference control group (CTRL) composed of aged matched healthy subjects, with the aim of finding features in the T1D patients' GM to be related with the onset of the disease. Modulated metaproteins were found either by comparing T1D with CTRL and SIBL or by stratifying T1D by insulin need (IN), as a proxy of β-cells damage, showing some functional and taxonomic traits of the GM, possibly related to the disease onset at different stages of severity.}, }
@article {pmid36549660, year = {2023}, author = {Merritt, J and Kreth, J}, title = {Illuminating the oral microbiome and its host interactions: tools and approaches for molecular microbiology studies.}, journal = {FEMS microbiology reviews}, volume = {47}, number = {6}, pages = {}, pmid = {36549660}, issn = {1574-6976}, support = {R01 DE029492/DE/NIDCR NIH HHS/United States ; R21 DE029612/DE/NIDCR NIH HHS/United States ; R35 DE028252/DE/NIDCR NIH HHS/United States ; DE022083/NH/NIH HHS/United States ; }, mesh = {Humans ; *Dysbiosis ; *Microbiota/genetics ; Bacteria/genetics ; Symbiosis ; }, abstract = {Advancements in DNA sequencing technologies within the last decade have stimulated an unprecedented interest in the human microbiome, largely due the broad diversity of human diseases found to correlate with microbiome dysbiosis. As a direct consequence of these studies, a vast number of understudied and uncharacterized microbes have been identified as potential drivers of mucosal health and disease. The looming challenge in the field is to transition these observations into defined molecular mechanistic studies of symbiosis and dysbiosis. In order to meet this challenge, many of these newly identified microbes will need to be adapted for use in experimental models. Consequently, this review presents a comprehensive overview of the molecular microbiology tools and techniques that have played crucial roles in genetic studies of the bacteria found within the human oral microbiota. Here, we will use specific examples from the oral microbiome literature to illustrate the biology supporting these techniques, why they are needed in the field, and how such technologies have been implemented. It is hoped that this information can serve as a useful reference guide to help catalyze molecular microbiology studies of the many new understudied and uncharacterized species identified at different mucosal sites in the body.}, }
@article {pmid36547746, year = {2022}, author = {Akouris, PP and Chmiel, JA and Stuivenberg, GA and Kiattiburut, W and Bjazevic, J and Razvi, H and Grohe, B and Goldberg, HA and Burton, JP and Al, KF}, title = {Osteopontin phosphopeptide mitigates calcium oxalate stone formation in a Drosophila melanogaster model.}, journal = {Urolithiasis}, volume = {51}, number = {1}, pages = {19}, pmid = {36547746}, issn = {2194-7236}, mesh = {Animals ; *Calcium Oxalate/metabolism ; Drosophila melanogaster ; *Kidney Calculi/drug therapy/metabolism ; *Osteopontin/pharmacology/therapeutic use ; *Phosphopeptides/pharmacology/therapeutic use ; Disease Models, Animal ; }, abstract = {Kidney stone disease affects nearly one in ten individuals and places a significant economic strain on global healthcare systems. Despite the high frequency of stones within the population, effective preventative strategies are lacking and disease prevalence continues to rise. Osteopontin (OPN) is a urinary protein that can inhibit the formation of renal calculi in vitro. However, the efficacy of OPN in vivo has yet to be determined. Using an established Drosophila melanogaster model of calcium oxalate urolithiasis, we demonstrated that a 16-residue synthetic OPN phosphopeptide effectively reduced stone burden in vivo. Oral supplementation with this peptide altered crystal morphology of calcium oxalate monohydrate (COM) in a similar manner to previous in vitro studies, and the presence of the OPN phosphopeptide during COM formation and adhesion significantly reduced crystal attachment to mammalian kidney cells. Altogether, this study is the first to show that an OPN phosphopeptide can directly mitigate calcium oxalate urolithiasis formation in vivo by modulating crystal morphology. These findings suggest that OPN supplementation is a promising therapeutic approach and may be clinically useful in the management of urolithiasis in humans.}, }
@article {pmid36544495, year = {2022}, author = {Wortelboer, K and Koopen, AM and Herrema, H and de Vos, WM and Nieuwdorp, M and Kemper, EM}, title = {From fecal microbiota transplantation toward next-generation beneficial microbes: The case of Anaerobutyricum soehngenii.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1077275}, pmid = {36544495}, issn = {2296-858X}, abstract = {The commensal gut microbiota is important for human health and well-being whereas deviations of the gut microbiota have been associated with a multitude of diseases. Restoration of a balanced and diverse microbiota by fecal microbiota transplantation (FMT) has emerged as a potential treatment strategy and promising tool to study causality of the microbiota in disease pathogenesis. However, FMT comes with logistical challenges and potential safety risks, such as the transfer of pathogenic microorganisms, undesired phenotypes or an increased risk of developing disease later in life. Therefore, a more controlled, personalized mixture of cultured beneficial microbes might prove a better alternative. Most of these beneficial microbes will be endogenous commensals to the host without a long history of safe and beneficial use and are therefore commonly referred to as next-generation probiotics (NGP) or live biotherapeutic products (LBP). Following a previous FMT study within our group, the commensal butyrate producer Anaerobutyricum spp. (previously named Eubacterium hallii) was found to be associated with improved insulin-sensitivity in subjects with the metabolic syndrome. After the preclinical testing with Anaerobutyricum soehngenii in mice models was completed, the strain was produced under controlled conditions and several clinical studies evaluating its safety and efficacy in humans were performed. Here, we describe and reflect on the development of A. soehngenii for clinical use, providing practical guidance for the development and testing of NGPs and reflecting on the current regulatory framework.}, }
@article {pmid36544282, year = {2023}, author = {Bai, X and Xu, Q and Zhang, W and Wang, C}, title = {The Gut-Eye Axis: Correlation Between the Gut Microbiota and Autoimmune Dry Eye in Individuals With Sjögren Syndrome.}, journal = {Eye &amp; contact lens}, volume = {49}, number = {1}, pages = {1-7}, doi = {10.1097/ICL.0000000000000953}, pmid = {36544282}, issn = {1542-233X}, mesh = {Humans ; *Sjogren's Syndrome/complications ; *Gastrointestinal Microbiome ; *Autoimmune Diseases/complications/therapy ; Dysbiosis/complications ; *Dry Eye Syndromes/etiology/therapy ; }, abstract = {The impact of gut microbiota on human health, autoimmunity, and disease occurrence has long been recognized since the advancement of metagenomic sequencing technology has enabled a new level of perspective on the human microbiome. Emerging findings also suggest the existence of a gut-eye axis, wherein gut dysbiosis may be a crucial factor affecting the onset and progression of multiple ocular diseases. Sjögren syndrome (SS) is a chronic autoimmune disease mainly affecting the exocrine glands, primarily the lacrimal gland in the eye, resulting in severe dry eye. Although there are currently various treatments for environmental dry eye, the efficacy for SS-related autoimmune dry eye is limited, and new and more effective therapies still need to be explored. The latest studies have demonstrated that the gut microbiota plays a key role in the pathogenesis of autoimmune dry eye. This review describes the effect of gut microbiota on the ocular surface of autoimmune dry eye; introduces the presumable pathways forming the "gut dysbiosis-ocular surface-lacrimal gland axis"; discusses the advantages of restoring intestinal microecology to treat dry eye by fecal microbiota transplantation or probiotics, which are expected to provide perspectives into the correlation between the gut microbiome and dry eye; enhance our understanding of the pathogenesis in autoimmune dry eye; and be useful in the development of future interventions of dry eye by regulating the gut microbiota.}, }
@article {pmid36541798, year = {2023}, author = {Gupta, S and Poret, AJ and Hashemi, D and Eseonu, A and Yu, SH and D'Gama, J and Neel, VA and Lieberman, TD}, title = {Cutaneous Surgical Wounds Have Distinct Microbiomes from Intact Skin.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0330022}, pmid = {36541798}, issn = {2165-0497}, support = {UL1 TR002541/TR/NCATS NIH HHS/United States ; }, mesh = {Humans ; *Surgical Wound ; Staphylococcus aureus ; Skin/microbiology ; *Microbiota ; Bacteria ; *Skin Neoplasms ; }, abstract = {Infections are relatively rare following cutaneous surgical procedures, despite the potential for wound exposure to pathogens both during surgery and throughout the healing process. Although gut commensals are believed to reduce the risk of intestinal infections, an analogous role for skin commensals has not been described. In fact, the microbiome of normally healing surgical skin wounds has not yet been profiled using culture-independent techniques. We characterized the wound microbiome in 53 patients who underwent skin cancer surgery and healed without signs or symptoms of infection. A week after surgery, several bacterial species displayed significant differences in relative abundance when compared to control, nonoperated skin from the same patient. The relative abundance of the most common bacterium found on intact skin, Cutibacterium acnes, was reduced in wounds 5-fold. Staphylococcus aureus, a frequent cause of postoperative skin infections, was enriched 6.4-fold in clinically noninfected wounds, suggesting active suppression of pathogenicity. Finally, members of the Corynebacterium genus were the dominant organism in postoperative wounds, making up 37% of the average wound microbiome. The enrichment of these bacteria in normally healing wounds suggests that they might be capable of providing colonization resistance. Future studies focused on the biological and clinical significance of the wound microbiome may shed light on normal wound healing and potential therapeutic opportunities to mitigate infection risk. IMPORTANCE Commensal bacteria on skin may limit the ability of pathogenic bacteria to cause clinically significant infections. The bacteria on healing acute wounds, which might provide such a protective effect, have not been described using culture-independent approaches in the absence of antibiotics. We compare the microbiome of wounds a week after skin cancer removal surgery with intact skin from the same patient. We find that the potentially pathogenic species S. aureus is common on these healing wounds despite the absence of symptoms or signs of infection. We report that bacteria often considered as potential skin probiotics, including Staphylococcus epidermidis, do not reach high relative abundance in wound microbiomes. In contrast, specific members of the Corynebacterium genus, rarely associated with infections, were significantly enriched in healing wounds compared to intact skin. Future work is needed to see if Corynebacterium species or derivatives thereof could be employed to lower the risk of wound infection.}, }
@article {pmid36541771, year = {2023}, author = {Bhattacharjee, D and Flores, C and Woelfel-Monsivais, C and Seekatz, AM}, title = {Diversity and Prevalence of Clostridium innocuum in the Human Gut Microbiota.}, journal = {mSphere}, volume = {8}, number = {1}, pages = {e0056922}, pmid = {36541771}, issn = {2379-5042}, support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; P20 GM109094/GM/NIGMS NIH HHS/United States ; }, mesh = {Prevalence ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Firmicutes ; Humans ; *Clostridium/genetics ; }, abstract = {Clostridia are a polyphyletic group of Gram-positive, spore-forming anaerobes in the Firmicutes phylum that significantly impact metabolism and functioning of the human gastrointestinal tract. Recently, Clostridia were divided into two separate classes, Clostridia and Erysipelotrichia, based on phenotypic and 16S rRNA gene-based differences. While Clostridia include many well-known pathogenic bacteria, Erysipelotrichia remain relatively uncharacterized, particularly regarding their role as a pathogen versus commensal. Despite wide recognition as a commensal, the erysipelotrichial species Clostridium innocuum has recently been associated with various disease states. To further understand the ecological and potential virulent role of C. innocuum, we conducted a genomic comparison across 38 C. innocuum isolates and 194 publicly available genomes. Based on colony morphology, we isolated multiple C. innocuum cultivars from the feces of healthy human volunteers (n = 5). Comparison of the 16S rRNA gene of our isolates against publicly available microbiota data sets in healthy individuals suggests a high prevalence of C. innocuum across the human population (>80%). Analysis of single nucleotide polymorphisms (SNPs) across core genes and average nucleotide identify (ANI) revealed the presence of four clades among all available genomes (n = 232 total). Investigation of carbohydrate and protein utilization pathways, including comparison against the carbohydrate-activating enzyme (CAZyme) database, demonstrated inter- and intraclade differences that were further substantiated in vitro. Collectively, these data indicate genetic variance within the C. innocuum species that may help clarify its role in human disease and health. IMPORTANCE Clostridia are a group of medically important anaerobes as both commensals and pathogens. Recently, a new class of Erysipelotrichia containing a number of reassigned clostridial species has emerged, including Clostridium innocuum. Recent studies have implicated C. innocuum as a potential causative agent of diarrhea in patients from whom Clostridioides difficile could not be isolated. Using genomic and in vitro comparison, this study sought to characterize C. innocuum in the healthy human gut. Our analyses suggest that C. innocuum is a highly prevalent and diverse species, demonstrating clade-specific differences in metabolism and potential virulence. Collectively, this study is the first investigation into a broader description of C. innocuum as a human gut inhabitant.}, }
@article {pmid36541643, year = {2023}, author = {Hanttu, AM and Pekkala, S and Satokari, R and Hartikainen, AK and Arkkila, P and Pietiläinen, KH and Sutinen, JP}, title = {Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study.}, journal = {AIDS (London, England)}, volume = {37}, number = {2}, pages = {323-332}, doi = {10.1097/QAD.0000000000003419}, pmid = {36541643}, issn = {1473-5571}, mesh = {Humans ; Raltegravir Potassium/therapeutic use ; *Anti-HIV Agents/therapeutic use ; *HIV Infections/drug therapy ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Benzoxazines/therapeutic use ; Protease Inhibitors/therapeutic use ; Inflammation/drug therapy ; }, abstract = {OBJECTIVE: To study gut microbiota before and 24 weeks after a single antiretroviral agent switch.<br><br>DESIGN: HIV-positive patients with efavirenz (EFV) or a protease inhibitor (PI)-based antiretroviral therapy (ART) were randomized to switch EFV or PI to raltegravir (RAL group, n&#x200a;=&#x200a;19) or to continue unchanged ART (EFV/PI group, n&#x200a;=&#x200a;22). Age and weight-matched HIV-negative participants (n&#x200a;=&#x200a;10) were included for comparison.<br><br>METHODS: Microbiota was analyzed using 16S rRNA sequencing. Serum intestinal fatty acid-binding protein (I-FABP) and serum lipopolysaccharide-binding protein (LBP) were measured as gut permeability markers. Three-day food diaries were collected.<br><br>RESULTS: At week 24, microbiota diversity (Chao1 index) was higher in RAL than the EFV/PI group (P&#x200a;=&#x200a;0.014), and RAL group did not differ from HIV-negative participants. In subgroup analysis switching from EFV (P&#x200a;=&#x200a;0.043), but not from a PI to RAL increased Chao1. At week 24, RAL and EFV/PI group differed in the relative abundance of Prevotella 9 (higher in RAL, P&#x200a;=&#x200a;0.01), Phascolarctobacterium and Bacteroides (lower in RAL, P&#x200a;=&#x200a;0.01 and P&#x200a;=&#x200a;0.03). Dietary intakes did not change during the study and do not explain microbiota differences. Also, I-FABP and LBP remained unchanged.<br><br>CONCLUSION: Here we demonstrate that a single ART agent switch caused microbiota alterations, most importantly, an increase in diversity with EFV to RAL switch. Previously, we reported weight gain, yet reduced inflammation in this cohort. The observed microbiota differences between RAL and EFV/PI groups may be associated with reduced inflammation and/or increase in weight. Further studies are needed to evaluate inflammatory and metabolic capacity of microbiota with ART switches.}, }
@article {pmid36537820, year = {2023}, author = {Mantegazza, G and Gargari, G and Duncan, R and Consalez, F and Taverniti, V and Riso, P and Guglielmetti, S}, title = {Ready-To-Eat Rocket Salads as Potential Reservoir of Bacteria for the Human Microbiome.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0297022}, pmid = {36537820}, issn = {2165-0497}, mesh = {Humans ; Food Microbiology ; Colony Count, Microbial ; *Salads/microbiology ; Agar ; RNA, Ribosomal, 16S/genetics ; Vegetables/microbiology ; Bacteria ; *Microbiota ; }, abstract = {Reportedly, Western-type diets may induce the loss of key microbial taxa within the gastrointestinal microbiota, promoting the onset of noncommunicable diseases. It was hypothesized that the consumption of raw vegetables could contribute to the maintenance of the intestinal microbial community structure. In this context, we explored bacteria associated with commercial rocket salads produced through different farming practices: traditional (conventional, organic, and integrated) and vertical farming. Viable counts of mesophilic bacteria and lactic acid bacteria (LAB) were performed on plate count agar (PCA) and de Man-Rogosa-Sharpe (MRS) agar at pH 5.7, whereas metataxonomics through 16S rRNA gene sequencing was used to profile total bacteria associated with rocket salads. We found that rocket salads from vertical farming had much fewer viable bacteria and had a bacterial community structure markedly different from that of rocket salads from traditional farming. Furthermore, although α- and β-diversity analyses did not differentiate rocket samples according to farming techniques, several bacterial taxa distinguished organic and integrated from conventional farming salads, suggesting that farming practices could affect the taxonomic composition of rocket bacterial communities. LAB were isolated from only traditional farming samples and belonged to different species, which were variably distributed among samples and could be partly associated with farming practices. Finally, the INFOGEST protocol for in vitro simulation of gastrointestinal digestion revealed that several taxonomically different rocket-associated bacteria (particularly LAB) could survive gastrointestinal transit. This study suggests that commercial ready-to-eat rocket salads harbor live bacteria that possess the ability to survive gastrointestinal transit, potentially contributing to the taxonomic structure of the human gut microbiota. IMPORTANCE Western-type diets are composed of foods with a reduced amount of naturally occurring microorganisms. It was hypothesized that a microbe-depleted diet can favor the alteration of the human intestinal microbial ecosystem, therefore contributing to the onset of chronic metabolic and immune diseases currently recognized as the most significant causes of death in the developed world. Here, we studied the microorganisms that are associated with commercial ready-to-eat rocket salads produced through different farming practices. We showed that rocket salad (a widely consumed vegetal food frequently eaten raw) may be a source of lactic acid bacteria and other microbes that can survive gastrointestinal transit, potentially increasing the biodiversity of the intestinal microbiota. This deduction may be valid for virtually all vegetal foods that are consumed raw.}, }
@article {pmid36537130, year = {2022}, author = {Balskus, EP}, title = {Elucidating the Chemistry and Biology of the Human Microbiome.}, journal = {Biochemistry}, volume = {61}, number = {24}, pages = {2777-2778}, doi = {10.1021/acs.biochem.2c00652}, pmid = {36537130}, issn = {1520-4995}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Biology ; }, }
@article {pmid36534203, year = {2022}, author = {Jesus, HNR and Ramos, JN and Rocha, DJPG and Alves, DA and Silva, CS and Cruz, JVO and Vieira, VV and Souza, C and Santos, LS and Navas, J and Ramos, RTJ and Azevedo, V and Aguiar, ERGR and Mattos-Guaraldi, AL and Pacheco, LGC}, title = {The pan-genome of the emerging multidrug-resistant pathogen Corynebacterium striatum.}, journal = {Functional &amp; integrative genomics}, volume = {23}, number = {1}, pages = {5}, pmid = {36534203}, issn = {1438-7948}, support = {BOL0505/2018//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado da Bahia/ ; BOL0505/2018//Funda&#xe7;&#xe3;o de Amparo &#xe0; Pesquisa do Estado da Bahia/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CAPES-PROCAD 071/2013//Coordena&#xe7;&#xe3;o de Aperfei&#xe7;oamento de Pessoal de N&#xed;vel Superior/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; CNPq N&#xba; 09/2018//Conselho Nacional de Desenvolvimento Cient&#xed;fico e Tecnol&#xf3;gico/ ; MCT/FINEP/CT-INFRA01/2013//Financiadora de Estudos e Projetos/ ; }, mesh = {Humans ; *Corynebacterium ; *Anti-Bacterial Agents ; Phenotype ; Virulence Factors/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Microbial Sensitivity Tests ; }, abstract = {Corynebacterium striatum, a common constituent of the human skin microbiome, is now considered an emerging multidrug-resistant pathogen of immunocompromised and chronically ill patients. However, little is known about the molecular mechanisms in the transition from colonization to the multidrug-resistant (MDR) invasive phenotype in clinical isolates. This study performed a comprehensive pan-genomic analysis of C. striatum, including isolates from "normal skin microbiome" and from MDR infections, to gain insights into genetic factors contributing to pathogenicity and multidrug resistance in this species. For this, three novel genome sequences were obtained from clinical isolates of C. striatum of patients from Brazil, and other 24 complete or draft C. striatum genomes were retrieved from GenBank, including the ATCC6940 isolate from the Human Microbiome Project. Analysis of C. striatum strains demonstrated the presence of an open pan-genome (α = 0.852803) containing 3816 gene families, including 15 antimicrobial resistance (AMR) genes and 32 putative virulence factors. The core and accessory genomes included 1297 and 1307 genes, respectively. The identified AMR genes are primarily associated with resistance to aminoglycosides and tetracyclines. Of these, 66.6% are present in genomic islands, and four AMR genes, including aac(6')-ib7, are located in a class 1-integron. In conclusion, our data indicated that C. striatum possesses genomic characteristics favorable to the invasive phenotype, with high genomic plasticity, a robust genetic arsenal for iron acquisition, and important virulence determinants and AMR genes present in mobile genetic elements.}, }
@article {pmid36530685, year = {2022}, author = {Tozzo, P and Delicati, A and Caenazzo, L}, title = {Human microbiome and microbiota identification for preventing and controlling healthcare-associated infections: A systematic review.}, journal = {Frontiers in public health}, volume = {10}, number = {}, pages = {989496}, pmid = {36530685}, issn = {2296-2565}, mesh = {Humans ; *Cross Infection/prevention &amp; control/microbiology ; *Microbiota ; Delivery of Health Care ; }, abstract = {OBJECTIVE: This systematic review describes the role of the human microbiome and microbiota in healthcare-associated infections (HAIs). Studies on the microbiota of patients, healthcare environment (HE), medical equipment, or healthcare workers (HCW) and how it could be transmitted among the different subjects will be described in order to define alarming risk factors for HAIs spreading and to identify strategies for HAIs control or prevention.<br><br>METHODS: This review was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After retrieval in databases, identification, and screening of available records, 36 published studies were considered eligible and included in the review.<br><br>RESULTS: A multifaceted approach is required and the analyses of the many factors related to human microbiota, which can influence HAIs onset, could be of paramount importance in their prevention and control. In this review, we will focus mainly on the localization, transmission, and prevention of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) bacteria and Clostridium difficile which are the most common pathogens causing HAIs.<br><br>CONCLUSIONS: Healthcare workers' microbiota, patient's microbiota, environmental and medical equipment microbiota, ecosystem characteristics, ways of transmission, cleaning strategies, and the microbial resistome should be taken into account for future studies on more effective preventive and therapeutic strategies against HAIs.}, }
@article {pmid36527169, year = {2024}, author = {Zhang, Y and Zhang, H and Xu, T and Zeng, L and Liu, F and Huang, X and Liu, Q}, title = {Interactions among microorganisms open up a new world for anti-infectious therapy.}, journal = {The FEBS journal}, volume = {291}, number = {8}, pages = {1615-1631}, doi = {10.1111/febs.16705}, pmid = {36527169}, issn = {1742-4658}, support = {202110403093//National Innovation and Entrepreneurship Training Program for College Students/ ; 31760261//National Natural Science Foundation of China/ ; 32060040//National Natural Science Foundation of China/ ; 32260193//National Natural Science Foundation of China/ ; 82203032//National Natural Science Foundation of China/ ; 20202BAB206062//Natural Science Foundation of Jiangxi Province/ ; 20212BCJ23036//Training Plan for Academic and Technical Leaders of Major Disciplines in Jiangxi Province-Youth Talent Project/ ; }, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Symbiosis ; Fungi ; Bacteria/genetics ; }, abstract = {The human microbiome, containing bacteria, fungi, and viruses, is a community that coexists peacefully with humans most of the time, but with the potential to cause disease under certain conditions. When the environment changes or certain stimuli are received, microbes may interact with each other, causing or increasing the severity of disease in a host. With the appropriate methods, we can make these microbiota work for us, creating new applications for human health. This review discusses the wide range of interactions between microorganisms that result in an increase in susceptibility to, severity of, and mortality of diseases, and also briefly introduces how microorganisms interact with each other directly or indirectly. The study of microbial interactions and their mechanisms has revealed a new world of treatments for infectious disease. The regulation of the balance between intestinal flora, the correct application of probiotics, and the development of effective drugs by symbiosis all demonstrate the great contributions of the microbiota to human health and its powerful potential value. Consequently, the study of interactions between microorganisms plays an essential role in identifying the causes of diseases and the development of treatments.}, }
@article {pmid36525272, year = {2022}, author = {Lahtinen, P and Juuti, A and Luostarinen, M and Niskanen, L and Liukkonen, T and Tillonen, J and Kössi, J and Ilvesmäki, V and Viljakka, M and Satokari, R and Arkkila, P}, title = {Effectiveness of Fecal Microbiota Transplantation for Weight Loss in Patients With Obesity Undergoing Bariatric Surgery: A Randomized Clinical Trial.}, journal = {JAMA network open}, volume = {5}, number = {12}, pages = {e2247226}, pmid = {36525272}, issn = {2574-3805}, mesh = {Female ; Humans ; *Obesity, Morbid/surgery ; Fecal Microbiota Transplantation ; Weight Loss ; *Bariatric Surgery ; Obesity/surgery ; }, abstract = {IMPORTANCE: Severe obesity is a major health concern. However, a few patients remain resistant to bariatric surgery and other treatments. Animal studies suggest that weight may be altered by fecal microbiota transplantation (FMT) from a lean donor.<br><br>OBJECTIVE: To determine whether FMT from a lean donor reduces body weight and further improves the results of bariatric surgery.<br><br>This double-blinded, placebo-controlled, multicenter, randomized clinical trial was conducted in 2018 to 2021 among adult individuals with severe obesity treated at 2 bariatric surgery centers in Finland and included 18 months of follow-up. Patients eligible for bariatric surgery were recruited for the study. Data were analyzed from March 2021 to May 2022.<br><br>INTERVENTIONS: FMT from a lean donor or from the patient (autologous placebo) was administered by gastroscopy into the duodenum. Bariatric surgery was performed 6 months after the baseline intervention using laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG).<br><br>MAIN OUTCOMES AND MEASURES: The main outcome was weight reduction measured as the percentage of total weight loss (TWL).<br><br>RESULTS: Forty-one patients were recruited to participate in the study and were included in the final analysis (29 women [71.1%]; mean [SD] age, 48.7 [8.7] years; mean [SD] body mass index, 42.5 [6.0]). A total of 21 patients received FMT from a lean donor, and 20 received an autologous placebo. Six months after FMT, 34 patients underwent LRYGB and 4 underwent LSG. Thirty-four patients (82.9%) attended the last visit 18 months after the baseline visit. The percentage of TWL at 6 months was 4.8% (95% CI, 2.7% to 7.0%; P&#x2009;<&#x2009;.001) in the FMT group and 4.6% (95% CI, 1.5% to 7.6%; P&#x2009;=&#x2009;.006) in the placebo group, but no difference was observed between the groups. At 18 months from the baseline (ie, 12 months after surgery), the percentage of TWL was 25.3% (95% CI, 19.5 to 31.1; P&#x2009;<&#x2009;.001) in the FMT group and 25.2% (95% CI, 20.2 to 30.3; P&#x2009;<&#x2009;.001) in the placebo group; however, no difference was observed between the groups.<br><br>CONCLUSIONS AND RELEVANCE: FMT did not affect presurgical and postsurgical weight loss. Further studies are needed to elucidate the possible role of FMT in obesity.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03391817.}, }
@article {pmid36512373, year = {2023}, author = {Hurley, JC}, title = {Structural equation modelling the impact of antimicrobials on the human microbiome. Colonization resistance versus colonization susceptibility as case studies.}, journal = {The Journal of antimicrobial chemotherapy}, volume = {78}, number = {2}, pages = {328-337}, doi = {10.1093/jac/dkac408}, pmid = {36512373}, issn = {1460-2091}, mesh = {Humans ; Latent Class Analysis ; *Microbiota ; *Anti-Infective Agents/pharmacology ; Bacteria ; }, abstract = {The impact of antimicrobials on the human microbiome and its relationship to human health are of great interest. How antimicrobial exposure might drive change within specific constituents of the microbiome to effect clinically relevant endpoints is difficult to study. Clinical investigation of each step within a network of causation would be challenging if done 'step-by-step'. An analytic tool of great potential to clinical microbiome research is structural equation modelling (SEM), which has a long history of applications to research questions arising within subject areas as diverse as psychology and econometrics. SEM enables postulated models based on a network of causation to be tested en bloc by confrontation with data derived from the literature. Case studies for the potential application of SEM techniques are colonization resistance (CR) and its counterpart, colonization susceptibility (CS), wherein specific microbes within the microbiome are postulated to either impede (CR) or facilitate (CS) invasive infection with pathogenic bacteria. These postulated networks have three causation steps: exposure to specific antimicrobials are key drivers, clinically relevant infection endpoints are the measurable observables and the activity of key microbiome constituents mediating CR or CS, which may be unobservable, appear as latent variables in the model. SEM methods have potential application towards evaluating the activity of specific antimicrobial agents within postulated networks of causation using clinically derived data.}, }
@article {pmid36511710, year = {2023}, author = {Meng, J and Tao, J and Abu, Y and Sussman, DA and Girotra, M and Franceschi, D and Roy, S}, title = {HIV-Positive Patients on Antiretroviral Therapy Have an Altered Mucosal Intestinal but Not Oral Microbiome.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0247222}, pmid = {36511710}, issn = {2165-0497}, support = {F31 DA053795/DA/NIDA NIH HHS/United States ; R01 DA043252/DA/NIDA NIH HHS/United States ; R01 DA044582/DA/NIDA NIH HHS/United States ; R01 DA047089/DA/NIDA NIH HHS/United States ; R01 DA050542/DA/NIDA NIH HHS/United States ; }, mesh = {Humans ; *HIV Infections/drug therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; *Gastrointestinal Microbiome/genetics ; Intestinal Mucosa/microbiology ; Bacteria/genetics ; }, abstract = {This study characterized compositional and functional shifts in the intestinal and oral microbiome in HIV-positive patients on antiretroviral therapy compared to HIV-negative individuals. Seventy-nine specimens were collected from 5 HIV-positive and 12 control subjects from five locations (colon brush, colon wash, terminal ileum [TI] brush, TI wash, and saliva) during colonoscopy and at patient visits. Microbiome composition was characterized using 16S rRNA sequencing, and microbiome function was predicted using bioinformatics tools (PICRUSt and BugBase). Our analysis indicated that the β-diversity of all intestinal samples (colon brush, colon wash, TI brush, and TI wash) from patients with HIV was significantly different from patients without HIV. Specifically, bacteria from genera Prevotella, Fusobacterium, and Megasphaera were more abundant in samples from HIV-positive patients. On the other hand, bacteria from genera Ruminococcus, Blautia, and Clostridium were more abundant in samples from HIV-negative patients. Additionally, HIV-positive patients had higher abundances of biofilm-forming and pathogenic bacteria. Furthermore, pathways related to translation and nucleotide metabolism were elevated in HIV-positive patients, whereas pathways related to lipid and carbohydrate metabolism were positively correlated with samples from HIV-negative patients. Our analyses further showed variations in microbiome composition in HIV-positive and negative patients by sampling site. Samples from colon wash, colon brush, and TI wash were significant between groups, while samples from TI brush and saliva were not significant. Taken together, here, we report altered intestinal microbiome composition and predicted function in patients with HIV compared to uninfected patients, though we found no changes in the oral microbiome. IMPORTANCE Over 37 million people worldwide are living with HIV. Although the availability of antiretroviral therapy has significantly reduced the number of AIDS-related deaths, individuals living with HIV are at increased risk for opportunistic infections. We now know that HIV interacts with the trillions of bacteria, fungi, and viruses in the human body termed the microbiome. Only a limited number of previous studies have compared variations in the oral and gastrointestinal microbiome with HIV infection. Here, we detail how the oral and gastrointestinal microbiome changes with HIV infection, having used 5 different sampling sites to gain a more comprehensive view of these changes by location. Our results show site-specific changes in the intestinal microbiome associated with HIV infection. Additionally, we show that while there were significant changes in the intestinal microbiome, there were no significant changes in the oral microbiome.}, }
@article {pmid36509925, year = {2023}, author = {Peng, G and Sinkko, HM and Alenius, H and Lozano, N and Kostarelos, K and Bräutigam, L and Fadeel, B}, title = {Graphene oxide elicits microbiome-dependent type 2 immune responses via the aryl hydrocarbon receptor.}, journal = {Nature nanotechnology}, volume = {18}, number = {1}, pages = {42-48}, pmid = {36509925}, issn = {1748-3395}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Receptors, Aryl Hydrocarbon/genetics/metabolism ; Zebrafish/metabolism ; Zebrafish Proteins/genetics/metabolism ; Immunity, Innate ; Lymphocytes/metabolism ; *Microbiota ; }, abstract = {The gut microbiome produces metabolites that interact with the aryl hydrocarbon receptor (AhR), a key regulator of immune homoeostasis in the gut[1,2]. Here we show that oral exposure to graphene oxide (GO) modulates the composition of the gut microbiome in adult zebrafish, with significant differences in wild-type versus ahr2-deficient animals. Furthermore, GO was found to elicit AhR-dependent induction of cyp1a and homing of lck[+] cells to the gut in germ-free zebrafish larvae when combined with the short-chain fatty acid butyrate. To obtain further insights into the immune responses to GO, we used single-cell RNA sequencing to profile cells from whole germ-free embryos as well as cells enriched for lck. These studies provided evidence for the existence of innate lymphoid cell (ILC)-like cells[3] in germ-free zebrafish. Moreover, GO endowed with a 'corona' of microbial butyrate triggered the induction of ILC2-like cells with attributes of regulatory cells. Taken together, this study shows that a nanomaterial can influence the crosstalk between the microbiome and immune system in an AhR-dependent manner.}, }
@article {pmid36509338, year = {2023}, author = {Guimarães, VHD and Marinho, BM and Motta-Santos, D and Mendes, GDRL and Santos, SHS}, title = {Nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome.}, journal = {The Journal of nutritional biochemistry}, volume = {113}, number = {}, pages = {109252}, doi = {10.1016/j.jnutbio.2022.109252}, pmid = {36509338}, issn = {1873-4847}, mesh = {Humans ; *Metabolic Syndrome/metabolism ; *Gastrointestinal Microbiome/physiology ; Renin-Angiotensin System ; Obesity/metabolism ; *Probiotics ; Prebiotics ; }, abstract = {Obesity and metabolic disorders represent a significant global health problem and the gut microbiota plays an important role in modulating systemic homeostasis. Recent evidence shows that microbiota and its signaling pathways may affect the whole metabolism and the Renin-Angiotensin System (RAS), which in turn seems to modify microbiota. The present review aimed to investigate nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome components. A description of metabolic changes was obtained based on relevant scientific literature. The molecular and physiological mechanisms that impact the human microbiome were addressed, including the gut microbiota associated with obesity, diabetes, and hepatic steatosis. The RAS interaction signaling and modulation were analyzed. Strategies including the use of prebiotics, symbiotics, probiotics, and biotechnology may affect the gut microbiota and its impact on human health.}, }
@article {pmid36500264, year = {2022}, author = {Chen, L and Yuan, F and Chen, S and Li, X and Kong, L and Zhang, W}, title = {Potential Role of Host Microbiome in Areca Nut-Associated Carcinogenesis and Addiction.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {23}, pages = {}, pmid = {36500264}, issn = {1420-3049}, support = {No. 81874329 and 82073945//National Natural Science Foundation of China/ ; B2013-097//Scientific Research Project of Hunan Provincial Health Commission/ ; 2021YFA1301200//National Key R&amp;D Program of China/ ; 2018SK50907//Science and Technology Innovation Program of Hunan Provinc/ ; }, mesh = {Humans ; Areca/adverse effects ; Mastication ; *Behavior, Addictive ; *Microbiota ; Polyphenols ; }, abstract = {Areca nut (AN) is widely consumed all over the world, bringing great harm to human health and economy. Individuals with AN chewing are at high risk of cardiovascular disease and impaired immune system and metabolic system. Despite a growing number of studies having reported on the adverse effects brought by AN chewing, the exact mechanism of it is limited and the need for additional exploration remains. In recent years, the interaction between microorganisms, especially intestinal microorganism and host, has been extensively studied. AN chewing might disrupt the oral and intestinal microbiota communities through direct connect with the microbes it contains, altering PH, oxygen of oral and intestinal microenvironment, and disturbing the immune homeostasis. These mechanisms provide insights into the interplay between areca nut and host microbiota. Emerging studies have proposed that bidirectional interaction between polyphenols and intestinal microbes might play a potential role in the divergence of polyphenol, extracted from AN, among individuals with or without AN-induced cancer development and progression. Although some AN chewers have been aware of the harmful effects brought by AN, they cannot abolish this habit because of the addiction of AN. Increasing studies have tried to revealed that gut microbiota might influence the onset/development of addictive behaviors. Altogether, this review summarizes the possible reasons for the disturbance of host microbiota caused by areca nut chewing and clarifies the complex interaction between human microbiome and major constituents and the addiction and carcinogenicity of AN, tempting to provide novel insights into the development and utilization of it, and to control the adverse consequences caused by AN chewing.}, }
@article {pmid36498975, year = {2022}, author = {Del Chierico, F and Rapini, N and Deodati, A and Matteoli, MC and Cianfarani, S and Putignani, L}, title = {Pathophysiology of Type 1 Diabetes and Gut Microbiota Role.}, journal = {International journal of molecular sciences}, volume = {23}, number = {23}, pages = {}, pmid = {36498975}, issn = {1422-0067}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Diabetes Mellitus, Type 1/genetics ; Dysbiosis ; *Microbiota ; *Islets of Langerhans ; }, abstract = {Type 1 diabetes (T1D) is a multifactorial autoimmune disease driven by T-cells against the insulin-producing islet β-cells, resulting in a marked loss of β-cell mass and function. Although a genetic predisposal increases susceptibility, the role of epigenetic and environmental factors seems to be much more significant. A dysbiotic gut microbial profile has been associated with T1D patients. Moreover, new evidence propose that perturbation in gut microbiota may influence the T1D onset and progression. One of the prominent features in clinically silent phase before the onset of T1D is the presence of a microbiota characterized by low numbers of commensals butyrate producers, thus negatively influencing the gut permeability. The loss of gut permeability leads to the translocation of microbes and microbial metabolites and could lead to the activation of immune cells. Moreover, microbiota-based therapies to slow down disease progression or reverse T1D have shown promising results. Starting from this evidence, the correction of dysbiosis in early life of genetically susceptible individuals could help in promoting immune tolerance and thus in reducing the autoantibodies production. This review summarizes the associations between gut microbiota and T1D for future therapeutic perspectives and other exciting areas of research.}, }
@article {pmid36478853, year = {2022}, author = {Peters, SL and Morowitz, MJ and Hettich, RL}, title = {Antibiotic resistance and host immune system-induced metal bactericidal control are key factors for microbial persistence in the developing human preterm infant gut microbiome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {958638}, pmid = {36478853}, issn = {1664-302X}, abstract = {The human gut microbiome, which develops and stabilizes during the early stages of infant life, plays an essential role in host health through the production of metabolic resources and the stimulation and training of the immune system. To study colonization and community functional dynamics of the microbiota based on responses to host immune processes during the normal and dysbiotic establishment of the gut, metaproteomics was conducted on 91 fecal samples collected over the first 90 days of life from 17 hospitalized premature infants. Microbial responses to antibiotic administration and host-imposed metal bactericidal control correlated with community assembly and resiliency of microbes in the developing preterm gut. Specifically, proteins related to antibiotic resistance and metal homeostasis mechanisms were predominant in persisting members in the infant gut environment over the first several weeks of life. Overall, this metaproteomics study provides a unique approach to examine the temporal expansion and resilience of microbial colonization, as it allows simultaneous examination of both host and microbial metabolic activities. Understanding the interplay between host and microbes may elucidate the microbiome's potential immunomodulatory roles relevant to necrotizing enterocolitis and other dysbiotic conditions in preterm infants.}, }
@article {pmid36476670, year = {2022}, author = {Jochum, M and Lee, MD and Curry, K and Zaksas, V and Vitalis, E and Treangen, T and Aagaard, K and Ternus, KL}, title = {Analysis of bronchoalveolar lavage fluid metatranscriptomes among patients with COVID-19 disease.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {21125}, pmid = {36476670}, issn = {2045-2322}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; T32 HD098068/HD/NICHD NIH HHS/United States ; T32 HL098069/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Bronchoalveolar Lavage Fluid ; *COVID-19 ; Gene Ontology ; }, abstract = {To better understand the potential relationship between COVID-19 disease and hologenome microbial community dynamics and functional profiles, we conducted a multivariate taxonomic and functional microbiome comparison of publicly available human bronchoalveolar lavage fluid (BALF) metatranscriptome samples amongst COVID-19 (n = 32), community acquired pneumonia (CAP) (n = 25), and uninfected samples (n = 29). We then performed a stratified analysis based on mortality amongst the COVID-19 cohort with known outcomes of deceased (n = 10) versus survived (n = 15). Our overarching hypothesis was that there are detectable and functionally significant relationships between BALF microbial metatranscriptomes and the severity of COVID-19 disease onset and progression. We observed 34 functionally discriminant gene ontology (GO) terms in COVID-19 disease compared to the CAP and uninfected cohorts, and 21 GO terms functionally discriminant to COVID-19 mortality (q < 0.05). GO terms enriched in the COVID-19 disease cohort included hydrolase activity, and significant GO terms under the parental terms of biological regulation, viral process, and interspecies interaction between organisms. Notable GO terms associated with COVID-19 mortality included nucleobase-containing compound biosynthetic process, organonitrogen compound catabolic process, pyrimidine-containing compound biosynthetic process, and DNA recombination, RNA binding, magnesium and zinc ion binding, oxidoreductase activity, and endopeptidase activity. A Dirichlet multinomial mixtures clustering analysis resulted in a best model fit using three distinct clusters that were significantly associated with COVID-19 disease and mortality. We additionally observed discriminant taxonomic differences associated with COVID-19 disease and mortality in the genus Sphingomonas, belonging to the Sphingomonadacae family, Variovorax, belonging to the Comamonadaceae family, and in the class Bacteroidia, belonging to the order Bacteroidales. To our knowledge, this is the first study to evaluate significant differences in taxonomic and functional signatures between BALF metatranscriptomes from COVID-19, CAP, and uninfected cohorts, as well as associating these taxa and microbial gene functions with COVID-19 mortality. Collectively, while this data does not speak to causality nor directionality of the association, it does demonstrate a significant relationship between the human microbiome and COVID-19. The results from this study have rendered testable hypotheses that warrant further investigation to better understand the causality and directionality of host-microbiome-pathogen interactions.}, }
@article {pmid36475896, year = {2023}, author = {Kumar, T and Bryant, M and Cantrell, K and Song, SJ and McDonald, D and Tubb, HM and Farmer, S and Lukacz, ES and Brubaker, L and Knight, R}, title = {Effects of Variation in Urine Sample Storage Conditions on 16S Urogenital Microbiome Analyses.}, journal = {mSystems}, volume = {8}, number = {1}, pages = {e0102922}, pmid = {36475896}, issn = {2379-5077}, support = {T32 GM007198/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; United States ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Quality of Life ; *Microbiota/genetics ; Urine Specimen Collection ; *Urinary Tract Infections ; *Urinary Incontinence ; }, abstract = {Replicability is a well-established challenge in microbiome research with a variety of contributing factors at all stages, from sample collection to code execution. Here, we focus on voided urine sample storage conditions for urogenital microbiome analysis. Using urine samples collected from 10 adult females, we investigated the microbiome preservation efficacy of AssayAssure Genelock (Genelock), compared with no preservative, under different temperature conditions. We varied temperature over 48 h in order to examine the impact of conditions samples may experience with home voided urine collection and shipping to a central biorepository. The following common lab and shipping conditions were investigated: -20°C, ambient temperature, 4°C, freeze-thaw cycle, and heat cycle. At 48 h, all samples were stored at -80°C until processing. After generating 16S rRNA gene amplicon sequencing data using the highly sensitive KatharoSeq protocol, we observed individual variation in both alpha and beta diversity metrics below interhuman differences, corroborating reports of individual microbiome variability in other specimen types. While there was no significant difference in beta diversity when comparing Genelock versus no preservative, we did observe a higher concordance with Genelock samples shipped at colder temperatures (-20°C and 4°C) when compared with the samples shipped at -20°C without preservative. Our results indicate that Genelock does not introduce a significant amount of microbial bias when used on a range of temperatures and is most effective at colder temperatures. IMPORTANCE The urogenital microbiome is an understudied yet important human microbiome niche. Research has been stimulated by the relatively recent discovery that urine is not sterile; urinary tract microbes have been linked to health problems, including urinary infections, incontinence, and cancer. The quality of life and economic impact of UTIs and urgency incontinence alone are enormous, with $3.5 billion and $82.6 billion, respectively, spent in the United States. annually. Given the low biomass of urine, novelty of the field, and limited reproducibility evidence, it is critical to study urine sample storage conditions to optimize scientific rigor. Efficient and reliable preservation methods inform methods for home self-sample collection and shipping, increasing the potential use in larger-scale studies. Here, we examined both buffer and temperature variation effects on 16S rRNA gene amplicon sequencing results from urogenital samples, providing data on the consequences of common storage methods on urogenital microbiome results.}, }
@article {pmid36475759, year = {2023}, author = {Chen, BY and Lin, WZ and Li, YL and Bi, C and Du, LJ and Liu, Y and Zhou, LJ and Liu, T and Xu, S and Shi, CJ and Zhu, H and Wang, YL and Sun, JY and Liu, Y and Zhang, WC and Zhang, Z and Zhang, HL and Zhu, YQ and Duan, SZ}, title = {Characteristics and Correlations of the Oral and Gut Fungal Microbiome with Hypertension.}, journal = {Microbiology spectrum}, volume = {11}, number = {1}, pages = {e0195622}, pmid = {36475759}, issn = {2165-0497}, mesh = {Humans ; *Mycobiome ; *Gastrointestinal Microbiome/physiology ; *Microbiota ; *Hypertension ; Mouth ; Feces/microbiology ; Fungi/genetics ; }, abstract = {The mycobiome is an essential constituent of the human microbiome and is associated with various diseases. However, the role of oral and gut fungi in hypertension (HTN) remains largely unexplored. In this study, saliva, subgingival plaques, and feces were collected from 36 participants with HTN and 24 healthy controls for metagenomic sequencing. The obtained sequences were analyzed using the Kraken2 taxonomic annotation pipeline to assess fungal composition and diversity. Correlations between oral and gut fungi and clinic parameters, between fungi within the same sample types, and between different sample types were identified by Spearman's correlation analysis. Overall, the subgingival fungal microbiome had substantially higher alpha diversity than the salivary and fecal fungal microbiomes. The fungal microbiomes of the three sample types displayed distinct beta diversity from each other. Oral fungi but not gut fungi in HTN had beta diversity significantly different from that of controls. Among the fungi shared in the oral cavity and gut, Exophiala was the genus with the most notable changes. Exophiala spinifera was the most abundant salivary species in HTN. Some fungal species directly correlated with blood pressure, including gut Exophiala xenobiotica and Exophiala mesophila. The markedly impaired ecological cocorrelation networks of oral and gut fungi in HTN suggested compromised association among fungal species. Most fungi were shared in the oral cavity and gut, and their correlations suggested the potential interplays between oral and gut fungi. In conclusion, the oral cavity and intestine have unique fungal ecological environments. The fungal enrichment and ecology in HTN, the correlations between oral and gut fungi, and the associations between oral and gut fungi and clinical parameters suggest an important role that the fungal microbiome may play in HTN. IMPORTANCE Our study fills the gap in human studies investigating the oral and gut fungal microbiota in association with blood pressure. It characterizes the diversity and composition of the oral and gut fungal microbiome in human subjects, elucidates the dysbiosis of fungal ecology in a hypertensive population, and establishes oral-gut fungal correlations and fungus-clinical parameter correlations. Targeting fungi in the oral cavity and/or gut may provide novel strategies for the prevention and treatment of hypertension.}, }
@article {pmid36475017, year = {2022}, author = {Khan, AZ and Badar, S and O'Callaghan, KM and Zlotkin, S and Roth, DE}, title = {Fecal Iron Measurement in Studies of the Human Intestinal Microbiome.}, journal = {Current developments in nutrition}, volume = {6}, number = {10}, pages = {nzac143}, pmid = {36475017}, issn = {2475-2991}, abstract = {Iron is an essential micronutrient for humans and their intestinal microbiota. Host intestinal cells and iron-dependent bacteria compete for intraluminal iron, so the composition and functions of the gut microbiota may influence iron availability. Studies of the effects of the microbiota or probiotic interventions on host iron absorption may be particularly relevant to settings with high burdens of iron deficiency and gastrointestinal infections, since inflammation reduces iron bioavailability and unabsorbed intraluminal iron may modify the composition of the microbiota. The quantification of stool iron content may serve as an indicator of the amount of intraluminal iron to which the intestinal microbiota is exposed, which is particularly relevant for studies of the effect of iron on the intestinal microbiome, where fecal samples collected for purposes of microbiome characterization can be leveraged for stool iron analysis. However, few studies are available to guide researchers in the selection and implementation of stool iron assays, particularly because cross-comparison of available methods is limited in literature. This review aims to describe the available stool iron quantification methods and highlight their potential application in studies of iron-microbiome relationships, with a focus on pediatric research. MS-based methods offer high sensitivity and precision, but the need for expensive equipment and the high per-sample and maintenance costs may limit their widespread use. Conversely, colorimetric assays offer lower cost, ease of use, and rapid turnaround times but have thus far been optimized primarily for blood-derived matrices rather than stool. Further research efforts are needed to validate and standardize methods for stool iron assessment and to determine if the incorporation of such analyses in human microbiome studies 1) yields insights into the interactions between intestinal microbiota and iron and 2) contributes to the development of interventions that mitigate iron deficiency and promote a healthy microbiome.}, }
@article {pmid36473543, year = {2023}, author = {Li, C}, title = {Understanding interactions among diet, host and gut microbiota for personalized nutrition.}, journal = {Life sciences}, volume = {312}, number = {}, pages = {121265}, doi = {10.1016/j.lfs.2022.121265}, pmid = {36473543}, issn = {1879-0631}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Diet ; *Microbiota ; Host Microbial Interactions ; }, abstract = {Human responses to the same diets may vary to a large extent, depending on the complex diet-host-microbiota interactions. Recent scientific advance has indicated that this diet-host-microbiota interaction could be quantified to develop strategies for improving individual health (personalized nutrition). Compared to the host related factors (which are difficult to manipulate), the gut microbiome is more readily modulated by dietary exposures and has important roles in affecting human health via the synthesis of various bioactive compounds and participating in the digestion and absorption process of macro- and micronutrients. Therefore, gut microbiota alterations induced by diets could possibly be utilized to improve human health in a targeted manner. However, limitations in the processing and analysis of 'big-data' concerning human microbiome still restrict the translational capacity of diet-host-microbiota interactions into tools to improve personalized human health. In the current review, recent advances in terms of understanding the specific diet-host-microbiota interactions were summarized, aiming to help the development of strategies for personalized nutrition.}, }
@article {pmid36468852, year = {2022}, author = {Velez-Cortes, F and Wang, H}, title = {Characterization and Spatial Mapping of the Human Gut Metasecretome.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0071722}, pmid = {36468852}, issn = {2379-5077}, support = {R01 AI132403/AI/NIAID NIH HHS/United States ; R01 DK118044/DK/NIDDK NIH HHS/United States ; R21 AI146817/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Bacteria/genetics ; Bacterial Proteins/genetics ; *Gastrointestinal Microbiome/genetics ; Metagenome ; Phylogeny ; }, abstract = {Bacterially secreted proteins play an important role in microbial physiology and ecology in many environments, including the mammalian gut. While gut microbes have been extensively studied over the past decades, little is known about the proteins that they secrete into the gastrointestinal tract. In this study, we developed and applied a computational pipeline to a comprehensive catalog of human-associated metagenome-assembled genomes in order to predict and analyze the bacterial metasecretome of the human gut, i.e., the collection of proteins secreted out of the cytoplasm by human gut bacteria. We identified the presence of large and diverse families of secreted carbohydrate-active enzymes and assessed their phylogenetic distributions across different taxonomic groups, which revealed an enrichment in Bacteroidetes and Verrucomicrobia. By mapping secreted proteins to available metagenomic data from endoscopic sampling of the human gastrointestinal tract, we specifically pinpointed regions in the upper and lower intestinal tract along the lumen and mucosa where specific glycosidases are secreted by resident microbes. The metasecretome analyzed in this study constitutes the most comprehensive list of secreted proteins produced by human gut bacteria reported to date and serves as a useful resource for the microbiome research community. IMPORTANCE Bacterially secreted proteins are necessary for the proper functioning of bacterial cells and communities. Secreted proteins provide bacterial cells with the ability to harvest resources from the exterior, import these resources into the cell, and signal to other bacteria. In the human gut microbiome, these actions impact host health and allow the maintenance of a healthy gut bacterial community. We utilized computational tools to identify the major components of human gut bacterially secreted proteins and determined their spatial distribution in the gastrointestinal tract. Our analysis of human gut bacterial secreted proteins will allow a better understanding of the impact of gut bacteria on human health and represents a step toward identifying new protein functions with interesting applications in biomedicine and industry.}, }
@article {pmid36461079, year = {2022}, author = {Verkola, M and Takala, M and Nykäsenoja, S and Olkkola, S and Kurittu, P and Kiljunen, S and Tuomala, H and Järvinen, A and Heikinheimo, A}, title = {Low-level colonization of methicillin-resistant Staphylococcus aureus in pigs is maintained by slowly evolving, closely related strains in Finnish pig farms.}, journal = {Acta veterinaria Scandinavica}, volume = {64}, number = {1}, pages = {34}, pmid = {36461079}, issn = {1751-0147}, support = {304832//Academy of Finland/ ; }, mesh = {Swine ; Animals ; Farms ; *Methicillin-Resistant Staphylococcus aureus/genetics ; Finland/epidemiology ; Livestock ; Skin ; }, abstract = {BACKGROUND: Over the past two decades, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has become widely prevalent in pig production in Europe. The carriage status of LA-MRSA is known to vary among individual pigs, but bacterial load in pigs has rarely been studied. We assessed the quantity of LA-MRSA in nasal and skin samples of pigs and investigated the genetic diversity of the strains together with sequenced strains from national surveillance and pathology samples from the Finnish Food Authority. On two farms with assumed MRSA-positive status, farm 1 and farm 2, 10 healthy pigs were sampled three times during 2 weeks from the nares and skin (study A). On farm 1, 54 additional pigs were sampled and from confirmed MRSA-positive animals, 10 were randomly selected and transported to a clean, controlled environment for further sampling (study B). From the samples taken on farms 1 and 2 and in the controlled environment, MRSA was isolated both by direct plating and enrichment on selective media. spa types, multilocus sequence types, staphylococcal cassette chromosome mec types, resistance and virulence genes were determined. Core genome multilocus sequence typing (cgMLST) analysis was performed, including the sequences deriving from the surveillance/pathology samples from the Finnish Food Authority.<br><br>RESULTS: All pigs on farm&#xa0;1 carried LA-MRSA in the nares at all three time points and five pigs on farm&#xa0;2 at one time point. Nasal quantity varied between 10 and 10[3]&#xa0;CFU/swab and quantity on the skin between 10 and 10[2]&#xa0;CFU/swab. In the controlled environment, MRSA was detected in at least one of the nasal samples from each animal. spa type t034 was predominant. cgMLST showed one cluster with minimum allele differences between 0 and 11.<br><br>CONCLUSIONS: The study shows predominantly low-level carriage (<&#x2009;10[3]&#xa0;CFU/swab) of LA-MRSA on farms. In the controlled environment we observed a decline in nasal carriage but constant skin carriage. cgMLST showed that strains of spa type t034 are closely related at the national level.}, }
@article {pmid36460704, year = {2022}, author = {Kim, HS and Kim, DW and Kim, S and Choe, S}, title = {Biochemical characterization of the two novel mgCas12a proteins from the human gut metagenome.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {20857}, pmid = {36460704}, issn = {2045-2322}, mesh = {Humans ; *Metagenome ; Amino Acid Sequence ; *Endonucleases ; Biological Assay ; Biotechnology ; }, abstract = {CRISPR/Cas9 and Cas12a belonging to the Class II CRISPR system are characterized by a single-component effector protein. Despite unique features of Cas12a like DNA cleavage with 5' staggered ends and a single crRNA, Cas12a has not been adopted in biotechnological applications to the similar extent as Cas9. To better understand the CRISPR/Cas12 systems, we selected two candidates, designated mgCas12a-1 and mgCas12a-2, from an analysis of the human microbiome metagenome (mg) and provided biochemical characterization. These new Cas12a proteins shared about 37% identity in amino acid sequences and shared the same direct repeat sequences in the crRNA with FnCas12a from Francisella novicida. The purification yield of the recombinant proteins was up to 3.6-fold greater than that of FnCas12a. In cell-free DNA cleavage assays, both mgCas12a proteins showed the higher cleavage efficiencies when Mn[2+] was provided with KCl (< 100 mM) than tested other divalent ions. They were able to tolerate ranges of pH points and temperature, and showed the highest cleavage efficiencies at pH 8.0 and 50 °C. In addition, mgCas12a proteins showed 51% less crRNA-independent and 56% less crRNA-dependent non-specific nuclease activity upon prolonged incubation than did FnCas12a. Considering their greater yield in protein preparation and reduced non-specific nuclease activity, our findings may expedite the use of Cas12a especially when genome editing needs to be practiced with the form of ribonucleoproteins.}, }
@article {pmid36458216, year = {2022}, author = {Kalia, VC and Gong, C and Shanmugam, R and Lee, JK}, title = {Prospecting Microbial Genomes for Biomolecules and Their Applications.}, journal = {Indian journal of microbiology}, volume = {62}, number = {4}, pages = {516-523}, pmid = {36458216}, issn = {0046-8991}, abstract = {Bioactive molecules of microbial origin are finding increasing biotechnological applications. Their sources range from the terrestrial, marine, and endophytic to the human microbiome. These biomolecules have unique chemical structures and related groups, which enable them to improve the efficiency of the bioprocesses. This review focuses on the applications of biomolecules in bioremediation, agriculture, food, pharmaceutical industries, and human health.}, }
@article {pmid36458093, year = {2022}, author = {Larsen, PE and Dai, Y}, title = {Modeling interaction networks between host, diet, and bacteria predicts obesogenesis in a mouse model.}, journal = {Frontiers in molecular biosciences}, volume = {9}, number = {}, pages = {1059094}, pmid = {36458093}, issn = {2296-889X}, abstract = {Host-microbiome interactions are known to have substantial effects on human health, but the diversity of the human microbiome makes it difficult to definitively attribute specific microbiome features to a host phenotype. One approach to overcoming this challenge is to use animal models of host-microbiome interaction, but it must be determined that relevant aspects of host-microbiome interactions are reflected in the animal model. One such experimental validation is an experiment by Ridura et al. In that experiment, transplanting a microbiome from a human into a mouse also conferred the human donor's obesity phenotype. We have aggregated a collection of previously published host-microbiome mouse-model experiments and combined it with thousands of sequenced and annotated bacterial genomes and metametabolomic pathways. Three computational models were generated, each model reflecting an aspect of host-microbiome interactions: 1) Predict the change in microbiome community structure in response to host diet using a community interaction network, 2) Predict metagenomic data from microbiome community structure, and 3) Predict host obesogenesis from modeled microbiome metagenomic data. These computationally validated models were combined into an integrated model of host-microbiome-diet interactions and used to replicate the Ridura experiment in silico. The results of the computational models indicate that network-based models are significantly more predictive than similar but non-network-based models. Network-based models also provide additional insight into the molecular mechanisms of host-microbiome interaction by highlighting metabolites and metabolic pathways proposed to be associated with microbiome-based obesogenesis. While the models generated in this study are likely too specific to the animal models and experimental conditions used to train our models to be of general utility in a broader understanding of obesogenesis, the approach detailed here is expected to be a powerful tool of investigating multiple types of host-microbiome interactions.}, }
@article {pmid36457513, year = {2022}, author = {Liu, B and Li, Y and Suo, L and Zhang, W and Cao, H and Wang, R and Luan, J and Yu, X and Dong, L and Wang, W and Xu, S and Lu, S and Shi, M}, title = {Characterizing microbiota and metabolomics analysis to identify candidate biomarkers in lung cancer.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {1058436}, pmid = {36457513}, issn = {2234-943X}, abstract = {BACKGROUND: Lung cancer is the leading malignant disease and cause of cancer-related death worldwide. Most patients with lung cancer had insignificant early symptoms so that most of them were diagnosed at an advanced stage. In addition to factors such as smoking, pollution, lung microbiome and its metabolites play vital roles in the development of lung cancer. However, the interaction between lung microbiota and carcinogenesis is lack of systematically characterized and controversial. Therefore, the purpose of this study was to excavate the features of the lung microbiota and metabolites in patients and verify potential biomarkers for lung cancer diagnosis.<br><br>METHODS: Lung tissue flushing solutions and bronchoalveolar lavage fluid samples came from patients with lung cancer and non-lung cancer. The composition and variations of the microbiota and metabolites in samples were explored using muti-omics technologies including 16S rRNA amplicon sequencing, metagenomics and metabolomics.<br><br>RESULTS: The metabolomics analysis indicated that 40 different metabolites, such as 9,10-DHOME, sphingosine, and cysteinyl-valine, were statistically significant between two groups (VIP > 1 and P < 0.05). These metabolites were significantly enriched into 11 signal pathways including sphingolipid, autophagy and apoptosis signaling pathway (P < 0.05). The analysis of lung microbiota showed that significant changes reflected the decrease of microbial diversity, changes of distribution of microbial taxa, and variability of the correlation networks of lung microbiota in lung cancer patients. In particular, we found that oral commensal microbiota and multiple probiotics might be connected with the occurrence and progression of lung cancer. Moreover, our study found 3 metabolites and 9 species with significantly differences, which might be regarded as the potential clinical diagnostic markers associated with lung cancer.<br><br>CONCLUSIONS: Lung microbiota and metabolites might play important roles in the pathogenesis of lung cancer, and the altered metabolites and microbiota might have the potential to be clinical diagnostic markers and therapeutic targets associated with lung cancer.}, }
@article {pmid36453887, year = {2022}, author = {Zhang, W and Han, N and Zhang, T and Qiang, Y and Peng, X and Li, X and Kan, B}, title = {The Spatial Features and Temporal Changes in the Gut Microbiota of a Healthy Chinese Population.}, journal = {Microbiology spectrum}, volume = {10}, number = {6}, pages = {e0131022}, pmid = {36453887}, issn = {2165-0497}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Cohort Studies ; East Asian People ; *Microbiota ; Feces/microbiology ; }, abstract = {In this study, we aimed to understand the characteristics of the gut microbial composition in a healthy Chinese population and to evaluate if they differed across different regions. In addition, we aimed to understand the changes in the gut microbial composition over time. We collected 239 fecal samples from healthy Chinese adults living in four regions and performed a 1-year time cohort study in a small population in Beijing. The Chinese gut microbiota share 34 core bacterial genera and 39 core bacterial species, which exist in all collected samples. Several disease-related microorganisms (DRMs), virulence factors, and antibiotic resistance genes were found in one or more healthy Chinese samples. Differences in gut microbiota were observed in samples from different regions, locations, individuals, and time points. Compared to other factors, time was associated with a lower degree of change in the gut microbiota. Our findings revealed spatial and temporal changes in the gut microbiota of healthy Chinese individuals. Compared to fecal microbiomes of 152 samples in the publicly released the Human Microbiome Project (HMP) project from the United States, samples in this study have higher variability in the fecal microbiome, with higher richness, Shannon diversity indices, and Pielou evenness indexes, at both the genus and species levels. The microbiota data obtained in this study will provide a detailed basis for further understanding the composition of the gut microbiota in the healthy Chinese population. IMPORTANCE China accounts for approximately 1/5th of the world's total population. Differences in environment, ethnicity, and living habits could impart unique features to the structure of the gut microbiota of Chinese individuals. In 2016, we started to investigate healthy Chinese people and their gut microbiomes. Phase I results for 16S rRNA amplicons have been released. However, owing to the limitations of 16S rRNA amplicon sequencing, the gut microbiome of a healthy Chinese population could not be examined thoroughly at the species level, and the detailed changes in the gut microbiota over time need to be investigated. To address these knowledge gaps, we started a phase II study and investigated the basis for variations in the gut microbiome composition in a healthy Chinese population at the species level using shotgun metagenomics technology. In the phase II study, we also conducted a time scale analysis of fecal samples from healthy Chinese subjects, as a pioneered study, which quantitatively clarified the changes in the gut microbiota at both the spatial and temporal levels and elucidated the distribution pattern of DRMs in healthy Chinese individuals.}, }
@article {pmid36453834, year = {2023}, author = {Ndika, J and Suojalehto, H and Lindström, I and Airaksinen, L and Wisgrill, L and Alenius, H and Karisola, P}, title = {Systemic gene signature of inhaled corticosteroid treatment in allergic asthma to flour.}, journal = {Allergy}, volume = {78}, number = {2}, pages = {592-595}, doi = {10.1111/all.15605}, pmid = {36453834}, issn = {1398-9995}, mesh = {Humans ; *Flour ; *Asthma/drug therapy/genetics ; Adrenal Cortex Hormones/therapeutic use ; Administration, Inhalation ; }, }
@article {pmid36452234, year = {2022}, author = {Wang, Z and Li, L and Wang, S and Wei, J and Qu, L and Pan, L and Xu, K}, title = {The role of the gut microbiota and probiotics associated with microbial metabolisms in cancer prevention and therapy.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {1025860}, pmid = {36452234}, issn = {1663-9812}, abstract = {Cancer is the second leading cause of elevated mortality worldwide. Thus, the development of drugs and treatments is needed to enhance the survival rate of the cancer-affected population. Recently, gut microbiota research in the healthy development of the human body has garnered widespread attention. Many reports indicate that changes in the gut microbiota are strongly associated with chronic inflammation-related diseases, including colitis, liver disease, and cancer within the intestine and the extraintestinal tract. Different gut bacteria are vital in the occurrence and development of tumors within the gut and extraintestinal tract. The human gut microbiome has significant implications for human physiology, including metabolism, nutrient absorption, and immune function. Moreover, diet and lifestyle habits are involved in the evolution of the human microbiome throughout the lifetime of the host and are involved in drug metabolism. Probiotics are a functional food with a protective role in cancer development in animal models. Probiotics alter the gut microbiota in the host; thus, beneficial bacterial activity is stimulated, and detrimental activity is inhibited. Clinical applications have revealed that some probiotic strains could reduce the occurrence of postoperative inflammation among cancer patients. An association network was constructed by analyzing the previous literature to explore the role of probiotics from the anti-tumor perspective. Therefore, it provides direction and insights for research on tumor treatment.}, }
@article {pmid36448728, year = {2022}, author = {Paone, P and Suriano, F and Jian, C and Korpela, K and Delzenne, NM and Van Hul, M and Salonen, A and Cani, PD}, title = {Prebiotic oligofructose protects against high-fat diet-induced obesity by changing the gut microbiota, intestinal mucus production, glycosylation and secretion.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2152307}, pmid = {36448728}, issn = {1949-0984}, mesh = {Mice ; Animals ; Prebiotics ; Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; Glycosylation ; *Diabetes Mellitus, Type 2 ; Obesity/prevention &amp; control ; Bacteroidetes ; Mucus ; }, abstract = {Obesity is a major risk factor for the development of type 2 diabetes and cardiovascular diseases, and gut microbiota plays a key role in influencing the host energy homeostasis. Moreover, obese mice have a different gut microbiota composition, associated with an alteration of the intestinal mucus layer, which represents the interface between the bacteria and the host. We previously demonstrated that prebiotic treatment with oligofructose (FOS) counteracted the effects of diet-induced obesity, together with changes in the gut microbiota composition, but it is not known if the intestinal mucus layer could be involved. In this study, we found that, in addition to preventing high-fat diet (HFD) induced obesity in mice, the treatment with FOS increased the expression of numerous genes involved in mucus production, glycosylation and secretion, the expression of both secreted and transmembrane mucins, and the differentiation and number of goblet cells. These results were associated with significant changes in the gut microbiota composition, with FOS significantly increasing the relative and absolute abundance of the bacterial genera Odoribacter, Akkermansia, two unknown Muribaculaceae and an unknown Ruminococcaceae. Interestingly, all these bacterial genera had a negative association with metabolic parameters and a positive association with markers of the mucus layer. Our study shows that FOS treatment is able to prevent HFD-induced metabolic disorders, at least in part, by acting on all the processes of the mucus production. These data suggest that targeting the mucus and the gut microbiota by using prebiotics could help to prevent or mitigate obesity and related disorders.}, }
@article {pmid36444784, year = {2023}, author = {Pereira, MS and Kriegel, MA}, title = {Evolving concepts of host-pathobiont interactions in autoimmunity.}, journal = {Current opinion in immunology}, volume = {80}, number = {}, pages = {102265}, doi = {10.1016/j.coi.2022.102265}, pmid = {36444784}, issn = {1879-0372}, mesh = {Humans ; Autoimmunity ; *Autoimmune Diseases/etiology ; Autoantigens ; *Microbiota ; Mucous Membrane ; }, abstract = {Autoimmune diseases are complex, multifactorial diseases with a polygenic trait and diverse environmental factors that contribute to triggering and exacerbating each disorder. The human microbiome is increasingly implicated in the multistep pathogenesis of autoimmune diseases. We summarize here the latest developments in the field of how the microbiota interacts with the host on a cellular and molecular level. We review how pathobionts evolve within the gut of autoimmune-prone hosts to translocate to secondary lymphoid tissues. On mucosal sites and in non-gut tissues, pathobionts trigger autoimmune pathways through various mechanisms, including cross-reactivity with autoantigens and secretion of metabolites that alter immune functions. A better understanding of these mechanisms will hasten the development of unconventional therapeutic approaches for autoimmune diseases.}, }
@article {pmid36443470, year = {2022}, author = {Jang, H and Koh, H and Gu, W and Kang, B}, title = {Integrative web cloud computing and analytics using MiPair for design-based comparative analysis with paired microbiome data.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {20465}, pmid = {36443470}, issn = {2045-2322}, mesh = {Humans ; Cloud Computing ; *Microbiota ; *Gastrointestinal Microbiome ; Mouth ; Skin ; }, abstract = {Pairing (or blocking) is a design technique that is widely used in comparative microbiome studies to efficiently control for the effects of potential confounders (e.g., genetic, environmental, or behavioral factors). Some typical paired (block) designs for human microbiome studies are repeated measures designs that profile each subject's microbiome twice (or more than twice) (1) for pre and post treatments to see the effects of a treatment on microbiome, or (2) for different organs of the body (e.g., gut, mouth, skin) to see the disparity in microbiome between (or across) body sites. Researchers have developed a sheer number of web-based tools for user-friendly microbiome data processing and analytics, though there is no web-based tool currently available for such paired microbiome studies. In this paper, we thus introduce an integrative web-based tool, named MiPair, for design-based comparative analysis with paired microbiome data. MiPair is a user-friendly web cloud service that is built with step-by-step data processing and analytic procedures for comparative analysis between (or across) groups or between baseline and other groups. MiPair employs parametric and non-parametric tests for complete or incomplete block designs to perform comparative analyses with respect to microbial ecology (alpha- and beta-diversity) and taxonomy (e.g., phylum, class, order, family, genus, species). We demonstrate its usage through an example clinical trial on the effects of antibiotics on gut microbiome. MiPair is an open-source software that can be run on our web server (http://mipair.micloud.kr) or on user's computer (https://github.com/yj7599/mipairgit).}, }
@article {pmid36441207, year = {2023}, author = {Wei, Y and Wang, Z and Liu, Y and Liao, B and Zong, Y and Shi, Y and Liao, M and Wang, J and Zhou, X and Cheng, L and Ren, B}, title = {Extracellular vesicles of Candida albicans regulate its own growth through the L-arginine/nitric oxide pathway.}, journal = {Applied microbiology and biotechnology}, volume = {107}, number = {1}, pages = {355-367}, pmid = {36441207}, issn = {1432-0614}, support = {82071106//National Natural Science Foundation of China/ ; 82271033//National Natural Science Foundation of China/ ; 81600858//National Natural Science Foundation of China/ ; 81870778//National Natural Science Foundation of China/ ; 81991500//National Natural Science Foundation of China/ ; 81991501//National Natural Science Foundation of China/ ; 2021YFQ0064//Key Research and Development Projects of Science and Technology Department of Sichuan Province/ ; 2020YJ0227//Applied Basic Research Program of Sichuan Province/ ; 2022-YF05-01401-SN//Technology Innovation R&amp;D Project of Chengdu/ ; RCDWJS2021-19//Research Funding from West China School/Hospital of Stomatology Sichuan University/ ; }, mesh = {Humans ; *Candida albicans ; Nitric Oxide/metabolism ; Reactive Oxygen Species/metabolism ; *Extracellular Vesicles/metabolism ; Arginine/metabolism ; }, abstract = {Candida albicans is the main conditional pathogenic fungus among the human microbiome. Extracellular vesicles (EVs) secreted by C. albicans are important for its pathogenesis. However, the effects and mechanisms of EVs on C. albicans own growth are not clear. Here, we isolated EVs from C. albicans cells grown in four culture media, including RPMI 1640, DMEM, YPD, and YNB, and measured their effects on the own growth of C. albicans in these media. All the C. albicans EVs from the four media could promote the growth of C. albicans in RPMI 1640 and DMEM media, but had no effects in YPD and YNB media, indicating that the effects of EVs on C. albicans growth were dependent on some media contents. By comparing the media contents and transcriptome analysis, arginine was identified as the key factor for the growth promotion of C. albicans EVs. EVs activated the L-arginine/nitric oxide pathway to promote the growth of C. albicans through that EVs increased the NO levels and upregulated the expression of NO dioxygenase gene YHB1 to reduce the intracellular reactive oxygen species (ROS) and cell apoptosis. During the host cell infections, C. albicans EVs synergistically enhanced the destructive effects of C. albicans to host cells, including RAW264.7, HOK, TR146, and HGEC, suggesting that the growth promotion by EVs enhanced the pathogenesis of C. albicans. Our results demonstrated the important roles of EVs on C. albicans own growth for the first time and highlight its synergism with C. albicans to increase the pathogenesis. KEY POINTS: • C. albicans extracellular vesicles (EVs) promoted its own growth. • EVs activated the l-arginine/NO pathway to reduce ROS and apoptosis of C. albicans. • EVs enhanced the damage to the host cell caused by C. albicans.}, }
@article {pmid36438051, year = {2022}, author = {Tong, L and Constancias, F and Hou, A and Chua, SL and Drautz-Moses, DI and Schuster, SC and Yang, L and Williams, RBH and Kjelleberg, S}, title = {Shotgun metagenomic sequencing analysis of ocular surface microbiome in Singapore residents with mild dry eye.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {1034131}, pmid = {36438051}, issn = {2296-858X}, abstract = {The ocular surface microbiome has implications for ocular surface inflammation and immunology. Previous shotgun metagenomics analyses were performed in China, showing results that differed according to environment and age. Patients with Sjogren's syndrome were reported to have altered conjunctival microbiome, but such studies have not been done in milder dry eye. The aim of this study is to describe the conjunctival microbiome in people with mild dry eye in Singapore. Samples were collected from 14 participants with mild dry eye and 10 age-matched comparison participants recruited from Singapore National Eye Centre (SNEC) clinics. Shotgun metagenomic sequencing analysis was employed to evaluate the conjunctival microbiome composition. Proteobacteria formed the predominant phylum in the conjunctiva. As in a study from a coastal city in China, Achromobacter spp. was numerically most abundant. Compared to age-matched controls, the conjunctival microbial composition in mild dry eye was similar. Several microorganisms, including Streptococcus spp. increased in representation with age, and the abundance of Staphylococcus correlated with Schirmer readings. In addition, when cultured corneal epithelial cells were exposed to three strains of Achromobacter xylosoxidans, cytokines such as TNF-α and IL-6 were upregulated in the cell lysates and supernatants. Ourresults suggest that age is an important factor that affects composition of the conjunctival microbiome, and relative abundance of specific microorganism may vary according to the environment of the human host.}, }
@article {pmid36435302, year = {2023}, author = {Hussain, A and Patwekar, U and Mongad, DS and Shouche, YS}, title = {Strategizing the human microbiome for small molecules: Approaches and perspectives.}, journal = {Drug discovery today}, volume = {28}, number = {2}, pages = {103459}, doi = {10.1016/j.drudis.2022.103459}, pmid = {36435302}, issn = {1878-5832}, mesh = {Humans ; *Microbiota/genetics ; Genomics ; Host Microbial Interactions ; }, abstract = {Studies of the human microbiome are providing a deeper understanding of its significance to human health, and increasing evidence links the microbiota with several diseases. Nevertheless, the exact mechanisms involved in human-microbe interactions are mostly undefined. The genomic potential of the human microbiome to biosynthesize distinct molecules outmatches its known chemical space, and small-molecule discovery in this context remains in its infancy. The profiling of microbiome-derived small molecules and their contextualization through cause-effect mechanistic studies may provide a better understanding of host-microbe interactions, guide new therapeutic interventions, and modulate microbiome-based therapies. This review describes the advances, approaches, and allied challenges in mining new microbial scaffolds from the human microbiome using genomic, microbe cultivation, and chemical analytic platforms. In the future, the complete biological characterization of a single microbe-derived molecule that has a specific therapeutic application could resolve the current limitations of microbiota-modulating therapies.}, }
@article {pmid36432588, year = {2022}, author = {Pino, A and Vaccalluzzo, A and Caggia, C and Balzaretti, S and Vanella, L and Sorrenti, V and Ronkainen, A and Satokari, R and Randazzo, CL}, title = {Lacticaseibacillus rhamnosus CA15 (DSM 33960) as a Candidate Probiotic Strain for Human Health.}, journal = {Nutrients}, volume = {14}, number = {22}, pages = {}, pmid = {36432588}, issn = {2072-6643}, mesh = {Female ; Humans ; Caco-2 Cells ; Antioxidants/pharmacology ; Ecosystem ; Hydrogen Peroxide ; Bacterial Adhesion ; *Lacticaseibacillus rhamnosus ; *Probiotics ; }, abstract = {Lactobacilli with probiotic properties have emerged as promising tools for both the prevention and treatment of vaginal dysbiosis. The present study aimed to study the in vitro probiotic potential of the Lacticaseibacillus rhamnosus CA15 (DSM 33960) strain isolated from a healthy vaginal ecosystem. The strain was evaluated for both functional (antagonistic activity against pathogens; H2O2, organic acid, and lactic acid production; antioxidant and anti-inflammatory activities; ability to adhere to intestinal mucus and to both CaCo-2 and VK7/E6E7 cell lines; exopolysaccharide production; surface properties; and ability to survive during gastrointestinal transit) and safety (hemolytic, DNase, and gelatinase activities; mucin degradation ability; production of biogenic amines; and resistance to antimicrobials) characteristics. Data revealed that the tested strain was able to antagonize a broad spectrum of vaginal pathogens. In addition, the adhesion capacity to both vaginal and intestinal cell lines, as well as anti-inflammatory and antioxidant activities, was detected. The ability of the Lacticaseibacillus rhamnosus CA15 (DSM 33960) strain to survive under harsh environmental conditions occurring during the gastrointestinal passage suggests its possible oral delivery. Thus, in vitro data highlighted interesting probiotic properties of the CA15 (DSM 33960) strain, which could represent a valuable candidate for in vivo vaginal infections treatment.}, }
@article {pmid36430609, year = {2022}, author = {Tilocca, B and Soggiu, A and Iavarone, F and Greco, V and Putignani, L and Ristori, MV and Macari, G and Spina, AA and Morittu, VM and Ceniti, C and Piras, C and Bonizzi, L and Britti, D and Urbani, A and Figeys, D and Roncada, P}, title = {The Functional Characteristics of Goat Cheese Microbiota from a One-Health Perspective.}, journal = {International journal of molecular sciences}, volume = {23}, number = {22}, pages = {}, pmid = {36430609}, issn = {1422-0067}, support = {AIM1879147 - 2 (Bruno Tilocca)//Attraction International Mobility-AIM, PON-FSE/ ; }, mesh = {Animals ; *Cheese/analysis ; Goats/genetics ; RNA, Ribosomal, 16S/genetics ; *One Health ; Bacteria/genetics ; *Microbiota/genetics ; }, abstract = {Goat cheese is an important element of the Mediterranean diet, appreciated for its health-promoting features and unique taste. A pivotal role in the development of these characteristics is attributed to the microbiota and its continuous remodeling over space and time. Nevertheless, no thorough study of the cheese-associated microbiota using two metaomics approaches has previously been conducted. Here, we employed 16S rRNA gene sequencing and metaproteomics to explore the microbiota of a typical raw goat milk cheese at various ripening timepoints and depths of the cheese wheel. The 16S rRNA gene-sequencing and metaproteomics results described a stable microbiota ecology across the selected ripening timepoints, providing evidence for the microbiologically driven fermentation of goat milk products. The important features of the microbiota harbored on the surface and in the core of the cheese mass were highlighted in both compositional and functional terms. We observed the rind microbiota struggling to maintain the biosafety of the cheese through competition mechanisms and/or by preventing the colonization of the cheese by pathobionts of animal or environmental origin. The core microbiota was focused on other biochemical processes, supporting its role in the development of both the health benefits and the pleasant gustatory nuances of goat cheese.}, }
@article {pmid36426891, year = {2022}, author = {Najmanová, L and Vídeňská, P and Cahová, M}, title = {Healthy microbiome - a mere idea or a sound concept?.}, journal = {Physiological research}, volume = {71}, number = {6}, pages = {719-738}, pmid = {36426891}, issn = {1802-9973}, mesh = {Humans ; *Microbiota/physiology ; }, abstract = {Hundreds of studies in last decades have aimed to compare the microbiome of patients suffering from diverse diseases with that of healthy controls. The microbiome-related component was additionally identified in pathophysiology of many diseases formerly considered to depend only on the host physiology. This, however, opens important questions like: "What is the healthy microbiome?" or "Is it possible to define it unequivocally?". In this review, we describe the main hindrances complicating the definition of "healthy microbiome" in terms of microbiota composition. We discuss the human microbiome from the perspective of classical ecology and we advocate for the shift from the stress on microbiota composition to the functions that microbiome ensures for the host. Finally, we propose to leave the concept of ideal healthy microbiome and replace it by focus on microbiome advantageous for the host, which always depends on the specific context like the age, genetics, dietary habits, body site or physiological state.}, }
@article {pmid36426699, year = {2022}, author = {Wang, SS and Song, F and Wei, XW and Gu, HY and Zhang, K and Zhou, YX and Jiang, LR and Luo, HB}, title = {Research Progress on the Application of Human Oral Microbiome in Forensic Individual Identification.}, journal = {Fa yi xue za zhi}, volume = {38}, number = {4}, pages = {526-532}, doi = {10.12116/j.issn.1004-5619.2021.510101}, pmid = {36426699}, issn = {1004-5619}, mesh = {Humans ; *Microbiota ; Forensic Medicine ; }, abstract = {The oral cavity is the second largest microbial bank in humans after the intestinal canal, colonizing a large number of microorganisms including viruses, bacteria, archaea, fungi and protozoa. The great number of microbial cells, good DNA stability, and individual has a unique microbial community, these characteristics make the human microbiome expected to become a new biomarker for forensic individual identification. This article describes the characteristics of human oral microorganisms and microbial molecular markers in detail, analyzes the potential application value of microorganisms in forensic individual identification, and reviews the research progress of human oral microorganisms in forensic individual identification.}, }
@article {pmid36421395, year = {2022}, author = {Silva, DG and Domingues, CPF and Figueiredo, JF and Dionisio, F and Botelho, A and Nogueira, T}, title = {Estuarine Aquacultures at the Crossroads of Animal Production and Antibacterial Resistance: A Metagenomic Approach to the Resistome.}, journal = {Biology}, volume = {11}, number = {11}, pages = {}, pmid = {36421395}, issn = {2079-7737}, support = {ALG-01-0145-FEDER-028824//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; UI/BD/153078/2022//Funda&#xe7;&#xe3;o para a Ci&#xea;ncia e Tecnologia/ ; }, abstract = {It is recognized that the spread of antibiotic resistance (AR) genes among aquatic environments, including aquaculture and the human environment, can have detrimental effects on human and animal health and the ecosystem. Thus, when transmitted to the human microbiome or pathogens, resistance genes risk human health by compromising the eventual treatment of infections with antibiotic therapy. This study aimed to define the resistance profile of aquaculture farms and their potential risk for spreading. Twenty-four sediments from oyster and gilthead sea bream aquaculture farms located in three Portuguese river estuaries (17 sediments from Sado, 4 from Aveiro, and 3 from Lima) were studied by comparative metagenomic analysis. The computation of the diversity of genes conferring resistance per antibiotic class revealed a significant increase in aminoglycosides, beta-lactams, disinfectants, quinolones, and tetracyclines counts. In all geographic locations under study, the most diverse AR genes confer resistance to the macrolides, tetracyclines and oxazolidinones classes, all of which are medically important for human and animal therapies, as well as resistance to disinfectants. The diversity of mobile genetic elements correlated with the number of AR genes such as tetracyclines, suggesting that AR could be easily mobilized among bacterial genomes and microbiomes.}, }
@article {pmid36419417, year = {2022}, author = {Hickman, B and Kirjavainen, PV and Täubel, M and de Vos, WM and Salonen, A and Korpela, K}, title = {Determinants of bacterial and fungal microbiota in Finnish home dust: Impact of environmental biodiversity, pets, and occupants.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {1011521}, pmid = {36419417}, issn = {1664-302X}, abstract = {The indoors is where many humans spend most of their time, and are strongly exposed to indoor microbiota, which may have multifaceted effects on health. Therefore, a comprehensive understanding of the determinants of indoor microbiota is necessary. We collected dust samples from 295 homes of families with young children in the Helsinki region of Finland and analyzed the bacterial and fungal composition based on the 16S rRNA and ITS DNA sequences. Microbial profiles were combined with extensive survey data on family structure, daily life, and physical characteristics of the home, as well as additional external environmental information, such as land use, and vegetational biodiversity near the home. Using permutational multivariate analysis of variance we explained 18% of the variation of the relative abundance between samples within bacterial composition, and 17% of the fungal composition with the explanatory variables. The fungal community was dominated by the phyla Basidiomycota, and Ascomycota; the bacterial phyla Proteobacteria, Firmicutes, Cyanobacteria, and Actinobacteria were dominant. The presence of dogs, multiple children, and firewood were significantly associated with both the fungal and bacterial composition. Additionally, fungal communities were associated with land use, biodiversity in the area, and the type of building, while bacterial communities were associated with the human inhabitants and cleaning practices. A distinction emerged between members of Ascomycota and Basidiomycota, Ascomycota being more abundant in homes with greater surrounding natural environment, and potential contact with the environment. The results suggest that the fungal composition is strongly dependent on the transport of outdoor environmental fungi into homes, while bacteria are largely derived from the inhabitants.}, }
@article {pmid36416582, year = {2023}, author = {Samami, E and Aleebrahim-Dehkordi, E and Mohebalizadeh, M and Yaribash, S and Saghazadeh, A and Rezaei, N}, title = {Inosine, gut microbiota, and cancer immunometabolism.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {324}, number = {1}, pages = {E1-E8}, doi = {10.1152/ajpendo.00207.2022}, pmid = {36416582}, issn = {1522-1555}, mesh = {Animals ; Humans ; *Gastrointestinal Microbiome ; *Neoplasms/therapy ; T-Lymphocytes ; Inosine/metabolism/pharmacology ; Carcinogenesis ; Mammals/metabolism ; Tumor Microenvironment ; }, abstract = {This article briefly reviews cancer immunity and the role of gut microbiota in carcinogenesis, followed by an understanding of mechanisms by which inosine is involved in cancer immunometabolism. The immune system plays a paradoxical role in cancer treatment. Antitumor immunity depends on the T-cell priming against tumor antigens, whereas inflammatory mediators trigger the protumor signaling in the tumor microenvironment. Studies link the microbiome with metabolism and immunity-two main factors implicated in carcinogenesis. Gut microbiota has been shown to affect both antitumor immunity and protumor immune signaling. There is mounting evidence that the human microbiome can play a role in the immunotherapeutic effects, both response and resistance. Inosine-5'-monophosphate dehydrogenase (IMPDH) is a highly conservative enzyme widely expressed in mammals. Cell signaling pathways use molecular inosine, a crucial secondary metabolite in purine metabolism and a molecular messenger. Recent research has identified inosine as a critical regulator of immune checkpoint inhibition (ICI) therapeutic response in various tumor types. Some bacterial species were found to produce inosine or its metabolite hypoxanthine and induce T-helper 1 differentiation and effector functions via the inosine-A2AR-cAMP-PKA pathway upon ICI therapy. Also, inosine acts as a substitute carbon source for T-cell metabolism in glucose-restricted environments, i.e., the tumor microenvironment, assisting T-cell proliferation and differentiation while enhancing sensitivity to ICI, reinforcing the notion that inosine metabolism might contribute to antitumor immunity. Also, inosine is a potent agonist of the adenosine receptor, A2AR, and A2AR signaling can affect T-cell responses and antitumor immunity, making the inosine-A2AR pathway blockage a candidate for cancer treatment. Further research is required to investigate inosine as a cancer immunometabolism therapy.}, }
@article {pmid36416540, year = {2022}, author = {Haffner, JJ and Katemauswa, M and Kagone, TS and Hossain, E and Jacobson, D and Flores, K and Parab, AR and Obregon-Tito, AJ and Tito, RY and Reyes, LM and Troncoso-Corzo, L and Guija-Poma, E and Meda, N and Carabin, H and Honap, TP and Sankaranarayanan, K and Lewis, CM and McCall, LI}, title = {Untargeted Fecal Metabolomic Analyses across an Industrialization Gradient Reveal Shared Metabolites and Impact of Industrialization on Fecal Microbiome-Metabolome Interactions.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0071022}, pmid = {36416540}, issn = {2379-5077}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; R25 AI147376/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; *Industrial Development ; RNA, Ribosomal, 16S/genetics ; Metabolomics/methods ; Metabolome ; *Microbiota/genetics ; }, abstract = {The metabolome is a central determinant of human phenotypes and includes the plethora of small molecules produced by host and microbiome or taken up from exogenous sources. However, studies of the metabolome have so far focused predominantly on urban, industrialized populations. Through an untargeted metabolomic analysis of 90 fecal samples from human individuals from Africa and the Americas-the birthplace and the last continental expansion of our species, respectively-we characterized a shared human fecal metabolome. The majority of detected metabolite features were ubiquitous across populations, despite any geographic, dietary, or behavioral differences. Such shared metabolite features included hyocholic acid and cholesterol. However, any characterization of the shared human fecal metabolome is insufficient without exploring the influence of industrialization. Here, we show chemical differences along an industrialization gradient, where the degree of industrialization correlates with metabolomic changes. We identified differential metabolite features such as amino acid-conjugated bile acids and urobilin as major metabolic correlates of these behavioral shifts. Additionally, coanalyses with over 5,000 publicly available human fecal samples and cooccurrence probability analyses with the gut microbiome highlight connections between the human fecal metabolome and gut microbiome. Our results indicate that industrialization significantly influences the human fecal metabolome, but diverse human lifestyles and behavior still maintain a shared human fecal metabolome. This study represents the first characterization of the shared human fecal metabolome through untargeted analyses of populations along an industrialization gradient. IMPORTANCE As the world becomes increasingly industrialized, understanding the biological consequences of these lifestyle shifts and what it means for past, present, and future human health is critical. Indeed, industrialization is associated with rises in allergic and autoimmune health conditions and reduced microbial diversity. Exploring these health effects on a chemical level requires consideration of human lifestyle diversity, but understanding the significance of any differences also requires knowledge of what molecular components are shared between human groups. Our study reveals the key chemistry of the human gut as defined by varied industrialization-based differences and ubiquitous shared features. Ultimately, these novel findings extend our knowledge of human molecular biology, especially as it is influenced by lifestyle and behavior, and provide steps toward understanding how human biology has changed over our species' history.}, }
@article {pmid36414613, year = {2022}, author = {Quagliariello, A and Modi, A and Innocenti, G and Zaro, V and Conati Barbaro, C and Ronchitelli, A and Boschin, F and Cavazzuti, C and Dellù, E and Radina, F and Sperduti, A and Bondioli, L and Ricci, S and Lognoli, M and Belcastro, MG and Mariotti, V and Caramelli, D and Mariotti Lippi, M and Cristiani, E and Martino, ME and Muntoni, IM and Lari, M}, title = {Ancient oral microbiomes support gradual Neolithic dietary shifts towards agriculture.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6927}, pmid = {36414613}, issn = {2041-1723}, mesh = {Humans ; *Agriculture ; *Microbiota ; Diet ; Farmers ; Italy ; }, abstract = {The human microbiome has recently become a valuable source of information about host life and health. To date little is known about how it may have evolved during key phases along our history, such as the Neolithic transition towards agriculture. Here, we shed light on the evolution experienced by the oral microbiome during this transition, comparing Palaeolithic hunter-gatherers with Neolithic and Copper Age farmers that populated a same restricted area in Italy. We integrate the analysis of 76 dental calculus oral microbiomes with the dietary information derived from the identification of embedded plant remains. We detect a stronger deviation from the hunter-gatherer microbiome composition in the last part of the Neolithic, while to a lesser extent in the early phases of the transition. Our findings demonstrate that the introduction of agriculture affected host microbiome, supporting the hypothesis of a gradual transition within the investigated populations.}, }
@article {pmid36413391, year = {2023}, author = {Carson, MD and Warner, AJ and Hathaway-Schrader, JD and Geiser, VL and Kim, J and Gerasco, JE and Hill, WD and Lemasters, JJ and Alekseyenko, AV and Wu, Y and Yao, H and Aguirre, JI and Westwater, C and Novince, CM}, title = {Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice.}, journal = {JCI insight}, volume = {8}, number = {1}, pages = {}, pmid = {36413391}, issn = {2379-3708}, support = {P30 DK123704/DK/NIDDK NIH HHS/United States ; I01 CX000930/CX/CSRD VA/United States ; R01 AG067510/AG/NIA NIH HHS/United States ; K08 DE025337/DE/NIDCR NIH HHS/United States ; P20 GM130457/GM/NIGMS NIH HHS/United States ; R01 DE029637/DE/NIDCR NIH HHS/United States ; P01 AG036675/AG/NIA NIH HHS/United States ; R01 DE021134/DE/NIDCR NIH HHS/United States ; T32 DE017551/DE/NIDCR NIH HHS/United States ; P20 GM121342/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Mice ; Anti-Bacterial Agents/adverse effects ; Bile Acids and Salts/metabolism ; Liver/metabolism ; Mice, Inbred C57BL ; *Minocycline/pharmacology ; *Osteogenesis ; }, abstract = {Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut/bone signaling axis. However, our prior work supports that a gut/liver signaling axis contributes to gut microbiota effects on bone. Our purpose was to investigate the effects of minocycline, a systemic antibiotic treatment for adolescent acne, on pubertal/postpubertal skeletal maturation. Sex-matched specific pathogen-free (SPF) and germ-free (GF) C57BL/6T mice were administered a clinically relevant minocycline dose from age 6-12 weeks. Minocycline caused dysbiotic shifts in the gut bacteriome and impaired skeletal maturation in SPF mice but did not alter the skeletal phenotype in GF mice. Minocycline administration in SPF mice disrupted the intestinal farnesoid X receptor/fibroblast growth factor 15 axis, a gut/liver endocrine axis supporting systemic bile acid homeostasis. Minocycline-treated SPF mice had increased serum conjugated bile acids that were farnesoid X receptor (FXR) antagonists, suppressed osteoblast function, decreased bone mass, and impaired bone microarchitecture and fracture resistance. Stimulating osteoblasts with the serum bile acid profile from minocycline-treated SPF mice recapitulated the suppressed osteogenic phenotype found in vivo, which was mediated through attenuated FXR signaling. This work introduces bile acids as a potentially novel mediator of gut/liver signaling actions contributing to gut microbiota effects on bone.}, }
@article {pmid36404489, year = {2022}, author = {Loganathan, T and Priya Doss C, G}, title = {The influence of machine learning technologies in gut microbiome research and cancer studies - A review.}, journal = {Life sciences}, volume = {311}, number = {Pt A}, pages = {121118}, doi = {10.1016/j.lfs.2022.121118}, pmid = {36404489}, issn = {1879-0631}, mesh = {Humans ; *Gastrointestinal Microbiome ; Machine Learning ; *Microbiota ; *Neoplasms ; }, abstract = {Gut microbial profiles induce cancer growth and impact treatment effectiveness, tolerance, and safety. There is still more to discover about the relationship between diseases and the microbiota and its clinical consequences. Even though much of the study is still in its early phases, the 'omics' technologies were widely used for microbiome analysis due to the increased size of datasets available in public databases. However, recognizing the potential of these new technologies is difficult at times, limiting our ability to analyze a vast amount of available data critically. In this context, two subsets of AI methods, Machine Learning (ML) and Deep Learning (DL), can aid clinicians in analyzing and comprehending these large datasets. Here, we reviewed the most up-to-date ML methodologies, databases, and tools used in human microbiome research. The proposed review forecast the use of ML in microbiome research involving associations and clinical applications for diagnostics, prognostics, and therapies.}, }
@article {pmid36399893, year = {2023}, author = {Sharma, S and Hegde, P and Panda, S and Orimoloye, MO and Aldrich, CC}, title = {Drugging the microbiome: targeting small microbiome molecules.}, journal = {Current opinion in microbiology}, volume = {71}, number = {}, pages = {102234}, doi = {10.1016/j.mib.2022.102234}, pmid = {36399893}, issn = {1879-0364}, mesh = {Humans ; Pharmaceutical Preparations ; *Microbiota/physiology ; }, abstract = {The human microbiome represents a large and diverse collection of microbes that plays an integral role in human physiology and pathophysiology through interactions with the host and within the microbial community. While early work exploring links between microbiome signatures and diseases states has been associative, emerging evidence demonstrates the metabolic products of the human microbiome have more proximal causal effects on disease phenotypes. The therapeutic implications of this shift are profound as manipulation of the microbiome by the administration of live biotherapeutics, ongoing, can now be pursued alongside research efforts toward describing inhibitors of key microbiome enzymes involved in the biosynthesis of metabolites implicated in various disease states and processing of host-derived metabolites. With growing interest in 'drugging the microbiome', we review few notable microbial metabolites for which traditional drug-development campaigns have yielded compounds with therapeutic promise.}, }
@article {pmid36394327, year = {2022}, author = {Mann, E and Shekarriz, S and Surette, MG}, title = {Human Gut Metagenomes Encode Diverse GH156 Sialidases.}, journal = {Applied and environmental microbiology}, volume = {88}, number = {23}, pages = {e0175522}, pmid = {36394327}, issn = {1098-5336}, mesh = {Humans ; Glycoside Hydrolases/genetics ; *Metagenome ; *Neuraminidase/genetics/metabolism ; Polysaccharides ; Sialic Acids/metabolism ; Gastrointestinal Microbiome ; }, abstract = {The intestinal lining is protected by a mucous barrier composed predominantly of complex carbohydrates. Gut microbes employ diverse glycoside hydrolases (GHs) to liberate mucosal sugars as a nutrient source to facilitate host colonization. Intensive catabolism of mucosal glycans, however, may contribute to barrier erosion, pathogen encroachment, and inflammation. Sialic acid is an acidic sugar featured at terminal positions of host glycans. Characterized sialidases from the microbiome belong to the GH33 family, according to CAZy (Carbohydrate-Active enZYmes Database). In 2018 a functional metagenomics screen using thermal spring DNA uncovered the founding member of the GH156 sialidase family, the presence of which has yet to be reported in the context of the human microbiome. A subset of GH156 sequences from the CAZy database containing key sialidase residues was used to build a hidden Markov model. HMMsearch against public databases revealed ~10× more putative GH156 sialidases than currently cataloged by CAZy. Represented phyla include Bacteroidota, Verrucomicrobiota, and Firmicutes_A from human microbiomes, all of which play notable roles in carbohydrate fermentation. Analyses of metagenomic data sets revealed that GH156s are frequently encoded in metagenomes, with a greater variety and abundance of GH156 genes observed in traditional hunter-gatherer or agriculturalist societies than in industrialized societies, particularly relative to individuals with inflammatory bowel disease (IBD). Nineteen GH156s were recombinantly expressed and assayed for sialidase activity. The five GH156 sialidases identified here share limited sequence identity to each other or the founding GH156 family member and are representative of a large subset of the family. IMPORTANCE Sialic acids occupy terminal positions of human glycans where they act as receptors for microbes, toxins, and immune signaling molecules. Microbial enzymes that remove sialic acids, sialidases, are abundant in the human microbiome where they may contribute to shaping the microbiota community structure or contribute to pathology. Furthermore, sialidases have proven to hold therapeutic potential for cancer therapy. Here, we examined the sequence space of a sialidase family of enzymes, GH156, previously unknown in the human gut environment. Our analyses suggest that human populations with disparate dietary practices harbor distinct varieties and abundances of GH156-encoding genes. Furthermore, we demonstrate the sialidase activity of 5 gut-derived GH156s. These results expand the diversity of sialidases that may contribute to host glycan degradation, and these sequences may have biotechnological or clinical utility.}, }
@article {pmid36394178, year = {2022}, author = {Bjarnsholt, T and Ralfkiaer, U and Malone, M}, title = {APMIS 2022 focus issue on human microbiome in disease and pathology.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {130}, number = {12}, pages = {689}, doi = {10.1111/apm.13283}, pmid = {36394178}, issn = {1600-0463}, mesh = {Humans ; *Microbiota ; Disease ; Periodicals as Topic ; }, }
@article {pmid36385397, year = {2023}, author = {Schoch, JJ and Gauthier, J and Gharaibeh, RZ and Jobin, C and Bohannon, M and Neu, J and Parker, L}, title = {Skin microbiome sampling in the preterm neonate.}, journal = {Pediatric dermatology}, volume = {40}, number = {1}, pages = {129-131}, pmid = {36385397}, issn = {1525-1470}, support = {KL2 TR001429/TR/NCATS NIH HHS/United States ; 1KL2TROO1429/TR/NCATS NIH HHS/United States ; //Society for Pediatric Dermatology/ ; //Pediatric Dermatology Research Alliance/ ; }, mesh = {Infant, Newborn ; Humans ; *Infant, Premature ; Skin ; *Microbiota ; }, abstract = {Despite advances in our understanding of the human microbiome, there exist significant knowledge gaps in our understanding of the skin microbiome of the preterm neonate. Herein, we describe skin microbiome sampling of six preterm neonates at multiple timepoints, and compare the skin microbiome samples to environmental (crib/isolette swabs) and negative controls. Samples of the same type (skin, crib, control) were more similar than when compared by week or by patient.}, }
@article {pmid36384106, year = {2022}, author = {Bootz-Maoz, H and Pearl, A and Melzer, E and Malnick, S and Sharon, E and Bennet, Y and Tsentsarevsky, R and Abuchatzera, S and Amidror, S and Aretz, E and Azriel, S and Gam Ze Letova, C and Naama, M and Shoval, I and Yaron, O and Karako-Lampert, S and Bel, S and Yissachar, N}, title = {Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome.}, journal = {Cell reports}, volume = {41}, number = {7}, pages = {111657}, doi = {10.1016/j.celrep.2022.111657}, pmid = {36384106}, issn = {2211-1247}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy ; Diet, Carbohydrate-Restricted ; *Gastrointestinal Microbiome ; Homeostasis ; }, abstract = {Changes in microbiome composition are associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet, clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infuse gut organ cultures with longitudinal microbiota samples collected from therapy-naive patients with irritable bowel syndrome (IBS) under a low-fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diet. We show that post-diet microbiota regulates intestinal expression of inflammatory and neuro-muscular gene sets. Specifically, we identify Bifidobacterium adolescentis as a diet-sensitive pathobiont that alters tight junction integrity and disrupts gut barrier functions. Collectively, we present a pathway discovery platform for mechanistic dissection and identification of functional diet-host-microbiota modules. Our data support the hypothesis that the gut microbiota mediates the beneficial effects of a low-FODMAP diet and reinforce the potential feasibility of microbiome-based therapies in IBS.}, }
@article {pmid36380339, year = {2022}, author = {Haque, MM and Yerex, K and Kelekis-Cholakis, A and Duan, K}, title = {Advances in novel therapeutic approaches for periodontal diseases.}, journal = {BMC oral health}, volume = {22}, number = {1}, pages = {492}, pmid = {36380339}, issn = {1472-6831}, mesh = {Humans ; *Quorum Sensing ; Biofilms ; *Periodontal Diseases/therapy ; Bacteria ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {Periodontal diseases are pathological processes resulting from infections and inflammation affecting the periodontium or the tissue surrounding and supporting the teeth. Pathogenic bacteria living in complex biofilms initiate and perpetuate this disease in susceptible hosts. In some cases, broad-spectrum antibiotic therapy has been a treatment of choice to control bacterial infection. However, increasing antibiotic resistance among periodontal pathogens has become a significant challenge when treating periodontal diseases. Thanks to the improved understanding of the pathogenesis of periodontal disease, which involves the host immune response, and the importance of the human microbiome, the primary goal of periodontal therapy has shifted, in recent years, to the restoration of homeostasis in oral microbiota and its harmonious balance with the host periodontal tissues. This shift in therapeutic goals and the drug resistance challenge call for alternative approaches to antibiotic therapy that indiscriminately eliminate harmful or beneficial bacteria. In this review, we summarize the recent advancement of alternative methods and new compounds that offer promising potential for the treatment and prevention of periodontal disease. Agents that target biofilm formation, bacterial quorum-sensing systems and other virulence factors have been reviewed. New and exciting microbiome approaches, such as oral microbiota replacement therapy and probiotic therapy for periodontal disease, are also discussed.}, }
@article {pmid36378489, year = {2022}, author = {Gupta, VK and Bakshi, U and Chang, D and Lee, AR and Davis, JM and Chandrasekaran, S and Jin, YS and Freeman, MF and Sung, J}, title = {TaxiBGC: a Taxonomy-Guided Approach for Profiling Experimentally Characterized Microbial Biosynthetic Gene Clusters and Secondary Metabolite Production Potential in Metagenomes.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0092522}, pmid = {36378489}, issn = {2379-5077}, support = {R35 GM133475/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Metagenome/genetics ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Computational Biology ; Multigene Family/genetics ; }, abstract = {Biosynthetic gene clusters (BGCs) in microbial genomes encode bioactive secondary metabolites (SMs), which can play important roles in microbe-microbe and host-microbe interactions. Given the biological significance of SMs and the current profound interest in the metabolic functions of microbiomes, the unbiased identification of BGCs from high-throughput metagenomic data could offer novel insights into the complex chemical ecology of microbial communities. Currently available tools for predicting BGCs from shotgun metagenomes have several limitations, including the need for computationally demanding read assembly, predicting a narrow breadth of BGC classes, and not providing the SM product. To overcome these limitations, we developed taxonomy-guided identification of biosynthetic gene clusters (TaxiBGC), a command-line tool for predicting experimentally characterized BGCs (and inferring their known SMs) in metagenomes by first pinpointing the microbial species likely to harbor them. We benchmarked TaxiBGC on various simulated metagenomes, showing that our taxonomy-guided approach could predict BGCs with much-improved performance (mean F1 score, 0.56; mean PPV score, 0.80) compared with directly identifying BGCs by mapping sequencing reads onto the BGC genes (mean F1 score, 0.49; mean PPV score, 0.41). Next, by applying TaxiBGC on 2,650 metagenomes from the Human Microbiome Project and various case-control gut microbiome studies, we were able to associate BGCs (and their SMs) with different human body sites and with multiple diseases, including Crohn's disease and liver cirrhosis. In all, TaxiBGC provides an in silico platform to predict experimentally characterized BGCs and their SM production potential in metagenomic data while demonstrating important advantages over existing techniques. IMPORTANCE Currently available bioinformatics tools to identify BGCs from metagenomic sequencing data are limited in their predictive capability or ease of use to even computationally oriented researchers. We present an automated computational pipeline called TaxiBGC, which predicts experimentally characterized BGCs (and infers their known SMs) in shotgun metagenomes by first considering the microbial species source. Through rigorous benchmarking techniques on simulated metagenomes, we show that TaxiBGC provides a significant advantage over existing methods. When demonstrating TaxiBGC on thousands of human microbiome samples, we associate BGCs encoding bacteriocins with different human body sites and diseases, thereby elucidating a possible novel role of this antibiotic class in maintaining the stability of microbial ecosystems throughout the human body. Furthermore, we report for the first time gut microbial BGC associations shared among multiple pathologies. Ultimately, we expect our tool to facilitate future investigations into the chemical ecology of microbial communities across diverse niches and pathologies.}, }
@article {pmid36364808, year = {2022}, author = {Drake, AM and Coughlan, MT and Christophersen, CT and Snelson, M}, title = {Resistant Starch as a Dietary Intervention to Limit the Progression of Diabetic Kidney Disease.}, journal = {Nutrients}, volume = {14}, number = {21}, pages = {}, pmid = {36364808}, issn = {2072-6643}, mesh = {Animals ; Humans ; Resistant Starch ; Starch/therapeutic use/metabolism ; *Diabetic Nephropathies/prevention &amp; control ; Dietary Fiber/therapeutic use/metabolism ; Fatty Acids, Volatile/metabolism ; *Diabetes Mellitus ; }, abstract = {Diabetes is the leading cause of kidney disease, and as the number of individuals with diabetes increases there is a concomitant increase in the prevalence of diabetic kidney disease (DKD). Diabetes contributes to the development of DKD through a number of pathways, including inflammation, oxidative stress, and the gut-kidney axis, which may be amenable to dietary therapy. Resistant starch (RS) is a dietary fibre that alters the gut microbial consortium, leading to an increase in the microbial production of short chain fatty acids. Evidence from animal and human studies indicate that short chain fatty acids are able to attenuate inflammatory and oxidative stress pathways, which may mitigate the progression of DKD. In this review, we evaluate and summarise the evidence from both preclinical models of DKD and clinical trials that have utilised RS as a dietary therapy to limit the progression of DKD.}, }
@article {pmid36362106, year = {2022}, author = {Piccioni, A and Rosa, F and Manca, F and Pignataro, G and Zanza, C and Savioli, G and Covino, M and Ojetti, V and Gasbarrini, A and Franceschi, F and Candelli, M}, title = {Gut Microbiota and Clostridium difficile: What We Know and the New Frontiers.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362106}, issn = {1422-0067}, mesh = {Humans ; *Clostridioides difficile ; *Gastrointestinal Microbiome/physiology ; *Enterocolitis, Pseudomembranous/microbiology ; *Clostridium Infections/microbiology ; *Microbiota ; }, abstract = {Our digestive system, particularly our intestines, harbors a vast amount of microorganisms, whose genetic makeup is referred to as the microbiome. Clostridium difficile is a spore-forming Gram-positive bacterium, which can cause an infection whose symptoms range from asymptomatic colonization to fearsome complications such as the onset of toxic megacolon. The relationship between gut microbiota and Clostridium difficile infection has been studied from different perspectives. One of the proposed strategies is to be able to specifically identify which types of microbiota alterations are most at risk for the onset of CDI. In this article, we understood once again how crucial the role of the human microbiota is in health and especially how crucial it becomes, in the case of its alteration, for the individual's disease. Clostridium difficile infection is an emblematic example of how a normal and physiological composition of the human microbiome can play a very important role in immune defense against such a fearsome disease.}, }
@article {pmid36362056, year = {2022}, author = {Ustianowska, K and Ustianowski, &#x141; and Machaj, F and Gorący, A and Rosik, J and Szostak, B and Szostak, J and Pawlik, A}, title = {The Role of the Human Microbiome in the Pathogenesis of Pain.}, journal = {International journal of molecular sciences}, volume = {23}, number = {21}, pages = {}, pmid = {36362056}, issn = {1422-0067}, mesh = {Female ; Humans ; *Visceral Pain/pathology ; Brain/pathology ; Dysbiosis/pathology ; *Microbiota ; *Gastrointestinal Microbiome/physiology ; *Probiotics ; *Chronic Pain ; }, abstract = {Understanding of the gut microbiome's role in human physiology developed rapidly in recent years. Moreover, any alteration of this microenvironment could lead to a pathophysiological reaction of numerous organs. It results from the bidirectional communication of the gastrointestinal tract with the central nervous system, called the gut-brain axis. The signals in the gut-brain axis are mediated by immunological, hormonal, and neural pathways. However, it is also influenced by microorganisms in the gut. The disturbances in the gut-brain axis are associated with gastrointestinal syndromes, but recently their role in the development of different types of pain was reported. The gut microbiome could be the factor in the central sensitization of chronic pain by regulating microglia, astrocytes, and immune cells. Dysbiosis could lead to incorrect immune responses, resulting in the development of inflammatory pain such as endometriosis. Furthermore, chronic visceral pain, associated with functional gastrointestinal disorders, could result from a disruption in the gut microenvironment. Any alteration in the gut-brain axis could also trigger migraine attacks by affecting cytokine expression. Understanding the gut microbiome's role in pain pathophysiology leads to the development of analgetic therapies targeting microorganisms. Probiotics, FODMAP diet, and fecal microbiota transplantation are reported to be beneficial in treating visceral pain.}, }
@article {pmid36357382, year = {2022}, author = {Liu, Y and Elworth, RAL and Jochum, MD and Aagaard, KM and Treangen, TJ}, title = {De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6799}, pmid = {36357382}, issn = {2041-1723}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; R01 DK128187/DK/NIDDK NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; T32 HL098069/HL/NHLBI NIH HHS/United States ; R01 NR014792/NR/NINR NIH HHS/United States ; T32 HD098068/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Biomass ; *Microbiota/genetics ; Metagenomics/methods ; Metagenome ; Specimen Handling ; }, abstract = {Computational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low-biomass environments. Contamination from DNA extraction kits or sampling lab environments leaves taxonomic "bread crumbs" across multiple distinct sample types. Here we describe Squeegee, a de novo contamination detection tool that is based upon this principle, allowing the detection of microbial contaminants when negative controls are unavailable. On the low-biomass samples, we compare Squeegee predictions to experimental negative control data and show that Squeegee accurately recovers putative contaminants. We analyze samples of varying biomass from the Human Microbiome Project and identify likely, previously unreported kit contamination. Collectively, our results highlight that Squeegee can identify microbial contaminants with high precision and thus represents a computational approach for contaminant detection when negative controls are unavailable.}, }
@article {pmid36351016, year = {2022}, author = {Chen, J and Zhang, P and Zhao, Y and Zhao, J and Wu, X and Zhang, R and Cha, R and Yao, Q and Gao, Y}, title = {Nitroreductase-instructed supramolecular assemblies for microbiome regulation to enhance colorectal cancer treatments.}, journal = {Science advances}, volume = {8}, number = {45}, pages = {eadd2789}, pmid = {36351016}, issn = {2375-2548}, mesh = {Humans ; Mice ; Animals ; *Colorectal Neoplasms/drug therapy/pathology ; Fusobacterium nucleatum/physiology ; *Gastrointestinal Microbiome ; Nitroreductases ; }, abstract = {The development of human microbiome has collectively correlated the sophisticated interactions between Fusobacterium nucleatum and colorectal cancers (CRCs). However, the treatment of CRC via disruption of gastrointestinal flora remains less explored. Aiming at the up-regulated activity of nitroreductase in F. nucleatum-infected tumors, here, we developed the nitroreductase-instructed supramolecular self-assembly. The designed assembly precursors underwent enzymatic transformation to form assemblies, which agglutinated F. nucleatum and eradicated the targeted bacteria. These assemblies with anti-F. nucleatum activity could further alleviate the bacteria-induced drug resistance effect, thus sensitizing CRC cells against chemo-drugs. Eventually, in mice bearing F. nucleatum-infected CRC, the local introduction of nitroreductase-instructed assemblies could efficiently inhibit the tumor growth. Overall, this study incorporated nitroreductase to broaden the toolbox of enzyme-instructed supramolecular self-assembly. The local introduction of nitroreductase-instructed assemblies could target F. nucleatum to eliminate its contribution to CRC drug resistance and ameliorate chemotherapy outcomes.}, }
@article {pmid36348188, year = {2022}, author = {Rasmussen, N}, title = {René Dubos, the Autochthonous Flora, and the Discovery of the Microbiome.}, journal = {Journal of the history of biology}, volume = {55}, number = {3}, pages = {537-558}, pmid = {36348188}, issn = {1573-0387}, mesh = {Animals ; Humans ; *Microbiota ; *Anthozoa ; Symbiosis ; }, abstract = {Now characterised by high-throughput sequencing methods that enable the study of microbes without lab culture, the human "microbiome" (the microbial flora of the body) is said to have revolutionary implications for biology and medicine. According to many experts, we must now understand ourselves as "holobionts" like lichen or coral, multispecies superorganisms that consist of animal and symbiotic microbes in combination, because normal physiological function depends on them. Here I explore the 1960s research of biologist René Dubos, a forerunner figure mentioned in some historical accounts of the microbiome, and argue that he arrived at the superorganism concept 40 years before the Human Microbiome Project. This raises the question of why his contribution was not hailed as revolutionary at the time and why Dubos is not remembered for it.}, }
@article {pmid36342297, year = {2022}, author = {Mirabelli, C and Santos-Ferreira, N and Gillilland, MG and Cieza, RJ and Colacino, JA and Sexton, JZ and Neyts, J and Taube, S and Rocha-Pereira, J and Wobus, CE}, title = {Human Norovirus Efficiently Replicates in Differentiated 3D-Human Intestinal Enteroids.}, journal = {Journal of virology}, volume = {96}, number = {22}, pages = {e0085522}, pmid = {36342297}, issn = {1098-5514}, support = {UL1TR002240//UM | Michigan Institute for Clinical and Health Research (MICHR)/ ; P30 ES017885/ES/NIEHS NIH HHS/United States ; P30ES017885//HHS | NIH | OSC | Common Fund (NIH Common Fund)/ ; R01 ES028802/ES/NIEHS NIH HHS/United States ; P30DK034933//HHS | NIH | OSC | Common Fund (NIH Common Fund)/ ; }, mesh = {Humans ; *Norovirus/physiology ; Pyrazoles ; *Caliciviridae Infections ; *Gastroenteritis ; Antiviral Agents/pharmacology ; }, abstract = {Human norovirus (HNoV) accounts for one-fifth of all acute viral gastroenteritis worldwide and an economic burden of ~$60 billion globally. The lack of treatment options against HNoV is in part due to the lack of cultivation systems. Recently, a model of infection in biopsy-derived human intestinal enteroids (HIE) has been described: 3D-HIE are first dispersed in 2D-monolayers and differentiated prior to infection, resulting in a labor-intensive, time-consuming procedure. Here, we present an alternative protocol for HNoV infection of 3D-HIE. We found that 3D-HIE differentiated as efficiently as 2D-monolayers. In addition, immunofluorescence-based quantification of UEA-1, a lectin that stains the villus brush border, revealed that ~80% of differentiated 3D-HIE spontaneously undergo polarity inversion, allowing for viral infection without the need for microinjection. Infection with HNoV GII.4-positive stool samples attained a fold-increase over inoculum of ~2 Log10 at 2 days postinfection or up to 3.5 Log10 when ruxolitinib, a JAK1/2-inhibitor, was added. Treatment of GII.4-infected 3D-HIE with the polymerase inhibitor 2'-C-Methylcytidine (2CMC) and other antivirals showed a reduction in viral infection, suggesting that 3D-HIE are an excellent platform to test anti-infectives. The transcriptional host response to HNoV was then investigated by RNA sequencing in infected versus uninfected 3D-HIE in the presence of ruxolitinib to focus on virus-associated signatures while limiting interferon-stimulated gene signatures. The analysis revealed upregulated hormone and neurotransmitter signal transduction pathways and downregulated glycolysis and hypoxia-response pathways upon HNoV infection. Overall, 3D-HIE have proven to be a highly robust model to study HNoV infection, screen antivirals, and to investigate the host response to HNoV infection. IMPORTANCE The human norovirus (HNoV) clinical and socio-economic impact calls for immediate action in the development of anti-infectives. Physiologically relevant in vitro models are hence needed to study HNoV biology, tropism, and mechanisms of viral-associated disease, and also as a platform to identify antiviral agents. Biopsy-derived human intestinal enteroids are a biomimetic of the intestinal epithelium and were recently described as a model that supports HNoV infection. However, the established protocol is time-consuming and labor-intensive. Therefore, we sought to develop a simplified and robust alternative model of infection in 3D enteroids that undergoes differentiation and spontaneous polarity inversion. Advantages of this model are the shorter experimental time, better infection yield, and spatial integrity of the intestinal epithelium. This model is potentially suitable for the study of other pathogens that infect intestinal cells from the apical surface but also for unraveling the interactions between intestinal epithelium and indigenous bacteria of the human microbiome.}, }
@article {pmid36337619, year = {2022}, author = {Akimbekov, NS and Digel, I and Yerezhepov, AY and Shardarbek, RS and Wu, X and Zha, J}, title = {Nutritional factors influencing microbiota-mediated colonization resistance of the oral cavity: A literature review.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {1029324}, pmid = {36337619}, issn = {2296-861X}, abstract = {The oral cavity is a key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems. The oral microbiota is a vital part of the human microbiome. It has been developed through mutual interactions among the environment, host physiological state, and microbial community composition. Indigenious microbiota of the oral cavity is one of the factors that prevent adhesion and invasion of pathogens on the mucous membrane, i.e., the development of the infectious process and thereby participating in the implementation of one of the mechanisms of local immunity-colonization resistance. The balance between bacterial symbiosis, microbial virulence, and host resistance ensures the integrity of the oral cavity. In this review we have tried to address how nutritional factors influence integrity of the oral indigenous microbiota and its involvement in colonization resistance.}, }
@article {pmid36335804, year = {2023}, author = {Cuozzo, S and de Moreno de LeBlanc, A and LeBlanc, JG and Hoffmann, N and Tortella, GR}, title = {Streptomyces genus as a source of probiotics and its potential for its use in health.}, journal = {Microbiological research}, volume = {266}, number = {}, pages = {127248}, doi = {10.1016/j.micres.2022.127248}, pmid = {36335804}, issn = {1618-0623}, mesh = {Animals ; *Streptomyces ; *Probiotics ; *Gastrointestinal Microbiome ; *Microbiota ; Anti-Bacterial Agents/pharmacology ; }, abstract = {The effect of a probiotic on gut microbiota depends not only on the species of microorganism but specifically on the strain. In human beings, as in other animals, specific probiotics have been associated with numerous beneficial properties, which include weight modulation (gain or loss), immune modulation, and prevention of many disorders such as lactose intolerance, cardiovascular diseases, and antibiotic-associated diarrhoea. Streptomyces are an essential group of soil bacteria in the Actinomycetes family. They are related to producing a wide range of secondary metabolites known for their beneficial effects on human health. However, according to the human microbiome analysis, a lower prevalence of Streptomyces genus exists than in other non-human microbiomes. This difference can be associated with current lifestyles. In this article, we review the benefits associated with different compounds produced by Streptomyces, with a particular focus on the production of exopolysaccharides, antibiotics, and other secondary metabolites and the potential innovative use of Streptomyces spp. as probiotics.}, }
@article {pmid36329122, year = {2022}, author = {Clarke, T and Brinkac, L and Greco, C and Alleyne, AT and Carrasco, P and Inostroza, C and Tau, T and Wisitrasameewong, W and Torralba, MG and Nelson, K and Singh, H}, title = {Sampling from four geographically divergent young female populations demonstrates forensic geolocation potential in microbiomes.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {18547}, pmid = {36329122}, issn = {2045-2322}, support = {2015-R2-CX-K036//National Institute of Justice/ ; }, mesh = {Humans ; Female ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; DNA, Bacterial/genetics ; Feces/microbiology ; Specimen Handling ; }, abstract = {Studies of human microbiomes using new sequencing techniques have increasingly demonstrated that their ecologies are partly determined by the lifestyle and habits of individuals. As such, significant forensic information could be obtained from high throughput sequencing of the human microbiome. This approach, combined with multiple analytical techniques demonstrates that bacterial DNA can be used to uniquely identify an individual and to provide information about their life and behavioral patterns. However, the transformation of these findings into actionable forensic information, including the geolocation of the samples, remains limited by incomplete understanding of the effects of confounding factors and the paucity of diverse sequences. We obtained 16S rRNA sequences of stool and oral microbiomes collected from 206 young and healthy females from four globally diverse populations, in addition to supporting metadata, including dietary and medical information. Analysis of these microbiomes revealed detectable geolocation signals between the populations, even for populations living within the same city. Accounting for other lifestyle variables, such as diet and smoking, lessened but does not remove the geolocation signal.}, }
@article {pmid36322821, year = {2022}, author = {Saleem, A and Ikram, A and Dikareva, E and Lahtinen, E and Matharu, D and Pajari, AM and de Vos, WM and Hasan, F and Salonen, A and Jian, C}, title = {Unique Pakistani gut microbiota highlights population-specific microbiota signatures of type 2 diabetes mellitus.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2142009}, pmid = {36322821}, issn = {1949-0984}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome/genetics ; *Diabetes Mellitus, Type 2/microbiology ; Pakistan ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Bacteria/genetics ; *Actinobacteria/genetics ; }, abstract = {Biogeographic variations in the gut microbiota are pivotal to understanding the global pattern of host-microbiota interactions in prevalent lifestyle-related diseases. Pakistani adults, having an exceptionally high prevalence of type 2 diabetes mellitus (T2D), are one of the most understudied populations in microbiota research to date. The aim of the present study is to examine the gut microbiota across individuals from Pakistan and other populations of non-industrialized and industrialized lifestyles with a focus on T2D. The fecal samples from 94 urban-dwelling Pakistani adults with and without T2D were profiled by bacterial 16S ribosomal RNA gene and fungal internal transcribed spacer (ITS) region amplicon sequencing and eubacterial qPCR, and plasma samples quantified for circulating levels of lipopolysaccharide-binding protein (LBP) and the activation ability of Toll-like receptor (TLR)-signaling. Publicly available datasets generated with comparable molecular methods were retrieved for comparative analysis of the bacterial microbiota. Overall, urbanized Pakistanis' gut microbiota was similar to that of transitional or non-industrialized populations, depleted in Akkermansiaceae and enriched in Prevotellaceae (dominated by the non-Westernized clades of Prevotella copri). The relatively high proportion of Atopobiaceae appeared to be a unique characteristic of the Pakistani gut microbiota. The Pakistanis with T2D had elevated levels of LBP and TLR-signaling in circulation as well as gut microbial signatures atypical of other populations, e.g., increased relative abundance of Libanicoccus/Parolsenella, limiting the inter-population extrapolation of gut microbiota-based classifiers for T2D. Taken together, our findings call for a more global representation of understudied populations to extend the applicability of microbiota-based diagnostics and therapeutics.}, }
@article {pmid36321825, year = {2022}, author = {Stuivenberg, GA and Chmiel, JA and Akouris, PP and Burton, JP and Reid, G}, title = {Probiotic Bifidobacteria Mitigate the Deleterious Effects of para-Cresol in a Drosophila melanogaster Toxicity Model.}, journal = {mSphere}, volume = {7}, number = {6}, pages = {e0044622}, pmid = {36321825}, issn = {2379-5042}, mesh = {Animals ; Drosophila melanogaster ; Uremic Toxins ; *Probiotics/therapeutic use ; *Renal Insufficiency, Chronic/therapy/microbiology ; Sulfates ; Sodium Channels ; *Drosophila Proteins ; }, abstract = {Renal impairment associated with chronic kidney disease (CKD) causes the buildup of uremic toxins that are deleterious to patient health. Current therapies that manage toxin accumulation in CKD offer an incomplete therapeutic effect against toxins such as para-cresol (p-cresol) and p-cresyl sulfate. Probiotic therapies can exploit the wealth of microbial diversity to reduce toxin accumulation. Using in vitro culture techniques, strains of lactobacilli and bifidobacteria from a 24-strain synbiotic were investigated for their ability to remove p-cresol. Four strains of bifidobacteria internalized p-cresol from the extracellular environment. The oral supplementation of these toxin-clearing probiotics was more protective than control strains in a Drosophila melanogaster toxicity model. Bifidobacterial supplementation was also associated with higher abundance of lactobacilli in the gut microbiota of p-cresol-exposed flies. The present findings suggest that these strains might reduce p-cresol in the gut in addition to increasing the prevalence of other beneficial bacteria, such as lactobacilli, and should be tested clinically to normalize the dysbiotic gut microbiota observed in CKD patients. IMPORTANCE Chronic kidney disease (CKD) affects approximately 10% of the global population and has limited treatment options. The accumulation of gut microbiota-derived uremic toxins, such as para-cresol (p-cresol) and p-cresyl sulfate, is associated with the onset of comorbidities (i.e., atherosclerosis and cognitive disorders) in CKD. Unfortunately, dialysis, the gold standard therapy is unable to remove these toxins from the bloodstream due to their highly protein-bound nature. Some strains of Bifidobacterium have metabolic properties that may be useful in managing uremic toxicity. Using a Drosophila model, the present work highlights why dosing with certain probiotic strains may be clinically useful in CKD management.}, }
@article {pmid36321381, year = {2022}, author = {Das, BK}, title = {Altered gut microbiota in hepatocellular carcinoma: Insights into the pathogenic mechanism and preclinical to clinical findings.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {130}, number = {12}, pages = {719-740}, doi = {10.1111/apm.13282}, pmid = {36321381}, issn = {1600-0463}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Carcinoma, Hepatocellular/pathology ; *Liver Neoplasms/pathology ; Dysbiosis/complications ; *Probiotics/therapeutic use ; *Non-alcoholic Fatty Liver Disease ; }, abstract = {Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. It is usually the result of pre-existing liver damage caused by hepatitis B and/or C virus infection, alcohol consumption, nonalcoholic steatohepatitis (NASH), aflatoxin exposure, liver cirrhosis, obesity, and diabetes. A growing body of evidence suggests that gut microbes have a role in cancer genesis. More research into the microbiome gut-liver axis has recently contributed to understanding how the gut microbiome facilitates liver disease or even HCC progression. This review focuses on the preclinical results of gut-related hepatocarcinogenesis and probiotics, prebiotics, and antibiotics as therapeutic interventions to maintain gut microbial flora and minimize HCC-associated symptoms. Understanding the mechanistic link between the gut microbiota, host, and cancer progression could aid us in elucidating the cancer-related pathways and drive us toward preventing HCC-associated gut microbiota dysbiosis.}, }
@article {pmid36319696, year = {2023}, author = {Tierney, BT and Versalovic, J and Fasano, A and Petrosino, JF and Chumpitazi, BP and Mayer, EA and Boetes, J and Smits, G and Parkar, SG and Voreades, N and Kartal, E and Al-Ghalith, GA and Pane, M and Bron, PA and Reid, G and Dhir, R and Mason, CE}, title = {Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial.}, journal = {Pediatric research}, volume = {93}, number = {7}, pages = {2005-2013}, pmid = {36319696}, issn = {1530-0447}, mesh = {Child ; Humans ; Infant ; *Synbiotics ; Gastrointestinal Tract/microbiology ; *Probiotics/therapeutic use ; Constipation/therapy ; Feces/microbiology ; Double-Blind Method ; }, abstract = {BACKGROUND: Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children.<br><br>METHODS: Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n&#x2009;=&#x2009;33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n&#x2009;=&#x2009;31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo.<br><br>RESULTS: Treatment increased (p&#x2009;<&#x2009;0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p&#x2009;=&#x2009;0.00074).<br><br>CONCLUSIONS: These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children.<br><br>IMPACT: Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.}, }
@article {pmid36318354, year = {2022}, author = {Zhan, Y and Liu, Q and Zhang, B and Huang, X and Lu, Q}, title = {Recent advances in systemic lupus erythematosus and microbiota: from bench to bedside.}, journal = {Frontiers of medicine}, volume = {16}, number = {5}, pages = {686-700}, pmid = {36318354}, issn = {2095-0225}, mesh = {Humans ; Female ; *Gastrointestinal Microbiome ; *Lupus Erythematosus, Systemic/genetics/therapy ; *Microbiota ; Autoimmunity ; Immune System ; }, abstract = {Systemic lupus erythematosus (SLE) is a complicated autoimmune disease affecting multiple systems and organs. It is highly heterogeneous, and it preferentially affects women at childbearing age, causing worldwide social burden. The pathogenesis of SLE mostly involves genetic predisposition, epigenetic dysregulation, overactivation of the immune system, and environment factors. Human microbiome, which is mostly composed of microbiota colonized in the gut, skin, and oral cavity, provides a natural microbiome barrier against environmental risks. The past decade of research has demonstrated a strong association between microbiota and metabolic diseases or gastrointestinal diseases. However, the role of microbiota in autoimmunity remains largely unknown until recently, when the technological and methodological progress facilitates further microbiota research in SLE. In this review, the latest research about the role and mechanisms of microbiota in SLE and the advances in the development of diagnostic and therapeutic strategies based on microbiota for SLE were summarized.}, }
@article {pmid36317983, year = {2023}, author = {Aggarwal, N and Kitano, S and Puah, GRY and Kittelmann, S and Hwang, IY and Chang, MW}, title = {Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies.}, journal = {Chemical reviews}, volume = {123}, number = {1}, pages = {31-72}, pmid = {36317983}, issn = {1520-6890}, mesh = {Humans ; *Microbiota ; Technology ; }, abstract = {The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.}, }
@article {pmid36315176, year = {2022}, author = {Sadekov, TS and Boyko, AN and Omarova, MA and Rogovskii, VS and Zhilenkova, OG and Zatevalov, AM and Mironov, AY}, title = {Evaluation of the structure of the human microbiome in multiple sclerosis by the concentrations of microbial markers in the blood.}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {67}, number = {10}, pages = {600-606}, doi = {10.51620/0869-2084-2022-67-10-600-606}, pmid = {36315176}, issn = {0869-2084}, support = {22-15-00284//The Russian Science Foundation/ ; }, mesh = {Humans ; *Multiple Sclerosis ; Plasmalogens ; *Microbiota ; Bacteria/genetics ; Endotoxins/analysis ; Biomarkers ; }, abstract = {The relationship between multiple sclerosis and the state of the human microbiome was studied, namely, the change in the representation of microbiota phylotypes, the proportion of coccal flora, the proportion of anaerobic, gram-negative, proteolytically active microflora, as well as the concentration of markers of bacterial plasmalogen and endotoxin in the blood. Microbiome studies were carried out by gas chromatography - mass spectrometry of microbial markers in the blood. A statistically significant increase in blood concentrations of the total level of microbial markers of bacterial plasmalogen and endotoxin was determined in multiple sclerosis, which may be associated with an increase in the permeability of the intestinal wall. In multiple sclerosis, the proportion of coccal, gram-negative, anaerobic microflora with a proteolytic type of metabolic activity increases. The correlations of the representation of microbiota phylotypes change due to the switching of the direct relationship Proteobacteria-Bacteroides to Proteobacteria-Firmicutes. In multiple sclerosis, Actinobacteria and Proteobacteria increase and Firmicutes decrease. Conclusion. The multiple sclerosis disease may be associated with pathological changes in the structure of the microbiome and the growth of endotoxemia, which may be one of the factors in the pathogenesis of the disease. New laboratory markers for diagnosing and predicting the course of MS have been proposed.}, }
@article {pmid36307422, year = {2022}, author = {Wang, Y and Jian, C}, title = {Sustainable plant-based ingredients as wheat flour substitutes in bread making.}, journal = {NPJ science of food}, volume = {6}, number = {1}, pages = {49}, pmid = {36307422}, issn = {2396-8370}, abstract = {Bread as a staple food has been predominantly prepared from refined wheat flour. The world's demand for food is rising with increased bread consumption in developing countries where climate conditions are unsuitable for wheat cultivation. This reliance on wheat increases the vulnerability to wheat supply shocks caused by force majeure or man-made events, in addition to negative environmental and health consequences. In this review, we discuss the contribution to the sustainability of food systems by partially replacing wheat flour with various types of plant ingredients in bread making, also known as composite bread. The sustainable sources of non-wheat flours, their example use in bread making and potential health and nutritional benefits are summarized. Non-wheat flours pose techno-functional challenges due to significantly different properties of their proteins compared to wheat gluten, and they often contain off-favor compounds that altogether limit the consumer acceptability of final bread products. Therefore, we detail recent advances in processing strategies to improve the sensory and nutritional profiles of composite bread. A special focus is laid on fermentation, for its accessibility and versatility to apply to different ingredients and scenarios. Finally, we outline research needs that require the synergism between sustainability science, human nutrition, microbiomics and food science.}, }
@article {pmid36301976, year = {2022}, author = {Armstrong, D and Dregan, A and Ashworth, M and White, P}, title = {Prior antibiotics and risk of subsequent Herpes zoster: A population-based case control study.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276807}, pmid = {36301976}, issn = {1932-6203}, mesh = {Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Child ; Herpesvirus 3, Human ; Case-Control Studies ; Anti-Bacterial Agents/adverse effects ; *Herpes Zoster ; *Chickenpox ; }, abstract = {BACKGROUND: The effect of antibiotics on the human microbiome is now well established, but their indirect effect on the related immune response is less clear. The possible association of Herpes zoster, which involves a reactivation of a previous varicella zoster virus infection, with prior antibiotic exposure might indicate a potential link with the immune response.<br><br>METHODS: A case-control study was carried out using a clinical database, the UK's Clinical Practice Research Datalink. A total of 163,754 patients with varicella zoster virus infection and 331,559 age/sex matched controls were identified and their antibiotic exposure over the previous 10 years, and longer when data permitted, was identified. Conditional logistic regression was used to identify the association between antibiotic exposure and subsequent infection in terms of volume and timing.<br><br>RESULTS: The study found an association of antibiotic prescription and subsequent risk of varicella zoster virus infection (adjusted odds ratio of 1.50; 95%CIs: 1.42-1.58). The strongest association was with a first antibiotic over 10 years ago (aOR: 1.92; 95%CIs: 1.88-1.96) which was particularly pronounced in the younger age group of 18 to 50 (aOR 2.77; 95%CIs: 1.95-3.92).<br><br>CONCLUSIONS: By finding an association between prior antibiotics and Herpes zoster this study has shown that antibiotics may be involved in the reactivation of the varicella zoster virus. That effect, moreover, may be relatively long term. This indirect effect of antibiotics on viruses, possibly mediated through their effect on the microbiome and immune system, merits further study.}, }
@article {pmid36301483, year = {2023}, author = {Pereira, GC}, title = {An Automated Strategy to Handle Antigenic Variability in Immunisation Protocols, Part I: Nanopore Sequencing of Infectious Agent Variants.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2575}, number = {}, pages = {305-321}, pmid = {36301483}, issn = {1940-6029}, mesh = {Humans ; SARS-CoV-2/genetics ; *Nanopore Sequencing ; *COVID-19/prevention &amp; control ; Immunization ; Antigenic Variation ; RNA, Messenger ; *Zika Virus/genetics ; *Zika Virus Infection ; }, abstract = {Infectious agents often challenge therapeutics, from antibiotics resistance to antigenic variability affecting inoculation measures. Over the last decades, genome sequencing arose as an important ally to address such challenges. In bacterial infection, whole-genome-sequencing (WGS) supports tracking pathogenic alterations affecting the human microbiome. In viral infection, the analysis of the relevant sequence of nucleotides helps with determining historical variants of a virus and elucidates details about infection clusters and their distribution. Additionally, genome sequencing is now an important step in inoculation protocols, isolating target genes to design more robust immunisation assays. Ultimately, genetic engineering has empowered repurposing at scale, allowing long-lasting repeating clinical trials to be automated within a much shorter time-frame, by adjusting existing protocols. This is particularly important during sanitary emergencies as the ones caused by the 2014 West African Ebola outbreak, the Zika virus rapid spread in both South and North America in 2015, followed by Asia in 2016, and the pandemic caused by the SARS-CoV-2, which has infected more than 187 million people and caused more than 4 million deaths, worldwide, as per July 2021 statistics. In this scenery, this chapter presents a novel fully automated strategy to handle antigenic variability in immunisation protocols. The methodology comprises of two major steps (1) nanopore sequencing of infectious agent variants - the focus is on the SARS-CoV-2 and its variants; followed by (2) mRNA vector design for immunotherapy. This chapter presents the nanopore sequencing step and Chapter 17 introduces a protocol for mRNA vector design.}, }
@article {pmid36288274, year = {2022}, author = {France, MT and Brown, SE and Rompalo, AM and Brotman, RM and Ravel, J}, title = {Identification of shared bacterial strains in the vaginal microbiota of related and unrelated reproductive-age mothers and daughters using genome-resolved metagenomics.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0275908}, pmid = {36288274}, issn = {1932-6203}, support = {R01 AI116799/AI/NIAID NIH HHS/United States ; R01 NR015495/NR/NINR NIH HHS/United States ; R01 AI060892/AI/NIAID NIH HHS/United States ; }, mesh = {Child ; Humans ; Female ; Adolescent ; *Microbiota/genetics ; Vagina/microbiology ; Reproduction ; Bacteria/genetics ; Metagenomics ; }, abstract = {It has been suggested that the human microbiome might be vertically transmitted from mother to offspring and that early colonizers may play a critical role in development of the immune system. Studies have shown limited support for the vertical transmission of the intestinal microbiota but the derivation of the vaginal microbiota remains largely unknown. Although the vaginal microbiota of children and reproductive age women differ in composition, the vaginal microbiota could be vertically transmitted. To determine whether there was any support for this hypothesis, we examined the vaginal microbiota of daughter-mother pairs from the Baltimore metropolitan area (ages 14-27, 32-51; n = 39). We assessed whether the daughter's microbiota was similar in composition to their mother's using metataxonomics. Permutation tests revealed that while some pairs did have similar vaginal microbiota, the degree of similarity did not exceed that expected by chance. Genome-resolved metagenomics was used to identify shared bacterial strains in a subset of the families (n = 22). We found a small number of bacterial strains that were shared between mother-daughter pairs but identified more shared strains between individuals from different families, indicating that vaginal bacteria may display biogeographic patterns. Earlier-in-life studies are needed to demonstrate vertical transmission of the vaginal microbiota.}, }
@article {pmid36287108, year = {2023}, author = {Ponziani, FR and Nesci, A and Caputo, C and Salvatore, L and Picca, A and Del Chierico, F and Paroni Sterbini, F and Marzetti, E and Di Giorgio, A and Santoro, L and Putignani, L and Gasbarrini, A and Santoliquido, A and Pompili, M}, title = {High prevalence of lower limb atherosclerosis is linked with the gut-liver axis in patients with primary biliary cholangitis.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {43}, number = {2}, pages = {370-380}, pmid = {36287108}, issn = {1478-3231}, mesh = {Humans ; Female ; *Liver Cirrhosis, Biliary/complications ; *Non-alcoholic Fatty Liver Disease/epidemiology/complications ; Tumor Necrosis Factor-alpha ; *Hypercholesterolemia/complications ; Prevalence ; Vascular Cell Adhesion Molecule-1 ; *Atherosclerosis/epidemiology/complications ; Lower Extremity ; }, abstract = {BACKGROUND AND AIMS: Hypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer an increased risk of cardiovascular disease. We aimed to evaluate the prevalence of peripheral arterial disease in PBC women and its association with the gut-liver axis and systemic inflammation.<br><br>METHODS: Thirty patients affected by PBC and hypercholesterolemia were enrolled, with equal-sized groups of women with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRL). All patients underwent Doppler ultrasound examination of peripheral arteries, assessment of flow-mediated dilation, quantification of circulating cytokines and vasoactive mediators and characterization of the gut microbiota.<br><br>RESULTS: PBC patients had a higher prevalence of lower extremity arterial disease (LEAD) defined as atherosclerotic plaques in any of femoral, popliteal and/or tibial arteries compared with both NAFLD and CTRL women (83.3% vs. 53.3% and 50%, respectively; p&#xa0;=&#x2009;.01). Factors associated with LEAD at univariate analysis were VCAM-1 (p&#xa0;=&#x2009;.002), ICAM-1 (p&#xa0;=&#x2009;.003), and TNF-alpha (p&#xa0;=&#x2009;.04) serum levels, but only VCAM-1 (OR 1.1, 95% CI 1.0-1.1; p&#xa0;=&#x2009;.04) and TNF-alpha (OR 1.12, 95% CI 0.99-1.26; p&#xa0;=&#x2009;.04) were confirmed as independent predictors in the multivariate model. Gut microbiota analysis revealed that Acidaminococcus (FDR&#xa0;=&#xa0;0.0008), Bifidobacterium (FDR&#xa0;=&#xa0;0.001) and Oscillospira (FDR&#xa0;=&#xa0;0.03) were differentially expressed among groups. Acidaminococcus, which was increased in PBC, was positively correlated with TNF-alpha serum levels. Down-regulation of metabolic pathways linked to fatty acid and butyrate metabolism, glyoxylate metabolism and branched-chain amino acids degradation was found in the functional gut metagenome of PBC women.<br><br>CONCLUSIONS: LEAD is common in patients affected by PBC and is associated with inflammatory markers and alterations in the gut-liver axis.}, }
@article {pmid36286197, year = {2022}, author = {Jones, RP and Ponomarenko, A}, title = {Roles for Pathogen Interference in Influenza Vaccination, with Implications to Vaccine Effectiveness (VE) and Attribution of Influenza Deaths.}, journal = {Infectious disease reports}, volume = {14}, number = {5}, pages = {710-758}, pmid = {36286197}, issn = {2036-7430}, abstract = {Pathogen interference is the ability of one pathogen to alter the course and clinical outcomes of infection by another. With up to 3000 species of human pathogens the potential combinations are vast. These combinations operate within further immune complexity induced by infection with multiple persistent pathogens, and by the role which the human microbiome plays in maintaining health, immune function, and resistance to infection. All the above are further complicated by malnutrition in children and the elderly. Influenza vaccination offers a measure of protection for elderly individuals subsequently infected with influenza. However, all vaccines induce both specific and non-specific effects. The specific effects involve stimulation of humoral and cellular immunity, while the nonspecific effects are far more nuanced including changes in gene expression patterns and production of small RNAs which contribute to pathogen interference. Little is known about the outcomes of vaccinated elderly not subsequently infected with influenza but infected with multiple other non-influenza winter pathogens. In this review we propose that in certain years the specific antigen mix in the seasonal influenza vaccine inadvertently increases the risk of infection from other non-influenza pathogens. The possibility that vaccination could upset the pathogen balance, and that the timing of vaccination relative to the pathogen balance was critical to success, was proposed in 2010 but was seemingly ignored. Persons vaccinated early in the winter are more likely to experience higher pathogen interference. Implications to the estimation of vaccine effectiveness and influenza deaths are discussed.}, }
@article {pmid36284711, year = {2022}, author = {Keren, R and Méheust, R and Santini, JM and Thomas, A and West-Roberts, J and Banfield, JF and Alvarez-Cohen, L}, title = {Global genomic analysis of microbial biotransformation of arsenic highlights the importance of arsenic methylation in environmental and human microbiomes.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {559-572}, pmid = {36284711}, issn = {2001-0370}, support = {P42 ES004705/ES/NIEHS NIH HHS/United States ; }, abstract = {Arsenic is a ubiquitous toxic element, the global cycle of which is highly affected by microbial redox reactions and assimilation into organoarsenic compounds through sequential methylation reactions. While microbial biotransformation of arsenic has been studied for decades, the past years have seen the discovery of multiple new genes related to arsenic metabolism. Still, most studies focus on a small set of key genes or a small set of cultured microorganisms. Here, we leveraged the recently greatly expanded availability of microbial genomes of diverse organisms from lineages lacking cultivated representatives, including those reconstructed from metagenomes, to investigate genetic repertoires of taxonomic and environmental controls on arsenic metabolic capacities. Based on the collection of arsenic-related genes, we identified thirteen distinct metabolic guilds, four of which combine the aio and ars operons. We found that the best studied phyla have very different combinations of capacities than less well-studied phyla, including phyla lacking isolated representatives. We identified a distinct arsenic gene signature in the microbiomes of humans exposed or likely exposed to drinking water contaminated by arsenic and that arsenic methylation is important in soil and in human microbiomes. Thus, the microbiomes of humans exposed to arsenic have the potential to exacerbate arsenic toxicity. Finally, we show that machine learning can predict bacterial arsenic metabolism capacities based on their taxonomy and the environment from which they were sampled.}, }
@article {pmid36281758, year = {2024}, author = {Yadav, M and Chauhan, NS}, title = {Role of gut-microbiota in disease severity and clinical outcomes.}, journal = {Briefings in functional genomics}, volume = {23}, number = {1}, pages = {24-37}, doi = {10.1093/bfgp/elac037}, pmid = {36281758}, issn = {2041-2657}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis ; Diet ; Patient Acuity ; }, abstract = {A delicate balance of nutrients, antigens, metabolites and xenobiotics in body fluids, primarily managed by diet and host metabolism, governs human health. Human gut microbiota is a gatekeeper to nutrient bioavailability, pathogens exposure and xenobiotic metabolism. Human gut microbiota starts establishing during birth and evolves into a resilient structure by adolescence. It supplements the host's metabolic machinery and assists in many physiological processes to ensure health. Biotic and abiotic stressors could induce dysbiosis in gut microbiota composition leading to disease manifestations. Despite tremendous scientific advancements, a clear understanding of the involvement of gut microbiota dysbiosis during disease onset and clinical outcomes is still awaited. This would be important for developing an effective and sustainable therapeutic intervention. This review synthesizes the present scientific knowledge to present a comprehensive picture of the role of gut microbiota in the onset and severity of a disease.}, }
@article {pmid36280324, year = {2022}, author = {Gupta, A and Singh, V and Mani, I}, title = {Dysbiosis of human microbiome and infectious diseases.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {33-51}, doi = {10.1016/bs.pmbts.2022.06.016}, pmid = {36280324}, issn = {1878-0814}, mesh = {Humans ; Dysbiosis ; Prebiotics ; *Gastrointestinal Microbiome ; *Microbiota ; *Probiotics ; Bacteria ; *Communicable Diseases ; }, abstract = {Since birth, the human body gets colonized by various communities of symbiotic or commensal microorganisms and they persist till the death of an individual. The human microbiome is comprised of the genomes of microorganisms such as viruses, archaea, eukaryotes, protozoa, and, most remarkably, bacteria. The development of "omics" technologies gave way to the Human Microbiome Project (HMP) which aimed at exploring the collection of microbial genes and genomes inhabiting the human body. Eubiosis, i.e., a healthy and balanced composition of such microbes contributes to the metabolic function, protection against pathogens and provides nutrients and energy to the host. Whereas, an imbalance in the diversity of microorganisms, termed dysbiosis, greatly influences the state of health and disease. This chapter summarizes the impact of gut bacteria on the well-being of humans and highlights the protective role played by the human microbiota during bacterial and viral infections. The condition of dysbiosis and how it plays a role in the establishment of various infections and metabolic disorders such as Clostridioides difficile infection (CFI), inflammatory bowel disease (IBD), cancer, periodontitis, and obesity are described in detail. Further, treatments such as fecal transplantation, probiotics, prebiotics, phage therapy, and CRISPR/Cas system, which target gut microbiota during digestive diseases are also discussed.}, }
@article {pmid36280323, year = {2022}, author = {Ahrodia, T and Yodhaanjali, JR and Das, B}, title = {Vaginal microbiome dysbiosis in preterm birth.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {309-329}, doi = {10.1016/bs.pmbts.2022.08.001}, pmid = {36280323}, issn = {1878-0814}, mesh = {Infant, Newborn ; Pregnancy ; Female ; Humans ; *Premature Birth ; Dysbiosis ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Lactobacillus/genetics/metabolism ; Bacteria/metabolism ; Lactic Acid/metabolism ; }, abstract = {All the environmentally exposed surfaces of the human body harbor ecologically distinct microbial communities with a mutualistic beneficial relationship. Depending on the body sites, microbes may provide metabolic functions, protection against pathogens, and signaling molecules to modulate host physiology and reduce disease susceptibility. Our recent understanding of the vaginal microbiome based on culture-independent 16S rRNA gene sequencing indicates that Lactobacillus-dominated microbial communities of healthy women play an important role in decreasing susceptibility to several urogenital diseases, including bacterial, fungal and viral infections. The findings of shotgun sequencing of the vaginal microbiome suggest that microbial-derived lactic acid, bacteriostatic, bactericidal molecules, and lower vaginal pH mediate such protections and regulations. Bacterial species, the dominant component of the vaginal microbiome, also play a key role in determining the gestation period and birth outcomes of reproductive-age women. The presence of Lactobacillus crispatus species in the vaginal milieu reduces the risk of preterm delivery in women of Asian ancestry. A deeper knowledge of the vaginal microbiota's role in the succession and development of newborn gut bacteria would also be beneficial. The microbiome of the mother changes throughout pregnancy and is linked to the microbiome of the newborn. This chapter highlights updated information and new opportunities for human microbiome research, focusing on the assessment of the risk of preterm birth.}, }
@article {pmid36280321, year = {2022}, author = {Alam, MJ and Puppala, V and Uppulapu, SK and Das, B and Banerjee, SK}, title = {Human microbiome and cardiovascular diseases.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {231-279}, doi = {10.1016/bs.pmbts.2022.07.012}, pmid = {36280321}, issn = {1878-0814}, mesh = {Humans ; *Cardiovascular Diseases ; Dysbiosis ; *Gastrointestinal Microbiome ; Bacteria ; Inflammation/complications ; }, abstract = {A number of microorganisms are co-evolved with the host, among which bacteria are the predominant organisms in the colonic site. The human microbiota contributes to various physiological functions, including the digestion and degradation of food components, harvesting of inaccessible nutrients, immune system regulation, maintenance of gut barrier function, and regulation of brain function and behavior. Microbes in the gut produce a wealth of metabolites from the exogenous dietary substances or endogenous metabolic compounds produced by the host and the resident microorganisms. These microbial-derived metabolites are the major factors in the host-microbiota cross-talk and influence the host's cardiometabolic health directly or indirectly depending on the structure and function of the microbial community. Evidence suggests that the perturbation in the composition and function of gut microbiota (referred to as gut dysbiosis) is associated with the development of several diseased conditions such as that of the gastrointestinal tract or colorectal cancer, metabolic diseases such as obesity, diabetes, immune disorders e.g. asthma, allergies, depression, anxiety and cardiometabolic disease. Several pathological conditions in the gastrointestinal tract may impair the intestinal barrier that allows translocation of bacteria and their metabolites to a remote organ such as the heart, which may ultimately be associated with systemic inflammation and the development of CVDs. In this chapter, we will discuss various gut microbiota-dependent metabolites, which have a significant role in cardiovascular diseases' pathologic processes and their risk factors. Finally, we will discuss the therapeutic potential of the gut-metabolite-heart axis as a novel target for the treatment of CVD and highlight the current updates and exciting directions for future research.}, }
@article {pmid36279192, year = {2023}, author = {Nguyen, NA and Huang, X and Cabrera, LE and Pekkarinen, PT and Nowlan, K and Strandin, T and Kantele, A and Vapalahti, O and Heinonen, S and Kekäläinen, E}, title = {A comprehensive assessment of four whole blood stabilizers for flow-cytometric analysis of leukocyte populations.}, journal = {Cytometry. Part A : the journal of the International Society for Analytical Cytology}, volume = {103}, number = {4}, pages = {313-324}, doi = {10.1002/cyto.a.24700}, pmid = {36279192}, issn = {1552-4930}, support = {323499//Academy of Finland/ ; //Lastentautien Tutkimuss&#xe4;&#xe4;ti&#xf6;/ ; //Sigrid Jus&#xe9;liuksen S&#xe4;&#xe4;ti&#xf6;/ ; //Suomen L&#xe4;&#xe4;ketieteen S&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Humans ; Flow Cytometry ; *Proteomics ; *COVID-19 ; Leukocytes ; Granulocytes ; }, abstract = {Though cryopreservation of cell fractions is widely used in flow cytometry studies, whole blood cryopreservation is more challenging due to the presence of erythrocytes and effects of fixatives commonly used for preservation. Here, we evaluated and compared head-to-head the performance of four commercial whole blood cryopreservation kits; (1) Cytodelics, (2) Stable-Lyse V2 and Stable-Store V2 (SLSS-V2), (3) Proteomic stabilizer (PROT-1), and (4) Transfix. We found that PROT-1, Transfix, and Cytodelics maintained the distribution of major leukocyte subsets-granulocytes, T cells, natural killer cells, and B cells, on a comparable level to unpreserved samples, despite the attenuation of fluorescence intensities in flow cytometric assays. Moreover, these three stabilizers also maintained the activated phenotypes of neutrophils upon stimulation with N-formylmethionyl-leucyl-phenylalanine and lipopolysaccharides. The upregulation of adhesion molecules (CD11b), Fc receptors (CD16), and granule proteins (CD66b), as well as the shedding of surface L-selectin (CD62L), was conserved most efficiently in PROT-1 and Cytodelics when compared to samples only treated with erythrocyte lysing. However, none of the stabilizers provided a reliable detection of CCR7 for accurate quantification of T cell maturation stages. We also evaluated the performance of Cytodelics in longitudinal clinical samples obtained from acute COVID-19 patients, where it allowed reliable detection of lymphopenia and granulocyte expansion. These results support the feasibility of whole blood cryopreservation for immunophenotyping by flow cytometry, particularly in longitudinal studies. In conclusion, the performance of different stabilizers is variable and therefore the choice of stabilizers should depend on cell type of interest, as well as antibody clones and experimental design of each study.}, }
@article {pmid36278460, year = {2022}, author = {Suryaletha, K and Savithri, AV and Nayar, SA and Asokan, S and Rajeswary, D and Thomas, S}, title = {Demystifying Bacteriocins of Human Microbiota by Genome Guided Prospects: An Impetus to Rekindle the Antimicrobial Research.}, journal = {Current protein &amp; peptide science}, volume = {23}, number = {12}, pages = {811-822}, pmid = {36278460}, issn = {1875-5550}, mesh = {Humans ; *Bacteriocins/genetics/pharmacology ; Anti-Bacterial Agents/pharmacology ; *Microbiota ; Bacteria/genetics ; }, abstract = {The human microbiome is a reservoir of potential bacteriocins that can counteract multidrug resistant bacterial pathogens. Unlike antibiotics, bacteriocins selectively inhibit a spectrum of competent bacteria and are said to safeguard gut commensals, reducing the chance of dysbiosis. Bacteriocinogenic probiotics or bacteriocins of human origin will be more pertinent in human physiological conditions for therapeutic applications to act against invading pathogens. Recent advancement in the omics approach enables the mining of diverse and novel bacteriocins by identifying biosynthetic gene clusters from the human microbial genome, pangenome or shotgun metagenome, which is a breakthrough in the discovery line of novel bacteriocins. This review summarizes the most recent trends and therapeutic potential of bacteriocins of human microbial origin, the advancement in the in silico algorithms and databases in the discovery of novel bacteriocin, and how to bridge the gap between the discovery of bacteriocin genes from big datasets and their in vitro production. Besides, the later part of the review discussed the various impediments in their clinical applications and possible solution to bring them into the frontline therapeutics to control infections, thereby meeting the challenges of global antimicrobial resistance.}, }
@article {pmid36274732, year = {2022}, author = {Matharu, D and Ponsero, AJ and Dikareva, E and Korpela, K and Kolho, KL and de Vos, WM and Salonen, A}, title = {Bacteroides abundance drives birth mode dependent infant gut microbiota developmental trajectories.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {953475}, pmid = {36274732}, issn = {1664-302X}, abstract = {BACKGROUND AND AIMS: Birth mode and other early life factors affect a newborn's microbial colonization with potential long-term health effects. Individual variations in early life gut microbiota development, especially their effects on the functional repertoire of microbiota, are still poorly characterized. This study aims to provide new insights into the gut microbiome developmental trajectories during the first year of life.<br><br>METHODS: Our study comprised 78 term infants sampled at 3 weeks, 3 months, 6 months, and 12 months (n = 280 total samples), and their mothers were sampled in late pregnancy (n = 50). Fecal DNA was subjected to shotgun metagenomic sequencing. Infant samples were studied for taxonomic and functional maturation, and maternal microbiota was used as a reference. Hierarchical clustering on taxonomic profiles was used to identify the main microbiota developmental trajectories in the infants, and their associations with perinatal and postnatal factors were assessed.<br><br>RESULTS: In line with previous studies, infant microbiota composition showed increased alpha diversity and decreased beta diversity by age, converging toward an adult-like profile. However, we did not observe an increase in functional alpha diversity, which was stable and comparable with the mother samples throughout all the sampling points. Using a de novo clustering approach, two main infant microbiota clusters driven by Bacteroidaceae and Clostridiaceae emerged at each time point. The clusters were associated with birth mode and their functions differed mainly in terms of biosynthetic and carbohydrate degradation pathways, some of which consistently differed between the clusters for all the time points. The longitudinal analysis indicated three main microbiota developmental trajectories, with the majority of the infants retaining their characteristic cluster until 1 year. As many as 40% of vaginally delivered infants were grouped with infants delivered by C-section due to their clear and persistent depletion in Bacteroides. Intrapartum antibiotics, any perinatal or postnatal factors, maternal microbiota composition, or other maternal factors did not explain the depletion in Bacteroides in the subset of vaginally born infants.<br><br>CONCLUSION: Our study provides an enhanced understanding of the compositional and functional early life gut microbiota trajectories, opening avenues for investigating elusive causes that influence non-typical microbiota development.}, }
@article {pmid36274714, year = {2022}, author = {Zheng, Y and Shi, J and Chen, Q and Deng, C and Yang, F and Wang, Y}, title = {Identifying individual-specific microbial DNA fingerprints from skin microbiomes.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {960043}, pmid = {36274714}, issn = {1664-302X}, abstract = {Skin is an important ecosystem that links the human body and the external environment. Previous studies have shown that the skin microbial community could remain stable, even after long-term exposure to the external environment. In this study, we explore two questions: Do there exist strains or genetic variants in skin microorganisms that are individual-specific, temporally stable, and body site-independent? And if so, whether such microorganismal genetic variants could be used as markers, called "fingerprints" in our study, to identify donors? We proposed a framework to capture individual-specific DNA microbial fingerprints from skin metagenomic sequencing data. The fingerprints are identified on the frequency of 31-mers free from reference genomes and sequence alignments. The 616 metagenomic samples from 17 skin sites at 3-time points from 12 healthy individuals from Integrative Human Microbiome Project were adopted. Ultimately, one contig for each individual is assembled as a fingerprint. And results showed that 89.78% of the skin samples despite body sites could identify their donors correctly. It is observed that 10 out of 12 individual-specific fingerprints could be aligned to Cutibacterium acnes. Our study proves that the identified fingerprints are temporally stable, body site-independent, and individual-specific, and can identify their donors with enough accuracy. The source code of the genetic identification framework is freely available at https://github.com/Ying-Lab/skin_fingerprint.}, }
@article {pmid36271144, year = {2023}, author = {Zhang, F and Lau, RI and Liu, Q and Su, Q and Chan, FKL and Ng, SC}, title = {Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {20}, number = {5}, pages = {323-337}, pmid = {36271144}, issn = {1759-5053}, mesh = {Humans ; *COVID-19 ; SARS-CoV-2 ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; *Microbiota ; }, abstract = {The gastrointestinal tract is involved in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gut microbiota has important roles in viral entry receptor angiotensin-converting enzyme 2 (ACE2) expression, immune homeostasis, and crosstalk between the gut and lungs, the 'gut-lung axis'. Emerging preclinical and clinical studies indicate that the gut microbiota might contribute to COVID-19 pathogenesis and disease outcomes; SARS-CoV-2 infection was associated with altered intestinal microbiota and correlated with inflammatory and immune responses. Here, we discuss the cutting-edge evidence on the interactions between SARS-CoV-2 infection and the gut microbiota, key microbial changes in relation to COVID-19 severity and host immune dysregulations with the possible underlying mechanisms, and the conceivable consequences of the pandemic on the human microbiome and post-pandemic health. Finally, potential modulatory strategies of the gut microbiota are discussed. These insights could shed light on the development of microbiota-based interventions for COVID-19.}, }
@article {pmid36270682, year = {2022}, author = {Ahrodia, T and Das, S and Bakshi, S and Das, B}, title = {Structure, functions, and diversity of the healthy human microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {53-82}, doi = {10.1016/bs.pmbts.2022.07.003}, pmid = {36270682}, issn = {1878-0814}, mesh = {Humans ; *Microbiota ; Bacteria/genetics ; Metagenome ; *Gastrointestinal Microbiome ; Archaea ; }, abstract = {Taxonomic composition and functional potency of microbes associated with different parts of the human body have largely been explored by culture-independent metagenome sequencing. The diverse microbiota living throughout the human body is made up of thousands of microbial taxa from all three domains of life: Archaea, Bacteria, and Eukarya. Microbial load and functional potency in different body sites are well distinct and have minimal resemblance at higher taxonomic levels between the two habitats. The highest microbial load, diversity, and functional potency including biosynthesis of essential nutrients, chemical modifications of dietary components, and sources of immunomodulatory molecules, are found in the gut microbiome. However, the inter-individual diversity and dynamics of the human microbiome in a given body habitat vary greatly over time. Both environmental factors and host genetics contribute significantly to shaping microbial community structure and its stability. A basic understanding of native microbial compositions and their functional potency and stability in different parts of healthy humans living across geography will help us to identify disease-specific microbiota and develop potential microbiome-based therapeutics. Here, we updated our current understanding of the diversity, dynamics, and functional potency of microbiomes associated with different parts of the human body.}, }
@article {pmid36270681, year = {2022}, author = {Ghosh, TS and Das, M}, title = {Emerging tools for understanding the human microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {29-51}, doi = {10.1016/bs.pmbts.2022.06.027}, pmid = {36270681}, issn = {1878-0814}, mesh = {Humans ; *High-Throughput Nucleotide Sequencing/methods ; *Microbiota ; Metagenome ; Metagenomics/methods ; Computational Biology/methods ; }, abstract = {Recent advances in sequencing technologies, experimental protocols and approaches in data generation and analysis have enabled us to investigate the human microbiome at an unprecedented level of resolution. The current chapter aims to provide an understanding of the different computational and bioinformatic strategies adopted to answer the different questions of a typical microbiome investigation and how the upstream DNA sequencing methodologies can affect this. The chapter enlist the state-of-the-art in metagenomic data analysis along with the available strategies to perform an integrated investigation of the human microbiome along with other data layers.}, }
@article {pmid36270680, year = {2022}, author = {Pant, A and Das, B}, title = {Microbiome-based therapeutics: Opportunity and challenges.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {229-262}, doi = {10.1016/bs.pmbts.2022.07.006}, pmid = {36270680}, issn = {1878-0814}, mesh = {Humans ; *Microbiota ; *Probiotics ; }, abstract = {The autochthonous microbial communities comprising symbionts, commensals, and opportunistic pathogens living throughout the human body profoundly contribute to health by reducing disease susceptibility and maturing host immunity. The community compositions and functional repertoires of microbiomes present in the different body habitats are dynamic. The structural and functional balance of the human microbiome could be modulated by environmental factors, lifestyle, and host genetics. Several functions of the microbial community directly or indirectly modulate host cellular signaling pathways that are associated with energy assimilation, sensing and responding to environmental signals through the neuroendocrine pathways, and resistance against colonization of allochthonous microbiota with disease-causing potential. Both culture-dependent and independent characterizations of microbial community compositions and their functional attributes help us to recognize the importance of microbial diversity in individual's health and identify the microbes and their metabolites associated with health and diseases. Such an in-depth understanding of the human microbiome created avenues of microbiome-based translation research, which led to the discovery and development of large numbers of medical therapies. In this chapter, we discuss the current success of microbiome-based therapies for infectious and metabolic diseases, and the major bottleneck and challenges of translational research with the community of symbiotic microorganisms.}, }
@article {pmid36270674, year = {2022}, author = {Das, B}, title = {An introduction to human microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {191}, number = {1}, pages = {1-28}, doi = {10.1016/bs.pmbts.2022.06.026}, pmid = {36270674}, issn = {1878-0814}, mesh = {Humans ; *Microbiota ; Dysbiosis ; Bacteria ; Archaea ; Host Microbial Interactions ; }, abstract = {The microbiome is an assemblage of a complex community of microbes (bacteria, archaea, fungi, algae, protists, and viruses) and their biomolecules occupying a well-defined habitat in or on a living or non-living object. All the environmentally exposed surfaces of the human body are colonized with trillions of microbes from all three major domains of life, including bacteria, archea, and microscopic eukarya. However, the richness, abundance, and functional potency of microbial taxa living in different parts of the human body are distinct. The Presence of common microbial taxa in different body habitats is also very rare. With the recent development of next generation sequencing technologies, it has been established that the indigenous microbial community in the human body and their functional attributes within a given body habitat vary over time, between ethnic groups and health status of the host. Perturbation of homeostasis in community structures or functions due to any extrinsic factors can alter mutualistic host-microbe interactions and may lead to disease. In addition, the dysbiotic state of the microbiome can also affect the efficacy of therapeutics, prolong treatment duration and lead to undesired treatment outcomes. In this chapter, structure, functions, diversity and dynamics of human microbiome in health and diseases, factors that alter microbial composition, interactions between microbial taxa and xenobiotics, and therapeutic efficacy of drugs in dysbiotic conditions are highlighted.}, }
@article {pmid36268225, year = {2022}, author = {Khorsand, B and Asadzadeh Aghdaei, H and Nazemalhosseini-Mojarad, E and Nadalian, B and Nadalian, B and Houri, H}, title = {Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn's disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1015890}, pmid = {36268225}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative ; *Crohn Disease/microbiology ; *Gastrointestinal Microbiome/genetics ; Metagenome ; Escherichia coli ; Siderophores ; Lipopolysaccharides ; *Inflammatory Bowel Diseases/microbiology ; Feces/microbiology ; *Escherichia coli Infections ; Sulfur ; Nitrogen ; }, abstract = {OBJECTIVES: A number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn's disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.<br><br>METHODS: Metagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi'omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.<br><br>RESULTS: Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.<br><br>CONCLUSIONS: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.}, }
@article {pmid36266277, year = {2022}, author = {Sauvaitre, T and Van Landuyt, J and Durif, C and Roussel, C and Sivignon, A and Chalancon, S and Uriot, O and Van Herreweghen, F and Van de Wiele, T and Etienne-Mesmin, L and Blanquet-Diot, S}, title = {Role of mucus-bacteria interactions in Enterotoxigenic Escherichia coli (ETEC) H10407 virulence and interplay with human microbiome.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {86}, pmid = {36266277}, issn = {2055-5008}, mesh = {Humans ; *Enterotoxigenic Escherichia coli/physiology ; Interleukin-8/genetics ; Virulence ; Diarrhea ; Caco-2 Cells ; *Escherichia coli Infections/microbiology ; Travel ; *Microbiota ; Bacteria ; Mucus ; Mucins ; }, abstract = {The intestinal mucus layer has a dual role in human health constituting a well-known microbial niche that supports gut microbiota maintenance but also acting as a physical barrier against enteric pathogens. Enterotoxigenic Escherichia coli (ETEC), the major agent responsible for traveler's diarrhea, is able to bind and degrade intestinal mucins, representing an important but understudied virulent trait of the pathogen. Using a set of complementary in vitro approaches simulating the human digestive environment, this study aimed to describe how the mucus microenvironment could shape different aspects of the human ETEC strain H10407 pathophysiology, namely its survival, adhesion, virulence gene expression, interleukin-8 induction and interactions with human fecal microbiota. Using the TNO gastrointestinal model (TIM-1) simulating the physicochemical conditions of the human upper gastrointestinal (GI) tract, we reported that mucus secretion and physical surface sustained ETEC survival, probably by helping it to face GI stresses. When integrating the host part in Caco2/HT29-MTX co-culture model, we demonstrated that mucus secreting-cells favored ETEC adhesion and virulence gene expression, but did not impede ETEC Interleukin-8 (IL-8) induction. Furthermore, we proved that mucosal surface did not favor ETEC colonization in a complex gut microbial background simulated in batch fecal experiments. However, the mucus-specific microbiota was widely modified upon the ETEC challenge suggesting its role in the pathogen infectious cycle. Using multi-targeted in vitro approaches, this study supports the major role played by mucus in ETEC pathophysiology, opening avenues in the design of new treatment strategies.}, }
@article {pmid36264944, year = {2022}, author = {Mäenpää, K and Wang, S and Ilves, M and El-Nezami, H and Alenius, H and Sinkko, H and Karisola, P}, title = {Skin microbiota of oxazolone-induced contact hypersensitivity mouse model.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0276071}, pmid = {36264944}, issn = {1932-6203}, mesh = {Mice ; Animals ; Oxazolone ; RNA, Ribosomal, 16S/genetics ; Olive Oil ; Acetone ; *Microbiota ; Disease Models, Animal ; *Dermatitis, Allergic Contact ; Inflammation ; Bacteria ; }, abstract = {Contact allergy is a common skin allergy, which can be studied utilising contact hypersensitivity (CHS) animal model. However, it is not clear, whether CHS is a suitable model to investigate skin microbiota interactions. We characterised the effect of contact dermatitis on the skin microbiota and studied the biological effects of oxazolone (OXA) -induced inflammation on skin thickness, immune cell numbers and changes of the microbiota in CHS mouse model (n = 72) for 28 days. Through 16S rRNA gene sequencing we defined the composition of bacterial communities and associations of bacteria with inflammation. We observed that the vehicle solution of acetone and olive oil induced bacterial community changes on day 1, and OXA-induced changes were observed mainly on day 7. Many of the notably enriched bacteria present in the OXA-challenged positive group represented the genus Faecalibaculum which were most likely derived from the cage environment. Additionally, skin inflammation correlated negatively with Streptococcus, which is considered a native skin bacterium, and positively with Muribacter muris, which is typical in oral environment. Skin inflammation favoured colonisation of cage-derived faecal bacteria, and additionally mouse grooming transferred oral bacteria on the skin. Due to the observed changes, we conclude that CHS model could be used for certain skin microbiome-related research set-ups. However, since vehicle exposure can alter the skin microbiome as such, future studies should include considerations such as careful control sampling and statistical tests to account for potential confounding factors.}, }
@article {pmid36261456, year = {2022}, author = {Moitinho-Silva, L and Degenhardt, F and Rodriguez, E and Emmert, H and Juzenas, S and Möbus, L and Uellendahl-Werth, F and Sander, N and Baurecht, H and Tittmann, L and Lieb, W and Gieger, C and Peters, A and Ellinghaus, D and Bang, C and Franke, A and Weidinger, S and Rühlemann, MC}, title = {Host genetic factors related to innate immunity, environmental sensing and cellular functions are associated with human skin microbiota.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6204}, pmid = {36261456}, issn = {2041-1723}, mesh = {Humans ; Genome-Wide Association Study ; *Microbiota/genetics ; Skin ; Immunity, Innate/genetics ; *Gastrointestinal Microbiome/genetics ; }, abstract = {Despite the increasing knowledge about factors shaping the human microbiome, the host genetic factors that modulate the skin-microbiome interactions are still largely understudied. This contrasts with recent efforts to characterize host genes that influence the gut microbiota. Here, we investigated the effect of genetics on skin microbiota across three different skin microenvironments through meta-analyses of genome-wide association studies (GWAS) of two population-based German cohorts. We identified 23 genome-wide significant loci harboring 30 candidate genes involved in innate immune signaling, environmental sensing, cell differentiation, proliferation and fibroblast activity. However, no locus passed the strict threshold for study-wide significance (P < 6.3 × 10[-10] for 80 features included in the analysis). Mendelian randomization (MR) analysis indicated the influence of staphylococci on eczema/dermatitis and suggested modulating effects of the microbiota on other skin diseases. Finally, transcriptional profiles of keratinocytes significantly changed after in vitro co-culturing with Staphylococcus epidermidis, chosen as a representative of skin commensals. Seven candidate genes from the GWAS were found overlapping with differential expression in the co-culturing experiments, warranting further research of the skin commensal and host genetic makeup interaction.}, }
@article {pmid36258167, year = {2022}, author = {Vikramdeo, KS and Anand, S and Pierce, JY and Singh, AP and Singh, S and Dasgupta, S}, title = {Distribution of microbiota in cervical preneoplasia of racially disparate populations.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {1074}, pmid = {36258167}, issn = {1471-2407}, support = {R01 CA224306/CA/NCI NIH HHS/United States ; R01 CA231925/CA/NCI NIH HHS/United States ; CA231925, CA224306/NH/NIH HHS/United States ; }, mesh = {Female ; Humans ; Papillomaviridae/genetics ; RNA, Ribosomal, 16S/genetics ; *Papillomavirus Infections/complications ; Dysbiosis ; *Uterine Cervical Neoplasms/pathology ; *Microbiota/genetics ; *Uterine Cervical Dysplasia/epidemiology ; }, abstract = {BACKGROUNDS: Microbiome dysbiosis is an important contributing factor in tumor development and thus may be a risk predictor for human malignancies. In the United States, women with Hispanic/Latina (HIS) and African American (AA) background have a higher incidence of cervical cancer and poorer outcomes than Caucasian American (CA) women.<br><br>METHODS: Here, we assessed the distribution pattern of microbiota in cervical intraepithelial neoplasia (CIN) lesions obtained from HIS (n&#x2009;=&#x2009;12), AA (n&#x2009;=&#x2009;12), and CA (n&#x2009;=&#x2009;12) women, who were screened for CC risk assessment. We employed a 16S rRNA gene sequencing approach adapted from the NIH-Human Microbiome Project to identify the microbial niche in all CIN lesions (n&#x2009;=&#x2009;36).<br><br>RESULTS: We detected an appreciably decreased abundance of beneficial Lactobacillus in the CIN lesions of the AA and HIS women compared to the CA women. Differential abundance of potentially pathogenic Prevotella, Delftia, Gardnerella, and Fastidiosipila was also evident among the various racial groups. An increased abundance of Micrococcus was also evident in AA and HIS women compared to the CA women. The detection level of Rhizobium was higher among the AA ad CA women compared to the HIS women. In addition to the top 10 microbes, a unique niche of 27 microbes was identified exclusively in women with a histopathological diagnosis of CIN. Among these microbes, a group of 8 microbiota; Rubellimicrobium, Podobacter, Brevibacterium, Paracoccus, Atopobium, Brevundimonous, Comamonous, and Novospingobium was detected only in the CIN lesions obtained from AA and CA women.<br><br>CONCLUSIONS: Microbial dysbiosis in the cervical epithelium represented by an increased ratio of potentially pathogenic to beneficial microbes may be associated with increased CC risk disparities. Developing a race-specific reliable panel of microbial markers could be beneficial for CC risk assessment, disease prevention, and/or therapeutic guidance.}, }
@article {pmid36250060, year = {2022}, author = {Monshizadeh, M and Zomorodi, S and Mortensen, K and Ye, Y}, title = {Revealing bacteria-phage interactions in human microbiome through the CRISPR-Cas immune systems.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {933516}, pmid = {36250060}, issn = {2235-2988}, support = {R01 AI108888/AI/NIAID NIH HHS/United States ; R01 AI143254/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/genetics ; *Bacteriophages/genetics ; CRISPR-Cas Systems ; Humans ; Immune System ; *Microbiota/genetics ; }, abstract = {The human gut microbiome is composed of a diverse consortium of microorganisms. Relatively little is known about the diversity of the bacteriophage population and their interactions with microbial organisms in the human microbiome. Due to the persistent rivalry between microbial organisms (hosts) and phages (invaders), genetic traces of phages are found in the hosts' CRISPR-Cas adaptive immune system. Mobile genetic elements (MGEs) found in bacteria include genetic material from phage and plasmids, often resultant from invasion events. We developed a computational pipeline (BacMGEnet), which can be used for inference and exploratory analysis of putative interactions between microbial organisms and MGEs (phages and plasmids) and their interaction network. Given a collection of genomes as the input, BacMGEnet utilizes computational tools we have previously developed to characterize CRISPR-Cas systems in the genomes, which are then used to identify putative invaders from publicly available collections of phage/prophage sequences. In addition, BacMGEnet uses a greedy algorithm to summarize identified putative interactions to produce a bacteria-MGE network in a standard network format. Inferred networks can be utilized to assist further examination of the putative interactions and for discovery of interaction patterns. Here we apply the BacMGEnet pipeline to a few collections of genomic/metagenomic datasets to demonstrate its utilities. BacMGEnet revealed a complex interaction network of the Phocaeicola vulgatus pangenome with its phage invaders, and the modularity analysis of the resulted network suggested differential activities of the different P. vulgatus' CRISPR-Cas systems (Type I-C and Type II-C) against some phages. Analysis of the phage-bacteria interaction network of human gut microbiome revealed a mixture of phages with a broad host range (resulting in large modules with many bacteria and phages), and phages with narrow host range. We also showed that BacMGEnet can be used to infer phages that invade bacteria and their interactions in wound microbiome. We anticipate that BacMGEnet will become an important tool for studying the interactions between bacteria and their invaders for microbiome research.}, }
@article {pmid36241544, year = {2022}, author = {Sánchez-Manubens, J and Henares, D and Muñoz-Almagro, C and Brotons de Los Reyes, P and Timoneda, N and Antón, J}, title = {Characterization of the nasopharyngeal microbiome in patients with Kawasaki disease.}, journal = {Anales de pediatria}, volume = {97}, number = {5}, pages = {300-309}, doi = {10.1016/j.anpede.2022.08.001}, pmid = {36241544}, issn = {2341-2879}, mesh = {Child ; Humans ; RNA, Ribosomal, 16S/genetics/analysis ; Case-Control Studies ; *Mucocutaneous Lymph Node Syndrome ; Nasopharynx/chemistry/microbiology ; *Microbiota/genetics ; Corynebacterium/genetics ; }, abstract = {INTRODUCTION: The aetiology of Kawasaki disease (KD) remains unknown. Several studies have linked the human microbiome with some diseases. However, there are limited studies on the role of the respiratory microbiome in KD. The aim of our study was to make a more thorough analysis of the causes and processes that increase the susceptibility to KD.<br><br>METHODS: Case-control study comparing the respiratory microbiome of KD patients with that of healthy children. The V3-V4 region of the 16S rRNA bacterial gene and 16 respiratory viruses were analysed by real-time polimerase-chain reaction. We used the Ribosomal Database Project (RDP) version 11.5 (taxonomic assignment).<br><br>RESULTS: The initial sample included 11 cases and 11 controls matched for age, sex and seasonality. One of the cases was excluded to poor sample quality. The final analysis included 10 cases and 10 controls. In the case group, the analysis detected Haemophilus, Moraxella, Streptococcus and Corynebacterium species (27.62%, 19.71%, 25.28%, 11.86%, respectively). In the control group, it found Haemophilus, Streptococcus, Moraxella, and Dolosigranulum species (38.59%, 23.71%, 16.08, 8.93%, respectively). We found a higher relative abundance of Corynebacterium in patients with KD (11.86% vs. 1.55%; P&#x202f;=&#x202f;0.004).<br><br>CONCLUSIONS: To our knowledge, this is the first study that has found differences in the composition of the respiratory microbiome between patients with KD and healthy controls. The relative abundance of Corynebacterium spp. was greater in the KD group. This study shows differences in the microbiome between cases and controls, which suggests that the microbiome may play a role in facilitating the development of KD.}, }
@article {pmid36240246, year = {2022}, author = {Gauthier, NPG and Locher, K and MacDonald, C and Chorlton, SD and Charles, M and Manges, AR}, title = {Alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity.}, journal = {PloS one}, volume = {17}, number = {10}, pages = {e0275815}, pmid = {36240246}, issn = {1932-6203}, mesh = {*COVID-19 ; Humans ; *Microbiota ; Nasopharynx ; Pandemics/prevention &amp; control ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2 ; Severity of Illness Index ; }, abstract = {OBJECTIVES: The COVID-19 pandemic and ensuing public health emergency has emphasized the need to study SARS-CoV-2 pathogenesis. The human microbiome has been shown to regulate the host immune system and may influence host susceptibility to viral infection, as well as disease severity. Several studies have assessed whether compositional alterations in the nasopharyngeal microbiota are associated with SARS-CoV-2 infection. However, the results of these studies were varied, and many did not account for disease severity. This study aims to examine whether compositional differences in the nasopharyngeal microbiota are associated with SARS-CoV-2 infection status and disease severity.<br><br>METHODS: We performed Nanopore full-length 16S rRNA sequencing on 194 nasopharyngeal swab specimens from hospitalized and community-dwelling SARS-CoV-2-infected and uninfected individuals. Sequence data analysis was performed using the BugSeq 16S analysis pipeline.<br><br>RESULTS: We found significant beta (PERMANOVA p < 0.05), but not alpha (Kruskal-Wallis p > 0.05) diversity differences in the nasopharyngeal microbiota among our study groups. We identified several differentially abundant taxa associated with SARS-CoV-2 infection status and disease severity using ALDEx2. Finally, we observed a trend towards higher abundance of Enterobacteriaceae in specimens from hospitalized SARS-CoV-2-infected patients.<br><br>CONCLUSIONS: This study identified several alterations in the nasopharyngeal microbiome associated with SARS-CoV-2 infection status and disease severity. Understanding the role of the microbiome in infection susceptibility and severity may open new avenues of research for disease prevention and treatment.}, }
@article {pmid36238714, year = {2022}, author = {Merrill, BD and Carter, MM and Olm, MR and Dahan, D and Tripathi, S and Spencer, SP and Yu, B and Jain, S and Neff, N and Jha, AR and Sonnenburg, ED and Sonnenburg, JL}, title = {Ultra-deep Sequencing of Hadza Hunter-Gatherers Recovers Vanishing Gut Microbes.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {36238714}, issn = {2692-8205}, support = {DP1 AT009892/AT/NCCIH NIH HHS/United States ; F32 DK128865/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; }, abstract = {The gut microbiome is a key modulator of immune and metabolic health. Human microbiome data is biased towards industrialized populations, providing limited understanding of the distinct and diverse non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing and strain cultivation on 351 fecal samples from the Hadza, hunter-gatherers in Tanzania, and comparative populations in Nepal and California. We recover 94,971 total genomes of bacteria, archaea, bacteriophages, and eukaryotes, 43% of which are absent from existing unified datasets. Analysis of in situ growth rates, genetic pN/pS signatures, high-resolution strain tracking, and 124 gut-resident species vanishing in industrialized populations reveals differentiating dynamics of the Hadza gut microbiome. Industrialized gut microbes are enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource that expands our understanding of microbes capable of colonizing the human gut and clarifies the extensive perturbation brought on by the industrialized lifestyle.}, }
@article {pmid36232866, year = {2022}, author = {Uzelac, M and Li, Y and Chakladar, J and Li, WT and Ongkeko, WM}, title = {Archaea Microbiome Dysregulated Genes and Pathways as Molecular Targets for Lung Adenocarcinoma and Squamous Cell Carcinoma.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36232866}, issn = {1422-0067}, mesh = {*Adenocarcinoma of Lung/pathology ; Archaea/genetics ; *Carcinoma, Non-Small-Cell Lung/genetics ; *Carcinoma, Squamous Cell/pathology ; Female ; Humans ; *Lung Neoplasms/pathology ; Male ; *Microbiota/genetics ; }, abstract = {The human microbiome is a vast collection of microbial species that exist throughout the human body and regulate various bodily functions and phenomena. Of the microbial species that exist in the human microbiome, those within the archaea domain have not been characterized to the extent of those in more common domains, despite their potential for unique metabolic interaction with host cells. Research has correlated tumoral presence of bacterial microbial species to the development and progression of lung cancer; however, the impacts and influences of archaea in the microbiome remain heavily unexplored. Within the United States lung cancer remains highly fatal, responsible for over 100,000 deaths every year with a 5-year survival rate of roughly 22.9%. This project attempts to investigate specific archaeal species' correlation to lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) incidence, patient staging, death rates across individuals of varying ages, races, genders, and smoking-statuses, and potential molecular targets associated with archaea microbiome. Archaeal species abundance was assessed across lung tissue samples of 527 LUAD patients, 479 LUSC patients, and 99 healthy individuals. Nine archaeal species were found to be of significantly altered abundance in cancerous samples as compared to normal counterparts, 6 of which are common to both LUAD and LUSC subgroups. Several of these species are of the taxonomic class Thermoprotei or the phylum Euryarchaeota, both known to contain metabolic processes distinct from most bacterial species. Host-microbe metabolic interactions may be responsible for the observed correlation of these species' abundance with cancer incidence. Significant microbes were correlated to patient gene expression to reveal genes of altered abundance with respect to high and low archaeal presence. With these genes, cellular oncogenic signaling pathways were analyzed for enrichment across cancer and normal samples. In comparing gene expression between LUAD and adjacent normal samples, 2 gene sets were found to be significantly enriched in cancers. In LUSC comparison, 6 sets were significantly enriched in cancer, and 34 were enriched in normals. Microbial counts across healthy and cancerous patients were then used to develop a machine-learning based predictive algorithm, capable of distinguishing lung cancer patients from healthy normal with 99% accuracy.}, }
@article {pmid36231000, year = {2022}, author = {Prakash, A and Nourianpour, M and Senok, A and Atiomo, W}, title = {Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota.}, journal = {Cells}, volume = {11}, number = {19}, pages = {}, pmid = {36231000}, issn = {2073-4409}, mesh = {Dysbiosis/complications/microbiology ; *Endometrial Neoplasms ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; *Polycystic Ovary Syndrome ; }, abstract = {Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the 'Human Microbiome Project' in 2016. We obtained 200 articles by inputting keywords such as 'gut microbiome', 'gut microbiota', 'gut dysbiosis', 'PCOS', and 'endometrial cancer' into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.}, }
@article {pmid36220576, year = {2022}, author = {Campana, AM and Laue, HE and Shen, Y and Shrubsole, MJ and Baccarelli, AA}, title = {Assessing the role of the gut microbiome at the interface between environmental chemical exposures and human health: Current knowledge and challenges.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {315}, number = {}, pages = {120380}, pmid = {36220576}, issn = {1873-6424}, support = {P30 CA023108/CA/NCI NIH HHS/United States ; T32 CA134286/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Environmental Exposure ; *Microbiota ; *Environmental Pollutants/toxicity ; Hazardous Substances/toxicity ; }, abstract = {The explosion of microbiome research over the past decade has shed light on the various ways that external factors interact with the human microbiome to drive health and disease. Each individual is exposed to more than 300 environmental chemicals every day. Accumulating evidence indicates that the microbiome is involved in the early response to environmental toxicants and biologically mediates their adverse effects on human health. However, few review articles to date provided a comprehensive framework for research and translation of the role of the gut microbiome in environmental health science. This review summarizes current evidence on environmental compounds and their effect on the gut microbiome, discusses the involved compound metabolic pathways, and covers environmental pollution-induced gut microbiota disorders and their long-term outcomes on host health. We conclude that the gut microbiota may crucially mediate and modify the disease-causing effects of environmental chemicals. Consequently, gut microbiota needs to be further studied to assess the complete toxicity of environmental exposures. Future research in this field is required to delineate the key interactions between intestinal microbiota and environmental pollutants and further to elucidate the long-term human health effects.}, }
@article {pmid36219547, year = {2022}, author = {Zubeldia-Varela, E and Barker-Tejeda, TC and Obeso, D and Villaseñor, A and Barber, D and Pérez-Gordo, M}, title = {Microbiome and Allergy: New Insights and Perspectives.}, journal = {Journal of investigational allergology &amp; clinical immunology}, volume = {32}, number = {5}, pages = {327-344}, doi = {10.18176/jiaci.0852}, pmid = {36219547}, issn = {1018-9068}, mesh = {Allergens ; Dysbiosis ; *Food Hypersensitivity ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies are increasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immune response to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skin microbiota and atopic dermatitis, and between gut microbiota and food allergy. The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics are the techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerably in recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased. Thus, more and more studies are proposing mechanisms for intervention in the microbiota. In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous, and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases. Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy.}, }
@article {pmid36215042, year = {2023}, author = {Wishart, DS and Oler, E and Peters, H and Guo, A and Girod, S and Han, S and Saha, S and Lui, VW and LeVatte, M and Gautam, V and Kaddurah-Daouk, R and Karu, N}, title = {MiMeDB: the Human Microbial Metabolome Database.}, journal = {Nucleic acids research}, volume = {51}, number = {D1}, pages = {D611-D620}, pmid = {36215042}, issn = {1362-4962}, support = {U19 AG063744/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Metabolomics ; *Proteomics ; Metabolome/genetics ; Databases, Factual ; Data Management ; }, abstract = {The Human Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the human exposome and (iv) all of these 'omes' to human health. MiMeDB was established to consolidate the growing body of data connecting the human microbiome and the chemicals it produces to both health and disease. MiMeDB contains detailed taxonomic, microbiological and body-site location data on most known human microbes (bacteria and fungi). This microbial data is linked to extensive genomic and proteomic sequence data that is closely coupled to colourful interactive chromosomal maps. The database also houses detailed information about all the known metabolites generated by these microbes, their structural, chemical and spectral properties, the reactions and enzymes responsible for these metabolites and the primary exposome sources (food, drug, cosmetic, pollutant, etc.) that ultimately lead to the observed microbial metabolites in humans. Additional, extensively referenced data about the known or presumptive health effects, measured biosample concentrations and human protein targets for these compounds is provided. All of this information is housed in richly annotated, highly interactive, visually pleasing database that has been designed to be easy to search, easy to browse and easy to navigate. Currently MiMeDB contains data on 626 health effects or bioactivities, 1904 microbes, 3112 references, 22 054 reactions, 24 254 metabolites or exposure chemicals, 648 861 MS and NMR spectra, 6.4 million genes and 7.6 billion DNA bases. We believe that MiMeDB represents the kind of integrated, multi-omic or systems biology database that is needed to enable comprehensive multi-omic integration.}, }
@article {pmid36209213, year = {2022}, author = {Wang, C and Zhang, L and Jiang, X and Ma, W and Geng, H and Wang, X and Li, M}, title = {Toward efficient and high-fidelity metagenomic data from sub-nanogram DNA: evaluation of library preparation and decontamination methods.}, journal = {BMC biology}, volume = {20}, number = {1}, pages = {225}, pmid = {36209213}, issn = {1741-7007}, mesh = {DNA/genetics ; *Decontamination ; Endonucleases/genetics ; Gene Library ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenomics/methods ; Reproducibility of Results ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Shotgun metagenomic sequencing has greatly expanded the understanding of microbial communities in various biological niches. However, it is still challenging to efficiently convert sub-nanogram DNA to high-quality metagenomic libraries and obtain high-fidelity data, hindering the exploration of niches with low microbial biomass.<br><br>RESULTS: To cope with this challenge comprehensively, we evaluated the performance of various library preparation methods on 0.5&#xa0;pg-5&#xa0;ng synthetic microbial community DNA, characterized contaminants, and further applied different in silico decontamination methods. First, we discovered that whole genome amplification prior to library construction led to worse outcomes than preparing libraries directly. Among different non-WGA-based library preparation methods, we found the endonuclease-based method being generally good for different amounts of template and the tagmentation-based method showing specific advantages with 0.5&#xa0;pg template, based on evaluation metrics including fidelity, proportion of designated reads, and reproducibility. The load of contaminating DNA introduced by library preparation varied from 0.01 to 15.59&#xa0;pg for different kits and accounted for 0.05 to 45.97% of total reads. A considerable fraction of the contaminating reads were mapped to human commensal and pathogenic microbes, thus potentially leading to erroneous conclusions in human microbiome studies. Furthermore, the best performing in silico decontamination method in our evaluation, Decontam-either, was capable of recovering the real microbial community from libraries where contaminants accounted for less than 10% of total reads, but not from libraries with heavy and highly varied contaminants.<br><br>CONCLUSIONS: This study demonstrates that high-quality metagenomic data can be obtained from samples with sub-nanogram microbial DNA by combining appropriate library preparation and in silico decontamination methods and provides a general reference for method selection for samples with varying microbial biomass.}, }
@article {pmid36207756, year = {2022}, author = {Park, HM and Park, Y and Berani, U and Bang, E and Vankerschaver, J and Van Messem, A and De Neve, W and Shim, H}, title = {In silico optimization of RNA-protein interactions for CRISPR-Cas13-based antimicrobials.}, journal = {Biology direct}, volume = {17}, number = {1}, pages = {27}, pmid = {36207756}, issn = {1745-6150}, mesh = {Anti-Bacterial Agents ; Bacteria/genetics ; *CRISPR-Cas Systems ; Humans ; *RNA, Bacterial ; Ribonucleases/genetics/metabolism ; }, abstract = {RNA-protein interactions are crucial for diverse biological processes. In prokaryotes, RNA-protein interactions enable adaptive immunity through CRISPR-Cas systems. These defence systems utilize CRISPR RNA (crRNA) templates acquired from past infections to destroy foreign genetic elements through crRNA-mediated nuclease activities of Cas proteins. Thanks to the programmability and specificity of CRISPR-Cas systems, CRISPR-based antimicrobials have the potential to be repurposed as new types of antibiotics. Unlike traditional antibiotics, these CRISPR-based antimicrobials can be designed to target specific bacteria and minimize detrimental effects on the human microbiome during antibacterial therapy. In this study, we explore the potential of CRISPR-based antimicrobials by optimizing the RNA-protein interactions of crRNAs and Cas13 proteins. CRISPR-Cas13 systems are unique as they degrade specific foreign RNAs using the crRNA template, which leads to non-specific RNase activities and cell cycle arrest. We show that a high proportion of the Cas13 systems have no colocalized CRISPR arrays, and the lack of direct association between crRNAs and Cas proteins may result in suboptimal RNA-protein interactions in the current tools. Here, we investigate the RNA-protein interactions of the Cas13-based systems by curating the validation dataset of Cas13 protein and CRISPR repeat pairs that are experimentally validated to interact, and the candidate dataset of CRISPR repeats that reside on the same genome as the currently known Cas13 proteins. To find optimal CRISPR-Cas13 interactions, we first validate the 3-D structure prediction of crRNAs based on their experimental structures. Next, we test a number of RNA-protein interaction programs to optimize the in silico docking of crRNAs with the Cas13 proteins. From this optimized pipeline, we find a number of candidate crRNAs that have comparable or better in silico docking with the Cas13 proteins of the current tools. This study fully automatizes the in silico optimization of RNA-protein interactions as an efficient preliminary step for designing effective CRISPR-Cas13-based antimicrobials.}, }
@article {pmid36202806, year = {2022}, author = {Shetty, SA and Kuipers, B and Atashgahi, S and Aalvink, S and Smidt, H and de Vos, WM}, title = {Author Correction: Inter-species metabolic interactions in an in-vitro minimal human gut microbiome of core bacteria.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {76}, doi = {10.1038/s41522-022-00339-3}, pmid = {36202806}, issn = {2055-5008}, }
@article {pmid36198908, year = {2023}, author = {VanEvery, H and Franzosa, EA and Nguyen, LH and Huttenhower, C}, title = {Microbiome epidemiology and association studies in human health.}, journal = {Nature reviews. Genetics}, volume = {24}, number = {2}, pages = {109-124}, pmid = {36198908}, issn = {1471-0064}, support = {T32 DK007703/DK/NIDDK NIH HHS/United States ; K23 DK125838/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Genome-Wide Association Study ; *Microbiota/genetics ; High-Throughput Nucleotide Sequencing ; }, abstract = {Studies of the human microbiome share both technical and conceptual similarities with genome-wide association studies and genetic epidemiology. However, the microbiome has many features that differ from genomes, such as its temporal and spatial variability, highly distinct genetic architecture and person-to-person variation. Moreover, there are various potential mechanisms by which distinct aspects of the human microbiome can relate to health outcomes. Recent advances, including next-generation sequencing and the proliferation of multi-omic data types, have enabled the exploration of the mechanisms that connect microbial communities to human health. Here, we review the ways in which features of the microbiome at various body sites can influence health outcomes, and we describe emerging opportunities and future directions for advanced microbiome epidemiology.}, }
@article {pmid36189340, year = {2022}, author = {Poroyko, V and Manuel, ER and Ilina, E}, title = {Editorial: The human microbiome: A new frontier in personalized cancer therapy.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1028120}, doi = {10.3389/fcimb.2022.1028120}, pmid = {36189340}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Neoplasms/therapy ; }, }
@article {pmid36189145, year = {2022}, author = {Kasperkiewicz, K and Świerzko, AS and Michalski, M and Eppa, &#x141; and Skurnik, M and Żuber, Z and Cedzyński, M}, title = {Antibodies Recognizing Yersinia enterocolitica Lipopolysaccharides of Various Chemotypes in Synovial Fluids From Patients With Juvenile Idiopathic Arthritis.}, journal = {Journal of immunology research}, volume = {2022}, number = {}, pages = {9627934}, pmid = {36189145}, issn = {2314-7156}, mesh = {Animals ; Antibodies/metabolism ; Antigens, Bacterial ; *Arthritis, Juvenile ; Lectins/metabolism ; Lipid A ; Lipopolysaccharides ; Mice ; O Antigens ; Synovial Fluid ; *Yersinia enterocolitica ; }, abstract = {Yersinia enterocolitica O:3 (YeO3) is considered to be associated with reactive arthritis (ReA), and its lipopolysaccharide (LPS) has been detected in synovial fluids from patients. Interestingly, YeO3 wild-type LPS was processed by host cells, resulting in truncated LPS molecules presenting the core region. Previously, we reported the immunogenicity but not adjuvanticity of YeO3 LPSs of wild (S) type, Ra, Rd, or Re chemotypes in mice. Here, we demonstrate the presence of YeO3 LPS chemotype-specific antibodies in all analyzed synovial fluids (SF) from patients with juvenile idiopathic arthritis (JIA). Interestingly, the high titer of antibodies specific for the Kdo-lipid A region was found in most tested SF. In contrast, only a few were positive for antibodies recognizing O-specific polysaccharides. Western blot analysis revealed the presence of antibodies reacting with fast-migrating LPS fractions and enterobacterial common antigen (ECA) in synovial fluid samples. Our data also suggest the importance of LPS-associated ECA for the antigenicity of endotoxin. Furthermore, we confirmed in vitro that Yersinia LPS processing leads to the exposure of its core region and enhanced potency of complement lectin pathway activation.}, }
@article {pmid36179671, year = {2022}, author = {Dohlman, AB and Klug, J and Mesko, M and Gao, IH and Lipkin, SM and Shen, X and Iliev, ID}, title = {A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors.}, journal = {Cell}, volume = {185}, number = {20}, pages = {3807-3822.e12}, pmid = {36179671}, issn = {1097-4172}, support = {R35 GM122465/GM/NIGMS NIH HHS/United States ; R01 DK121977/DK/NIDDK NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; R01 AI163007/AI/NIAID NIH HHS/United States ; R01 DK113136/DK/NIDDK NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; R01 DK119795/DK/NIDDK NIH HHS/United States ; U01 CA214300/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers ; Candida/genetics ; DNA, Fungal ; Fungi/genetics ; Humans ; *Lung Neoplasms ; *Mycobiome ; }, abstract = {Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites revealed tumor-associated mycobiomes at up to 1 fungal cell per 10[4] tumor cells. In lung cancer, Blastomyces was associated with tumor tissues. In stomach cancers, high rates of Candida were linked to the expression of pro-inflammatory immune pathways, while in colon cancers Candida was predictive of metastatic disease and attenuated cellular adhesions. Across multiple GI sites, several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival. The presence of Candida in human GI tumors was confirmed by external ITS sequencing of tumor samples and by culture-dependent analysis in an independent cohort. These data implicate the mycobiota in the pathogenesis of GI cancers and suggest that tumor-associated fungal DNA may serve as diagnostic or prognostic biomarkers.}, }
@article {pmid36175995, year = {2022}, author = {Carpén, N and Brodin, P and de Vos, WM and Salonen, A and Kolho, KL and Andersson, S and Helve, O}, title = {Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial.}, journal = {BMC pediatrics}, volume = {22}, number = {1}, pages = {565}, pmid = {36175995}, issn = {1471-2431}, mesh = {Cesarean Section/adverse effects ; Child, Preschool ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Intestines ; Milk, Human ; Pregnancy ; Randomized Controlled Trials as Topic ; }, abstract = {BACKGROUND: A complication of elective cesarean section (CS) delivery is its interference with the normal intestinal colonization of the infant, affecting the immune and metabolic signaling in early life- a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluate, in CS-delivered infants, whether the normal intestinal microbiome and its early life development can be restored by immediate postnatal transfer of maternal fecal microbiota (FMT) to the newborn, and how this procedure influences the maturation of the immune system.<br><br>METHODS: Sixty healthy mothers with planned elective CS are recruited and screened thoroughly for infections. A maternal fecal sample is taken prior to delivery and processed according to a transplantation protocol. After double blinded randomization, half of the newborns will receive a diluted aliquot of their own mother's stool orally administered in breast milk during the first feeding while the other half will be similarly treated with a placebo. The infants are clinically followed, and fecal samples are gathered weekly until the age of 4&#xa0;weeks, then at the ages of 8&#xa0;weeks, 3, 6, 12 and 24&#xa0;months. The parents fill in questionnaires until the age of 24&#xa0;months. Blood samples are taken at the age of 2-3&#xa0;days and 3, 6, 12 and 24&#xa0;months to assess development of major immune cell populations and plasma proteins throughout the first years of life.<br><br>DISCUSSION: This is the first study to assess long-time effects on the intestinal microbiome and the development of immune system of a maternal fecal transplant given to term infants born by CS.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04173208 , registration date 21.11.2019.}, }
@article {pmid36175428, year = {2022}, author = {Peters, SL and Borges, AL and Giannone, RJ and Morowitz, MJ and Banfield, JF and Hettich, RL}, title = {Experimental validation that human microbiome phages use alternative genetic coding.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5710}, pmid = {36175428}, issn = {2041-1723}, support = {R01 GM103600/GM/NIGMS NIH HHS/United States ; }, mesh = {*Bacteriophages/genetics ; Chromatography, Liquid ; Codon, Terminator ; Glutamine ; Humans ; *Microbiota/genetics ; Proteomics ; Tandem Mass Spectrometry ; }, abstract = {Previous bioinformatic analyses of metagenomic data have indicated that bacteriophages can use genetic codes different from those of their host bacteria. In particular, reassignment of stop codon TAG to glutamine (a variation known as 'genetic code 15') has been predicted. Here, we use LC-MS/MS-based metaproteomics of human fecal samples to provide experimental evidence of the use of genetic code 15 in two crAss-like phages. Furthermore, the proteomic data from several phage structural proteins supports the reassignment of the TAG stop codon to glutamine late in the phage infection cycle. Thus, our work experimentally validates the expression of genetic code 15 in human microbiome phages.}, }
@article {pmid36174236, year = {2022}, author = {Jokela, R and Korpela, K and Jian, C and Dikareva, E and Nikkonen, A and Saisto, T and Skogberg, K and de Vos, WM and Kolho, KL and Salonen, A}, title = {Quantitative insights into effects of intrapartum antibiotics and birth mode on infant gut microbiota in relation to well-being during the first year of life.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2095775}, pmid = {36174236}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents/pharmacology ; Cephalosporins ; Cesarean Section ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Monobactams ; Penicillins ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Birth mode and maternal intrapartum (IP) antibiotics affect infants' gut microbiota development, but their relative contribution to absolute bacterial abundances and infant health has not been studied. We compared the effects of Cesarean section (CS) delivery and IP antibiotics on infant gut microbiota development and well-being over the first year. We focused on 92 healthy infants born between gestational weeks 37-42 vaginally without antibiotics (N = 26), with IP penicillin (N = 13) or cephalosporin (N = 7) or by CS with IP cephalosporin (N = 33) or other antibiotics (N = 13). Composition and temporal development analysis of the gut microbiota concentrated on 5 time points during the first year of life using 16S rRNA gene amplicon sequencing, integrated with qPCR to obtain absolute abundance estimates. A mediation analysis was carried out to identify taxa linked to gastrointestinal function and discomfort (crying, defecation frequency, and signs of gastrointestinal symptoms), and birth interventions. Based on absolute abundance estimates, the depletion of Bacteroides spp. was found specifically in CS birth, while decreased bifidobacteria and increased Bacilli were common in CS birth and exposure to IP antibiotics in vaginal delivery. The abundances of numerous taxa differed between the birth modes among cephalosporin-exposed infants. Penicillin had a milder impact on the infant gut microbiota than cephalosporin. CS birth and maternal IP antibiotics had both specific and overlapping effects on infants' gut microbiota development. The resulting deviations in the gut microbiota are associated with increased defecation rate, flatulence, perceived stomach pain, and intensity of crying in infancy.}, }
@article {pmid36172175, year = {2022}, author = {Mousa, WK}, title = {The microbiome-product colibactin hits unique cellular targets mediating host-microbe interaction.}, journal = {Frontiers in pharmacology}, volume = {13}, number = {}, pages = {958012}, pmid = {36172175}, issn = {1663-9812}, abstract = {The human microbiota produces molecules that are evolved to interact with the diverse cellular machinery of both the host and microbes, mediating health and diseases. One of the most puzzling microbiome molecules is colibactin, a genotoxin encoded in some commensal and extraintestinal microbes and is implicated in initiating colorectal cancer. The colibactin cluster was discovered more than 15 years ago, and most of the research studies have been focused on revealing the biosynthesis and precise structure of the cryptic encoded molecule(s) and the mechanism of carcinogenesis. In 2022, the Balskus group revealed that colibactin not only hits targets in the eukaryotic cell machinery but also in the prokaryotic cell. To that end, colibactin crosslinks the DNA resulting in activation of the SOS signaling pathway, leading to prophage induction from bacterial lysogens and modulation of virulence genes in pathogenic species. These unique activities of colibactin highlight its ecological role in shaping gut microbial communities and further consequences that impact human health. This review dives in-depth into the molecular mechanisms underpinning colibactin cellular targets in eukaryotic and prokaryotic cells, aiming to understand the fine details of the role of secreted microbiome chemistry in mediating host-microbe and microbe-microbe interactions. This understanding translates into a better realization of microbiome potential and how this could be advanced to future microbiome-based therapeutics or diagnostic biomarkers.}, }
@article {pmid36171273, year = {2022}, author = {Oduaran, OH and Bhatt, AS}, title = {Equitable partnerships and the path to inclusive, innovative and impactful human microbiome research.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {11}, pages = {683-684}, pmid = {36171273}, issn = {1759-5053}, support = {U54 HG006938/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; }, }
@article {pmid36171082, year = {2023}, author = {Jalanka, J and Gunn, D and Singh, G and Krishnasamy, S and Lingaya, M and Crispie, F and Finnegan, L and Cotter, P and James, L and Nowak, A and Major, G and Spiller, RC}, title = {Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery.}, journal = {Gut}, volume = {72}, number = {3}, pages = {451-459}, pmid = {36171082}, issn = {1468-3288}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Humans ; Cohort Studies ; RNA, Ribosomal, 16S/genetics ; *Gastroenteritis ; *Microbiota ; *Campylobacter Infections ; *Campylobacter ; *Enteritis ; *Irritable Bowel Syndrome ; }, abstract = {OBJECTIVES: Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics.<br><br>DESIGN: A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, <40&#x2009;days) as well as 40-60&#x2009;days and >80&#x2009;days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing.<br><br>RESULTS: PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria.<br><br>CONCLUSION: The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD.<br><br>TRIAL REGISTRATION NUMBER: NCT02040922.}, }
@article {pmid36168359, year = {2022}, author = {Sheldon, JM and Alonso, N}, title = {The Therapeutic Benefits of Single and Multi-Strain Probiotics on Mean Daily Crying Time and Key Inflammatory Markers in Infantile Colic.}, journal = {Cureus}, volume = {14}, number = {8}, pages = {e28363}, pmid = {36168359}, issn = {2168-8184}, abstract = {Infantile colic is a functional gastrointestinal disorder in which a healthy infant displays paroxysms of intense crying or fussiness. Although this condition is self-limited, it causes significant distress for parents and may be linked to long-term health concerns for children. The microbiome of infants with colic has been correlated with increased dysbiosis or imbalance of commensal bacteria. This dysbiosis may ultimately lead to changes in infants' immunological profiles, favoring markers linked to inflammation, including specific cytokines, calprotectin, and genetic markers. Therapeutic regimens such as probiotics may be helpful in modifying the gut microbial composition, thereby influencing the presence of inflammatory markers and potentially reducing colic symptoms in infants. This review provides a summary of the findings from 10 randomized, placebo-controlled, double-blinded studies conducted in the past five years with the aim of examining the potential therapeutic benefits of probiotics in infantile colic. The articles were selected through PubMed and Google Scholar using the keywords infantile colic, microbiome, probiotics, cytokines, dysbiosis, inflammatory markers, and lactobacilli. We summarize the results of these studies to explore the potential anti-inflammatory therapeutic benefits of single and multi-strain probiotic formulations on daily crying time and key inflammatory markers in infants with colic. The research largely shows the beneficial role of probiotics, largely of the lactobacillus genus, in the reduction of colic symptoms and the reduction of key inflammatory markers. However, some studies demonstrated an insignificant effect of certain probiotic strains in symptom management. Further research is necessary to better understand the anti-inflammatory properties of probiotics and determine the role this could have on the manifestation of colic in infants.}, }
@article {pmid36163368, year = {2022}, author = {Yang, Q and Van Haute, M and Korth, N and Sattler, SE and Toy, J and Rose, DJ and Schnable, JC and Benson, AK}, title = {Genetic analysis of seed traits in Sorghum bicolor that affect the human gut microbiome.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {5641}, pmid = {36163368}, issn = {2041-1723}, mesh = {Crops, Agricultural ; Edible Grain/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; Polyphenols ; *Proanthocyanidins ; Seeds/genetics ; *Sorghum/genetics ; }, abstract = {Prebiotic fibers, polyphenols and other molecular components of food crops significantly affect the composition and function of the human gut microbiome and human health. The abundance of these, frequently uncharacterized, microbiome-active components vary within individual crop species. Here, we employ high throughput in vitro fermentations of pre-digested grain using a human microbiome to identify segregating genetic loci in a food crop, sorghum, that alter the composition and function of human gut microbes. Evaluating grain produced by 294 sorghum recombinant inbreds identifies 10 loci in the sorghum genome associated with variation in the abundance of microbial taxa and/or microbial metabolites. Two loci co-localize with sorghum genes regulating the biosynthesis of condensed tannins. We validate that condensed tannins stimulate the growth of microbes associated with these two loci. Our work illustrates the potential for genetic analysis to systematically discover and characterize molecular components of food crops that influence the human gut microbiome.}, }
@article {pmid36160151, year = {2022}, author = {Aboul Naga, SH and Hassan, LM and El Zanaty, RT and Refaat, M and Amin, RH and Ragab, G and Soliman, MM}, title = {Behçet uveitis: Current practice and future perspectives.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {968345}, pmid = {36160151}, issn = {2296-858X}, abstract = {Described as early as Hippocrates in his "Third Book of Endemic Diseases," Behçet's Disease (BD), also known as "The Silk Road Disease" following its initial demographics, consists of a triad of recurrent oro-genital ulcers and associated uveitis. Current demographics and rising percentages of patients seen far beyond the Silk Road in Ocular Inflammatory Disease and Uveitis Clinics list BD uveitis as one of the frontliners of non-infectious autoinflammatory eye diseases. Clinical features of BD and juvenile-onset BD are detailed alongside various approaches in classification and suggested algorithms for diagnosis that are outlined in this review. With the ongoing Human Microbiome Project and studies such as the MAMBA study, the role of the human microbiome in BD is highlighted in the pathophysiology of BD to include the current research and literature perspective. Furthermore, with the advancement of recent diagnostic and investigative techniques, especially in the field of Optical Coherence Tomography (OCT), disease-related characteristics are updated to encompass SD, EDI and OCT-angiography characteristics of BD. Having entered the era of biologic therapy, the role of various specific cytokine-blocking biologic drugs, such as TNF-α inhibitors (e.g., adalimumab, infliximab), interferon α-2a inhibitors, IL-6 and IL-1 inhibitors are presented and contrasted alongside the conventional immunosuppressant drugs and the classic old gold standard: corticosteroids (systemic or local). Finally, with the ongoing SARS-CoV-2 pandemic, it was not possible to conclude the review without reviewing the latest evidence-based literature reporting BD morbidity in this era, the observed pattern and treatment recommendations as well as those related to reported post-vaccine complications and emergence of BD.}, }
@article {pmid36157871, year = {2022}, author = {Maslennikov, R and Efremova, I and Ivashkin, V and Zharkova, M and Poluektova, E and Shirokova, E and Ivashkin, K}, title = {Effect of probiotics on hemodynamic changes and complications associated with cirrhosis: A pilot randomized controlled trial.}, journal = {World journal of hepatology}, volume = {14}, number = {8}, pages = {1667-1677}, pmid = {36157871}, issn = {1948-5182}, abstract = {BACKGROUND: Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance.<br><br>AIM: To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial.<br><br>METHODS: This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis; 24 patients received probiotics (Saccharomyces boulardii) for 3 mo, and 16 patients received a placebo over the same period. Liver function and the systemic hemodynamic status were evaluated pre- and post-intervention. Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators. Cardiac output and systemic vascular resistance were calculated.<br><br>RESULTS: Following a 3-mo course of probiotics in comparison to the control group, we observed amelioration of hyperdynamic circulation [a decrease in cardiac output (P = 0.026) and an increase in systemic vascular resistance (P = 0.026)] and systemic inflammation [a decrease in serum C-reactive protein levels (P = 0.044)], with improved liver function [an increase in serum albumin (P = 0.001) and a decrease in the value of Child-Pugh score (P = 0.001)] as well as a reduction in the severity of ascites (P = 0.022), hepatic encephalopathy (P = 0.048), and cholestasis [a decrease in serum alkaline phosphatase (P = 0.016) and serum gamma-glutamyl transpeptidase (P = 0.039) activity] and an increase in platelet counts (P < 0.001) and serum sodium level (P = 0.048).<br><br>CONCLUSION: Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.}, }
@article {pmid36155349, year = {2022}, author = {Kumari, P and Prakash, P and Yadav, S and Saran, V}, title = {Microbiome analysis: An emerging forensic investigative tool.}, journal = {Forensic science international}, volume = {340}, number = {}, pages = {111462}, doi = {10.1016/j.forsciint.2022.111462}, pmid = {36155349}, issn = {1872-6283}, mesh = {Animals ; Female ; Forensic Medicine/methods ; Humans ; *Microbiota ; Narcotics ; Saliva ; Soil ; }, abstract = {Microbial diversity's potential has been investigated in medical and therapeutic studies throughout the last few decades. However, its usage in forensics is increasing due to its effectiveness in circumstances when traditional approaches fail to provide a decisive opinion or are insufficient in forming a concrete opinion. The application of human microbiome may serve in detecting the type of stains of saliva and vaginal fluid, as well as in attributing the stains to the individual. Similarly, the microbiome makeup of a soil sample may be utilised to establish geographic origin or to associate humans, animals, or things with a specific area, additionally microorganisms influence the decay process which may be used in depicting the Time Since death. Further in detecting the traces of the amount and concentration of alcohol, narcotics, and other forensically relevant compounds in human body or visceral tissues as they also affect the microbial community within human body. Beside these, there is much more scope of microbiomes to be explored in terms of forensic investigation, this review focuses on multidimensional approaches to human microbiomes from a forensic standpoint, implying the potential of microbiomes as an emerging tool for forensic investigations such as individual variability via skin microbiomes, reconstructing crime scene, and linking evidence to individual.}, }
@article {pmid36154442, year = {2022}, author = {Saha, UB and Saroj, SD}, title = {Lactic acid bacteria: prominent player in the fight against human pathogens.}, journal = {Expert review of anti-infective therapy}, volume = {20}, number = {11}, pages = {1435-1453}, doi = {10.1080/14787210.2022.2128765}, pmid = {36154442}, issn = {1744-8336}, mesh = {Humans ; *Lactobacillales ; Lactobacillus ; *Bacterial Infections/drug therapy/microbiology ; Bacteria ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {INTRODUCTION: The human microbiome is a unique repository of diverse bacteria. Over 1000 microbial species reside in the human gut, which predominantly influences the host's internal environment and plays a significant role in host health. Lactic acid bacteria have long been employed for multiple purposes, ranging from food to medicines. Lactobacilli, which are often used in commercial food fermentation, have improved to the point that they might be helpful in medical applications.<br><br>AREAS COVERED: This review summarises various clinical and experimental evidence on efficacy of lactobacilli in treating a wide range of infections. Both laboratory based and clinical studies have been discussed.<br><br>EXPERT OPINION: Lactobacilli are widely accepted as safe biological treatments and host immune modulators (GRAS- Generally regarded as safe) by the US Food and Drug Administration and Qualified Presumption of Safety. Understanding the molecular mechanisms of lactobacilli in the treatment and pathogenicity of bacterial infections can help with the prediction and development of innovative therapeutics aimed at pathogens which have gained resistance to antimicrobials. To formulate effective lactobacilli based therapy significant research on the effectiveness of different lactobacilli strains and its association with demographic distribution is required. Also, the side effects of such therapy needs to be evaluated.}, }
@article {pmid36153116, year = {2022}, author = {White, MG and Wargo, JA}, title = {The Microbiome in Gastrointestinal Cancers.}, journal = {Gastroenterology clinics of North America}, volume = {51}, number = {3}, pages = {667-680}, pmid = {36153116}, issn = {1558-1942}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA219896/CA/NCI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, mesh = {*Gastrointestinal Neoplasms ; Humans ; Immune System ; *Microbiota ; }, abstract = {The human microbiome has been recognized as increasingly important to health and disease. This is especially prescient in the development of various cancers, their progression, and the microbiome's modulation of various anticancer therapeutics. Mechanisms behind these interactions have been increasingly well described through modulation of the host immune system as well as induction of genetic changes and local inactivation of cancer therapeutics. Here, we review these associations for a variety of gastrointestinal malignancies as well as contemporary strategies proposed to leverage these associations to improve cancer treatment outcomes.}, }
@article {pmid36151926, year = {2023}, author = {Pedro, N and Brucato, N and Cavadas, B and Lisant, V and Camacho, R and Kinipi, C and Leavesley, M and Pereira, L and Ricaut, FX}, title = {First insight into oral microbiome diversity in Papua New Guineans reveals a specific regional signature.}, journal = {Molecular ecology}, volume = {32}, number = {10}, pages = {2551-2564}, doi = {10.1111/mec.16702}, pmid = {36151926}, issn = {1365-294X}, mesh = {Humans ; Australia ; Geography ; *Microbiota/genetics ; Papua New Guinea ; *Mouth/microbiology ; }, abstract = {The oral microbiota is a highly complex and diversified part of the human microbiome. Being located at the interface between the human body and the exterior environment, this microbiota can deepen our understanding of the environmental impacts on the global status of human health. This research topic has been well addressed in Westernized populations, but these populations only represent a fraction of human diversity. Papua New Guinea hosts very diverse environments and one of the most unique human biological diversities worldwide. In this study we performed the first known characterization of the oral microbiome in 85 Papua New Guinean individuals living in different environments, using a qualitative and quantitative approach. We found a significant geographical structure of the Papua New Guineans oral microbiome, especially in the groups most isolated from urban spaces. In comparison to other global populations, two bacterial genera related to iron absorption were significantly more abundant in Papua New Guineans and Aboriginal Australians, which suggests a shared oral microbiome signature. Further studies will be needed to confirm and explore this possible regional-specific oral microbiome profile.}, }
@article {pmid36151873, year = {2022}, author = {Begum, N and Harzandi, A and Lee, S and Uhlen, M and Moyes, DL and Shoaie, S}, title = {Host-mycobiome metabolic interactions in health and disease.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2121576}, pmid = {36151873}, issn = {1949-0984}, support = {BB/S016899/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Fungi ; *Gastrointestinal Microbiome ; Humans ; Microbial Interactions ; *Microbiota ; *Mycobiome ; }, abstract = {Fungal communities (mycobiome) have an important role in sustaining the resilience of complex microbial communities and maintenance of homeostasis. The mycobiome remains relatively unexplored compared to the bacteriome despite increasing evidence highlighting their contribution to host-microbiome interactions in health and disease. Despite being a small proportion of the total species, fungi constitute a large proportion of the biomass within the human microbiome and thus serve as a potential target for metabolic reprogramming in pathogenesis and disease mechanism. Metabolites produced by fungi shape host niches, induce immune tolerance and changes in their levels prelude changes associated with metabolic diseases and cancer. Given the complexity of microbial interactions, studying the metabolic interplay of the mycobiome with both host and microbiome is a demanding but crucial task. However, genome-scale modelling and synthetic biology can provide an integrative platform that allows elucidation of the multifaceted interactions between mycobiome, microbiome and host. The inferences gained from understanding mycobiome interplay with other organisms can delineate the key role of the mycobiome in pathophysiology and reveal its role in human disease.}, }
@article {pmid36146653, year = {2022}, author = {Yutin, N and Rayko, M and Antipov, D and Mutz, P and Wolf, YI and Krupovic, M and Koonin, EV}, title = {Varidnaviruses in the Human Gut: A Major Expansion of the Order Vinavirales.}, journal = {Viruses}, volume = {14}, number = {9}, pages = {}, pmid = {36146653}, issn = {1999-4915}, support = {Intramural funds/NH/NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/genetics ; *Bacteriophages/genetics ; Capsid Proteins/genetics ; Humans ; Intestines ; Phylogeny ; Prophages/genetics ; *Viruses ; }, abstract = {Bacteriophages play key roles in the dynamics of the human microbiome. By far the most abundant components of the human gut virome are tailed bacteriophages of the realm Duplodnaviria, in particular, crAss-like phages. However, apart from duplodnaviruses, the gut virome has not been dissected in detail. Here we report a comprehensive census of a minor component of the gut virome, the tailless bacteriophages of the realm Varidnaviria. Tailless phages are primarily represented in the gut by prophages, that are mostly integrated in genomes of Alphaproteobacteria and Verrucomicrobia and belong to the order Vinavirales, which currently consists of the families Corticoviridae and Autolykiviridae. Phylogenetic analysis of the major capsid proteins (MCP) suggests that at least three new families should be established within Vinavirales to accommodate the diversity of prophages from the human gut virome. Previously, only the MCP and packaging ATPase genes were reported as conserved core genes of Vinavirales. Here we report an extended core set of 12 proteins, including MCP, packaging ATPase, and previously undetected lysis enzymes, that are shared by most of these viruses. We further demonstrate that replication system components are frequently replaced in the genomes of Vinavirales, suggestive of selective pressure for escape from yet unknown host defenses or avoidance of incompatibility with coinfecting related viruses. The results of this analysis show that, in a sharp contrast to marine viromes, varidnaviruses are a minor component of the human gut virome. Moreover, they are primarily represented by prophages, as indicated by the analysis of the flanking genes, suggesting that there are few, if any, lytic varidnavirus infections in the gut at any given time. These findings complement the existing knowledge of the human gut virome by exploring a group of viruses that has been virtually overlooked in previous work.}, }
@article {pmid36144238, year = {2022}, author = {Liu, M and Nieuwdorp, M and de Vos, WM and Rampanelli, E}, title = {Microbial Tryptophan Metabolism Tunes Host Immunity, Metabolism, and Extraintestinal Disorders.}, journal = {Metabolites}, volume = {12}, number = {9}, pages = {}, pmid = {36144238}, issn = {2218-1989}, support = {TKI-PPP Health-Holland, 2020//Top Consortia for Knowledge and Innovation (TKI-PPP) grant/ ; }, abstract = {The trillions of commensal microorganisms comprising the gut microbiota have received growing attention owing to their impact on host physiology. Recent advances in our understandings of the host-microbiota crosstalk support a pivotal role of microbiota-derived metabolites in various physiological processes, as they serve as messengers in the complex dialogue between commensals and host immune and endocrine cells. In this review, we highlight the importance of tryptophan-derived metabolites in host physiology, and summarize the recent findings on the role of tryptophan catabolites in preserving intestinal homeostasis and fine-tuning immune and metabolic responses. Furthermore, we discuss the latest evidence on the effects of microbial tryptophan catabolites, describe their mechanisms of action, and discuss how perturbations of microbial tryptophan metabolism may affect the course of intestinal and extraintestinal disorders, including inflammatory bowel diseases, metabolic disorders, chronic kidney diseases, and cardiovascular diseases.}, }
@article {pmid36143456, year = {2022}, author = {Olunoiki, E and Rehner, J and Bischoff, M and Koshel, E and Vogt, T and Reichrath, J and Becker, SL}, title = {Characteristics of the Skin Microbiome in Selected Dermatological Conditions: A Narrative Review.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {9}, pages = {}, pmid = {36143456}, issn = {2075-1729}, abstract = {The skin is the largest and outermost organ of the human body. The microbial diversity of the skin can be influenced by several variable factors such as physiological state, lifestyle, and geographical locations. Recent years have seen increased interest in research aiming at an improved understanding of the relationship between the human microbiota and several diseases. Albeit understudied, interesting correlations between the skin microbiota and several dermatological conditions have been observed. Studies have shown that a decrease or increase in the abundance of certain microbial communities can be implicated in several dermatological pathologies. This narrative review (i) examines the role of the skin microbiota in the maintenance of skin homeostasis and health, (ii) provides examples on how some common skin diseases (acne inversa, candidiasis, psoriasis) are associated with the dysbiosis of microbial communities, and (iii) describes how recent research approaches used in skin microbiome studies may lead to improved, more sensitive diagnostics and individual therapeutics in the foreseeable future.}, }
@article {pmid36142163, year = {2022}, author = {Del Chierico, F and Conta, G and Matteoli, MC and Fierabracci, A and Reddel, S and Macari, G and Gardini, S and Guarrasi, V and Levi Mortera, S and Marzano, V and Vernocchi, P and Sciubba, F and Marini, F and Deodati, A and Rapini, N and Cianfarani, S and Miccheli, A and Putignani, L}, title = {Gut Microbiota Functional Traits, Blood pH, and Anti-GAD Antibodies Concur in the Clinical Characterization of T1D at Onset.}, journal = {International journal of molecular sciences}, volume = {23}, number = {18}, pages = {}, pmid = {36142163}, issn = {1422-0067}, support = {Ricerca Corrente 2017, 2018, 2019 and 5 &#x2030; 2020, assigned to LP//Italian Ministry of Health/ ; }, mesh = {Biomarkers/metabolism ; Clostridiales/metabolism ; *Diabetes Mellitus, Type 1 ; *Gastrointestinal Microbiome ; Humans ; Hydrogen-Ion Concentration ; Isobutyrates ; Malonates ; Purines ; Pyrimidines ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and [1]H-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA1c levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D.}, }
@article {pmid36140010, year = {2022}, author = {Riva, V and Patania, G and Riva, F and Vergani, L and Crotti, E and Mapelli, F}, title = {Acinetobacter baylyi Strain BD413 Can Acquire an Antibiotic Resistance Gene by Natural Transformation on Lettuce Phylloplane and Enter the Endosphere.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {9}, pages = {}, pmid = {36140010}, issn = {2079-6382}, support = {2018-0995//Fondazione Cariplo/ ; }, abstract = {Antibiotic resistance spread must be considered in a holistic framework which comprises the agri-food ecosystems, where plants can be considered a bridge connecting water and soil habitats with the human microbiome. However, the study of horizontal gene transfer events within the plant microbiome is still overlooked. Here, the environmental strain Acinetobacter baylyi BD413 was used to study the acquisition of extracellular DNA (exDNA) carrying an antibiotic resistance gene (ARG) on lettuce phylloplane, performing experiments at conditions (i.e., plasmid quantities) mimicking those that can be found in a water reuse scenario. Moreover, we assessed how the presence of a surfactant, a co-formulant widely used in agriculture, affected exDNA entry in bacteria and plant tissues, besides the penetration and survival of bacteria into the leaf endosphere. Natural transformation frequency in planta was comparable to that occurring under optimal conditions (i.e., temperature, nutrient provision, and absence of microbial competitors), representing an entrance pathway of ARGs into an epiphytic bacterium able to penetrate the endosphere of a leafy vegetable. The presence of the surfactant determined a higher presence of culturable transformant cells in the leaf tissues but did not significantly increase exDNA entry in A. baylyi BD413 cells and lettuce leaves. More research on HGT (Horizontal Gene Transfer) mechanisms in planta should be performed to obtain experimental data on produce safety in terms of antibiotic resistance.}, }
@article {pmid36130094, year = {2022}, author = {Smith, C and Van Haute, MJ and Xian, Y and Segura Munoz, RR and Liu, S and Schmaltz, RJ and Ramer-Tait, AE and Rose, DJ}, title = {Carbohydrate utilization by the gut microbiome determines host health responsiveness to whole grain type and processing methods.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2126275}, pmid = {36130094}, issn = {1949-0984}, mesh = {Animals ; Blood Glucose ; Diet ; Edible Grain/metabolism ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Humans ; Mice ; Triticum/metabolism ; *Whole Grains ; }, abstract = {Little is known about how interactions among grain processing, grain type, and carbohydrate utilization (CU) by the microbiome influence the health benefits of whole grains. Therefore, two whole grains - brown rice and whole wheat - and two processing methods - boiling (porridge) and extrusion - were studied for their effects on host metabolic outcomes in mice harboring human microbiomes previously shown in vitro to have high or low CU. Mice carrying either microbiome experienced increases in body weight and glycemia when consuming Western diets supplemented with extruded grains versus porridge. However, mice with the high but not low CU microbiome also gained more weight and fat over time and were less glucose tolerant when consuming extruded grain diets. In high CU microbiome mice, the exacerbated negative health outcomes associated with extrusion were related to altered abundances of Lachnospiraceae and Ruminococcaceae as well as elevated sugar degradation and colonic acetate production. The amplicon sequence variants (ASVs) associated with extruded and porridge diets in this in vivo study were not the same as those identified in our prior in vitro study; however, the predicted functions were highly correlated. In conclusion, mice harboring both high and low CU microbiomes responded to the whole grain diets similarly, except the high CU microbiome mice exhibited exacerbated effects due to excessive acetate production, indicating that CU by the microbiome is linked to host metabolic health outcomes. Our work demonstrates that a greater understanding of food processing effects on the microbiome is necessary for developing foods that promote rather than diminish host health.Abbreviations: CU- carbohydrate utilization; SCFA- short-chain fatty acids; GF- germ-free; HMA, human-microbiome associated; ipGTT- intraperitoneal glucose tolerance test; HOMA-IR- Homeostatic Model Assessment for Insulin Resistance; AUC- area under the glycemia curve; ASV- amplicon sequence variant; lf- low-fat; wd- Western diet; wd_wwp- Western diet containing whole wheat porridge; wd_wwe- Western diet containing whole wheat extrudate; wd_bre- Western diet containing brown rice extrudate; wd_extr- Western diet containing either whole wheat or brown rice extrudate.}, }
@article {pmid36127929, year = {2022}, author = {Mao, J and Ma, LI}, title = {DIRICHLET-TREE MULTINOMIAL MIXTURES FOR CLUSTERING MICROBIOME COMPOSITIONS.}, journal = {The annals of applied statistics}, volume = {16}, number = {3}, pages = {1476-1499}, pmid = {36127929}, issn = {1932-6157}, support = {R01 GM135440/GM/NIGMS NIH HHS/United States ; }, abstract = {Studying the human microbiome has gained substantial interest in recent years, and a common task in the analysis of these data is to cluster microbiome compositions into subtypes. This subdivision of samples into subgroups serves as an intermediary step in achieving personalized diagnosis and treatment. In applying existing clustering methods to modern microbiome studies including the American Gut Project (AGP) data, we found that this seemingly standard task, however, is very challenging in the microbiome composition context due to several key features of such data. Standard distance-based clustering algorithms generally do not produce reliable results as they do not take into account the heterogeneity of the cross-sample variability among the bacterial taxa, while existing model-based approaches do not allow sufficient flexibility for the identification of complex within-cluster variation from cross-cluster variation. Direct applications of such methods generally lead to overly dispersed clusters in the AGP data and such phenomenon is common for other microbiome data. To overcome these challenges, we introduce Dirichlet-tree multinomial mixtures (DTMM) as a Bayesian generative model for clustering amplicon sequencing data in microbiome studies. DTMM models the microbiome population with a mixture of Dirichlet-tree kernels that utilizes the phylogenetic tree to offer a more flexible covariance structure in characterizing within-cluster variation, and it provides a means for identifying a subset of signature taxa that distinguish the clusters. We perform extensive simulation studies to evaluate the performance of DTMM and compare it to state-of-the-art model-based and distance-based clustering methods in the microbiome context, and carry out a validation study on a publicly available longitudinal data set to confirm the biological relevance of the clusters. Finally, we report a case study on the fecal data from the AGP to identify compositional clusters among individuals with inflammatory bowel disease and diabetes. Among our most interesting findings is that enterotypes (i.e., gut microbiome clusters) are not always defined by the most dominant species as previous analyses had assumed, but can involve a number of less abundant OTUs, which cannot be identified with existing distance-based and method-based approaches.}, }
@article {pmid36111766, year = {2023}, author = {Askari, H and Shojaei-Zarghani, S and Raeis-Abdollahi, E and Jahromi, HK and Abdullahi, PR and Daliri, K and Tajbakhsh, A and Rahmati, L and Safarpour, AR}, title = {The Role of Gut Microbiota in Inflammatory Bowel Disease-Current State of the Art.}, journal = {Mini reviews in medicinal chemistry}, volume = {23}, number = {13}, pages = {1376-1389}, doi = {10.2174/1389557522666220914093331}, pmid = {36111766}, issn = {1875-5607}, mesh = {Humans ; *Gastrointestinal Microbiome ; Dysbiosis/complications/microbiology ; *Inflammatory Bowel Diseases ; Inflammation/complications ; *MicroRNAs/genetics ; }, abstract = {The human microbiome comprises the genomes of the microbiota that live on and within humans, such as protozoa, archaea, eukaryotes, viruses, and most bacteria. Gastrointestinal disorders such as inflammatory bowel disease, colon cancer, celiac disease, and irritable bowel syndrome can all be triggered by a change in gut flora. The alteration of the gut microbiota (also known as "gut dysbiosis") is affected by host genetics, nutrition, antibiotics, and inflammation, and it is associated with the development of inflammatory bowel disease (IBD). Also, intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation are frequently detected in individuals with severe IBD, which may be attributed to impaired miRNA expression functions. While the exact mechanisms of how Gut Microbiota may cause IBD and intestinal epithelial dysfunction are still debated, recent data point toward the possibility that hormones, gender and miRNAs expression are modifiable contributors to IBD. This review summarizes the current evidence for an association between hormones, gender and miRNAs and Gut Microbiota in IBD and discusses potential mechanisms by which gut microbiota may impact IBD. The study also outlines critical unanswered topics that need to be solved to enhance IBD prevention and treatment in people with gut dysbiosis.}, }
@article {pmid36109637, year = {2022}, author = {Ianiro, G and Punčochář, M and Karcher, N and Porcari, S and Armanini, F and Asnicar, F and Beghini, F and Blanco-Míguez, A and Cumbo, F and Manghi, P and Pinto, F and Masucci, L and Quaranta, G and De Giorgi, S and Sciumè, GD and Bibbò, S and Del Chierico, F and Putignani, L and Sanguinetti, M and Gasbarrini, A and Valles-Colomer, M and Cammarota, G and Segata, N}, title = {Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases.}, journal = {Nature medicine}, volume = {28}, number = {9}, pages = {1913-1923}, pmid = {36109637}, issn = {1546-170X}, support = {U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; *Clostridium Infections/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols.}, }
@article {pmid36109636, year = {2022}, author = {Schmidt, TSB and Li, SS and Maistrenko, OM and Akanni, W and Coelho, LP and Dolai, S and Fullam, A and Glazek, AM and Hercog, R and Herrema, H and Jung, F and Kandels, S and Orakov, A and Thielemann, R and von Stetten, M and Van Rossum, T and Benes, V and Borody, TJ and de Vos, WM and Ponsioen, CY and Nieuwdorp, M and Bork, P}, title = {Drivers and determinants of strain dynamics following fecal microbiota transplantation.}, journal = {Nature medicine}, volume = {28}, number = {9}, pages = {1902-1912}, pmid = {36109636}, issn = {1546-170X}, mesh = {*Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome/genetics ; Gastrointestinal Tract ; Humans ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic intervention for inflammatory diseases of the gastrointestinal tract, but its clinical mode of action and subsequent microbiome dynamics remain poorly understood. Here we analyzed metagenomes from 316 FMTs, sampled pre and post intervention, for the treatment of ten different disease indications. We quantified strain-level dynamics of 1,089 microbial species, complemented by 47,548 newly constructed metagenome-assembled genomes. Donor strain colonization and recipient strain resilience were mostly independent of clinical outcomes, but accurately predictable using LASSO-regularized regression models that accounted for host, microbiome and procedural variables. Recipient factors and donor-recipient complementarity, encompassing entire microbial communities to individual strains, were the main determinants of strain population dynamics, providing insights into the underlying processes that shape the post-FMT gut microbiome. Applying an ecology-based framework to our findings indicated parameters that may inform the development of more effective, targeted microbiome therapies in the future, and suggested how patient stratification can be used to enhance donor microbiota colonization or the displacement of recipient microbes in clinical practice.}, }
@article {pmid36109427, year = {2023}, author = {Nidhi, S and Tripathi, P and Tripathi, V}, title = {Phylogenetic Analysis of Anti-CRISPR and Member Addition in the Families.}, journal = {Molecular biotechnology}, volume = {65}, number = {2}, pages = {273-281}, pmid = {36109427}, issn = {1559-0305}, mesh = {Humans ; Phylogeny ; *Bacteria/genetics ; *Bacteriophages/genetics ; Metagenome ; CRISPR-Cas Systems ; }, abstract = {CRISPR-Cas is a widespread anti-viral adaptive immune system in the microorganisms. Viruses living in bacteria or some phages carry anti-CRISPR proteins to evade immunity by CRISPR-Cas. The anti-CRISPR proteins are prevalent in phages capable of lying dormant in a CRISPR-carrying host, while their orthologs frequently found in virulent phages. Here, we propose a probabilistic strategy of ancestral sequence reconstruction (ASR) and Hidden Markov Model (HMM) profile search to fish out sequences of anti-CRISPR proteins from environmental metagenomic, human microbiome metagenomic, human microbiome reference genome, and NCBI's non-redundant databases. Our results revealed that the metagenome database dark matter might contain anti-CRISPR encoding genes.}, }
@article {pmid36108037, year = {2022}, author = {Schul, M and Mason, A and Ushijima, B and Sneed, JM}, title = {Microbiome and Metabolome Contributions to Coral Health and Disease.}, journal = {The Biological bulletin}, volume = {243}, number = {1}, pages = {76-83}, doi = {10.1086/720971}, pmid = {36108037}, issn = {1939-8697}, mesh = {Animals ; *Anthozoa ; Anti-Bacterial Agents ; Bacteria ; *Biological Products ; Humans ; Metabolome ; *Microbiota ; }, abstract = {AbstractCoral populations are declining worldwide as a result of increased environmental stressors, including disease. Coral health is greatly dependent on complex interactions between the host animal and its associated microbial symbionts. While relatively understudied, there is growing evidence that the coral microbiome contributes to the health and resilience of corals in a variety of ways, similar to more well-studied systems, such as the human microbiome. Many of these interactions are dependent upon the production and exchange of natural products, including antibacterial compounds, quorum-sensing molecules, internal signaling molecules, nutrients, and so on. While advances in sequencing, culturing, and metabolomic techniques have aided in moving forward the understanding of coral microbiome interactions, current sequence and metabolite databases are lacking, hindering detailed descriptions of the microbes and metabolites involved. This review focuses on the roles of coral microbiomes in health and disease processes of coral hosts, with special attention to the coral metabolome. We discuss what is currently known about the relationship between the coral microbiome and disease, of beneficial microbial products or services, and how the manipulation of the coral microbiome may chemically benefit the coral host against disease. Understanding coral microbiome-metabolome interactions is critical to assisting management, conservation, and restoration strategies.}, }
@article {pmid36103827, year = {2022}, author = {Wang, X and Pang, K and Wang, J and Zhang, B and Liu, Z and Lu, S and Xu, X and Zhu, L and Zhou, Z and Niu, M and Gao, J and Li, J and Zhao, F and Wu, J}, title = {Microbiota dysbiosis in primary Sjögren's syndrome and the ameliorative effect of hydroxychloroquine.}, journal = {Cell reports}, volume = {40}, number = {11}, pages = {111352}, doi = {10.1016/j.celrep.2022.111352}, pmid = {36103827}, issn = {2211-1247}, mesh = {Dysbiosis/complications/drug therapy/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Humans ; Hydroxychloroquine/pharmacology/therapeutic use ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; *Sjogren's Syndrome/complications/drug therapy ; }, abstract = {The human microbiome plays an important role in autoimmune diseases. However, there is limited knowledge regarding the microbiota in individuals with primary Sjögren's syndrome (pSS). Here, we perform 16S ribosomal RNA gene sequencing of fecal, oral, and vaginal samples from a cohort of 133 individuals with pSS, 56 with non-pSS, and 40 healthy control (HC) individuals. Dysbiosis in the gut, oral, and vaginal microbiome is evident in patients with pSS, and oral samples demonstrate the greatest extent of microbial variation. Multiple key indicator bacteria and clinical characteristics are identified across different body sites, implying that microbial dysbiosis has important roles in the pathogenesis of pSS. Furthermore, we observe pSS-like dysbiosis in individuals with pre-clinical pSS or non-pSS-related disease, revealing that microbial shifts could appear prior to pSS. After hydroxychloroquine (HCQ) treatment, microbial dysbiosis in individuals with pSS is partially resolved, although the microbiota composition remain disordered. These results contribute to the overall understanding of the relationship between the microbiome and pSS.}, }
@article {pmid36103557, year = {2022}, author = {Wikström, T and Abrahamsson, S and Bengtsson-Palme, J and Ek, J and Kuusela, P and Rekabdar, E and Lindgren, P and Wennerholm, UB and Jacobsson, B and Valentin, L and Hagberg, H}, title = {Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery.}, journal = {Clinical and translational medicine}, volume = {12}, number = {9}, pages = {e1023}, pmid = {36103557}, issn = {2001-1326}, mesh = {Bacteria ; Bodily Secretions ; *Body Fluids ; Female ; Humans ; Infant, Newborn ; Pregnancy ; *Premature Birth/epidemiology/genetics ; Transcriptome/genetics ; Vagina/microbiology ; }, abstract = {BACKGROUND: Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term.<br><br>METHODS: Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery&#xa0;<37 + 0&#xa0;weeks) two term controls were randomized (39 + 0 to 40 + 6&#xa0;weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses.<br><br>RESULTS: We found 17 human genes to be differentially expressed (false discovery rate, FDR&#xa0;<&#xa0;0.05) in the preterm group (n =&#xa0;48) compared to the term group (n =&#xa0;96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR&#xa0;<&#xa0;0.05). We found 11 individual bacterial species to be differentially expressed (FDR&#xa0;<&#xa0;0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups.<br><br>CONCLUSIONS: In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD.}, }
@article {pmid36101364, year = {2022}, author = {Loiko, N and Kanunnikov, O and Gannesen, A and Kovalenko, V and Vishnyakova, A and Axelrod, V and Litti, Y}, title = {Brain Natriuretic Peptide (BNP) Affects Growth and Stress Tolerance of Representatives of the Human Microbiome, Micrococcus luteus C01 and Alcaligenes faecalis DOS7.}, journal = {Biology}, volume = {11}, number = {7}, pages = {}, pmid = {36101364}, issn = {2079-7737}, support = {19-74-10071//Russian Science Foundation/ ; 122040800164-6//Ministry of Science and Higher Education of the Russian Federation/ ; 122040400089-6//FIC CP RAS FFZE-2022-0011/ ; }, abstract = {Brain natriuretic peptide (BNP) is secreted by the ventricles of the heart during overload to signal heart failure. Slight bilateral skin itching induced by BNP has been associated with response activity of the skin microbiota. In this work, we studied the effect of 25-250,000 pg BNP/mL on the growth, long-term survival, and stress (H2O2, antibiotics, salinity, heat and pH shock) resistance of human symbiont bacteria: Gram-positive Micrococcus luteus C01 and Gram-negative Alcaligenes faecalis DOS7. The effect of BNP turned out to be dose-dependent. Up to 250 pg BNP/mL made bacteria more stress resistant. At 2500 pg BNP/mL (heart failure) the thermosensitivity of the bacteria increased. Almost all considered BNP concentrations increased the resistance of bacteria to the action of tetracycline and ciprofloxacin. Both bacteria survived 1.3-1.7 times better during long-term (up to 4 months) storage. Our findings are important both for clinical medical practice and for practical application in other areas. For example, BNP can be used to obtain stress-resistant bacteria, which is important in the collection of microorganisms, as well as for the production of bacterial preparations and probiotics for cosmetology, agriculture, and waste management.}, }
@article {pmid36099461, year = {2022}, author = {Mangutov, EO and Alieva, AA and Kharseeva, GG and Voronina, NA and Alekseeva, LP and Evdokimova, VV and Yakusheva, OA and Popivnenko, MD}, title = {Corynebacterium spp.: relationship of pathogenic properties and antimicrobial resistance.}, journal = {Klinicheskaia laboratornaia diagnostika}, volume = {67}, number = {9}, pages = {519-524}, doi = {10.51620/0869-2084-2022-67-9-519-524}, pmid = {36099461}, issn = {0869-2084}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; *Anti-Infective Agents/pharmacology ; Corynebacterium ; *Corynebacterium Infections/drug therapy/microbiology ; Drug Resistance, Bacterial/genetics ; Humans ; }, abstract = {Corynebacterium spp. are part of the human microbiome, but can cause the development of inflammatory diseases of various localization. Purpose - to evaluate the relationship between pathogenic properties and resistance to antimicrobial drugs (AMD) of Corynebacterium spp. from patients with inflammatory diseases of the respiratory tract. Strains of Corynebacterium spp. isolated from patients with inflammatory diseases of the respiratory tract (99 pcs.) and practically healthy individuals (33 pcs.). Isolates were identified by mass spectrometric method (MALDI-ToFMS), their adhesive and invasive activity on Hep-2 cells, cytopathic effect (CPE) in CHO-K1 cell culture, and resistance to antimicrobial drugs (AMD) were determined. Indicators of adhesion (3.65±0.679(CFU±m)x102/ml), invasion (1.72±0.230 (CFU±m)x102/ml), cytotoxicity (69.1±3.8% of dead CHO-K1 cells) Corynebasterium spp. strains isolated from patients are higher (p≤0.05) than similar indicators in practically healthy people. 90.9% of isolates from patients had resistance to AMD, in most cases (57.6±4.9%) resistance to only one AMP was noted, less often to two (25.2±4.3%), three or more (8.08±2.7%). According to the results of correlation-regression analysis, pathogenic properties (adhesiveness, invasiveness, cytotoxicity) of Corynebacterium spp. strains isolated from patients are in close direct relationship with resistance to AMD. This indicates the importance of identifying strains of non-diphtheria corynebacteria resistant to AMDs, which, under the influence of developing resistance to AMDs, can increase their pathogenic potential, moving from commensalism to parasitism.}, }
@article {pmid36098525, year = {2022}, author = {Wang, Y and Guo, A and Liu, Z and Zou, Y and Zhu, W and Wu, S and Zhang, S and Guo, X and Zhang, S and Pu, L and Zhu, XQ and Zhu, G and Cai, X and Wang, S}, title = {Expansion of Opportunistic Enteric Fungal Pathogens and Occurrence of Gut Inflammation in Human Liver Echinococcosis.}, journal = {Microbiology spectrum}, volume = {10}, number = {5}, pages = {e0145322}, pmid = {36098525}, issn = {2165-0497}, mesh = {Humans ; Candida ; *Dysbiosis/microbiology ; *Echinococcosis/complications ; Feces/microbiology ; Fungi ; Inflammation ; Leukocyte L1 Antigen Complex ; Liver ; Aspergillus ; *Opportunistic Infections/microbiology ; }, abstract = {Increasing evidence shows that the gut fungal mycobiota is implicated in human disease. However, its relationship with chronic helminth infections, which cause immunosuppression and affect over 1 billion people worldwide, remains unexplored. In this study, we investigated the gut mycobiome and its associations with gut homeostasis in a severe helminth disease worldwide: liver echinococcosis. Fecal samples from 63 patients and 42 healthy controls were collected to characterize the fungal signatures using ITS1 sequencing, QIIME pipeline, and machine learning analysis. The levels of fecal calprotectin and serological anti-Saccharomyces cerevisiae antibodies (ASCA) in these subjects were experimentally measured. We found that fungal microbiota was significantly skewed in disease, with an overrepresentation of Aspergillus, Candida, Geotrichum, Kazachstania, and Penicillium and a decrease of Fusarium. Machine learning analysis revealed that the altered fungal features could efficiently predict infection with high sensitivity and specificity (area under the curve [AUC] = 0.93). The dysbiosis was characterized by expansions of multiple opportunistic pathogens (Aspergillus spp. and Candida spp.). Clinical association analysis revealed that host immunity might link to the expansions of the invasive fungi. Accompanying the opportunistic pathogen expansion, the levels of fungi-associated fecal calprotectin and serological ASCA in the patients were elevated, suggesting that gut inflammation and microbiota translocation occurred in this generally assumed extraintestinal disease. This study highlights enteric fungal pathogen expansions and increased levels of markers for fungi-associated mucosal inflammation and intestinal permeability as hallmarks of liver echinococcosis. IMPORTANCE Helminth infection affects over 1 billion people worldwide. However, its relationship with the gut mycobiome remains unknown. Among the most prevalent helminth diseases, human hydatid disease (echinococcosis) is highlighted as one of the most important (second/third for alveolar/cystic echinococcosis) foodborne parasitic diseases at the global level. Herein, we investigated the mycobiome and gut homeostasis (i.e., inflammation and permeability) in human echinococcosis. Our results revealed that fungal dysbiosis with an expansion of opportunistic pathogens and increased levels of fecal calprotectin and serum ASCA are hallmarks of human liver echinococcosis. Host immunity is associated with enteric fungal expansions. These findings suggest that an extraintestinal helminth infection is able to alter gut fungal microbiota and impair gut homeostasis, which resembles concomitant gut symptoms in inflammatory gut-related diseases (e.g., AIDS). In clinical practice, physicians need to take cautious medical consideration of gut health for nonintestinal helminth diseases.}, }
@article {pmid36094440, year = {2024}, author = {Baky, MH and Salah, M and Ezzelarab, N and Shao, P and Elshahed, MS and Farag, MA}, title = {Insoluble dietary fibers: structure, metabolism, interactions with human microbiome, and role in gut homeostasis.}, journal = {Critical reviews in food science and nutrition}, volume = {64}, number = {7}, pages = {1954-1968}, doi = {10.1080/10408398.2022.2119931}, pmid = {36094440}, issn = {1549-7852}, mesh = {Humans ; *Microbiota ; *Gastrointestinal Microbiome ; Homeostasis ; *Probiotics ; Dietary Fiber/metabolism ; }, abstract = {Consumption of food rich in dietary fibers (DFs) has been long recognized to exert an overall beneficial effect on human health. This review aims to provide a holistic overview on how IDFs impact human gut health either directly, or through modulation of the gut microbiome. Several databases were searched for collecting papers such as PubMed, Google Scholar, Web of Science, Scopus and Reaxys from 2000 till 2022. Firstly, an overview of the chemical structure of the various IDFs and the pathways employed by gut microbiota for their degradation is provided. The impact of IDFs on microbial community structure and pathogens colonization inside the human gut was discussed. Finally, the impact of IDFs on gut homeostasis and systemic effects at the cellular level, as well as the overall immunological benefits of IDFs consumption were analyzed. IDFs viz., cellulose, hemicellulose, resistant starch, and lignin found enriched in food are discussed for these effects. IDFs were found to induce gut immunity, improve intestinal integrity and mucosal proliferation, and favor adhesion of probiotics and hence improve human health. Also, IDFs were concluded to improve the bioavailability of plant polyphenols and improve their health-related functional roles. Ultimately, dietary fibers processing by modification shows potential to enhance fibers-based functional food production, in addition to increase the economic value and usage of food-rich fibers and their by-products.}, }
@article {pmid36093611, year = {2022}, author = {Korpela, K and de Vos, WM}, title = {Infant gut microbiota restoration: state of the art.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2118811}, pmid = {36093611}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents ; Cesarean Section ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Pregnancy ; }, abstract = {The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. Recent years have witnessed an accumulation of understanding of the process of the colonization and development of the gut microbiota in infants. The natural gut microbiota colonization during birth is frequently disrupted due to C-section birth or intrapartum or postpartum antibiotic exposure, and consequently aberrant gut microbiota development is common. On a positive note, research has shown that restoration of normal gut microbiota development is feasible. We discuss here the current understanding of the infant microbiota, provide an overview of the sources of disturbances, and critically evaluate the evidence on early life gut microbiota restoration for improved health outcomes by analyzing published data from infant gut microbiota restoration studies.}, }
@article {pmid36088157, year = {2022}, author = {Czibulka, A}, title = {Probiotics for Otolaryngologic Disorders.}, journal = {Otolaryngologic clinics of North America}, volume = {55}, number = {5}, pages = {939-946}, doi = {10.1016/j.otc.2022.06.003}, pmid = {36088157}, issn = {1557-8259}, mesh = {Diet ; Humans ; *Otolaryngology ; *Otorhinolaryngologic Diseases/therapy ; *Probiotics/therapeutic use ; }, abstract = {Chronic low-level inflammation is a causative factor in many of our common diseases. Switching to an anti-inflammatory diet is an important step that patients can take in for rectifying this risk factor. In this review, the author discusses the essential components of an anti-inflammatory diet and its contribution not only to the overall well-being but also to the body's defense against disease. The human microbiome is reviewed in detail and dietary connections and recommendations are explained for several otolaryngologic conditions.}, }
@article {pmid36087619, year = {2022}, author = {Wang, S and Kang, X and Alenius, H and Wong, SH and Karisola, P and El-Nezami, H}, title = {Oral exposure to Ag or TiO2 nanoparticles perturbed gut transcriptome and microbiota in a mouse model of ulcerative colitis.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {169}, number = {}, pages = {113368}, doi = {10.1016/j.fct.2022.113368}, pmid = {36087619}, issn = {1873-6351}, mesh = {Animals ; Mice ; *Colitis, Ulcerative/chemically induced/metabolism ; *Colon/drug effects/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Mice, Inbred C57BL ; RNA/metabolism ; *Silver/toxicity ; *Titanium/toxicity ; Transcriptome ; *Gastrointestinal Microbiome ; *Metal Nanoparticles/toxicity ; }, abstract = {Silver (nAg) and titanium dioxide (nTiO2) nanoparticles improve texture, flavour or anti-microbial properties of various food products and packaging materials. Despite their increased oral exposure, their potential toxicities in the dysfunctional intestine are unclear. Here, the effects of ingested nAg or nTiO2 on inflamed colon were revealed in a mouse model of chemical-induced acute ulcerative colitis. Mice (eight/group) were exposed to nAg or nTiO2 by oral gavage for 10 consecutive days. We characterized disease phenotypes, histology, and alterations in colonic transcriptome (RNA sequencing) and gut microbiome (16S sequencing). Oral exposure to nAg caused only minor changes in phenotypic hallmarks of colitic mice but induced extensive responses in gene expression enriching processes of apoptotic cell death and RNA metabolism. Instead, ingested nTiO2 yielded shorter colon, aggravated epithelial hyperplasia and deeper infiltration of inflammatory cells. Both nanoparticles significantly changed the gut microbiota composition, resulting in loss of diversity and increase of potential pathobionts. They also increased colonic mucus and abundance of Akkermansia muciniphila. Overall, nAg and nTiO2 induce dissimilar immunotoxicological changes at the molecular and microbiome level in the context of colon inflammation. The results provide valuable information for evaluation of utilizing metallic nanoparticles in food products for the vulnerable population.}, }
@article {pmid36084152, year = {2022}, author = {Pinto, S and Benincà, E and van Nes, EH and Scheffer, M and Bogaards, JA}, title = {Species abundance correlations carry limited information about microbial network interactions.}, journal = {PLoS computational biology}, volume = {18}, number = {9}, pages = {e1010491}, pmid = {36084152}, issn = {1553-7358}, mesh = {Bacteria ; Cross-Sectional Studies ; Humans ; *Microbial Interactions ; *Microbiota ; Phylogeny ; }, abstract = {Unraveling the network of interactions in ecological communities is a daunting task. Common methods to infer interspecific interactions from cross-sectional data are based on co-occurrence measures. For instance, interactions in the human microbiome are often inferred from correlations between the abundances of bacterial phylogenetic groups across subjects. We tested whether such correlation-based methods are indeed reliable for inferring interaction networks. For this purpose, we simulated bacterial communities by means of the generalized Lotka-Volterra model, with variation in model parameters representing variability among hosts. Our results show that correlations can be indicative for presence of bacterial interactions, but only when measurement noise is low relative to the variation in interaction strengths between hosts. Indication of interaction was affected by type of interaction network, process noise and sampling under non-equilibrium conditions. The sign of a correlation mostly coincided with the nature of the strongest pairwise interaction, but this is not necessarily the case. For instance, under rare conditions of identical interaction strength, we found that competitive and exploitative interactions can result in positive as well as negative correlations. Thus, cross-sectional abundance data carry limited information on specific interaction types. Correlations in abundance may hint at interactions but require independent validation.}, }
@article {pmid36078075, year = {2022}, author = {Bachmann, R and Van Hul, M and Baldin, P and Léonard, D and Delzenne, NM and Belzer, C and Ouwerkerk, JP and Repsilber, D and Rangel, I and Kartheuser, A and Brummer, RJ and De Vos, WM and Cani, PD}, title = {Akkermansia muciniphila Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism.}, journal = {Cells}, volume = {11}, number = {17}, pages = {}, pmid = {36078075}, issn = {2073-4409}, mesh = {*Akkermansia ; Animals ; Colon/microbiology/pathology ; Humans ; Mice ; *Myeloid Differentiation Factor 88/metabolism ; *Peritonitis/metabolism/therapy ; Pilot Projects ; Verrucomicrobia/metabolism ; *Wound Healing/genetics/physiology ; }, abstract = {Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. Akkermansia muciniphila has shown beneficial effects on the gut barrier function. Whether A. muciniphila reduces peritonitis and mortality during colonic leakage is unknown. Whether A. muciniphila can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live A. muciniphila prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to A. muciniphila for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, A.-muciniphila-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to A. muciniphila exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. A. muciniphila improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of A. muciniphila is well tolerated and changes the expression of genes involved in the immune pathways.}, }
@article {pmid36073919, year = {2022}, author = {Wang, YR and Zhu, T and Kong, FQ and Duan, YY and Galzote, C and Quan, ZX}, title = {Infant Mode of Delivery Shapes the Skin Mycobiome of Prepubescent Children.}, journal = {Microbiology spectrum}, volume = {10}, number = {5}, pages = {e0226722}, pmid = {36073919}, issn = {2165-0497}, mesh = {Infant ; Infant, Newborn ; Child ; Female ; Pregnancy ; Humans ; Aged ; *Mycobiome ; *Microbiota ; Skin/microbiology ; Candida ; Fungi/genetics ; }, abstract = {Characterizing the skin mycobiome is necessary to define its association with the host immune system, particularly in children. In this study, we describe the skin mycobiome on the face, ventral forearm, and calf of 72 prepubescent children (aged 1 to 10 years) and their mothers, based on internal transcribed spacer (ITS) amplicon sequencing. The age and delivery mode at birth are the most influential factors shaping the skin mycobiome. Compared with that of the vaginally born children, the skin mycobiome of caesarean-born children is assembled by predominantly deterministic niche-based processes and exhibits a more fragile microbial network at all three sampling sites. Moreover, vaginal delivery leads to clearer intra- and interindividual specialization of fungal structures with increasing age; this phenomenon is not observed in caesarean-born children. The maternal correlation with children also differs based on the mode of delivery; specifically, the mycobiomes of vaginally born children at younger ages are more strongly correlated with vagina-associated fungal genera (Candida and Rhodotorula), whereas those of caesarean-delivered children at elder age include more skin-associated and airborne fungal genera (Malassezia and Alternaria). Based on this ecological framework, our results suggest that the delivery mode is significantly associated with maturation of the skin fungal community in children. IMPORTANCE Human skin is permanently colonized by microbes starting at birth. The hygiene hypothesis suggests that a lack of early-life immune imprinting weakens the body's resilience against atopic disorders later in life. To better understand fungal colonization following early-life periods affected by interruption, we studied the skin mycobiomes of 73 children and their mothers. Our results suggest a differentiation of the skin mycobiomes between caesarean-born and vaginally born children. Caesarean-born children exhibit a mycobiome structure with more fitted deterministic niche-based processes, a fragile network, and an unchanged microbial dissimilarity over time. In vaginally born children, this dissimilarity increases with age. The results indicate that initial microbial colonization has a long-term impact on a child's skin mycobiome. We believe that these findings will inspire further investigations of the "hygiene hypothesis" in the human microbiome, especially in providing novel insights into influences on the development of the early-life microbiome.}, }
@article {pmid36071979, year = {2022}, author = {Piazzesi, A and Putignani, L}, title = {Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {958346}, pmid = {36071979}, issn = {1664-302X}, abstract = {Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.}, }
@article {pmid36069455, year = {2022}, author = {Maringanti, VS and Bucci, V and Gerber, GK}, title = {MDITRE: Scalable and Interpretable Machine Learning for Predicting Host Status from Temporal Microbiome Dynamics.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0013222}, pmid = {36069455}, issn = {2379-5077}, support = {R01 GM130777/GM/NIGMS NIH HHS/United States ; 1R01GM130777//HHS | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Machine Learning ; Software ; Metagenomics/methods ; }, abstract = {Longitudinal microbiome data sets are being generated with increasing regularity, and there is broad recognition that these studies are critical for unlocking the mechanisms through which the microbiome impacts human health and disease. However, there is a dearth of computational tools for analyzing microbiome time-series data. To address this gap, we developed an open-source software package, Microbiome Differentiable Interpretable Temporal Rule Engine (MDITRE), which implements a new highly efficient method leveraging deep-learning technologies to derive human-interpretable rules that predict host status from longitudinal microbiome data. Using semi-synthetic and a large compendium of publicly available 16S rRNA amplicon and metagenomics sequencing data sets, we demonstrate that in almost all cases, MDITRE performs on par with or better than popular uninterpretable machine learning methods, and orders-of-magnitude faster than the prior interpretable technique. MDITRE also provides a graphical user interface, which we show through case studies can be used to derive biologically meaningful interpretations linking patterns of microbiome changes over time with host phenotypes. IMPORTANCE The human microbiome, or collection of microbes living on and within us, changes over time. Linking these changes to the status of the human host is crucial to understanding how the microbiome influences a variety of human diseases. Due to the large scale and complexity of microbiome data, computational methods are essential. Existing computational methods for linking changes in the microbiome to the status of the human host are either unable to scale to large and complex microbiome data sets or cannot produce human-interpretable outputs. We present a new computational method and software package that overcomes the limitations of previous methods, allowing researchers to analyze larger and more complex data sets while producing easily interpretable outputs. Our method has the potential to enable new insights into how changes in the microbiome over time maintain health or lead to disease in humans and facilitate the development of diagnostic tests based on the microbiome.}, }
@article {pmid36068280, year = {2022}, author = {Kaiyrlykyzy, A and Kozhakhmetov, S and Babenko, D and Zholdasbekova, G and Alzhanova, D and Olzhayev, F and Baibulatova, A and Kushugulova, AR and Askarova, S}, title = {Study of gut microbiota alterations in Alzheimer's dementia patients from Kazakhstan.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {15115}, pmid = {36068280}, issn = {2045-2322}, mesh = {Aged ; *Alzheimer Disease ; Bacteria/genetics ; Bacteroides/genetics ; Faecalibacterium/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Humans ; Kazakhstan ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {We have investigated the diversity and composition of gut microbiotas isolated from AD (Alzheimer's disease) patients (n = 41) and healthy seniors (n = 43) from Nur-Sultan city (Kazakhstan). The composition of the gut microbiota was characterized by 16S ribosomal RNA sequencing. Our results demonstrated significant differences in bacterial abundance at phylum, class, order, and genus levels in AD patients compared to healthy aged individuals. Relative abundance analysis has revealed increased amount of taxa belonging to Acidobacteriota, Verrucomicrobiota, Planctomycetota and Synergistota phyla in AD patients. Among bacterial genera, microbiotas of AD participants were characterized by a decreased amount of Bifidobacterium, Clostridia bacterium, Castellaniella, Erysipelotrichaceae UCG-003, Roseburia, Tuzzerella, Lactobacillaceae and Monoglobus. Differential abundance analysis determined enriched genera of Christensenellaceae R-7 group, Prevotella, Alloprevotella, Eubacterium coprostanoligenes group, Ruminococcus, Flavobacterium, Ohtaekwangia, Akkermansia, Bacteroides sp. Marseille-P3166 in AD patients, whereas Levilactobacillus, Lactiplantibacillus, Tyzzerella, Eubacterium siraeum group, Monoglobus, Bacteroides, Erysipelotrichaceae UCG-003, Veillonella, Faecalibacterium, Roseburia, Haemophilus were depleted. We have also found correlations between some bacteria taxa and blood serum biochemical parameters. Adiponectin was correlated with Acidimicrobiia, Faecalibacterium, Actinobacteria, Oscillospiraceae, Prevotella and Christensenellaceae R-7. The Christensenellaceae R-7 group and Acidobacteriota were correlated with total bilirubin, while Firmicutes, Acidobacteriales bacterium, Castellaniella alcaligenes, Lachnospiraceae, Christensenellaceae and Klebsiella pneumoniae were correlated with the level of CRP in the blood of AD patients. In addition, we report the correlations found between disease severity and certain fecal bacteria. This is the first reported study demonstrating gut microbiota alterations in AD in the Central Asian region.}, }
@article {pmid36063358, year = {2023}, author = {Piazzesi, A and Putignani, L}, title = {Impact of helminth-microbiome interactions on childhood health and development-A clinical perspective.}, journal = {Parasite immunology}, volume = {45}, number = {4}, pages = {e12949}, doi = {10.1111/pim.12949}, pmid = {36063358}, issn = {1365-3024}, mesh = {Animals ; Child ; Humans ; *Helminths ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Humans have co-existed with parasites for virtually the entirety of our existence as a species. Today, nearly one third of the human population is infected with at least one helminthic species, most of which reside in the intestinal tract, where they have co-evolved alongside the human gut microbiota (GM). Appreciation for the interconnected relationship between helminths and GM has increased in recent years. Here, we review the evidence of how helminths and GM can influence various aspects of childhood development and the onset of paediatric diseases. We discuss the emerging evidence of how many of the changes that parasitic worms inflict on their host is enacted through gut microbes. In this light, we argue that helminth-induced microbiota modifications are of great importance in both facing the global challenge of overcoming parasitic infections, and in replicating helminthic protective effects against inflammatory diseases. We propose that deepening our knowledge of helminth-microbiota interactions will uncover novel, safer and more effective therapeutic strategies in combatting an array of childhood disorders.}, }
@article {pmid36059540, year = {2022}, author = {Puhlmann, ML and de Vos, WM}, title = {Intrinsic dietary fibers and the gut microbiome: Rediscovering the benefits of the plant cell matrix for human health.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {954845}, pmid = {36059540}, issn = {1664-3224}, mesh = {Dietary Fiber/metabolism ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/metabolism ; Humans ; Plant Cells/metabolism ; Plants/metabolism ; }, abstract = {Dietary fibers contribute to structure and storage reserves of plant foods and fundamentally impact human health, partly by involving the intestinal microbiota, notably in the colon. Considerable attention has been given to unraveling the interaction between fiber type and gut microbiota utilization, focusing mainly on single, purified fibers. Studying these fibers in isolation might give us insights into specific fiber effects, but neglects how dietary fibers are consumed daily and impact our digestive tract: as intrinsic structures that include the cell matrix and content of plant tissues. Like our ancestors we consume fibers that are entangled in a complex network of plants cell walls that further encapsulate and shield intra-cellular fibers, such as fructans and other components from immediate breakdown. Hence, the physiological behavior and consequent microbial breakdown of these intrinsic fibers differs from that of single, purified fibers, potentially entailing unexplored health effects. In this mini-review we explain the difference between intrinsic and isolated fibers and discuss their differential impact on digestion. Subsequently, we elaborate on how food processing influences intrinsic fiber structure and summarize available human intervention studies that used intrinsic fibers to assess gut microbiota modulation and related health outcomes. Finally, we explore current research gaps and consequences of the intrinsic plant tissue structure for future research. We postulate that instead of further processing our already (extensively) processed foods to create new products, we should minimize this processing and exploit the intrinsic health benefits that are associated with the original cell matrix of plant tissues.}, }
@article {pmid36053959, year = {2022}, author = {Pepe, J and Rossi, M and Battafarano, G and Vernocchi, P and Conte, F and Marzano, V and Mariani, E and Mortera, SL and Cipriani, C and Rana, I and Buonuomo, PS and Bartuli, A and De Martino, V and Pelle, S and Pascucci, L and Toniolo, RM and Putignani, L and Minisola, S and Del Fattore, A}, title = {Characterization of Extracellular Vesicles in Osteoporotic Patients Compared to Osteopenic and Healthy Controls.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {37}, number = {11}, pages = {2186-2200}, pmid = {36053959}, issn = {1523-4681}, mesh = {Humans ; Female ; Leukocytes, Mononuclear/metabolism ; Proteomics ; *Extracellular Vesicles/metabolism ; *MicroRNAs/genetics/metabolism ; Biomarkers/metabolism ; }, abstract = {Extracellular vesicles (EVs) are mediators of a range of pathological conditions. However, their role in bone loss disease has not been well understood. In this study we characterized plasma EVs of 54 osteoporotic (OP) postmenopausal women compared to 48 osteopenic (OPN) and 44 healthy controls (CN), and we investigated their effects on osteoclasts and osteoblasts. We found no differences between the three groups in terms of anthropometric measurements and biochemical evaluation of serum calcium, phosphate, creatinine, PTH, 25-hydroxy vitamin D and bone biomarkers, except for an increase of CTX level in OP group. FACS analysis revealed that OP patients presented a significantly increased number of EVs and RANKL[+] EVs compared with both CN and OPN subjects. Total EVs are negatively associated with the lumbar spine T-score and femoral neck T-score. Only in the OPN patients we observed a positive association between the total number of EVs and RANKL[+] EVs with the serum RANKL. In vitro studies revealed that OP EVs supported osteoclastogenesis of healthy donor peripheral blood mononuclear cells at the same level observed following RANKL and M-CSF treatment, reduced the ability of mesenchymal stem cells to differentiate into osteoblasts, while inducing an increase of OSTERIX and RANKL expression in mature osteoblasts. The analysis of miRNome revealed that miR-1246 and miR-1224-5p were the most upregulated and downregulated in OP EVs; the modulated EV-miRNAs in OP and OPN compared to CN are related to osteoclast differentiation, interleukin-13 production and regulation of canonical WNT pathway. A proteomic comparison between OPN and CN EVs evidenced a decrease in fibrinogen, vitronectin, and clusterin and an increase in coagulation factors and apolipoprotein, which was also upregulated in OP EVs. Interestingly, an increase in RANKL[+] EVs and exosomal miR-1246 was also observed in samples from patients affected by Gorham-Stout disease, suggesting that EVs could be good candidate as bone loss disease biomarkers. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).}, }
@article {pmid36053301, year = {2022}, author = {Frost, F}, title = {[Introduction to the microbiome].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {63}, number = {10}, pages = {1015-1021}, pmid = {36053301}, issn = {2731-7099}, mesh = {Bacteria ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Obesity/therapy ; }, abstract = {The human body is colonized by a multitude of different microbes that are collectively referred to as the human microbiome. Gut microbes account for the largest proportion of these. They constitute a barrier against foreign pathogens, carry out important metabolic functions and regulate the immune system, thereby making them essential for the maintenance of health. The most important determinants of the gut microbiome structure in the general population include exocrine pancreatic function, genetics, nutrition, age, sex, and obesity. Changes in the gut microbiome have also been linked to a variety of diseases not limited to gastrointestinal disorders. Typical microbiome changes in disease include a loss of diversity and beneficial bacteria or an increase in opportunistic pathogens. This may result in a proinflammatory and unstable microbiome. Knowledge about the microbiome is rapidly increasing and microbiome modulation therapies have already been implemented in clinical practice. Therefore, basic knowledge about the microbiome is essential for all medical professionals in order for them to advise and treat their patients properly.}, }
@article {pmid36051769, year = {2022}, author = {Yu, Y and Wen, H and Li, S and Cao, H and Li, X and Ma, Z and She, X and Zhou, L and Huang, S}, title = {Emerging microfluidic technologies for microbiome research.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {906979}, pmid = {36051769}, issn = {1664-302X}, abstract = {The importance of the microbiome is increasingly prominent. For example, the human microbiome has been proven to be strongly associated with health conditions, while the environmental microbiome is recognized to have a profound influence on agriculture and even the global climate. Furthermore, the microbiome can serve as a fascinating reservoir of genes that encode tremendously valuable compounds for industrial and medical applications. In the past decades, various technologies have been developed to better understand and exploit the microbiome. In particular, microfluidics has demonstrated its strength and prominence in the microbiome research. By taking advantage of microfluidic technologies, inherited shortcomings of traditional methods such as low throughput, labor-consuming, and high-cost are being compensated or bypassed. In this review, we will summarize a broad spectrum of microfluidic technologies that have addressed various needs in the field of microbiome research, as well as the achievements that were enabled by the microfluidics (or technological advances). Finally, how microfluidics overcomes the limitations of conventional methods by technology integration will also be discussed.}, }
@article {pmid36050385, year = {2022}, author = {Hoegenauer, C and Hammer, HF and Mahnert, A and Moissl-Eichinger, C}, title = {Methanogenic archaea in the human gastrointestinal tract.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {12}, pages = {805-813}, pmid = {36050385}, issn = {1759-5053}, support = {P 32697/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Humans ; *Archaea/physiology ; *Euryarchaeota ; Gastrointestinal Tract/microbiology ; Methane ; Bacteria ; }, abstract = {The human microbiome is strongly interwoven with human health and disease. Besides bacteria, viruses and eukaryotes, numerous archaea are located in the human gastrointestinal tract and are responsible for methane production, which can be measured in clinical methane breath analyses. Methane is an important readout for various diseases, including intestinal methanogen overgrowth. Notably, the archaea responsible for methane production are largely overlooked in human microbiome studies due to their non-bacterial biology and resulting detection issues. As such, their importance for health and disease remains largely unclear to date, in particular as not a single archaeal representative has been deemed to be pathogenic. In this Perspective, we discuss the current knowledge on the clinical relevance of methanogenic archaea. We explain the archaeal unique response to antibiotics and their negative and positive effects on human physiology, and present the current understanding of the use of methane as a diagnostic marker.}, }
@article {pmid36048299, year = {2022}, author = {Yi, B and Chen, H}, title = {Power law analysis of the human milk microbiome.}, journal = {Archives of microbiology}, volume = {204}, number = {9}, pages = {585}, pmid = {36048299}, issn = {1432-072X}, support = {GREKF21-06//Key Laboratory of Microbial Resources and Drug Development in Guizhou Province/ ; 202001BA070001-100//Applied Basic Research Foundation of Yunnan Province/ ; A0604//National Science and Technology Planning Project/ ; 202101BA070001-018//Yunnan Province Local University (Part) Basic Research for Youths/ ; }, mesh = {Ecology ; Female ; Humans ; *Microbiota ; *Milk, Human ; Models, Biological ; }, abstract = {The human breast milk microbiome (HMM) has far reached health implications for both mothers and infants, and understanding the structure and dynamics of milk microbial communities is therefore of critical biomedical importance. Community heterogeneity, which has certain commonalities with familiar diversity but also with certain fundamental differences, is an important aspect of community structure and dynamics. Taylor's (1961) power law (TPL) (Nature, 1961) was discovered to govern the mean-variance power function relationship of population abundances and can be used to characterize population spatial aggregation (heterogeneity) and/or temporal stability. TPL was further extended to the community level to measure community spatial heterogeneity and/or temporal stability (Ma 2015, Molecular Ecology). Here, we applied TPL extensions (TPLE) to analyze the heterogeneity of the human milk microbiome by reanalyzing 12 datasets (2115 samples) of the healthy human milk microbiome. Our analysis revealed that the TPLE heterogeneity parameter (b) is rather stable across the 12 datasets, and there were approximately no statistically significant differences among ¾ of the datasets, which is consistent with the hypothesis that the heterogeneity scaling (i.e., change across individuals) of the human microbiome, including HMM, is rather stable or even constant. For this, we built a TPLE model for the pooled 12 datasets (b = 1.906), which can therefore represent the scaling rate of community-level spatial heterogeneity of HMM across individuals. Similarly, we also analyzed mixed-species ("averaged virtual species") level heterogeneity of HMM, and it was found that the mixed-species level heterogeneity was smaller than the heterogeneity at the previously mentioned community level (1.620 vs. 1.906).}, }
@article {pmid36047711, year = {2023}, author = {Stefanaki, E and Kalaitzidou, I and Aristou, M and Lakoumentas, J and Galanakis, E and Xepapadaki, P}, title = {Prenatal antibiotic exposure increases the risk of infant atopic dermatitis: data from a Greek cohort.}, journal = {European annals of allergy and clinical immunology}, volume = {55}, number = {6}, pages = {271-277}, doi = {10.23822/EurAnnACI.1764-1489.266}, pmid = {36047711}, issn = {1764-1489}, mesh = {Child ; Infant ; Humans ; Female ; Pregnancy ; Male ; *Dermatitis, Atopic/diagnosis/epidemiology ; Greece/epidemiology ; Anti-Bacterial Agents/adverse effects ; Cesarean Section/adverse effects ; *Prenatal Exposure Delayed Effects/epidemiology ; Risk Factors ; *Food Hypersensitivity/epidemiology ; }, abstract = {Background. The human microbiome is important due to the impact it has on host immunologic development and allergy-associated diseases. This study aimed to investigate the impact of prenatal exposure to antibiotics on the incidence of atopic dermatitis (AD) in children at 18 months of age. Methods. Mothers were interviewed at baseline, in the maternity ward and by phone questionnaire after 18 months. Demographic data, mode of delivery, yoghurt consumption, antibiotic and other drug use during pregnancy, atopic history, diagnosis of AD and history of infections in the offspring were noted. Results. 385 mothers were interviewed at baseline. 231 (60%) mothers with 236 children responded at follow up. Cesarean section was reported in 116 (50.2%) deliveries while antibiotic use during pregnancy in 55/231 (23.8%) women. 43/236 (18.22%) infants were diagnosed with AD. Intravenous antibiotic use was associated with a 7.7 increased risk of AD diagnosis in the offspring (95%CI 1.23-48.27, p = 0.029). An increased odd for AD was recorded for mothers 30-40 years of age (OR 4.50, 95%CI 1.08-18.7, p = 0.039). No significant association between cesarean section and AD (p = 0.70) was recorded. In multivariate analysis, reported food allergy (OR 8.03, 95%CI 2.30-27.97, p = 0.001) and otitis media episodes in children (OR 3.76, 95%CI 1.60-8.83, p = 0.002) were significantly associated with AD diagnosis. Conclusions. An increased risk of AD was recorded only when antibiotics were given prenatally by intravenous route and in women between 30-40 years of age. Children with food allergy had an increased risk for AD. The relatively high percentage of cesarean sections was not a risk factor for AD.}, }
@article {pmid36046741, year = {2022}, author = {Nie, F and Wang, L and Huang, Y and Yang, P and Gong, P and Feng, Q and Yang, C}, title = {Characteristics of Microbial Distribution in Different Oral Niches of Oral Squamous Cell Carcinoma.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {905653}, pmid = {36046741}, issn = {2235-2988}, mesh = {Bacteria/genetics ; *Carcinoma, Squamous Cell ; *Head and Neck Neoplasms ; Humans ; *Microbiota ; *Mouth Neoplasms/diagnosis ; Squamous Cell Carcinoma of Head and Neck ; }, abstract = {Oral squamous cell carcinoma (OSCC), one of the most common malignant tumors of the head and neck, is closely associated with the presence of oral microbes. However, the microbiomes of different oral niches in OSCC patients and their association with OSCC have not been adequately characterized. In this study, 305 samples were collected from 65 OSCC patients, including tumor tissue, adjacent normal tissue (paracancerous tissue), cancer surface tissue, anatomically matched contralateral normal mucosa, saliva, and tongue coat. 16S ribosomal DNA (16S rDNA) sequencing was used to compare the microbial composition, distribution, and co-occurrence network of different oral niches. The association between the microbiome and the clinical features of OSCC was also characterized. The oral microbiome of OSCC patients showed a regular ecological distribution. Tumor and paracancerous tissues were more microbially diverse than other oral niches. Cancer surface, contralateral normal mucosa, saliva, and tongue coat showed similar microbial compositions, especially the contralateral normal mucosa and saliva. Periodontitis-associated bacteria of the genera Fusobacterium, Prevotella, Porphyromonas, Campylobacter, and Aggregatibacter, and anaerobic bacteria were enriched in tumor samples. The microbiome was highly correlated with tumor clinicopathological features, with several genera (Lautropia, Asteroleplasma, Parvimonas, Peptostreptococcus, Pyramidobacter, Roseburia, and Propionibacterium) demonstrating a relatively high diagnostic power for OSCC metastasis, potentially providing an indicator for the development of OSCC.}, }
@article {pmid36040412, year = {2023}, author = {Höyhtyä, M and Korpela, K and Saqib, S and Junkkari, S and Nissilä, E and Nikkonen, A and Dikareva, E and Salonen, A and de Vos, WM and Kolho, KL}, title = {Quantitative Fecal Microbiota Profiles Relate to Therapy Response During Induction With Tumor Necrosis Factor α Antagonist Infliximab in Pediatric Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {29}, number = {1}, pages = {116-124}, pmid = {36040412}, issn = {1536-4844}, mesh = {Humans ; Child ; Infliximab/therapeutic use ; Tumor Necrosis Factor-alpha ; Tumor Necrosis Factor Inhibitors ; *Inflammatory Bowel Diseases/drug therapy ; Feces/chemistry ; *Microbiota ; Leukocyte L1 Antigen Complex/analysis ; }, abstract = {BACKGROUND: The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease.<br><br>METHODS: We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children's Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value <100 &#xb5;g/g at week 6. Intestinal microbiota were analyzed by 16S ribosomal RNA gene amplicon sequencing using the Illumina MiSeq platform. We analyzed total bacterial counts using quantitative polymerase chain reaction and transformed the relative abundances into absolute abundances based on the total counts.<br><br>RESULTS: At baseline, the intestinal microbiota in the treatment responsive group (n&#x2005;=&#x2005;10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n&#x2005;=&#x2005;19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline.<br><br>CONCLUSIONS: High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes.}, }
@article {pmid36037921, year = {2022}, author = {Nava, AR and Daneshian, L and Sarma, H}, title = {Antibiotic resistant genes in the environment-exploring surveillance methods and sustainable remediation strategies of antibiotics and ARGs.}, journal = {Environmental research}, volume = {215}, number = {Pt 1}, pages = {114212}, doi = {10.1016/j.envres.2022.114212}, pmid = {36037921}, issn = {1096-0953}, mesh = {Animals ; *Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Genes, Bacterial ; Humans ; Wastewater/analysis ; *Water Pollutants, Chemical ; }, abstract = {Antibiotic Resistant Genes (ARGs) are an emerging environmental health threat due to the potential change in the human microbiome and selection for the emergence of antibiotic resistant bacteria. The rise of antibiotic resistant bacteria has caused a global health burden. The WHO (world health organization) predicts a rise in deaths due to antibiotic resistant infections. Since bacteria can acquire ARGs through horizontal transmission, it is important to assess the dissemination of antibioticresistant genes from anthropogenic sources. There are several sources of antibiotics, antibiotic resistant bacteria and genes in the environment. These include wastewater treatment plants, landfill leachate, agricultural, animal industrial sources and estuaries. The use of antibiotics is a worldwide practice that has resulted in the evolution of resistance to antibiotics. Our review provides a more comprehensive look into multiple sources of ARG's and antibiotics rather than one. Moreover, we focus on effective surveillance methods of ARGs and antibiotics and sustainable abiotic and biotic remediation strategies for removal and reduction of antibiotics and ARGs from both terrestrial and aquatic environments. Further, we consider the impact on public health as this problem cannot be addressed without a global transdisciplinary effort.}, }
@article {pmid36014376, year = {2022}, author = {Jo, H and Kim, SY and Kang, BH and Baek, C and Kwon, JE and Jeang, JW and Heo, YM and Kim, HB and Heo, CY and Kang, SM and Shin, BH and Nam, DY and Lee, YG and Kang, SC and Lee, DG}, title = {Staphylococcus epidermidis Cicaria, a Novel Strain Derived from the Human Microbiome, and Its Efficacy as a Treatment for Hair Loss.}, journal = {Molecules (Basel, Switzerland)}, volume = {27}, number = {16}, pages = {}, pmid = {36014376}, issn = {1420-3049}, mesh = {Adenosine ; Alopecia ; Biotin ; Hair Follicle ; Humans ; *Microbiota ; *Staphylococcus epidermidis ; }, abstract = {The skin tissue of the scalp is unique from other skin tissues because it coexists with hair, and many differences in microbial composition have been confirmed. In scalp tissues, hair loss occurs due to a combination of internal and external factors, and several studies are being conducted to counteract this. However, not many studies have addressed hair loss from the perspective of the microbiome. In this study, subjects with hair loss and those with normal scalps were set as experimental and control groups, respectively. In the experimental group, hair loss had progressed, and there was a large difference in microbiome composition compared to the group with normal scalps. In particular, differences in Accumulibacter, Staphylococcus, and Corynebacterium were found. From Staphylococcus epidermidis Cicaria, two active components were isolated as a result of repeated column chromatography. Spectroscopic data led to the determination of chemical structures for adenosine and biotin. Fractions were obtained, and ex vivo tests were conducted using hair follicles derived from human scalp tissue. When the microbiome adenosine-treated group was compared to the control group, hair follicle length was increased, and hair root diameter was maintained during the experimental periods. In addition, the Cicaria culture medium and the microbial adenosine- and biotin-treated groups maintained the anagen phase, reducing progression to the catagen phase in the hair growth cycle. In conclusion, it was confirmed that the Cicaria culture medium and the microbial adenosine and biotin derived from the culture were effective in inhibiting hair loss.}, }
@article {pmid36014023, year = {2022}, author = {Ouwerkerk, JP and Tytgat, HLP and Elzinga, J and Koehorst, J and Van den Abbeele, P and Henrissat, B and Gueimonde, M and Cani, PD and Van de Wiele, T and Belzer, C and de Vos, WM}, title = {Comparative Genomics and Physiology of Akkermansia muciniphila Isolates from Human Intestine Reveal Specialized Mucosal Adaptation.}, journal = {Microorganisms}, volume = {10}, number = {8}, pages = {}, pmid = {36014023}, issn = {2076-2607}, support = {BOF12-GOA-008//Ghent University/ ; Advanced Grand 250172 - Microbes Inside/ERC_/European Research Council/International ; Spinoza Award Willem M. de Vos/NWO_/Dutch Research Council/Netherlands ; SIAM Gravity Grant 024.002.002/NWO_/Dutch Research Council/Netherlands ; FRFS-WELBIO: WELBIO-CR-2022A-02//Fund for Scientific Research/ ; }, abstract = {Akkermansia muciniphila is a champion of mucin degradation in the human gastrointestinal tract. Here, we report the isolation of six novel strains from healthy human donors and their genomic, proteomic and physiological characterization in comparison to the type-strains A. muciniphila MucT and A. glycaniphila PytT. Complete genome sequencing revealed that, despite their large genomic similarity (>97.6%), the novel isolates clustered into two distinct subspecies of A. muciniphila: Amuc1, which includes the type-strain MucT, and AmucU, a cluster of unassigned strains that have not yet been well characterized. CRISPR analysis showed all strains to be unique and confirmed that single healthy subjects can carry more than one A. muciniphila strain. Mucin degradation pathways were strongly conserved amongst all isolates, illustrating the exemplary niche adaptation of A. muciniphila to the mucin interface. This was confirmed by analysis of the predicted glycoside hydrolase profiles and supported by comparing the proteomes of A. muciniphila strain H2, belonging to the AmucU cluster, to MucT and A. glycaniphila PytT (including 610 and 727 proteins, respectively). While some intrinsic resistance was observed among the A. muciniphila straind, none of these seem to pose strain-specific risks in terms of their antibiotic resistance patterns nor a significant risk for the horizontal transfer of antibiotic resistance determinants, opening the way to apply the type-strain MucT or these new A. muciniphila strains as next generation beneficial microbes.}, }
@article {pmid36013941, year = {2022}, author = {Harel, N and Reshef, L and Biran, D and Brenner, S and Ron, EZ and Gophna, U}, title = {Effect of Solar Radiation on Skin Microbiome: Study of Two Populations.}, journal = {Microorganisms}, volume = {10}, number = {8}, pages = {}, pmid = {36013941}, issn = {2076-2607}, abstract = {Here, we examined the skin microbiome of two groups of healthy volunteers living on the Mediterranean coast with different exposures to sun radiation. One group, exposed to the sun in the summer, was compared with a group covered with clothing throughout the year. The seasonal effects on the skin microbiome of three body sites were determined before and after summer. Surprisingly, at the phyla level, there were no significant differences in microbiome diversity between the groups. Furthermore, within each group, there were no significant seasonal differences in high-abundance species at any of the sampling sites. These results suggest that the skin microbiome, developed over years, remains stable even after several months of exposure to summer weather, direct sunlight and humidity. However, in the group exposed to the sun during the summer months, there were significant differences in low-abundance species in sun-exposed areas of the skin (the inner and outer arm). These subtle changes in low-abundance species are interesting, and their effect on skin physiology should be studied further.}, }
@article {pmid36010611, year = {2022}, author = {Huwart, SJP and de Wouters d'Oplinter, A and Rastelli, M and Van Hul, M and de Vos, WM and Luquet, S and Cani, PD and Everard, A}, title = {Food Reward Alterations during Obesity Are Associated with Inflammation in the Striatum in Mice: Beneficial Effects of Akkermansia muciniphila.}, journal = {Cells}, volume = {11}, number = {16}, pages = {}, pmid = {36010611}, issn = {2073-4409}, mesh = {Akkermansia ; Animals ; Inflammation/metabolism ; Male ; Mice ; Mice, Obese ; *Obesity/metabolism ; Reward ; *Verrucomicrobia/metabolism ; }, abstract = {The reward system involved in hedonic food intake presents neuronal and behavioral dysregulations during obesity. Moreover, gut microbiota dysbiosis during obesity promotes low-grade inflammation in peripheral organs and in the brain contributing to metabolic alterations. The mechanisms underlying reward dysregulations during obesity remain unclear. We investigated if inflammation affects the striatum during obesity using a cohort of control-fed or diet-induced obese (DIO) male mice. We tested the potential effects of specific gut bacteria on the reward system during obesity by administrating Akkermansia muciniphila daily or a placebo to DIO male mice. We showed that dysregulations of the food reward are associated with inflammation and alterations in the blood-brain barrier in the striatum of obese mice. We identified Akkermansia muciniphila as a novel actor able to improve the dysregulated reward behaviors associated with obesity, potentially through a decreased activation of inflammatory pathways and lipid-sensing ability in the striatum. These results open a new field of research and suggest that gut microbes can be considered as an innovative therapeutic approach to attenuate reward alterations in obesity. This study provides substance for further investigations of Akkermansia muciniphila-mediated behavioral improvements in other inflammatory neuropsychiatric disorders.}, }
@article {pmid36010298, year = {2022}, author = {Günther, V and Allahqoli, L and Watrowski, R and Maass, N and Ackermann, J and von Otte, S and Alkatout, I}, title = {Vaginal Microbiome in Reproductive Medicine.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {36010298}, issn = {2075-4418}, abstract = {The human microbiome has been given increasing importance in recent years. The establishment of sequencing-based technology has made it possible to identify a large number of bacterial species that were previously beyond the scope of culture-based technologies. Just as microbiome diagnostics has emerged as a major point of focus in science, reproductive medicine has developed into a subject of avid interest, particularly with regard to causal research and treatment options for implantation failure. Thus, the vaginal microbiome is discussed as a factor influencing infertility and a promising target for treatment options. The present review provides an overview of current research concerning the impact of the vaginal microbiome on the outcome of reproductive measures. A non-Lactobacillus-dominated microbiome was shown to be associated with dysbiosis, possibly even bacterial vaginosis. This imbalance has a negative impact on implantation rates in assisted reproductive technologies and may also be responsible for habitual abortions. Screening of the microbiome in conjunction with antibiotic and/or probiotic treatment appears to be one way of improving pregnancy outcomes.}, }
@article {pmid36003766, year = {2022}, author = {Liang, J and Li, T and Zhao, J and Wang, C and Sun, H}, title = {Current understanding of the human microbiome in glioma.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {781741}, pmid = {36003766}, issn = {2234-943X}, abstract = {There is mounting evidence that the human microbiome is highly associated with a wide variety of central nervous system diseases. However, the link between the human microbiome and glioma is rarely noticed. The exact mechanism of microbiota to affect glioma remains unclear. Recent studies have demonstrated that the microbiome may affect the development, progress, and therapy of gliomas, including the direct impacts of the intratumoral microbiome and its metabolites, and the indirect effects of the gut microbiome and its metabolites. Glioma-related microbiome (gut microbiome and intratumoral microbiome) is associated with both tumor microenvironment and tumor immune microenvironment, which ultimately influence tumorigenesis, progression, and responses to treatment. In this review, we briefly summarize current knowledge regarding the role of the glioma-related microbiome, focusing on its gut microbiome fraction and a brief description of the intratumoral microbiome, and put forward the prospects in which microbiome can be applied in the future and some challenges still need to be solved.}, }
@article {pmid36001521, year = {2023}, author = {Shen, Y and Zhu, J and Deng, Z and Lu, W and Wang, H}, title = {EnsDeepDP: An Ensemble Deep Learning Approach for Disease Prediction Through Metagenomics.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {20}, number = {2}, pages = {986-998}, doi = {10.1109/TCBB.2022.3201295}, pmid = {36001521}, issn = {1557-9964}, mesh = {Humans ; Metagenomics ; *Deep Learning ; Algorithms ; Machine Learning ; *Microbiota/genetics ; }, abstract = {A growing number of studies show that the human microbiome plays a vital role in human health and can be a crucial factor in predicting certain human diseases. However, microbiome data are often characterized by the limited samples and high-dimensional features, which pose a great challenge for machine learning methods. Therefore, this paper proposes a novel ensemble deep learning disease prediction method that combines unsupervised and supervised learning paradigms. First, unsupervised deep learning methods are used to learn the potential representation of the sample. Afterwards, the disease scoring strategy is developed based on the deep representations as the informative features for ensemble analysis. To ensure the optimal ensemble, a score selection mechanism is constructed, and performance boosting features are engaged with the original sample. Finally, the composite features are trained with gradient boosting classifier for health status decision. For case study, the ensemble deep learning flowchart has been demonstrated on six public datasets extracted from the human microbiome profiling. The results show that compared with the existing algorithms, our framework achieves better performance on disease prediction.}, }
@article {pmid35998206, year = {2022}, author = {Li, J and George Markowitz, RH and Brooks, AW and Mallott, EK and Leigh, BA and Olszewski, T and Zare, H and Bagheri, M and Smith, HM and Friese, KA and Habibi, I and Lawrence, WM and Rost, CL and Lédeczi, &#xc1; and Eeds, AM and Ferguson, JF and Silver, HJ and Bordenstein, SR}, title = {Individuality and ethnicity eclipse a short-term dietary intervention in shaping microbiomes and viromes.}, journal = {PLoS biology}, volume = {20}, number = {8}, pages = {e3001758}, pmid = {35998206}, issn = {1545-7885}, support = {P30 DK058404/DK/NIDDK NIH HHS/United States ; R01 DK117144/DK/NIDDK NIH HHS/United States ; T32 HG008341/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Ethnicity ; Feces ; Female ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota/genetics ; Virome ; }, abstract = {Many diseases linked with ethnic health disparities associate with changes in microbial communities in the United States, but the causes and persistence of ethnicity-associated microbiome variation are not understood. For instance, microbiome studies that strictly control for diet across ethnically diverse populations are lacking. Here, we performed multiomic profiling over a 9-day period that included a 4-day controlled vegetarian diet intervention in a defined geographic location across 36 healthy Black and White females of similar age, weight, habitual diets, and health status. We demonstrate that individuality and ethnicity account for roughly 70% to 88% and 2% to 10% of taxonomic variation, respectively, eclipsing the effects a short-term diet intervention in shaping gut and oral microbiomes and gut viromes. Persistent variation between ethnicities occurs for microbial and viral taxa and various metagenomic functions, including several gut KEGG orthologs, oral carbohydrate active enzyme categories, cluster of orthologous groups of proteins, and antibiotic-resistant gene categories. In contrast to the gut and oral microbiome data, the urine and plasma metabolites tend to decouple from ethnicity and more strongly associate with diet. These longitudinal, multiomic profiles paired with a dietary intervention illuminate previously unrecognized associations of ethnicity with metagenomic and viromic features across body sites and cohorts within a single geographic location, highlighting the importance of accounting for human microbiome variation in research, health determinants, and eventual therapies. Trial Registration: ClinicalTrials.gov ClinicalTrials.gov Identifier: NCT03314194.}, }
@article {pmid35997152, year = {2022}, author = {Titécat, M and Rousseaux, C and Dubuquoy, C and Foligné, B and Rahmouni, O and Mahieux, S and Desreumaux, P and Woolston, J and Sulakvelidze, A and Wannerberger, K and Neut, C}, title = {Safety and Efficacy of an AIEC-targeted Bacteriophage Cocktail in a Mice Colitis Model.}, journal = {Journal of Crohn's &amp; colitis}, volume = {16}, number = {10}, pages = {1617-1627}, doi = {10.1093/ecco-jcc/jjac064}, pmid = {35997152}, issn = {1876-4479}, support = {//Ferring/ ; }, mesh = {Animals ; Humans ; Mice ; Bacterial Adhesion ; *Bacteriophages ; *Colitis/pathology ; Disease Models, Animal ; Dysbiosis/complications ; Escherichia coli ; Escherichia coli Infections/complications/microbiology/pathology ; Intestinal Mucosa/pathology ; }, abstract = {BACKGROUND AND AIMS: Adherent invasive Escherichia coli [AIEC] are recovered with a high frequency from the gut mucosa of Crohn's disease patients and are believed to contribute to the dysbiosis and pathogenesis of this inflammatory bowel disease. In this context, bacteriophage therapy has been proposed for specifically targeting AIEC in the human gut with no deleterious impact on the commensal microbiota.<br><br>METHODS: The in vitro efficacy and specificity of a seven lytic phage cocktail [EcoActive&#x2122;] was assessed against [i] 210 clinical AIEC strains, and [ii] 43 non-E. coli strains belonging to the top 12 most common bacterial genera typically associated with a healthy human microbiome. These data were supported by in vivo safety and efficacy assays conducted on healthy and AIEC-colonized mice, respectively.<br><br>RESULTS: The EcoActive cocktail was effective in vitro against 95% of the AIEC strains and did not lyse any of the 43 non-E. coli commensal strains, in contrast to conventional antibiotics. Long-term administration of the EcoActive cocktail to healthy mice was safe and did not induce dysbiosis according to metagenomic data. Using a murine model of induced colitis of animals infected with the AIEC strain LF82, we found that a single administration of the cocktail failed to alleviate inflammatory symptoms, while mice receiving the cocktail twice a day for 15 days were protected from clinical and microscopical manifestations of inflammation.<br><br>CONCLUSIONS: Collectively, the data support the approach of AIEC-targeted phage therapy as safe and effective treatment for reducing AIEC levels in the gut of IBD patients.}, }
@article {pmid35996476, year = {2022}, author = {Clark, KA and Bushin, LB and Seyedsayamdost, MR}, title = {RaS-RiPPs in Streptococci and the Human Microbiome.}, journal = {ACS bio &amp; med chem Au}, volume = {2}, number = {4}, pages = {328-339}, pmid = {35996476}, issn = {2694-2437}, abstract = {Radical S-adenosylmethionine (RaS) enzymes have quickly advanced to one of the most abundant and versatile enzyme superfamilies known. Their chemistry is predicated upon reductive homolytic cleavage of a carbon-sulfur bond in cofactor S-adenosylmethionine forming an oxidizing carbon-based radical, which can initiate myriad radical transformations. An emerging role for RaS enzymes is their involvement in the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a natural product family that has become known as RaS-RiPPs. These metabolites are especially prevalent in human and mammalian microbiomes because the complex chemistry of RaS enzymes gives rise to correspondingly complex natural products with minimal cellular energy and genomic fingerprint, a feature that is advantageous in microbes with small, host-adapted genomes in competitive environments. Herein, we review the discovery and characterization of RaS-RiPPs from the human microbiome with a focus on streptococcal bacteria. We discuss the varied chemical modifications that RaS enzymes introduce onto their peptide substrates and the diverse natural products that they give rise to. The majority of RaS-RiPPs remain to be discovered, providing an intriguing avenue for future investigations at the intersection of metalloenzymology, chemical ecology, and the human microbiome.}, }
@article {pmid35993728, year = {2022}, author = {Vander Haar, EL and Wu, G and Gyamfi-Bannerman, C and Thomas, C and Wapner, RJ and Reddy, UM and Zhao, L and Silver, RM and Goldenberg, RL and Han, YW}, title = {Microbial Analysis of Umbilical Cord Blood Reveals Novel Pathogens Associated with Stillbirth and Early Preterm Birth.}, journal = {mBio}, volume = {13}, number = {5}, pages = {e0203622}, pmid = {35993728}, issn = {2150-7511}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; R01 CA192111/CA/NCI NIH HHS/United States ; R01 DE029532/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; Infant, Newborn ; Pregnancy ; Female ; *Stillbirth/epidemiology ; Fetal Blood ; RNA, Ribosomal, 16S/genetics ; *Premature Birth/epidemiology ; Gestational Age ; }, abstract = {Stillbirths account for half of all perinatal mortality, but the underlying cause of a significant portion of the cases remains unknown. We set out to test the potential role and extent of microbial infection in stillbirth through a case-control analysis of fetal cord blood collected from the multisite Stillbirth Collaborative Research Network. Cases (n = 60) were defined as stillbirths at >20 weeks of gestation, and controls (n = 176) were live births. The bacterial presence, abundance, and composition were analyzed by endpoint PCR of full-length 16S rRNA and the V4 amplicon sequence variants (ASVs). The results demonstrate that bacterial prevalence and abundance were both significantly increased in stillbirth, even after adjusting for maternal age, race, body mass index, number of pregnancies, gestational age, and multiple gestations. Composition of bacterial communities in the cord blood also differed significantly. Using a group of 25 ASVs differentially abundant between the two groups, a Random Forest classification model achieved an accuracy score of 0.76 differentiating stillbirth and live birth, with Group B Streptococcus as the most enriched species in stillbirth. Positive PCR was also significantly associated with early preterm birth. A group of oral anaerobes, including Actinomyces, Campylobacter, Fusobacterium, Peptostreptococcus, Porphyromonas, and Prevotella, were enriched in live early preterm birth, suggesting possible oral origin of infection. Our ASV-based microbiome analysis revealed specific candidate pathogens associated with infections in stillbirth and early preterm birth. The cord blood microbial signatures may be markers of adverse pregnancy outcomes. Our study will help identify possible mechanism of infection and improve our ability to prevent stillbirth and early preterm birth. IMPORTANCE Stillbirth accounts for half of all perinatal mortality, but the underlying cause of a substantial portion of all cases remains elusive. We examined the umbilical cord blood microbiome in stillbirths (n = 60) and live births (n = 176) and discovered that the bacterial prevalence and abundance were significantly higher in stillbirths than live births. The microbial compositions also differed significantly. Group B Streptococcus was the most prevalent species detected in stillbirth. In addition, pathogens previously unknown to be associated with stillbirth were identified. A group of oral anaerobes including Fusobacterium nucleatum were found to be specifically enriched in the cord blood in early preterm live birth. This is by far the most comprehensive study to examine the microbial signatures in umbilical cord blood. Cord blood microbial signatures may be markers for adverse birth outcomes. Detection of key microbial signatures will help identify individuals at risk and develop effective preventative strategies.}, }
@article {pmid35993719, year = {2022}, author = {Baker, JL}, title = {Using Nanopore Sequencing to Obtain Complete Bacterial Genomes from Saliva Samples.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0049122}, pmid = {35993719}, issn = {2379-5077}, support = {K99 DE029228/DE/NIDCR NIH HHS/United States ; K99-DE029228//HHS | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; }, mesh = {Humans ; Sequence Analysis, DNA/methods ; *Nanopore Sequencing/methods ; Saliva ; Genome, Bacterial/genetics ; *Microbiota/genetics ; Bacteria/genetics ; }, abstract = {Obtaining complete, high-quality reference genomes is essential to the study of any organism. Recent advances in nanopore sequencing, as well as genome assembly and analysis methods, have made it possible to obtain complete bacterial genomes from metagenomic (i.e., multispecies) samples, including those from the human microbiome. In this study, methods are presented to obtain complete bacterial genomes from human saliva using complementary Oxford Nanopore (ONT) and Illumina sequencing. Applied to 3 human saliva samples, these methods resulted in 11 complete bacterial genomes: 3 Saccharibacteria clade G6 (also known as Ca. Nanogingivalaceae HMT-870), 1 Saccharibacteria clade G1 HMT-348, 2 Rothia mucilaginosa, 2 Actinomyces graevenitzii, 1 Mogibacterium diversum, 1 Lachnospiraceae HMT-096, and 1 Lancefieldella parvula; and one circular chromosome of Ruminococcaceae HMT-075 (which likely has at least 2 chromosomes). The 4 Saccharibacteria genomes, as well as the Actinomyces graeventizii genomes, represented the first complete genomes from their respective bacterial taxa. Aside from the complete genomes, the assemblies contained 147 contigs of over 500,000 bp each and thousands of smaller contigs, together representing a myriad of additional draft genomes including many which are likely nearly complete. The complete genomes enabled highly accurate pangenome analysis, which identified unique and missing features of each genome compared to its closest relatives with complete genomes available in public repositories. These features provide clues as to the lifestyle and ecological role of these bacteria within the human oral microbiota, which will be particularly useful in designing future studies of the taxa that have never been isolated or cultivated. IMPORTANCE Obtaining complete and accurate genomes is crucial to the study of any organism. Previously, obtaining complete genomes of bacteria, including those of the human microbiome, frequently required isolation of the organism, as well as low-throughput, manual sequencing methods to resolve repeat regions. Advancements in long-read sequencing technologies, including Oxford Nanopore (ONT), have made it possible to obtain complete, closed bacterial genomes from metagenomic samples. This study reports methods to obtain complete genomes from the human oral microbiome using complementary ONT and Illumina sequencing of saliva samples. Eleven complete genomes were obtained from 3 human saliva samples, with genomes of Saccharibacteria HMT-870, Saccharibacteria HMT-348, and Actinomyces graeventzii being the first complete genomes from their respective taxa. Obtaining complete bacterial genomes in a high-throughput manner will help illuminate the metabolic and ecological roles of important members of the human microbiota, particularly those that have remained recalcitrant to isolation and cultivation.}, }
@article {pmid35992695, year = {2022}, author = {Puce, L and Hampton-Marcell, J and Trabelsi, K and Ammar, A and Chtourou, H and Boulares, A and Marinelli, L and Mori, L and Cotellessa, F and Currà, A and Trompetto, C and Bragazzi, NL}, title = {Swimming and the human microbiome at the intersection of sports, clinical, and environmental sciences: A scoping review of the literature.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {984867}, pmid = {35992695}, issn = {1664-302X}, abstract = {The human microbiota is comprised of more than 10-100 trillion microbial taxa and symbiotic cells. Two major human sites that are host to microbial communities are the gut and the skin. Physical exercise has favorable effects on the structure of human microbiota and metabolite production in sedentary subjects. Recently, the concept of "athletic microbiome" has been introduced. To the best of our knowledge, there exists no review specifically addressing the potential role of microbiomics for swimmers, since each sports discipline requires a specific set of techniques, training protocols, and interactions with the athletic infrastructure/facility. Therefore, to fill in this gap, the present scoping review was undertaken. Four studies were included, three focusing on the gut microbiome, and one addressing the skin microbiome. It was found that several exercise-related variables, such as training volume/intensity, impact the athlete's microbiome, and specifically the non-core/peripheral microbiome, in terms of its architecture/composition, richness, and diversity. Swimming-related power-/sprint- and endurance-oriented activities, acute bouts and chronic exercise, anaerobic/aerobic energy systems have a differential impact on the athlete's microbiome. Therefore, their microbiome can be utilized for different purposes, including talent identification, monitoring the effects of training methodologies, and devising ad hoc conditioning protocols, including dietary supplementation. Microbiomics can be exploited also for clinical purposes, assessing the effects of exposure to swimming pools and developing potential pharmacological strategies to counteract the insurgence of skin infections/inflammation, including acne. In conclusion, microbiomics appears to be a promising tool, even though current research is still limited, warranting, as such, further studies.}, }
@article {pmid35989602, year = {2022}, author = {Lieberman, TD}, title = {Detecting bacterial adaptation within individual microbiomes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {377}, number = {1861}, pages = {20210243}, pmid = {35989602}, issn = {1471-2970}, support = {DP2 GM140922/GM/NIGMS NIH HHS/United States ; }, mesh = {Acclimatization ; Bacteria/genetics ; Genome ; Genomics ; Humans ; *Microbiota ; }, abstract = {The human microbiome harbours a large capacity for within-person adaptive mutations. Commensal bacterial strains can stably colonize a person for decades, and billions of mutations are generated daily within each person's microbiome. Adaptive mutations emerging during health might be driven by selective forces that vary across individuals, vary within an individual, or are completely novel to the human population. Mutations emerging within individual microbiomes might impact the immune system, the metabolism of nutrients or drugs, and the stability of the community to perturbations. Despite this potential, relatively little attention has been paid to the possibility of adaptive evolution within complex human-associated microbiomes. This review discusses the promise of studying within-microbiome adaptation, the conceptual and technical limitations that may have contributed to an underappreciation of adaptive de novo mutations occurring within microbiomes to date, and methods for detecting recent adaptive evolution. This article is part of a discussion meeting issue 'Genomic population structures of microbial pathogens'.}, }
@article {pmid35987373, year = {2022}, author = {Dalton, KR and Louis, LM and Fandiño-Del-Rio, M and Rule, AM and Pool, W and Randolph, K and Thomas, S and Davis, MF and Quirós-Alcalá, L}, title = {Microbiome alterations from volatile organic compounds (VOC) exposures among workers in salons primarily serving women of color.}, journal = {Environmental research}, volume = {214}, number = {Pt 4}, pages = {114125}, pmid = {35987373}, issn = {1096-0953}, support = {K01 OD019918/OD/NIH HHS/United States ; R01 HD097692/HD/NICHD NIH HHS/United States ; T32 ES007141/ES/NIEHS NIH HHS/United States ; T42 OH008428/OH/NIOSH CDC HHS/United States ; }, mesh = {Female ; Humans ; Biomarkers ; *Microbiota ; *Occupational Exposure/adverse effects/analysis ; RNA, Ribosomal, 16S ; Staphylococcus aureus ; *Volatile Organic Compounds/analysis/toxicity ; Black or African American ; *Beauty Culture ; Ethnic and Racial Minorities ; }, abstract = {Salon workers, especially those serving an ethnically and racially diverse clientele (i.e., Black/Latina), may experience disparately high levels of workplace exposures to respiratory irritants, including volatile organic compounds (VOCs). Salon workers are also reported to have a greater risk of developing respiratory conditions compared to the general population. Emerging evidence suggests that occupational chemical exposures may alter the human microbiome and that these alterations may be an important mechanism by which workplace VOC exposures adversely impact respiratory health. This preliminary research investigated the potential effects of 28 VOC urinary biomarkers on the 16S rRNA nasal microbiome in 40 workers from salons primarily serving women of color (Black and Dominican salons) compared to office workers. Our exploratory analysis revealed significant differences in microbial composition by worker group; namely dissimilar levels of Staphylococcus species (S. epidermidis and S. aureus, specifically) in salon workers compared to office workers, and higher alpha diversity levels in workers in Dominican salons compared to workers in Black salons. Within-sample alpha diversity levels tended to be decreased with higher VOC urinary biomarker concentrations, significantly for carbon disulfide, acrolein, acrylonitrile, crotonaldehyde, and vinyl chloride biomarkers. Our research highlights that occupational exposures, particularly to chemicals like VOCs, can impact the respiratory microbiome in the vulnerable salon worker group. Further understanding of the potential effects of chemical mixtures on microbial composition may provide key insights to respiratory health and other adverse health outcomes, as well as direct prevention efforts in this largely historically understudied occupational population.}, }
@article {pmid35986342, year = {2022}, author = {Che, H and Xiong, Q and Ma, J and Chen, S and Wu, H and Xu, H and Hou, B}, title = {Association of Helicobacter pylori infection with survival outcomes in advanced gastric cancer patients treated with immune checkpoint inhibitors.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {904}, pmid = {35986342}, issn = {1471-2407}, mesh = {*Carcinoma, Non-Small-Cell Lung/drug therapy ; *Helicobacter Infections/complications/drug therapy ; *Helicobacter pylori ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; *Lung Neoplasms/drug therapy ; Prospective Studies ; Retrospective Studies ; *Stomach Neoplasms ; }, abstract = {BACKGROUND: Accumulating evidence has revealed that the gut microbiota influences the effectiveness of immune checkpoint inhibitors (ICIs) in cancer patients. As a part of the human microbiome, Helicobacter pylori (H. pylori) was reported to be associated with reduced effectiveness of anti-PD1 immunotherapy in patients with non-small-cell lung cancer (NSCLC). Gastric cancer is more closely related to H. pylori, so we conducted a retrospective analysis to verify whether the association of H. pylori and effectiveness is applicable to advanced gastric cancer (AGC) patients.<br><br>MATERIAL AND METHODS: AGC patients who had evidence of H. pylori and received anti-PD-1 antibodies were enrolled in the study. The differences in the disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) between the H. pylori-positive group and the negative group were compared.<br><br>RESULTS: A total of 77 patients were included in this study; 34 patients were H. pylori positive, and the prevalence of H. pylori infection was 44.2%. Compared with the H. pylori-negative group, patients in the H. pylori-positive group had a higher risk of nonclinical response to anti-PD-1 antibody, with an OR of 2.91 (95% CI: 1.13-7.50). Patients in the H. pylori-negative group had a longer OS and PFS than those in the positive group, with an estimated median OS of 17.5&#xa0;months vs. 6.2&#xa0;months (HR&#x2009;=&#x2009;2.85, 95% CI: 1.70-4.78; P&#x2009;=&#x2009;0.021) and a median PFS of 8.4&#xa0;months vs. 2.7&#xa0;months (HR&#x2009;=&#x2009;3.11, 95% CI: 1.96-5.07, P&#x2009;=&#x2009;0.008). Multivariate analysis indicated that H. pylori infection was independently associated with PFS (HR&#x2009;=&#x2009;1.90, 95% CI: 1.10-3.30; P&#x2009;=&#x2009;0.022).<br><br>CONCLUSION: Our study unveils for the first time that H. pylori infection is associated with the outcome of immunotherapy for AGC patients. Multicenter, large sample and prospective clinical studies are needed to verify the association.}, }
@article {pmid35984746, year = {2022}, author = {Scheithauer, TPM and Herrema, H and Yu, H and Bakker, GJ and Winkelmeijer, M and Soukhatcheva, G and Dai, D and Ma, C and Havik, SR and Balvers, M and Davids, M and Meijnikman, AS and Aydin, &#xd6; and van den Born, BH and Besselink, MG and Busch, OR and de Brauw, M and van de Laar, A and Belzer, C and Stahl, M and de Vos, WM and Vallance, BA and Nieuwdorp, M and Verchere, CB and van Raalte, DH}, title = {Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2111951}, pmid = {35984746}, issn = {1949-0984}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; *Diabetes Mellitus, Type 2/microbiology ; *Flagellin/genetics/metabolism ; *Gastrointestinal Microbiome ; Humans ; Inflammation/metabolism ; Insulin ; *Insulin-Secreting Cells/metabolism ; Mice ; }, abstract = {Hyperglycemia and type 2 diabetes (T2D) are caused by failure of pancreatic beta cells. The role of the gut microbiota in T2D has been studied, but causal links remain enigmatic. Obese individuals with or without T2D were included from two independent Dutch cohorts. Human data were translated in vitro and in vivo by using pancreatic islets from C57BL6/J mice and by injecting flagellin into obese mice. Flagellin is part of the bacterial locomotor appendage flagellum, present in gut bacteria including Enterobacteriaceae, which we show to be more abundant in the gut of individuals with T2D. Subsequently, flagellin induces a pro-inflammatory response in pancreatic islets mediated by the Toll-like receptor (TLR)-5 expressed on resident islet macrophages. This inflammatory response is associated with beta-cell dysfunction, characterized by reduced insulin gene expression, impaired proinsulin processing and stress-induced insulin hypersecretion in vitro and in vivo in mice. We postulate that increased systemically disseminated flagellin in T2D is a contributing factor to beta-cell failure in time and represents a novel therapeutic target.}, }
@article {pmid37850145, year = {2022}, author = {Cochrane, RR and Shrestha, A and Severo de Almeida, MM and Agyare-Tabbi, M and Brumwell, SL and Hamadache, S and Meaney, JS and Nucifora, DP and Say, HH and Sharma, J and Soltysiak, MPM and Tong, C and Van Belois, K and Walker, EJL and Lachance, MA and Gloor, GB and Edgell, DR and Shapiro, RS and Karas, BJ}, title = {Superior Conjugative Plasmids Delivered by Bacteria to Diverse Fungi.}, journal = {Biodesign research}, volume = {2022}, number = {}, pages = {9802168}, pmid = {37850145}, issn = {2693-1257}, abstract = {Fungi are nature's recyclers, allowing for ecological nutrient cycling and, in turn, the continuation of life on Earth. Some fungi inhabit the human microbiome where they can provide health benefits, while others are opportunistic pathogens that can cause disease. Yeasts, members of the fungal kingdom, have been domesticated by humans for the production of beer, bread, and, recently, medicine and chemicals. Still, the great untapped potential exists within the diverse fungal kingdom. However, many yeasts are intractable, preventing their use in biotechnology or in the development of novel treatments for pathogenic fungi. Therefore, as a first step for the domestication of new fungi, an efficient DNA delivery method needs to be developed. Here, we report the creation of superior conjugative plasmids and demonstrate their transfer via conjugation from bacteria to 7 diverse yeast species including the emerging pathogen Candida auris. To create our superior plasmids, derivatives of the 57 kb conjugative plasmid pTA-Mob 2.0 were built using designed gene deletions and insertions, as well as some unintentional mutations. Specifically, a cluster mutation in the promoter of the conjugative gene traJ had the most significant effect on improving conjugation to yeasts. In addition, we created Golden Gate assembly-compatible plasmid derivatives that allow for the generation of custom plasmids to enable the rapid insertion of designer genetic cassettes. Finally, we demonstrated that designer conjugative plasmids harboring engineered restriction endonucleases can be used as a novel antifungal agent, with important applications for the development of next-generation antifungal therapeutics.}, }
@article {pmid35982466, year = {2022}, author = {Hurley, JC}, title = {Candida and the Gram-positive trio: testing the vibe in the ICU patient microbiome using structural equation modelling of literature derived data.}, journal = {Emerging themes in epidemiology}, volume = {19}, number = {1}, pages = {7}, pmid = {35982466}, issn = {1742-7622}, abstract = {BACKGROUND: Whether Candida interacts with Gram-positive bacteria, such as Staphylococcus aureus, coagulase negative Staphylococci (CNS) and Enterococci, to enhance their invasive potential from the microbiome of ICU patients remains unclear. Several effective anti-septic, antibiotic, anti-fungal, and non-decontamination based interventions studied for prevention of ventilator associated pneumonia (VAP) and other ICU acquired infections among patients receiving prolonged mechanical ventilation (MV) are known to variably impact Candida colonization. The collective observations within control and intervention groups from numerous ICU infection prevention studies enables tests of these postulated microbial interactions in the clinical context.<br><br>METHODS: Four candidate generalized structural equation models (GSEM), each with Staphylococcus aureus, CNS and Enterococci colonization, defined as latent variables, were confronted with blood culture and respiratory tract isolate data derived from 460 groups of ICU patients receiving prolonged MV from 283 infection prevention studies.<br><br>RESULTS: Introducing interaction terms between Candida colonization and each of S aureus (coefficient&#x2009;+&#x2009;0.40; 95% confidence interval&#x2009;+&#x2009;0.24 to&#x2009;+&#x2009;0.55), CNS (+&#x2009;0.68;&#x2009;+&#x2009;0.34 to&#x2009;+&#x2009;1.0) and Enterococcal (+&#x2009;0.56;&#x2009;+&#x2009;0.33 to&#x2009;+&#x2009;0.79) colonization (all as latent variables) improved the fit for each model. The magnitude and significance level of the interaction terms were similar to the positive associations between exposure to topical antibiotic prophylaxis (TAP) on Enterococcal (+&#x2009;0.51;&#x2009;+&#x2009;0.12 to&#x2009;+&#x2009;0.89) and Candida colonization (+&#x2009;0.98;&#x2009;+&#x2009;0.35 to&#x2009;+&#x2009;1.61) versus the negative association of TAP with S aureus (-&#xa0;0.45; -&#xa0;0.70 to -&#xa0;0.20) colonization and the negative association of anti-fungal exposure and Candida colonization (-&#xa0;1.41; -&#xa0;1.6 to -&#xa0;0.72).<br><br>CONCLUSIONS: GSEM modelling of published ICU infection prevention data enables the postulated interactions between Candida and Gram-positive bacteria to be tested using clinically derived data. The optimal model implies interactions occurring in the human microbiome facilitating bacterial invasion and infection. This interaction might also account for the paradoxically high bacteremia incidences among studies of TAP in ICU patients.}, }
@article {pmid35978666, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Alieva, A and Poluektova, E and Kudryavtseva, A and Krasnov, G and Zharkova, M and Zharikov, Y}, title = {Gut dysbiosis and body composition in cirrhosis.}, journal = {World journal of hepatology}, volume = {14}, number = {6}, pages = {1210-1225}, pmid = {35978666}, issn = {1948-5182}, abstract = {BACKGROUND: Gut dysbiosis and changes in body composition (i.e., a decrease in the proportion of muscle mass and an increase in extracellular fluid) are common in cirrhosis.<br><br>AIM: To study the relationship between the gut microbiota and body composition in cirrhosis.<br><br>METHODS: This observational study included 46 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Multifrequency bioelectrical impedance analysis was performed to assess body composition in these patients.<br><br>RESULTS: An increase in fat mass and a decrease in body cell mass were noted in 23/46 (50.0%) and 15/46 (32.6%) patients, respectively. Changes in the gut microbiome were not independently associated with the fat mass percentage in cirrhosis. The abundance of Bacteroidaceae (P = 0.041) and Eggerthella (P = 0.001) increased, whereas that of Erysipelatoclostridiaceae (P = 0.006), Catenibacterium (P = 0.021), Coprococcus (P = 0.033), Desulfovibrio (P = 0.043), Intestinimonas (P = 0.028), and Senegalimassilia (P = 0.015) decreased in the gut microbiome of patients with body cell mass deficiency. The amount of extracellular fluid increased in 22/46 (47.6%) patients. Proteobacteria abundance (P < 0.001) increased, whereas Firmicutes (P = 0.023), Actinobacteria (P = 0.026), Bacilli (P = 0.008), Anaerovoraceceae (P = 0.027), Christensenellaceae (P = 0.038), Eggerthellaceae (P = 0.047), Erysipelatoclostridiaceae (P = 0.015), Erysipelotrichaceae (P = 0.003), Oscillospiraceae (P = 0.024), Rikenellaceae (P = 0.002), Collinsella (P = 0.030), Hungatella (P = 0.040), Peptococcaceae (P = 0.023), Slackia (P = 0.008), and Senegalimassilia (P = 0.024) abundance decreased in these patients. Patients with clinically significant ascites (n = 9) had a higher abundance of Proteobacteria (P = 0.031) and a lower abundance of Actinobacteria (P = 0.019) and Bacteroidetes (P = 0.046) than patients without clinically significant ascites (n = 37).<br><br>CONCLUSION: Changes in the amount of body cell mass and extracellular fluid are associated with changes in the gut microbiome in cirrhosis patients.}, }
@article {pmid35978282, year = {2022}, author = {Nel Van Zyl, K and Whitelaw, AC and Hesseling, AC and Seddon, JA and Demers, AM and Newton-Foot, M}, title = {Fungal diversity in the gut microbiome of young South African children.}, journal = {BMC microbiology}, volume = {22}, number = {1}, pages = {201}, pmid = {35978282}, issn = {1471-2180}, support = {/WT_/Wellcome Trust/United Kingdom ; MR/M007340/1/MRC_/Medical Research Council/United Kingdom ; MR/R007942/1/MRC_/Medical Research Council/United Kingdom ; UM1 AI106716/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Bacteria/genetics ; Candida ; Child ; Female ; Fungi/genetics ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; South Africa ; Vitamin A ; }, abstract = {BACKGROUND: The fungal microbiome, or mycobiome, is a poorly described component of the gut ecosystem and little is known about its structure and development in children. In South Africa, there have been no culture-independent evaluations of the child gut mycobiota. This study aimed to characterise the gut mycobiota and explore the relationships between fungi and bacteria in the gut microbiome of children from Cape Town communities.<br><br>METHODS: Stool samples were collected from children enrolled in the TB-CHAMP clinical trial. Internal transcribed spacer 1 (ITS1) gene sequencing was performed on a total of 115 stool samples using the Illumina MiSeq platform. Differences in fungal diversity and composition in relation to demographic, clinical, and environmental factors were investigated, and correlations between fungi and previously described bacterial populations in the same samples were described.<br><br>RESULTS: Taxa from the genera Candida and Saccharomyces were detected in all participants. Differential abundance analysis showed that Candida&#xa0;spp. were significantly more abundant in children younger than 2&#xa0;years compared to older children. The gut mycobiota was less diverse than the bacterial microbiota of the same participants, consistent with the findings of other human microbiome studies. The variation in richness and evenness of fungi was substantial, even between individuals of the same age. There was significant association between vitamin A supplementation and higher fungal alpha diversity (p&#x2009;=&#x2009;0.047), and girls were shown to have lower fungal alpha diversity (p&#x2009;=&#x2009;0.003). Co-occurrence between several bacterial taxa and Candida albicans was observed.<br><br>CONCLUSIONS: The dominant fungal taxa in our study population were similar to those reported in other paediatric studies; however, it remains difficult to identify the true core gut mycobiota due to the challenges set by the low abundance of gut fungi and the lack of true gut colonising species. The connection between the microbiota, vitamin A supplementation, and growth and immunity warrants exploration, especially in populations at risk for micronutrient deficiencies. While we were able to provide insight into the gut mycobiota of young South African children, further functional studies are necessary to explain the role of the mycobiota and the correlations between bacteria and fungi in human health.}, }
@article {pmid35975994, year = {2022}, author = {Hendrickson, EL and Bor, B and Kerns, KA and Lamont, EI and Chang, Y and Liu, J and Cen, L and Schulte, F and Hardt, M and Shi, W and He, X and McLean, JS}, title = {Transcriptome of Epibiont Saccharibacteria Nanosynbacter lyticus Strain TM7x During the Establishment of Symbiosis.}, journal = {Journal of bacteriology}, volume = {204}, number = {9}, pages = {e0011222}, pmid = {35975994}, issn = {1098-5530}, support = {K99 DE027719/DE/NIDCR NIH HHS/United States ; R01 AI087946/AI/NIAID NIH HHS/United States ; T90 DE021984/DE/NIDCR NIH HHS/United States ; KL2 TR000421/TR/NCATS NIH HHS/United States ; R00 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 AI132818/AI/NIAID NIH HHS/United States ; R01 DE031274/DE/NIDCR NIH HHS/United States ; S10 OD023603/OD/NIH HHS/United States ; KL2 TR002317/TR/NCATS NIH HHS/United States ; }, mesh = {Arginine/metabolism ; Bacteria/genetics ; Genome, Bacterial ; Humans ; Peptidoglycan/metabolism ; *Symbiosis ; *Transcriptome ; }, abstract = {Saccharibacteria Nanosynbacter lyticus strain TM7x is a member of the broadly distributed candidate phylum radiation. These bacteria have ultrasmall cell sizes, have reduced genomes, and live as epibionts on the surfaces of other bacteria. The mechanisms by which they establish and maintain this relationship are not yet fully understood. The transcriptomes of the epibiont TM7x and its host bacteria Schaalia odontolytica strain XH001 were captured across the establishment of symbiosis during both the initial interaction and stable symbiosis. The results showed a dynamic interaction with large shifts in gene expression for both species between the initial encounter and stable symbiosis, notably in transporter genes. During stable symbiosis, the host XH001 showed higher gene expression for peptidoglycan biosynthesis, mannosylation, cell cycle and stress-related genes, whereas it showed lower expression of chromosomal partitioning genes. This was consistent with the elongated cell shape seen in XH001 infected with TM7x and our discovery that infection resulted in thickened cell walls. Within TM7x, increased pili, type IV effector genes, and arginine catabolism/biosynthesis gene expression during stable symbiosis implied a key role for these functions in the interaction. Consistent with its survival and persistence in the human microbiome as an obligate epibiont with reduced de novo biosynthetic capacities, TM7x also showed higher levels of energy production and peptidoglycan biosynthesis, but lower expression of stress-related genes, during stable symbiosis. These results imply that TM7x and its host bacteria keep a delicate balance in order to sustain an episymbiotic lifestyle. IMPORTANCE Nanosynbacter lyticus type strain TM7x is the first cultivated member of the Saccharibacteria and the candidate phyla radiation (CPR). It was discovered to be ultrasmall in cell size with a highly reduced genome that establishes an obligate epibiotic relationship with its host bacterium. The CPR is a large, monophyletic radiation of bacteria with reduced genomes that includes Saccharibacteria. The vast majority of the CPR have yet to be cultivated, and our insights into these unique organisms to date have been derived from only a few Saccharibacteria species. Being obligate parasites, it is unknown how these ultrasmall Saccharibacteria, which are missing many de novo biosynthetic pathways, are maintained at a high prevalence within the human microbiome as well as in the environment.}, }
@article {pmid35968909, year = {2022}, author = {Zhang, Y and Li, P and Ma, Y and Wang, J and Chen, Y}, title = {Artificial intelligence accelerates the mining of bioactive small molecules from human microbiome.}, journal = {Clinical and translational medicine}, volume = {12}, number = {8}, pages = {e1011}, pmid = {35968909}, issn = {2001-1326}, mesh = {*Artificial Intelligence ; Humans ; *Microbiota ; }, }
@article {pmid35966698, year = {2022}, author = {Jones, J and Reinke, SN and Mousavi-Derazmahalleh, M and Palmer, DJ and Christophersen, CT}, title = {Changes to the Gut Microbiome in Young Children Showing Early Behavioral Signs of Autism.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {905901}, pmid = {35966698}, issn = {1664-302X}, abstract = {The human gut microbiome has increasingly been associated with autism spectrum disorder (ASD), which is a neurological developmental disorder, characterized by impairments to social interaction. The ability of the gut microbiota to signal across the gut-brain-microbiota axis with metabolites, including short-chain fatty acids, impacts brain health and has been identified to play a role in the gastrointestinal and developmental symptoms affecting autistic children. The fecal microbiome of older children with ASD has repeatedly shown particular shifts in the bacterial and fungal microbial community, which are significantly different from age-matched neurotypical controls, but it is still unclear whether these characteristic shifts are detectable before diagnosis. Early microbial colonization patterns can have long-lasting effects on human health, and pre-emptive intervention may be an important mediator to more severe autism. In this study, we characterized both the microbiome and short-chain fatty acid concentrations of fecal samples from young children between 21 and 40 months who were showing early behavioral signs of ASD. The fungal richness and acetic acid concentrations were observed to be higher with increasing autism severity, and the abundance of several bacterial taxa also changed due to the severity of ASD. Bacterial diversity and SCFA concentrations were also associated with stool form, and some bacterial families were found with differential abundance according to stool firmness. An exploratory analysis of the microbiome associated with pre-emptive treatment also showed significant differences at multiple taxonomic levels. These differences may impact the microbial signaling across the gut-brain-microbiota axis and the neurological development of the children.}, }
@article {pmid35966676, year = {2022}, author = {Wei, Q and Li, Z and Gu, Z and Liu, X and Krutmann, J and Wang, J and Xia, J}, title = {Shotgun metagenomic sequencing reveals skin microbial variability from different facial sites.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {933189}, pmid = {35966676}, issn = {1664-302X}, abstract = {Biogeography (body site) is known to be one of the main factors influencing the composition of the skin microbial community. However, site-associated microbial variability at a fine-scale level was not well-characterized since there was a lack of high-resolution recognition of facial microbiota across kingdoms by shotgun metagenomic sequencing. To investigate the explicit microbial variance in the human face, 822 shotgun metagenomic sequencing data from Han Chinese recently published by our group, in combination with 97 North American samples from NIH Human Microbiome Project (HMP), were reassessed. Metagenomic profiling of bacteria, fungi, and bacteriophages, as well as enriched function modules from three facial sites (forehead, cheek, and the back of the nose), was analyzed. The results revealed that skin microbial features were more alike in the forehead and cheek while varied from the back of the nose in terms of taxonomy and functionality. Analysis based on biogeographic theories suggested that neutral drift with niche selection from the host could possibly give rise to the variations. Of note, the abundance of porphyrin-producing species, i.e., Cutibacterium acnes, Cutibacterium avidum, Cutibacterium granulosum, and Cutibacterium namnetense, was all the highest in the back of the nose compared with the forehead/cheek, which was consistent with the highest porphyrin level on the nose in our population. Sequentially, the site-associated microbiome variance was confirmed in American populations; however, it was not entirely consistent. Furthermore, our data revealed correlation patterns between Propionibacterium acnes bacteriophages with genus Cutibacterium at different facial sites in both populations; however, C. acnes exhibited a distinct correlation with P. acnes bacteriophages in Americans/Chinese. Taken together, in this study, we explored the fine-scale facial site-associated changes in the skin microbiome and provided insight into the ecological processes underlying facial microbial variations.}, }
@article {pmid35964945, year = {2022}, author = {Kapoor, B and Gulati, M and Rani, P and Gupta, R}, title = {Psoriasis: Interplay between dysbiosis and host immune system.}, journal = {Autoimmunity reviews}, volume = {21}, number = {11}, pages = {103169}, doi = {10.1016/j.autrev.2022.103169}, pmid = {35964945}, issn = {1873-0183}, mesh = {Humans ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Prebiotics ; *Probiotics/therapeutic use ; *Psoriasis ; Immune System ; Bacteria ; }, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of both gut and skin microbiota in the pathogenesis of psoriasis. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts, have been identified as possible triggers for recurrent episodes of psoriasis. Mechanistically, gut dysbiosis leads to "leaky gut syndrome" via disruption of epithelial bilayer, thereby, resulting in translocation of bacteria and other endotoxins to systemic circulation, which in turn, results in inflammatory response. Similarly, skin dysbiosis disrupts the cutaneous homeostasis, leading to invasion of bacteria and other pathogens to deeper layers of skin or even systemic circulation further enhanced by injury caused by pruritus-induced scratching, and elicit innate and adaptive inflammation. The present review explores the correlation of both skin and gut microbiota dysbiosis with psoriasis. Also, the studies highlighting the potential of bacteriotherapeutic approaches including probiotics, prebiotics, metabiotics, and fecal microbiota transplantation for the management of psoriasis have been discussed.}, }
@article {pmid35959873, year = {2022}, author = {Mashyn, S and Borodanov, S and Klymenko, O and Lev, I and Shipova, K}, title = {THE ROLE OF LACTOBACILLI IN THE HUMAN MICROBIOME AND METHODS OF THEIR CULTIVATION AND PRESERVATION.}, journal = {Georgian medical news}, volume = {}, number = {326}, pages = {23-35}, pmid = {35959873}, issn = {1512-0112}, mesh = {Bacteria ; Humans ; Lactobacillus/physiology ; *Microbiota ; *Probiotics ; }, abstract = {The extremely important role of the microbiome for human life and health has long been known. Many studies around the world are devoted to studying the mechanisms of action and functions of various bacteria that are permanent residents of our body. Connections between the bacteria of our microbiome and all organs and systems of the human body (intestine, brain, nervous and cardiovascular systems) have been identified. However, the effect of bacteria can be positive or negative, which affects the emergence and development of diseases or promotes healing. Genus Lactobacillus is one of the most numerous populations of bacteria in the human body. Moreover, they have a significant positive effect on health. Scientists are actively researching methods of cultivating and using bacteria of this genus in the pharmaceutical and industrial fields. Most probiotics contain lactobacilli strains. Therefore, the study of methods of cultivation and storage of lactobacilli in order to find ways to improve their viability and functionality and, at the same time, the invention of options to protect cell culture from various harmful factors is extremely important. In our review, we considered the importance of the microbiome for human health and the role of bacteria of the genus Lactobacillus as its component. Scientific works on studying the mechanisms of influence of lactobacilli on the functional capacity of human organs and systems have been studied. Much of the review is devoted to the study of lactobacilli cultivation methods, the diversity of culture media, and the importance of their components to improve the viability of lactobacilli culture because they are quite demanding and vulnerable. Attention is also paid to the development of methods of storage of grown cultures of bacterial cells and their improvement in order to obtain functional and suitable for further use in the pharmacological and industrial areas of bacterial strains.}, }
@article {pmid35958597, year = {2022}, author = {Livson, S and Virtanen, S and Lokki, AI and Holster, T and Rahkonen, L and Kalliala, I and Nieminen, P and Salonen, A and Meri, S}, title = {Cervicovaginal Complement Activation and Microbiota During Pregnancy and in Parturition.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {925630}, pmid = {35958597}, issn = {1664-3224}, mesh = {Bacteria/genetics ; Complement Activation ; *Complement Factor B ; Female ; Gardnerella vaginalis/genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; LIM Domain Proteins ; *Microbiota/genetics ; Muscle Proteins ; Parturition ; Pregnancy ; Vagina/microbiology ; }, abstract = {BACKGROUND: Vaginal microbiome and the local innate immune defense, including the complement system, contribute to anti- and proinflammatory homeostasis during pregnancy and parturition. The relationship between commensal vaginal bacteria and complement activation during pregnancy and delivery is not known.<br><br>OBJECTIVE: To study the association of the cervicovaginal microbiota composition to activation and regulation of the complement system during pregnancy and labor.<br><br>STUDY DESIGN: We recruited women during late pregnancy (weeks 41 + 5 to 42 + 0, n=48) and women in active labor (weeks 38 + 4 to 42 + 2, n=25). Mucosal swabs were taken from the external cervix and lateral fornix of the vagina. From the same sampling site, microbiota was analyzed with 16S RNA gene amplicon sequencing. A Western blot technique was used to detect complement C3, C4 and factor B activation and presence of complement inhibitors. For semiquantitative analysis, the bands of the electrophoresed proteins in gels were digitized on a flatbed photo scanner and staining intensities were analyzed using ImageJ/Fiji win-64 software. Patient data was collected from medical records and questionnaires.<br><br>RESULTS: The vaginal microbiota was Lactobacillus-dominant in most of the samples (n=60), L. iners and L. crispatus being the dominant species. L. gasseri and L. jensenii were found to be more abundant during pregnancy than active labor. L. jensenii abundance correlated with C4 activation during pregnancy but not in labor. Gardnerella vaginalis was associated with C4 activation both during pregnancy and labor. The amount of L. gasseri correlated with factor B activation during pregnancy but not during labor. Atopobium vaginae was more abundant during pregnancy than labor and correlated with C4 activation during labor and with factor B activation during pregnancy. Activation of the alternative pathway factor B was significantly stronger during pregnancy compared to labor. During labor complement activation may be inhibited by the abundant presence of factor H and FHL1.<br><br>CONCLUSIONS: These results indicate that bacterial composition of the vaginal microbiota could have a role in the local activation and regulation of complement-mediated inflammation during pregnancy. At the time of parturition complement activation appears to be more strictly regulated than during pregnancy.}, }
@article {pmid35951092, year = {2022}, author = {Parker, KD and Mueller, JL and Westfal, M and Goldstein, AM and Ward, NL}, title = {A pilot study characterizing longitudinal changes in fecal microbiota of patients with Hirschsprung-associated enterocolitis.}, journal = {Pediatric surgery international}, volume = {38}, number = {11}, pages = {1541-1553}, pmid = {35951092}, issn = {1437-9813}, support = {DK098696-01A1/GM/NIGMS NIH HHS/United States ; 2P20GM103432/GM/NIGMS NIH HHS/United States ; DK098696-01A1/GM/NIGMS NIH HHS/United States ; 2P20GM103432/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Child ; *Enterocolitis/etiology ; Feces ; *Hirschsprung Disease/surgery ; Humans ; Mice ; *Microbiota ; Pilot Projects ; }, abstract = {PURPOSE: Hirschsprung disease is a neurointestinal disease that occurs due to failure of enteric neural crest-derived cells to complete their rostrocaudal migration along the gut mesenchyme, resulting in aganglionosis along variable lengths of the distal bowel. Despite the effective surgery that removes the aganglionic segment, children with Hirschsprung disease remain at high risk for developing a potentially life-threatening enterocolitis (Hirschsprung-associated enterocolitis). Although the etiology of this enterocolitis remains poorly understood, several recent studies in both mouse models and in human subjects suggest potential involvement of gastrointestinal microbiota in the underlying pathogenesis of Hirschsprung-associated enterocolitis.<br><br>METHODS: We present the first study to exploit the Illumina MiSeq next-generation sequencing platform within a longitudinal framework focused on microbiomes of Hirschsprung-associated enterocolitis in five patients. We analyzed bacterial communities from fecal samples collected at different timepoints starting from active enterocolitis and progressing into remission.<br><br>RESULTS: We observed compositional differences between patients largely attributable to variability in age at the time of sample collection. Remission samples across patients exhibited compositional similarity, including enrichment of Blautia, while active enterocolitis samples showed substantial variability in composition.<br><br>CONCLUSIONS: Overall, our findings provide continued support for the role of GI microbiota in the pathogenesis of Hirschsprung-associated enterocolitis.}, }
@article {pmid35947353, year = {2023}, author = {Dickerson, F and Dilmore, AH and Godoy-Vitorino, F and Nguyen, TT and Paulus, M and Pinto-Tomas, AA and Moya-Roman, C and Zuniga-Chaves, I and Severance, EG and Jeste, DV}, title = {The Microbiome and Mental Health Across the Lifespan.}, journal = {Current topics in behavioral neurosciences}, volume = {61}, number = {}, pages = {119-140}, pmid = {35947353}, issn = {1866-3370}, mesh = {Humans ; Aged ; Longevity ; Mental Health ; *Alzheimer Disease ; *Microbiota ; *Schizophrenia ; }, abstract = {INTRODUCTION: The combined genetic material of the microorganisms in the human body, known as the microbiome, is being increasingly recognized as a major determinant of human health and disease. Although located predominantly on mucosal surfaces, these microorganisms have profound effects on brain functioning through the gut-brain axis.<br><br>METHOD: The content of the chapter is based on a study group session at the annual meeting of the American College of Neuropsychopharmacology (ACNP). The objective was to discuss the emerging relationship between the human microbiome and mental health as relevant to ACNP's interests in developing and evaluating novel neuropsychiatric treatment strategies. The focus is on specific brain disorders, such as schizophrenia, substance use, and Alzheimer's disease, as well as on broader clinical issues such as suicidality, loneliness and wisdom in old age, and longevity.<br><br>RESULTS: Studies of schizophrenia indicate that the microbiome of individuals with this disorder differs from that of non-psychiatric comparison groups in terms of diversity and composition. Differences are also found in microbial metabolic pathways. An early study in substance use disorders found that individuals with this disorder have lower levels of beta diversity in their oral microbiome than a comparison group. This measure, along with others, was used to distinguish individuals with substance use disorders from controls. In terms of suicidality, there is preliminary evidence that persons who have made a suicide attempt differ from psychiatric and non-psychiatric comparison groups in measures of beta diversity. Exploratory studies in Alzheimer's disease indicate that gut microbes may contribute to disease pathogenesis by regulating innate immunity and neuroinflammation and thus influencing brain function. In another study looking at the microbiome in older adults, positive associations were found between wisdom and alpha diversity and negative associations with subjective loneliness. In other studies of older adults, here with a focus on longevity, individuals with healthy aging and unusually long lives had an abundance of specific microorganisms which distinguished them from other individuals.<br><br>DISCUSSION: Future studies would benefit from standardizing methods of sample collection, processing, and analysis. There is also a need for the standardized collection of relevant demographic and clinical data, including diet, medications, cigarette smoking, and other potentially confounding factors. While still in its infancy, research to date indicates a role for the microbiome in mental health disorders and conditions. Interventions are available which can modulate the microbiome and lead to clinical improvements. These include microbiome-altering medications as well as probiotic microorganisms capable of modulating the inflammation in the brain through the gut-brain axis. This research holds great promise in terms of developing new methods for the prevention and treatment of a range of human brain disorders.}, }
@article {pmid35945268, year = {2023}, author = {Turunen, J and Tejesvi, MV and Suokas, M and Virtanen, N and Paalanne, N and Kaisanlahti, A and Reunanen, J and Tapiainen, T}, title = {Bacterial extracellular vesicles in the microbiome of first-pass meconium in newborn infants.}, journal = {Pediatric research}, volume = {93}, number = {4}, pages = {887-896}, pmid = {35945268}, issn = {1530-0447}, mesh = {Infant, Newborn ; Pregnancy ; Female ; Infant ; Humans ; *Meconium/microbiology ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Bacteria/genetics ; Anti-Bacterial Agents ; }, abstract = {BACKGROUND: Bacterial extracellular vesicles (EVs) are more likely to cross biological barriers than whole-cell bacteria. We previously observed EV-sized particles by electron microscopy in the first-pass meconium of newborn infants. We hypothesized that EVs may be of bacterial origin and represent a novel entity in the human microbiome during fetal and perinatal periods.<br><br>METHODS: We extracted EVs from first-pass meconium samples of 17 newborn infants and performed bacterial 16S rRNA gene sequencing of the vesicles. We compared the EV content from the meconium samples of infants based on the delivery mode, and in vaginal delivery samples, based on the usage of intrapartum antibiotics.<br><br>RESULTS: We found bacterial EVs in all first-pass meconium samples. All EV samples had bacterial RNA. Most of the phyla present in the samples were Firmicutes (62%), Actinobacteriota (18%), Proteobacteria (10%), and Bacteroidota (7.3%). The most abundant genera were Streptococcus (21%) and Staphylococcus (17%). The differences between the delivery mode and exposure to antibiotics were not statistically significant.<br><br>CONCLUSIONS: Bacterial EVs were present in the first-pass meconium of newborn infants. Bacterial EVs may represent an important novel feature of the gut microbiome during fetal and perinatal periods.<br><br>IMPACT: We show that bacterial extracellular vesicles are present in the microbiome of first-pass meconium in newborn infants. This is a novel finding. To our knowledge, this is the first study to report the presence of bacterial extracellular vesicles in the gut microbiome during fetal and perinatal periods. This finding is important because bacterial extracellular vesicles are more likely to cross biological barriers than whole-cell bacteria. Thus, the early gut microbiome may potentially interact with the host through bacterial EVs.}, }
@article {pmid35936744, year = {2022}, author = {Zhou, X and Kandalai, S and Hossain, F and Zheng, Q}, title = {Tumor microbiome metabolism: A game changer in cancer development and therapy.}, journal = {Frontiers in oncology}, volume = {12}, number = {}, pages = {933407}, pmid = {35936744}, issn = {2234-943X}, abstract = {Accumulating recent evidence indicates that the human microbiome plays essential roles in pathophysiological states, including cancer. The tumor microbiome, an emerging concept that has not yet been clearly defined, has been proven to influence both cancer development and therapy through complex mechanisms. Small molecule metabolites produced by the tumor microbiome through unique biosynthetic pathways can easily diffuse into tissues and penetrate cell membranes through transporters or free diffusion, thus remodeling the signaling pathways of cancer and immune cells by interacting with biomacromolecules. Targeting tumor microbiome metabolism could offer a novel perspective for not only understanding cancer progression but also developing new strategies for the treatment of multiple cancer types. Here, we summarize recent advances regarding the role the tumor microbiome plays as a game changer in cancer biology. Specifically, the metabolites produced by the tumor microbiome and their potential effects on the cancer development therapy are discussed to understand the importance of the microbial metabolism in the tumor microenvironment. Finally, new anticancer therapeutic strategies that target tumor microbiome metabolism are reviewed and proposed to provide new insights in clinical applications.}, }
@article {pmid35935217, year = {2022}, author = {Buttimer, C and Sutton, T and Colom, J and Murray, E and Bettio, PH and Smith, L and Bolocan, AS and Shkoporov, A and Oka, A and Liu, B and Herzog, JW and Sartor, RB and Draper, LA and Ross, RP and Hill, C}, title = {Impact of a phage cocktail targeting Escherichia coli and Enterococcus faecalis as members of a gut bacterial consortium in vitro and in vivo.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {936083}, pmid = {35935217}, issn = {1664-302X}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; }, abstract = {Escherichia coli and Enterococcus faecalis have been implicated as important players in human gut health that have been associated with the onset of inflammatory bowel disease (IBD). Bacteriophage (phage) therapy has been used for decades to target pathogens as an alternative to antibiotics, but the ability of phage to shape complex bacterial consortia in the lower gastrointestinal tract is not clearly understood. We administered a cocktail of six phages (either viable or heat-inactivated) targeting pro-inflammatory Escherichia coli LF82 and Enterococcus faecalis OG1RF as members of a defined community in both a continuous fermenter and a murine colitis model. The two target strains were members of a six species simplified human microbiome consortium (SIHUMI-6). In a 72-h continuous fermentation, the phage cocktail caused a 1.1 and 1.5 log (log10 genome copies/mL) reduction in E. faecalis and E. coli numbers, respectively. This interaction was accompanied by changes in the numbers of other SIHUMI-6 members, with an increase of Lactiplantibacillus plantarum (1.7 log) and Faecalibacterium prausnitzii (1.8 log). However, in germ-free mice colonized by the same bacterial consortium, the same phage cocktail administered twice a week over nine weeks did not cause a significant reduction of the target strains. Mice treated with active or inactive phage had similar levels of pro-inflammatory cytokines (IFN-y/IL12p40) in unstimulated colorectal colonic strip cultures. However, histology scores of the murine lower GIT (cecum and distal colon) were lower in the viable phage-treated mice, suggesting that the phage cocktail did influence the functionality of the SIHUMI-6 consortium. For this study, we conclude that the observed potential of phages to reduce host populations in in vitro models did not translate to a similar outcome in an in vivo setting, with this effect likely brought about by the reduction of phage numbers during transit of the mouse GIT.}, }
@article {pmid35934639, year = {2022}, author = {Peuranpää, P and Holster, T and Saqib, S and Kalliala, I and Tiitinen, A and Salonen, A and Hautamäki, H}, title = {Female reproductive tract microbiota and recurrent pregnancy loss: a nested case-control study.}, journal = {Reproductive biomedicine online}, volume = {45}, number = {5}, pages = {1021-1031}, doi = {10.1016/j.rbmo.2022.06.008}, pmid = {35934639}, issn = {1472-6491}, mesh = {Pregnancy ; Female ; Humans ; Case-Control Studies ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Vagina/microbiology ; *Abortion, Habitual ; }, abstract = {RESEARCH QUESTION: Is the composition of the endometrial or vaginal microbiota associated with recurrent pregnancy loss (RPL)?<br><br>DESIGN: Endometrial and vaginal samples were collected from 47 women with two or more consecutive pregnancy losses and 39 healthy control women without a history of pregnancy loss, between March 2018 and December 2020 at Helsinki University Hospital, Helsinki, Finland. The compositions of the endometrial and vaginal microbiota, analysed using 16S rRNA gene amplicon sequencing, were compared between the RPL and control women, and between individual vaginal and endometrial samples. The mycobiota composition was analysed using internal transcribed spacer 1 amplicon sequencing for a descriptive summary. The models were adjusted for body mass index, age and parity. False discovery rate-corrected P-values (q-values) were used to define nominal statistical significance at q&#xa0;<&#xa0;0.05.<br><br>RESULTS: Lactobacillus crispatus was less abundant in the endometrial samples of women with RPL compared with controls (mean relative abundance 17.2% versus 45.6%, q&#x202f;=&#x202f;0.04). Gardnerella vaginalis was more abundant in the RPL group than in controls in both endometrial (12.4% versus 5.8%, q&#xa0;<&#xa0;0.001) and vaginal (8.7% versus 5.7%, q&#x202f;=&#x202f;0.002) samples. The individual vaginal and endometrial microbial compositions correlated strongly (R&#x202f;=&#x202f;0.85, P&#xa0;<&#xa0;0.001). Fungi were detected in 22% of the endometrial and 36% of the vaginal samples.<br><br>CONCLUSIONS: Dysbiosis of the reproductive tract microbiota is associated with RPL and may represent a novel risk factor for pregnancy losses.}, }
@article {pmid35933808, year = {2022}, author = {Huang, J and Liu, W and Kang, W and He, Y and Yang, R and Mou, X and Zhao, W}, title = {Effects of microbiota on anticancer drugs: Current knowledge and potential applications.}, journal = {EBioMedicine}, volume = {83}, number = {}, pages = {104197}, pmid = {35933808}, issn = {2352-3964}, mesh = {*Antineoplastic Agents/pharmacology/therapeutic use ; Biomarkers ; Fecal Microbiota Transplantation ; Humans ; Immune Checkpoint Inhibitors ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments. We anticipate that future clinical and preclinical studies will highlight the significance of human microbiome as a promising target towards precision medicine in cancer therapies. FUNDING: National Key Research and Development Program of China (2020YFA0907800), Shenzhen Science and Technology Innovation Program (KQTD20200820145822023) and National Natural Science Foundation of China (31900056 and 32000096).}, }
@article {pmid35933769, year = {2022}, author = {Morlock, GE and Morlock, JA and Cardak, AD and Mehl, A}, title = {Potential of simple, rapid, and non-target planar bioassay screening of veterinary drug residues.}, journal = {Journal of chromatography. A}, volume = {1679}, number = {}, pages = {463392}, doi = {10.1016/j.chroma.2022.463392}, pmid = {35933769}, issn = {1873-3778}, mesh = {Animals ; Anti-Bacterial Agents ; Biological Assay ; Chromatography, High Pressure Liquid ; *Drug Residues ; Fluoroquinolones ; Humans ; Milk ; *Veterinary Drugs ; }, abstract = {Veterinary drug residues in food samples of animal origin are currently analyzed by target analysis using high-performance liquid chromatography combined with sophisticated mass spectrometers. Since the results are only partially consistent with the microbiological results and positive findings occur rarely (in the per mil range in Germany), the potential of a simple planar bioassay screening was studied in the field of veterinary drug residue analysis. Using only a simple dilution of the milk for sample preparation, it was challenging to meet the maximum residue limits for antibiotic drug residues, exemplarily shown for the screening of two fluoroquinolones. However, the potential was evident for a simple, rapid, eco-friendly, and non-target screening without expensive instrumentation. Regardless of whether it is an active metabolite, contaminant, degradation product, or veterinary drug residue, the effect indicated on the planar surface due to bioassay detection will most likely also affect the human microbiome when consumed. The non-target screening of the milk samples revealed compounds with substantial antibacterial effects, which were not in the previous focus of interest. These antibacterial compounds will most likely also affect the human microbiome. Is it only the regulated antibiotic residues or generally all antibiotic compounds in a sample that count for consumer protection? The current prevailing understanding of food safety and antimicrobial resistance, based on the results of target (rather than effect) analyses, is being challenged. Non-target planar bioassay screening has been shown to fill a current gap by providing an understanding of inconsistencies and complementing routine target analysis of veterinary drug residues. As a highlight, it provides the full picture of the real levels of active compounds, regardless of the permitted limits of antibiotics.}, }
@article {pmid35931735, year = {2022}, author = {Kim, K and Lee, S and Park, SC and Kim, NE and Shin, C and Lee, SK and Jung, Y and Yoon, D and Kim, H and Kim, S and Hwang, GS and Won, S}, title = {Role of an unclassified Lachnospiraceae in the pathogenesis of type 2 diabetes: a longitudinal study of the urine microbiome and metabolites.}, journal = {Experimental &amp; molecular medicine}, volume = {54}, number = {8}, pages = {1125-1132}, pmid = {35931735}, issn = {2092-6413}, mesh = {Acetoacetates ; *Diabetes Mellitus, Type 2/complications ; Glycated Hemoglobin ; Humans ; Longitudinal Studies ; *Microbiota ; Prospective Studies ; }, abstract = {Recent investigations have revealed that the human microbiome plays an essential role in the occurrence of type 2 diabetes (T2D). However, despite the importance of understanding the involvement of the microbiota throughout the body in T2D, most studies have focused specifically on the intestinal microbiota. Extracellular vesicles (EVs) have been recently found to provide important evidence regarding the mechanisms of T2D pathogenesis, as they act as key messengers between intestinal microorganisms and the host. Herein, we explored microorganisms potentially associated with T2D by tracking changes in microbiota-derived EVs from patient urine samples collected three times over four years. Mendelian randomization analysis was conducted to evaluate the causal relationships among microbial organisms, metabolites, and clinical measurements to provide a comprehensive view of how microbiota can influence T2D. We also analyzed EV-derived metagenomic (N = 393), clinical (N = 5032), genomic (N = 8842), and metabolite (N = 574) data from a prospective longitudinal Korean community-based cohort. Our data revealed that GU174097_g, an unclassified Lachnospiraceae, was associated with T2D (β = -189.13; p = 0.00006), and it was associated with the ketone bodies acetoacetate and 3-hydroxybutyrate (r = -0.0938 and -0.0829, respectively; p = 0.0022 and 0.0069, respectively). Furthermore, a causal relationship was identified between acetoacetate and HbA1c levels (β = 0.0002; p = 0.0154). GU174097_g reduced ketone body levels, thus decreasing HbA1c levels and the risk of T2D. Taken together, our findings indicate that GU174097_g may lower the risk of T2D by reducing ketone body levels.}, }
@article {pmid35930417, year = {2022}, author = {Maybee, J and Pearson, T and Elliott, L}, title = {The Gut-Brain-Microbiome Connection: Can Probiotics Decrease Anxiety and Depression?.}, journal = {Issues in mental health nursing}, volume = {43}, number = {11}, pages = {996-1003}, doi = {10.1080/01612840.2022.2106525}, pmid = {35930417}, issn = {1096-4673}, mesh = {Humans ; Depression/drug therapy ; *Probiotics/therapeutic use ; Anxiety/therapy ; Brain ; *Microbiota ; }, abstract = {Anxiety and depression are highly prevalent mood disorders worldwide. Complete remission of symptoms is often difficult to achieve, despite following recommended treatment guidelines. Numerous antidepressants and anxiolytics exist, and new drugs are being developed constantly, yet the incidence of common mood disorders continues to rise. Despite the prevalence of these issues, mental health treatment has not evolved much in recent years. An exciting area of research uncovered in the past decade is the gut-brain-microbiome axis, a bi-directional communication pathway. Because the human microbiome is closely related to mood, research is being done to investigate whether probiotic supplementation could potentially affect symptoms of anxiety and depression.}, }
@article {pmid35928983, year = {2022}, author = {Hakimjavadi, H and George, SH and Taub, M and Dodds, LV and Sanchez-Covarrubias, AP and Huang, M and Pearson, JM and Slomovitz, BM and Kobetz, EN and Gharaibeh, R and Sowamber, R and Pinto, A and Chamala, S and Schlumbrecht, MP}, title = {The vaginal microbiome is associated with endometrial cancer grade and histology.}, journal = {Cancer research communications}, volume = {2}, number = {6}, pages = {447-455}, pmid = {35928983}, issn = {2767-9764}, support = {P30 CA240139/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; Female ; *Endometrial Neoplasms/genetics ; Vagina/microbiology ; Hysterectomy ; *Microbiota/genetics ; *Carcinoma ; }, abstract = {The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: 1) benign gynecologic disease (controls, n=11), 2) low-grade endometrial carcinoma (n=30), and 3) high-grade endometrial carcinoma (n=20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign vs carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.}, }
@article {pmid35928158, year = {2022}, author = {Díez López, C and Montiel González, D and Vidaki, A and Kayser, M}, title = {Prediction of Smoking Habits From Class-Imbalanced Saliva Microbiome Data Using Data Augmentation and Machine Learning.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {886201}, pmid = {35928158}, issn = {1664-302X}, abstract = {Human microbiome research is moving from characterization and association studies to translational applications in medical research, clinical diagnostics, and others. One of these applications is the prediction of human traits, where machine learning (ML) methods are often employed, but face practical challenges. Class imbalance in available microbiome data is one of the major problems, which, if unaccounted for, leads to spurious prediction accuracies and limits the classifier's generalization. Here, we investigated the predictability of smoking habits from class-imbalanced saliva microbiome data by combining data augmentation techniques to account for class imbalance with ML methods for prediction. We collected publicly available saliva 16S rRNA gene sequencing data and smoking habit metadata demonstrating a serious class imbalance problem, i.e., 175 current vs. 1,070 non-current smokers. Three data augmentation techniques (synthetic minority over-sampling technique, adaptive synthetic, and tree-based associative data augmentation) were applied together with seven ML methods: logistic regression, k-nearest neighbors, support vector machine with linear and radial kernels, decision trees, random forest, and extreme gradient boosting. K-fold nested cross-validation was used with the different augmented data types and baseline non-augmented data to validate the prediction outcome. Combining data augmentation with ML generally outperformed baseline methods in our dataset. The final prediction model combined tree-based associative data augmentation and support vector machine with linear kernel, and achieved a classification performance expressed as Matthews correlation coefficient of 0.36 and AUC of 0.81. Our method successfully addresses the problem of class imbalance in microbiome data for reliable prediction of smoking habits.}, }
@article {pmid35928143, year = {2022}, author = {Alves-Barroco, C and Brito, PH and Santos-Sanches, I and Fernandes, AR}, title = {Phylogenetic analysis and accessory genome diversity reveal insight into the evolutionary history of Streptococcus dysgalactiae.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {952110}, pmid = {35928143}, issn = {1664-302X}, abstract = {Streptococcus dysgalactiae (SD) is capable of infecting both humans and animals and causing a wide range of invasive and non-invasive infections. With two subspecies, the taxonomic status of subspecies of SD remains controversial. Subspecies equisimilis (SDSE) is an important human pathogen, while subspecies dysgalactiae (SDSD) has been considered a strictly animal pathogen; however, occasional human infections by this subspecies have been reported in the last few years. Moreover, the differences between the adaptation of SDSD within humans and other animals are still unknown. In this work, we provide a phylogenomic analysis based on the single-copy core genome of 106 isolates from both the subspecies and different infected hosts (animal and human hosts). The accessory genome of this species was also analyzed for screening of genes that could be specifically involved with adaptation to different hosts. Additionally, we searched putatively adaptive traits among prophage regions to infer the importance of transduction in the adaptation of SD to different hosts. Core genome phylogenetic relationships segregate all human SDSE in a single cluster separated from animal SD isolates. The subgroup of bovine SDSD evolved from this later clade and harbors a specialized accessory genome characterized by the presence of specific virulence determinants (e.g., cspZ) and carbohydrate metabolic functions (e.g., fructose operon). Together, our results indicate a host-specific SD and the existence of an SDSD group that causes human-animal cluster infections may be due to opportunistic infections, and that the exact incidence of SDSD human infections may be underestimated due to failures in identification based on the hemolytic patterns. However, more detailed research into the isolation of human SD is needed to assess whether it is a carrier phenomenon or whether the species can be permanently integrated into the human microbiome, making it ready to cause opportunistic infections.}, }
@article {pmid35913976, year = {2022}, author = {Gu, W and Moon, J and Chisina, C and Kang, B and Park, T and Koh, H}, title = {MiCloud: A unified web platform for comprehensive microbiome data analysis.}, journal = {PloS one}, volume = {17}, number = {8}, pages = {e0272354}, pmid = {35913976}, issn = {1932-6203}, mesh = {Cross-Sectional Studies ; Data Analysis ; *Gastrointestinal Microbiome/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Microbiota/genetics ; }, abstract = {The recent advance in massively parallel sequencing has enabled accurate microbiome profiling at a dramatically lowered cost. Then, the human microbiome has been the subject of intensive investigation in public health and medicine. In the meanwhile, researchers have developed lots of microbiome data analysis methods, protocols, and/or tools. Among those, especially, the web platforms can be highlighted because of the user-friendly interfaces and streamlined protocols for a long sequence of analytic procedures. However, existing web platforms can handle only a categorical trait of interest, cross-sectional study design, and the analysis with no covariate adjustment. We therefore introduce here a unified web platform, named MiCloud, for a binary or continuous trait of interest, cross-sectional or longitudinal/family-based study design, and with or without covariate adjustment. MiCloud handles all such types of analyses for both ecological measures (i.e., alpha and beta diversity indices) and microbial taxa in relative abundance on different taxonomic levels (i.e., phylum, class, order, family, genus and species). Importantly, MiCloud also provides a unified analytic protocol that streamlines data inputs, quality controls, data transformations, statistical methods and visualizations with vastly extended utility and flexibility that are suited to microbiome data analysis. We illustrate the use of MiCloud through the United Kingdom twin study on the association between gut microbiome and body mass index adjusting for age. MiCloud can be implemented on either the web server (http://micloud.kr) or the user's computer (https://github.com/wg99526/micloudgit).}, }
@article {pmid35899413, year = {2022}, author = {Steiner, HE and Patterson, HK and Giles, JB and Karnes, JH}, title = {Bringing pharmacomicrobiomics to the clinic through well-designed studies.}, journal = {Clinical and translational science}, volume = {15}, number = {10}, pages = {2303-2315}, pmid = {35899413}, issn = {1752-8062}, support = {R01 HL156993/HL/NHLBI NIH HHS/United States ; R01HL158686/HL/NHLBI NIH HHS/United States ; T32 ES007091/ES/NIEHS NIH HHS/United States ; R01 HL158686/HL/NHLBI NIH HHS/United States ; K01 HL143137/HL/NHLBI NIH HHS/United States ; K01HL143137/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Drug-Related Side Effects and Adverse Reactions ; Gastrointestinal Microbiome/physiology ; *Microbiota ; Reproducibility of Results ; }, abstract = {Pharmacomicrobiomic studies investigate drug-microbiome interactions, such as the effect of microbial variation on drug response and disposition. Studying and understanding the interactions between the gut microbiome and drugs is becoming increasingly relevant to clinical practice due to its potential for avoiding adverse drug reactions or predicting variability in drug response. The highly variable nature of the human microbiome presents significant challenges to assessing microbes' influence. Studies aiming to explore drug-microbiome interactions should be well-designed to account for variation in the microbiome over time and collect data on confounders such as diet, disease, concomitant drugs, and other environmental factors. Here, we assemble a set of important considerations and recommendations for the methodological features required for performing a pharmacomicrobiomic study in humans with a focus on the gut microbiome. Consideration of these factors enable discovery, reproducibility, and more accurate characterization of the relationships between a given drug and the microbiome. Furthermore, appropriate interpretation and dissemination of results from well-designed studies will push the field closer to clinical relevance and implementation.}, }
@article {pmid35899309, year = {2022}, author = {Ye, P and Qiao, X and Tang, W and Wang, C and He, H}, title = {Testing latent class of subjects with structural zeros in negative binomial models with applications to gut microbiome data.}, journal = {Statistical methods in medical research}, volume = {31}, number = {11}, pages = {2237-2254}, doi = {10.1177/09622802221115881}, pmid = {35899309}, issn = {1477-0334}, mesh = {Humans ; *Gastrointestinal Microbiome ; Models, Statistical ; Computer Simulation ; Poisson Distribution ; }, abstract = {Human microbiome research has become a hot-spot in health and medical research in the past decade due to the rapid development of modern high-throughput. Typical data in a microbiome study consisting of the operational taxonomic unit counts may have over-dispersion and/or structural zero issues. In such cases, negative binomial models can be applied to address the over-dispersion issue, while zero-inflated negative binomial models can be applied to address both issues. In practice, it is essential to know if there is zero-inflation in the data before applying negative binomial or zero-inflated negative binomial models because zero-inflated negative binomial models may be unnecessarily complex and difficult to interpret, or may even suffer from convergence issues if there is no zero-inflation in the data. On the other hand, negative binomial models may yield invalid inferences if the data does exhibit excessive zeros. In this paper, we develop a new test for detecting zero-inflation resulting from a latent class of subjects with structural zeros in a negative binomial regression model by directly comparing the amount of observed zeros with what would be expected under the negative binomial regression model. A closed form of the test statistic as well as its asymptotic properties are derived based on estimating equations. Intensive simulation studies are conducted to investigate the performance of the new test and compare it with the classical Wald, likelihood ratio, and score tests. The tests are also applied to human gut microbiome data to test latent class in microbial genera.}, }
@article {pmid35889831, year = {2022}, author = {Sharon, I and Quijada, NM and Pasolli, E and Fabbrini, M and Vitali, F and Agamennone, V and Dötsch, A and Selberherr, E and Grau, JH and Meixner, M and Liere, K and Ercolini, D and de Filippo, C and Caderni, G and Brigidi, P and Turroni, S}, title = {The Core Human Microbiome: Does It Exist and How Can We Find It? A Critical Review of the Concept.}, journal = {Nutrients}, volume = {14}, number = {14}, pages = {}, pmid = {35889831}, issn = {2072-6643}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Metagenomics/methods ; *Microbiota ; Sequence Analysis, DNA ; }, abstract = {The core microbiome, which refers to a set of consistent microbial features across populations, is of major interest in microbiome research and has been addressed by numerous studies. Understanding the core microbiome can help identify elements that lead to dysbiosis, and lead to treatments for microbiome-related health states. However, defining the core microbiome is a complex task at several levels. In this review, we consider the current state of core human microbiome research. We consider the knowledge that has been gained, the factors limiting our ability to achieve a reliable description of the core human microbiome, and the fields most likely to improve that ability. DNA sequencing technologies and the methods for analyzing metagenomics and amplicon data will most likely facilitate higher accuracy and resolution in describing the microbiome. However, more effort should be invested in characterizing the microbiome's interactions with its human host, including the immune system and nutrition. Other components of this holobiontic system should also be emphasized, such as fungi, protists, lower eukaryotes, viruses, and phages. Most importantly, a collaborative effort of experts in microbiology, nutrition, immunology, medicine, systems biology, bioinformatics, and machine learning is probably required to identify the traits of the core human microbiome.}, }
@article {pmid35888986, year = {2022}, author = {Rajakaruna, S and Pérez-Burillo, S and Kramer, DL and Rufián-Henares, J&#xc1; and Paliy, O}, title = {Dietary Melanoidins from Biscuits and Bread Crust Alter the Structure and Short-Chain Fatty Acid Production of Human Gut Microbiota.}, journal = {Microorganisms}, volume = {10}, number = {7}, pages = {}, pmid = {35888986}, issn = {2076-2607}, abstract = {Melanoidins are the products of the Maillard reaction between carbonyl and amino groups of macromolecules and are readily formed in foods, especially during heat treatment. In this study we utilized the three-stage Human Gut Simulator system to assess the effect of providing melanoidins extracted from either biscuits or bread crust to the human gut microbiota. Addition of melanoidins to the growth medium led to statistically significant alterations in the microbial community composition, and it increased short-chain fatty acid and antioxidant production by the microbiota. The magnitude of these changes was much higher for cultures grown with biscuit melanoidins. Several lines of evidence indicate that such differences between these melanoidin sources might be due to the presence of lipid components in biscuit melanoidin structures. Because melanoidins are largely not degraded by human gastrointestinal enzymes, they provide an additional source of microbiota-accessible nutrients to our gut microbes.}, }
@article {pmid35888025, year = {2022}, author = {Ratanapokasatit, Y and Laisuan, W and Rattananukrom, T and Petchlorlian, A and Thaipisuttikul, I and Sompornrattanaphan, M}, title = {How Microbiomes Affect Skin Aging: The Updated Evidence and Current Perspectives.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {35888025}, issn = {2075-1729}, abstract = {The skin has a multifactorial aging process, caused by both intrinsic and extrinsic factors. A major theory of aging involves cellular senescence or apoptosis resulting from oxidative damage as the skin's antioxidant system tends to weaken with age. The human microbiota is a complex ecosystem that is made up of microorganisms (bacteria, fungi, and viruses). Both gut and skin microbiota have essential roles in the protection against invading pathogens, mediating inflammatory conditions, and the modulation of the immune system which is involved in both innate and adaptive immune responses. However, the human microbiome could be changed during the life stage and affected by various perturbations. An alteration of the intestinal bacteria results in "microbial dysbiosis" which is associated with the influence of various diseases, including aging. The skin interactome is a novel integration of the "genome-microbiome-exposome" that plays a significant role in skin aging and skin health. Mitigating the negative impacts of factors influencing the skin interactome should be the future strategy to protect, prevent, and delay skin aging along with preserving healthy skin conditions. This review summarizes the current evidence on how human microbiomes affect skin aging and demonstrates the possible interventions, relating to human microbiomes, to modulate skin health and aging. Probiotics-based products are currently available mainly for the add-on treatment of many dermatologic conditions. However, at this point, there are limited clinical studies on skin anti-aging purposes and more are required as this evolving concept is on the rise and might provide an insight into future therapeutic options.}, }
@article {pmid35886007, year = {2022}, author = {Hua, X and Song, L and Yu, G and Vogtmann, E and Goedert, JJ and Abnet, CC and Landi, MT and Shi, J}, title = {MicrobiomeGWAS: A Tool for Identifying Host Genetic Variants Associated with Microbiome Composition.}, journal = {Genes}, volume = {13}, number = {7}, pages = {}, pmid = {35886007}, issn = {2073-4425}, mesh = {*Genome-Wide Association Study ; Humans ; Lung ; *Microbiota/genetics ; Polymorphism, Single Nucleotide/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The microbiome is the collection of all microbial genes and can be investigated by sequencing highly variable regions of 16S ribosomal RNA (rRNA) genes. Evidence suggests that environmental factors and host genetics may interact to impact human microbiome composition. Identifying host genetic variants associated with human microbiome composition not only provides clues for characterizing microbiome variation but also helps to elucidate biological mechanisms of genetic associations, prioritize genetic variants, and improve genetic risk prediction. Since a microbiota functions as a community, it is best characterized by β diversity; that is, a pairwise distance matrix. We develop a statistical framework and a computationally efficient software package, microbiomeGWAS, for identifying host genetic variants associated with microbiome β diversity with or without interacting with an environmental factor. We show that the score statistics have positive skewness and kurtosis due to the dependent nature of the pairwise data, which makes p-value approximations based on asymptotic distributions unacceptably liberal. By correcting for skewness and kurtosis, we develop accurate p-value approximations, whose accuracy was verified by extensive simulations. We exemplify our methods by analyzing a set of 147 genotyped subjects with 16S rRNA microbiome profiles from non-malignant lung tissues. Correcting for skewness and kurtosis eliminated the dramatic deviation in the quantile-quantile plots. We provided preliminary evidence that six established lung cancer risk SNPs were collectively associated with microbiome composition for both unweighted (p = 0.0032) and weighted (p = 0.011) UniFrac distance matrices. In summary, our methods will facilitate analyzing large-scale genome-wide association studies of the human microbiome.}, }
@article {pmid35885645, year = {2022}, author = {Hajjo, R and Sabbah, DA and Al Bawab, AQ}, title = {Unlocking the Potential of the Human Microbiome for Identifying Disease Diagnostic Biomarkers.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {7}, pages = {}, pmid = {35885645}, issn = {2075-4418}, support = {2019-2020/23/07//Deanship of Scientific Research at Al-Zaytoonah University of Jordan/ ; }, abstract = {The human microbiome encodes more than three million genes, outnumbering human genes by more than 100 times, while microbial cells in the human microbiota outnumber human cells by 10 times. Thus, the human microbiota and related microbiome constitute a vast source for identifying disease biomarkers and therapeutic drug targets. Herein, we review the evidence backing the exploitation of the human microbiome for identifying diagnostic biomarkers for human disease. We describe the importance of the human microbiome in health and disease and detail the use of the human microbiome and microbiota metabolites as potential diagnostic biomarkers for multiple diseases, including cancer, as well as inflammatory, neurological, and metabolic diseases. Thus, the human microbiota has enormous potential to pave the road for a new era in biomarker research for diagnostic and therapeutic purposes. The scientific community needs to collaborate to overcome current challenges in microbiome research concerning the lack of standardization of research methods and the lack of understanding of causal relationships between microbiota and human disease.}, }
@article {pmid35883998, year = {2022}, author = {Inchingolo, AD and Malcangi, G and Semjonova, A and Inchingolo, AM and Patano, A and Coloccia, G and Ceci, S and Marinelli, G and Di Pede, C and Ciocia, AM and Mancini, A and Palmieri, G and Barile, G and Settanni, V and De Leonardis, N and Rapone, B and Piras, F and Viapiano, F and Cardarelli, F and Nucci, L and Bordea, IR and Scarano, A and Lorusso, F and Palermo, A and Costa, S and Tartaglia, GM and Corriero, A and Brienza, N and Di Venere, D and Inchingolo, F and Dipalma, G}, title = {Oralbiotica/Oralbiotics: The Impact of Oral Microbiota on Dental Health and Demineralization: A Systematic Review of the Literature.}, journal = {Children (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {35883998}, issn = {2227-9067}, abstract = {The oral microbiota plays a vital role in the human microbiome and oral health. Imbalances between microbes and their hosts can lead to oral and systemic disorders such as diabetes or cardiovascular disease. The purpose of this review is to investigate the literature evidence of oral microbiota dysbiosis on oral health and discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis; both have enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches as ORALBIOTICA for oral diseases such as demineralization. PubMed, Web of Science, Google Scholar, Scopus, Cochrane Library, EMBEDDED, Dentistry &amp; Oral Sciences Source via EBSCO, APA PsycINFO, APA PsyArticles, and DRUGS@FDA were searched for publications that matched our topic from January 2017 to 22 April 2022, with an English language constraint using the following Boolean keywords: ("microbio*" and "demineralization*") AND ("oral microbiota" and "demineralization"). Twenty-two studies were included for qualitative analysis. As seen by the studies included in this review, the balance of the microbiota is unstable and influenced by oral hygiene, the presence of orthodontic devices in the oral cavity and poor eating habits that can modify its composition and behavior in both positive and negative ways, increasing the development of demineralization, caries processes, and periodontal disease. Under conditions of dysbiosis, favored by an acidic environment, the reproduction of specific bacterial strains increases, favoring cariogenic ones such as Bifidobacterium dentium, Bifidobacterium longum, and S. mutans, than S. salivarius and A. viscosus, and increasing of Firmicutes strains to the disadvantage of Bacteroidetes. Microbial balance can be restored by using probiotics and prebiotics to manage and treat oral diseases, as evidenced by mouthwashes or dietary modifications that can influence microbiota balance and prevent or slow disease progression.}, }
@article {pmid35877336, year = {2022}, author = {Lai, Y and Mi, J and Feng, Q}, title = {Fusobacterium nucleatum and Malignant Tumors of the Digestive Tract: A Mechanistic Overview.}, journal = {Bioengineering (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {35877336}, issn = {2306-5354}, support = {ZR2021MC098//Natural Science Foundation of Shandong Province/ ; }, abstract = {Fusobacterium nucleatum (F. nucleatum) is an oral anaerobe that plays a role in several oral diseases. However, F. nucleatum is also found in other tissues of the digestive tract, and several studies have recently reported that the level of F. nucleatum is significantly elevated in malignant tumors of the digestive tract. F. nucleatum is proposed as one of the risk factors in the initiation and progression of digestive tract malignant tumors. In this review, we summarize recent reports on F. nucleatum and its role in digestive tract cancers and evaluate the mechanisms underlying the action of F. nucleatum in digestive tract cancers.}, }
@article {pmid35875231, year = {2022}, author = {Stuivenberg, G and Daisley, B and Akouris, P and Reid, G}, title = {In vitro assessment of histamine and lactate production by a multi-strain synbiotic.}, journal = {Journal of food science and technology}, volume = {59}, number = {9}, pages = {3419-3427}, pmid = {35875231}, issn = {0022-1155}, abstract = {Recent studies suggest histamine and d-lactate may negatively impact host health. As excess histamine is deleterious to the host, the identification of bacterial producers has contributed to concerns over the consumption of probiotics or live microorganisms in fermented food items. Some probiotic products have been suspected of inducing d-lactic-acidosis; an illness associated with neurocognitive symptoms such as ataxia. The goals of the present study were to test the in vitro production of histamine and d-lactate by a 24-strain daily synbiotic and to outline methods that others can use to test for their production. Using enzymatic based assays, no significant production of histamine was observed compared to controls (P > 0.05), while d-lactate production was comparable to a commercially available probiotic with no associated health risk. These assays provide a means to add to the safety profile of synbiotic and probiotic products.}, }
@article {pmid35873161, year = {2022}, author = {Romani, L and Del Chierico, F and Macari, G and Pane, S and Ristori, MV and Guarrasi, V and Gardini, S and Pascucci, GR and Cotugno, N and Perno, CF and Rossi, P and Villani, A and Bernardi, S and Campana, A and Palma, P and Putignani, L and , }, title = {The Relationship Between Pediatric Gut Microbiota and SARS-CoV-2 Infection.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {908492}, pmid = {35873161}, issn = {2235-2988}, mesh = {Adult ; Bacteroides/genetics ; Bifidobacterium/genetics ; *COVID-19/complications ; Child ; Clostridium/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; Humans ; RNA, Ribosomal, 16S/genetics ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome ; }, abstract = {This is the first study on gut microbiota (GM) in children affected by coronavirus disease 2019 (COVID-19). Stool samples from 88 patients with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and 95 healthy subjects were collected (admission: 3-7 days, discharge) to study GM profile by 16S rRNA gene sequencing and relationship to disease severity. The study group was divided in COVID-19 (68), Non-COVID-19 (16), and MIS-C (multisystem inflammatory syndrome in children) (4). Correlations among GM ecology, predicted functions, multiple machine learning (ML) models, and inflammatory response were provided for COVID-19 and Non-COVID-19 cohorts. The GM of COVID-19 cohort resulted as dysbiotic, with the lowest α-diversity compared with Non-COVID-19 and CTRLs and by a specific β-diversity. Its profile appeared enriched in Faecalibacterium, Fusobacterium, and Neisseria and reduced in Bifidobacterium, Blautia, Ruminococcus, Collinsella, Coprococcus, Eggerthella, and Akkermansia, compared with CTRLs (p < 0.05). All GM paired-comparisons disclosed comparable results through all time points. The comparison between COVID-19 and Non-COVID-19 cohorts highlighted a reduction of Abiotrophia in the COVID-19 cohort (p < 0.05). The GM of MIS-C cohort was characterized by an increase of Veillonella, Clostridium, Dialister, Ruminococcus, and Streptococcus and a decrease of Bifidobacterium, Blautia, Granulicatella, and Prevotella, compared with CTRLs. Stratifying for disease severity, the GM associated to "moderate" COVID-19 was characterized by lower α-diversity compared with "mild" and "asymptomatic" and by a GM profile deprived in Neisseria, Lachnospira, Streptococcus, and Prevotella and enriched in Dialister, Acidaminococcus, Oscillospora, Ruminococcus, Clostridium, Alistipes, and Bacteroides. The ML models identified Staphylococcus, Anaerostipes, Faecalibacterium, Dorea, Dialister, Streptococcus, Roseburia, Haemophilus, Granulicatella, Gemmiger, Lachnospira, Corynebacterium, Prevotella, Bilophila, Phascolarctobacterium, Oscillospira, and Veillonella as microbial markers of COVID-19. The KEGG ortholog (KO)-based prediction of GM functional profile highlighted 28 and 39 KO-associated pathways to COVID-19 and CTRLs, respectively. Finally, Bacteroides and Sutterella correlated with proinflammatory cytokines regardless disease severity. Unlike adult GM profiles, Faecalibacterium was a specific marker of pediatric COVID-19 GM. The durable modification of patients' GM profile suggested a prompt GM quenching response to SARS-CoV-2 infection since the first symptoms. Faecalibacterium and reduced fatty acid and amino acid degradation were proposed as specific COVID-19 disease traits, possibly associated to restrained severity of SARS-CoV-2-infected children. Altogether, this evidence provides a characterization of the pediatric COVID-19-related GM.}, }
@article {pmid35872253, year = {2022}, author = {Kantele, A and Mero, S and Lääveri, T}, title = {Doxycycline as an antimalarial: Impact on travellers' diarrhoea and doxycycline resistance among various stool bacteria - Prospective study and literature review.}, journal = {Travel medicine and infectious disease}, volume = {49}, number = {}, pages = {102403}, doi = {10.1016/j.tmaid.2022.102403}, pmid = {35872253}, issn = {1873-0442}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; *Antimalarials/pharmacology/therapeutic use ; Bacteria ; Diarrhea/drug therapy/microbiology ; Doxycycline/pharmacology/therapeutic use ; Enterobacteriaceae ; *Enterobacteriaceae Infections/microbiology ; Humans ; Prospective Studies ; Travel ; Travel-Related Illness ; beta-Lactamases ; }, abstract = {BACKGROUND: Antibiotics predispose travellers to acquire multidrug-resistant bacteria, such as extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). Although widely used in antimalarial prophylaxis, doxycycline has scarcely been studied in this respect.<br><br>METHODS: We explored the impact of doxycycline on rates of traveller's diarrhoea (TD), ESBL-PE acquisition and, particularly, doxycycline co-resistance among travel-acquired ESBL-PE in a sample of 412 visitors to low- and middle-income countries. We reviewed the literature on traveller studies of doxycycline/tetracycline resistance among stool pathogens and the impact of doxycycline on TD rates, ESBL-PE acquisition, and doxycycline/tetracycline resistance.<br><br>RESULTS: The TD rates were similar for doxycycline users (32/46; 69.6%) and non-users (256/366; 69.9%). Of the 90 travel-acquired ESBL-PE isolates, 84.4% were co-resistant to doxycycline: 100% (11/11) among users and 82.3% (65/79) among non-users. The literature on doxycycline's effect on TD was not conclusive nor did it support a recent decline in doxycycline resistance. Although doxycycline did not increase ESBL-PE acquisition, doxycycline-resistance among stool pathogens proved more frequent for users than non-users.<br><br>CONCLUSIONS: Our prospective data and the literature review together suggest the following: 1) doxycycline does not prevent TD; 2) doxycycline use favours acquisition of doxy/tetracycline-co-resistant intestinal bacteria; 3) although doxycycline does not predispose to travel-related ESBL-PE acquisition per se, it selects ESBL-PE strains co-resistant to doxycycline; 4) doxycycline resistance rates are high among stool bacteria in general with no evidence of any tendency to decrease.}, }
@article {pmid35869172, year = {2022}, author = {Maarsingh, JD and Łaniewski, P and Herbst-Kralovetz, MM}, title = {Immunometabolic and potential tumor-promoting changes in 3D cervical cell models infected with bacterial vaginosis-associated bacteria.}, journal = {Communications biology}, volume = {5}, number = {1}, pages = {725}, pmid = {35869172}, issn = {2399-3642}, support = {3P30CA023074-39S3//Division of Cancer Prevention, National Cancer Institute (NCI Division of Cancer Prevention)/ ; }, mesh = {Bacteria/*classification/pathogenicity ; Cervix Uteri/cytology/*microbiology ; Female ; Humans ; *Microbiota ; Tumor Microenvironment ; Uterine Cervical Neoplasms/*etiology/microbiology ; Vaginosis, Bacterial/complications/immunology/metabolism/*microbiology ; }, abstract = {Specific bacteria of the human microbiome influence carcinogenesis at diverse anatomical sites. Bacterial vaginosis (BV) is the most common vaginal disorder in premenopausal women that is associated with gynecologic sequelae, including cervical cancer. BV-associated microorganisms, such as Fusobacterium, Lancefieldella, Peptoniphilus, and Porphyromonas have been associated with gynecologic and other cancers, though the pro-oncogenic mechanisms employed by these bacteria are poorly understood. Here, we integrated a multi-omics approach with our three-dimensional (3-D) cervical epithelial cell culture model to investigate how understudied BV-associated bacteria linked to gynecologic neoplasia influence hallmarks of cancer in vitro. Lancefieldella parvulum and Peptoniphilus lacrimalis elicited robust proinflammatory responses in 3-D cervical cells. Fusobacterium nucleatum and Fusobacterium gonidiaformans modulated metabolic hallmarks of cancer corresponding to accumulation of 2-hydroxyglutarate, pro-inflammatory lipids, and signs of oxidative stress and genotoxic hydrogen sulfide. This study provides mechanistic insights into how gynecologic cancer-associated bacteria might facilitate a tumor-promoting microenvironment in the human cervix.}, }
@article {pmid35868276, year = {2022}, author = {Lloréns-Rico, V and Simcock, JA and Huys, GRB and Raes, J}, title = {Single-cell approaches in human microbiome research.}, journal = {Cell}, volume = {185}, number = {15}, pages = {2725-2738}, doi = {10.1016/j.cell.2022.06.040}, pmid = {35868276}, issn = {1097-4172}, mesh = {Bacteria/genetics ; Genome, Microbial ; Host Microbial Interactions ; Humans ; *Microbiota ; Sequence Analysis, RNA ; Single-Cell Analysis ; }, abstract = {Microbial culturing and meta-omic profiling technologies have significantly advanced our understanding of the taxonomic and functional variation of the human microbiome and its impact on host processes. The next increase in resolution will come by understanding the role of low-abundant and less-prevalent bacteria and the study of individual cell behaviors that underlie the complexity of microbial ecosystems. To this aim, single-cell techniques are being rapidly developed to isolate, culture, and characterize the genomes and transcriptomes of individual microbes in complex communities. Here, we discuss how these single-cell technologies are providing unique insights into the biology and behavior of human microbiomes.}, }
@article {pmid35863030, year = {2022}, author = {Rhoades, NS and Cinco, IR and Hendrickson, SM and Slifka, MK and Messaoudi, I}, title = {Taxonomic and Functional Shifts in the Perinatal Gut Microbiome of Rhesus Macaques.}, journal = {Microbiology spectrum}, volume = {10}, number = {4}, pages = {e0081422}, pmid = {35863030}, issn = {2165-0497}, support = {P51 OD011092/OD/NIH HHS/United States ; }, mesh = {Adult ; Animals ; Butyrates ; Feces ; Female ; Folic Acid ; *Gastrointestinal Microbiome/physiology ; Humans ; Infant, Newborn ; Macaca mulatta/genetics/metabolism ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; Starch ; }, abstract = {Pregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal health. One of the factors believed to critically modulate these physiological changes is the maternal gut microbiome. However, the dynamic changes in this community during the perinatal period remain understudied. Clinical studies can be complicated by confounding variables like diet and other drivers of heterogeneity in the human microbiome. Therefore, in this study, we conducted a longitudinal analysis of the fecal microbiome obtained during the pregnancy and postpartum periods in 26 captive rhesus macaques using 16S rRNA gene amplicon sequencing and shotgun metagenomics. Shifts at both the taxonomic and functional potential level were detected when comparing pregnancy to postpartum samples. Taxonomically, Alloprevotella, Actinobacillus, and Anaerovibrio were enriched in the gut microbiome during pregnancy, while Treponema, Lachnospiraceae, and Methanosphaera were more abundant postpartum. Functionally, the gut microbiome during pregnancy was associated with increased abundance in pathways involving the production of the short-chain fatty acid (SCFA) butyrate, while pathways associated with starch degradation and folate transformation were more abundant during the postpartum period. These data demonstrate dramatic changes in the maternal gut microbiome even in the absence of dietary changes and suggest that rhesus macaques could provide a valuable model to determine how changes in the microbiome correlate to other physiological changes in pregnancy. IMPORTANCE Pregnancy and the postpartum period are characterized by a myriad of metabolic and physiological adaptations needed to support fetal growth and maternal health. The maternal gut microbiome is believed to play a key role during this period but remains underexplored. Here, we report significant shifts in the taxonomic landscape and functional potential of the gut microbiome in 26 pregnant rhesus macaques during the transition from pregnancy to the postpartum period, despite shared dietary and environmental exposures. Increased abundance of pathways involved in the production of the short-chain fatty acid butyrate could play a critical role in modulating the maternal immune system and regulating fetal tolerance. On the other hand, increased abundance of pathways associated with starch degradation and folate transformation during the postpartum period could be important for meeting the metabolic demands of breastfeeding and neonatal growth.}, }
@article {pmid35863001, year = {2022}, author = {Khan, MT and Mahmud, A and Hasan, M and Azim, KF and Begum, MK and Rolin, MH and Akter, A and Mondal, SI}, title = {Proteome Exploration of Legionella pneumophila To Identify Novel Therapeutics: a Hierarchical Subtractive Genomics and Reverse Vaccinology Approach.}, journal = {Microbiology spectrum}, volume = {10}, number = {4}, pages = {e0037322}, pmid = {35863001}, issn = {2165-0497}, mesh = {Anti-Bacterial Agents ; Epitopes ; Genomics ; Humans ; *Legionella pneumophila/genetics ; *Legionnaires' Disease/drug therapy/prevention &amp; control ; Molecular Docking Simulation ; *Proteome ; Toll-Like Receptor 2 ; Vaccinology ; }, abstract = {Legionella pneumophila is the causative agent of a severe type of pneumonia (lung infection) called Legionnaires' disease. It is emerging as an antibiotic-resistant strain day by day. Hence, identifying novel drug targets and vaccine candidates is essential to fight against this pathogen. Here, attempts were taken through a subtractive genomics approach on the complete proteome of L. pneumophila to address the challenges of multidrug resistance. A total of 2,930 proteins from L. pneumophila proteome were investigated through diverse subtractive proteomics approaches, e.g., identification of human nonhomologous and pathogen-specific essential proteins, druggability and "anti-target" analysis, subcellular localization prediction, human microbiome nonhomology screening, and protein-protein interaction studies to find out effective drug and vaccine targets. Only three fulfilled these criteria and were proposed as novel drug targets against L. pneumophila. Furthermore, outer membrane protein TolB was identified as a potential vaccine target with a better antigenicity score. Antigenicity and transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis, and a molecular docking approach were adopted to generate the most potent epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes, along with suitable adjuvant and linkers. The designed vaccine construct showed higher binding interaction with different major histocompatibility complex (MHC) molecules and human immune TLR-2 receptors with minimum deformability at the molecular level. The present study aids the development of novel therapeutics and vaccine candidates for efficient treatment and prevention of L. pneumophila infections. However, further wet-lab-based phenotypic and genomic investigations and in vivo trials are highly recommended to validate our prediction experimentally. IMPORTANCE Legionella pneumophila is a human pathogen distributed worldwide, causing Legionnaires' disease (LD), a severe form of pneumonia and respiratory tract infection. L. pneumophila is emerging as an antibiotic-resistant strain, and controlling LD is now difficult. Hence, developing novel drugs and vaccines against L. pneumophila is a major research priority. Here, the complete proteome of L. pneumophila was considered for subtractive genomics approaches to address the challenge of antimicrobial resistance. Our subtractive proteomics approach identified three potential drug targets that are promising for future application. Furthermore, a possible vaccine candidate, "outer membrane protein TolB," was proposed using reverse vaccinology analysis. The constructed vaccine candidate showed higher binding interaction with MHC molecules and human immune TLR-2 receptors at the molecular level. Overall, the present study aids in developing novel therapeutics and vaccine candidates for efficient treatment of the infections caused by L. pneumophila.}, }
@article {pmid35861908, year = {2022}, author = {Fabbrocini, G and Ferrillo, M and Donnarumma, M and Papale, A and Pinto, D and Rinaldi, F}, title = {A Randomized, Double-Blind, Placebo-Controlled, Multicentric Study to Evaluate the Efficacy and the Tolerability of a Class II Medical Device in the Treatment of Mild and Moderate Acne.}, journal = {Dermatology and therapy}, volume = {12}, number = {8}, pages = {1835-1845}, pmid = {35861908}, issn = {2193-8210}, abstract = {INTRODUCTION: Several options are available to treat acne lesions, including topical benzoyl peroxide, topical retinoids, topical antibiotics, oral antibiotics, hormonal therapy, isotretinoin, and procedural therapies, such as light and laser therapies, although these cause side effects. This study aimed to establish the efficacy and tolerability of a class IIa medical device containing lactic acid, azelaic acid/polyglyceryl-3 copolymer, azelamidopropyl dimethyl amine, and bifida ferment lysate for the treatment of mild and moderate acne lesions.<br><br>METHODS: A randomized, double-blind, placebo-controlled, multicentric study was carried out in which 60 persons of both genders aged&#x2009;&#x2265;&#x2009;16&#xa0;years affected by mild or moderate acne were enrolled. Each person used the product twice daily for 2&#xa0;months. The clinical score (classified as absent, mild, moderate, and severe) of lesions such as blackheads, whiteheads, papules and pustules, erythema, desquamation, sebum secretion, and porphyrins production by a wood lamp was evaluated on the basis of a dermatologist's visual assessment at baseline (t0) and after 2&#xa0;months of treatment (t1), and the results were compared between groups. Digital photographic images were also taken.<br><br>RESULTS: Sixty subjects concluded the trial. It was observed that subjects treated with the medical device (group I) showed overall improvement in the analyzed acne lesions compared with placebo (group II) after 2&#xa0;months of treatment. The efficacy of the treatment was also expressed as partial and total clearance. The medical device produced higher percentages of both partial and total clearance in all analyzed parameters, compared with the placebo group. The study was safe and well tolerated.<br><br>CONCLUSIONS: It was observed that the participants showed an overall improvement of the analyzed lesions in comparison with the placebo group, without adverse events during the trial. Hence, the medical device was found to be safe and effective in the treatment of mild or moderate acne.}, }
@article {pmid35856563, year = {2022}, author = {Lesniak, NA and Schubert, AM and Flynn, KJ and Leslie, JL and Sinani, H and Bergin, IL and Young, VB and Schloss, PD}, title = {The Gut Bacterial Community Potentiates Clostridioides difficile Infection Severity.}, journal = {mBio}, volume = {13}, number = {4}, pages = {e0118322}, pmid = {35856563}, issn = {2150-7511}, support = {T32 AI007528/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; R01 GM099514/GM/NIGMS NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; U2C DK110768/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/genetics ; Bile Acids and Salts ; *Clostridioides difficile ; *Clostridium Infections/microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {The severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, and creatinine levels as well as C. difficile ribotype and toxin genes have been associated with disease severity. However, it is unclear whether specific members of the gut microbiota are associated with variations in disease severity. The gut microbiota is known to interact with C. difficile during infection. Perturbations to the gut microbiota are necessary for C. difficile to colonize the gut. The gut microbiota can inhibit C. difficile colonization through bile acid metabolism, nutrient consumption, and bacteriocin production. Here, we sought to demonstrate that members of the gut bacterial communities can also contribute to disease severity. We derived diverse gut communities by colonizing germfree mice with different human fecal communities. The mice were then infected with a single C. difficile ribotype 027 clinical isolate, which resulted in moribundity and histopathologic differences. The variation in severity was associated with the human fecal community that the mice received. Generally, bacterial populations with pathogenic potential, such as Enterococcus, Helicobacter, and Klebsiella, were associated with more-severe outcomes. Bacterial groups associated with fiber degradation and bile acid metabolism, such as Anaerotignum, Blautia, Lactonifactor, and Monoglobus, were associated with less-severe outcomes. These data indicate that, in addition to the host and C. difficile subtype, populations of gut bacteria can influence CDI disease severity. IMPORTANCE Clostridioides difficile colonization can be asymptomatic or develop into an infection ranging in severity from mild diarrhea to toxic megacolon, sepsis, and death. Models that predict severity and guide treatment decisions are based on clinical factors and C. difficile characteristics. Although the gut microbiome plays a role in protecting against CDI, its effect on CDI disease severity is unclear and has not been incorporated into disease severity models. We demonstrated that variation in the microbiome of mice colonized with human feces yielded a range of disease outcomes. These results revealed groups of bacteria associated with both severe and mild C. difficile infection outcomes. Gut bacterial community data from patients with CDI could improve our ability to identify patients at risk of developing more severe disease and improve interventions that target C. difficile and the gut bacteria to reduce host damage.}, }
@article {pmid35838756, year = {2022}, author = {Ksiezarek, M and Grosso, F and Ribeiro, TG and Peixe, L}, title = {Genomic diversity of genus Limosilactobacillus.}, journal = {Microbial genomics}, volume = {8}, number = {7}, pages = {}, pmid = {35838756}, issn = {2057-5858}, mesh = {*Genome ; *Genomics ; Lactobacillaceae ; }, abstract = {The genus Limosilactobacillus (formerly Lactobacillus) contains multiple species considered to be adapted to vertebrates, yet their genomic diversity has not been explored. In this study, we performed comparative genomic analysis of Limosilactobacillus (22 species; 332 genomes) isolated from different niches, further focusing on human strains (11 species; 74 genomes) and their adaptation features to specific body sites. Phylogenomic analysis of Limosilactobacillus showed misidentification of some strains deposited in public databases and existence of putative novel Limosilactobacillus species. The pangenome analysis revealed a remarkable genomic diversity (only 1.3 % of gene clusters are shared), and we did not observe a strong association of the accessory genome with different niches. The pangenome of Limosilactobacillus reuteri and Limosilactobacillus fermentum was open, suggesting that acquisition of genes is still occurring. Although most Limosilactobacillus were predicted as antibiotic susceptible (83%), acquired antibiotic-resistance genes were common in L. reuteri from food-producing animals. Genes related to lactic acid isoform production (>95 %) and putative bacteriocins (70.2%) were identified in most Limosilactobacillus strains, while prophages (55.4%) and CRISPR-Cas systems (32.0%) were less prevalent. Among strains from human sources, several metabolic pathways were predicted as conserved and completed. Their accessory genome was highly variable and did not cluster according to different human body sites, with some exceptions (urogenital Limosilactobacillus vaginalis , Limosilactobacillus portuensis , Limosilactobacillus urinaemulieris and Limosilactobacillus coleohominis or gastrointestinal Limosilactobacillus mucosae). Moreover, we identified 12 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologues that were significantly enriched in strains from particular body sites. We concluded that evolution of the highly diverse Limosilactobacillus is complex and not always related to niche or human body site origin.}, }
@article {pmid35835996, year = {2022}, author = {Merli, P and Massa, M and Russo, A and Rea, F and Del Chierico, F and Galaverna, F and Del Bufalo, F and Pane, S and Algeri, M and Romeo, EF and Masucci, L and De Angelis, P and Putignani, L and Locatelli, F}, title = {Fecal microbiota transplantation for the treatment of steroid-refractory, intestinal, graft-versus-host disease in a pediatric patient.}, journal = {Bone marrow transplantation}, volume = {57}, number = {10}, pages = {1600-1603}, pmid = {35835996}, issn = {1476-5365}, mesh = {Child ; Fecal Microbiota Transplantation ; *Graft vs Host Disease/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Steroids ; }, }
@article {pmid35832621, year = {2022}, author = {Balaji, A and Sapoval, N and Seto, C and Leo Elworth, RA and Fu, Y and Nute, MG and Savidge, T and Segarra, S and Treangen, TJ}, title = {KOMB: K-core based de novo characterization of copy number variation in microbiomes.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {3208-3222}, pmid = {35832621}, issn = {2001-0370}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {Characterizing metagenomes via kmer-based, database-dependent taxonomic classification has yielded key insights into underlying microbiome dynamics. However, novel approaches are needed to track community dynamics and genomic flux within metagenomes, particularly in response to perturbations. We describe KOMB, a novel method for tracking genome level dynamics within microbiomes. KOMB utilizes K-core decomposition to identify Structural variations (SVs), specifically, population-level Copy Number Variation (CNV) within microbiomes. K-core decomposition partitions the graph into shells containing nodes of induced degree at least K, yielding reduced computational complexity compared to prior approaches. Through validation on a synthetic community, we show that KOMB recovers and profiles repetitive genomic regions in the sample. KOMB is shown to identify functionally-important regions in Human Microbiome Project datasets, and was used to analyze longitudinal data and identify keystone taxa in Fecal Microbiota Transplantation (FMT) samples. In summary, KOMB represents a novel graph-based, taxonomy-oblivious, and reference-free approach for tracking CNV within microbiomes. KOMB is open source and available for download at https://gitlab.com/treangenlab/komb.}, }
@article {pmid35814671, year = {2022}, author = {Vacca, M and Porrelli, A and Calabrese, FM and Lippolis, T and Iacobellis, I and Celano, G and Pinto, D and Russo, F and Giannelli, G and De Angelis, M}, title = {How Metabolomics Provides Novel Insights on Celiac Disease and Gluten-Free Diet: A Narrative Review.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {859467}, pmid = {35814671}, issn = {1664-302X}, abstract = {Celiac disease (CD) is an inflammatory autoimmune disorder triggered by the ingestion of gluten from wheat and other cereals. Nowadays, its positive diagnosis is based on invasive approaches such as the histological examination of intestinal biopsies and positive serology screening of antibodies. After proven diagnosis, the only admissible treatment for CD individuals is strict life-long adherence to gluten-free diet (GFD), although it is not a conclusive therapy. Acting by different mechanisms and with different etiologies, both CD and GFD have a great impact on gut microbiota that result in a different taxa composition. Altered production of specific metabolites reflects these microbiota changes. In this light, the currently available literature reports some suggestions about the possible use of specific metabolites, detected by meta-omics analyses, as potential biomarkers for a CD non-invasive diagnosis. To highlight insights about metabolomics application in CD study, we conducted a narrative dissertation of selected original articles published in the last decade. By applying a systematic search, it clearly emerged how the metabolomic signature appears to be contradictory, as well as poorly investigated.}, }
@article {pmid35810835, year = {2022}, author = {Johnson, KV and Steenbergen, L}, title = {Do common antibiotic treatments influence emotional processing?.}, journal = {Physiology &amp; behavior}, volume = {255}, number = {}, pages = {113900}, doi = {10.1016/j.physbeh.2022.113900}, pmid = {35810835}, issn = {1873-507X}, mesh = {Adult ; Animals ; Anti-Bacterial Agents/pharmacology ; Anxiety/drug therapy ; Brain/physiology ; *Emotions ; *Gastrointestinal Microbiome/physiology ; Humans ; }, abstract = {Antibiotics are among the most commonly prescribed medications worldwide, yet research in recent years has revealed the detrimental effect they can have on the human microbiome, with implications for health. The community of microorganisms inhabiting the gut has been shown to regulate physiological and neural processes. Since studies in both humans and animal models have revealed that the gut microbiome can affect the brain, influencing emotion and cognition, here we investigate whether antibiotic treatment is associated with changes in emotional processing and mood with a between-subject design in 105 young healthy adult volunteers, using both psychological tests and questionnaires. As both the immune system and vagal signalling can mediate the microbiome-gut-brain axis, we also assess whether there is any evidence of such changes in participant physiology. We find that individuals who have taken antibiotics in the past three months show a stronger emotional bias towards sadness and at a physiological level they have a higher heart rate (though this does not mediate the relationship with negative bias). While we cannot rule out a possible role of prior infection, our findings are in any case highly relevant in light of research revealing that antibiotics are linked to increased susceptibility to depression and anxiety. Our results also have implications for listing antibiotic use as an exclusion criterion in studies on emotional processing and psychophysiology.}, }
@article {pmid35809795, year = {2022}, author = {Mukherjee, AG and Wanjari, UR and Bradu, P and Murali, R and Kannampuzha, S and Loganathan, T and C, GPD and Prakash B P, A and Renu, K and Dey, A and Vellingiri, B and Valsala Gopalakrishnan, A}, title = {The crosstalk of the human microbiome in breast and colon cancer: A metabolomics analysis.}, journal = {Critical reviews in oncology/hematology}, volume = {176}, number = {}, pages = {103757}, doi = {10.1016/j.critrevonc.2022.103757}, pmid = {35809795}, issn = {1879-0461}, mesh = {*Breast Neoplasms/therapy ; *Colonic Neoplasms/diagnosis/therapy ; Dysbiosis ; Female ; Humans ; Metabolomics/methods ; *Microbiota ; }, abstract = {The human microbiome's role in colon and breast cancer is described in this review. Understanding how the human microbiome and metabolomics interact with breast and colon cancer is the chief area of this study. First, the role of the gut and distal microbiome in breast and colon cancer is investigated, and the direct relationship between microbial dysbiosis and breast and colon cancer is highlighted. This work also focuses on the many metabolomic techniques used to locate prospective biomarkers, make an accurate diagnosis, and research new therapeutic targets for cancer treatment. This review clarifies the influence of anti-tumor medications on the microbiota and the proactive measures that can be taken to treat cancer using a variety of therapies, including radiotherapy, chemotherapy, next-generation biotherapeutics, gene-based therapy, integrated omics technology, and machine learning.}, }
@article {pmid35804891, year = {2022}, author = {McKeon, MG and Gallant, JN and Kim, YJ and Das, SR}, title = {It Takes Two to Tango: A Review of Oncogenic Virus and Host Microbiome Associated Inflammation in Head and Neck Cancer.}, journal = {Cancers}, volume = {14}, number = {13}, pages = {}, pmid = {35804891}, issn = {2072-6694}, abstract = {While the two primary risk factors for head and neck squamous cell carcinoma (HNSCC) are alcohol and tobacco, viruses account for an important and significant upward trend in HNSCC incidence. Human papillomavirus (HPV) is the causative agent for a subset of oropharyngeal squamous cell carcinoma (OPSCC)-a cancer that is impacting a rapidly growing group of typically middle-aged non-smoking white males. While HPV is a ubiquitously present (with about 1% of the population having high-risk oral HPV infection at any one time), less than 1% of those infected with high-risk strains develop OPSCC-suggesting that additional cofactors or coinfections may be required. Epstein-Barr virus (EBV) is a similarly ubiquitous virus that is strongly linked to nasopharyngeal carcinoma (NPC). Both of these viruses cause cellular transformation and chronic inflammation. While dysbiosis of the human microbiome has been associated with similar chronic inflammation and the pathogenesis of mucosal diseases (including OPSCC and NPC), a significant knowledge gap remains in understanding the role of bacterial-viral interactions in the initiation, development, and progression of head and neck cancers. In this review, we utilize the known associations of HPV with OPSCC and EBV with NPC to investigate these interactions. We thoroughly review the literature and highlight how perturbations of the pharyngeal microbiome may impact host-microbiome-tumor-viral interactions-leading to tumor growth.}, }
@article {pmid35803930, year = {2022}, author = {Schneider, KM and Mohs, A and Gui, W and Galvez, EJC and Candels, LS and Hoenicke, L and Muthukumarasamy, U and Holland, CH and Elfers, C and Kilic, K and Schneider, CV and Schierwagen, R and Strnad, P and Wirtz, TH and Marschall, HU and Latz, E and Lelouvier, B and Saez-Rodriguez, J and de Vos, W and Strowig, T and Trebicka, J and Trautwein, C}, title = {Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3964}, pmid = {35803930}, issn = {2041-1723}, mesh = {Animals ; *Carcinoma, Hepatocellular/metabolism ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; *Liver Neoplasms/metabolism ; Mice ; *Microbiota ; Tumor Microenvironment ; }, abstract = {Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, and therapeutic options for advanced HCC are limited. Here, we observe that intestinal dysbiosis affects antitumor immune surveillance and drives liver disease progression towards cancer. Dysbiotic microbiota, as seen in Nlrp6[-/-] mice, induces a Toll-like receptor 4 dependent expansion of hepatic monocytic myeloid-derived suppressor cells (mMDSC) and suppression of T-cell abundance. This phenotype is transmissible via fecal microbiota transfer and reversible upon antibiotic treatment, pointing to the high plasticity of the tumor microenvironment. While loss of Akkermansia muciniphila correlates with mMDSC abundance, its reintroduction restores intestinal barrier function and strongly reduces liver inflammation and fibrosis. Cirrhosis patients display increased bacterial abundance in hepatic tissue, which induces pronounced transcriptional changes, including activation of fibro-inflammatory pathways as well as circuits mediating cancer immunosuppression. This study demonstrates that gut microbiota closely shapes the hepatic inflammatory microenvironment opening approaches for cancer prevention and therapy.}, }
@article {pmid35798805, year = {2022}, author = {Blum, FC and Whitmire, JM and Bennett, JW and Carey, PM and Ellis, MW and English, CE and Law, NN and Tribble, DR and Millar, EV and Merrell, DS}, title = {Nasal microbiota evolution within the congregate setting imposed by military training.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {11492}, pmid = {35798805}, issn = {2045-2322}, support = {Y1-Al-5072/AI/NIAID NIH HHS/United States ; }, mesh = {Cross-Sectional Studies ; Disease Susceptibility ; Georgia ; Humans ; Longitudinal Studies ; *Microbiota/genetics ; *Military Personnel/education ; *Nasal Cavity/microbiology ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Soft Tissue Infections/microbiology ; Staphylococcal Skin Infections/microbiology ; Staphylococcus aureus/genetics/isolation &amp; purification ; }, abstract = {The human microbiome is comprised of a complex and diverse community of organisms that is subject to dynamic changes over time. As such, cross-sectional studies of the microbiome provide a multitude of information for a specific body site at a particular time, but they fail to account for temporal changes in microbial constituents resulting from various factors. To address this shortcoming, longitudinal research studies of the human microbiome investigate the influence of various factors on the microbiome of individuals within a group or community setting. These studies are vital to address the effects of host and/or environmental factors on microbiome composition as well as the potential contribution of microbiome members during the course of an infection. The relationship between microbial constituents and disease development has been previously explored for skin and soft tissue infections (SSTIs) within congregate military trainees. Accordingly, approximately 25% of the population carries Staphylococcus aureus within their nasal cavity, and these colonized individuals are known to be at increased risk for SSTIs. To examine the evolution of the nasal microbiota of U.S. Army Infantry trainees, individuals were sampled longitudinally from their arrival at Fort Benning, Georgia, until completion of their training 90 days later. These samples were then processed to determine S. aureus colonization status and to profile the nasal microbiota using 16S rRNA gene-based methods. Microbiota stability differed dramatically among the individual trainees; some subjects exhibited great stability, some subjects showed gradual temporal changes and some subjects displayed a dramatic shift in nasal microbiota composition. Further analysis utilizing the available trainee metadata suggests that the major drivers of nasal microbiota stability may be S. aureus colonization status and geographic origin of the trainees. Nasal microbiota evolution within the congregate setting imposed by military training is a complex process that appears to be affected by numerous factors. This finding may indicate that future campaigns to prevent S. aureus colonization and future SSTIs among high-risk military trainees may require a 'personalized' approach.}, }
@article {pmid35794566, year = {2022}, author = {Sadrekarimi, H and Gardanova, ZR and Bakhshesh, M and Ebrahimzadeh, F and Yaseri, AF and Thangavelu, L and Hasanpoor, Z and Zadeh, FA and Kahrizi, MS}, title = {Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {301}, pmid = {35794566}, issn = {1479-5876}, mesh = {Bacteria ; Cell Transformation, Neoplastic ; Dysbiosis ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; *Microbiota ; }, abstract = {In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.}, }
@article {pmid35794200, year = {2022}, author = {Singh, S and Natalini, JG and Segal, LN}, title = {Lung microbial-host interface through the lens of multi-omics.}, journal = {Mucosal immunology}, volume = {15}, number = {5}, pages = {837-845}, pmid = {35794200}, issn = {1935-3456}, support = {R37 CA244775/CA/NCI NIH HHS/United States ; }, mesh = {Computational Biology ; Humans ; Lung ; *Microbiota ; }, abstract = {In recent years, our understanding of the microbial world within us has been revolutionized by the use of culture-independent techniques. The use of multi-omic approaches can now not only comprehensively characterize the microbial environment but also evaluate its functional aspects and its relationship with the host immune response. Advances in bioinformatics have enabled high throughput and in-depth analyses of transcripts, proteins and metabolites and enormously expanded our understanding of the role of the human microbiome in different conditions. Such investigations of the lower airways have specific challenges but as the field develops, new approaches will be facilitated. In this review, we focus on how integrative multi-omics can advance our understanding of the microbial environment and its effects on the host immune tone in the lungs.}, }
@article {pmid35784474, year = {2022}, author = {Mi, J and Wang, S and Liu, P and Liu, C and Zhuang, D and Leng, X and Zhang, Q and Bai, F and Feng, Q and Wu, X}, title = {CUL4B Upregulates RUNX2 to Promote the Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Epigenetically Repressing the Expression of miR-320c and miR-372/373-3p.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {921663}, pmid = {35784474}, issn = {2296-634X}, abstract = {Mesenchymal stem cells (MSCs) within the periodontal ligament (PDL), termed periodontal ligament stem cells (PDLSCs), have a self-renewing capability and a multidirectional differentiation potential. The molecular mechanisms that regulate multidirectional differentiation, such as the osteogenic differentiation of PDLSCs, remain to be elucidated. Cullin 4B (CUL4B), which assembles the CUL4B-RING ubiquitin ligase (CRL4B) complex, is involved in regulating a variety of developmental and physiological processes including the skeletal development and stemness of cancer stem cells. However, nothing is known about the possible role of CUL4B in the osteogenic differentiation of PDLSCs. Here, we found that knockdown of CUL4B decreased the proliferation, migration, stemness and osteogenic differentiation ability of PDLSCs. Mechanistically, we demonstrate that CUL4B cooperates with the PRC2 complex to repress the expression of miR-320c and miR-372/373-3p, which results in the upregulation of RUNX2, a master transcription factor (TF) that regulates osteogenic differentiation. In brief, the present study reveals the role of CUL4B as a new regulator of osteogenic differentiation in PDLSCs.}, }
@article {pmid35783436, year = {2022}, author = {Wang, L and Li, F and Gu, B and Qu, P and Liu, Q and Wang, J and Tang, J and Cai, S and Zhao, Q and Ming, Z}, title = {Metaomics in Clinical Laboratory: Potential Driving Force for Innovative Disease Diagnosis.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {883734}, pmid = {35783436}, issn = {1664-302X}, abstract = {Currently, more and more studies suggested that reductionism was lack of holistic and integrative view of biological processes, leading to limited understanding of complex systems like microbiota and the associated diseases. In fact, microbes are rarely present in individuals but normally live in complex multispecies communities. With the recent development of a variety of metaomics techniques, microbes could be dissected dynamically in both temporal and spatial scales. Therefore, in-depth understanding of human microbiome from different aspects such as genomes, transcriptomes, proteomes, and metabolomes could provide novel insights into their functional roles, which also holds the potential in making them diagnostic biomarkers in many human diseases, though there is still a huge gap to fill for the purpose. In this mini-review, we went through the frontlines of the metaomics techniques and explored their potential applications in clinical diagnoses of human diseases, e.g., infectious diseases, through which we concluded that novel diagnostic methods based on human microbiomes shall be achieved in the near future, while the limitations of these techniques such as standard procedures and computational challenges for rapid and accurate analysis of metaomics data in clinical settings were also examined.}, }
@article {pmid35777465, year = {2022}, author = {Yang, S and Wang, S and Wang, Y and Rong, R and Kim, J and Li, B and Koh, AY and Xiao, G and Li, Q and Liu, DJ and Zhan, X}, title = {MB-SupCon: Microbiome-based Predictive Models via Supervised Contrastive Learning.}, journal = {Journal of molecular biology}, volume = {434}, number = {15}, pages = {167693}, pmid = {35777465}, issn = {1089-8638}, support = {U01 AI169298/AI/NIAID NIH HHS/United States ; R01 GM126479/GM/NIGMS NIH HHS/United States ; R56 HG011035/HG/NHGRI NIH HHS/United States ; R01 CA231303/CA/NCI NIH HHS/United States ; R01 HG008983/HG/NHGRI NIH HHS/United States ; K24 AI150992/AI/NIAID NIH HHS/United States ; R01 CA245318/CA/NCI NIH HHS/United States ; U01 CA249245/CA/NCI NIH HHS/United States ; R35 GM136375/GM/NIGMS NIH HHS/United States ; R01 HG011035/HG/NHGRI NIH HHS/United States ; }, mesh = {Diabetes Mellitus, Type 2/genetics/microbiology ; Humans ; Inflammatory Bowel Diseases/genetics/microbiology ; *Metabolome ; Metabolomics/methods ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; *Supervised Machine Learning ; }, abstract = {Human microbiome consists of trillions of microorganisms. Microbiota can modulate the host physiology through molecule and metabolite interactions. Integrating microbiome and metabolomics data have the potential to predict different diseases more accurately. Yet, most datasets only measure microbiome data but without paired metabolome data. Here, we propose a novel integrative modeling framework, Microbiome-based Supervised Contrastive Learning Framework (MB-SupCon). MB-SupCon integrates microbiome and metabolome data to generate microbiome embeddings, which can be used to improve the prediction accuracy in datasets that only measure microbiome data. As a proof of concept, we applied MB-SupCon on 720 samples with paired 16S microbiome data and metabolomics data from patients with type 2 diabetes. MB-SupCon outperformed existing prediction methods and achieved high average prediction accuracies for insulin resistance status (84.62%), sex (78.98%), and race (80.04%). Moreover, the microbiome embeddings form separable clusters for different covariate groups in the lower-dimensional space, which enhances data visualization. We also applied MB-SupCon on a large inflammatory bowel disease study and observed similar advantages. Thus, MB-SupCon could be broadly applicable to improve microbiome prediction models in multi-omics disease studies.}, }
@article {pmid35776498, year = {2023}, author = {Hong, SY and Xia, QD and Yang, YY and Li, C and Zhang, JQ and Xu, JZ and Qin, BL and Xun, Y and Wang, SG}, title = {The role of microbiome: a novel insight into urolithiasis.}, journal = {Critical reviews in microbiology}, volume = {49}, number = {2}, pages = {177-196}, doi = {10.1080/1040841X.2022.2045899}, pmid = {35776498}, issn = {1549-7828}, mesh = {Humans ; *Urolithiasis/complications ; *Urinary Calculi/etiology ; Kidney ; *Microbiota ; *Gastrointestinal Microbiome ; }, abstract = {Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.}, }
@article {pmid35769561, year = {2022}, author = {Ndika, J and Karisola, P and Lahti, V and Fyhrquist, N and Laatikainen, T and Haahtela, T and Alenius, H}, title = {Epigenetic Differences in Long Non-coding RNA Expression in Finnish and Russian Karelia Teenagers With Contrasting Risk of Allergy and Asthma.}, journal = {Frontiers in allergy}, volume = {3}, number = {}, pages = {878862}, pmid = {35769561}, issn = {2673-6101}, abstract = {BACKGROUND: Previously, we investigated skin microbiota and blood cell gene expression in Finnish and Russian teenagers with contrasting incidence of allergic conditions. The microbiota and transcriptomic signatures were distinctly different, with high Acinetobacter abundance and suppression of genes regulating innate immune response in healthy subjects.<br><br>OBJECTIVE: Here, we investigated long non-coding RNA (lncRNA) expression profiles of blood mononuclear cells (PBMC) from healthy and allergic subjects, to identify lncRNAs that act at the interphase of microbiome-mediated immune homeostasis in allergy/asthma.<br><br>METHODS: Genome-wide co-expression network analyses of blood cell lncRNA/mRNA expression was integrated with skin microbiota profiles of Finnish (69) and Russian (75) subjects. Selected lncRNAs were validated by stimulation of cohort-derived PBMCs and a macrophage cell model with birch pollen allergen (Betv1) or lipopolysaccharide, respectively.<br><br>RESULTS: Finnish and Russian PBMCs were differentiated by 3,818 lncRNA transcripts. In the Finnish subjects with high prevalence of allergy and asthma, a subset of 37 downregulated lncRNAs (including, FAM155A-IT1 and LOC400958) were identified. They were part of a co-expression network with 20 genes known to be related to asthma and allergic rhinitis (R > 0.95). Incidentally, all these 20 genes were also components of pathways corresponding to cellular response to bacterium. The Finnish and Russian samples were also differentiated by the abundance of 176 bacterial OTU (operational taxonomic units). The subset of 37 lncRNAs, associated with allergy, was most correlated with the abundance of Acinetobacter (R > +0.5), Jeotgalicoccus (R > +0.5), Corynebacterium (R < -0.5) and Micrococcus (R < -0.5).<br><br>CONCLUSION: In Finnish and Russian teenagers with contrasting allergy and asthma prevalence, epigenetic differences in lncRNA expression appear to be important components of the underlying microbiota-immune interactions. Unraveling the functions of the 37 differing lncRNAs may be the key to understanding microbiome-immune crosstalk, and to develop clinically relevant biomarkers.}, }
@article {pmid35768415, year = {2022}, author = {Kainulainen, V and von Schantz-Fant, C and Kovanen, RM and Potdar, S and Laamanen, K and Saarela, J and Satokari, R}, title = {Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {50}, pmid = {35768415}, issn = {2055-5008}, mesh = {Bifidobacterium/genetics/metabolism ; *Bifidobacterium bifidum/genetics ; Caco-2 Cells ; HT29 Cells ; Humans ; Infant ; RNA, Small Interfering/genetics/metabolism ; }, abstract = {Bifidobacterium spp. are abundant gut commensals, especially in breast-fed infants. Bifidobacteria are associated with many health-promoting effects including maintenance of epithelial barrier and integrity as well as immunomodulation. However, the protective mechanisms of bifidobacteria on intestinal epithelium at molecular level are poorly understood. In this study, we developed a high-throughput in vitro screening assay to explore binding receptors of intestinal epithelial cells for Bifidobacterium bifidum. Short interfering RNAs (siRNA) were used to silence expression of each gene in the Caco-2 cell line one by one. The screen yielded four cell surface proteins, SERPINB3, LGICZ1, PKD1 and PAQR6, which were identified as potential receptors as the siRNA knock-down of their expression decreased adhesion of B. bifidum to the cell line repeatedly during the three rounds of siRNA screening. Furthermore, blocking of these host cell proteins by specific antibodies decreased the binding of B. bifidum significantly to Caco-2 and HT29 cell lines. All these molecules are located on the surface of epithelial cells and three out of four, SERPINB3, PKD1 and PAQR6, are involved in the regulation of cellular processes related to proliferation, differentiation and apoptosis as well as inflammation and immunity. Our results provide leads to the first steps in the mechanistic cascade of B. bifidum-host interactions leading to regulatory effects in the epithelium and may partly explain how this commensal bacterium is able to promote intestinal homeostasis.}, }
@article {pmid35761544, year = {2022}, author = {Farias da Cruz, M and Baraúna Magno, M and Alves Jural, L and Pimentel, TC and Masterson Tavares Pereira Ferreira, D and Almeida Esmerino, E and Luis Paiva Anciens Ramos, G and Vicente Gomila, J and Cristina Silva, M and Cruz, AGD and da Silva Fidalgo, TK and Cople Maia, L}, title = {Probiotics and dairy products in dentistry: A bibliometric and critical review of randomized clinical trials.}, journal = {Food research international (Ottawa, Ont.)}, volume = {157}, number = {}, pages = {111228}, doi = {10.1016/j.foodres.2022.111228}, pmid = {35761544}, issn = {1873-7145}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Bibliometrics ; *COVID-19 ; Child ; *Dental Caries/prevention &amp; control ; Dentistry ; Humans ; Milk/microbiology ; *Periodontal Diseases ; *Probiotics/therapeutic use ; Randomized Controlled Trials as Topic ; }, abstract = {The oral environment is an essential part of the human microbiome. The consumption of probiotic products may improve the oral microbiota and reduce the risk of diseases. This paper presents a bibliometric and critical review of randomized clinical trials (RCTs) that used probiotics to analyze oral parameters in humans. RCTs carried out with no age, gender, and ethnicity restrictions and published in the pre-COVID-19 period were included. Furthermore, the utilization of probiotic dairy products to improve oral health is discussed. The bibliometric review demonstrated that 'Microbiology,' 'Dental caries,' and 'Streptococcus mutants' were the most highlighted keywords. Furthermore, Sweden and India have the highest number of publications. The most prevalent outcomes were 'salivary parameters,' 'periodontal disease,' and 'dental caries.' The most used vehicles for probiotic administration were pharmaceutical formulas and dairy products. The administration of probiotic dairy products could modify the oral microbiota (reductions in S. mutans counts), influence the caries development and periodontal disease in children, adolescents, adults, and the elderly, and improve gingival health. The main probiotic dairy products investigated were milk, fermented milk, yogurt, kefir, curd, and cheese. Lacticaseibacillus paracasei SD1 was the most used probiotic culture. The studies demonstrated that the probiotic effect lasted 2-4 weeks after discontinuing consumption. However, the results depended on the subject type, study design, probiotic strain and concentration, and dairy product type. In conclusion, probiotic dairy products are promising alternatives to improve oral health.}, }
@article {pmid35759916, year = {2022}, author = {Kervinen, K and Holster, T and Saqib, S and Virtanen, S and Stefanovic, V and Rahkonen, L and Nieminen, P and Salonen, A and Kalliala, I}, title = {Parity and gestational age are associated with vaginal microbiota composition in term and late term pregnancies.}, journal = {EBioMedicine}, volume = {81}, number = {}, pages = {104107}, pmid = {35759916}, issn = {2352-3964}, mesh = {Cesarean Section ; Cross-Sectional Studies ; Female ; Gestational Age ; Humans ; Infant, Newborn ; *Microbiota/genetics ; Parity ; Pregnancy ; *Premature Birth ; RNA, Ribosomal, 16S/genetics ; Vagina ; }, abstract = {BACKGROUND: Vaginal microbiota and its potential contribution to preterm birth is under intense research. However, only few studies have investigated the vaginal microbiota in later stages of pregnancy or at the onset of labour.<br><br>METHODS: We used 16S rRNA gene amplicon sequencing to analyse cross-sectional vaginal swab samples from 324 Finnish women between 37-42 weeks of gestation, sampled before elective caesarean section, at the onset of spontaneous labour, and in pregnancies lasting &#x2265;41 weeks of gestation. Microbiota data were combined with comprehensive clinical data to identify factors associated with microbiota variation.<br><br>FINDINGS: Vaginal microbiota composition associated strongly with advancing gestational age and parity, i.e. presence of previous deliveries. Absence of previous deliveries was a strong predictor of Lactobacillus crispatus dominated vaginal microbiota, and the relative abundance of L. crispatus was higher in late term pregnancies, especially among nulliparous women.<br><br>INTERPRETATION: This study identified late term pregnancy and reproductive history as factors underlying high abundance of gynaecological health-associated L. crispatus in pregnant women. Our results suggest that the vaginal microbiota affects or reflects the regulation of the duration of gestation and labour onset, with potentially vast clinical utilities. Further studies are needed to address the causality and the mechanisms on how previous labour, but not pregnancy, affects the vaginal microbiota. Parity and gestational age should be accounted for in future studies on vaginal microbiota and reproductive outcomes.<br><br>FUNDING: This research was supported by EU H2020 programme Sweet Crosstalk ITN (814102), Academy of Finland, State Research Funding, and University of Helsinki.}, }
@article {pmid35756062, year = {2022}, author = {Vernocchi, P and Ristori, MV and Guerrera, S and Guarrasi, V and Conte, F and Russo, A and Lupi, E and Albitar-Nehme, S and Gardini, S and Paci, P and Ianiro, G and Vicari, S and Gasbarrini, A and Putignani, L}, title = {Gut Microbiota Ecology and Inferred Functions in Children With ASD Compared to Neurotypical Subjects.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {871086}, pmid = {35756062}, issn = {1664-302X}, abstract = {Autism spectrum disorders (ASDs) is a multifactorial neurodevelopmental disorder. The communication between the gastrointestinal (GI) tract and the central nervous system seems driven by gut microbiota (GM). Herein, we provide GM profiling, considering GI functional symptoms, neurological impairment, and dietary habits. Forty-one and 35 fecal samples collected from ASD and neurotypical children (CTRLs), respectively, (age range, 3-15 years) were analyzed by 16S targeted-metagenomics (the V3-V4 region) and inflammation and permeability markers (i.e., sIgA, zonulin lysozyme), and then correlated with subjects' metadata. Our ASD cohort was characterized as follows: 30/41 (73%) with GI functional symptoms; 24/41 (58%) picky eaters (PEs), with one or more dietary needs, including 10/41 (24%) with food selectivity (FS); 36/41 (88%) presenting high and medium autism severity symptoms (HMASSs). Among the cohort with GI symptoms, 28/30 (93%) showed HMASSs, 17/30 (57%) were picky eaters and only 8/30 (27%) with food selectivity. The remaining 11/41 (27%) ASDs without GI symptoms that were characterized by HMASS for 8/11 (72%) and 7/11 (63%) were picky eaters. GM ecology was investigated for the overall ASD cohort versus CTRLs; ASDs with GI and without GI, respectively, versus CTRLs; ASD with GI versus ASD without GI; ASDs with HMASS versus low ASSs; PEs versus no-PEs; and FS versus absence of FS. In particular, the GM of ASDs, compared to CTRLs, was characterized by the increase of Proteobacteria, Bacteroidetes, Rikenellaceae, Pasteurellaceae, Klebsiella, Bacteroides, Roseburia, Lactobacillus, Prevotella, Sutterella, Staphylococcus, and Haemophilus. Moreover, Sutterella, Roseburia and Fusobacterium were associated to ASD with GI symptoms compared to CTRLs. Interestingly, ASD with GI symptoms showed higher value of zonulin and lower levels of lysozyme, which were also characterized by differentially expressed predicted functional pathways. Multiple machine learning models classified correctly 80% overall ASDs, compared with CTRLs, based on Bacteroides, Lactobacillus, Prevotella, Staphylococcus, Sutterella, and Haemophilus features. In conclusion, in our patient cohort, regardless of the evaluation of many factors potentially modulating the GM profile, the major phenotypic determinant affecting the GM was represented by GI hallmarks and patients' age.}, }
@article {pmid35750322, year = {2022}, author = {Kelly, MS and Bunyavanich, S and Phipatanakul, W and Lai, PS}, title = {The Environmental Microbiome, Allergic Disease, and Asthma.}, journal = {The journal of allergy and clinical immunology. In practice}, volume = {10}, number = {9}, pages = {2206-2217.e1}, pmid = {35750322}, issn = {2213-2201}, support = {R01 AI147028/AI/NIAID NIH HHS/United States ; U01 AI110397/AI/NIAID NIH HHS/United States ; U19 AI136053/AI/NIAID NIH HHS/United States ; U01 AI160082/AI/NIAID NIH HHS/United States ; K23 ES023700/ES/NIEHS NIH HHS/United States ; R01 AI144119/AI/NIAID NIH HHS/United States ; K24 AI106822/AI/NIAID NIH HHS/United States ; R01 AI118833/AI/NIAID NIH HHS/United States ; R38 HL150212/HL/NHLBI NIH HHS/United States ; }, mesh = {*Asthma/complications ; Environmental Exposure/adverse effects ; Humans ; *Hypersensitivity/epidemiology/etiology ; *Microbiota ; }, abstract = {The environmental microbiome represents the entirety of the microbes and their metabolites that we encounter in our environments. A growing body of evidence supports the role of the environmental microbiome in risk for and severity of allergic diseases and asthma. The environmental microbiome represents a ubiquitous, lifelong exposure to non-self antigens. During the critical window between birth and 1 year of life, interactions between our early immune system and the environmental microbiome have 2 consequences: our individual microbiome is populated by environmental microbes, and our immune system is trained regarding which antigens to tolerate. During this time, a diversity of exposures appears largely protective, dramatically decreasing the risk of developing allergic diseases and asthma. As we grow older, our interactions with the environmental microbiome change. While it continues to exert influence over the composition of the human microbiome, the environmental microbiome becomes increasingly a source for antigenic stimulation and infection. The same microbial exposure protective against disease development may exacerbate disease severity. Although much has been learned about the importance of the environmental microbiome in allergic disease, much more remains to be understood about these complicated interactions between our environment, our microbiome, our immune system, and disease.}, }
@article {pmid35748030, year = {2022}, author = {Pang, Z and Launonen, H and Korpela, R and Vapaatalo, H}, title = {Local aldosterone synthesis in the large intestine of mouse: An ex vivo incubation study.}, journal = {The Journal of international medical research}, volume = {50}, number = {6}, pages = {3000605221105163}, pmid = {35748030}, issn = {1473-2300}, mesh = {*Aldosterone ; Angiotensin II/pharmacology ; Animals ; Corticosterone ; *Cytochrome P-450 CYP11B2 ; Humans ; Intestine, Large/metabolism ; Male ; Mice ; Mice, Inbred DBA ; Sodium ; }, abstract = {OBJECTIVE: To investigate the regulation of local aldosterone synthesis by physiological stimulants in the murine gut.<br><br>METHODS: Male mice were fed for 14 days with normal, high (1.6%) or low (0.01%) sodium diets. Tissue liver receptor homolog-1 and aldosterone in the colon and caecum were detected using an enzyme-linked immunosorbent assay (ELISA). Released corticosterone and aldosterone in tissue incubation experiments after stimulation with angiotensin II (Ang II) and dibutyryl-cAMP (DBA; the second messenger of adrenocorticotropic hormone) were assayed using an ELISA. Tissue aldosterone synthase (CYP11B2) protein levels were measured using an ELISA and Western blots.<br><br>RESULTS: In incubated colon tissues, aldosterone synthase levels were increased by a low-sodium diet; and by Ang II and DBA in the normal diet group. Release of aldosterone into the incubation buffer was increased from the colon by a low-sodium diet and decreased by a high-sodium diet in parallel with changes in aldosterone synthase levels. In mice fed a normal diet, colon incubation with both Ang II and DBA increased the release of aldosterone as well as its precursor corticosterone.<br><br>CONCLUSION: Local aldosterone synthesis in the large intestine is stimulated by a low-sodium diet, dibutyryl-cAMP and Ang II similar to the adrenal glands.}, }
@article {pmid35744617, year = {2022}, author = {García-Mato, E and Martínez-Lamas, L and Álvarez-Fernández, M and Varela-Aneiros, I and Diniz-Freitas, M and Limeres-Posse, J and Diz-Dios, P}, title = {Molecular Detection of Streptococcus downii sp. nov. from Dental Plaque Samples from Patients with Down Syndrome and Non-Syndromic Individuals.}, journal = {Microorganisms}, volume = {10}, number = {6}, pages = {}, pmid = {35744617}, issn = {2076-2607}, abstract = {A new bacterial species has recently been identified in the dental plaque of an adolescent with Down syndrome. The species is known as Streptococcus downii sp. nov. (abbreviated to S. downii), and it inhibits the growth of S. mutans and certain periodontal pathogens. The aim of this study was to determine the distribution of S. downii in the oral cavity of individuals with Down syndrome. Methods: A specific polymerase chain reaction for the operon of bacteriocin (class IIb lactobin A/cerein 7B family) was designed to detect S. downii in individuals with Down syndrome (n = 200) and in the general population (n = 100). We also compared the whole genome of S. downii and the regions related to its bacteriocins against 127 metagenomes of supragingival plaque of the "Human Microbiome Project". Results: We detected the specific gene of the S. downii bacteriocin in an individual with Down syndrome (Cq, 34.52; GE/μL, 13.0) and in an individual of the non-syndromic control group (Cq, 34.78 Cq; GE/μL, 4.93). The prevalence of S. downii was ≤1% both in Down syndrome and in the general population, which did not allow for clinical-microbiological correlations to be established. This result was confirmed by detecting only one metagenome with an ANIm with approximately 95% homology and with 100% homology with ORFs that code class IIb lactobiocin A/cerein 7B bacteriocins among the 127 metagenomes of the "Human Microbiome Project" tested. Conclusions: The detection rate of S. downii in the supragingival dental plaque was very low, both in the Down syndrome individuals and in the non-syndromic controls. A clinical-microbiological correlation could therefore not be established.}, }
@article {pmid35743789, year = {2022}, author = {Graziani, C and Laterza, L and Talocco, C and Pizzoferrato, M and Di Simone, N and D'Ippolito, S and Ricci, C and Gervasoni, J and Persichilli, S and Del Chierico, F and Marzano, V and Mortera, SL and Primiano, A and Poscia, A and Ponziani, FR and Putignani, L and Urbani, A and Petito, V and Di Vincenzo, F and Masi, L and Lopetuso, LR and Cammarota, G and Romualdi, D and Lanzone, A and Gasbarrini, A and Scaldaferri, F}, title = {Intestinal Permeability and Dysbiosis in Female Patients with Recurrent Cystitis: A Pilot Study.}, journal = {Journal of personalized medicine}, volume = {12}, number = {6}, pages = {}, pmid = {35743789}, issn = {2075-4426}, abstract = {Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli. Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC (n = 16) were enrolled and compared with healthy female subjects (n = 15) and patients with chronic gastrointestinal (GI) disorders (n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections.}, }
@article {pmid35743209, year = {2022}, author = {Guan, Z and Feng, Q}, title = {Chitosan and Chitooligosaccharide: The Promising Non-Plant-Derived Prebiotics with Multiple Biological Activities.}, journal = {International journal of molecular sciences}, volume = {23}, number = {12}, pages = {}, pmid = {35743209}, issn = {1422-0067}, support = {82071122//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Chitin ; *Chitosan/chemistry ; Humans ; Oligosaccharides/chemistry/pharmacology ; Prebiotics ; Prospective Studies ; }, abstract = {Biodegradable chitin is the second-most abundant natural polysaccharide, widely existing in the exoskeletons of crabs, shrimps, insects, and the cell walls of fungi. Chitosan and chitooligosaccharide (COS, also named chitosan oligosaccharide) are the two most important deacetylated derivatives of chitin. Compared with chitin, chitosan and COS not only have more satisfactory physicochemical properties but also exhibit additional biological activities, which cause them to be widely applied in the fields of food, medicine, and agriculture. Additionally, due to their significant ability to improve gut microbiota, chitosan and COS are deemed prospective prebiotics. Here, we introduced the production, physicochemical properties, applications, and pharmacokinetic characteristics of chitosan and COS. Furthermore, we summarized the latest research on their antioxidant, anti-inflammatory, and antimicrobial activities. Research progress on the prebiotic functions of chitosan and COS is particularly reviewed. We creatively analyzed and discussed the mechanisms and correlations underlying these activities of chitosan and COS and their physicochemical properties. Our work enriched people's understanding of these non-plant-derived prebiotics. Based on this review, the future directions of research on chitosan and COS are explored. Collectively, optimizing the production technology of chitin derivatives and enriching understanding of their biological functions will shed more light on their capability to improve human health.}, }
@article {pmid35741811, year = {2022}, author = {Wu, Q and O'Malley, J and Datta, S and Gharaibeh, RZ and Jobin, C and Karagas, MR and Coker, MO and Hoen, AG and Christensen, BC and Madan, JC and Li, Z}, title = {MarZIC: A Marginal Mediation Model for Zero-Inflated Compositional Mediators with Applications to Microbiome Data.}, journal = {Genes}, volume = {13}, number = {6}, pages = {}, pmid = {35741811}, issn = {2073-4425}, support = {UH3 OD023275/OD/NIH HHS/United States ; R01 GM123014/GM/NIGMS NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; P30 CA023108/CA/NCI NIH HHS/United States ; P01 ES022832/ES/NIEHS NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, mesh = {Computer Simulation ; Humans ; *Microbiota/genetics ; *Models, Statistical ; Research Design ; }, abstract = {BACKGROUND: The human microbiome can contribute to pathogeneses of many complex diseases by mediating disease-leading causal pathways. However, standard mediation analysis methods are not adequate to analyze the microbiome as a mediator due to the excessive number of zero-valued sequencing reads in the data and that the relative abundances have to sum to one. The two main challenges raised by the zero-inflated data structure are: (a) disentangling the mediation effect induced by the point mass at zero; and (b) identifying the observed zero-valued data points that are not zero (i.e., false zeros).<br><br>METHODS: We develop a novel marginal mediation analysis method under the potential-outcomes framework to address the issues. We also show that the marginal model can account for the compositional structure of microbiome data.<br><br>RESULTS: The mediation effect can be decomposed into two components that are inherent to the two-part nature of zero-inflated distributions. With probabilistic models to account for observing zeros, we also address the challenge with false zeros. A comprehensive simulation study and the application in a real microbiome study showcase our approach in comparison with existing approaches.<br><br>CONCLUSIONS: When analyzing the zero-inflated microbiome composition as the mediators, MarZIC approach has better performance than standard causal mediation analysis approaches and existing competing approach.}, }
@article {pmid35740129, year = {2022}, author = {Grada, A and Ghannoum, MA and Bunick, CG}, title = {Sarecycline Demonstrates Clinical Effectiveness against Staphylococcal Infections and Inflammatory Dermatoses: Evidence for Improving Antibiotic Stewardship in Dermatology.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {35740129}, issn = {2079-6382}, abstract = {Tetracycline class antibiotics are widely used for multiple skin diseases, including acne vulgaris, acne rosacea, cutaneous infections, inflammatory dermatoses, and autoimmune blistering disorders. Concerns about antibiotic resistance and protecting the human/host microbiome beg the question whether broad-spectrum tetracyclines such as doxycycline and minocycline should be prescribed at such a high rate by dermatologists when a narrow-spectrum tetracycline derivative, sarecycline, exists. We evaluated the clinical effectiveness of oral sarecycline against cutaneous staphylococcal infections, eyelid stye, and mucous membrane pemphigoid to determine whether sarecycline is a viable option for clinicians to practice improved antibiotic stewardship. We observed significant improvement in staphylococcal infections and inflammatory dermatoses with courses of oral sarecycline as short as 9 days, with no reported adverse events. These clinical findings are consistent with in vitro microbiological data and anti-inflammatory properties of sarecycline. Our data provides a strong rationale for clinicians to use narrow-spectrum sarecycline rather than broad-spectrum tetracyclines as a first-line agent in treating staphylococcal skin infections and inflammatory skin diseases for which tetracyclines are currently commonly employed. Such advancement in the practice paradigm in dermatology will enhance antibiotic stewardship, reduce risk of antibiotic resistance, protect the human microbiome, and provide patients with precision medicine care.}, }
@article {pmid35739354, year = {2022}, author = {Cani, PD and Depommier, C and Derrien, M and Everard, A and de Vos, WM}, title = {Author Correction: Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {10}, pages = {682}, doi = {10.1038/s41575-022-00650-6}, pmid = {35739354}, issn = {1759-5053}, }
@article {pmid35732630, year = {2022}, author = {Sharp, C and Foster, KR}, title = {Host control and the evolution of cooperation in host microbiomes.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3567}, pmid = {35732630}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 209397/Z/17/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Bacteria/genetics ; Biological Evolution ; *Microbiota/genetics ; Phylogeny ; *Symbiosis ; }, abstract = {Humans, and many other species, are host to diverse symbionts. It is often suggested that the mutual benefits of host-microbe relationships can alone explain cooperative evolution. Here, we evaluate this hypothesis with evolutionary modelling. Our model predicts that mutual benefits are insufficient to drive cooperation in systems like the human microbiome, because of competition between symbionts. However, cooperation can emerge if hosts can exert control over symbionts, so long as there are constraints that limit symbiont counter evolution. We test our model with genomic data of two bacterial traits monitored by animal immune systems. In both cases, bacteria have evolved as predicted under host control, tending to lose flagella and maintain butyrate production when host-associated. Moreover, an analysis of bacteria that retain flagella supports the evolution of host control, via toll-like receptor 5, which limits symbiont counter evolution. Our work puts host control mechanisms, including the immune system, at the centre of microbiome evolution.}, }
@article {pmid35729515, year = {2022}, author = {Dai, W and Li, C and Li, T and Hu, J and Zhang, H}, title = {Super-taxon in human microbiome are identified to be associated with colorectal cancer.}, journal = {BMC bioinformatics}, volume = {23}, number = {1}, pages = {243}, pmid = {35729515}, issn = {1471-2105}, support = {DMS-2112711//National Science Foundation, United States/ ; R01 HG010171/HG/NHGRI NIH HHS/United States ; R01 MH116527/MH/NIMH NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R01MH116527 and R01HG010171/NH/NIH HHS/United States ; }, mesh = {*Colorectal Neoplasms/genetics ; Firmicutes ; Humans ; *Microbiota/genetics ; Peptostreptococcus ; }, abstract = {BACKGROUND: Microbial communities in the human body, also known as human microbiota, impact human health, such as colorectal cancer (CRC). However, the different roles that microbial communities play in healthy and disease hosts remain largely unknown. The microbial communities are typically recorded through the taxa counts of operational taxonomic units (OTUs). The sparsity and high correlations among OTUs pose major challenges for understanding the microbiota-disease relation. Furthermore, the taxa data are structured in the sense that OTUs are related evolutionarily by a hierarchical structure.<br><br>RESULTS: In this study, we borrow the idea of super-variant from statistical genetics, and propose a new concept called super-taxon to exploit hierarchical structure of taxa for microbiome studies, which is essentially a combination of taxonomic units. Specifically, we model a genus which consists of a set of OTUs at low hierarchy and is designed to reflect both marginal and joint effects of OTUs associated with the risk of CRC to address these issues. We first demonstrate the power of super-taxon in detecting highly correlated OTUs. Then, we identify CRC-associated OTUs in two publicly available datasets via a discovery-validation procedure. Specifically, four species of two genera are found to be associated with CRC: Parvimonas micra, Parvimonas sp., Peptostreptococcus stomatis, and Peptostreptococcus anaerobius. More importantly, for the first time, we report the joint effect of Parvimonas micra and Parvimonas sp. (p&#x2009;=&#x2009;0.0084) as well as that of Peptostrepto-coccus stomatis and Peptostreptococcus anaerobius (p&#x2009;=&#x2009;8.21e-06) on CRC. The proposed approach provides a novel and useful tool for identifying disease-related microbes by taking the hierarchical structure of taxa into account and further sheds new lights on their potential joint effects as a community in disease development.<br><br>CONCLUSIONS: Our work shows that proposed approaches are effective to study the microbiota-disease relation taking into account for the sparsity, hierarchical and correlated structure among microbes.}, }
@article {pmid35729161, year = {2022}, author = {Zhang, L and Jonscher, KR and Zhang, Z and Xiong, Y and Mueller, RS and Friedman, JE and Pan, C}, title = {Islet autoantibody seroconversion in type-1 diabetes is associated with metagenome-assembled genomes in infant gut microbiomes.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3551}, pmid = {35729161}, issn = {2041-1723}, support = {R01 AT011618/AT/NCCIH NIH HHS/United States ; }, mesh = {Autoantibodies ; Child ; *Diabetes Mellitus, Type 1/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; Infant ; Metagenome/genetics ; Metagenomics/methods ; *Microbiota ; Seroconversion ; }, abstract = {The immune system of some genetically susceptible children can be triggered by certain environmental factors to produce islet autoantibodies (IA) against pancreatic β cells, which greatly increases their risk for Type-1 diabetes. An environmental factor under active investigation is the gut microbiome due to its important role in immune system education. Here, we study gut metagenomes that are de-novo-assembled in 887 at-risk children in the Environmental Determinants of Diabetes in the Young (TEDDY) project. Our results reveal a small set of core protein families, present in >50% of the subjects, which account for 64% of the sequencing reads. Time-series binning generates 21,536 high-quality metagenome-assembled genomes (MAGs) from 883 species, including 176 species that hitherto have no MAG representation in previous comprehensive human microbiome surveys. IA seroconversion is positively associated with 2373 MAGs and negatively with 1549 MAGs. Comparative genomics analysis identifies lipopolysaccharides biosynthesis in Bacteroides MAGs and sulfate reduction in Anaerostipes MAGs as functional signatures of MAGs with positive IA-association. The functional signatures in the MAGs with negative IA-association include carbohydrate degradation in lactic acid bacteria MAGs and nitrate reduction in Escherichia MAGs. Overall, our results show a distinct set of gut microorganisms associated with IA seroconversion and uncovered the functional genomics signatures of these IA-associated microorganisms.}, }
@article {pmid35724423, year = {2022}, author = {Smith, G and Manzano Marín, A and Reyes-Prieto, M and Ribeiro Antunes, CS and Ashworth, V and Goselle, ON and Jan, AAA and Moya, A and Latorre, A and Perotti, MA and Braig, HR}, title = {Human follicular mites: Ectoparasites becoming symbionts.}, journal = {Molecular biology and evolution}, volume = {39}, number = {6}, pages = {}, pmid = {35724423}, issn = {1537-1719}, abstract = {Most humans carry mites in the hair follicles of their skin for their entire lives. Follicular mites are the only metazoans tha continuously live on humans. We propose that Demodex folliculorum (Acari) represents a transitional stage from a host-injuring obligate parasite to an obligate symbiont. Here, we describe the profound impact of this transition on the genome and physiology of the mite. Genome sequencing revealed that the permanent host association of D. folliculorum led to an extensive genome reduction through relaxed selection and genetic drift, resulting in the smallest number of protein-coding genes yet identified among panarthropods. Confocal microscopy revealed that this gene loss coincided with an extreme reduction in the number of cells. Single uninucleate muscle cells are sufficient to operate each of the three segments that form each walking leg. While it has been assumed that the reduction of the cell number in parasites starts early in development, we identified a greater total number of cells in the last developmental stage (nymph) than in the terminal adult stage, suggesting that reduction starts at the adult or ultimate stage of development. This is the first evolutionary step in an arthropod species adopting a reductive, parasitic or endosymbiotic lifestyle. Somatic nuclei show underreplication at the diploid stage. Novel eye structures or photoreceptors as well as a unique human host melatonin-guided day/night rhythm are proposed for the first time. The loss of DNA repair genes coupled with extreme endogamy might have set this mite species on an evolutionary dead-end trajectory.}, }
@article {pmid35724325, year = {2023}, author = {}, title = {Retraction: Human microbiome and homeostasis: Insights into the key role of prebiotics, probiotics, and symbiotics.}, journal = {Critical reviews in food science and nutrition}, volume = {63}, number = {20}, pages = {4817}, doi = {10.1080/10408398.2022.2078104}, pmid = {35724325}, issn = {1549-7852}, }
@article {pmid35723343, year = {2022}, author = {Yoon, YC and Ahn, BH and Min, JW and Lee, KR and Park, SH and Kang, HC}, title = {Stimulatory Effects of Extracellular Vesicles Derived from Leuconostoc holzapfelii That Exists in Human Scalp on Hair Growth in Human Follicle Dermal Papilla Cells.}, journal = {Current issues in molecular biology}, volume = {44}, number = {2}, pages = {845-866}, pmid = {35723343}, issn = {1467-3045}, abstract = {Human hair follicle dermal papilla cells (HFDPCs) located in hair follicles (HFs) play a pivotal role in hair follicle morphogenesis, hair cycling, and hair growth. Over the past few decades, probiotic bacteria (PB) have been reported to have beneficial effects such as improved skin health, anti-obesity, and immuno-modulation for conditions including atopic dermatitis and inflammatory bowel disease (IBD). PB can secrete 50~150 nm sized extracellular vesicles (EVs) containing microbial DNA, miRNA, proteins, lipids, and cell wall components. These EVs can regulate communication between bacteria or between bacteria and their host. Although numerous biological effects of PB-EVs have been reported, the physiological roles of Leuconostoc holzapfelii (hs-Lh), which is isolated from human scalp tissue, and the extracellular vesicles derived from them (hs-LhEVs) are largely unknown. Herein, we investigated the effects of hs-LhEVs on hair growth in HFDPCs. We show that hs-LhEVs increase cell proliferation, migration, and regulate the cell cycle. Furthermore, hs-LhEVs were found to modulate the mRNA expression of hair-growth-related genes in vitro. These data demonstrate that hs-LhEVs can reduce apoptosis by modulating the cell cycle and promote hair growth by regulation via the Wnt/β-catenin signal transduction pathway.}, }
@article {pmid35723322, year = {2022}, author = {Jo, CS and Myung, CH and Yoon, YC and Ahn, BH and Min, JW and Seo, WS and Lee, DH and Kang, HC and Heo, YH and Choi, H and Hong, IK and Hwang, JS}, title = {The Effect of Lactobacillus plantarum Extracellular Vesicles from Korean Women in Their 20s on Skin Aging.}, journal = {Current issues in molecular biology}, volume = {44}, number = {2}, pages = {526-540}, pmid = {35723322}, issn = {1467-3045}, abstract = {Extracellular vesicles, which are highly conserved in most cells, contain biologically active substances. The vesicles and substances interact with cells and impact physiological mechanisms. The skin is the most external organ and is in direct contact with the external environment. Photoaging and skin damage are caused by extrinsic factors. The formation of wrinkles is a major indicator of skin aging and is caused by a decrease in collagen and hyaluronic acid. MMP-1 expression is also increased. Due to accruing damage, skin aging reduces the ability of the skin barrier, thereby lowering the skin's ability to contain water and increasing the amount of water loss. L. plantarum suppresses various harmful bacteria by secreting an antimicrobial substance. L. plantarum is also found in the skin, and research on the interactions between the bacteria and the skin is in progress. Although several studies have investigated L. plantarum, there are only a limited number of studies on extracellular vesicles (EV) derived from L. plantarum, especially in relation to skin aging. Herein, we isolated EVs that were secreted from L. plantarum of women in their 20s (LpEVs). We then investigated the effect of LpEVs on skin aging in CCD986sk. We showed that LpEVs modulated the mRNA expression of ECM related genes in vitro. Furthermore, LpEVs suppressed wrinkle formation and pigmentation in clinical trials. These results demonstrated that LpEVs have a great effect on skin aging by regulating ECM related genes. In addition, our study offers important evidence on the depigmentation effect of LpEVs.}, }
@article {pmid35720372, year = {2022}, author = {Krawczyk, KT and Locht, C and Kowalewicz-Kulbat, M}, title = {Halophilic Archaea Halorhabdus Rudnickae and Natrinema Salaciae Activate Human Dendritic Cells and Orient T Helper Cell Responses.}, journal = {Frontiers in immunology}, volume = {13}, number = {}, pages = {833635}, pmid = {35720372}, issn = {1664-3224}, mesh = {Cytokines ; Dendritic Cells ; *Halobacteriaceae ; Humans ; *Interleukin-13/pharmacology ; T-Lymphocytes, Helper-Inducer ; }, abstract = {Halophilic archaea are procaryotic organisms distinct from bacteria, known to thrive in hypersaline environments, including salt lakes, salterns, brines and salty food. They have also been identified in the human microbiome. The biological significance of halophiles for human health has rarely been examined. The interactions between halophilic archaea and human dendritic cells (DCs) and T cells have not been identified so far. Here, we show for the first time that the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae activate human monocyte-derived DCs, induce DC maturation, cytokine production and autologous T cell activation. In vitro both strains induced DC up-regulation of the cell-surface receptors CD86, CD80 and CD83, and cytokine production, including IL-12p40, IL-10 and TNF-α, but not IL-23 and IL-12p70. Furthermore, autologous CD4[+] T cells produced significantly higher amounts of IFN-γ and IL-13, but not IL-17A when co-cultured with halophile-stimulated DCs in comparison to T cells co-cultured with unstimulated DCs. IFN-γ was almost exclusively produced by naïve T cells, while IL-13 was produced by both naïve and memory CD4[+] T cells. Our findings thus show that halophilic archaea are recognized by human DCs and are able to induce a balanced cytokine response. The immunomodulatory functions of halophilic archaea and their potential ability to re-establish the immune balance may perhaps participate in the beneficial effects of halotherapies.}, }
@article {pmid35718251, year = {2022}, author = {Juarez, VM and Montalbine, AN and Singh, A}, title = {Microbiome as an immune regulator in health, disease, and therapeutics.}, journal = {Advanced drug delivery reviews}, volume = {188}, number = {}, pages = {114400}, pmid = {35718251}, issn = {1872-8294}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 AI132738/AI/NIAID NIH HHS/United States ; R21 AI160136/AI/NIAID NIH HHS/United States ; T32 GM008433/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria ; Humans ; *Microbiota/physiology ; *Neoplasms/microbiology ; Pharmaceutical Preparations ; Precision Medicine ; }, abstract = {New discoveries in drugs and drug delivery systems are focused on identifying and delivering a pharmacologically effective agent, potentially targeting a specific molecular component. However, current drug discovery and therapeutic delivery approaches do not necessarily exploit the complex regulatory network of an indispensable microbiota that has been engineered through evolutionary processes in humans or has been altered by environmental exposure or diseases. The human microbiome, in all its complexity, plays an integral role in the maintenance of host functions such as metabolism and immunity. However, dysregulation in this intricate ecosystem has been linked with a variety of diseases, ranging from inflammatory bowel disease to cancer. Therapeutics and bacteria have an undeniable effect on each other and understanding the interplay between microbes and drugs could lead to new therapies, or to changes in how existing drugs are delivered. In addition, targeting the human microbiome using engineered therapeutics has the potential to address global health challenges. Here, we present the challenges and cutting-edge developments in microbiome-immune cell interactions and outline novel targeting strategies to advance drug discovery and therapeutics, which are defining a new era of personalized and precision medicine.}, }
@article {pmid35717467, year = {2022}, author = {Shetty, SA and Kostopoulos, I and Geerlings, SY and Smidt, H and de Vos, WM and Belzer, C}, title = {Dynamic metabolic interactions and trophic roles of human gut microbes identified using a minimal microbiome exhibiting ecological properties.}, journal = {The ISME journal}, volume = {16}, number = {9}, pages = {2144-2159}, pmid = {35717467}, issn = {1751-7370}, support = {NRGWI.obrug.2018.005//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; 024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; }, mesh = {Bacteria/genetics ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; Mucins ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Microbe-microbe interactions in the human gut are influenced by host-derived glycans and diet. The high complexity of the gut microbiome poses a major challenge for unraveling the metabolic interactions and trophic roles of key microbes. Synthetic minimal microbiomes provide a pragmatic approach to investigate their ecology including metabolic interactions. Here, we rationally designed a synthetic microbiome termed Mucin and Diet based Minimal Microbiome (MDb-MM) by taking into account known physiological features of 16 key bacteria. We combined 16S rRNA gene-based composition analysis, metabolite measurements and metatranscriptomics to investigate community dynamics, stability, inter-species metabolic interactions and their trophic roles. The 16 species co-existed in the in vitro gut ecosystems containing a mixture of complex substrates representing dietary fibers and mucin. The triplicate MDb-MM's followed the Taylor's power law and exhibited strikingly similar ecological and metabolic patterns. The MDb-MM exhibited resistance and resilience to temporal perturbations as evidenced by the abundance and metabolic end products. Microbe-specific temporal dynamics in transcriptional niche overlap and trophic interaction network explained the observed co-existence in a competitive minimal microbiome. Overall, the present study provides crucial insights into the co-existence, metabolic niches and trophic roles of key intestinal microbes in a highly dynamic and competitive in vitro ecosystem.}, }
@article {pmid35713407, year = {2022}, author = {Shaffer, JP and Carpenter, CS and Martino, C and Salido, RA and Minich, JJ and Bryant, M and Sanders, K and Schwartz, T and Humphrey, G and Swafford, AD and Knight, R}, title = {A comparison of six DNA extraction protocols for 16S, ITS and shotgun metagenomic sequencing of microbial communities.}, journal = {BioTechniques}, volume = {73}, number = {1}, pages = {34-46}, pmid = {35713407}, issn = {1940-9818}, support = {R01 DK102932/DK/NIDDK NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; U01 AI124316/AI/NIAID NIH HHS/United States ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 HL134887/HL/NHLBI NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; }, mesh = {Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenomics/methods ; *Microbiota/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Microbial communities contain a broad phylogenetic diversity of organisms; however, the majority of methods center on describing bacteria and archaea. Fungi are important symbionts in many ecosystems and are potentially important members of the human microbiome, beyond those that can cause disease. To expand our analysis of microbial communities to include data from the fungal internal transcribed spacer (ITS) region, five candidate DNA extraction kits were compared against our standardized protocol for describing bacteria and archaea using 16S rRNA gene amplicon- and shotgun metagenomics sequencing. The results are presented considering a diverse panel of host-associated and environmental sample types and comparing the cost, processing time, well-to-well contamination, DNA yield, limit of detection and microbial community composition among protocols. Across all criteria, the MagMAX Microbiome kit was found to perform best. The PowerSoil Pro kit performed comparably but with increased cost per sample and overall processing time. The Zymo MagBead, NucleoMag Food and Norgen Stool kits were included.}, }
@article {pmid35705822, year = {2022}, author = {Ley, R}, title = {The human microbiome: there is much left to do.}, journal = {Nature}, volume = {606}, number = {7914}, pages = {435}, doi = {10.1038/d41586-022-01610-5}, pmid = {35705822}, issn = {1476-4687}, mesh = {Humans ; *Microbiota ; }, }
@article {pmid35698690, year = {2022}, author = {Anipindi, M and Bitetto, D}, title = {Diagnostic and Therapeutic Uses of the Microbiome in the Field of Oncology.}, journal = {Cureus}, volume = {14}, number = {5}, pages = {e24890}, pmid = {35698690}, issn = {2168-8184}, abstract = {Cancer is a leading cause of death worldwide and it can affect almost every part of the human body. Effective screening and early diagnosis of cancers is extremely difficult due to the multifactorial etiology of the disease and delayed presentation of the patients. The available treatments are usually not specific to the affected organ system, leading to intolerable systemic side effects and early withdrawal from therapies. In vivo and in vitro studies have revealed an association of specific microbiome signatures with individual cancers. The cancer-related human microbiome has also been shown to affect the response of tissues to chemotherapy, immunotherapy, and radiation. This is an excellent opportunity for us to design specific screening markers using the microbiome to prevent cancers and diagnose them early. We can also develop precise treatments that can target cancer-affected specific organ systems and probably use a lesser dose of chemotherapy or radiation for the same effect. This prevents adverse effects and early cessation of treatments. However, we need further studies to exactly clarify and characterize these associations. In this review article, we focus on the association of the microbiome with individual cancers and highlight its future role in cancer screenings, diagnosis, prognosis, and treatments.}, }
@article {pmid35697549, year = {2022}, author = {Droz, L and Jannel, R and Rupprecht, CDD}, title = {Living through multispecies societies: Approaching the microbiome with Imanishi Kinji.}, journal = {Endeavour}, volume = {46}, number = {1-2}, pages = {100814}, doi = {10.1016/j.endeavour.2022.100814}, pmid = {35697549}, issn = {1873-1929}, mesh = {Humans ; *Microbiota ; *Research/classification/trends ; }, abstract = {Recent research about the microbiome points to a picture in which we, humans, are 'living through' nature, and nature itself is living in us. Our bodies are hosting-and depend on-the multiple species that constitute human microbiota. This article will discuss current research on the microbiome through the ideas of Japanese ecologist Imanishi Kinji (1902-1992). First, some of Imanishi's key ideas regarding the world of living beings and multispecies societies are presented. Second, seven types of relationships concerning the human microbiome, human beings, and the environment are explored. Third, inspired by Imanishi's work, this paper develops the idea of dynamic, porous, and complex multispecies societies in which different living beings or species are codependent on others, including microbiota and human beings.}, }
@article {pmid35694384, year = {2022}, author = {Ene, A and Stegman, N and Wolfe, A and Putonti, C}, title = {Genomic insights into Lactobacillus gasseri and Lactobacillus paragasseri.}, journal = {PeerJ}, volume = {10}, number = {}, pages = {e13479}, pmid = {35694384}, issn = {2167-8359}, mesh = {Female ; Humans ; *Lactobacillus gasseri/genetics ; RNA, Ribosomal, 16S/genetics ; Genomics ; Mouth ; Prophages/genetics ; }, abstract = {BACKGROUND: Antimicrobial and antifungal species are essential members of the healthy human microbiota. Several different species of lactobacilli that naturally inhabit the human body have been explored for their probiotic capabilities including strains of the species Lactobacillus gasseri. However, L. gasseri (identified by 16S rRNA gene sequencing) has been associated with urogenital symptoms. Recently a new sister taxon of L. gasseri was described: L. paragasseri. L. paragasseri is also posited to have probiotic qualities.<br><br>METHODS: Here, we present a genomic investigation of all (n&#xa0;=&#xa0;79) publicly available genome assemblies for both species. These strains include isolates from the vaginal tract, gastrointestinal tract, urinary tract, oral cavity, wounds, and lungs.<br><br>RESULTS: The two species cannot be distinguished from short-read sequencing of the 16S rRNA as the full-length gene sequences differ only by two nucleotides. Based upon average nucleotide identity (ANI), we identified 20 strains deposited as L. gasseri that are in fact representatives of L. paragasseri. Investigation of the genic content of the strains of these two species suggests recent divergence and/or frequent gene exchange between the two species. The genomes frequently harbored intact prophage sequences, including prophages identified in strains of both species. To further explore the antimicrobial potential associated with both species, genome assemblies were examined for biosynthetic gene clusters. Gassericin T and S were identified in 46 of the genome assemblies, with all L. paragasseri strains including one or both bacteriocins. This suggests that the properties once ascribed to L. gasseri may better represent the L.&#xa0;paragasseri species.}, }
@article {pmid35693065, year = {2022}, author = {Ozma, MA and Abbasi, A and Akrami, S and Lahouty, M and Shahbazi, N and Ganbarov, K and Pagliano, P and Sabahi, S and Köse, &#x15e; and Yousefi, M and Dao, S and Asgharzadeh, M and Hosseini, H and Kafil, HS}, title = {Postbiotics as the key mediators of the gut microbiota-host interactions.}, journal = {Le infezioni in medicina}, volume = {30}, number = {2}, pages = {180-193}, pmid = {35693065}, issn = {2532-8689}, abstract = {The priority of the Sustainable Development Goals for 2022 is to reduce all causes related to mortality. In this regard, microbial bioactive compounds with characteristics such as optimal compatibility and close interaction with the host immune system are considered a novel therapeutic approach. The fermentation process is one of the most well-known pathways involved in the natural synthesis of a diverse range of postbiotics. However, some postbiotics are a type of probiotic response behavior to environmental stimuli that usually play well-known biological roles. Also, postbiotics with unique structure and function are key mediators between intestinal microbiota and host cellular processes/metabolic pathways that play a significant role in maintaining homeostasis. By further understanding the nature of parent microbial cells, factors affecting their metabolic pathways, and the development of compatible extraction and identification methods, it is possible to achieve certain formulations of postbiotics with special efficiencies, which in turn will significantly improve the performance of health systems (especially in developing countries) toward a wide range of acute/chronic diseases. The present review aims to describe the fundamental role of postbiotics as the key mediators of the microbiota-host interactions. Besides, it presents the available current evidence regarding the interaction between postbiotics and host cells through potential cell receptors, stimulation/improvement of immune system function, and the enhancement of the composition and function of the human microbiome.}, }
@article {pmid35692002, year = {2022}, author = {Song, WJ and Kang, WY and Liu, XM and Sun, L and Feng, Q and Ge, SH}, title = {[Study on the dynamic changes of oral microbiota in type 2 diabetes patients with periodontitis after initial periodontal therapy].}, journal = {Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology}, volume = {57}, number = {6}, pages = {585-594}, doi = {10.3760/cma.j.cn112144-20220228-00076}, pmid = {35692002}, issn = {1002-0098}, support = {82170964, 81873716//National Nature Science Foundation of China/ ; ts20190975//The Construction Engineering Special Fund of "Taishan Scholars" of Shandong Province/ ; }, mesh = {Bacteria/genetics ; *Chronic Periodontitis/microbiology/therapy ; *Dental Plaque/microbiology ; *Diabetes Mellitus, Type 2/complications/therapy ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Objectives: To clarify the effect of initial periodontal therapy on the dynamic changes of oral (saliva, dorsal tongue and subgingival plaque) microbiota in periodontitis patients with or without type 2 diabetes mellitus (T2DM). Methods: A total of 14 patients with chronic periodontitis (CP group) and 14 CP patients with T2DM (CP-T2DM group) were included from Department of Periodontology, School and Hospital of Stomatology,Cheeloo College of Medicine, Shandong University. The microbial samples were collected from saliva, dorsal tongue and subgingival plaque of first molars at baseline, 1.5 and 3 months after initial periodontal therapy, and were detected by 16S rRNA (V3-V4 region) gene sequencing. The sequencing data were analyzed to obtain microbial distribution and community structure information. The same professional periodontist evaluated the periodontal status of patients according to periodontitis detection indices before and after initial periodontal therapy. Meanwhile, patients' blood samples were collected and related metabolic indices were evaluated. Results: After initial periodontal therapy, the glycosylated hemoglobin levels [(7.46±1.69)%] in CP-T2DM group were significantly improved than that at baseline [(7.65±1.34)%] (t=0.52,P=0.610). The probing depth of the sampling sites [CP group: (2.94±0.46) mm, CP-T2DM group: (2.95±0.35) mm] and bleeding index (CP group: 1.91±0.42, CP-T2DM group: 1.67±0.49) at 3 months after treatment were significantly decreased than the probing depth [CP group: (3.99±0.77) mm, CP-T2DM group: (3.80±0.76) mm] (F=25.61, P<0.001; F=17.63, P<0.001) and bleeding index (CP group: 3.03±0.52, CP-T2DM group: 2.54±0.65) (F=28.43, P<0.001; F=20.21, P<0.001) at baseline. The flora analysis showed that the α and β diversity indices of the same sites in the CP and CP-T2DM groups did not change significantly before and after the initial therapy, but the bacterial abundance at each site changed. There were commonalities and differences in the microbial composition of each site in the CP and CP-T2DM groups. Among them, the relative abundance of Proteobacteria in saliva and dorsal tongue samples of the two groups after treatment was basically consistent with the change trend in the subgingival plaque microbes. In the subgingival plaque of the CP group, the relative abundance of Proteobacteria showed a gradual increase with the prolongation of initial periodontal therapy; while in the CP-T2DM group, it showed a trend of first increase and then decrease. Syntrophy, Dethiosulfate, Methanobacteriaceae and TG5 in CP and CP-T2DM groups were all significantly dominant bacteria in subgingival plaque at baseline (P<0.05). Moreover, in the CP-T2DM group Spirochetes also showed a significant advantage. At 1.5 months after treatment, Rhizobacteria, Alcaligenes, Comamomons, Delftia, Blautella, etc. were dominant in subgingival plaque (P<0.05). Firmicutes, Clostridia/Clostridiales, Enterococci and Ruminococci showed significant differences at 3 months (P<0.05). Conclusions: Plaques in saliva and tongue dorsal could reflect the effects of initial periodontal therapy on the dynamic changes of microorganisms to a certain extent. CP and CP-T2DM patients had differences in microbial composition and responses to initial periodontal therapy.}, }
@article {pmid35689685, year = {2023}, author = {Mills, JG and Selway, CA and Thomas, T and Weyrich, LS and Lowe, AJ}, title = {Schoolyard Biodiversity Determines Short-Term Recovery of Disturbed Skin Microbiota in Children.}, journal = {Microbial ecology}, volume = {86}, number = {1}, pages = {658-669}, pmid = {35689685}, issn = {1432-184X}, mesh = {Humans ; Child ; *Microbiota ; Biodiversity ; Forests ; Skin ; }, abstract = {Creating biodiverse urban habitat has been proposed, with growing empirical support, as an intervention for increasing human microbial diversity and reducing associated diseases. However, ecological understanding of urban biodiversity interventions on human skin microbiota remains limited. Here, we experimentally test the hypotheses that disturbed skin microbiota recover better in outdoor schoolyard environments and that greater biodiversity provides a greater response. Repeating the experiment three times, we disturbed skin microbiota of fifty-seven healthy 10-to-11-year-old students with a skin swab (i.e., cleaning), then exposed them to one school environment-either a 'classroom' (n = 20), 'sports field' (n = 14), or biodiverse 'forest' (n = 23)-for 45 min. Another skin swab followed the exposure to compare 'before' and 'after' microbial communities. After 45 min, the disturbance immediately followed by outdoor exposure, especially the 'forest', had an enriching and diversifying effect on skin microbiota, while 'classroom' exposure homogenised inter-personal variability. Each effect compounded over consecutive days indicating longer-term exposure outcomes. The experimental disturbance also reduced the core skin microbiota, and only outdoor environments were able to replenish lost species richness to core membership (n species > 50% prevalent). Overall, we find that environmental setting, especially including biodiversity, is important in human microbiota recovery periods and that the outdoors provide resilience to skin communities. This work also has implications for the inclusion of short periods of outside or forest exposure in school scheduling. Future investigations of the health impacts of permanent urban biodiversity interventions are needed.}, }
@article {pmid35689474, year = {2022}, author = {Diociaiuti, A and Giancristoforo, S and Calò Carducci, FI and Bracaglia, C and Boni, A and Pane, S and Onetti Muda, A and De Benedetti, F and Putignani, L and El Hachem, M}, title = {Auricular leishmaniasis in a child successfully treated with intralesional amphotericin B.}, journal = {Pediatric dermatology}, volume = {39}, number = {5}, pages = {832-833}, pmid = {35689474}, issn = {1525-1470}, mesh = {Amphotericin B/therapeutic use ; *Antiprotozoal Agents/therapeutic use ; Child ; *Ear Auricle ; Family ; Humans ; *Leishmaniasis, Cutaneous/diagnosis/drug therapy ; }, abstract = {Cutaneous leishmaniasis (CL) is the most frequent form of leishmaniasis. The auricle is an extremely rare site for CL in the Old World. Auricular CL may be mistaken for other entities, such as relapsing polychondritis (RP). Here we report a pediatric case of Old World auricular CL mimicking RP in a child successfully treated with intralesional liposomal amphotericin B.}, }
@article {pmid35686484, year = {2022}, author = {Chen, Y and Rudolph, SE and Longo, BN and Pace, F and Roh, TT and Condruti, R and Gee, M and Watnick, PI and Kaplan, DL}, title = {Bioengineered 3D Tissue Model of Intestine Epithelium with Oxygen Gradients to Sustain Human Gut Microbiome.}, journal = {Advanced healthcare materials}, volume = {11}, number = {16}, pages = {e2200447}, pmid = {35686484}, issn = {2192-2659}, support = {P41 EB002520/EB/NIBIB NIH HHS/United States ; P41 EB027062/EB/NIBIB NIH HHS/United States ; S10 OD021624/OD/NIH HHS/United States ; U19 AI131126/AI/NIAID NIH HHS/United States ; }, mesh = {Epithelium ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa ; *Microbiota ; Oxygen ; }, abstract = {The human gut microbiome is crucial to hosting physiology and health. Therefore, stable in vitro coculture of primary human intestinal cells with a microbiome community is essential for understanding intestinal disease progression and revealing novel therapeutic targets. Here, a three-dimensional scaffold system is presented to regenerate an in vitro human intestinal epithelium that recapitulates many functional characteristics of the native small intestines. The epithelium, derived from human intestinal enteroids, contains mature intestinal epithelial cells and possesses selectively permeable barrier functions. Importantly, by properly positioning the scaffolds cultured under normal atmospheric conditions, two physiologically relevant oxygen gradients, a proximal-to-distal oxygen gradient along the gastrointestinal (GI) tract, and a radial oxygen gradient across the epithelium, are distinguished in the tissues when the lumens are faced up and down in cultures, respectively. Furthermore, the presence of the low oxygen gradients supported the coculture of intestinal epithelium along with a complex living commensal gut microbiome (including obligate anaerobes) to simulate temporal microbiome dynamics in the native human gut. This unique silk scaffold platform may enable the exploration of microbiota-related mechanisms of disease pathogenesis and host-pathogen dynamics in infectious diseases including the potential to explore the human microbiome-gut-brain axis and potential novel microbiome-based therapeutics.}, }
@article {pmid35679312, year = {2022}, author = {Wedenoja, S and Saarikivi, A and Mälkönen, J and Leskinen, S and Lehto, M and Adeshara, K and Tuokkola, J and Nikkonen, A and Merras-Salmio, L and Höyhtyä, M and Hörkkö, S and Haaramo, A and Salonen, A and de Vos, WM and Korpela, K and Kolho, KL}, title = {Fecal microbiota in congenital chloride diarrhea and inflammatory bowel disease.}, journal = {PloS one}, volume = {17}, number = {6}, pages = {e0269561}, pmid = {35679312}, issn = {1932-6203}, mesh = {Biomarkers ; Butyrates ; *Crohn Disease/microbiology ; Diarrhea/congenital/genetics ; Feces/microbiology ; Follow-Up Studies ; *Gastrointestinal Microbiome/genetics ; Humans ; *Inflammatory Bowel Diseases/microbiology ; Metabolism, Inborn Errors ; *Microbiota ; Quality of Life ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND AND AIMS: Subjects with congenital chloride diarrhea (CLD; a defect in solute carrier family 26 member 3 (SLC26A3)) are prone to inflammatory bowel disease (IBD). We investigated fecal microbiota in CLD and CLD-associated IBD. We also tested whether microbiota is modulated by supplementation with the short-chain fatty acid butyrate.<br><br>SUBJECTS AND METHODS: We recruited 30 patients with CLD for an observational 3-week follow-up study. Thereafter, 16 consented to oral butyrate substitution for a 3-week observational period. Fecal samples, collected once a week, were assayed for calprotectin and potential markers of inflammation, and studied by 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing and compared to that of 19 healthy controls and 43 controls with Crohn's disease. Data on intestinal symptoms, diet and quality of life were collected.<br><br>RESULTS: Patients with CLD had increased abundances of Proteobacteria, Veillonella, and Prevotella, and lower abundances of normally dominant taxa Ruminococcaceae and Lachnospiraceae when compared with healthy controls and Crohn&#xb4;s disease. No major differences in fecal microbiota were found between CLD and CLD-associated IBD (including two with yet untreated IBD). Butyrate was poorly tolerated and showed no major effects on fecal microbiota or biomarkers in CLD.<br><br>CONCLUSIONS: Fecal microbiota in CLD is different from that of healthy subjects or Crohn&#xb4;s disease. Unexpectedly, no changes in the microbiota or fecal markers characterized CLD-associated IBD, an entity with high frequency among patients with CLD.}, }
@article {pmid35678287, year = {2022}, author = {Hou, Y and Tan, T and Guo, Z and Ji, Y and Hu, J and Zhang, Y}, title = {Gram-selective antibacterial peptide hydrogels.}, journal = {Biomaterials science}, volume = {10}, number = {14}, pages = {3831-3844}, doi = {10.1039/d2bm00558a}, pmid = {35678287}, issn = {2047-4849}, mesh = {Animals ; Humans ; Mice ; *Anti-Bacterial Agents/chemistry/pharmacology ; *Gram-Negative Bacteria ; Gram-Positive Bacteria ; Hydrogels/chemistry/pharmacology ; Microbial Sensitivity Tests ; Peptides ; }, abstract = {The human microbiome plays fundamental roles in human health and disease. However, widely used broad-spectrum antibiotics severely disrupt human-related microbial communities, eventually leading to resistant bacteria, posing a growing threat to global medical health. Antimicrobial peptides (AMPs) are promising antimicrobial agents that barely cause bacterial resistance. Excellent broad-spectrum antimicrobial activities have been achieved using hydrogels self-assembled from AMPs, but there is still a lack of AMP hydrogels that can target Gram-positive and Gram-negative bacteria. Herein, several hydrogels self-assembled from AMPs, termed IK1, IK3, and IK4, were designed and synthesized. In vitro antibacterial results indicated that the IK1 and IK4 hydrogels specifically targeted Gram-positive and Gram-negative bacteria, respectively, while the IK3 hydrogel targeted both Gram-positive and Gram-negative bacteria. The desired broad-spectrum or Gram-selective AMP hydrogels are believed to be obtained through the rational design of the hydrophilicity, hydrophobicity, and charge properties of the peptide molecules. Good in vivo Gram-selective antibacterial properties and the ability to promote wound healing have been demonstrated via treating mouse wound models with these AMP hydrogels. We believe that these Gram-selective AMP hydrogels could potentially have important applications in treating common recurring infections.}, }
@article {pmid35676823, year = {2023}, author = {Dedrick, RM and Smith, BE and Cristinziano, M and Freeman, KG and Jacobs-Sera, D and Belessis, Y and Whitney Brown, A and Cohen, KA and Davidson, RM and van Duin, D and Gainey, A and Garcia, CB and Robert George, CR and Haidar, G and Ip, W and Iredell, J and Khatami, A and Little, JS and Malmivaara, K and McMullan, BJ and Michalik, DE and Moscatelli, A and Nick, JA and Tupayachi Ortiz, MG and Polenakovik, HM and Robinson, PD and Skurnik, M and Solomon, DA and Soothill, J and Spencer, H and Wark, P and Worth, A and Schooley, RT and Benson, CA and Hatfull, GF}, title = {Phage Therapy of Mycobacterium Infections: Compassionate Use of Phages in 20 Patients With Drug-Resistant Mycobacterial Disease.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {76}, number = {1}, pages = {103-112}, pmid = {35676823}, issn = {1537-6591}, support = {K08 HL139994/HL/NHLBI NIH HHS/United States ; R35 GM131729/GM/NIGMS NIH HHS/United States ; R01 HL090991/HL/NHLBI NIH HHS/United States ; K23 AI154546/AI/NIAID NIH HHS/United States ; R01 HL146228/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; Compassionate Use Trials ; *Phage Therapy ; *Bacteriophages ; Pharmaceutical Preparations ; *Mycobacterium ; *Mycobacterium Infections, Nontuberculous/microbiology ; *Cystic Fibrosis/microbiology ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {BACKGROUND: Nontuberculous Mycobacterium infections, particularly Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases. Treatment is challenging due to intrinsic antibiotic resistance. Bacteriophage therapy represents a potentially novel approach. Relatively few active lytic phages are available and there is great variation in phage susceptibilities among M. abscessus isolates, requiring personalized phage identification.<br><br>METHODS: Mycobacterium isolates from 200 culture-positive patients with symptomatic disease were screened for phage susceptibilities. One or more lytic phages were identified for 55 isolates. Phages were administered intravenously, by aerosolization, or both to 20 patients on a compassionate use basis and patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid.<br><br>RESULTS: No adverse reactions attributed to therapy were seen in any patient regardless of the pathogen, phages administered, or the route of delivery. Favorable clinical or microbiological responses were observed in 11 patients. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4 cases, but were not consistently associated with unfavorable responses in others. Eleven patients were treated with only a single phage, and no phage resistance was observed in any of these.<br><br>CONCLUSIONS: Phage treatment of Mycobacterium infections is challenging due to the limited repertoire of therapeutically useful phages, but favorable clinical outcomes in patients lacking any other treatment options support continued development of adjunctive phage therapy for some mycobacterial infections.}, }
@article {pmid35672071, year = {2022}, author = {Shahzad, M and Andrews, SC and Ul-Haq, Z}, title = {Exploring the role of Microbiome in Susceptibility, Treatment Response and Outcome among Tuberculosis Patients from Pakistan: study protocol for a prospective cohort study (Micro-STOP).}, journal = {BMJ open}, volume = {12}, number = {6}, pages = {e058463}, pmid = {35672071}, issn = {2044-6055}, mesh = {Case-Control Studies ; Cohort Studies ; Humans ; *Microbiota ; Pakistan ; Prospective Studies ; *Tuberculosis/drug therapy ; }, abstract = {INTRODUCTION: Tuberculosis (TB) caused by Mycobacterium tuberculosis is a common infectious disease associated with significant morbidity and mortality, especially in low-income and middle-income countries. Successful treatment of the disease requires prolonged intake (6-8 months) of multiple antibiotics with potentially detrimental consequences on the composition and functional potential of the human microbiome. The protocol described in the current study aims to identify microbiome (oral and gut) signatures associated with TB pathogenesis, treatment response and outcome in humans.<br><br>METHODS AND ANALYSIS: Four hundred and fifty, newly diagnosed patients with TB from three district levels (Peshawar, Mardan and Swat) TB diagnosis and treatment centres, will be recruited in this non-interventional, prospective cohort study and will be followed and monitored until treatment completion. Demographic and dietary intake data, anthropometric measurement and blood, stool and salivary rinse samples will be collected at baseline, day 15, month-2 and end of the treatment. Additionally, we will recruit age (&#xb1;3 years) and sex-matched healthy controls (n=30). Blood sampling will allow monitoring of the immune response during the treatment, while salivary rinse and faecal samples will allow monitoring of dynamic changes in oral and gut microbiome diversity. Within this prospective cohort study, a nested case-control study design will be conducted to assess perturbations in oral and gut microbiome diversity (microbial dysbiosis) and immune response and compare between the patients groups (treatment success vs failure).<br><br>ETHICS AND DISSEMINATION: The study has received ethics approval from the Ethic Board of Khyber Medical University Peshawar, and administrative approval from Provincial TB Control Programme of Khyber Pakhtunkhwa, Pakistan. The study results will be presented in national and international conferences and published in peer-reviewed journals.<br><br>TRIAL REGISTRATION NUMBER: NCT04985994.}, }
@article {pmid35668366, year = {2022}, author = {Girgis, HZ}, title = {MeShClust v3.0: high-quality clustering of DNA sequences using the mean shift algorithm and alignment-free identity scores.}, journal = {BMC genomics}, volume = {23}, number = {1}, pages = {423}, pmid = {35668366}, issn = {1471-2164}, mesh = {*Algorithms ; Base Sequence ; Cluster Analysis ; Computational Biology ; Humans ; *Microbiota ; Software ; }, abstract = {BACKGROUND: Tools for accurately clustering biological sequences are among the most important tools in computational biology. Two pioneering tools for clustering sequences are CD-HIT and UCLUST, both of which are fast and consume reasonable amounts of memory; however, there is a big room for improvement in terms of cluster quality. Motivated by this opportunity for improving cluster quality, we applied the mean shift algorithm in MeShClust v1.0. The mean shift algorithm is an instance of unsupervised learning. Its strong theoretical foundation guarantees the convergence to the true cluster centers. Our implementation of the mean shift algorithm in MeShClust v1.0 was a step forward. In this work, we scale up the algorithm by adapting an out-of-core strategy while utilizing alignment-free identity scores in a new tool: MeShClust v3.0.<br><br>RESULTS: We evaluated CD-HIT, MeShClust v1.0, MeShClust v3.0, and UCLUST on 22 synthetic sets and five real sets. These data sets were designed or selected for testing the tools in terms of scalability and different similarity levels among sequences comprising clusters. On the synthetic data sets, MeShClust v3.0 outperformed the related tools on all sets in terms of cluster quality. On two real data sets obtained from human microbiome and maize transposons, MeShClust v3.0 outperformed the related tools by wide margins, achieving 55%-300% improvement in cluster quality. On another set that includes degenerate viral sequences, MeShClust v3.0 came third. On two bacterial sets, MeShClust v3.0 was the only applicable tool because of the long sequences in these sets. MeShClust v3.0 requires more time and memory than the related tools; almost all personal computers at the time of this writing can accommodate such requirements. MeShClust v3.0 can estimate an important parameter that controls cluster membership with high accuracy.<br><br>CONCLUSIONS: These results demonstrate the high quality of clusters produced by MeShClust v3.0 and its ability to apply the mean shift algorithm to large data sets and long sequences. Because clustering tools are utilized in many studies, providing high-quality clusters will help with deriving accurate biological knowledge.}, }
@article {pmid35665543, year = {2022}, author = {Chueachavalit, C and Meephansan, J and Payungporn, S and Sawaswong, V and Chanchaem, P and Wongpiyabovorn, J and Thio, HB}, title = {Comparison of Malassezia spp. colonization between human skin exposed to high- and low-ambient air pollution.}, journal = {Experimental dermatology}, volume = {31}, number = {9}, pages = {1454-1461}, doi = {10.1111/exd.14622}, pmid = {35665543}, issn = {1600-0625}, mesh = {*Air Pollution/adverse effects ; Dysbiosis ; Humans ; *Malassezia ; *Microbiota ; Skin/microbiology ; }, abstract = {The skin microbiota is essential for human health; altered skin microbiome colonization and homeostasis may be associated with several inflammatory skin conditions and other inflammatory diseases. Malassezia spp. are commensal fungi commonly found on the human skin, and they also play a pathogenic role in various skin diseases. It is hypothesized that the exposure of human skin to air pollution might be associated with Malassezia spp. colonization. The aim of this study was to compare Malassezia spp. colonization on healthy human skin between people living in two major cities in Thailand with different air qualities: one city with highly polluted ambient air and the other with less polluted air. Skin microbiome samples from 66 participants were collected using swabbing and scraping techniques. The skin fungal composition was analysed using high-throughput sequencing based on internal transcribed spacer 2 (ITS2) rDNA. A significant difference was found in alpha and beta diversities and the relative abundance of fungal profiles between the groups. The relative abundance of Malassezia spp. was found to be significantly higher in the highly polluted area than in the less polluted area. This study demonstrates that high-ambient air pollution may alter Malassezia spp. colonization on healthy human skin, which could lead to dysbiosis of the cutaneous ecosystem and eventually result in some skin disorders.}, }
@article {pmid35664318, year = {2022}, author = {Chen, Q and Lin, S and Song, C}, title = {An Adaptive and Robust Test for Microbial Community Analysis.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {846258}, pmid = {35664318}, issn = {1664-8021}, abstract = {In microbiome studies, researchers measure the abundance of each operational taxon unit (OTU) and are often interested in testing the association between the microbiota and the clinical outcome while conditional on certain covariates. Two types of approaches exists for this testing purpose: the OTU-level tests that assess the association between each OTU and the outcome, and the community-level tests that examine the microbial community all together. It is of considerable interest to develop methods that enjoy both the flexibility of OTU-level tests and the biological relevance of community-level tests. We proposed MiAF, a method that adaptively combines p-values from the OTU-level tests to construct a community-level test. By borrowing the flexibility of OTU-level tests, the proposed method has great potential to generate a series of community-level tests that suit a range of different microbiome profiles, while achieving the desirable high statistical power of community-level testing methods. Using simulation study and real data applications in a smoker throat microbiome study and a HIV patient stool microbiome study, we demonstrated that MiAF has comparable or better power than methods that are specifically designed for community-level tests. The proposed method also provides a natural heuristic taxa selection.}, }
@article {pmid35664224, year = {2022}, author = {Wang, L and Zhang, W and Wu, X and Liang, X and Cao, L and Zhai, J and Yang, Y and Chen, Q and Liu, H and Zhang, J and Ding, Y and Zhu, F and Tang, J}, title = {MIAOME: Human microbiome affect the host epigenome.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {2455-2463}, pmid = {35664224}, issn = {2001-0370}, abstract = {Besides the genetic factors having tremendous influences on the regulations of the epigenome, the microenvironmental factors have recently gained extensive attention for their roles in affecting the host epigenome. There are three major types of microenvironmental factors: microbiota-derived metabolites (MDM), microbiota-derived components (MDC) and microbiota-secreted proteins (MSP). These factors can regulate host physiology by modifying host gene expression through the three highly interconnected epigenetic mechanisms (e.g. histone modifications, DNA modifications, and non-coding RNAs). However, no database was available to provide the comprehensive factors of these types. Herein, a database entitled 'Human Microbiome Affect The Host Epigenome (MIAOME)' was constructed. Based on the types of epigenetic modifications confirmed in the literature review, the MIAOME database captures 1068 (63 genus, 281 species, 707 strains, etc.) human microbes, 91 unique microbiota-derived metabolites &amp; components (16 fatty acids, 10 bile acids, 10 phenolic compounds, 10 vitamins, 9 tryptophan metabolites, etc.) derived from 967 microbes; 50 microbes that secreted 40 proteins; 98 microbes that directly influence the host epigenetic modification, and provides 3 classifications of the epigenome, including (1) 4 types of DNA modifications, (2) 20 histone modifications and (3) 490 ncRNAs regulations, involved in 160 human diseases. All in all, MIAOME has compiled the information on the microenvironmental factors influence host epigenome through the scientific literature and biochemical databases, and allows the collective considerations among the different types of factors. It can be freely assessed without login requirement by all users at: http://miaome.idrblab.net/ttd/.}, }
@article {pmid35661736, year = {2022}, author = {Cohen, LJ and Han, SM and Lau, P and Guisado, D and Liang, Y and Nakashige, TG and Ali, T and Chiang, D and Rahman, A and Brady, SF}, title = {Unraveling function and diversity of bacterial lectins in the human microbiome.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {3101}, pmid = {35661736}, issn = {2041-1723}, support = {K08 DK109287/DK/NIDDK NIH HHS/United States ; P41 GM103694/GM/NIGMS NIH HHS/United States ; R01 AT009562/AT/NCCIH NIH HHS/United States ; R35 GM122559/GM/NIGMS NIH HHS/United States ; R24 GM098791/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/metabolism ; Humans ; *Lectins/metabolism ; Mice ; *Microbiota ; Plants/metabolism ; }, abstract = {The mechanisms by which commensal organisms affect human physiology remain poorly understood. Lectins are non-enzymatic carbohydrate binding proteins that all organisms employ as part of establishing a niche, evading host-defenses and protecting against pathogens. Although lectins have been extensively studied in plants, bacterial pathogens and human immune cells for their role in disease pathophysiology and as therapeutics, the role of bacterial lectins in the human microbiome is largely unexplored. Here we report on the characterization of a lectin produced by a common human associated bacterium that interacts with myeloid cells in the blood and intestine. In mouse and cell-based models, we demonstrate that this lectin induces distinct immunologic responses in peripheral and intestinal leukocytes and that these responses are specific to monocytes, macrophages and dendritic cells. Our analysis of human microbiota sequencing data reveal thousands of unique sequences that are predicted to encode lectins, many of which are highly prevalent in the human microbiome yet completely uncharacterized. Based on the varied domain architectures of these lectins we predict they will have diverse effects on the human host. The systematic investigation of lectins in the human microbiome should improve our understanding of human health and provide new therapeutic opportunities.}, }
@article {pmid35659718, year = {2022}, author = {Almand, AT and Anderson, AP and Hitt, BD and Sitko, JC and Joy, RM and Easter, BD and Almand, EA}, title = {The influence of perceived stress on the human microbiome.}, journal = {BMC research notes}, volume = {15}, number = {1}, pages = {193}, pmid = {35659718}, issn = {1756-0500}, mesh = {Dysbiosis ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; RNA, Ribosomal, 16S ; Stress, Psychological ; }, abstract = {OBJECTIVE: Microbial dysbiosis, a shift from commensal to pathogenic microbiota, is often associated with mental health and the gut-brain axis, where dysbiosis in the gut may be linked to dysfunction in the brain. Many studies focus on dysbiosis induced by clinical events or traumatic incidents; however, many professions in austere or demanding environments may encounter continuously compounded stressors. This study seeks to explore the relationship between microbial populations and stress, both perceived and biochemical.<br><br>RESULTS: Eight individuals enrolled in the study to provide a longitudinal assessment of the impact of stress on gut health, with four individuals providing enough samples for analysis. Eleven core microbial genera were identified, although the relative abundance of these genera and other members of the microbial population shifted over time. Although our results indicate a potential relationship between perceived stress and microbial composition of the gut, no association with biochemical stress was observed. Increases in perceived stress seem to elucidate a change in potentially beneficial Bacteroides, with a loss in Firmicutes phyla. This shift occurred in multiple individuals, whereas using cortisol as a stress biomarker showed contradictory responses. These preliminary data provide a potential mechanism for gut monitoring, while identifying targets for downstream modulation.}, }
@article {pmid35658516, year = {2022}, author = {Naud, S and Ibrahim, A and Valles, C and Maatouk, M and Bittar, F and Tidjani Alou, M and Raoult, D}, title = {Candidate Phyla Radiation, an Underappreciated Division of the Human Microbiome, and Its Impact on Health and Disease.}, journal = {Clinical microbiology reviews}, volume = {35}, number = {3}, pages = {e0014021}, pmid = {35658516}, issn = {1098-6618}, mesh = {Bacteria ; Dysbiosis ; Humans ; *Microbiota ; Mouth/microbiology ; }, abstract = {Candidate phyla radiation (CPR) is an emerging division of the bacterial domain within the human microbiota. Still poorly known, these microorganisms were first described in the environment in 1981 as "ultramicrobacteria" with a cell volume under 0.1 μm[3] and were first associated with the human oral microbiota in 2007. The evolution of technology has been paramount for the study of CPR within the human microbiota. In fact, since these ultramicrobacteria have yet to be axenically cultured despite ongoing efforts, progress in imaging technology has allowed their observation and morphological description. Although their genomic abilities and taxonomy are still being studied, great strides have been made regarding their taxonomic classification, as well as their lifestyle. In addition, advancements in next-generation sequencing and the continued development of bioinformatics tools have allowed their detection as commensals in different human habitats, including the oral cavity and gastrointestinal and genital tracts, thus highlighting CPR as a nonnegligible part of the human microbiota with an impact on physiological settings. Conversely, several pathologies present dysbiosis affecting CPR levels, including inflammatory, mucosal, and infectious diseases. In this exhaustive review of the literature, we provide a historical perspective on the study of CPR, an overview of the methods available to study these organisms and a description of their taxonomy and lifestyle. In addition, their distribution in the human microbiome is presented in both homeostatic and dysbiotic settings. Future efforts should focus on developing cocultures and, if possible, axenic cultures to obtain isolates and therefore genomes that would provide a better understanding of these ultramicrobacteria, the importance of which in the human microbiome is undeniable.}, }
@article {pmid35654877, year = {2022}, author = {Stockdale, SR and Harrington, RS and Shkoporov, AN and Khokhlova, EV and Daly, KM and McDonnell, SA and O'Reagan, O and Nolan, JA and Sheehan, D and Lavelle, A and Draper, LA and Shanahan, F and Ross, RP and Hill, C}, title = {Metagenomic assembled plasmids of the human microbiome vary across disease cohorts.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {9212}, pmid = {35654877}, issn = {2045-2322}, mesh = {Humans ; *Inflammatory Bowel Diseases/genetics/microbiology ; Metagenome ; Metagenomics ; *Microbiota ; Plasmids/genetics ; }, abstract = {We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample β-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome α-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.}, }
@article {pmid35654142, year = {2022}, author = {Bhoite, SS and Han, Y and Ruotolo, BT and Chapman, MR}, title = {Mechanistic insights into accelerated α-synuclein aggregation mediated by human microbiome-associated functional amyloids.}, journal = {The Journal of biological chemistry}, volume = {298}, number = {7}, pages = {102088}, pmid = {35654142}, issn = {1083-351X}, support = {R01 GM118651/GM/NIGMS NIH HHS/United States ; }, mesh = {*Amyloid/metabolism ; Animals ; Escherichia coli ; *Escherichia coli Proteins/metabolism ; Humans ; Mice ; *Microbiota ; Parkinson Disease/pathology ; *Protein Aggregation, Pathological ; *alpha-Synuclein/metabolism ; }, abstract = {The gut microbiome has been shown to have key implications in the pathogenesis of Parkinson's disease (PD). The Escherichia coli functional amyloid CsgA is known to accelerate α-synuclein aggregation in vitro and induce PD symptoms in mice. However, the mechanism governing CsgA-mediated acceleration of α-synuclein aggregation is unclear. Here, we show that CsgA can form stable homodimeric species that correlate with faster α-synuclein amyloid aggregation. Furthermore, we identify and characterize new CsgA homologs encoded by bacteria present in the human microbiome. These CsgA homologs display diverse aggregation kinetics, and they differ in their ability to modulate α-synuclein aggregation. Remarkably, we demonstrate that slowing down CsgA aggregation leads to an increased acceleration of α-synuclein aggregation, suggesting that the intrinsic amyloidogenicity of gut bacterial CsgA homologs affects their ability to accelerate α-synuclein aggregation. Finally, we identify a complex between CsgA and α-synuclein that functions as a platform to accelerate α-synuclein aggregation. Taken together, our work reveals complex interplay between bacterial amyloids and α-synuclein that better informs our understanding of PD causation.}, }
@article {pmid35650275, year = {2022}, author = {Pausan, MR and Blohs, M and Mahnert, A and Moissl-Eichinger, C}, title = {The sanitary indoor environment-a potential source for intact human-associated anaerobes.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {44}, pmid = {35650275}, issn = {2055-5008}, support = {P 30796/FWF_/Austrian Science Fund FWF/Austria ; P 32697/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Archaea/genetics ; Humans ; *Microbiota/genetics ; Oxygen ; RNA, Ribosomal, 16S/genetics ; Symbiosis ; }, abstract = {A healthy human microbiome relies on the interaction with and exchange of microbes that takes place between the human body and its environment. People in high-income countries spend most of their time indoors and for this reason, the built environment (BE) might represent a potent source of commensal microbes. Anaerobic microbes are of particular interest, as researchers have not yet sufficiently clarified how the human microbiome acquires oxygen-sensitive microbes. We sampled the bathrooms in ten households and used propidium monoazide (PMA) to assess the viability of the collected prokaryotes. We compared the microbiome profiles based on 16S rRNA gene sequencing and confirmed our results by genetic and cultivation-based analyses. Quantitative and qualitative analysis revealed that most of the microbial taxa in the BE samples are human-associated. Less than 25% of the prokaryotic signatures originate from intact cells, indicating that aerobic and stress resistant taxa display an apparent survival advantage. However, we also confirmed the presence of intact, strictly anaerobic taxa on bathroom floors, including methanogenic archaea. As methanogens are regarded as highly sensitive to aerobic conditions, oxygen-tolerance experiments were performed with human-associated isolates to validate their survival. These results show that human-associated methanogens can survive oxic conditions for at least 6 h. We collected strong evidence that supports the hypothesis that obligate anaerobic taxa can survive in the BE for a limited amount of time. This suggests that the BE serves as a potential source of anaerobic human commensals.}, }
@article {pmid35643079, year = {2022}, author = {Guthrie, L and Spencer, SP and Perelman, D and Van Treuren, W and Han, S and Yu, FB and Sonnenburg, ED and Fischbach, MA and Meyer, TW and Sonnenburg, JL}, title = {Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {6}, pages = {863-874.e4}, pmid = {35643079}, issn = {1934-6069}, support = {R01 DK101674/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 DK007056/DK/NIDDK NIH HHS/United States ; F32 AG062119/AG/NIA NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; }, mesh = {Diet ; *Gastrointestinal Microbiome ; Humans ; Indican ; Metabolome ; *Microbiota ; }, abstract = {Gut microbiota metabolism of dietary compounds generates a vast array of microbiome-dependent metabolites (MDMs), which are highly variable between individuals. The uremic MDMs (uMDMs) phenylacetylglutamine (PAG), p-cresol sulfate (PCS), and indoxyl sulfate (IS) accumulate during renal failure and are associated with poor outcomes. Targeted dietary interventions may reduce toxic MDM generation; however, it is unclear if inter-individual differences in diet or gut microbiome dominantly contribute to MDM variance. Here, we use a 7-day homogeneous average American diet to standardize dietary precursor availability in 21 healthy individuals. During dietary homogeneity, the coefficient of variation in PAG, PCS, and IS (primary outcome) did not decrease, nor did inter-individual variation in most identified metabolites; other microbiome metrics showed no or modest responses to the intervention. Host identity and age are dominant contributors to variability in MDMs. These results highlight the potential need to pair dietary modification with microbial therapies to control MDM profiles.}, }
@article {pmid35641786, year = {2022}, author = {Cani, PD and Depommier, C and Derrien, M and Everard, A and de Vos, WM}, title = {Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {19}, number = {10}, pages = {625-637}, pmid = {35641786}, issn = {1759-5053}, mesh = {*Akkermansia ; Animals ; Humans ; Intestines/microbiology ; Obesity/microbiology ; *Verrucomicrobia/physiology ; }, abstract = {Ever since Akkermansia muciniphila was discovered and characterized two decades ago, numerous studies have shown that the lack or decreased abundance of this commensal bacterium was linked with multiple diseases (such as obesity, diabetes, liver steatosis, inflammation and response to cancer immunotherapies). Although primarily based on simple associations, there are nowadays an increasing number of studies moving from correlations to causality. The causal evidence derived from a variety of animal models performed in different laboratories and recently was also recapitulated in a human proof-of-concept trial. In this Review, we cover the history of the discovery of A. muciniphila and summarize the numerous findings and main mechanisms of action by which this intestinal symbiont improves health. A comparison of this microorganism with other next-generation beneficial microorganisms that are being developed is also made.}, }
@article {pmid35638779, year = {2022}, author = {Attai, H and Wilde, J and Liu, R and Chopyk, J and Garcia, AG and Allen-Vercoe, E and Pride, D}, title = {Bacteriophage-Mediated Perturbation of Defined Bacterial Communities in an In Vitro Model of the Human Gut.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0113522}, pmid = {35638779}, issn = {2165-0497}, mesh = {Animals ; Bacteria ; *Bacteriophages ; Bacteroidetes ; Feces/microbiology ; Gastrointestinal Tract/microbiology ; Humans ; Mice ; *Microbiota ; *Viruses ; }, abstract = {The study of bacteriophage communities reproducing in the gastrointestinal tract is limited by the quality of model systems supporting experimental manipulation in vitro. Traditionally, studies aiming to experimentally address phage-bacteria dynamics have utilized gnotobiotic mice inoculated with defined bacterial communities. While mouse models simulate complex interactions between microbes and their host, they also forestall the study of phage-bacteria dynamics in isolation of host factors. Here, we established a method for manipulating phage-bacteria dynamics using an in vitro chemostat bioreactor model of the distal human gut. We create defined communities representing a subset of bacteria in the feces of two human individuals, cultivated these communities in chemostat bioreactors, developed methods to purify the autochthonous viromes associated with each cultured community, and trialed a system for transmitting live or heat-killed viruses between chemostat bioreactors to decipher outcomes of virus-mediated perturbation. We found that allochthonous viromes were detectable via metagenomic sequencing against the autochthonous virome background and that shifts in bacterial community diversity and composition were detectable in relation to time posttreatment. These microbiome composition changes spanned multiple phyla, including Bacteroidetes, Firmicutes, and Actinobacteria. We also found that compositional changes occurred when using live viruses regardless of whether intrasubject or intersubject viruses were used as the perturbation agents. Our results supported the use of chemostat bioreactors as a platform for studying complex bacteria-phage dynamics in vitro. IMPORTANCE Bacteriophages are relatively ubiquitous in the environment and are highly abundant in the human microbiome. Phages can be commonly transmitted between close contacts, but the impact that such transmissions may have on their bacteria counterparts in our microbiomes is unknown. We developed a chemostat cultivation system to simulate individual-specific features of human distal gut microbiota that can be used to transmit phages between ecosystems and measure their impacts on the microbiota. We used this system to transfer phage communities between chemostats that represented different human subjects. We found that there were significant effects on overall microbiota diversity and changes in the relative abundances of Bacteroidetes, Firmicutes, and Actinobacteria, when intersubject perturbations were performed, compared to intrasubject perturbations. These changes were observed when perturbations were performed using live phages, but not when heat-killed phages were used, and they support the use of chemostat systems for studying complex human bacteria-phage dynamics.}, }
@article {pmid35636654, year = {2022}, author = {Bryan, NS and Burleigh, MC and Easton, C}, title = {The oral microbiome, nitric oxide and exercise performance.}, journal = {Nitric oxide : biology and chemistry}, volume = {125-126}, number = {}, pages = {23-30}, doi = {10.1016/j.niox.2022.05.004}, pmid = {35636654}, issn = {1089-8611}, mesh = {Bacteria/metabolism ; Exercise ; Humans ; *Microbiota ; Nitrates/metabolism ; Nitric Oxide/metabolism ; *Nitrites/metabolism ; Nitrogen Oxides/metabolism ; }, abstract = {The human microbiome comprises ∼10[13]-10[14] microbial cells which form a symbiotic relationship with the host and play a critical role in the regulation of human metabolism. In the oral cavity, several species of bacteria are capable of reducing nitrate to nitrite; a key precursor of the signaling molecule nitric oxide. Nitric oxide has myriad physiological functions, which include the maintenance of cardiovascular homeostasis and the regulation of acute and chronic responses to exercise. This article provides a brief narrative review of the research that has explored how diversity and plasticity of the oral microbiome influences nitric oxide bioavailability and related physiological outcomes. There is unequivocal evidence that dysbiosis (e.g. through disease) or disruption (e.g. by use of antiseptic mouthwash or antibiotics) of the oral microbiota will suppress nitric oxide production via the nitrate-nitrite-nitric oxide pathway and negatively impact blood pressure. Conversely, there is preliminary evidence to suggest that proliferation of nitrate-reducing bacteria via the diet or targeted probiotics can augment nitric oxide production and improve markers of oral health. Despite this, it is yet to be established whether purposefully altering the oral microbiome can have a meaningful impact on exercise performance. Future research should determine whether alterations to the composition and metabolic activity of bacteria in the mouth influence the acute responses to exercise and the physiological adaptations to exercise training.}, }
@article {pmid35633673, year = {2022}, author = {Maestre-Carballa, L and Navarro-López, V and Martinez-Garcia, M}, title = {A Resistome Roadmap: From the Human Body to Pristine Environments.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {858831}, pmid = {35633673}, issn = {1664-302X}, abstract = {A comprehensive characterization of the human body resistome [sets of antibiotic resistance genes (ARGs)] is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut, and oral cavity) of healthy subjects from the Human Microbiome Project (HMP) and addressed the potential dispersion of ARGs in pristine environments. A total of 28,714 ARGs belonging to 235 different ARG types were found in the HMP proteome dataset (n = 9.1 × 10[7] proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high interindividual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, whereas the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). The fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide-lincosamide-streptogramin (MLS) or tetracycline. Most ARGs belonged to common bacterial commensals and multidrug resistance trait were predominant in the nares and vagina. Many ARGs detected here were considered as low risk for human health, whereas only a few of them, such as BlaZ, dfrA14, dfrA17, or tetM, were classified as high-risk ARG. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n = 271 samples; 77 Gb of sequencing data and 2.1 × 10[8] proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host-microbes and environments as a whole.}, }
@article {pmid35633665, year = {2022}, author = {El-Chami, C and Choudhury, R and Mohammedsaeed, W and McBain, AJ and Kainulainen, V and Lebeer, S and Satokari, R and O'Neill, CA}, title = {Multiple Proteins of Lacticaseibacillus rhamnosus GG Are Involved in the Protection of Keratinocytes From the Toxic Effects of Staphylococcus aureus.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {875542}, pmid = {35633665}, issn = {1664-302X}, abstract = {We have previously shown that lysates of Lacticaseibacillus rhamnosus GG confer protection to human keratinocytes against Staphylococcus aureus. L. rhamnosus GG inhibits the growth of S. aureus as well as competitively excludes and displaces the pathogen from keratinocytes. In this study, we have specifically investigated the anti-adhesive action. We have tested the hypothesis that this activity is due to quenching of S. aureus binding sites on keratinocytes by molecules within the Lacticaseibacillus lysate. Trypsinisation or heat treatment removed the protective effect of the lysate suggesting the involvement of proteins as effector molecules. Column separation of the lysate and analysis of discrete fractions in adhesion assays identified a fraction of moderate hydrophobicity that possessed all anti-adhesive functions. Immunoblotting demonstrated that this fraction contained the pilus protein, SpaC. Recombinant SpaC inhibited staphylococcal adhesion to keratinocytes in a dose-dependent manner and improved keratinocyte viability following challenge with viable S. aureus. However, SpaC did not confer the full anti-adhesive effects of the LGG lysate and excluded but did not displace S. aureus from keratinocytes. Further purification produced four protein-containing peaks (F1-F4). Of these, F4, which had the greatest column retention time, was the most efficacious in anti-staphylococcal adhesion and keratinocyte viability assays. Identification of proteins by mass spectrometry showed F4 to contain several known "moonlighting proteins"-i.e., with additional activities to the canonical function, including enolase, Triosephosphate isomerase (TPI), Glyceraldehyde 3 phosphate dehydrogenase (G3P) and Elongation factor TU (EF-Tu). Of these, only enolase and TPI inhibited S. aureus adhesion and protected keratinocytes viability in a dose-dependent manner. These data suggest that inhibition of staphylococcal binding by the L. rhamnosus GG lysate is mediated by SpaC and specific moonlight proteins.}, }
@article {pmid35632464, year = {2022}, author = {Brogna, C and Brogna, B and Bisaccia, DR and Lauritano, F and Marino, G and Montano, L and Cristoni, S and Prisco, M and Piscopo, M}, title = {Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?.}, journal = {Vaccines}, volume = {10}, number = {5}, pages = {}, pmid = {35632464}, issn = {2076-393X}, abstract = {SARS-CoV-2 has become one of the most studied viruses of the last century. It was assumed that the only possible host for these types of viruses was mammalian eukaryotic cells. Our recent studies show that microorganisms in the human gastrointestinal tract affect the severity of COVID-19 and for the first time provide indications that the virus might replicate in gut bacteria. In order to further support these findings, in the present work, cultures of bacteria from the human microbiome and SARS-CoV-2 were analyzed by electron and fluorescence microscopy. The images presented in this article, in association with the nitrogen ([15]N) isotope-labeled culture medium experiment, suggest that SARS-CoV-2 could also infect bacteria in the gut microbiota, indicating that SARS-CoV-2 could act as a bacteriophage. Our results add new knowledge to the understanding of the mechanisms of SARS-CoV-2 infection and fill gaps in the study of the interactions between SARS-CoV-2 and non-mammalian cells. These findings could be useful in suggesting specific new pharmacological solutions to support the vaccination campaign.}, }
@article {pmid35631758, year = {2022}, author = {Harutyunyan, N and Kushugulova, A and Hovhannisyan, N and Pepoyan, A}, title = {One Health Probiotics as Biocontrol Agents: One Health Tomato Probiotics.}, journal = {Plants (Basel, Switzerland)}, volume = {11}, number = {10}, pages = {}, pmid = {35631758}, issn = {2223-7747}, support = {10-15/I-5; 21AG-4D065//State Committee of Science/ ; }, abstract = {Tomato (Lycopersicon esculentum) is one of the most popular and valuable vegetables in the world. The most common products of its industrial processing in the food industry are juice, tomato paste, various sauces, canned or sun-dried fruits and powdered products. Tomato fruits are susceptible to bacterial diseases, and bacterial contamination can be a risk factor for the safety of processed tomato products. Developments in bioinformatics allow researchers to discuss target probiotic strains from an existing large number of probiotic strains for any link in the soil-plant-animal-human chain. Based on the literature and knowledge on the "One Health" concept, this study relates to the suggestion of a new term for probiotics: "One Health probiotics", beneficial for the unity of people, animals, and the environment. Strains of Lactiplantibacillus plantarum, having an ability to ferment a broad spectrum of plant carbohydrates, probiotic effects in human, and animal health, as well as being found in dairy products, vegetables, sauerkraut, pickles, some cheeses, fermented sausages, fish products, and rhizospheric soil, might be suggested as one of the probable candidates for "One Health" probiotics (also, for "One Health-tomato" probiotics) for the utilization in agriculture, food processing, and healthcare.}, }
@article {pmid35631036, year = {2022}, author = {Pane, S and Putignani, L}, title = {Cryptosporidium: Still Open Scenarios.}, journal = {Pathogens (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {35631036}, issn = {2076-0817}, abstract = {Cryptosporidiosis is increasingly identified as a leading cause of childhood diarrhea and malnutrition in both low-income and high-income countries. The strong impact on public health in epidemic scenarios makes it increasingly essential to identify the sources of infection and understand the transmission routes in order to apply the right prevention or treatment protocols. The objective of this literature review was to present an overview of the current state of human cryptosporidiosis, reviewing risk factors, discussing advances in the drug treatment and epidemiology, and emphasizing the need to identify a government system for reporting diagnosed cases, hitherto undervalued.}, }
@article {pmid35629374, year = {2022}, author = {Puigbò, P and Leino, LI and Rainio, MJ and Saikkonen, K and Saloniemi, I and Helander, M}, title = {Does Glyphosate Affect the Human Microbiota?.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {5}, pages = {}, pmid = {35629374}, issn = {2075-1729}, support = {311077//Academy of Finland/ ; N/A//Turku Collegium for Science, Medicine and Technology/ ; }, abstract = {Glyphosate is the world's most widely used agrochemical. Its use in agriculture and gardening has been proclaimed safe because humans and other animals do not have the target enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). However, increasing numbers of studies have demonstrated risks to humans and animals because the shikimate metabolic pathway is present in many microbes. Here, we assess the potential effect of glyphosate on healthy human microbiota. Our results demonstrate that more than one-half of human microbiome are intrinsically sensitive to glyphosate. However, further empirical studies are needed to determine the effect of glyphosate on healthy human microbiota.}, }
@article {pmid35629064, year = {2022}, author = {Arjunan, P and Swaminathan, R}, title = {Do Oral Pathogens Inhabit the Eye and Play a Role in Ocular Diseases?.}, journal = {Journal of clinical medicine}, volume = {11}, number = {10}, pages = {}, pmid = {35629064}, issn = {2077-0383}, abstract = {Fascinatingly, the immune-privileged healthy eye has a small unique population of microbiota. The human microbiome project led to continuing interest in the ocular microbiome. Typically, ocular microflorae are commensals of low diversity that colonize the external and internal sites of the eye, without instigating any disorders. Ocular commensals modulate immunity and optimally regulate host defense against pathogenic invasion, both on the ocular surface and neuroretina. Yet, any alteration in this symbiotic relationship culminates in the perturbation of ocular homeostasis and shifts the equilibrium toward local or systemic inflammation and, in turn, impaired visual function. A compositional variation in the ocular microbiota is associated with surface disorders such as keratitis, blepharitis, and conjunctivitis. Nevertheless, innovative studies now implicate non-ocular microbial dysbiosis in glaucoma, age-related macular degeneration (AMD), uveitis, and diabetic retinopathy. Accordingly, prompt identification of the extra-ocular etiology and a methodical understanding of the mechanisms of invasion and host-microbial interaction is of paramount importance for preventative and therapeutic interventions for vision-threatening conditions. This review article aims to explore the current literature evidence to better comprehend the role of oral pathogens in the etiopathogenesis of ocular diseases, specifically AMD.}, }
@article {pmid35628138, year = {2022}, author = {Linkens, AMA and van Best, N and Niessen, PM and Wijckmans, NEG and de Goei, EEC and Scheijen, JLJM and van Dongen, MCJM and van Gool, CCJAW and de Vos, WM and Houben, AJHM and Stehouwer, CDA and Eussen, SJMP and Penders, J and Schalkwijk, CG}, title = {A 4-Week Diet Low or High in Advanced Glycation Endproducts Has Limited Impact on Gut Microbial Composition in Abdominally Obese Individuals: The deAGEing Trial.}, journal = {International journal of molecular sciences}, volume = {23}, number = {10}, pages = {}, pmid = {35628138}, issn = {1422-0067}, support = {95105002//Netherlands Organisation for Health Research and Development/ ; 2016.00.1865//Dutch Diabetes Research Foundation/ ; }, mesh = {Cross-Sectional Studies ; Diet ; Double-Blind Method ; *Gastrointestinal Microbiome ; *Glycation End Products, Advanced/administration &amp; dosage ; Humans ; *Obesity/diet therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Dietary advanced glycation endproducts (AGEs), abundantly present in Westernized diets, are linked to negative health outcomes, but their impact on the gut microbiota has not yet been well investigated in humans. We investigated the effects of a 4-week isocaloric and macronutrient-matched diet low or high in AGEs on the gut microbial composition of 70 abdominally obese individuals in a double-blind parallel-design randomized controlled trial (NCT03866343). Additionally, we investigated the cross-sectional associations between the habitual intake of dietary dicarbonyls, reactive precursors to AGEs, and the gut microbial composition, as assessed by 16S rRNA amplicon-based sequencing. Despite a marked percentage difference in AGE intake, we observed no differences in microbial richness and the general community structure. Only the Anaerostipes spp. had a relative abundance >0.5% and showed differential abundance (0.5 versus 1.11%; p = 0.028, after low- or high-AGE diet, respectively). While the habitual intake of dicarbonyls was not associated with microbial richness or a general community structure, the intake of 3-deoxyglucosone was especially associated with an abundance of several genera. Thus, a 4-week diet low or high in AGEs has a limited impact on the gut microbial composition of abdominally obese humans, paralleling its previously observed limited biological consequences. The effects of dietary dicarbonyls on the gut microbiota composition deserve further investigation.}, }
@article {pmid35625219, year = {2022}, author = {Skurnik, M}, title = {Can Bacteriophages Replace Antibiotics?.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {5}, pages = {}, pmid = {35625219}, issn = {2079-6382}, support = {2016//Jane and Aatos Erkko Foundation/ ; }, abstract = {Increasing antibiotic resistance numbers force both scientists and politicians to tackle the problem, and preferably without any delay. The application of bacteriophages as precision therapy to treat bacterial infections, phage therapy, has received increasing attention during the last two decades. While it looks like phage therapy is here to stay, there is still a lot to do. Medicine regulatory authorities are working to deliver clear instructions to carry out phage therapy. Physicians need to get more practical experience on treatments with phages. In this opinion article I try to place phage therapy in the context of the health care system and state that the use phages for precision treatments will require a seamless chain of events from the patient to the phage therapy laboratory to allow for the immediate application of phages therapeutically. It is not likely that phages will replace antibiotics, however, they will be valuable in the treatment of infections caused by multidrug resistant bacteria. Antibiotics will nevertheless remain the main treatment for a majority of infections.}, }
@article {pmid35624309, year = {2022}, author = {Gavin, DP and Reen, FJ and Rocha-Martin, J and Abreu-Castilla, I and Woods, DF and Foley, AM and Sánchez-Murcia, PA and Schwarz, M and O'Neill, P and Maguire, AR and O'Gara, F}, title = {Author Correction: Genome mining and characterisation of a novel transaminase with remote stereoselectivity.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {8947}, doi = {10.1038/s41598-022-12801-5}, pmid = {35624309}, issn = {2045-2322}, }
@article {pmid35620320, year = {2022}, author = {Li, X and Wang, L and Ma, S and Lin, S and Wang, C and Wang, H}, title = {Combination of Oxalobacter Formigenes and Veillonella Parvula in Gastrointestinal Microbiota Related to Bile-Acid Metabolism as a Biomarker for Hypertensive Nephropathy.}, journal = {International journal of hypertension}, volume = {2022}, number = {}, pages = {5999530}, pmid = {35620320}, issn = {2090-0384}, abstract = {The human microbiome is a mixed group of microorganisms, which individually consists of 10-100 trillion symbiotic microbial cells. The relationship between gastrointestinal microbiota and blood pressure has been verified and the intestinal microbiota of chronic kidney disease (CKD) patients in the distribution of bacterial species is different from the flora of people with no CKD. The purpose of this research is to study the different intestinal microbiota of hypertensive patients with and without nephropathy and to find possible biomarkers of hypertensive nephropathy (H-CKD). The subjects of this research were divided into three groups, healthy control group, hypertension group, and hypertensive nephropathy group. Sequencing, bioinformatics, and statistical analysis were performed on the 16S rRNA gene of the subjects' stool samples. This research study showed the differences of intestinal flora as biomarkers in hypertension patients with and without nephropathy; it investigated the relationship of the differences in the intestinal microbiota with bile-acid metabolism; it also explored bile-acid metabolism mechanism of intestinal microbiota differences in hypertension with or without nephropathy. In summary, the difference in the combination of O. formigenes and V. parvula in the gastrointestinal microbiota is related to bile-acid metabolism in hypertensive patients and can be one of the factors causing CKD. It is the first time to report such a biomarker or pathogenic factor of H-CKD in the world.}, }
@article {pmid35616767, year = {2022}, author = {Hasan, R and Bose, S and Roy, R and Paul, D and Rawat, S and Nilwe, P and Chauhan, NK and Choudhury, S}, title = {Tumor tissue-specific bacterial biomarker panel for colorectal cancer: Bacteroides massiliensis, Alistipes species, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, Corynebacterium appendicis.}, journal = {Archives of microbiology}, volume = {204}, number = {6}, pages = {348}, pmid = {35616767}, issn = {1432-072X}, support = {4.9.36-011//Sir Ganga Ram Hospital, Research and Development programme/ ; }, mesh = {Bacteria/genetics ; Bacteroides ; Bacteroidetes ; *Bifidobacterium pseudocatenulatum/genetics ; Biomarkers, Tumor/genetics ; *Colorectal Neoplasms/diagnosis/microbiology ; Corynebacterium ; *Gastrointestinal Microbiome/genetics ; Humans ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Human microbiome studies have shown diversity to exist among different ethnic populations. However, studies pertaining to the microbial composition of CRC among the Indian population have not been well explored. We aimed to decipher the microbial signature in tumor tissues from North Indian CRC patients. Next-generation sequencing of tumor and adjacent tissue-derived bacterial 16S rRNA V3-V4 hypervariable regions was performed to investigate the abundance of specific microbes. The expression profile analysis deciphered a decreased diversity among the tumor-associated microbial communities. At the phyla level, Proteobacteria was differentially expressed in CRC tissues than adjacent normal. Further, DeSeq2 normalization identified 4 out of 79 distinct species (p < 0.005) only in CRC, Bacteroides massiliensis, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, and Corynebacterium appendicis. Thus, the findings suggest that microbial signatures can be used as putative biomarkers in diagnosis, prognosis and treatment management of CRC.}, }
@article {pmid35611465, year = {2022}, author = {Gulliver, EL and Young, RB and Chonwerawong, M and D'Adamo, GL and Thomason, T and Widdop, JT and Rutten, EL and Rossetto Marcelino, V and Bryant, RV and Costello, SP and O'Brien, CL and Hold, GL and Giles, EM and Forster, SC}, title = {Review article: the future of microbiome-based therapeutics.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {56}, number = {2}, pages = {192-208}, pmid = {35611465}, issn = {1365-2036}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.<br><br>AIM: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development.<br><br>METHODS: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'.<br><br>RESULTS: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics.<br><br>CONCLUSIONS: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation.}, }
@article {pmid35608350, year = {2022}, author = {Tong, X and Yu, X and Du, Y and Su, F and Liu, Y and Li, H and Liu, Y and Mu, K and Liu, Q and Li, H and Zhu, J and Xu, H and Xiao, F and Li, Y}, title = {Peripheral Blood Microbiome Analysis via Noninvasive Prenatal Testing Reveals the Complexity of Circulating Microbial Cell-Free DNA.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0041422}, pmid = {35608350}, issn = {2165-0497}, mesh = {*Cell-Free Nucleic Acids/genetics ; *Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human ; Humans ; *Microbiota/genetics ; *Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; }, abstract = {While circulating cell-free DNA (cfDNA) is becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a microbial cfDNA baseline in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Because noninvasive prenatal testing (NIPT) shares many similarities with the sequencing protocol of metagenomics, we utilized the standard low-pass whole-genome-sequencing-based NIPT to establish a microbial cfDNA baseline in healthy people. Sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening were retrospectively collected and reanalyzed for microbiome DNA screening. It was found that more than 95% of exogenous cfDNA was from bacteria, 3% from eukaryotes, and 0.4% from viruses, indicating the gut/environment origins of many microorganisms. Overall and regional abundance patterns were well illustrated, with huge regional diversity and complexity, and unique interspecies and symbiotic relationships were observed for TORCH organisms (Toxoplasma gondii, others [Treponema pallidum {causing syphilis}, hepatitis B virus {HBV}, and human parvovirus B19 {HPV-B19}], rubella virus, cytomegalovirus [CMV], and herpes simplex virus [HSV]) and another common virus, Epstein-Barr virus (EBV). To sum up, our study revealed the complexity of the baseline circulating microbial cfDNA and showed that microbial cfDNA sequencing results need to be interpreted in a more comprehensive manner. IMPORTANCE While circulating cell-free DNA (cfDNA) has been becoming a powerful marker for noninvasive identification of infectious pathogens in liquid biopsy specimens, a baseline for microbial cfDNA in healthy individuals is urgently needed for the proper interpretation of microbial cfDNA sequencing results in clinical metagenomics. Standard low-pass whole-genome-sequencing-based NIPT shares many similarities with the sequencing protocol for metagenomics and could provide a microbial cfDNA baseline in healthy people; thus, a reference cfDNA data set of the human microbiome was established with sequencing data from a total of 107,763 peripheral blood samples of healthy pregnant women undergoing NIPT screening. Our study revealed the complexity of circulating microbial cfDNA and indicated that microbial cfDNA sequencing results need to be interpreted in a more comprehensive manner, especially with regard to geographic patterns and coexistence networks.}, }
@article {pmid35603752, year = {2023}, author = {Nabizadeh, E and Sadeghi, J and Ahangarzadeh Rezaee, M and Hasani, A and Samadi Kafil, H and Ghotaslou, A and Kadkhoda, H and Ghotaslou, R}, title = {Interaction Between Altered Gut Microbiota and Sepsis: A Hypothesis or an Authentic Fact?.}, journal = {Journal of intensive care medicine}, volume = {38}, number = {1}, pages = {121-131}, doi = {10.1177/08850666221102796}, pmid = {35603752}, issn = {1525-1489}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; *Microbiota ; *Sepsis ; Immune System ; }, abstract = {Sepsis, as an important public health concern, is one of the leading causes of death in hospitals around the world, accounting for 25% of all deaths. Nowadays, several factors contribute to the development of sepsis. The role of the gut microbiota and the response state of the aberrant immune system is dominant. The effect of the human microbiome on health is undeniable, and gut microbiota is even considered a body organ. It is now clear that the alteration in the normal balance of the microbiota (dysbiosis) is associated with a change in the status of immune system responses. Owing to the strong association between the gut microbiota and its metabolites particularly short-chain fatty acids with many illnesses, the gut microbiota has a unique position in the research of microbiologists and even clinicians. This review aimed to analyze studies' results on the association between microbiota and sepsis, with a substantial understanding of their relationship. As a result, an extensive and comprehensive search was conducted on this issue in existing databases.}, }
@article {pmid35601739, year = {2022}, author = {Issilbayeva, A and Ainabekova, B and Zhetkenev, S and Meiramova, A and Akhmetova, Z and Karina, K and Kozhakhmetov, S and Nurgaziyev, M and Chulenbayeva, L and Poddighe, D and Kunz, J and Kushugulova, A}, title = {Association Study of Anticitrullinated Peptide Antibody Status with Clinical Manifestations and SNPs in Patients Affected with Rheumatoid Arthritis: A Pilot Study.}, journal = {Disease markers}, volume = {2022}, number = {}, pages = {2744762}, pmid = {35601739}, issn = {1875-8630}, mesh = {*Arthritis, Rheumatoid ; Autoantibodies ; Female ; Genome-Wide Association Study ; Humans ; Peptides ; Pilot Projects ; *Polymorphism, Single Nucleotide ; }, abstract = {INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia.<br><br>METHODS: Our study included 70 RA patients. Patients' blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. Results and Conclusion. Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin.<br><br>CONCLUSION: Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.}, }
@article {pmid35599315, year = {2022}, author = {Jian, C and Silvestre, MP and Middleton, D and Korpela, K and Jalo, E and Broderick, D and de Vos, WM and Fogelholm, M and Taylor, MW and Raben, A and Poppitt, S and Salonen, A}, title = {Gut microbiota predicts body fat change following a low-energy diet: a PREVIEW intervention study.}, journal = {Genome medicine}, volume = {14}, number = {1}, pages = {54}, pmid = {35599315}, issn = {1756-994X}, mesh = {Adipose Tissue/metabolism ; Adult ; Butyrates/pharmacology ; Diet ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Overweight/metabolism ; *Prediabetic State ; RNA, Ribosomal, 16S/genetics ; Weight Loss ; }, abstract = {BACKGROUND: Low-energy diets (LEDs) comprise commercially formulated food products that provide between 800 and 1200 kcal/day (3.3-5 MJ/day) to aid body weight loss. Recent small-scale studies suggest that LEDs are associated with marked changes in the gut microbiota that may modify the effect of the LED on host metabolism and weight loss. We investigated how the gut microbiota changed during 8 weeks of total meal replacement LED and determined their associations with host response in a sub-analysis of 211 overweight adults with pre-diabetes participating in the large multicentre PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) clinical trial.<br><br>METHODS: Microbial community composition was analysed by Illumina sequencing of the hypervariable V3-V4 regions of the 16S ribosomal RNA (rRNA) gene. Butyrate production capacity was estimated by qPCR targeting the butyryl-CoA:acetate CoA-transferase gene. Bioinformatics and statistical analyses, such as comparison of alpha and beta diversity measures, correlative and differential abundances analysis, were undertaken on the 16S rRNA gene sequences of 211 paired (pre- and post-LED) samples as well as their integration with the clinical, biomedical and dietary datasets for predictive modelling.<br><br>RESULTS: The overall composition of the gut microbiota changed markedly and consistently from pre- to post-LED (P = 0.001), along with increased richness and diversity (both P < 0.001). Following the intervention, the relative abundance of several genera previously associated with metabolic improvements (e.g., Akkermansia and Christensenellaceae R-7 group) was significantly increased (P < 0.001), while flagellated Pseudobutyrivibrio, acetogenic Blautia and Bifidobacterium spp. were decreased (all P < 0.001). Butyrate production capacity was reduced (P < 0.001). The changes in microbiota composition and predicted functions were significantly associated with body weight loss (P < 0.05). Baseline gut microbiota features were able to explain ~25% of variation in total body fat change (post-pre-LED).<br><br>CONCLUSIONS: The gut microbiota and individual taxa were significantly influenced by the LED intervention and correlated with changes in total body fat and body weight in individuals with overweight and pre-diabetes. Despite inter-individual variation, the baseline gut microbiota was a strong predictor of total body fat change during the energy restriction period.<br><br>TRIAL REGISTRATION: The PREVIEW trial was prospectively registered at ClinicalTrials.gov (NCT01777893) on January 29, 2013.}, }
@article {pmid35593892, year = {2022}, author = {Hansen, ME and Yasmin, SO and Wolfrum, S and Carreira, EM}, title = {Total Synthesis of Mutanobactins A, B from the Human Microbiome: Macrocyclization and Thiazepanone Assembly in a Single Step.}, journal = {Angewandte Chemie (International ed. in English)}, volume = {61}, number = {28}, pages = {e202203051}, pmid = {35593892}, issn = {1521-3773}, mesh = {Cyclization ; Humans ; Lipopeptides/chemistry ; *Microbiota ; *Peptides, Cyclic/chemistry ; Solid-Phase Synthesis Techniques ; }, abstract = {We report the first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome. A rapid, solid-phase peptide synthesis (SPPS) based route delivers these natural products from a cascade of cyclization reactions. This versatile process was also employed in a streamlined synthesis of mutanobactin D. Additionally, we provide an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block.}, }
@article {pmid35590169, year = {2021}, author = {Song, SJ and Wang, J and Martino, C and Jiang, L and Thompson, WK and Shenhav, L and McDonald, D and Marotz, C and Harris, PR and Hernandez, CD and Henderson, N and Ackley, E and Nardella, D and Gillihan, C and Montacuti, V and Schweizer, W and Jay, M and Combellick, J and Sun, H and Garcia-Mantrana, I and Gil Raga, F and Collado, MC and Rivera-Viñas, JI and Campos-Rivera, M and Ruiz-Calderon, JF and Knight, R and Dominguez-Bello, MG}, title = {Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.}, journal = {Med (New York, N.Y.)}, volume = {2}, number = {8}, pages = {951-964.e5}, pmid = {35590169}, issn = {2666-6340}, support = {DP1 AT010885/AT/NCCIH NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {*Cesarean Section/adverse effects ; Citizenship ; Female ; Humans ; Infant ; Infant, Newborn ; Longitudinal Studies ; *Microbiota/genetics ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth.<br><br>METHODS: Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth.<br><br>FINDINGS: Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study.<br><br>CONCLUSIONS: The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth.<br><br>FUNDING: C&amp;D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.}, }
@article {pmid35589762, year = {2022}, author = {Szóstak, N and Szymanek, A and Havránek, J and Tomela, K and Rakoczy, M and Samelak-Czajka, A and Schmidt, M and Figlerowicz, M and Majta, J and Milanowska-Zabel, K and Handschuh, L and Philips, A}, title = {The standardisation of the approach to metagenomic human gut analysis: from sample collection to microbiome profiling.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {8470}, pmid = {35589762}, issn = {2045-2322}, mesh = {DNA ; Humans ; Metagenome ; *Metagenomics/methods ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; }, abstract = {In recent years, the number of metagenomic studies increased significantly. Wide range of factors, including the tremendous community complexity and variability, is contributing to the challenge in reliable microbiome community profiling. Many approaches have been proposed to overcome these problems making hardly possible to compare results of different studies. The significant differences between procedures used in metagenomic research are reflected in a variation of the obtained results. This calls for the need for standardisation of the procedure, to reduce the confounding factors originating from DNA isolation, sequencing and bioinformatics analyses in order to ensure that the differences in microbiome composition are of a true biological origin. Although the best practices for metagenomics studies have been the topic of several publications and the main aim of the International Human Microbiome Standard (IHMS) project, standardisation of the procedure for generating and analysing metagenomic data is still far from being achieved. To highlight the difficulties in the standardisation of metagenomics methods, we thoroughly examined each step of the analysis of the human gut microbiome. We tested the DNA isolation procedure, preparation of NGS libraries for next-generation sequencing, and bioinformatics analysis, aimed at identifying microbial taxa. We showed that the homogenisation time is the leading factor impacting sample diversity, with the recommendation for a shorter homogenisation time (10 min). Ten minutes of homogenisation allows for better reflection of the bacteria gram-positive/gram-negative ratio, and the obtained results are the least heterogenous in terms of beta-diversity of samples microbial composition. Besides increasing the homogenisation time, we observed further potential impact of the library preparation kit on the gut microbiome profiling. Moreover, our analysis revealed that the choice of the library preparation kit influences the reproducibility of the results, which is an important factor that has to be taken into account in every experiment. In this study, a tagmentation-based kit allowed for obtaining the most reproducible results. We also considered the choice of the computational tool for determining the composition of intestinal microbiota, with Kraken2/Bracken pipeline outperforming MetaPhlAn2 in our in silico experiments. The design of an experiment and a detailed establishment of an experimental protocol may have a serious impact on determining the taxonomic profile of the intestinal microbiome community. Results of our experiment can be helpful for a wide range of studies that aim to better understand the role of the gut microbiome, as well as for clinical purposes.}, }
@article {pmid35579554, year = {2022}, author = {Sim, M and Lee, J and Wy, S and Park, N and Lee, D and Kwon, D and Kim, J}, title = {Generation and application of pseudo-long reads for metagenome assembly.}, journal = {GigaScience}, volume = {11}, number = {}, pages = {}, pmid = {35579554}, issn = {2047-217X}, mesh = {High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenome ; Metagenomics/methods ; *Microbiota/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Metagenomic assembly using high-throughput sequencing data is a powerful method to construct microbial genomes in environmental samples without cultivation. However, metagenomic assembly, especially when only short reads are available, is a complex and challenging task because mixed genomes of multiple microorganisms constitute the metagenome. Although long read sequencing technologies have been developed and have begun to be used for metagenomic assembly, many metagenomic studies have been performed based on short reads because the generation of long reads requires higher sequencing cost than short reads.<br><br>RESULTS: In this study, we present a new method called PLR-GEN. It creates pseudo-long reads from metagenomic short reads based on given reference genome sequences by considering small sequence variations existing in individual genomes of the same or different species. When applied to a mock community data set in the Human Microbiome Project, PLR-GEN dramatically extended short reads in length of 101&#xa0;bp to pseudo-long reads with N50 of 33&#xa0;Kbp and 0.4% error rate. The use of these pseudo-long reads generated by PLR-GEN resulted in an obvious improvement of metagenomic assembly in terms of the number of sequences, assembly contiguity, and prediction of species and genes.<br><br>CONCLUSIONS: PLR-GEN can be used to generate artificial long read sequences without spending extra sequencing cost, thus aiding various studies using metagenomes.}, }
@article {pmid35579384, year = {2022}, author = {Furber, MJW and Young, GR and Holt, GS and Pyle, S and Davison, G and Roberts, MG and Roberts, JD and Howatson, G and Smith, DL}, title = {Gut Microbial Stability is Associated with Greater Endurance Performance in Athletes Undertaking Dietary Periodization.}, journal = {mSystems}, volume = {7}, number = {3}, pages = {e0012922}, pmid = {35579384}, issn = {2379-5077}, mesh = {Humans ; *Gastrointestinal Microbiome ; Physical Endurance ; Diet ; Athletes ; Dietary Carbohydrates ; }, abstract = {Dietary manipulation with high-protein or high-carbohydrate content are frequently employed during elite athletic training, aiming to enhance athletic performance. Such interventions are likely to impact upon gut microbial content. This study explored the impact of acute high-protein or high-carbohydrate diets on measured endurance performance and associated gut microbial community changes. In a cohort of well-matched, highly trained endurance runners, we measured performance outcomes, as well as gut bacterial, viral (FVP), and bacteriophage (IV) communities in a double-blind, repeated-measures design randomized control trial (RCT) to explore the impact of dietary intervention with either high-protein or high-carbohydrate content. High-dietary carbohydrate improved time-trial performance by +6.5% (P < 0.03) and was associated with expansion of Ruminococcus and Collinsella bacterial spp. Conversely, high dietary protein led to a reduction in performance by -23.3% (P = 0.001). This impact was accompanied by significantly reduced diversity (IV: P = 0.04) and altered composition (IV and FVP: P = 0.02) of the gut phageome as well as enrichment of both free and inducible Sk1virus and Leuconostoc bacterial populations. Greatest performance during dietary modification was observed in participants with less substantial shifts in community composition. Gut microbial stability during acute dietary periodization was associated with greater athletic performance in this highly trained, well-matched cohort. Athletes, and those supporting them, should be mindful of the potential consequences of dietary manipulation on gut flora and implications for performance, and periodize appropriately. IMPORTANCE Dietary periodization is employed to improve endurance exercise performance but may impact on gut microbial communities. Bacteriophage are implicated in bacterial cell homeostasis and have been identified as biomarkers of disequilibrium in the gut ecosystem possibly brought about through dietary periodization. We find high-carbohydrate and high-protein diets to have opposing impacts on endurance performance in highly trained athlete populations. Reduced performance is linked with disturbance of microbial stasis in the gut. We demonstrate bacteriophage communities are the most sensitive component of the gut microbiota to increased gut stress following dietary manipulation. Athletes undertaking dietary periodization should be aware of potential negative impacts of drastic changes to dietary composition on gut microbial stasis and, in turn, endurance performance.}, }
@article {pmid35577973, year = {2022}, author = {Mangola, SM and Lund, JR and Schnorr, SL and Crittenden, AN}, title = {Ethical microbiome research with Indigenous communities.}, journal = {Nature microbiology}, volume = {7}, number = {6}, pages = {749-756}, pmid = {35577973}, issn = {2058-5276}, support = {RM1 HG009042/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; }, abstract = {Human-microbiome interactions have been associated with evolutionary, cultural and environmental processes. With clinical applications of microbiome research now feasible, it is crucial that the science conducted, particularly among Indigenous communities, adheres to principles of inclusion. This necessitates a transdisciplinary dialogue to decide how biological samples are collected and who benefits from the research and any derived products. As a group of scholars working at the interface of biological and social science, we offer a candid discussion of the lessons learned from our own research and introduce one approach to carry out ethical microbiome research with Indigenous communities.}, }
@article {pmid35577391, year = {2022}, author = {Kantele, A and Paajanen, J and Turunen, S and Pakkanen, SH and Patjas, A and Itkonen, L and Heiskanen, E and Lappalainen, M and Desquilbet, L and Vapalahti, O and Hielm-Björkman, A}, title = {Scent dogs in detection of COVID-19: triple-blinded randomised trial and operational real-life screening in airport setting.}, journal = {BMJ global health}, volume = {7}, number = {5}, pages = {}, pmid = {35577391}, issn = {2059-7908}, mesh = {Airports ; Animals ; *COVID-19/diagnosis ; Dogs ; Humans ; Odorants ; *SARS-CoV-2 ; }, abstract = {OBJECTIVE: To estimate scent dogs' diagnostic accuracy in identification of people infected with SARS-CoV-2 in comparison with reverse transcriptase polymerase chain reaction (RT-PCR). We conducted a randomised triple-blinded validation trial, and a real-life study at the Helsinki-Vantaa International Airport, Finland.<br><br>METHODS: Four dogs were trained to detect COVID-19 using skin swabs from individuals tested for SARS-CoV-2 by RT-PCR. Our controlled triple-blinded validation study comprised four identical sets of 420 parallel samples (from 114 individuals tested positive and 306 negative by RT-PCR), randomly presented to each dog over seven trial sessions. In a real-life setting the dogs screened skin swabs from 303 incoming passengers all concomitantly examined by nasal swab SARS-CoV-2 RT-PCR. Our main outcomes were variables of diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value) for scent dog identification in comparison with RT-PCR.<br><br>RESULTS: Our validation experiments had an overall accuracy of 92% (95% CI 90% to 93%), a sensitivity of 92% (95% CI 89% to 94%) and a specificity of 91% (95% CI 89% to 93%) compared with RT-PCR. For our dogs, trained using the wild-type virus, performance was less accurate for the alpha variant (89% for confirmed wild-type vs 36% for alpha variant, OR 14.0, 95%&#x2009;CI 4.5 to 43.4). In the real-life setting, scent detection and RT-PCR matched 98.7% of the negative swabs. Scant airport prevalence (0.47%) did not allow sensitivity testing; our only SARS-CoV-2 positive swab was not identified (alpha variant). However, ad hoc analysis including predefined positive spike samples showed a total accuracy of 98% (95% CI 97% to 99%).<br><br>CONCLUSIONS: This large randomised controlled triple-blinded validation study with a precalculated sample size conducted at an international airport showed that trained scent dogs screen airport passenger samples with high accuracy. One of our findings highlights the importance of continuous retraining as new variants emerge. Using scent dogs may present a valuable approach for high-throughput, rapid screening of large numbers of people.}, }
@article {pmid35572708, year = {2022}, author = {Vindenes, HK and Lin, H and Shigdel, R and Ringel-Kulka, T and Real, FG and Svanes, C and Peddada, SD and Bertelsen, RJ}, title = {Exposure to Antibacterial Chemicals Is Associated With Altered Composition of Oral Microbiome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {790496}, pmid = {35572708}, issn = {1664-302X}, abstract = {Antimicrobial chemicals are used as preservatives in cosmetics, pharmaceuticals, and food to prevent the growth of bacteria and fungi in the products. Unintentional exposure in humans to such chemicals is well documented, but whether they also interfere with human oral microbiome composition is largely unexplored. In this study, we explored whether the oral bacterial composition is affected by exposure to antibacterial and environmental chemicals. Gingival fluid, urine, and interview data were collected from 477 adults (18-47 years) from the RHINESSA study in Bergen, Norway. Urine biomarkers of triclosan, triclocarban, parabens, benzophenone-3, bisphenols, and 2,4- and 2,5-dichlorophenols (DCPs) were quantified (by mass spectrometry). Microbiome analysis was based on 16S amplicon sequencing. Diversity and differential abundance analyses were performed to identify how microbial communities may change when comparing groups of different chemical exposure. We identified that high urine levels (>75th percentile) of propyl parabens were associated with a lower abundance of bacteria genera TM7 [G-3], Helicobacter, Megasphaera, Mitsuokella, Tannerella, Propionibacteriaceae [G-2], and Dermabacter, as compared with low propylparaben levels (<25[th] percentile). High exposure to ethylparaben was associated with a higher abundance of Paracoccus. High urine levels of bisphenol A were associated with a lower abundance of Streptococcus and exposure to another environmental chemical, 2,4-DCP, was associated with a lower abundance of Treponema, Fretibacterium, and Bacteroidales [G-2]. High exposure to antibacterial and environmental chemicals was associated with an altered composition of gingiva bacteria; mostly commensal bacteria in the oral cavity. Our results highlight a need for a better understanding of how antimicrobial chemical exposure influences the human microbiome.}, }
@article {pmid35558108, year = {2022}, author = {Rosas-Plaza, S and Hernández-Terán, A and Navarro-Díaz, M and Escalante, AE and Morales-Espinosa, R and Cerritos, R}, title = {Human Gut Microbiome Across Different Lifestyles: From Hunter-Gatherers to Urban Populations.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {843170}, pmid = {35558108}, issn = {1664-302X}, abstract = {Human lifestyle and its relationship with the human microbiome has been a line of research widely studied. This is because, throughout human history, civilizations have experienced different environments and lifestyles that could have promoted changes in the human microbiome. The comparison between industrialized and non-industrialized human populations in several studies has allowed to observe variation in the microbiome structure due to the population lifestyle. Nevertheless, the lifestyle of human populations is a gradient where several subcategories can be described. Yet, it is not known how these different lifestyles of human populations affect the microbiome structure on a large scale. Therefore, the main goal of this work was the collection and comparison of 16S data from the gut microbiome of populations that have different lifestyles around the world. With the data obtained from 14 studies, it was possible to compare the gut microbiome of 568 individuals that represent populations of hunter-gatherers, agricultural, agropastoral, pastoral, and urban populations. Results showed that industrialized populations present less diversity than those from non-industrialized populations, as has been described before. However, by separating traditional populations into different categories, we were able to observe patterns that cannot be appreciated by encompassing the different traditional lifestyles in a single category. In this sense, we could confirm that different lifestyles exhibit distinct alpha and beta diversity. In particular, the gut microbiome of pastoral and agropastoral populations seems to be more similar to those of urban populations according to beta diversity analysis. Beyond that, beta diversity analyses revealed that bacterial composition reflects the different lifestyles, representing a transition from hunters-gatherers to industrialized populations. Also, we found that certain groups such as Bacteoidaceae, Lanchospiraceae, and Rickenellaceae have been favored in the transition to modern societies, being differentially abundant in urban populations. Thus, we could hypothesize that due to adaptive/ecological processes; multifunctional bacterial groups (e.g., Bacteroidaceae) could be replacing some functions lost in the transition to modern lifestyle.}, }
@article {pmid35549618, year = {2022}, author = {Chen, L and Zheng, T and Yang, Y and Chaudhary, PP and Teh, JPY and Cheon, BK and Moses, D and Schuster, SC and Schlundt, J and Li, J and Conway, PL}, title = {Integrative multiomics analysis reveals host-microbe-metabolite interplays associated with the aging process in Singaporeans.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2070392}, pmid = {35549618}, issn = {1949-0984}, mesh = {Adult ; Aged ; Aging ; Feces/microbiology ; *Gastrointestinal Microbiome/genetics ; Humans ; Male ; Metabolome ; Metagenomics ; Singapore ; Young Adult ; }, abstract = {The age-associated alterations in microbiomes vary across populations due to the influence of genetics and lifestyles. To the best of our knowledge, the microbial changes associated with aging have not yet been investigated in Singapore adults. We conducted shotgun metagenomic sequencing of fecal and saliva samples, as well as fecal metabolomics to characterize the gut and oral microbial communities of 62 healthy adult male Singaporeans, including 32 young subjects (age, 23.1 ± 1.4 years) and 30 elderly subjects (age, 69.0 ± 3.5 years). We identified 8 gut and 13 oral species that were differentially abundant in elderly compared to young subjects. By combining the gut and oral microbiomes, 25 age-associated oral-gut species connections were identified. Moreover, oral bacteria Acidaminococcus intestine and Flavonifractor plautii were less prevalent/abundant in elderly gut samples than in young gut samples, whereas Collinsella aerofaciens and Roseburia hominis showed the opposite trends. These results indicate the varied gut-oral communications with aging. Subsequently, we expanded the association studies on microbiome, metabolome and host phenotypic parameters. In particular, Eubacterium eligens increased in elderly compared to young subjects, and was positively correlated with triglycerides, which implies that the potential role of E. eligens in lipid metabolism is altered during the aging process. Our results demonstrated aging-associated changes in the gut and oral microbiomes, as well as the connections between metabolites and host-microbe interactions, thereby deepening the understanding of alterations in the human microbiome during the aging process in a Singapore population.}, }
@article {pmid35538552, year = {2022}, author = {van Best, N and Dominguez-Bello, MG and Hornef, MW and Jašarević, E and Korpela, K and Lawley, TD}, title = {Should we modulate the neonatal microbiome and what should be the goal?.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {74}, pmid = {35538552}, issn = {2049-2618}, support = {K01 DK121734/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome ; Goals ; *Microbiota ; }, }
@article {pmid35536453, year = {2022}, author = {Sexton, RE and Uddin, MH and Bannoura, S and Khan, HY and Mzannar, Y and Li, Y and Aboukameel, A and Al-Hallak, MN and Al-Share, B and Mohamed, A and Nagasaka, M and El-Rayes, B and Azmi, AS}, title = {Correction to: Connecting the human microbiome and pancreatic cancer.}, journal = {Cancer metastasis reviews}, volume = {41}, number = {2}, pages = {333}, doi = {10.1007/s10555-022-10037-3}, pmid = {35536453}, issn = {1573-7233}, }
@article {pmid35536037, year = {2022}, author = {Hu, C and Beyda, ND and Garey, KW}, title = {A Vancomycin HPLC Assay for Use in Gut Microbiome Research.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0168821}, pmid = {35536037}, issn = {2165-0497}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Chromatography, High Pressure Liquid/methods ; *Gastrointestinal Microbiome ; Humans ; Reproducibility of Results ; *Vancomycin/pharmacokinetics ; }, abstract = {The human microbiome project has revolutionized our understanding of the interaction between commensal microbes and human health. By far, the biggest perturbation of the microbiome involves use of broad-spectrum antibiotics excreted in the gut. Thus, pharmacodynamics of microbiome changes in relation to drug exposure pharmacokinetics is an emerging field. However, reproducibility studies are necessary to develop the field. A simple and fast high-performance liquid chromatography-photodiode array detector (HPLC) method was validated for quantitative fecal vancomycin analysis. Reproducibility of results were tested based on sample storage time, homogeneity of antibiotic within stool, and concentration consistency after lyophilization. The HPLC method enabled the complete elution of vancomycin within ~4.2 min on the reversed-phase C18 column under the isocratic elution mode, with excellent recovery (85% to 110%) over a 4-log, quantitative range (0.4-100 μg/mL). Relative standard derivations (RSD) of intra-day and inter-day results ranged from 0.4% to 5.4%. Using sample stool aliquots of various weights consistently demonstrated similar vancomycin concentrations (mean RSD: 6%; range: 2-16%). After correcting for water concentrations, vancomycin concentrations obtained after lyophilization were similar to the concentrations obtained from the original samples (RSD less than 10%). These methodologies establish sample condition standards for a quantitative HPLC to enable vancomycin pharmacokinetic studies with the human microbiome. IMPORTANCE Research on antibiotic effect on the gut microbiome is an emerging field with standardization of research methods needed. In this study, a simple and fast high-performance liquid chromatography method was validated for quantitative fecal vancomycin analysis. Reproducibility of results were tested to standardize storage time, homogeneity of antibiotic within stool, and concentration consistency after lyophilization. These methodologies establish sample condition standards for a quantitative HPLC to enable vancomycin pharmacokinetic studies with the human microbiome.}, }
@article {pmid35533688, year = {2022}, author = {Joachim, A and Schwerd, T and Hölz, H and Sokollik, C and Konrad, LA and Jordan, A and Lanzersdorfer, R and Schmidt-Choudhury, A and Hünseler, C and Adam, R}, title = {[Fecal Microbiota Transfer (FMT) in Children and Adolescents - Review and statement by the GPGE microbiome working group].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {60}, number = {6}, pages = {963-969}, doi = {10.1055/a-1801-0284}, pmid = {35533688}, issn = {1439-7803}, mesh = {Adolescent ; Child ; *Clostridioides difficile ; *Clostridium Infections/complications ; Dysbiosis/complications ; Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; *Microbiota ; Treatment Outcome ; }, abstract = {The human microbiome and especially the gastrointestinal microbiota are associated with health and disease. Disturbance in the composition or function of fecal microbiota (dysbiosis) plays a role in the development of pediatric gastrointestinal diseases. Fecal microbiota transfer (FMT) is a special intervention, where microbiota are transferred from a healthy donor.In this review we describe the current state of knowledge for FMT in pediatric patients. There is satisfactory evidence concerning FMT in patients with recurrent C. difficile infection. For inflammatory bowel disease, few studies show a potential benefit.Adverse events occurred frequently in clinical studies, but were mostly mild and transient. There are hardly any data on long-term side effects of FMT, which are particularly significant for pediatrics. In practice, there is uncertainty as to which application route, dosage or frequency should be used. Legally, donor stool is considered a drug in German-speaking countries, for which no marketing authorization exists.In conclusion, knowledge about physiology, efficacy and side effects of FMT is insufficient and legal concerns complicate its implementation. More studies on this topic are needed urgently.}, }
@article {pmid35531342, year = {2022}, author = {Yeo, LF and Lee, SC and Palanisamy, UD and Khalid, B and Ayub, Q and Lim, SY and Lim, YA and Phipps, ME}, title = {The Oral, Gut Microbiota and Cardiometabolic Health of Indigenous Orang Asli Communities.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {812345}, pmid = {35531342}, issn = {2235-2988}, mesh = {Bacteria/genetics ; *Cardiovascular Diseases ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Orang Asli (OA) of Malaysia have been relatively understudied where little is known about their oral and gut microbiomes. As human health is closely intertwined with the human microbiome, this study first assessed the cardiometabolic health in four OA communities ranging from urban, rural to semi-nomadic hunter-gatherers. The urban Temuan suffered from poorer cardiometabolic health while rural OA communities were undergoing epidemiological transition. The oral microbiota of the OA were characterised by sequencing the V4 region of the 16S rRNA gene. The OA oral microbiota were unexpectedly homogenous, with comparably low alpha diversity across all four communities. The rural Jehai and Temiar PP oral microbiota were enriched for uncharacterised bacteria, exhibiting potential for discoveries. This finding also highlights the importance of including under-represented populations in large cohort studies. The Temuan oral microbiota were also elevated in opportunistic pathogens such as Corynebacterium, Prevotella, and Mogibacterium, suggesting possible oral dysbiosis in these urban settlers. The semi-nomadic Jehai gut microbiota had the highest alpha diversity, while urban Temuan exhibited the lowest. Rural OA gut microbiota were distinct from urban-like microbiota and were elevated in bacteria genera such as Prevotella 2, Prevotella 9, Lachnospiraceae ND3007, and Solobacterium. Urban Temuan microbiota were enriched in Odoribacter, Blautia, Parabacetroides, Bacteroides and Ruminococcacecae UCG-013. This study brings to light the current health trend of these indigenous people who have minimal access to healthcare and lays the groundwork for future, in-depth studies in these populations.}, }
@article {pmid35518360, year = {2022}, author = {Gan, R and Zhou, F and Si, Y and Yang, H and Chen, C and Ren, C and Wu, J and Zhang, F}, title = {DBSCAN-SWA: An Integrated Tool for Rapid Prophage Detection and Annotation.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {885048}, pmid = {35518360}, issn = {1664-8021}, abstract = {As an intracellular form of a bacteriophage in the bacterial host genome, a prophage usually integrates into bacterial DNA with high specificity and contributes to horizontal gene transfer (HGT). With the exponentially increasing number of microbial sequences uncovered in genomic or metagenomics studies, there is a massive demand for a tool that is capable of fast and accurate identification of prophages. Here, we introduce DBSCAN-SWA, a command line software tool developed to predict prophage regions in bacterial genomes. DBSCAN-SWA runs faster than any previous tools. Importantly, it has great detection power based on analysis using 184 manually curated prophages, with a recall of 85% compared with Phage_Finder (63%), VirSorter (74%), and PHASTER (82%) for (Multi-) FASTA sequences. Moreover, DBSCAN-SWA outperforms the existing standalone prophage prediction tools for high-throughput sequencing data based on the analysis of 19,989 contigs of 400 bacterial genomes collected from Human Microbiome Project (HMP) project. DBSCAN-SWA also provides user-friendly result visualizations including a circular prophage viewer and interactive DataTables. DBSCAN-SWA is implemented in Python3 and is available under an open source GPLv2 license from https://github.com/HIT-ImmunologyLab/DBSCAN-SWA/.}, }
@article {pmid35512567, year = {2022}, author = {Martí-Marí, O and Martínez-Gualda, B and Fernández-Barahona, I and Mills, A and Abdelnabi, R and Noppen, S and Neyts, J and Schols, D and Camarasa, MJ and Herranz, F and Gago, F and San-Félix, A}, title = {Organotropic dendrons with high potency as HIV-1, HIV-2 and EV-A71 cell entry inhibitors.}, journal = {European journal of medicinal chemistry}, volume = {237}, number = {}, pages = {114414}, doi = {10.1016/j.ejmech.2022.114414}, pmid = {35512567}, issn = {1768-3254}, mesh = {*Dendrimers/chemistry ; *Enterovirus A, Human ; *Enterovirus Infections ; *HIV Fusion Inhibitors/pharmacology ; *HIV-1 ; HIV-2 ; Humans ; Virus Internalization ; }, abstract = {We have recently described a novel family of compounds of reduced size and dual anti-HIV and anti-EV71 activity that encompasses tripodal and tetrapodal derivatives. The tripodal prototype, AL-470, has a nitro group at the focal point of the central scaffold and three attached tryptophan residues, each of which bearing an isophthaloyl moiety at the C2 position of the indole ring. A nitro to amino substitution has allowed us now to introduce a chemically addressable functionality to perform further structural modifications consisting of both direct and linker-mediated attachment of several aromatic groups, including the fluorescent dye Alexa Fluor 647 and the antibody-recruiting 2,4-dinitrophenyl motif. Some of the derivatives turned out to be more potent and selective than AL-470 against HIV-1, HIV-2 and EV-A71. The fluorescent probe demonstrated a specific tropism for intestines and lungs, two important niches for the human microbiome in health and disease.}, }
@article {pmid35509426, year = {2022}, author = {Ianiro, G and Iorio, A and Porcari, S and Masucci, L and Sanguinetti, M and Perno, CF and Gasbarrini, A and Putignani, L and Cammarota, G}, title = {How the gut parasitome affects human health.}, journal = {Therapeutic advances in gastroenterology}, volume = {15}, number = {}, pages = {17562848221091524}, pmid = {35509426}, issn = {1756-283X}, abstract = {The human gut microbiome (GM) is a complex ecosystem that includes numerous prokaryotic and eukaryotic inhabitants. The composition of GM can influence an array of host physiological functions including immune development. Accumulating evidence suggest that several members of non-bacterial microbiota, including protozoa and helminths, that were earlier considered as pathogens, could have a commensal or beneficial relationship with the host. Here we examine the most recent data from omics studies on prokaryota-meiofauna-host interaction as well as the impact of gut parasitome on gut bacterial ecology and its role as 'immunological driver' in health and disease to glimpse new therapeutic perspectives.}, }
@article {pmid35495663, year = {2022}, author = {Zhang, Z and Feng, Q and Li, M and Li, Z and Xu, Q and Pan, X and Chen, W}, title = {Age-Related Cancer-Associated Microbiota Potentially Promotes Oral Squamous Cell Cancer Tumorigenesis by Distinct Mechanisms.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {852566}, pmid = {35495663}, issn = {1664-302X}, abstract = {The oral squamous cell cancer (OSCC) incidence in young patients has increased since the end of the last century; however, the underlying mechanism is still unclear. Oral microbiota dysbiosis was proven to be a tumorigenesis factor, and we propose that there is a distinct bacterial composition in young patients that facilitates the progression of OSCC. Twenty elderly (>60 years old) and 20 young (<50 years old) subjects were included in this study. OSCC tissue was collected during surgery, sent for 16S rDNA sequencing and analyzed by the QIIME 2 pipeline. The results showed that Ralstonia, Prevotella, and Ochrobactrum were significantly enriched in younger OSCC tissue microbiota, while Pedobacter was more abundant in elderly OSCC tissues. Fusobacterium had high relative abundance in both cohorts. At the phylum level, Proteobacteria was the dominant taxon in all samples. The functional study showed that there were significant differences in the taxa abundance from metabolic and signaling pathways. The results indicated that the microbiota of younger OSCC tissues differed from that of elderly OSCC tissues by both taxon composition and function, which partially explains the distinct roles of bacteria during tumorigenesis in these two cohorts. These findings provide insights into different mechanisms of the microbiota-cancer relationship with regard to aging.}, }
@article {pmid35495638, year = {2022}, author = {Jian, C and Kanerva, S and Qadri, S and Yki-Järvinen, H and Salonen, A}, title = {In vitro Effects of Bacterial Exposure on Secretion of Zonulin Family Peptides and Their Detection in Human Tissue Samples.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {848128}, pmid = {35495638}, issn = {1664-302X}, abstract = {Commercially available ELISAs for zonulin (pre-haptoglobin 2), a protein with tight junction regulatory activity in the epithelia, were recently shown to recognize other proteins that are structurally and functionally related to zonulin, termed zonulin family peptides (ZFPs). With little or no information about the identity and property of ZFPs, various commercial zonulin ELISA kits are widely utilized in research as a marker of intestinal permeability. Bacterial exposure is a known trigger for the secretion of zonulin, but it remains unclear whether distinct bacteria differ in their capability to stimulate zonulin secretion. We hypothesized that ZFPs are similar to zonulin regarding response to bacterial exposure and aimed to compare the effects of non-pathogenic, Gram-negative bacteria (Escherichia coli RY13 and E. coli K12 DH5α) and probiotic, Gram-positive bacteria (Lactobacillus rhamnosus GG and Bifidobacterium bifidum) on ZFP secretion in an in vitro model. Additionally, utilizing samples from human clinical trials, we correlated circulating levels of ZFPs to the gut bacteria and determined the presence of ZFPs in various human tissues. Unexpectedly, we found that the ZFPs quantified by the widely used IDK® Zonulin ELISA kits are specifically triggered by the exposure to live Lactobacillus rhamnosus GG in HT-29 cells, associated with absolute abundances of intestinal Lactobacillus and Bifidobacterium in adults, and are copious in the small intestine but undetectable in the liver or adipose tissue. These characteristics appear to be different from zonulin and highlight the need for further characterization of ZFPs recognized by commercially available and widely used "zonulin" ELISAs.}, }
@article {pmid35480328, year = {2022}, author = {Nkera-Gutabara, CK and Kerr, R and Scholefield, J and Hazelhurst, S and Naidoo, J}, title = {Microbiomics: The Next Pillar of Precision Medicine and Its Role in African Healthcare.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {869610}, pmid = {35480328}, issn = {1664-8021}, abstract = {Limited access to technologies that support early monitoring of disease risk and a poor understanding of the geographically unique biological and environmental factors underlying disease, represent significant barriers to improved health outcomes and precision medicine efforts in low to middle income countries. These challenges are further compounded by the rich genetic diversity harboured within Southern Africa thus necessitating alternative strategies for the prediction of disease risk and clinical outcomes in regions where accessibility to personalized healthcare remains limited. The human microbiome refers to the community of microorganisms (bacteria, archaea, fungi and viruses) that co-inhabit the human body. Perturbation of the natural balance of the gut microbiome has been associated with a number of human pathologies, and the microbiome has recently emerged as a critical determinant of drug pharmacokinetics and immunomodulation. The human microbiome should therefore not be omitted from any comprehensive effort towards stratified healthcare and would provide an invaluable and orthogonal approach to existing precision medicine strategies. Recent studies have highlighted the overarching effect of geography on gut microbial diversity as it relates to human health. Health insights from international microbiome datasets are however not yet verified in context of the vast geographical diversity that exists throughout the African continent. In this commentary we discuss microbiome research in Africa and its role in future precision medicine initiatives across the African continent.}, }
@article {pmid35479632, year = {2022}, author = {Vilne, B and Ķibilds, J and Siksna, I and Lazda, I and Valciņa, O and Krūmiņa, A}, title = {Could Artificial Intelligence/Machine Learning and Inclusion of Diet-Gut Microbiome Interactions Improve Disease Risk Prediction? Case Study: Coronary Artery Disease.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {627892}, pmid = {35479632}, issn = {1664-302X}, abstract = {Coronary artery disease (CAD) is the most common cardiovascular disease (CVD) and the main leading cause of morbidity and mortality worldwide, posing a huge socio-economic burden to the society and health systems. Therefore, timely and precise identification of people at high risk of CAD is urgently required. Most current CAD risk prediction approaches are based on a small number of traditional risk factors (age, sex, diabetes, LDL and HDL cholesterol, smoking, systolic blood pressure) and are incompletely predictive across all patient groups, as CAD is a multi-factorial disease with complex etiology, considered to be driven by both genetic, as well as numerous environmental/lifestyle factors. Diet is one of the modifiable factors for improving lifestyle and disease prevention. However, the current rise in obesity, type 2 diabetes (T2D) and CVD/CAD indicates that the "one-size-fits-all" approach may not be efficient, due to significant variation in inter-individual responses. Recently, the gut microbiome has emerged as a potential and previously under-explored contributor to these variations. Hence, efficient integration of dietary and gut microbiome information alongside with genetic variations and clinical data holds a great promise to improve CAD risk prediction. Nevertheless, the highly complex nature of meals combined with the huge inter-individual variability of the gut microbiome poses several Big Data analytics challenges in modeling diet-gut microbiota interactions and integrating these within CAD risk prediction approaches for the development of personalized decision support systems (DSS). In this regard, the recent re-emergence of Artificial Intelligence (AI) / Machine Learning (ML) is opening intriguing perspectives, as these approaches are able to capture large and complex matrices of data, incorporating their interactions and identifying both linear and non-linear relationships. In this Mini-Review, we consider (1) the most used AI/ML approaches and their different use cases for CAD risk prediction (2) modeling of the content, choice and impact of dietary factors on CAD risk; (3) classification of individuals by their gut microbiome composition into CAD cases vs. controls and (4) modeling of the diet-gut microbiome interactions and their impact on CAD risk. Finally, we provide an outlook for putting it all together for improved CAD risk predictions.}, }
@article {pmid35475626, year = {2022}, author = {Oliver, A and El Alaoui, K and Haunschild, C and Avelar-Barragan, J and Mendez Luque, LF and Whiteson, K and Fleischman, AG}, title = {Fecal Microbial Community Composition in Myeloproliferative Neoplasm Patients Is Associated with an Inflammatory State.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0003222}, pmid = {35475626}, issn = {2165-0497}, support = {P30 CA062203/CA/NCI NIH HHS/United States ; T32 CA060396/CA/NCI NIH HHS/United States ; }, mesh = {Chronic Disease ; Feces ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; *Myeloproliferative Disorders/pathology ; *Neoplasms ; }, abstract = {The capacity of the human microbiome to modulate inflammation in the context of cancer is becoming increasingly clear. Myeloproliferative neoplasms (MPNs) are chronic hematologic malignancies in which inflammation plays a key role in disease initiation, progression, and symptomatology. To better understand the composition of the gut microbiome in patients with MPN, triplicate fecal samples were collected from 25 MPN patients and 25 non-MPN controls. Although most of the variance between the microbial community compositions could be attributed to the individual (permutational analysis of variance [PERMANOVA], R[2] = 0.92, P = 0.001), 1.7% of the variance could be attributed to disease status (MPN versus non-MPN). When a more detailed analysis was performed, significantly fewer reads mapping to a species of Phascolarctobacterium, a microbe previously associated with reduced inflammation, were found in MPNs. Further, our data revealed an association between Parabacteroides and tumor necrosis factor alpha (TNF-α), an inflammatory cytokine elevated in MPNs. Taken together, our results indicate a significant difference in the microbiome of MPN patients compared to non-MPN controls, and we identify specific species which may have a role in the chronic inflammation central to this disease. IMPORTANCE MPNs are chronic blood cancers in which inflammation plays a key role in disease initiation, progression, and symptomatology. The gut microbiome modulates normal blood development and inflammation and may also impact the development and manifestation of blood cancers. Therefore, the microbiome may be an important modulator of inflammation in MPN and could potentially be leveraged therapeutically in this disease. However, the relationship between the gut microbiome and MPNs has not been defined. Therefore, we performed an evaluation of the MPN microbiome, comparing the microbiomes of MPN patients with healthy donors and between MPN patients with various states of disease.}, }
@article {pmid35466418, year = {2022}, author = {Mishra, AK and Müller, CL}, title = {Negative binomial factor regression with application to microbiome data analysis.}, journal = {Statistics in medicine}, volume = {41}, number = {15}, pages = {2786-2803}, pmid = {35466418}, issn = {1097-0258}, mesh = {*Data Analysis ; Factor Analysis, Statistical ; Feeding Behavior ; Gastrointestinal Microbiome ; Humans ; Life Style ; *Microbiota ; Regression Analysis ; United States ; }, abstract = {The human microbiome provides essential physiological functions and helps maintain host homeostasis via the formation of intricate ecological host-microbiome relationships. While it is well established that the lifestyle of the host, dietary preferences, demographic background, and health status can influence microbial community composition and dynamics, robust generalizable associations between specific host-associated factors and specific microbial taxa have remained largely elusive. Here, we propose factor regression models that allow the estimation of structured parsimonious associations between host-related features and amplicon-derived microbial taxa. To account for the overdispersed nature of the amplicon sequencing count data, we propose negative binomial reduced rank regression (NB-RRR) and negative binomial co-sparse factor regression (NB-FAR). While NB-RRR encodes the underlying dependency among the microbial abundances as outcomes and the host-associated features as predictors through a rank-constrained coefficient matrix, NB-FAR uses a sparse singular value decomposition of the coefficient matrix. The latter approach avoids the notoriously difficult joint parameter estimation by extracting sparse unit-rank components of the coefficient matrix sequentially, effectively delivering interpretable bi-clusters of taxa and host-associated factors. To solve the nonconvex optimization problems associated with these factor regression models, we present a novel iterative block-wise majorization procedure. Extensive simulation studies and an application to the microbial abundance data from the American Gut Project (AGP) demonstrate the efficacy of the proposed procedure. In the AGP data, we identify several factors that strongly link dietary habits and host life style to specific microbial families.}, }
@article {pmid35461664, year = {2022}, author = {Dash, HR and Das, S}, title = {Microbial community signatures for estimation of postmortem time intervals.}, journal = {Advances in applied microbiology}, volume = {118}, number = {}, pages = {91-113}, doi = {10.1016/bs.aambs.2022.02.002}, pmid = {35461664}, issn = {0065-2164}, mesh = {Autopsy ; Cadaver ; Humans ; *Microbiota ; *Postmortem Changes ; }, abstract = {The human body provides a complex ecosystem for symbiotic habitation of a huge number of microorganisms. These commensal microorganisms provide a huge benefit to the living host by acting against many deadly infections. Once the host dies, many changes in the complex ecosystem of the human body take place. The personalized microbes of a human body undergo successional change as many exogenous microbes attack the nutrient-rich cadaver after death. The succession pattern change of microbes in human cadaver allows postulating different models for estimation of Postmortem time interval (PMI). Estimation of PMI has a broad prospect from the criminal investigation point of view. Though many techniques are being used nowadays to estimate PMI, all of them have their pros and cons. With the advent of advanced molecular biological techniques, studies on the thanatomicrobiome of a human cadaver have gained pace and provide a superior alternative for conventional methods of PMI estimation. This chapter summarizes the recent advancements in the changes in signature microflora postmortem with change in human microenvironment to postulate a consensus model for estimation of PMI.}, }
@article {pmid35459927, year = {2022}, author = {Ventin-Holmberg, R and Höyhtyä, M and Saqib, S and Korpela, K and Nikkonen, A and Salonen, A and de Vos, WM and Kolho, KL}, title = {The gut fungal and bacterial microbiota in pediatric patients with inflammatory bowel disease introduced to treatment with anti-tumor necrosis factor-α.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {6654}, pmid = {35459927}, issn = {2045-2322}, mesh = {Bacteria/genetics ; Child ; *Crohn Disease/drug therapy ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/drug therapy/microbiology ; Infliximab/therapeutic use ; Leukocyte L1 Antigen Complex ; *Tumor Necrosis Factor-alpha/drug effects/therapeutic use ; }, abstract = {Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baseline Ruminococcus and calprotectin. Additionally, non-responders had higher abundance of Candida, while responders had higher abundance of Saccharomyces at the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future.}, }
@article {pmid35458152, year = {2022}, author = {Warner, JO and Warner, JA}, title = {The Foetal Origins of Allergy and Potential Nutritional Interventions to Prevent Disease.}, journal = {Nutrients}, volume = {14}, number = {8}, pages = {}, pmid = {35458152}, issn = {2072-6643}, mesh = {Animals ; Breast Feeding ; Cattle ; Diet ; Female ; Humans ; *Hypersensitivity ; Infant ; Lactation ; Milk ; Pregnancy ; }, abstract = {The first nine months from conception to birth involves greater changes than at any other time in life, affecting organogenesis, endocrine, metabolic and immune programming. It has led to the concept that the "first 1000 days" from conception to the second birthday are critical in establishing long term health or susceptibility to disease. Immune ontogeny is predominantly complete within that time and is influenced by the maternal genome, health, diet and environment pre-conception and during pregnancy and lactation. Components of the immunological protection of the pregnancy is the generation of Th-2 and T-regulatory cytokines with the consequence that neonatal adaptive responses are also biased towards Th-2 (allergy promoting) and T-regulatory (tolerance promoting) responses. Normally after birth Th-1 activity increases while Th-2 down-regulates and the evolving normal human microbiome likely plays a key role. This in turn will have been affected by maternal health, diet, exposure to antibiotics, mode of delivery, and breast or cow milk formula feeding. Complex gene/environment interactions affect outcomes. Many individual nutrients affect immune mechanisms and variations in levels have been associated with susceptibility to allergic disease. However, intervention trials employing single nutrient supplementation to prevent allergic disease have not achieved the expected outcomes suggested by observational studies. Investigation of overall dietary practices including fresh fruit and vegetables, fish, olive oil, lower meat intake and home cooked foods as seen in the Mediterranean and other healthy diets have been associated with reduced prevalence of allergic disease. This suggests that the "soup" of overall nutrition is more important than individual nutrients and requires further investigation both during pregnancy and after the infant has been weaned. Amongst all the potential factors affecting allergy outcomes, modification of maternal and infant nutrition and the microbiome are easier to employ than changing other aspects of the environment but require large controlled trials before recommending changes to current practice.}, }
@article {pmid35457956, year = {2022}, author = {Wang, S and Alenius, H and El-Nezami, H and Karisola, P}, title = {A New Look at the Effects of Engineered ZnO and TiO2 Nanoparticles: Evidence from Transcriptomics Studies.}, journal = {Nanomaterials (Basel, Switzerland)}, volume = {12}, number = {8}, pages = {}, pmid = {35457956}, issn = {2079-4991}, support = {307768//Academy of Finland/ ; }, abstract = {Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) have attracted a great deal of attention due to their excellent electrical, optical, whitening, UV-adsorbing and bactericidal properties. The extensive production and utilization of these NPs increases their chances of being released into the environment and conferring unintended biological effects upon exposure. With the increasingly prevalent use of the omics technique, new data are burgeoning which provide a global view on the overall changes induced by exposures to NPs. In this review, we provide an account of the biological effects of ZnO and TiO2 NPs arising from transcriptomics in in vivo and in vitro studies. In addition to studies on humans and mice, we also describe findings on ecotoxicology-related species, such as Danio rerio (zebrafish), Caenorhabditis elegans (nematode) or Arabidopsis thaliana (thale cress). Based on evidence from transcriptomics studies, we discuss particle-induced biological effects, including cytotoxicity, developmental alterations and immune responses, that are dependent on both material-intrinsic and acquired/transformed properties. This review seeks to provide a holistic insight into the global changes induced by ZnO and TiO2 NPs pertinent to human and ecotoxicology.}, }
@article {pmid35456813, year = {2022}, author = {Vera-Urbina, F and Dos Santos-Torres, MF and Godoy-Vitorino, F and Torres-Hernández, BA}, title = {The Gut Microbiome May Help Address Mental Health Disparities in Hispanics: A Narrative Review.}, journal = {Microorganisms}, volume = {10}, number = {4}, pages = {}, pmid = {35456813}, issn = {2076-2607}, support = {P20 GM103642/GM/NIGMS NIH HHS/United States ; U54 MD007600/MD/NIMHD NIH HHS/United States ; 5P20GM103642/GM/NIGMS NIH HHS/United States ; 5U54MD007600/MD/NIMHD NIH HHS/United States ; }, abstract = {The gut-brain axis is the biological connection between the enteric and the central nervous systems. Given the expansion of the microbial sciences with the new human microbiome field facilitated by the decrease in sequencing costs, we now know more about the role of gut microbiota in human health. In this short review, particular focus is given to the gut-brain axis and its role in psychiatric diseases such as anxiety and depression. Additionally, factors that contribute to changes in the gut-brain axis, including the gut microbiome, nutrition, the host's genome, and ethnic difference, are highlighted. Emphasis is given to the lack of studies on Hispanic populations, despite the fact this ethnic group has a higher prevalence of anxiety and depression in the US.}, }
@article {pmid35454968, year = {2022}, author = {Hu, C and Rzymski, P}, title = {Non-Photosynthetic Melainabacteria (Cyanobacteria) in Human Gut: Characteristics and Association with Health.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {4}, pages = {}, pmid = {35454968}, issn = {2075-1729}, abstract = {Gut microorganisms are comprised of thousands of species and play an important role in the host's metabolism, overall health status, and risk of disease. Recently, the discovery of non-photosynthetic cyanobacteria (class "Melainabacteria") in the human and animal gut triggered a broad interest in studying cyanobacteria's evolution, physiology, and ecological relevance of the Melainabacteria members. In the present paper, we review the general characteristics of Melainabacteria, their phylogeny, distribution, and ecology. The potential link between these microorganisms and human health is also discussed based on available human-microbiome studies. Their abundance tends to increase in patients with selected neurodegenerative, gastrointestinal, hepatic, metabolic, and respiratory diseases. However, the available evidence is correlative and requires further longitudinal studies. Although the research on Melainabacteria in the human gut is still in its infancy, elucidation of their role appears important in better understanding microbiome-human health interactions. Further studies aiming to identify particular gut cyanobacteria species, culture them in vitro, and characterize them on the molecular, biochemical, and physiological levels are encouraged.}, }
@article {pmid35453183, year = {2022}, author = {Agosta, M and Bencardino, D and Argentieri, M and Pansani, L and Sisto, A and Ciofi Degli Atti, ML and D'Amore, C and Putignani, L and Bagolan, P and Iacobelli, BD and Dotta, A and Martini, L and Di Chiara, L and Magnani, M and Perno, CF and Andreoni, F and Bernaschi, P}, title = {Prevalence and Molecular Typing of Carbapenemase-Producing Enterobacterales among Newborn Patients in Italy.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {11}, number = {4}, pages = {}, pmid = {35453183}, issn = {2079-6382}, abstract = {The spread of carbapenemase-producing Enterobacterales (CPE), especially Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli), is a serious public health threat in pediatric hospitals. The associated risk in newborns is due to their underdeveloped immune system and limited treatment options. The aim was to estimate the prevalence and circulation of CPE among the neonatal intensive units of a major pediatric hospital in Italy and to investigate their molecular features. A total of 124 CPE were isolated from rectal swabs of 99 newborn patients at Bambino Gesù Children's Hospital between July 2016 and December 2019. All strains were characterized by antimicrobial susceptibility testing, detection of resistance genes, and PCR-based replicon typing (PBRT). One strain for each PBRT profile of K. pneumoniae or E. coli was characterized by multilocus-sequence typing (MLST). Interestingly, the majority of strains were multidrug-resistant and carried the blaNDM gene. A large part was characterized by a multireplicon status, and FII, A/C, FIA (15%) was the predominant. Despite the limited size of collection, MLST analysis revealed a high number of Sequence Types (STs): 14 STs among 28 K. pneumoniae and 8 STs among 11 E. coli, with the prevalence of the well-known clones ST307 and ST131, respectively. This issue indicated that some strains shared the same circulating clone. We identified a novel, so far never described, ST named ST10555, found in one E. coli strain. Our investigation showed a high heterogeneity of CPE circulating among neonatal units, confirming the need to monitor their dissemination in the hospital also through molecular methods.}, }
@article {pmid35452382, year = {2022}, author = {Hua, X and Cao, Y and Morgan, DM and Miller, K and Chin, SM and Bellavance, D and Khalili, H}, title = {Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome.}, journal = {Journal of medical microbiology}, volume = {71}, number = {4}, pages = {}, doi = {10.1099/jmm.0.001512}, pmid = {35452382}, issn = {1473-5644}, mesh = {Child, Preschool ; Contraceptives, Oral/pharmacology ; Estradiol ; Female ; *Gastrointestinal Microbiome ; Gonadal Steroid Hormones ; Humans ; Testosterone ; }, abstract = {Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome.Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied.Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use.Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones.Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone.Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.}, }
@article {pmid35452117, year = {2022}, author = {Garcia-Vello, P and Tytgat, HLP and Gray, J and Elzinga, J and Di Lorenzo, F and Biboy, J and Vollmer, D and De Castro, C and Vollmer, W and de Vos, WM and Molinaro, A}, title = {Peptidoglycan from Akkermansia muciniphila MucT: chemical structure and immunostimulatory properties of muropeptides.}, journal = {Glycobiology}, volume = {32}, number = {8}, pages = {712-719}, doi = {10.1093/glycob/cwac027}, pmid = {35452117}, issn = {1460-2423}, support = {BB/R017409/1//BBSRC/ ; }, mesh = {Akkermansia ; Animals ; *Gastrointestinal Microbiome ; Humans ; Mice ; *Peptidoglycan ; Verrucomicrobia/physiology ; }, abstract = {Akkermansia muciniphila is an intestinal symbiont known to improve the gut barrier function in mice and humans. Various cell envelope components have been identified to play a critical role in the immune signaling of A. muciniphila, but the chemical composition and role of peptidoglycan (PG) remained elusive. Here, we isolated PG fragments from A. muciniphila MucT (ATCC BAA-835), analyzed their composition and evaluated their immune signaling capacity. Structurally, the PG of A. muciniphila was found to be noteworthy due of the presence of some nonacetylated glucosamine residues, which presumably stems from deacetylation of N-acetylglucosamine. Some of the N-acetylmuramic acid (MurNAc) subunits were O-acetylated. The immunological assays revealed that muropeptides released from the A. muciniphila PG could both activate the intracellular NOD1 and NOD2 receptors to a comparable extent as muropeptides from Escherichia coli BW25113. These data challenge the hypothesis that non-N-acetylattion of PG can be used as a NOD-1 evasion mechanism. Our results provide new insights into the diversity of cell envelope structures of key gut microbiota members and their role in steering host-microbiome interactions.}, }
@article {pmid35448562, year = {2022}, author = {Ventin-Holmberg, R and Saqib, S and Korpela, K and Nikkonen, A and Peltola, V and Salonen, A and de Vos, WM and Kolho, KL}, title = {The Effect of Antibiotics on the Infant Gut Fungal Microbiota.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {8}, number = {4}, pages = {}, pmid = {35448562}, issn = {2309-608X}, support = {TYH2021216, 308255//Pediatric Research Foundation (Finland), Helsinki University Hospital Research Fund and Academy of Finland/ ; }, abstract = {Antibiotics are commonly used drugs in infants, causing disruptions in the developing gut microbiota with possible detrimental long-term effects such as chronic inflammatory diseases. The focus has been on bacteria, but research shows that fungi might have an important role as well. There are only a few studies on the infant gut fungal microbiota, the mycobiota, in relation to antibiotic treatment. Here, the aim was to investigate the impact of antibiotics on the infant gut mycobiota, and the interkingdom associations between bacteria and fungi. We had 37 antibiotic-naïve patients suffering from respiratory syncytial virus, of which 21 received one to four courses of antibiotics due to complications, and 16 remained antibiotic-naïve throughout the study. Fecal samples were collected before, during and after antibiotic treatment with a follow-up period of up to 9.5 months. The gut mycobiota was studied by Illumina MiSeq sequencing of the ITS1 region. We found that antibiotic use affected the gut mycobiota, most prominently seen as a higher relative abundance of Candida (p < 0.001), and a higher fungal diversity (p = 0.005−0.04) and richness (p = 0.03) in the antibiotic-treated infants compared to the antibiotic-naïve ones at multiple timepoints. This indicates that the gut mycobiota could contribute to the long-term consequences of antibiotic treatments.}, }
@article {pmid35448490, year = {2022}, author = {Abot, A and Brochot, A and Pomié, N and Wemelle, E and Druart, C and Régnier, M and Delzenne, NM and de Vos, WM and Knauf, C and Cani, PD}, title = {Camu-Camu Reduces Obesity and Improves Diabetic Profiles of Obese and Diabetic Mice: A Dose-Ranging Study.}, journal = {Metabolites}, volume = {12}, number = {4}, pages = {}, pmid = {35448490}, issn = {2218-1989}, support = {ANR-18-CE14-0007-01//Agence Nationale de la Recherche/ ; IRP NeuroMicrobiota//Inserm/ ; A-Mansia Biotech S.A. grant//A-Mansia Biotech S.A./ ; Walloon Region grant//Walloon Region/ ; FRS-FNRS grant//Fund for Scientific Research/ ; }, abstract = {Overweight, obesity, and their comorbidities are currently considered a major public health concern. Today considerable efforts are still needed to develop efficient strategies able to attenuate the burden of these diseases. Nutritional interventions, some with plant extracts, present promising health benefits. In this study, we evaluated the action of Camu-Camu (Myrciaria dubia), an Amazonian fruit rich in polyphenols and vitamin C, on the prevention of obesity and associated disorders in mice and the abundance of Akkermansia muciniphila in both cecum and feces. Methods: We investigated the dose-response effects of Camu-Camu extract (CCE) in the context of high-fat-diet (HFD)-induced obesity. After 5 weeks of supplementation, we demonstrated that the two doses of CCE differently improved glucose and lipid homeostasis. The lowest CCE dose (62.5 mg/kg) preferentially decreased non-HDL cholesterol and free fatty acids (FFA) and increased the abundance of A. muciniphila without affecting liver metabolism, while only the highest dose of CCE (200 mg/kg) prevented excessive body weight gain, fat mass gain, and hepatic steatosis. Both doses decreased fasting hyperglycemia induced by HFD. In conclusion, the use of plant extracts, and particularly CCE, may represent an additional option in the support of weight management strategies and glucose homeostasis alteration by mechanisms likely independent from the modulation of A. muciniphila abundance.}, }
@article {pmid35447322, year = {2022}, author = {Patjas, A and Kantele, A}, title = {International travel and travelers' diarrhea - Increased risk of urinary tract infection.}, journal = {Travel medicine and infectious disease}, volume = {48}, number = {}, pages = {102331}, doi = {10.1016/j.tmaid.2022.102331}, pmid = {35447322}, issn = {1873-0442}, mesh = {Diarrhea/prevention &amp; control ; Female ; Humans ; Male ; Prospective Studies ; Risk Factors ; *Travel ; *Urinary Tract Infections/epidemiology ; }, abstract = {BACKGROUND: Urinary tract infections (UTIs) rank among the most common infections encountered in health care, with an annual incidence of 12% for women. Despite the vast numbers of international travels (over 1.5 billion annually), no prospective studies have had primary focus on UTIs during travel.<br><br>METHODS: We recruited in 2008-17 international travelers who all filled out pre- and post-travel questionnaires. Incidence rates of UTI were calculated separately for both sexes. Multivariable analyses were conducted to identify risk factors for UTI during travel.<br><br>RESULTS: In total 15/517 (2,9%) travelers acquired UTI during travel, yielding an annual incidence of 62% for female and 18% for male travelers. Travelers' diarrhea (TD) was identified as a factor predisposing to UTI (OR 9.2, 95% CI 1.5-+&#x221e;, p&#xa0;=&#xa0;0.011); all UTI cases were recorded by travelers with TD.<br><br>CONCLUSIONS: To our knowledge, this is the first prospective study with a primary focus on UTI during travel. Our data reveal that among travelers the incidence of UTI far exceeds that reported for the general population. TD was identified as a major risk factor for the infection. Our results suggest TD prevention as a means of also preventing UTI during travel.}, }
@article {pmid35446845, year = {2022}, author = {Giliberti, R and Cavaliere, S and Mauriello, IE and Ercolini, D and Pasolli, E}, title = {Host phenotype classification from human microbiome data is mainly driven by the presence of microbial taxa.}, journal = {PLoS computational biology}, volume = {18}, number = {4}, pages = {e1010066}, pmid = {35446845}, issn = {1553-7358}, mesh = {*Bacteria/genetics ; Humans ; Metagenome/genetics ; *Microbiota/genetics ; Phenotype ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Machine learning-based classification approaches are widely used to predict host phenotypes from microbiome data. Classifiers are typically employed by considering operational taxonomic units or relative abundance profiles as input features. Such types of data are intrinsically sparse, which opens the opportunity to make predictions from the presence/absence rather than the relative abundance of microbial taxa. This also poses the question whether it is the presence rather than the abundance of particular taxa to be relevant for discrimination purposes, an aspect that has been so far overlooked in the literature. In this paper, we aim at filling this gap by performing a meta-analysis on 4,128 publicly available metagenomes associated with multiple case-control studies. At species-level taxonomic resolution, we show that it is the presence rather than the relative abundance of specific microbial taxa to be important when building classification models. Such findings are robust to the choice of the classifier and confirmed by statistical tests applied to identifying differentially abundant/present taxa. Results are further confirmed at coarser taxonomic resolutions and validated on 4,026 additional 16S rRNA samples coming from 30 public case-control studies.}, }
@article {pmid35444617, year = {2022}, author = {Zhang, WH and Jin, ZY and Yang, ZH and Zhang, JY and Ma, XH and Guan, J and Sun, BL and Chen, X}, title = {Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {818111}, pmid = {35444617}, issn = {1664-302X}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a multi-factor disease characterized by alternating remission periods and repeated occurrence. It has been shown that fecal microbiota transplantation (FMT) is an emerging and effective approach for UC treatment. Since most existing studies chose adults as donors for fecal microbiota, we conducted this study to determine the long-term efficacy and safety of the microbiota from young UC patient donors and illustrate its specific physiological effects.<br><br>METHODS: Thirty active UC patients were enrolled and FMT were administered with the first colonoscopy and two subsequent enema/transendoscopic enteral tubing (TET) practical regimens in The First Affiliated Hospital of Anhui Medical University in China. Disease activity and inflammatory biomarkers were assessed 6&#x2009;weeks/over 1&#x2009;year after treatment. The occurrence of adverse events was also recorded. The samples from blood and mucosa were collected to detect the changes of inflammatory biomarkers and cytokines. The composition of gut and oral microbiota were also sampled and sequenced to confirm the alteration of microbial composition.<br><br>RESULTS: Twenty-seven patients completed the treatment, among which 16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission. Full Mayo score and calprotectin dropped significantly and remained stable over 1&#x2009;year. FMT also significantly reduced the levels of C-reactive protein (CRP), interleukin-1 beta (IL-1&#x3b2;), and interleukin-6 (IL-6). The gut microbiota altered significantly with increased bacterial diversity and decreased metabolic diversity in responsive patients. The pro-inflammatory enterobacteria decreased after FMT and the abundance of Collinsella increased. Accordingly, the altered metabolic functions, including antigen synthesis, amino acids metabolism, short chain fatty acid production, and vitamin K synthesis of microbiota, were also corrected by FMT.<br><br>CONCLUSION: Fecal microbiota transplantation seems to be safe and effective for active UC patients who are nonresponsive to mesalazine or prednisone in the long-term. FMT could efficiently downregulate pro-inflammatory cytokines to ameliorate the inflammation.}, }
@article {pmid35444249, year = {2022}, author = {Soininen, L and Roslund, MI and Nurminen, N and Puhakka, R and Laitinen, OH and Hyöty, H and Sinkkonen, A and , }, title = {Indoor green wall affects health-associated commensal skin microbiota and enhances immune regulation: a randomized trial among urban office workers.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {6518}, pmid = {35444249}, issn = {2045-2322}, mesh = {Bacteria ; Cytokines ; Humans ; Lactobacillus ; *Microbiota ; Skin ; }, abstract = {Urbanization reduces microbiological abundance and diversity, which has been associated with immune mediated diseases. Urban greening may be used as a prophylactic method to restore microbiological diversity in cities and among urbanites. This study evaluated the impact of air-circulating green walls on bacterial abundance and diversity on human skin, and on immune responses determined by blood cytokine measurements. Human subjects working in offices in two Finnish cities (Lahti and Tampere) participated in a two-week intervention, where green walls were installed in the rooms of the experimental group. Control group worked without green walls. Skin and blood samples were collected before (Day0), during (Day14) and two weeks after (Day28) the intervention. The relative abundance of genus Lactobacillus and the Shannon diversity of phylum Proteobacteria and class Gammaproteobacteria increased in the experimental group. Proteobacterial diversity was connected to the lower proinflammatory cytokine IL-17A level among participants in Lahti. In addition, the change in TGF-β1 levels was opposite between the experimental and control group. As skin Lactobacillus and the diversity of Proteobacteria and Gammaproteobacteria are considered advantageous for skin health, air-circulating green walls may induce beneficial changes in a human microbiome. The immunomodulatory potential of air-circulating green walls deserves further research attention.}, }
@article {pmid35441344, year = {2023}, author = {Roderburg, C and Loosen, SH and Joerdens, MS and Demir, M and Luedde, T and Kostev, K}, title = {Antibiotic therapy is associated with an increased incidence of cancer.}, journal = {Journal of cancer research and clinical oncology}, volume = {149}, number = {3}, pages = {1285-1293}, pmid = {35441344}, issn = {1432-1335}, mesh = {Humans ; Female ; Incidence ; Case-Control Studies ; Retrospective Studies ; Anti-Bacterial Agents/therapeutic use ; Penicillins ; Cephalosporins/therapeutic use ; *Breast Neoplasms/drug therapy ; *Hematologic Neoplasms/drug therapy ; }, abstract = {PURPOSE: There is a growing body of evidence suggesting the decisive involvement of the human microbiome in cancer development. The consumption of antibiotics may fundamentally change the microbiome and thereby create a precancerous environment promoting cancer development and growth. However, clinical data on the association between the consumption of antibiotics and cancer incidence have remained inconclusive. In this study, we quantified the association between the intake of different antibiotics and various cancer entities among outpatients from Germany.<br><br>METHODS: This retrospective case-control study based on the IQVIA Disease Analyzer database included 111,828 cancer patients and 111,828 non-cancer controls who were matched to cancer cases using propensity scores. Patients were categorized as non-users, low-consumption (up to 50th percentile), and high-consumption (above 50[th] percentile) users of antibiotics overall and for each antibiotic class. Multivariable logistic conditional regression models were used to study the association between antibiotic intake within 5&#xa0;years prior to the index date (first cancer diagnosis for cases or randomly selected date for controls) and cancer incidence.<br><br>RESULTS: The probability of cancer was significantly higher among patients with a history of antibiotic intake than in matched controls. Patients using penicillin or cephalosporins displayed a higher incidence of cancer, while the intake of tetracyclines and macrolides actually reduced the risk of cancer development slightly. A complex picture was observed in our cancer site-stratified analyses. Most notably, the consumption of penicillin was significantly and positively associated with cancer development in the respiratory organs only (low consumption OR: 1.33, 95% CI 1.20-1.47; high consumption OR 1.42, 95% CI 1.22-1.64) and cephalosporin consumption was significantly associated with respiratory organ cancer (low consumption OR: 1.32, 95% CI 1.17-1.48, high consumption OR: 1.47, 95% CI 1.29-1.66), breast cancer (high consumption OR: 1.40, 95% CI 1.25-1.56), and lymphoid and hematopoietic tissue cancer (high consumption OR: 1.50, 95% CI 1.35-1.66).<br><br>CONCLUSION: Our data strongly support the hypothesis that the intake of antibiotics is positively associated with the risk of cancer development.}, }
@article {pmid35440149, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Ufimtseva, A and Poluektova, E and Ulyanin, A}, title = {Clostridioides difficile co-infection in patients with COVID-19.}, journal = {Future microbiology}, volume = {17}, number = {}, pages = {653-663}, pmid = {35440149}, issn = {1746-0921}, mesh = {Anti-Bacterial Agents/adverse effects ; *COVID-19/complications ; *Clostridioides difficile ; *Clostridium Infections/complications/diagnosis/epidemiology ; *Coinfection/drug therapy ; Diarrhea/drug therapy ; Humans ; Retrospective Studies ; }, abstract = {Aim: To assess the impact of Clostridioides difficile infection on the course of COVID-19. Methods: The authors included 809 patients with COVID-19 in this retrospective study: 55 had C. difficile infection, 23 had C. difficile-negative antibiotic-associated diarrhea and 731 had no diarrhea. C. difficile in feces was determined by immunochromatographic test for its toxins. Results:C. difficile infection was associated with increased risk of death (hazard ratio = 2.6; p = 0.021), especially after 20 days of disease (hazard ratio = 6.5; p < 0.001). C. difficile infection-associated diarrhea was longer and more severe than C. difficile-negative antibiotic-associated diarrhea. Unlike patients with C. difficile-negative antibiotic-associated diarrhea, patients with C. difficile infection were admitted to the intensive care unit and needed mechanical ventilation more often than those without diarrhea. Conclusion:C. difficile infection worsens the course and prognosis of COVID-19.}, }
@article {pmid35440042, year = {2022}, author = {Wolf, PG and Cowley, ES and Breister, A and Matatov, S and Lucio, L and Polak, P and Ridlon, JM and Gaskins, HR and Anantharaman, K}, title = {Diversity and distribution of sulfur metabolic genes in the human gut microbiome and their association with colorectal cancer.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {64}, pmid = {35440042}, issn = {2049-2618}, support = {T32 CA057699/CA/NCI NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; R01 CA204808/CA/NCI NIH HHS/United States ; T32 GM008692/GM/NIGMS NIH HHS/United States ; T32 GM140935/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria ; *Carcinoma ; *Colorectal Neoplasms/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; Sulfates/metabolism ; Sulfur/metabolism ; Taurine/metabolism ; }, abstract = {BACKGROUND: Recent evidence implicates microbial sulfidogenesis as a potential trigger of colorectal cancer (CRC), highlighting the need for comprehensive knowledge of sulfur metabolism within the human gut. Microbial sulfidogenesis produces genotoxic hydrogen sulfide (H2S) in the human colon using inorganic (sulfate) and organic (taurine/cysteine/methionine) substrates; however, the majority of studies have focused on sulfate reduction using dissimilatory sulfite reductases (Dsr).<br><br>RESULTS: Here, we show that genes for microbial sulfur metabolism are more abundant and diverse than previously observed and are statistically associated with CRC. Using ~ 17,000 bacterial genomes from publicly available stool metagenomes, we studied the diversity of sulfur metabolic genes in 667 participants across different health statuses: healthy, adenoma, and carcinoma. Sulfidogenic genes were harbored by 142 bacterial genera and both organic and inorganic sulfidogenic genes were associated with carcinoma. Significantly, the anaerobic sulfite reductase (asr) genes were twice as abundant as dsr, demonstrating that Asr is likely a more important contributor to sulfate reduction in the human gut than Dsr. We identified twelve potential pathways for reductive taurine metabolism and discovered novel genera harboring these pathways. Finally, the prevalence of metabolic genes for organic sulfur indicates that these understudied substrates may be the most abundant source of microbially derived H2S.<br><br>CONCLUSIONS: Our findings significantly expand knowledge of microbial sulfur metabolism in the human gut. We show that genes for microbial sulfur metabolism in the human gut are more prevalent than previously known, irrespective of health status (i.e., in both healthy and diseased states). Our results significantly increase the diversity of pathways and bacteria that are associated with microbial sulfur metabolism in the human gut. Overall, our results have implications for understanding the role of the human gut microbiome and its potential contributions to the pathogenesis of CRC. Video abstract.}, }
@article {pmid35432240, year = {2022}, author = {Si, J and Choi, Y and Raes, J and Ko, G and You, HJ}, title = {Sputum Bacterial Metacommunities in Distinguishing Heterogeneity in Respiratory Health and Disease.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {719541}, pmid = {35432240}, issn = {1664-302X}, abstract = {BACKGROUND AND OBJECTIVE: Cluster-based analysis, or community typing, has been attempted as a method for studying the human microbiome in various body niches with the aim of reducing variations in the bacterial composition and linking the defined communities to host health and disease. In this study, we have presented the bacterial subcommunities in the healthy and the diseased population cohorts and have assessed whether these subcommunities can distinguish different host health conditions.<br><br>METHODS: We performed community typing analysis on the sputum microbiome dataset obtained from a healthy Korean twin-family cohort (n = 202) and an external chronic obstructive pulmonary disease (COPD) cohort (n = 324) and implemented a networks analysis to investigate the associations of bacterial metacommunities with host health parameters and microbial interactions in disease.<br><br>RESULTS: The analysis of the sputum microbiome of a healthy Korean cohort revealed high levels of interindividual variation, which was driven by two dominant bacteria: Neisseria and Prevotella. Community typing of the cohort samples identified three metacommunities, namely, Neisseria 1 (N1), Neisseria 2 (N2), and Prevotella (P), each of which showed different functional potential and links to host traits (e.g., triglyceride levels, waist circumference, and levels of high-sensitivity C-reactive protein). In particular, the Prevotella-dominant metacommunity showed a low-community diversity, which implies an adverse health association. Network analysis of the healthy twin cohort illustrated co-occurrence of Prevotella with pathogenic anaerobic bacteria; this bacterial cluster was negatively associated with high-density lipoproteins but positively correlated with waist circumference, blood pressure, and pack-years. Community typing of the external COPD cohort identified three sub-metacommunities: one exclusively comprising healthy subjects (HSs) and the other two (CS1 and CS2) comprising patients. The two COPD metacommunities, CS1 and CS2, showed different abundances of specific pathogens, such as Serratia and Moraxella, as well as differing functional potential and community diversity. Network analysis of the COPD cohort showed enhanced bacterial coexclusions in the CS metacommunities when compared with HS metacommunity.<br><br>CONCLUSION: Overall, our findings point to a potential association between pulmonary Prevotella and host health and disease, making it possible to implement community typing for the diagnosis of heterogenic respiratory disease.}, }
@article {pmid35431497, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Efremova, I and Poluektova, E and Kudryavtseva, A and Krasnov, G}, title = {Gut dysbiosis and small intestinal bacterial overgrowth as independent forms of gut microbiota disorders in cirrhosis.}, journal = {World journal of gastroenterology}, volume = {28}, number = {10}, pages = {1067-1077}, pmid = {35431497}, issn = {2219-2840}, mesh = {Bacteria/genetics ; Clostridiales ; Dysbiosis/microbiology ; Firmicutes/genetics ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis/diagnosis ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Gut dysbiosis and small intestinal bacterial overgrowth (SIBO) are commonly observed in patients with cirrhosis. Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis, dysbiosis and SIBO were always studied separately.<br><br>AIM: To study the relationship of gut dysbiosis and SIBO in cirrhosis.<br><br>METHODS: This observational study included 47 in-patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. SIBO was assessed using the lactulose hydrogen breath test.<br><br>RESULTS: SIBO was found in 24/47 (51.1%) patients. Patients with SIBO had a higher abundance of Firmicutes (P = 0.017) and Fusobacteria (P = 0.011), and a lower abundance of Bacteroidetes (P = 0.013) than patients without SIBO. This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia (P = 0.020) of the Lachnospiraceae family (P = 0.047), while the abundance of other major families of this phylum [Ruminococcaceae (P = 0.856), Peptostreptococcaceae (P = 0.066), Clostridiaceae (P = 0.463), Eubacteriaceae (P = 0.463), Lactobacillaceae (P = 0.413), and Veillonellaceae (P = 0.632)] did not differ significantly between the patients with and without SIBO. Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum [Bacteroidaceae (P = 0.014), Porphyromonadaceae (P = 0.002), and Rikenellaceae (P = 0.047)], with the exception of Prevotellaceae (P = 0.941). There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis [Proteobacteria (P = 0.790), Bacilli (P = 0.573), Enterobacteriaceae (P = 0.632), Streptococcaceae (P = 0.170), Staphylococcaceae (P = 0.450), and Enterococcaceae (P = 0.873)] between patients with and without SIBO.<br><br>CONCLUSION: Despite the differences observed in the gut microbiome between patients with and without SIBO, gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.}, }
@article {pmid35429105, year = {2022}, author = {Li, D and Van De Werfhorst, LC and Holden, PA}, title = {Genetic sequence data evidence that human faecal-associated HF183 sequences are on human skin and in urine.}, journal = {Journal of applied microbiology}, volume = {133}, number = {2}, pages = {232-240}, pmid = {35429105}, issn = {1365-2672}, support = {//Mr. Henry (Sam) Wheeler/ ; Proposition 84//the State of California Clean Beach Initiative/ ; }, mesh = {Environmental Monitoring/methods ; Feces ; Genetic Markers ; Humans ; Polymerase Chain Reaction/methods ; RNA, Ribosomal, 16S/genetics ; *Sewage ; *Water Microbiology ; }, abstract = {AIMS: The DNA marker HF183 is a partial 16S rRNA gene sequence highly specific to human-associated Bacteroides including Bacteroides dorei. While HF183 is used to assess human faecal contamination in aquatic environments worldwide, little is known about the existence of HF183 and B. dorei in human microbiomes outside of the human gastrointestinal tract and faeces.<br><br>METHODS AND RESULTS: Previously published human skin and urine microbiome data sets from five independent human body skin studies, the Human Microbiome Project (HMP) and three independent human urine studies were analysed. The HF183 gene sequence was detected in all skin data sets, with the ratios of positive samples ranging from 0.5% to 36.3%. Popliteal fossa (knee), volar forearm and inguinal (groin) creases were identified as hot spots. HF183 was detected in two of three urine data sets, with ratios of positive samples ranging from 0% to 37.5%. All HF183-containing sequences from these data sets were classified as associated with B. dorei.<br><br>CONCLUSIONS: HF183 is widespread on human skin and present in urine.<br><br>Skin and urine microbiomes could be sources of HF183 to environmental waters. Such non-faecal sources of HF183 might explain low concentrations of HF183 in recreational waters when swimmers are present.}, }
@article {pmid35427870, year = {2022}, author = {Mohammadzadeh, R and Mahnert, A and Duller, S and Moissl-Eichinger, C}, title = {Archaeal key-residents within the human microbiome: characteristics, interactions and involvement in health and disease.}, journal = {Current opinion in microbiology}, volume = {67}, number = {}, pages = {102146}, doi = {10.1016/j.mib.2022.102146}, pmid = {35427870}, issn = {1879-0364}, support = {P 30796/FWF_/Austrian Science Fund FWF/Austria ; P 32697/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {*Archaea/genetics ; Eukaryota ; Eukaryotic Cells ; Humans ; *Microbiota ; Phylogeny ; }, abstract = {Since the introduction of Archaea as new domain of life more than 40 years ago, they are no longer regarded as eccentric inhabitants of extreme ecosystems. These microorganisms are widespread in various moderate ecosystems, including eukaryotic hosts such as humans. Indeed, members of the archaeal community are now recognized as paramount constituents of human microbiome, while their definite role in disease or health is not fully elucidated and no archaeal pathogen has been reported. Here, we present a brief overview of archaea residing in and on the human body, with a specific focus on common lineages including Methanobrevibacter, Methanosphaeraand Methanomassilococcales.}, }
@article {pmid35421683, year = {2022}, author = {Safari, Z and Sadeghizadeh, M and Asgaritarghi, G and Bardania, H and Sadeghizadeh, D and Soudi, S}, title = {M13 phage coated surface elicits an anti-inflammatory response in BALB/c and C57BL/6 peritoneal macrophages.}, journal = {International immunopharmacology}, volume = {107}, number = {}, pages = {108654}, doi = {10.1016/j.intimp.2022.108654}, pmid = {35421683}, issn = {1878-1705}, mesh = {Animals ; Anti-Inflammatory Agents/metabolism ; Arginine ; *Bacteriophage M13/metabolism ; Cytokines/metabolism ; *Macrophages, Peritoneal ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; }, abstract = {Bacteriophages are one of the viral components of the human microbiome. M13 phages have recently been considered for immunotherapy because they can be detected by immune cells and stimulated immune responses. Macrophages are essential innate immune cells that respond to stimuli and direct subsequent immune responses. Therefore, it is crucial to evaluate the immunomodulatory effect of phage on macrophage function. For this purpose, peritoneal macrophages from BALB/c and C57BL/6 mice were cultured on the M13 phage, M13 phage-RGD, gelatin-coated, and un-coated wells. Then macrophages were examined for morphological characteristics, L. arginine metabolism, redox potential, inflammatory cytokine production, and phagocytic activity after two and seven days of culture. We observed that M13 phage-coated surfaces induced anti-inflammatory cytokines production and reduced inflammatory cytokines level of BALB/c and C57BL/6 macrophages at the steady-state and post LPS stimulation. In addition, L. arginine metabolism and phagocytic activity of macrophages were directed to the M2 phenotype by induction of arginase-1 and efferocytosis in the M13 phage-containing groups, respectively. The present study confirms the M13 phage's ability to polarize macrophages toward the M2 phenotype. However, using M13 phage in treating inflammatory diseases in animal models could determine their immunotherapy capacity in the future.}, }
@article {pmid35421341, year = {2022}, author = {Kostic, AD}, title = {The human microbiome: A coming of age story.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {4}, pages = {449-453}, doi = {10.1016/j.chom.2022.03.020}, pmid = {35421341}, issn = {1934-6069}, mesh = {Humans ; *Microbiota ; Research Personnel ; }, abstract = {The human microbiome field is coming of age, but it is still defining itself. I can say the same as an investigator who started his career in the early days of this expanding field. This commentary reflects on my Cell Host &amp; Microbe papers along this journey that captured the field's progress.}, }
@article {pmid35416697, year = {2022}, author = {Higashi, DL and McGuire, S and Abdelrahman, YM and Zou, Z and Qin, H and Anderson, D and Palmer, EA and Kreth, J and Merritt, J}, title = {Development of the First Tractable Genetic System for Parvimonas micra, a Ubiquitous Pathobiont in Human Dysbiotic Disease.}, journal = {Microbiology spectrum}, volume = {10}, number = {2}, pages = {e0046522}, pmid = {35416697}, issn = {2165-0497}, support = {R01 DE029492/DE/NIDCR NIH HHS/United States ; R21 DE029612/DE/NIDCR NIH HHS/United States ; R35 DE028252/DE/NIDCR NIH HHS/United States ; }, mesh = {Carcinogenesis ; *Firmicutes/genetics ; *Gram-Positive Bacteria ; Humans ; }, abstract = {Parvimonas micra is a Gram-positive obligate anaerobe and a typical member of the human microbiome. P. micra is among the most highly enriched species at numerous sites of mucosal dysbiotic disease and is closely associated with the development of multiple types of malignant tumors. Despite its strong association with disease, surprisingly little is known about P. micra pathobiology, which is directly attributable to its longstanding genetic intractability. To address this problem, we directly isolated a collection of P. micra strains from odontogenic abscess clinical specimens and then screened these isolates for natural competence. Amazingly, all of the P. micra clinical isolates exhibited various levels of natural competence, including the reference strain ATCC 33270. By exploiting this ability, we were able to employ cloning-independent methodologies to engineer and complement a variety of targeted chromosomal genetic mutations directly within low-passage-number clinical isolates. To develop a tractable genetic system for P. micra, we first adapted renilla-based bioluminescence for highly sensitive reporter studies. This reporter system was then applied for the development of the novel Theo+ theophylline-inducible riboswitch for tunable gene expression studies over a broad dynamic range. Finally, we demonstrate the feasibility of generating mariner-based transposon sequencing (Tn-seq) libraries for forward genetic screening in P. micra. With the availability of a highly efficient transformation protocol and the current suite of genetic tools, P. micra should now be considered a fully genetically tractable organism suitable for molecular genetic research. The methods presented here provide a clear path to investigate the understudied role of P. micra in polymicrobial infections and tumorigenesis. IMPORTANCE Parvimonas micra is among the most highly enriched species at numerous sites of mucosal dysbiotic disease and is closely associated with numerous cancers. Despite this, little is known about P. micra pathobiology, which is directly attributable to its longstanding genetic intractability. In this study, we provide the first report of P. micra natural competence and describe the only tractable genetic system for this species. The methods presented here will allow for the detailed study of P. micra and its role in infection and tumorigenesis.}, }
@article {pmid35410573, year = {2022}, author = {Walles, M and Pähler, A and Isin, EM and Weidolf, L}, title = {Meeting report of the second European biotransformation workshop.}, journal = {Xenobiotica; the fate of foreign compounds in biological systems}, volume = {52}, number = {4}, pages = {426-431}, doi = {10.1080/00498254.2022.2064253}, pmid = {35410573}, issn = {1366-5928}, mesh = {Biotransformation ; Humans ; *Immunoconjugates ; Peptides ; }, abstract = {Challenges and opportunities in the field of biotransformation were presented and discussed at the 2nd European Biotransformation workshop which was conducted virtually in collaboration with the DMDG on November 24/25, 2021. Here we summarise the presentations and discussions from this workshop.The following topics were covered:Regulatory requirements and biotransformation studies for antibody drug conjugates (ADCs) and antisense oligonucleotides (ASOs).Solutions for mass spectral data processing of peptides and oligonucleotides.Future outsourcing needs in biotransformation for new modalities.Established quantitative and qualitative workflows for metabolite identification.New in vitro systems to study new chemical entities (NCEs) with low metabolic turnover.New strategies on the timing of the human ADME (absorption, distribution, metabolism, excretion) study and to investigate the impact of human microbiome on drug development.}, }
@article {pmid35410233, year = {2022}, author = {Ghaffari, P and Shoaie, S and Nielsen, LK}, title = {Irritable bowel syndrome and microbiome; Switching from conventional diagnosis and therapies to personalized interventions.}, journal = {Journal of translational medicine}, volume = {20}, number = {1}, pages = {173}, pmid = {35410233}, issn = {1479-5876}, support = {BB/S016899/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; *Microbiota ; }, abstract = {The human microbiome has been linked to several diseases. Gastrointestinal diseases are still one of the most prominent area of study in host-microbiome interactions however the underlying microbial mechanisms in these disorders are not fully established. Irritable bowel syndrome (IBS) remains as one of the prominent disorders with significant changes in the gut microbiome composition and without definitive treatment. IBS has a severe impact on socio-economic and patient's lifestyle. The association studies between the IBS and microbiome have shed a light on relevance of microbial composition, and hence microbiome-based trials were designed. However, there are no clear evidence of potential treatment for IBS. This review summarizes the epidemiology and socioeconomic impact of IBS and then focus on microbiome observational and clinical trials. At the end, we propose a new perspective on using data-driven approach and applying computational modelling and machine learning to design microbiome-aware personalized treatment for IBS.}, }
@article {pmid35406091, year = {2022}, author = {Verstraeten, S and Sencio, V and Raise, A and Huillet, E and Layec, S and Deruyter, L and Heumel, S and Auger, S and Robert, V and Langella, P and Beney, L and Trottein, F and Thomas, M}, title = {Description of a Newly Isolated Blautia faecis Strain and Its Benefit in Mouse Models of Post-Influenza Secondary Enteric and Pulmonary Infections.}, journal = {Nutrients}, volume = {14}, number = {7}, pages = {}, pmid = {35406091}, issn = {2072-6643}, support = {ANR-16-CE29-0020 and ANR-17-CE15-0020-01//Agence Nationale de la Recherche/ ; }, mesh = {Animals ; *Clostridiales/classification/isolation &amp; purification ; Disease Models, Animal ; Humans ; Influenza, Human/complications ; Interleukin-8 ; Mice ; *Orthomyxoviridae Infections/complications ; *Pneumococcal Infections/microbiology/prevention &amp; control ; *Salmonella Infections, Animal/microbiology/prevention &amp; control ; Salmonella typhimurium ; Streptococcus pneumoniae ; }, abstract = {The expanding knowledge on the systemic influence of the human microbiome suggests that fecal samples are underexploited sources of new beneficial strains for extra-intestinal health. We have recently shown that acetate, a main circulating microbiota-derived molecule, reduces the deleterious effects of pulmonary Streptococcus pneumoniae and enteric Salmonella enterica serovar Typhimurium bacterial post-influenza superinfections. Considering the beneficial and broad effects of acetate, we intended to isolate a commensal strain, producing acetate and potentially exploitable in the context of respiratory infections. We designed successive steps to select intestinal commensals that are extremely oxygen-sensitive, cultivable after a freezing process, without a proinflammatory effect on IL-8 induction, and producing acetate. We have identified the Blautia faecis DSM33383 strain, which decreased the TNFα-induced production of IL-8 by the intestinal epithelial cell line HT-29. The beneficial effect of this bacterial strain was further studied in two preclinical models of post-influenza Streptococcus pneumoniae (S.p) and Salmonella enterica serovar Typhimurium (S.t) superinfection. The intragastrical administration of Blautia faecis DSM33383 led to protection in influenza-infected mice suffering from an S.p. and, to a lesser extent, from an S.t secondary infection. Altogether, this study showed that Blautia faecis DSM33383 could be a promising candidate for preventive management of respiratory infectious diseases.}, }
@article {pmid35399743, year = {2021}, author = {Hayes, CV and Eley, CV and Wood, F and Demirjian, A and McNulty, CAM}, title = {Knowledge and attitudes of adolescents towards the human microbiome and antibiotic resistance: a qualitative study.}, journal = {JAC-antimicrobial resistance}, volume = {3}, number = {2}, pages = {dlab039}, pmid = {35399743}, issn = {2632-1823}, abstract = {BACKGROUND: Antibiotic and dietary behaviour affect the human microbiome and influence antibiotic resistance development. Adolescents are a key demographic for influencing knowledge and behaviour change.<br><br>OBJECTIVES: To explore adolescents' knowledge and attitudes towards the microbiome and antibiotic resistance, and the capability, motivation and opportunity for educators to integrate microbiome teaching in schools.<br><br>METHODS: Qualitative study informed by the Theoretical Domains Framework (TDF) and COM-B model. Six educational establishments were purposively selected by rural/city and socioeconomic status, within Gloucestershire, South West England in 2019. Forty 14-18-year olds participated in focus groups, and eight science or health educators participated in interviews. Data were analysed thematically, double-coded and mapped to the TDF/COM-B.<br><br>RESULTS: Adolescents were aware of 'good microbes' in the body but lacked deeper knowledge. Adolescents' knowledge of, and intentions to use, antibiotics appropriately differed by their levels of scientific study. Adolescents lacked knowledge on the consequences of diet on the microbiome, and therefore lacked capability and motivation to change behaviour. Educators felt capable and motivated to teach microbiome topics but lacked opportunity though absence of topics in the national curriculum and lack of time to teach additional topics.<br><br>CONCLUSIONS: A disparity in knowledge of adolescents needs to be addressed through increasing antibiotic and microbiome topics in the national curriculum. Public antibiotic campaigns could include communication about the microbiome to increase awareness. Educational resources could motivate adolescents and improve their knowledge, skills and opportunity to improve diet and antibiotic use; so, supporting the UK antimicrobial resistance (AMR) national action plan.}, }
@article {pmid35399529, year = {2022}, author = {van Dijk, MC and de Kruijff, RM and Hagedoorn, PL}, title = {The Role of Iron in Staphylococcus aureus Infection and Human Disease: A Metal Tug of War at the Host-Microbe Interface.}, journal = {Frontiers in cell and developmental biology}, volume = {10}, number = {}, pages = {857237}, pmid = {35399529}, issn = {2296-634X}, abstract = {Iron deficiency anemia can be treated with oral or intravenous Fe supplementation. Such supplementation has considerable effects on the human microbiome, and on opportunistic pathogenic micro-organisms. Molecular understanding of the control and regulation of Fe availability at the host-microbe interface is crucial to interpreting the side effects of Fe supplementation. Here, we provide a concise overview of the regulation of Fe by the opportunistic pathogen Staphylococcus aureus. Ferric uptake regulator (Fur) plays a central role in controlling Fe uptake, utilization and storage in order to maintain a required value. The micro-organism has a strong preference for heme iron as an Fe source, which is enabled by the Iron-regulated surface determinant (Isd) system. The strategies it employs to overcome Fe restriction imposed by the host include: hijacking host proteins, replacing metal cofactors, and replacing functions by non-metal dependent enzymes. We propose that integrated omics approaches, which include metalloproteomics, are necessary to provide a comprehensive understanding of the metal tug of war at the host-microbe interface down to the molecular level.}, }
@article {pmid35399144, year = {2022}, author = {Badawy, S and Baka, ZAM and Abou-Dobara, MI and El-Sayed, AKA and Skurnik, M}, title = {Biological and molecular characterization of fEg-Eco19, a lytic bacteriophage active against an antibiotic-resistant clinical Escherichia coli isolate.}, journal = {Archives of virology}, volume = {167}, number = {5}, pages = {1333-1341}, pmid = {35399144}, issn = {1432-8798}, support = {288701//Academy of Finland/ ; 2016//Jane ja Aatos Erkon S&#xe4;&#xe4;ti&#xf6;/ ; }, mesh = {Anti-Bacterial Agents/pharmacology ; *Bacteriophages/genetics ; *Caudovirales/genetics ; Escherichia coli/genetics ; Genome, Viral ; Host Specificity ; }, abstract = {Characterization of bacteriophages facilitates better understanding of their biology, host specificity, genomic diversity, and adaptation to their bacterial hosts. This, in turn, is important for the exploitation of phages for therapeutic purposes, as the use of uncharacterized phages may lead to treatment failure. The present study describes the isolation and characterization of a bacteriophage effective against the important clinical pathogen Escherichia coli, which shows increasing accumulation of antibiotic resistance. Phage fEg-Eco19, which is specific for a clinical E. coli strain, was isolated from an Egyptian sewage sample. Phage fEg-Eco19 formed clear, sharp-edged, round plaques. Electron microscopy showed that the isolated phage is tailed and therefore belongs to the order Caudovirales, and morphologically, it resembles siphoviruses. The diameter of the icosahedral head of fEg-Eco19 is 68 ± 2 nm, and the non-contractile tail length and diameter are 118 ± 0.2 and 13 ± 0.6 nm, respectively. The host range of the phage was found to be narrow, as it infected only two out of 137 clinical E. coli strains tested. The phage genome is 45,805 bp in length with a GC content of 50.3% and contains 76 predicted genes. Comparison of predicted and experimental restriction digestion patterns allowed rough mapping of the physical ends of the phage genome, which was confirmed using the PhageTerm tool. Annotation of the predicted genes revealed gene products belonging to several functional groups, including regulatory proteins, DNA packaging and phage structural proteins, host lysis proteins, and proteins involved in DNA/RNA metabolism and replication.}, }
@article {pmid35395818, year = {2022}, author = {Shetty, SA and Kuipers, B and Atashgahi, S and Aalvink, S and Smidt, H and de Vos, WM}, title = {Inter-species Metabolic Interactions in an In-vitro Minimal Human Gut Microbiome of Core Bacteria.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {21}, pmid = {35395818}, issn = {2055-5008}, mesh = {Bacteria/genetics/metabolism ; Colon/microbiology ; Dietary Fiber ; Fatty Acids, Volatile ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Knowledge of the functional roles and interspecies interactions are crucial for improving our understanding of the human intestinal microbiome in health and disease. However, the complexity of the human intestinal microbiome and technical challenges in investigating it pose major challenges. In this proof-of-concept study, we rationally designed, assembled and experimentally tested a synthetic Diet-based Minimal Microbiome (Db-MM) consisting of ten core intestinal bacterial species that together are capable of efficiently converting dietary fibres into short chain fatty acids (SCFAs). Despite their genomic potential for metabolic competition, all ten bacteria coexisted during growth on a mixture of dietary fibres, including pectin, inulin, xylan, cellobiose and starch. By integrated analyses of metabolite production, community composition and metatranscriptomics-based gene expression data, we identified interspecies metabolic interactions leading to production of key SCFAs such as butyrate and propionate. While public goods, such as sugars liberated from colonic fibres, are harvested by non-degraders, some species thrive by cross-feeding on energetically challenging substrates, including the butyrogenic conversion of acetate and lactate. Using a reductionist approach in an in-vitro system combined with functional measurements, our study provides key insights into the complex interspecies metabolic interactions between core intestinal bacterial species.}, }
@article {pmid35393656, year = {2022}, author = {Manos, J}, title = {The human microbiome in disease and pathology.}, journal = {APMIS : acta pathologica, microbiologica, et immunologica Scandinavica}, volume = {130}, number = {12}, pages = {690-705}, pmid = {35393656}, issn = {1600-0463}, mesh = {Humans ; Adult ; Dysbiosis/microbiology ; *Diabetes Mellitus, Type 2 ; *Microbiota ; *Gastrointestinal Microbiome ; Bacteria ; }, abstract = {This narrative review seeks to examine the relationships between bacterial microbiomes and infectious disease. This is achieved by detailing how different human host microbiomes develop and function, from the earliest infant acquisitions of maternal and environmental species through to the full development of microbiomes by adulthood. Communication between bacterial species or communities of species within and outside of the microbiome is a factor in both maintenance of homeostasis and management of threats from the external environment. Dysbiosis of this homeostasis is key to understanding the development of disease states. Several microbiomes and the microbiota within are used as prime examples of how changes in species composition, particularly at the phylum level, leads to such diverse conditions as inflammatory bowel disease (IBD), type 2 diabetes, psoriasis, Parkinson's disease, reflux oesophagitis and others. The review examines spatial relationships between microbiomes to understand how dysbiosis in the gut microbiome in particular can influence diseases in distant host sites via routes such as the gut-lung, gut-skin and gut-brain axes. Microbiome interaction with host processes such as adaptive immunity is increasingly identified as critical to developing the capacity of the immune system to react to pathogens. Dysbiosis of essential bacteria involved in modification of host substrates such as bile acid components can result in development of Crohn's disease, small intestine bacterial overgrowth, hepatic cancer and obesity. Interactions between microbiomes in distantly located sites are being increasingly being identified, resulting in a 'whole of body' effect by the combined host microbiome.}, }
@article {pmid35392614, year = {2022}, author = {Du, Y and Feng, R and Chang, ET and Debelius, JW and Yin, L and Xu, M and Huang, T and Zhou, X and Xiao, X and Li, Y and Liao, J and Zheng, Y and Huang, G and Adami, HO and Zhang, Z and Cai, Y and Ye, W}, title = {Influence of Pre-treatment Saliva Microbial Diversity and Composition on Nasopharyngeal Carcinoma Prognosis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {831409}, pmid = {35392614}, issn = {2235-2988}, mesh = {Humans ; Nasopharyngeal Carcinoma ; *Nasopharyngeal Neoplasms/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Saliva/microbiology ; }, abstract = {BACKGROUND: The human microbiome has been reported to mediate the response to anticancer therapies. However, research about the influence of the oral microbiome on nasopharyngeal carcinoma (NPC) survival is lacking. We aimed to explore the effect of oral microbiota on NPC prognosis.<br><br>METHODS: Four hundred eighty-two population-based NPC cases in southern China between 2010 and 2013 were followed for survival, and their saliva samples were profiled using 16s rRNA sequencing. We analyzed associations of the oral microbiome diversity with mortality from all causes and NPC.<br><br>RESULTS: Within- and between-community diversities of saliva were associated with mortality with an average of 5.29 years follow-up. Lower Faith's phylogenetic diversity was related to higher all-cause mortality [adjusted hazard ratio (aHR), 1.52 (95% confidence interval (CI), 1.06-2.17)] and NPC-specific mortality [aHR, 1.57 (95% CI, 1.07-2.29)], compared with medium diversity, but higher phylogenetic diversity was not protective. The third principal coordinate (PC3) identified from principal coordinates analysis (PCoA) on Bray-Curtis distance was marginally associated with reduced all-cause mortality [aHR, 0.85 (95% CI, 0.73-1.00)], as was the first principal coordinate (PC1) from PCoA on weighted UniFrac [aHR, 0.86 (95% CI, 0.74-1.00)], but neither was associated with NPC-specific mortality. PC3 from robust principal components analysis was associated with lower all-cause and NPC-specific mortalities, with HRs of 0.72 (95% CI, 0.61-0.85) and 0.71 (95% CI, 0.60-0.85), respectively.<br><br>CONCLUSIONS: Oral microbiome may be an explanatory factor for NPC prognosis. Lower within-community diversity was associated with higher mortality, and certain measures of between-community diversity were related to mortality. Specifically, candidate bacteria were not related to mortality, suggesting that observed associations may be due to global patterns rather than particular pathogens.}, }
@article {pmid35392604, year = {2022}, author = {Glazier, VE}, title = {EFG1, Everyone's Favorite Gene in Candida albicans: A Comprehensive Literature Review.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {855229}, pmid = {35392604}, issn = {2235-2988}, mesh = {*Candida albicans ; *DNA-Binding Proteins/genetics/metabolism ; *Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Humans ; Hyphae ; *Transcription Factors/genetics/metabolism ; }, abstract = {Candida sp. are among the most common fungal commensals found in the human microbiome. Although Candida can be found residing harmlessly on the surface of the skin and mucosal membranes, these opportunistic fungi have the potential to cause superficial skin, nail, and mucus membrane infections as well as life threatening systemic infections. Severity of infection is dependent on both fungal and host factors including the immune status of the host. Virulence factors associated with Candida sp. pathogenicity include adhesin proteins, degradative enzymes, phenotypic switching, and morphogenesis. A central transcriptional regulator of morphogenesis, the transcription factor Efg1 was first characterized in Candida albicans in 1997. Since then, EFG1 has been referenced in the Candida literature over three thousand times, with the number of citations growing daily. Arguably one of the most well studied genes in Candida albicans, EFG1 has been referenced in nearly all contexts of Candida biology from the development of novel therapeutics to white opaque switching, hyphae morphology to immunology. In the review that follows we will synthesize the research that has been performed on this extensively studied transcription factor and highlight several important unanswered questions.}, }
@article {pmid35388189, year = {2022}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Author Correction: Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {7}, number = {5}, pages = {736}, doi = {10.1038/s41564-022-01118-8}, pmid = {35388189}, issn = {2058-5276}, support = {650451//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; 580924//Crohn's and Colitis Foundation (Crohn's &amp; Colitis Foundation)/ ; }, }
@article {pmid35382166, year = {2022}, author = {Yadav, M and Chauhan, NS}, title = {Microbiome therapeutics: exploring the present scenario and challenges.}, journal = {Gastroenterology report}, volume = {10}, number = {}, pages = {goab046}, pmid = {35382166}, issn = {2052-0034}, abstract = {Human gut-microbiome explorations have enriched our understanding of microbial colonization, maturation, and dysbiosis in health-and-disease subsets. The enormous metabolic potential of gut microbes and their role in the maintenance of human health is emerging, with new avenues to use them as therapeutic agents to overcome human disorders. Microbiome therapeutics are aimed at engineering the gut microbiome using additive, subtractive, or modulatory therapy with an application of native or engineered microbes, antibiotics, bacteriophages, and bacteriocins. This approach could overcome the limitation of conventional therapeutics by providing personalized, harmonized, reliable, and sustainable treatment. Its huge economic potential has been shown in the global therapeutics market. Despite the therapeutic and economical potential, microbiome therapeutics is still in the developing stage and is facing various technical and administrative issues that require research attention. This review aims to address the current knowledge and landscape of microbiome therapeutics, provides an overview of existing health-and-disease applications, and discusses the potential future directions of microbiome modulations.}, }
@article {pmid35380149, year = {2022}, author = {Kynkäänniemi, E and Lahtinen, MH and Jian, C and Salonen, A and Hatanpää, T and Mikkonen, KS and Pajari, AM}, title = {Correction: Gut microbiota can utilize prebiotic birch glucuronoxylan in production of short-chain fatty acids in rats.}, journal = {Food &amp; function}, volume = {13}, number = {8}, pages = {4770}, doi = {10.1039/d2fo90028a}, pmid = {35380149}, issn = {2042-650X}, abstract = {Correction for 'Gut microbiota can utilize prebiotic birch glucuronoxylan in production of short-chain fatty acids in rats' by Emma Kynkäänniemi et al., Food Funct., 2022, 13, 3746-3759, DOI: 10.1039/D1FO03922A.}, }
@article {pmid35371778, year = {2022}, author = {Segal, E and Bar Yosef, S and Axel, A and Keller, N and Shlaeffer, F and Amir, A and Efroni, G and Haberman, Y}, title = {Outbreak of Sepsis Following Surgery: Utilizing 16S RNA Sequencing To Detect the Source of Infection.}, journal = {Cureus}, volume = {14}, number = {2}, pages = {e22487}, pmid = {35371778}, issn = {2168-8184}, abstract = {Background Nosocomial infections are a significant health concern. Following surgery, infections are most commonly associated with the surgical site, yet there are other potential sources for infections after surgical interventions. Identification of the source of infections can be very challenging. Methodology An outbreak of postoperative infections following surgery led to intensive care unit (ICU) admission of patients immediately after the surgical procedure. The blood cultures of two patients were positive for Citrobacter freundii. The only connection between all cases was the anesthesiologist. An epidemiological inquiry could not definitively identify the source of the outbreak. Therefore, we utilized an RNA sequencing technique to evaluate the microbiome of the anesthesiologist and compared the results to bacteria cultured from the bloodstream of the two patients. Results The anesthesiologist's microbiome contained amplicons that were identical to those of the bacteria in the patient's bloodstream. Because Citrobacter freundii is an uncommon source of bloodstream infections, and in the normal human microbiome, the results establish the source of a cluster of infections to the anesthesiologist. Conclusions In cases of nosocomial infections, when conventional microbiological techniques do not clearly establish the source of the infection, using 16S RNA sequencing should be considered.}, }
@article {pmid35369727, year = {2022}, author = {Zhu, Q and Huang, S and Gonzalez, A and McGrath, I and McDonald, D and Haiminen, N and Armstrong, G and Vázquez-Baeza, Y and Yu, J and Kuczynski, J and Sepich-Poore, GD and Swafford, AD and Das, P and Shaffer, JP and Lejzerowicz, F and Belda-Ferre, P and Havulinna, AS and Méric, G and Niiranen, T and Lahti, L and Salomaa, V and Kim, HC and Jain, M and Inouye, M and Gilbert, JA and Knight, R}, title = {Phylogeny-Aware Analysis of Metagenome Community Ecology Based on Matched Reference Genomes while Bypassing Taxonomy.}, journal = {mSystems}, volume = {7}, number = {2}, pages = {e0016722}, pmid = {35369727}, issn = {2379-5077}, support = {RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; U24 CA248454/CA/NCI NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; F30 CA243480/CA/NCI NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Phylogeny ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Ecology ; }, abstract = {We introduce the operational genomic unit (OGU) method, a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing the diversity of microbial communities and their relevance to environmental factors. This approach is independent of taxonomic classification, granting the possibility of maximal resolution of community composition, and organizes features into an accurate hierarchy using a phylogenomic tree. The outputs are suitable for contemporary analytical protocols for community ecology, differential abundance, and supervised learning while supporting phylogenetic methods, such as UniFrac and phylofactorization, that are seldom applied to shotgun metagenomics despite being prevalent in 16S rRNA gene amplicon studies. As demonstrated in two real-world case studies, the OGU method produces biologically meaningful patterns from microbiome data sets. Such patterns further remain detectable at very low metagenomic sequencing depths. Compared with taxonomic unit-based analyses implemented in currently adopted metagenomics tools, and the analysis of 16S rRNA gene amplicon sequence variants, this method shows superiority in informing biologically relevant insights, including stronger correlation with body environment and host sex on the Human Microbiome Project data set and more accurate prediction of human age by the gut microbiomes of Finnish individuals included in the FINRISK 2002 cohort. We provide Woltka, a bioinformatics tool to implement this method, with full integration with the QIIME 2 package and the Qiita web platform, to facilitate adoption of the OGU method in future metagenomics studies. IMPORTANCE Shotgun metagenomics is a powerful, yet computationally challenging, technique compared to 16S rRNA gene amplicon sequencing for decoding the composition and structure of microbial communities. Current analyses of metagenomic data are primarily based on taxonomic classification, which is limited in feature resolution. To solve these challenges, we introduce operational genomic units (OGUs), which are the individual reference genomes derived from sequence alignment results, without further assigning them taxonomy. The OGU method advances current read-based metagenomics in two dimensions: (i) providing maximal resolution of community composition and (ii) permitting use of phylogeny-aware tools. Our analysis of real-world data sets shows that it is advantageous over currently adopted metagenomic analysis methods and the finest-grained 16S rRNA analysis methods in predicting biological traits. We thus propose the adoption of OGUs as an effective practice in metagenomic studies.}, }
@article {pmid35369525, year = {2022}, author = {Wang, S and Song, F and Gu, H and Wei, X and Zhang, K and Zhou, Y and Luo, H}, title = {Comparative Evaluation of the Salivary and Buccal Mucosal Microbiota by 16S rRNA Sequencing for Forensic Investigations.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {777882}, pmid = {35369525}, issn = {1664-302X}, abstract = {The human microbiome has emerged as a new potential biomarker for forensic investigations with the development of high-throughput sequencing and bioinformatic analysis during the last decade. The oral cavity has many different microbial habitats, with each habit colonized by specific and individualized microbiota. As saliva and buccal mucosa are common biological evidence in forensic science, understanding the differences of microbial communities between the two is important for forensic original identification. Moreover, the oral microbiota is individualized, whereas there are few studies on the application of forensic personal identification that need to be supplemented. In this study, Streptococcus was the most abundant genus, with an average relative abundance of 49.61% in the buccal mucosa, while in the saliva, Streptococcus, Veillonella, and Neisseria had similar proportions (20%, 15%, 16%) and were the dominant genera. The α and β diversity displayed a significant distinctness between the saliva and buccal mucosal groups. The community assembly mechanism stated that the deterministic process played a more significant effect in shaping the salivary bacterial community assembly than buccal mucosa, which explained the microbial differences. Of the test samples, 93.3% can be correctly classified with the random forest model based on the microbial differences. Targeting the low-abundance bacteria at the species level, 52% of experimental participants could be discriminated by using the observed unique bacterial species. In conclusion, the salivary bacterial community composition differed from that of the buccal mucosa and showed high richness and diversity. With the random forest model, the microbiota of saliva and buccal mucosa can be classified, which can be used in identifying the source of oral biological trace. Furthermore, each individual has a unique bacterial community pattern, and the presence or absence of unique bacteria and differences in the composition of the core oral microbiota are the key points for forensic personal discrimination that supplement the study of oral microbial application to forensic personal discrimination. Whether for original identification or personal discrimination, the oral microbiome has great potential for application.}, }
@article {pmid35369083, year = {2022}, author = {Rees, J and Fu, SC and Lo, J and Sambell, R and Lewis, JR and Christophersen, CT and Byrne, MF and Newton, RU and Boyle, S and Devine, A}, title = {How a 7-Week Food Literacy Cooking Program Affects Cooking Confidence and Mental Health: Findings of a Quasi-Experimental Controlled Intervention Trial.}, journal = {Frontiers in nutrition}, volume = {9}, number = {}, pages = {802940}, pmid = {35369083}, issn = {2296-861X}, abstract = {Obesity and mental health disorders are rising simultaneously with shifting dietary behavior away from home cooking, toward typically nutrition-poor and energy-dense convenience meals. Food literacy strongly influences nutrition choices. Community-based cooking interventions target barriers to healthy eating and facilitate development of food literacy skills, thereby potentially increasing preparation of home-cooked meals and positively influencing health. This study of 657 healthy Australian adults explored the efficacy of a 7-week cooking program in improving cooking confidence, whether this transferred to behavior surrounding food, and/or affected mental health. Significant post-program improvements in cooking confidence and satisfaction (all p < 0.001, η p 2 1.12 large), ability to change eating habits (p < 0.001) and overcome lifestyle barriers (p = 0.005) were observed for the intervention group but not control. Participation also improved mental and general health (all p < 0.05, η p 2 0.02 small). No changes were observed for acquisition and consumption of food, or nutrition knowledge in either group. This 7-week cooking program built cooking confidence and improved general and mental health but did not change dietary behavior. To further improve nutrition related behaviors associated with better mental health, more effort is needed to recruit those with below-average nutrition knowledge and interest in cooking.}, }
@article {pmid35366966, year = {2022}, author = {Monir, RL and Schoch, JJ}, title = {Clinical Relevance of the Microbiome in Pediatric Skin Disease: A Review.}, journal = {Dermatologic clinics}, volume = {40}, number = {2}, pages = {117-126}, doi = {10.1016/j.det.2021.12.001}, pmid = {35366966}, issn = {1558-0520}, mesh = {*Alopecia Areata ; Child ; *Dermatitis, Atopic ; Humans ; *Microbiota ; Skin ; *Skin Diseases ; }, abstract = {The human microbiome encompasses the microorganisms that live in and on the body. During the prenatal and infantile periods, foundations for the cutaneous and gut microbiomes are being established and refined concurrently with the development of immune function. Herein, we review the relevance of the microbiome to 5 conditions commonly encountered in pediatric dermatology: acne, alopecia areata, atopic dermatitis, psoriasis, and seborrheic dermatitis. Understanding the role microbes play in these conditions may establish the groundwork for future therapeutic interventions.}, }
@article {pmid35366417, year = {2022}, author = {Patel, JR and Oh, J and Wang, S and Crawford, JM and Isaacs, FJ}, title = {Cross-kingdom expression of synthetic genetic elements promotes discovery of metabolites in the human microbiome.}, journal = {Cell}, volume = {185}, number = {9}, pages = {1487-1505.e14}, pmid = {35366417}, issn = {1097-4172}, support = {EP-W-17-011/EPA/EPA/United States ; R01 CA215553/CA/NCI NIH HHS/United States ; T32 GM067543/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/metabolism ; *Biosynthetic Pathways ; Eukaryota/genetics/metabolism ; Genetic Engineering ; *Host Microbial Interactions ; Humans ; Metabolomics ; *Microbiota ; Synthetic Biology/*methods ; }, abstract = {Small molecules encoded by biosynthetic pathways mediate cross-species interactions and harbor untapped potential, which has provided valuable compounds for medicine and biotechnology. Since studying biosynthetic gene clusters in their native context is often difficult, alternative efforts rely on heterologous expression, which is limited by host-specific metabolic capacity and regulation. Here, we describe a computational-experimental technology to redesign genes and their regulatory regions with hybrid elements for cross-species expression in Gram-negative and -positive bacteria and eukaryotes, decoupling biosynthetic capacity from host-range constraints to activate silenced pathways. These synthetic genetic elements enabled the discovery of a class of microbiome-derived nucleotide metabolites-tyrocitabines-from Lactobacillus iners. Tyrocitabines feature a remarkable orthoester-phosphate, inhibit translational activity, and invoke unexpected biosynthetic machinery, including a class of "Amadori synthases" and "abortive" tRNA synthetases. Our approach establishes a general strategy for the redesign, expression, mobilization, and characterization of genetic elements in diverse organisms and communities.}, }
@article {pmid35366155, year = {2022}, author = {Sexton, RE and Uddin, MH and Bannoura, S and Khan, HY and Mzannar, Y and Li, Y and Aboukameel, A and Al-Hallak, MN and Al-Share, B and Mohamed, A and Nagasaka, M and El-Rayes, B and Azmi, AS}, title = {Connecting the Human Microbiome and Pancreatic Cancer.}, journal = {Cancer metastasis reviews}, volume = {41}, number = {2}, pages = {317-331}, pmid = {35366155}, issn = {1573-7233}, support = {R01 CA240607/CA/NCI NIH HHS/United States ; R37 CA215427/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; Pancreas ; *Pancreatic Neoplasms/etiology ; }, abstract = {Pancreatic cancer is a deadly disease that is increasing in incidence throughout the world. There are no clear causal factors associated with the incidence of pancreatic cancer; however, some correlation to smoking, diabetes and alcohol has been described. Recently, a few studies have linked the human microbiome (oral and gastrointestinal tract) to pancreatic cancer development. A perturbed microbiome has been shown to alter normal cells while promoting cancer-related processes such as increased cell signaling, immune system evasion and invasion. In this article, we will review in detail the alterations within the gut and oral microbiome that have been linked to pancreatic cancer and explore the ability of other microbiomes, such as the lung and skin microbiome, to contribute to disease development. Understanding ways to identify a perturbed microbiome can result in advancements in pancreatic cancer research and allow for prevention, earlier detection and alternative treatment strategies for patients.}, }
@article {pmid35362479, year = {2022}, author = {Wensel, CR and Pluznick, JL and Salzberg, SL and Sears, CL}, title = {Next-generation sequencing: insights to advance clinical investigations of the microbiome.}, journal = {The Journal of clinical investigation}, volume = {132}, number = {7}, pages = {}, pmid = {35362479}, issn = {1558-8238}, support = {R01 HG006677/HG/NHGRI NIH HHS/United States ; 27140/CRUK_/Cancer Research UK/United Kingdom ; R35 GM130151/GM/NIGMS NIH HHS/United States ; A27140/CRUK_/Cancer Research UK/United Kingdom ; R01 CA196845/CA/NCI NIH HHS/United States ; R56 DK107726/DK/NIDDK NIH HHS/United States ; }, mesh = {High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/methods ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA ; }, abstract = {Next-generation sequencing (NGS) technology has advanced our understanding of the human microbiome by allowing for the discovery and characterization of unculturable microbes with prediction of their function. Key NGS methods include 16S rRNA gene sequencing, shotgun metagenomic sequencing, and RNA sequencing. The choice of which NGS methodology to pursue for a given purpose is often unclear for clinicians and researchers. In this Review, we describe the fundamentals of NGS, with a focus on 16S rRNA and shotgun metagenomic sequencing. We also discuss pros and cons of each methodology as well as important concepts in data variability, study design, and clinical metadata collection. We further present examples of how NGS studies of the human microbiome have advanced our understanding of human disease pathophysiology across diverse clinical contexts, including the development of diagnostics and therapeutics. Finally, we share insights as to how NGS might further be integrated into and advance microbiome research and clinical care in the coming years.}, }
@article {pmid35360061, year = {2022}, author = {Reid, G and Dhir, R and Bron, PA}, title = {Fixing Functional GI Disorders Using Microbes: Easier Said Than Done.}, journal = {Frontiers in endocrinology}, volume = {13}, number = {}, pages = {804179}, pmid = {35360061}, issn = {1664-2392}, mesh = {*Gastrointestinal Diseases/therapy ; Humans ; }, }
@article {pmid35357819, year = {2022}, author = {Challa, AP and Hu, X and Zhang, YQ and Hymes, J and Wallace, BD and Karavadhi, S and Sun, H and Patnaik, S and Hall, MD and Shen, M}, title = {Virtual Screening for the Discovery of Microbiome β-Glucuronidase Inhibitors to Alleviate Cancer Drug Toxicity.}, journal = {Journal of chemical information and modeling}, volume = {62}, number = {7}, pages = {1783-1793}, pmid = {35357819}, issn = {1549-960X}, support = {R21 HD105304/HD/NICHD NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; ZIA TR000362/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Antineoplastic Agents/adverse effects ; *Drug-Related Side Effects and Adverse Reactions ; Early Detection of Cancer ; Enzyme Inhibitors/pharmacology ; Glycoproteins ; Humans ; *Microbiota ; *Neoplasms ; }, abstract = {Despite the potency of most first-line anti-cancer drugs, nonadherence to these drug regimens remains high and is attributable to the prevalence of "off-target" drug effects that result in serious adverse events (SAEs) like hair loss, nausea, vomiting, and diarrhea. Some anti-cancer drugs are converted by liver uridine 5'-diphospho-glucuronosyltransferases through homeostatic host metabolism to form drug-glucuronide conjugates. These sugar-conjugated metabolites are generally inactive and can be safely excreted via the biliary system into the gastrointestinal tract. However, β-glucuronidase (βGUS) enzymes expressed by commensal gut bacteria can remove the glucuronic acid moiety, producing the reactivated drug and triggering dose-limiting side effects. Small-molecule βGUS inhibitors may reduce this drug-induced gut toxicity, allowing patients to complete their full course of treatment. Herein, we report the discovery of novel chemical series of βGUS inhibitors by structure-based virtual high-throughput screening (vHTS). We developed homology models for βGUS and applied them to large-scale vHTS against nearly 400,000 compounds within the chemical libraries of the National Center for Advancing Translational Sciences at the National Institutes of Health. From the vHTS results, we cherry-picked 291 compounds via a multifactor prioritization procedure, providing 69 diverse compounds that exhibited positive inhibitory activity in a follow-up βGUS biochemical assay in vitro. Our findings correspond to a hit rate of 24% and could inform the successful downstream development of a therapeutic adjunct that targets the human microbiome to prevent SAEs associated with first-line, standard-of-care anti-cancer drugs.}, }
@article {pmid35357498, year = {2022}, author = {Gomez-Raya-Vilanova, MV and Leskinen, K and Bhattacharjee, A and Virta, P and Rosenqvist, P and Smith, JLR and Bayfield, OW and Homberger, C and Kerrinnes, T and Vogel, J and Pajunen, MI and Skurnik, M}, title = {The DNA polymerase of bacteriophage YerA41 replicates its T-modified DNA in a primer-independent manner.}, journal = {Nucleic acids research}, volume = {50}, number = {7}, pages = {3985-3997}, pmid = {35357498}, issn = {1362-4962}, support = {206377/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Bacteriophages/chemistry/genetics ; Capsid ; Cryoelectron Microscopy ; DNA, Viral/genetics ; DNA-Directed DNA Polymerase/genetics ; Genome, Viral/genetics ; Thymidine ; }, abstract = {Yersinia phage YerA41 is morphologically similar to jumbo bacteriophages. The isolated genomic material of YerA41 could not be digested by restriction enzymes, and used as a template by conventional DNA polymerases. Nucleoside analysis of the YerA41 genomic material, carried out to find out whether this was due to modified nucleotides, revealed the presence of a ca 1 kDa substitution of thymidine with apparent oligosaccharide character. We identified and purified the phage DNA polymerase (DNAP) that could replicate the YerA41 genomic DNA even without added primers. Cryo-electron microscopy (EM) was used to characterize structural details of the phage particle. The storage capacity of the 131 nm diameter head was calculated to accommodate a significantly longer genome than that of the 145 577 bp genomic DNA of YerA41 determined here. Indeed, cryo-EM revealed, in contrast to the 25 Å in other phages, spacings of 33-36 Å between shells of the genomic material inside YerA41 heads suggesting that the heavily substituted thymidine increases significantly the spacing of the DNA packaged inside the capsid. In conclusion, YerA41 appears to be an unconventional phage that packages thymidine-modified genomic DNA into its capsids along with its own DNAP that has the ability to replicate the genome.}, }
@article {pmid35355602, year = {2022}, author = {Montemari, AL and Marzano, V and Essa, N and Levi Mortera, S and Rossitto, M and Gardini, S and Selan, L and Vrenna, G and Onetti Muda, A and Putignani, L and Fiscarelli, EV}, title = {A Shaving Proteomic Approach to Unveil Surface Proteins Modulation of Multi-Drug Resistant Pseudomonas aeruginosa Strains Isolated From Cystic Fibrosis Patients.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {818669}, pmid = {35355602}, issn = {2296-858X}, abstract = {Cystic fibrosis (CF) is the most common rare disease caused by a mutation of the CF transmembrane conductance regulator gene encoding a channel protein of the apical membrane of epithelial cells leading to alteration of Na[+] and K[+] transport, hence inducing accumulation of dense and sticky mucus and promoting recurrent airway infections. The most detected bacterium in CF patients is Pseudomonas aeruginosa (PA) which causes chronic colonization, requiring stringent antibiotic therapies that, in turn induces multi-drug resistance. Despite eradication attempts at the first infection, the bacterium is able to utilize several adaptation mechanisms to survive in hostile environments such as the CF lung. Its adaptive machinery includes modulation of surface molecules such as efflux pumps, flagellum, pili and other virulence factors. In the present study we compared surface protein expression of PA multi- and pan-drug resistant strains to wild-type antibiotic-sensitive strains, isolated from the airways of CF patients with chronic colonization and recent infection, respectively. After shaving with trypsin, microbial peptides were analyzed by tandem-mass spectrometry on a high-resolution platform that allowed the identification of 174 differentially modulated proteins localized in the region from extracellular space to cytoplasmic membrane. Biofilm assay was performed to characterize all 26 PA strains in term of biofilm production. Among the differentially expressed proteins, 17 were associated to the virulome (e.g., Tse2, Tse5, Tsi1, PilF, FliY, B-type flagellin, FliM, PyoS5), six to the resistome (e.g., OprJ, LptD) and five to the biofilm reservoir (e.g., AlgF, PlsD). The biofilm assay characterized chronic antibiotic-resistant isolates as weaker biofilm producers than wild-type strains. Our results suggest the loss of PA early virulence factors (e.g., pili and flagella) and later expression of virulence traits (e.g., secretion systems proteins) as an indicator of PA adaptation and persistence in the CF lung environment. To our knowledge, this is the first study that, applying a shaving proteomic approach, describes adaptation processes of a large collection of PA clinical strains isolated from CF patients in early and chronic infection phases.}, }
@article {pmid35355005, year = {2022}, author = {Kamdar, S and Shin, S and Leishangthem, P and Francis, LF and Xu, X and Cheng, X}, title = {The colloidal nature of complex fluids enhances bacterial motility.}, journal = {Nature}, volume = {603}, number = {7903}, pages = {819-823}, pmid = {35355005}, issn = {1476-4687}, mesh = {Bacteria ; *Colloids ; *Ecosystem ; Humans ; Hydrodynamics ; Polymers ; }, abstract = {The natural habitats of microorganisms in the human microbiome, ocean and soil ecosystems are full of colloids and macromolecules. Such environments exhibit non-Newtonian flow properties, drastically affecting the locomotion of microorganisms[1-5]. Although the low-Reynolds-number hydrodynamics of swimming flagellated bacteria in simple Newtonian fluids has been well developed[6-9], our understanding of bacterial motility in complex non-Newtonian fluids is less mature[10,11]. Even after six decades of research, fundamental questions about the nature and origin of bacterial motility enhancement in polymer solutions are still under debate[12-23]. Here we show that flagellated bacteria in dilute colloidal suspensions display quantitatively similar motile behaviours to those in dilute polymer solutions, in particular a universal particle-size-dependent motility enhancement up to 80% accompanied by a strong suppression of bacterial wobbling[18,24]. By virtue of the hard-sphere nature of colloids, whose size and volume fraction we vary across experiments, our results shed light on the long-standing controversy over bacterial motility enhancement in complex fluids and suggest that polymer dynamics may not be essential for capturing the phenomenon[12-23]. A physical model that incorporates the colloidal nature of complex fluids quantitatively explains bacterial wobbling dynamics and mobility enhancement in both colloidal and polymeric fluids. Our findings contribute to the understanding of motile behaviours of bacteria in complex fluids, which are relevant for a wide range of microbiological processes[25] and for engineering bacterial swimming in complex environments[26,27].}, }
@article {pmid35344737, year = {2022}, author = {Houttu, N and Mokkala, K and Saleem, WT and Virtanen, S and Juhila, J and Koivuniemi, E and Pellonperä, O and Tertti, K and Luokola, P and Sorsa, T and Salonen, A and Lahti, L and Laitinen, K}, title = {Potential pathobionts in vaginal microbiota are affected by fish oil and/or probiotics intervention in overweight and obese pregnant women.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {149}, number = {}, pages = {112841}, doi = {10.1016/j.biopha.2022.112841}, pmid = {35344737}, issn = {1950-6007}, mesh = {*Bifidobacterium animalis ; C-Reactive Protein ; *Diabetes, Gestational ; Female ; Fish Oils/therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; *Lacticaseibacillus rhamnosus ; *Microbiota ; Obesity/therapy ; Overweight/therapy ; Pregnancy ; Pregnant People ; *Probiotics/therapeutic use ; RNA, Ribosomal, 16S ; }, abstract = {New means to stabilize the microbial balance during pregnancy could benefit maternal health. Our objectives were to investigate in overweight/obese pregnant women 1) the impact of long-chain polyunsaturated fatty acids (fish oil) and/or probiotics on the vaginal microbiota, 2) its relation to gestational diabetes mellitus (GDM) and 3) its interaction with vaginal active matrix metalloproteinase-8 (aMMP-8) and serum high sensitivity C-reactive protein (hsCRP) and phosphorylated insulin-like growth factor-binding protein-1 (phIGFBP-1), IGFBP-1 and aMMP-8. The women were allocated to fish oil + placebo, probiotics + placebo, fish oil + probiotics and placebo + placebo-groups, from early pregnancy onwards (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lacticaseibacillus rhamnosus HN001 (formerly Lactobacillus rhamnosus HN001) and Bifidobacterium animalis ssp. lactis 420, 10[10] colony-forming units each). Vaginal and serum samples (early pregnancy, n = 112; late pregnancy, n = 116), were analyzed for vaginal microbiota using 16S rRNA gene amplicon sequencing and vaginal aMMP-8 and serum hsCRP, aMMP-8, phIGFBP-1 and IGFBP-1 by immunoassays. GDM was diagnosed from a 2-h 75 g OGTT. ClinicalTrials.gov, NCT01922791. The intervention exerted effects on many low-abundant bacteria. Compared to the placebo-group, there was a lower abundance of potential pathobionts, namely Ureaplasma urealyticum in the fish oil-group, Ureaplasma, U. urealyticum and Prevotella disiens in the probiotics-group, Dialister invisus and Prevotella timonensis in the fish oil + probiotics-group. Moreover, probiotics decreased the abundance of a few potential pathobionts during pregnancy. Many bacteria were related to GDM. The vaginal aMMP-8 level correlated significantly with α-diversity and inversely with two Lactobacillus species. Dietary interventions, especially probiotics, may have beneficial effects on the vaginal microbiota during pregnancy.}, }
@article {pmid35343759, year = {2022}, author = {Berlinberg, AJ and Brar, A and Stahly, A and Gerich, ME and Fennimore, BP and Scott, FI and Kuhn, KA}, title = {A Novel Approach toward Less Invasive Multiomics Gut Analyses: a Pilot Study.}, journal = {Microbiology spectrum}, volume = {10}, number = {2}, pages = {e0244621}, pmid = {35343759}, issn = {2165-0497}, support = {T32 AR007534/AR/NIAMS NIH HHS/United States ; R01 AR075033/AR/NIAMS NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; }, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; Metabolomics/methods ; *Microbiota ; Pilot Projects ; }, abstract = {Newer 'omics approaches, such as metatranscriptomics and metabolomics, allow functional assessments of the interaction(s) between the gut microbiome and the human host. However, in order to generate meaningful data with these approaches, the method of sample collection is critical. Prior studies have relied on expensive and invasive means toward sample acquisition, such as intestinal biopsy, while other studies have relied on easier methods of collection, such as fecal samples that do not necessarily represent those microbes in contact with the host. In this pilot study, we attempt to characterize a novel, minimally invasive method toward sampling the human microbiome using mucosal cytology brush sampling compared to intestinal gut biopsy samples on 5 healthy participants undergoing routine screening colonoscopy. We compared metatranscriptomic analyses between the two collection methods and identified increased taxonomic evenness and beta diversity in the cytology brush samples and similar community transcriptional profiles between the two methods. Metabolomics assessment demonstrated striking differences between the two methods, implying a difference in bacterial-derived versus human-absorbed metabolites. Put together, this study supports the use of microbiome sampling with cytology brushes, but caution must be exercised when performing metabolomics assessment, as this represents differential metabolite production but not absorption by the host. IMPORTANCE In order to generate meaningful metabolomic and microbiome data, the method of sample collection is critical. This study utilizes and compares two methods for intestinal tissue collection for evaluation of metabolites and microbiomes, finding that using a brush to sample the microbiome provides valuable data. However, for metabolomics assessment, biopsy samples may still be required.}, }
@article {pmid35340443, year = {2022}, author = {Schiller, H and Young, C and Schulze, S and Tripepi, M and Pohlschroder, M}, title = {A Twist to the Kirby-Bauer Disk Diffusion Susceptibility Test: an Accessible Laboratory Experiment Comparing Haloferax volcanii and Escherichia coli Antibiotic Susceptibility to Highlight the Unique Cell Biology of Archaea.}, journal = {Journal of microbiology &amp; biology education}, volume = {23}, number = {1}, pages = {}, pmid = {35340443}, issn = {1935-7877}, abstract = {Archaea, once thought to only live in extreme environments, are present in many ecosystems, including the human microbiome, and they play important roles ranging from nutrient cycling to bioremediation. Yet this domain is often overlooked in microbiology classes and rarely included in laboratory exercises. Excluding archaea from high school and undergraduate curricula prevents students from learning the uniqueness and importance of this domain. Here, we have modified a familiar and popular microbiology experiment-the Kirby-Bauer disk diffusion antibiotic susceptibility test-to include, together with the model bacterium Escherichia coli, the model archaeon Haloferax volcanii. Students will learn the differences and similarities between archaea and bacteria by using antibiotics that target, for example, the bacterial peptidoglycan cell wall or the ribosome. Furthermore, the experiment provides a platform to reiterate basic cellular biology concepts that students may have previously discussed. We have developed two versions of this experiment, one designed for an undergraduate laboratory curriculum and the second, limited to H. volcanii, that high school students can perform in their classrooms. This nonpathogenic halophile can be cultured aerobically at ambient temperature in high-salt media, preventing contamination, making the experiment low-cost and safe for use in the high school setting.}, }
@article {pmid35338496, year = {2022}, author = {Palacios-García, I and Mhuireach, GA and Grasso-Cladera, A and Cryan, JF and Parada, FJ}, title = {The 4E approach to the human microbiome: Nested interactions between the gut-brain/body system within natural and built environments.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {44}, number = {6}, pages = {e2100249}, doi = {10.1002/bies.202100249}, pmid = {35338496}, issn = {1521-1878}, mesh = {Brain/physiology ; Built Environment ; Cognition/physiology ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; }, abstract = {The complexity of the human mind and its interaction with the environment is one of the main epistemological debates throughout history. Recent ideas, framed as the 4E perspective to cognition, highlight that human experience depends causally on both cerebral and extracranial processes, but also is embedded in a particular sociomaterial context and is a product of historical accumulation of trajectory changes throughout life. Accordingly, the human microbiome is one of the most intriguing actors modulating brain function and physiology. Here, we present the 4E approach to the Human Microbiome for understanding mental processes from a broader perspective, encompassing one's body physiology and environment throughout their lifespan, interconnected by microbiome community structure and dynamics. We review evidence supporting the approach theoretically and motivates the study of the global set of microbial ecosystem networks encountered by a person across their lifetime (from skin to gut to natural and built environments). We furthermore trace future empirical implementation of the approach. We finally discuss novel research opportunities and clinical interventions aimed toward developing low-cost/high-benefit integrative and personalized bio-psycho-socio-environmental treatments for mental health and including the brain-gut-microbiome axis.}, }
@article {pmid35336128, year = {2022}, author = {Ji, D and Sun, H and Yang, W and Gao, M and Xu, H}, title = {Transfer of Human Microbiome to Drosophila Gut Model.}, journal = {Microorganisms}, volume = {10}, number = {3}, pages = {}, pmid = {35336128}, issn = {2076-2607}, abstract = {Laboratory animals with human microbiome have increasingly been used to study the role of bacteria and host interaction. Drosophila melanogaster, as a model of microbiota-host interaction with high reproductive efficiency and high availability, has always been lacking studies of interaction with human gut microbiome. In this study, we attempted to use antibiotic therapy and human fecal exposure strategy to transfer the human microbiome to the drosophila. The method includes depleting the original intestinal bacteria using a broad-spectrum antibiotic and then introducing human microorganisms by a diet supplemented with donor's fecal samples. The sequencing results showed that 80-87.5% of the OTUs (Operational Taxonomic Units) from donor feces were adopted by the recipient drosophila following 30 days of observation. In comparison to females, the male recipient drosophila inherited more microbiota from the donor feces and had significantly increased lifespan as well as improved vertical climbing ability. Furthermore, distinctly differential expression patterns for age and insulin-like signaling-related genes were obtained for the male vs. female recipients. Only the male drosophila offspring acquired the characteristics of the donor fecal microbiota.}, }
@article {pmid35332832, year = {2022}, author = {Crits-Christoph, A and Hallowell, HA and Koutouvalis, K and Suez, J}, title = {Good microbes, bad genes? The dissemination of antimicrobial resistance in the human microbiome.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2055944}, pmid = {35332832}, issn = {1949-0984}, support = {DP5 OD029603/OD/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Drug Resistance, Bacterial/genetics ; *Gastrointestinal Microbiome/genetics ; Genes, Bacterial ; Humans ; Metagenomics ; *Microbiota/genetics ; }, abstract = {A global rise in antimicrobial resistance among pathogenic bacteria has proved to be a major public health threat, with the rate of multidrug-resistant bacterial infections increasing over time. The gut microbiome has been studied as a reservoir of antibiotic resistance genes (ARGs) that can be transferred to bacterial pathogens via horizontal gene transfer (HGT) of conjugative plasmids and mobile genetic elements (the gut resistome). Advances in metagenomic sequencing have facilitated the identification of resistome modulators, including live microbial therapeutics such as probiotics and fecal microbiome transplantation that can either expand or reduce the abundances of ARG-carrying bacteria in the gut. While many different gut microbes encode for ARGs, they are not uniformly distributed across, or transmitted by, various members of the microbiome, and not all are of equal clinical relevance. Both experimental and theoretical approaches in microbial ecology have been applied to understand differing frequencies of ARG horizontal transfer between commensal microbes as well as between commensals and pathogens. In this commentary, we assess the evidence for the role of commensal gut microbes in encoding antimicrobial resistance genes, the degree to which they are shared both with other commensals and with pathogens, and the host and environmental factors that can impact resistome dynamics. We further discuss novel sequencing-based approaches for identifying ARGs and predicting future transfer events of clinically relevant ARGs from commensals to pathogens.}, }
@article {pmid35330207, year = {2022}, author = {Panthee, B and Gyawali, S and Panthee, P and Techato, K}, title = {Environmental and Human Microbiome for Health.}, journal = {Life (Basel, Switzerland)}, volume = {12}, number = {3}, pages = {}, pmid = {35330207}, issn = {2075-1729}, abstract = {Microorganisms are an essential part of life on the earth and can exist in association with virtually any living thing. The environmental microbiome is much more diverse than the human microbiome. It is reported that most microbes existing in the environment are difficult to culture in the laboratory. Whereas both pathogenic and beneficial microbes may be prevailing in the environment, the human body can have three categories of microbes- beneficial, pathogenic, and opportunistic pathogenic. With at least 10-fold more cells than human cells, microbes as normal flora are critical for human survival. The microbes present in the human body play a crucial role in maintaining human health, and the environmental microbiome influences the human microbiome makeup. The interaction between the environmental and human microbiome highly influences human health, however it is poorly understood. In addition, as an established infection is associated with health-seeking behavior, a large number of studies have focused on the transmission and dynamics of infectious microorganisms than the noninfectious or beneficial ones. This review will summarize how the interaction between the environmental and human microbiome affects human health and identify approaches that might be beneficial for humans to improve health by being exposed to the natural environment.}, }
@article {pmid35324141, year = {2022}, author = {Adelfio, M and Ghezzi, CE}, title = {Long-Term In Vitro Culture Systems to Study Human Microbiome.}, journal = {ACS biomaterials science &amp; engineering}, volume = {8}, number = {11}, pages = {4613-4617}, pmid = {35324141}, issn = {2373-9878}, support = {R03 DE030224/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Dysbiosis ; *Microbiota ; Mammals ; }, abstract = {Microbial communities are eubiotic ecosystems that interact dynamically and synergistically with the human body. Imbalances in these interactions may cause dysbiosis by enhancing the occurrence of inflammatory conditions, such as periodontal or inflammatory bowel diseases. However, the mechanisms that lie behind eubiosis-dysbiosis transitions are still unclear and constantly being redefined. While the societal impact of these diseases is steadily increasing, the lack of a clear understanding behind the onset of the inflammatory conditions prevents the proper clinical strategies from being formulated. Although preclinical and clinical models and short-term planar in vitro cultures represent superb research tools, they are still lacking human relevance and long-term use. Bioreactors and organs-on-a-chip have attracted interest because of their ability to recreate and sustain the physical, structural, and mechanical features of the native environment, as well as to support long-term coculture of mammalian cells and the microbiome through modulation of pH and oxygen gradients. Existing devices, however, are still under development to sustain the microbiome-host coculture over long periods of time. In this scenario, to understand disease triggers and develop therapeutics, research efforts should command the development of three-dimensional constructs that would allow the investigation of processes underlying the microbial community assembly and how microorganisms influence host traits in both acute and chronic conditions.}, }
@article {pmid35321316, year = {2022}, author = {Carmona-Cruz, S and Orozco-Covarrubias, L and Sáez-de-Ocariz, M}, title = {The Human Skin Microbiome in Selected Cutaneous Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {834135}, pmid = {35321316}, issn = {2235-2988}, mesh = {*Alopecia Areata ; *Dermatitis, Atopic ; Humans ; *Microbiota ; *Psoriasis ; Skin ; }, abstract = {The human skin harbors a wide variety of microbes that, together with their genetic information and host interactions, form the human skin microbiome. The role of the human microbiome in the development of various diseases has lately gained interest. According to several studies, changes in the cutaneous microbiota are involved in the pathophysiology of several dermatoses. A better delineation of the human microbiome and its interactions with the innate and adaptive immune systems could lead to a better understanding of these diseases, as well as the opportunity to achieve new therapeutic modalities. The present review centers on the most recent knowledge on skin microbiome and its participation in the pathogenesis of several skin disorders: atopic and seborrheic dermatitis, alopecia areata, psoriasis and acne.}, }
@article {pmid35318071, year = {2022}, author = {Chen, M and Fan, HN and Chen, XY and Yi, YC and Zhang, J and Zhu, JS}, title = {Alterations in the saliva microbiome in patients with gastritis and small bowel inflammation.}, journal = {Microbial pathogenesis}, volume = {165}, number = {}, pages = {105491}, doi = {10.1016/j.micpath.2022.105491}, pmid = {35318071}, issn = {1096-1208}, mesh = {Dysbiosis/microbiology ; *Enteritis ; *Gastritis/microbiology ; Humans ; Inflammation/microbiology ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Saliva/microbiology ; }, abstract = {The oral microbiome is an important part of the human microbiome. Accumulating data have shown that oral microbiome alterations are closely related to multiple human diseases. However, salivary microbiota distributions remain unclear in patients with gastritis and small bowel inflammation. Magnetically guided capsule endoscopy (MGCE) is a noninvasive diagnostic tool for patients with gastritis and small bowel inflammation. Herein, we analysed the alterations in saliva microbiota in the normal, small intestinal inflammation and chronic gastritis groups through 16S rRNA gene amplicon sequencing. We found that the abundance of Lactobacillaceae was dramatically higher in chronic gastritis group than healthy individuals (p = 0.001). The levels of Porphyromonas and Faecalibaculum in gastritis samples were increased (p = 0.028; p = 0.006), and the enrichments of Faecalibaculum and Kosakonia in small intestine inflammation samples were elevated (p < 0.001; p = 0.002) compared to those in normal individuals. Our findings clarify the saliva microbiota components and their importance of specific bacteria in gastritis and small bowel inflammation.}, }
@article {pmid35303139, year = {2022}, author = {Bernabé, BP and Maki, PM and Dowty, SM and Salas, MLC and Shah, Z and Gilbert, JA}, title = {Correction to: Precision medicine in perinatal depression in light of the human microbiome.}, journal = {Psychopharmacology}, volume = {239}, number = {7}, pages = {2367}, doi = {10.1007/s00213-022-06102-y}, pmid = {35303139}, issn = {1432-2072}, }
@article {pmid35302439, year = {2022}, author = {Gehrig, JL and Portik, DM and Driscoll, MD and Jackson, E and Chakraborty, S and Gratalo, D and Ashby, M and Valladares, R}, title = {Finding the right fit: evaluation of short-read and long-read sequencing approaches to maximize the utility of clinical microbiome data.}, journal = {Microbial genomics}, volume = {8}, number = {3}, pages = {}, pmid = {35302439}, issn = {2057-5858}, mesh = {Humans ; Metagenome/genetics ; Metagenomics/methods ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {A long-standing challenge in human microbiome research is achieving the taxonomic and functional resolution needed to generate testable hypotheses about the gut microbiota's impact on health and disease. With a growing number of live microbial interventions in clinical development, this challenge is renewed by a need to understand the pharmacokinetics and pharmacodynamics of therapeutic candidates. While short-read sequencing of the bacterial 16S rRNA gene has been the standard for microbiota profiling, recent improvements in the fidelity of long-read sequencing underscores the need for a re-evaluation of the value of distinct microbiome-sequencing approaches. We leveraged samples from participants enrolled in a phase 1b clinical trial of a novel live biotherapeutic product to perform a comparative analysis of short-read and long-read amplicon and metagenomic sequencing approaches to assess their utility for generating clinical microbiome data. Across all methods, overall community taxonomic profiles were comparable and relationships between samples were conserved. Comparison of ubiquitous short-read 16S rRNA amplicon profiling to long-read profiling of the 16S-ITS-23S rRNA amplicon showed that only the latter provided strain-level community resolution and insight into novel taxa. All methods identified an active ingredient strain in treated study participants, though detection confidence was higher for long-read methods. Read coverage from both metagenomic methods provided evidence of active-ingredient strain replication in some treated participants. Compared to short-read metagenomics, approximately twice the proportion of long reads were assigned functional annotations. Finally, compositionally similar bacterial metagenome-assembled genomes (MAGs) were recovered from short-read and long-read metagenomic methods, although a greater number and more complete MAGs were recovered from long reads. Despite higher costs, both amplicon and metagenomic long-read approaches yielded added microbiome data value in the form of higher confidence taxonomic and functional resolution and improved recovery of microbial genomes compared to traditional short-read methodologies.}, }
@article {pmid35301310, year = {2022}, author = {Forster, SC and Liu, J and Kumar, N and Gulliver, EL and Gould, JA and Escobar-Zepeda, A and Mkandawire, T and Pike, LJ and Shao, Y and Stares, MD and Browne, HP and Neville, BA and Lawley, TD}, title = {Strain-level characterization of broad host range mobile genetic elements transferring antibiotic resistance from the human microbiome.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {1445}, pmid = {35301310}, issn = {2041-1723}, support = {/WT_/Wellcome Trust/United Kingdom ; 206194/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/genetics ; Drug Resistance, Microbial/genetics ; Genes, Bacterial ; *Host Specificity/genetics ; Humans ; Interspersed Repetitive Sequences/genetics ; *Microbiota/genetics ; }, abstract = {Mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) disseminate ARGs when they mobilise into new bacterial hosts. The nature of such horizontal gene transfer (HGT) events between human gut commensals and pathogens remain poorly characterised. Here, we compare 1354 cultured commensal strains (540 species) to 45,403 pathogen strains (12 species) and find 64,188 MGE-mediated ARG transfer events between the two groups using established methods. Among the 5931 MGEs, we find 15 broad host range elements predicted to have crossed different bacterial phyla while also occurring in animal and environmental microbiomes. We experimentally demonstrate that predicted broad host range MGEs can mobilise from commensals Dorea longicatena and Hungatella hathewayi to pathogen Klebsiella oxytoca, crossing phyla simultaneously. Our work establishes the MGE-mediated ARG dissemination network between human gut commensals and pathogens and highlights broad host range MGEs as targets for future ARG dissemination management.}, }
@article {pmid35295290, year = {2022}, author = {Zioutis, C and Seki, D and Bauchinger, F and Herbold, C and Berger, A and Wisgrill, L and Berry, D}, title = {Ecological Processes Shaping Microbiomes of Extremely Low Birthweight Infants.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {812136}, pmid = {35295290}, issn = {1664-302X}, support = {DOC 69/FWF_/Austrian Science Fund FWF/Austria ; P 27831/FWF_/Austrian Science Fund FWF/Austria ; }, abstract = {The human microbiome has been implicated in affecting health outcomes in premature infants, but the ecological processes governing early life microbiome assembly remain poorly understood. Here, we investigated microbial community assembly and dynamics in extremely low birth weight infants (ELBWI) over the first 2 weeks of life. We profiled the gut, oral cavity and skin microbiomes over time using 16S rRNA gene amplicon sequencing and evaluated the ecological forces shaping these microbiomes. Though microbiomes at all three body sites were characterized by compositional instability over time and had low body-site specificity (PERMANOVA, r [2] = 0.09, p = 0.001), they could nonetheless be clustered into four discrete community states. Despite the volatility of these communities, deterministic assembly processes were detectable in this period of initial microbial colonization. To further explore these deterministic dynamics, we developed a probabilistic approach in which we modeled microbiome state transitions in each ELBWI as a Markov process, or a "memoryless" shift, from one community state to another. This analysis revealed that microbiomes from different body sites had distinctive dynamics as well as characteristic equilibrium frequencies. Time-resolved microbiome sampling of premature infants may help to refine and inform clinical practices. Additionally, this work provides an analysis framework for microbial community dynamics based on Markov modeling that can facilitate new insights, not only into neonatal microbiomes but also other human-associated or environmental microbiomes.}, }
@article {pmid35288482, year = {2021}, author = {Launonen, H and Pang, Z and Linden, J and Siltari, A and Korpela, R and Vapaatalo, H}, title = {Evidence for local aldosterone synthesis in the large intestine of the mouse.}, journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society}, volume = {72}, number = {5}, pages = {}, doi = {10.26402/jpp.2021.5.15}, pmid = {35288482}, issn = {1899-1505}, mesh = {*Adrenal Cortex/metabolism ; *Aldosterone/biosynthesis ; Animals ; *Colon/metabolism ; *Cytochrome P-450 CYP11B2/genetics/metabolism ; Male ; Mice ; Sodium/metabolism ; }, abstract = {Aldosterone, the main physiological mineralocorticoid, regulates sodium and potassium balance in the distal convoluted tubule of the kidney. Aldosterone is synthesized from cholesterol in the adrenal cortex in a sequence of enzymatic steps. Recently however, several tissues or cells e.g. brain, heart, blood vessels, kidneys and adipocytes have been shown to possess capability to produce aldosterone locally, and there is some evidence that this occurs also in the intestine. Colon expresses mineralocorticoid receptors and is capable of synthesizing corticosterone, the second last intermediate on the route to aldosterone from cholesterol. Based on such reports and on our preliminary finding, we hypothesized that aldosterone could be synthesized locally in the intestine and therefore we measured the concentration of aldosterone as well as the protein and gene expression of aldosterone synthase (CYP11B2), an enzyme responsible on aldosterone synthesis, from the distal section of the gastrointestinal tract of 10-week-old Balb/c male mice. It is known that sodium deficiency regulates aldosterone synthesis in adrenal glands, therefore we fed the mice with low (0.01%), normal (0.2%) and high-sodium (1.6%) diets for 14 days. Here we report that, aldosterone was detected in colon and cecum samples. Measurable amounts of CYP11B2 protein were detected by Western blot and Elisa analysis from both intestinal tissues. We detected CYP11B2 gene expression from the large intestine along with immunohistochemical findings of CYP11B2 in colonic wall. Sodium depletion increased the aldosterone concentration in plasma compared to control and high-sodium groups as well as in the intestine compared to mice fed with the high-sodium diet. To summarize, this study further supports the presence of aldosterone and the enzyme needed to produce this mineralocorticoid in the murine large intestine.}, }
@article {pmid35278679, year = {2022}, author = {Wani, AK and Roy, P and Kumar, V and Mir, TUG}, title = {Metagenomics and artificial intelligence in the context of human health.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {100}, number = {}, pages = {105267}, doi = {10.1016/j.meegid.2022.105267}, pmid = {35278679}, issn = {1567-7257}, mesh = {Artificial Intelligence ; DNA ; Humans ; *Metagenomics/methods ; *Microbiota/genetics ; Sequence Analysis, DNA ; }, abstract = {Human microbiome is ubiquitous, dynamic, and site-specific consortia of microbial communities. The pathogenic nature of microorganisms within human tissues has led to an increase in microbial studies. Characterization of genera, like Streptococcus, Cutibacterium, Staphylococcus, Bifidobacterium, Lactococcus and Lactobacillus through culture-dependent and culture-independent techniques has been reported. However, due to the unique environment within human tissues, it is difficult to culture these microorganisms making their molecular studies strenuous. MGs offer a gateway to explore and characterize hidden microbial communities through a culture-independent mode by direct DNA isolation. By function and sequence-based MGs, Scientists can explore the mechanistic details of numerous microbes and their interaction with the niche. Since the data generated from MGs studies is highly complex and multi-dimensional, it requires accurate analytical tools to evaluate and interpret the data. Artificial intelligence (AI) provides the luxury to automatically learn the data dimensionality and ease its complexity that makes the disease diagnosis and disease response easy, accurate and timely. This review provides insight into the human microbiota and its exploration and expansion through MG studies. The review elucidates the significance of MGs in studying the changing microbiota during disease conditions besides highlighting the role of AI in computational analysis of MG data.}, }
@article {pmid35273169, year = {2022}, author = {Cai, YY and Huang, FQ and Lao, X and Lu, Y and Gao, X and Alolga, RN and Yin, K and Zhou, X and Wang, Y and Liu, B and Shang, J and Qi, LW and Li, J}, title = {Integrated metagenomics identifies a crucial role for trimethylamine-producing Lachnoclostridium in promoting atherosclerosis.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {11}, pmid = {35273169}, issn = {2055-5008}, mesh = {Animals ; *Atherosclerosis ; Choline ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Methylamines ; Mice ; }, abstract = {Microbial trimethylamine (TMA)-lyase activity promotes the development of atherosclerosis by generating of TMA, the precursor of TMA N-oxide (TMAO). TMAO is well documented, but same can not be said of TMA-producing bacteria. This work aimed to identify TMA-producing genera in human intestinal microbiota. We retrieved the genomes of human-associated microorganisms from the Human Microbiome Project database comprising 1751 genomes, Unified Human Gastrointestinal Genome collection consisting 4644 gut prokaryotes, recapitulated 4930 species-level genome bins and public gut metagenomic data of 2134 individuals from 11 populations. By sequence searching, 216 TMA-lyase-containing species from 102 genera were found to contain the homologous sequences of cntA/B, yeaW/X, and/or cutC/D. We identified 13 strains from 5 genera with cntA sequences, and 30 strains from 14 genera with cutC showing detectable relative abundance in healthy individuals. Lachnoclostridium (p = 2.9e-05) and Clostridium (p = 5.8e-04), the two most abundant cutC-containing genera, were found to be much higher in atherosclerotic patients compared with healthy persons. Upon incubation with choline (substrate), L. saccharolyticum effectively transformed it to TMA at a rate higher than 98.7% while that for C. sporogenes was 63.8-67.5% as detected by liquid chromatography-triple quadrupole mass spectrometry. In vivo studies further showed that treatment of L. saccharolyticum and choline promoted a significant increase in TMAO level in the serum of ApoE[-/-] mice with obvious accumulation of aortic plaque in same. This study discloses the significance and efficiency of the gut bacterium L. saccharolyticum in transforming choline to TMA and consequently promoting the development of atherosclerosis.}, }
@article {pmid35272051, year = {2022}, author = {Zhou, F and Gan, R and Zhang, F and Ren, C and Yu, L and Si, Y and Huang, Z}, title = {PHISDetector: A Tool to Detect Diverse In Silico Phage-host Interaction Signals for Virome Studies.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {20}, number = {3}, pages = {508-523}, pmid = {35272051}, issn = {2210-3244}, mesh = {Humans ; *Bacteriophages/genetics ; Virome ; Prophages/genetics ; Bacteria/genetics ; *Microbiota ; }, abstract = {Phage-microbe interactions are appealing systems to study coevolution, and have also been increasingly emphasized due to their roles in human health, disease, and the development of novel therapeutics. Phage-microbe interactions leave diverse signals in bacterial and phage genomic sequences, defined as phage-host interaction signals (PHISs), which include clustered regularly interspaced short palindromic repeats (CRISPR) targeting, prophage, and protein-protein interaction signals. In the present study, we developed a novel tool phage-host interaction signal detector (PHISDetector) to predict phage-host interactions by detecting and integrating diverse in silico PHISs, and scoring the probability of phage-host interactions using machine learning models based on PHIS features. We evaluated the performance of PHISDetector on multiple benchmark datasets and application cases. When tested on a dataset of 758 annotated phage-host pairs, PHISDetector yields the prediction accuracies of 0.51 and 0.73 at the species and genus levels, respectively, outperforming other phage-host prediction tools. When applied to on 125,842 metagenomic viral contigs (mVCs) derived from 3042 geographically diverse samples, a detection rate of 54.54% could be achieved. Furthermore, PHISDetector could predict infecting phages for 85.6% of 368 multidrug-resistant (MDR) bacteria and 30% of 454 human gut bacteria obtained from the National Institutes of Health (NIH) Human Microbiome Project (HMP). The PHISDetector can be run either as a web server (http://www.microbiome-bigdata.com/PHISDetector/) for general users to study individual inputs or as a stand-alone version (https://github.com/HIT-ImmunologyLab/PHISDetector) to process massive phage contigs from virome studies.}, }
@article {pmid35271353, year = {2022}, author = {Fobofou, SA and Savidge, T}, title = {Microbial metabolites: cause or consequence in gastrointestinal disease?.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {322}, number = {6}, pages = {G535-G552}, pmid = {35271353}, issn = {1522-1547}, support = {R01 NR013497/NR/NINR NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 DK130517/DK/NIDDK NIH HHS/United States ; P01 AI152999/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {*COVID-19 ; Dysbiosis/microbiology ; *Gastrointestinal Diseases ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancer, metabolic disorders, and opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiological host-microbiome interactions. Generally, to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles, and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short-chain fatty acids, polysaccharides, and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthesized by microbial biosynthetic gene clusters, including ribosomally synthesized and posttranslationally modified peptides (RiPPs), nonribosomal peptides (NRPs), polyketides (PKs), PK-NRP hybrids, and terpenes. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.}, }
@article {pmid35266930, year = {2022}, author = {Kynkäänniemi, E and Lahtinen, MH and Jian, C and Salonen, A and Hatanpää, T and Mikkonen, KS and Pajari, AM}, title = {Gut microbiota can utilize prebiotic birch glucuronoxylan in production of short-chain fatty acids in rats.}, journal = {Food &amp; function}, volume = {13}, number = {6}, pages = {3746-3759}, doi = {10.1039/d1fo03922a}, pmid = {35266930}, issn = {2042-650X}, mesh = {Animals ; Betula/metabolism ; Fatty Acids, Volatile/metabolism ; Female ; *Gastrointestinal Microbiome ; Male ; Prebiotics ; Rats ; Rats, Wistar ; Xylans ; }, abstract = {Birch-derived glucuronoxylan (GX)-rich hemicellulose extract is an abundantly available by-product of the forest industry. It has multifunctional food stabilizing properties, and is rich in fiber and polyphenols. Here, we studied its effects on colonic metabolism and gut microbiota in healthy rats. Male and female Wistar rats (n = 42) were fed AIN-93G-based diets with 10% (w/w) of either cellulose (control), a polyphenol and GX-rich extract (GXpoly), or a highly purified GX-rich extract (pureGX) for four weeks. Both the GXpoly and pureGX diets resulted in changes on the gut microbiota, especially in a higher abundance of Bifidobacteriaceae than the cellulose containing diet (p < 0.001). This coincided with higher concentrations of microbial metabolites in the luminal contents of the GX-fed than control rats, such as total short-chain fatty acids (SCFAs) (p < 0.001), acetate (p < 0.001), and N-nitroso compounds (NOCs) (p = 0.001). The difference in the concentration of NOCs was not seen when adjusted with fecal weight. GX supplementation supported the normal growth of the rats. Our results indicate that GXpoly and pureGX can favorably affect colonic metabolism and the gut microbiota. They have high potential to be used as prebiotic stabilizers to support more ecologically sustainable food production.}, }
@article {pmid35264784, year = {2022}, author = {Blaak, EE and de Vos, WM}, title = {Author Correction: Before the heart attack.}, journal = {Nature medicine}, volume = {28}, number = {4}, pages = {871}, doi = {10.1038/s41591-022-01764-9}, pmid = {35264784}, issn = {1546-170X}, }
@article {pmid35259160, year = {2022}, author = {Kieser, S and Zdobnov, EM and Trajkovski, M}, title = {Comprehensive mouse microbiota genome catalog reveals major difference to its human counterpart.}, journal = {PLoS computational biology}, volume = {18}, number = {3}, pages = {e1009947}, pmid = {35259160}, issn = {1553-7358}, mesh = {Animals ; Bacteria/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome/genetics ; Metagenomics ; Mice ; *Microbiota/genetics ; Phylogeny ; }, abstract = {Mouse is the most used model for studying the impact of microbiota on its host, but the repertoire of species from the mouse gut microbiome remains largely unknown. Accordingly, the similarity between human and mouse microbiomes at a low taxonomic level is not clear. We construct a comprehensive mouse microbiota genome (CMMG) catalog by assembling all currently available mouse gut metagenomes and combining them with published reference and metagenome-assembled genomes. The 41'798 genomes cluster into 1'573 species, of which 78.1% are uncultured, and we discovered 226 new genera, seven new families, and one new order. CMMG enables an unprecedented coverage of the mouse gut microbiome exceeding 86%, increases the mapping rate over four-fold, and allows functional microbiota analyses of human and mouse linking them to the driver species. Comparing CMMG to microbiota from the unified human gastrointestinal genomes shows an overlap of 62% at the genus but only 10% at the species level, demonstrating that human and mouse gut microbiota are largely distinct. CMMG contains the most comprehensive collection of consistently functionally annotated species of the mouse and human microbiome to date, setting the ground for analysis of new and reanalysis of existing datasets at an unprecedented depth.}, }
@article {pmid35258340, year = {2022}, author = {Modha, S and Robertson, DL and Hughes, J and Orton, RJ}, title = {Quantifying and Cataloguing Unknown Sequences within Human Microbiomes.}, journal = {mSystems}, volume = {7}, number = {2}, pages = {e0146821}, pmid = {35258340}, issn = {2379-5077}, support = {MC_UU_12014/12/MRC_/Medical Research Council/United Kingdom ; MR/S502479/1//UKRI | Medical Research Council (MRC)/ ; MC_UU_1201412//UKRI | Medical Research Council (MRC)/ ; }, mesh = {Animals ; Humans ; *Ursidae/genetics ; *Microbiota/genetics ; Metagenome ; Metagenomics ; Databases, Factual ; }, abstract = {Advances in genome sequencing technologies and lower costs have enabled the exploration of a multitude of known and novel environments and microbiomes. This has led to an exponential growth in the raw sequence data that are deposited in online repositories. Metagenomic and metatranscriptomic data sets are typically analysed with regard to a specific biological question. However, it is widely acknowledged that these data sets are comprised of a proportion of sequences that bear no similarity to any currently known biological sequence, and this so-called "dark matter" is often excluded from downstream analyses. In this study, a systematic framework was developed to assemble, identify, and measure the proportion of unknown sequences present in distinct human microbiomes. This framework was applied to 40 distinct studies, comprising 963 samples, and covering 10 different human microbiomes including fecal, oral, lung, skin, and circulatory system microbiomes. We found that while the human microbiome is one of the most extensively studied, on average 2% of assembled sequences have not yet been taxonomically defined. However, this proportion varied extensively among different microbiomes and was as high as 25% for skin and oral microbiomes that have more interactions with the environment. A rate of taxonomic characterization of 1.64% of unknown sequences being characterized per month was calculated from these taxonomically unknown sequences discovered in this study. A cross-study comparison led to the identification of similar unknown sequences in different samples and/or microbiomes. Both our computational framework and the novel unknown sequences produced are publicly available for future cross-referencing. Our approach led to the discovery of several novel viral genomes that bear no similarity to sequences in the public databases. Some of these are widespread as they have been found in different microbiomes and studies. Hence, our study illustrates how the systematic characterization of unknown sequences can help the discovery of novel microbes, and we call on the research community to systematically collate and share the unknown sequences from metagenomic studies to increase the rate at which the unknown sequence space can be classified.}, }
@article {pmid35254118, year = {2022}, author = {Hao, Z and Zhu, Y and Fu, Y and Yang, J and Meng, C and Dong, C and Liu, H}, title = {Effects of Long-Term Enclosed Environment on Human Health Based on the Analysis of Salivary Microbiota and Cytokines.}, journal = {Microbiology spectrum}, volume = {10}, number = {2}, pages = {e0025422}, pmid = {35254118}, issn = {2165-0497}, mesh = {Cytokines ; Humans ; Life Support Systems ; *Microbiota ; Saliva ; *Space Flight ; }, abstract = {The long-term exposure to enclosed environments may lead to chronic stress in crewmembers and affect their physical and mental state. Salivary microbiome and biomarkers of immune function are increasingly used in human health research. The "Lunar Palace 365" project, which was a 370-day, multicrew, enclosed experiment carried out in a ground-based bioregenerative life support system platform named Lunar Palace 1 (LP1). We investigated the temporal dynamics of the salivary microbiota and cytokines in the third phase of the "Lunar Palace 365" experiment, including 1 month before entering LP1 and 1 month after leaving Lp1. Results reveal no regular temporal change pattern in these parameters (highly abundant phyla and genera) during the experiment. Although the crewmembers' oral microbiota temporally changed, it recovered quickly after the study subjects left the enclosed environment. The levels of IL-6, IL-10, and TNF-α in crewmembers' saliva decreased after leaving the normal environment for the enclosed environment, indicating that their oral inflammatory response level was reduced. There were significant individual differences in crewmembers' salivary microbiota, however, the shared living space reduced these differences. Moreover, air microbiota might have also played a significant role in reducing the individual differences. In summary, the enclosed environment did not result in persistent changes in human salivary microbiota and oral immunity. This study provides some insights for studying the effect of enclosed controlled environments on human immunity and microbiome. IMPORTANCE Long-term exposure to space environments may influence the human microbiome, the human immune system, and the intricate balance between the two, causing impaired immunity and increased disease susceptibility. It was previously believed that the main potential factors of long-term spaceflight on human health were microgravity and radiation. However, the effects of long-term enclosed environments on human health were unclear. Bioregenerative life support systems (BLSS) is a good experimental model for studying the effects of enclosed environments on human systemic microbiota and immune disorders. We monitored the microbiota and cytokines in the saliva of crewmembers before they entered BLSS, during their stay in BLSS, and after leaving BLSS. The results indicated long-term closed environment will not cause persistent changes in human salivary microbiota and immunity.}, }
@article {pmid35253754, year = {2022}, author = {Kalecký, K and German, DC and Montillo, AA and Bottiglieri, T}, title = {Targeted Metabolomic Analysis in Alzheimer's Disease Plasma and Brain Tissue in Non-Hispanic Whites.}, journal = {Journal of Alzheimer's disease : JAD}, volume = {86}, number = {4}, pages = {1875-1895}, pmid = {35253754}, issn = {1875-8908}, support = {P30 AG019610/AG/NIA NIH HHS/United States ; }, mesh = {*Alzheimer Disease/metabolism ; Brain/metabolism ; Case-Control Studies ; Female ; Humans ; Metabolome ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Metabolites are biological compounds reflecting the functional activity of organs and tissues. Understanding metabolic changes in Alzheimer's disease (AD) can provide insight into potential risk factors in this multifactorial disease and suggest new intervention strategies or improve non-invasive diagnosis.<br><br>OBJECTIVE: In this study, we searched for changes in AD metabolism in plasma and frontal brain cortex tissue samples and evaluated the performance of plasma measurements as biomarkers.<br><br>METHODS: This is a case-control study with two tissue cohorts: 158 plasma samples (94 AD, 64 controls; Texas Alzheimer's Research and Care Consortium - TARCC) and 71 postmortem cortex samples (35 AD, 36 controls; Banner Sun Health Research Institute brain bank). We performed targeted mass spectrometry analysis of 630 compounds (106 small molecules: UHPLC-MS/MS, 524 lipids: FIA-MS/MS) and 232 calculated metabolic indicators with a metabolomic kit (Biocrates MxP&#xae; Quant 500).<br><br>RESULTS: We discovered disturbances (FDR&#x2264;0.05) in multiple metabolic pathways in AD in both cohorts including microbiome-related metabolites with pro-toxic changes, methylhistidine metabolism, polyamines, corticosteroids, omega-3 fatty acids, acylcarnitines, ceramides, and diglycerides. In AD, plasma reveals elevated triglycerides, and cortex shows altered amino acid metabolism. A cross-validated diagnostic prediction model from plasma achieves AUC&#x200a;=&#x200a;82% (CI95&#x200a;=&#x200a;75-88%); for females specifically, AUC&#x200a;=&#x200a;88% (CI95&#x200a;=&#x200a;80-95%). A reduced model using 20 features achieves AUC&#x200a;=&#x200a;79% (CI95&#x200a;=&#x200a;71-85%); for females AUC&#x200a;=&#x200a;84% (CI95&#x200a;=&#x200a;74-92%).<br><br>CONCLUSION: Our findings support the involvement of gut environment in AD and encourage targeting multiple metabolic areas in the design of intervention strategies, including microbiome composition, hormonal balance, nutrients, and muscle homeostasis.}, }
@article {pmid35249149, year = {2022}, author = {Rietjens, IMCM and Michael, A and Bolt, HM and Siméon, B and Andrea, H and Nils, H and Christine, K and Angela, M and Gloria, P and Daniel, R and Natalie, T and Gerhard, E}, title = {The role of endogenous versus exogenous sources in the exposome of putative genotoxins and consequences for risk assessment.}, journal = {Archives of toxicology}, volume = {96}, number = {5}, pages = {1297-1352}, pmid = {35249149}, issn = {1432-0738}, mesh = {Acrolein ; *Exposome ; Formaldehyde ; Humans ; Mutagens/toxicity ; Risk Assessment ; }, abstract = {The "totality" of the human exposure is conceived to encompass life-associated endogenous and exogenous aggregate exposures. Process-related contaminants (PRCs) are not only formed in foods by heat processing, but also occur endogenously in the organism as physiological components of energy metabolism, potentially also generated by the human microbiome. To arrive at a comprehensive risk assessment, it is necessary to understand the contribution of in vivo background occurrence as compared to the ingestion from exogenous sources. Hence, this review provides an overview of the knowledge on the contribution of endogenous exposure to the overall exposure to putative genotoxic food contaminants, namely ethanol, acetaldehyde, formaldehyde, acrylamide, acrolein, α,β-unsaturated alkenals, glycation compounds, N-nitroso compounds, ethylene oxide, furans, 2- and 3-MCPD, and glycidyl esters. The evidence discussed herein allows to conclude that endogenous formation of some contaminants appears to contribute substantially to the exposome. This is of critical importance for risk assessment in the cases where endogenous exposure is suspected to outweigh the exogenous one (e.g. formaldehyde and acrolein).}, }
@article {pmid35242744, year = {2022}, author = {Wodzanowski, KA and Caplan, JL and Kloxin, AM and Grimes, CL}, title = {Multiscale Invasion Assay for Probing Macrophage Response to Gram-Negative Bacteria.}, journal = {Frontiers in chemistry}, volume = {10}, number = {}, pages = {842602}, pmid = {35242744}, issn = {2296-2646}, support = {DP2 HL152424/HL/NHLBI NIH HHS/United States ; P20 GM103446/GM/NIGMS NIH HHS/United States ; P20 GM104316/GM/NIGMS NIH HHS/United States ; P30 GM110758/GM/NIGMS NIH HHS/United States ; }, abstract = {The immune system is a complex network of various cellular components that must differentiate between pathogenic bacteria and the commensal bacteria of the human microbiome, where misrecognition is linked to inflammatory disorders. Fragments of bacterial cell wall peptidoglycan bind to pattern recognition receptors within macrophages, leading to immune activation. To study this complex process, a methodology to remodel and label the bacterial cell wall of two different species of bacteria was established using copper (I) catalyzed azide-alkyne cycloaddition (CuAAC) and strain-promoted azide-alkyne cycloaddition (SPAAC). Additionally, an approach for three-dimensional (3D) culture of human macrophages and their invasion with relevant bacteria in a well-defined hydrogel-based synthetic matrix inspired by the microenvironment of the gut was established. Workflows were developed for human monocyte encapsulation and differentiation into macrophages in 3D culture with high viability. Bacteria invaded into macrophages permitted in situ peptidoglycan labeling. Macrophages exhibited biologically-relevant cytokine release in response to bacteria. This molecularly engineered, multi-dimensional bacteria-macrophage co-culture system will prove useful in future studies to observe immunostimulatory, bacterial fragment production and localization in the cell at the carbohydrate level for insights into how the immune system properly senses bacteria.}, }
@article {pmid35242322, year = {2022}, author = {Sammoni, A and Abdalah, A and Al-Aissami, M}, title = {Comamonas testosteroni bacteremia: A rare unusual pathogen detected in a burned patient: Case report and literature review.}, journal = {Annals of medicine and surgery (2012)}, volume = {75}, number = {}, pages = {103371}, pmid = {35242322}, issn = {2049-0801}, abstract = {INTRODUCTION AND IMPORTANCE: Comamonas testosteroni is a rare human pathogen that is not part of the human microbiome. There are only 51 cases reported worldwide with 7 cases resulted in death.<br><br>CASE PRESENTATION: We report a case of a 16-year-old boy with an extended burn complicated by catheter-related bloodstream C. testosteroni infection.<br><br>CLINICAL DISCUSSION: Comamonas species are usually community-acquired pathogens that are susceptible to a wide variety of antibiotics including aminoglycosides, fluoroquinolones, carbapenems, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and cephalosporins. However, in our case, we reported a nosocomial multidrug-resistant infection by C. testosteroni that responded only to colistin.<br><br>CONCLUSION: Reporting unusual cases of nosocomial sepsis due to rare multidrug-resistant pathogens is detrimental. As it sheds light on how virulent nosocomial infections are becoming, and can be very alarming to other practitioners and clinical microbiologists, in order to achieve a better awareness of the importance of controlled antibiotics use.}, }
@article {pmid35236930, year = {2022}, author = {Hofer, U}, title = {Skewed representation in human microbiome data.}, journal = {Nature reviews. Microbiology}, volume = {20}, number = {5}, pages = {253}, pmid = {35236930}, issn = {1740-1534}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid35234907, year = {2022}, author = {Kajova, M and Khawaja, T and Kantele, A}, title = {European hospitals as source of multidrug-resistant bacteria: analysis of travellers screened in Finland after hospitalization abroad.}, journal = {Journal of travel medicine}, volume = {29}, number = {4}, pages = {}, pmid = {35234907}, issn = {1708-8305}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria ; Drug Resistance, Multiple, Bacterial ; Escherichia coli ; Finland/epidemiology ; Hospitalization ; Hospitals ; Humans ; *Methicillin-Resistant Staphylococcus aureus ; Prevalence ; *Vancomycin-Resistant Enterococci ; }, abstract = {BACKGROUND: As hospitals have a high prevalence of multidrug-resistant organisms (MDRO), hospitalization abroad indicates for travellers an increased risk of acquiring MDRO-and carrying the strains home. Antimicrobial resistance (AMR) rates are highest in the (sub)tropics, whereas Europe is considered a lower risk region. Since AMR prevalences vary within Europe, we aimed to gather country-specific data on the risks for hospitalized travellers.<br><br>METHODS: At hospitals of the Helsinki and Uusimaa district in Finland, patients hospitalized abroad over the past 12&#xa0;months are systematically screened for methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-PE), carbapenemase-producing bacteria and vancomycin-resistant Enterococcus spp. (VRE). Among patients screened 2010-19, we selected those hospitalized in Europe, recorded their MDRO findings, infections and mortality, and analysed MDRO-associated risk factors.<br><br>RESULTS: Of the 1772 patients treated in 41 European countries, 16.6% (295) carried MDRO, 12.5% (221) ESBL-PE, 7.8% (138) solely ESBL-E. coli, 2.6% (46) MRSA, 2.2% (30) of those screened VRE and 2.2% (39) carbapenem-resistant Gram-negatives. Among those colonized, 9.8% (29) had symptomatic MDRO infections and 0.3% (one) died. Colonization was most frequently recorded for those treated in eastern and southern Europe, with Bulgaria, Cyprus and the Russian Federation scoring highest. MDRO colonization was associated with antibiotic treatment and showed a negative correlation with time from discharge to screening.<br><br>CONCLUSIONS: After hospitalization in European countries, ESBL-PE carriage was relatively common (12.5%), while other MDROs proved less frequent (<5%). Antibiotic treatment and short time since hospitalization abroad increased the risk of MDRO colonization. Clear differences between countries and regions were revealed, with highest rates in the east and the south.}, }
@article {pmid35234490, year = {2022}, author = {Tourlousse, DM and Narita, K and Miura, T and Ohashi, A and Matsuda, M and Ohyama, Y and Shimamura, M and Furukawa, M and Kasahara, K and Kameyama, K and Saito, S and Goto, M and Shimizu, R and Mishima, R and Nakayama, J and Hosomi, K and Kunisawa, J and Terauchi, J and Sekiguchi, Y and Kawasaki, H}, title = {Characterization and Demonstration of Mock Communities as Control Reagents for Accurate Human Microbiome Community Measurements.}, journal = {Microbiology spectrum}, volume = {10}, number = {2}, pages = {e0191521}, pmid = {35234490}, issn = {2165-0497}, mesh = {DNA ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Indicators and Reagents ; Metagenomics/methods ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Sequence Analysis, DNA/methods ; }, abstract = {Standardization and quality assurance of microbiome community analysis by high-throughput DNA sequencing require widely accessible and well-characterized reference materials. Here, we report on newly developed DNA and whole-cell mock communities to serve as control reagents for human gut microbiota measurements by shotgun metagenomics and 16S rRNA gene amplicon sequencing. The mock communities were formulated as near-even blends of up to 20 bacterial species prevalent in the human gut, span a wide range of genomic guanine-cytosine (GC) contents, and include multiple strains with Gram-positive type cell walls. Through a collaborative study, we carefully characterized the mock communities by shotgun metagenomics, using previously developed standardized protocols for DNA extraction and sequencing library construction. Further, we validated fitness of the mock communities for revealing technically meaningful differences among protocols for DNA extraction and metagenome/16S rRNA gene amplicon library construction. Finally, we used the mock communities to reveal varying performance of metagenome-based taxonomic profilers and the impact of trimming and filtering of sequencing reads on observed species profiles. The latter showed that aggressive preprocessing of reads may result in substantial GC-dependent bias and should thus be carefully evaluated to minimize unintended effects on species abundances. Taken together, the mock communities are expected to support a myriad of applications that rely on well-characterized control reagents, ranging from evaluation and optimization of methods to assessment of reproducibility in interlaboratory studies and routine quality control. IMPORTANCE Application of high-throughput DNA sequencing has greatly accelerated human microbiome research and its translation into new therapeutic and diagnostic capabilities. Microbiome community analyses results can, however, vary considerably across studies or laboratories, and establishment of measurement standards to improve accuracy and reproducibility has become a priority. The here-developed mock communities, which are available from the NITE Biological Resource Center (NBRC) at the National Institute of Technology and Evaluation (NITE, Japan), provide well-characterized control reagents that allow users to judge the accuracy of their measurement results. Widespread and consistent adoption of the mock communities will improve reproducibility and comparability of microbiome community analyses, thereby supporting and accelerating human microbiome research and development.}, }
@article {pmid37462964, year = {2022}, author = {Kong, XB and Dong, ZL and Wang, ZP}, title = {[Human microbiome and chronic prostatitis / chronic pelvic pain syndrome: An update].}, journal = {Zhonghua nan ke xue = National journal of andrology}, volume = {28}, number = {3}, pages = {243-246}, pmid = {37462964}, issn = {1009-3591}, mesh = {Male ; Humans ; Chronic Disease ; *Prostatitis ; Pelvic Pain ; *Microbiota ; *Chronic Pain ; }, abstract = {The significance of symbiotic microorganisms in the human body was recognized with the advancing of the concept of human microbiome and the development of related studies and technologies. These microorganisms play important roles in metabolism, immune regulation, the maintenance of health, and the development and progression of diseases in the human body. Recent studies show that chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is related with human microbiome, mainly involving the urogenital tract, intestinal canal, and oral cavity. This review summarizes the studies on the relationship between the human microbiome and CP/CPPS in recent years.}, }
@article {pmid35222791, year = {2022}, author = {Beghelli, D and Zallocco, L and Barbalace, MC and Paglia, S and Strocchi, S and Cirilli, I and Marzano, V and Putignani, L and Lupidi, G and Hrelia, S and Giusti, L and Angeloni, C}, title = {Pterostilbene Promotes Mean Lifespan in Both Male and Female Drosophila Melanogaster Modulating Different Proteins in the Two Sexes.}, journal = {Oxidative medicine and cellular longevity}, volume = {2022}, number = {}, pages = {1744408}, pmid = {35222791}, issn = {1942-0994}, mesh = {Animals ; Anti-Inflammatory Agents/metabolism ; Antioxidants/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster ; Female ; Longevity/*drug effects/genetics ; Male ; Oxidative Stress/drug effects ; Proteome/drug effects/metabolism ; Sex Factors ; Stilbenes/*pharmacology ; }, abstract = {Aging is a multifactorial phenomenon characterized by degenerative processes closely connected to oxidative damage and chronic inflammation. Recently, many studies have shown that natural bioactive compounds are useful in delaying the aging process. In this work, we studied the effects of an in vivo supplementation of the stilbenoid pterostilbene on lifespan extension in Drosophila melanogaster. We found that the average lifespan of flies of both sexes was increased by pterostilbene supplementation with a higher effect in females. The expression of longevity related genes (Sir2, Foxo, and Notch) was increased in both sexes but with different patterns. Pterostilbene counteracted oxidative stress induced by ethanol and paraquat and up-regulated the antioxidant enzymes Ho e Trxr-1 in male but not in female flies. On the other hand, pterostilbene decreased the inflammatory mediators dome and egr only in female flies. Proteomic analysis revealed that pterostilbene modulates 113 proteins in male flies and only 9 in females. Only one of these proteins was modulated by pterostilbene in both sexes: vacuolar H[+] ATPase 68 kDa subunit 2 (Vha68-2) that was strongly down-regulated. These findings suggest a potential role of pterostilbene in increasing lifespan both in male and female flies by mechanisms that seem to be different in the two sexes, highlighting the need to conduct nutraceutical supplementation studies on males and females separately in order to give more reliable results.}, }
@article {pmid35216302, year = {2022}, author = {Shi, Y and Wang, G and Lau, HC and Yu, J}, title = {Metagenomic Sequencing for Microbial DNA in Human Samples: Emerging Technological Advances.}, journal = {International journal of molecular sciences}, volume = {23}, number = {4}, pages = {}, pmid = {35216302}, issn = {1422-0067}, support = {2020YFA0509200/2020YFA0509203//National Key R&amp;D Program of China/ ; T21-705/20-N//RGC Theme-based Res Scheme Hong Kong/ ; C4039-19GF, C7065-18GF//RGC Collaborative Research Fund/ ; 14163817//RGC-GRF Hong Kong/ ; Vice-Chancellor's Discretionary Fund//Chinese University of Hong Kong/ ; }, mesh = {DNA/genetics ; *High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenome ; *Metagenomics/methods ; Sequence Analysis, DNA/methods ; Technology ; }, abstract = {Whole genome metagenomic sequencing is a powerful platform enabling the simultaneous identification of all genes from entirely different kingdoms of organisms in a complex sample. This technology has revolutionised multiple areas from microbiome research to clinical diagnoses. However, one of the major challenges of a metagenomic study is the overwhelming non-microbial DNA present in most of the host-derived specimens, which can inundate the microbial signals and reduce the sensitivity of microorganism detection. Various host DNA depletion methods to facilitate metagenomic sequencing have been developed and have received considerable attention in this context. In this review, we present an overview of current host DNA depletion approaches along with explanations of their underlying principles, advantages and disadvantages. We also discuss their applications in laboratory microbiome research and clinical diagnoses and, finally, we envisage the direction of the further perfection of metagenomic sequencing in samples with overabundant host DNA.}, }
@article {pmid35215830, year = {2022}, author = {Skurnik, M}, title = {Editorial of Viruses Special Issue on Phage-Host Interactions 2021.}, journal = {Viruses}, volume = {14}, number = {2}, pages = {}, doi = {10.3390/v14020236}, pmid = {35215830}, issn = {1999-4915}, mesh = {Bacteria/*virology ; Bacteriophages/genetics/*physiology ; *Host Microbial Interactions ; Host Specificity ; }, abstract = {Viruses has now published two Special Issues on phage-host interactions, the latest under the name Phage-Host Interactions 2021 [...].}, }
@article {pmid35212478, year = {2022}, author = {Patangia, DV and Anthony Ryan, C and Dempsey, E and Paul Ross, R and Stanton, C}, title = {Impact of antibiotics on the human microbiome and consequences for host health.}, journal = {MicrobiologyOpen}, volume = {11}, number = {1}, pages = {e1260}, pmid = {35212478}, issn = {2045-8827}, mesh = {Adult ; Animals ; Anti-Bacterial Agents/administration &amp; dosage/*pharmacology ; Child ; Female ; Humans ; Infant ; Infant, Newborn ; Microbiota/*drug effects ; Pregnancy ; }, abstract = {It is well established that the gut microbiota plays an important role in host health and is perturbed by several factors including antibiotics. Antibiotic-induced changes in microbial composition can have a negative impact on host health including reduced microbial diversity, changes in functional attributes of the microbiota, formation, and selection of antibiotic-resistant strains making hosts more susceptible to infection with pathogens such as Clostridioides difficile. Antibiotic resistance is a global crisis and the increased use of antibiotics over time warrants investigation into its effects on microbiota and health. In this review, we discuss the adverse effects of antibiotics on the gut microbiota and thus host health, and suggest alternative approaches to antibiotic use.}, }
@article {pmid35208921, year = {2022}, author = {Reddel, S and Pascucci, GR and Foligno, S and Del Chierico, F and Vernocchi, P and Marzullo, A and Pattumelli, MG and Palma, P and Salvatori, G and Putignani, L}, title = {A Parallel Tracking of Salivary and Gut Microbiota Profiles Can Reveal Maturation and Interplay of Early Life Microbial Communities in Healthy Infants.}, journal = {Microorganisms}, volume = {10}, number = {2}, pages = {}, pmid = {35208921}, issn = {2076-2607}, support = {Ricerca Corrente 2016, 2017, 778 2018, 2019 and 5 &#x2030; 2020//Italian Ministry of Health/ ; 201903_DICOFARM//DICOFARM/ ; }, abstract = {In this study, the onset and shaping of the salivary and gut microbiota in healthy newborns during the first period of life has been followed, evaluating the impact of salivary microbiota on the development of early fecal microbial communities. The microbiota of 80 salivary and 82 fecal samples that were collected from healthy newborns in the first six months of life, was investigated by 16S rRNA amplicon profiling. The microbial relationship within and between the saliva and gut ecosystems was determined by correlation heatmaps and co-occurrence networks. Streptococcus and Staphylococcus appeared as early commensals in the salivary microbiota, dominating this ecosystem through the time, while Fusobacterium, Prevotella, Porphyromonas, Granulicatella, and Veillonella were late colonizers. Enterobacteriaceae, Staphylococcus and Streptococcus were gut pioneers, followed by the anaerobic Bifidobacterium, Veillonella, Eggerthella, and Bacteroides. Streptococcus, Staphylococcus, and Veillonella were shared by the gut and saliva ecosystems. The saliva and gut microbiota seem to evolve independently, driven by local adaptation strategies, except for the oral Streptococcus and Veillonella that are involved in gut microbiota development as seeding species. This study offers a piece of knowledge on how the oral microbiota may affect the gut microbiota in healthy newborns, shedding light onto new microbial targets for the development of therapies for early life intestinal dysbiosis.}, }
@article {pmid35208736, year = {2022}, author = {Stuivenberg, GA and Burton, JP and Bron, PA and Reid, G}, title = {Why Are Bifidobacteria Important for Infants?.}, journal = {Microorganisms}, volume = {10}, number = {2}, pages = {}, pmid = {35208736}, issn = {2076-2607}, support = {Unknown//Natural Sciences and Engineering Research Council/ ; }, abstract = {The presence of Bifidobacterium species in the maternal vaginal and fecal microbiota is arguably an evolutionary trait that allows these organisms to be primary colonizers of the newborn intestinal tract. Their ability to utilize human milk oligosaccharides fosters their establishment as core health-promoting organisms throughout life. A reduction in their abundance in infants has been shown to increase the prevalence of obesity, diabetes, metabolic disorder, and all-cause mortality later in life. Probiotic strains have been developed as supplements for premature babies and to counter some of these ailments as well as to confer a range of health benefits. The ability to modulate the immune response and produce short-chain fatty acids, particularly acetate and butyrate, that strengthen the gut barrier and regulate the gut microbiome, makes Bifidobacterium a core component of a healthy infant through adulthood.}, }
@article {pmid35208194, year = {2022}, author = {Yan, D and Cao, L and Zhou, M and Mohimani, H}, title = {TransDiscovery: Discovering Biotransformation from Human Microbiota by Integrating Metagenomic and Metabolomic Data.}, journal = {Metabolites}, volume = {12}, number = {2}, pages = {}, pmid = {35208194}, issn = {2218-1989}, support = {DP2 GM137413/GM/NIGMS NIH HHS/United States ; DP2GM137413//National Institute of Health/ ; }, abstract = {The human microbiome is a complex community of microorganisms, their enzymes, and the molecules they produce or modify. Recent studies show that imbalances in human microbial ecosystems can cause disease. Our microbiome affects our health through the products of biochemical reactions catalyzed by microbial enzymes (microbial biotransformations). Despite their significance, currently, there are no systematic strategies for identifying these chemical reactions, their substrates and molecular products, and their effects on health and disease. We present TransDiscovery, a computational algorithm that integrates molecular networks (connecting related molecules with similar mass spectra), association networks (connecting co-occurring molecules and microbes) and knowledge bases of microbial enzymes to discover microbial biotransformations, their substrates, and their products. After searching the metabolomics and metagenomics data from the American Gut Project and the Global Foodomic Project, TranDiscovery identified 17 potentially novel biotransformations from the human gut microbiome, along with the corresponding microbial species, substrates, and products.}, }
@article {pmid35204374, year = {2022}, author = {Bschleipfer, T and Karl, I}, title = {Bladder Microbiome in the Context of Urological Disorders-Is There a Biomarker Potential for Interstitial Cystitis?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {2}, pages = {}, pmid = {35204374}, issn = {2075-4418}, abstract = {Since the development of modern cultivation and sequencing techniques, the human microbiome has increasingly become the focus of scientific attention. Even in the bladder, long considered to be a sterile niche, a highly variable and complex microbial colonization has now been demonstrated. Especially in the context of diseases such as interstitial cystitis, whose etiopathogenesis is largely unknown, and whose diagnosis is based on a process of exclusion of confusable diseases, science hopes to gain far-reaching insights for etiology and diagnosis, including the identification of potential biomarkers. While for functional disorders such as urge urinary incontinence and overactive bladder syndrome, initial associations have been demonstrated between reduced microbial diversity and increased symptomatology, as well as shifts in the abundance of specific microorganisms such as Lactobacillus or Proteus, studies in interstitial cystitis show conflicting results and have failed to identify a putative organism or urotype that clearly distinguishes the urinary microbiome of patients with IC/BPS from that of healthy controls. At the present time, therefore, the new insights into the bladder microbiome and its potential influence on urologic disease cannot yet be used in the context of elucidating possible etiopathogenetic causes, as well as in the use of a biomarker for diagnostic or prognostic purposes. Further studies should focus primarily on uniform procedures and detection methods to achieve better comparability of results and increase the likelihood of detecting hidden patterns.}, }
@article {pmid35203519, year = {2022}, author = {Craciun, CI and Neag, MA and Catinean, A and Mitre, AO and Rusu, A and Bala, C and Roman, G and Buzoianu, AD and Muntean, DM and Craciun, AE}, title = {The Relationships between Gut Microbiota and Diabetes Mellitus, and Treatments for Diabetes Mellitus.}, journal = {Biomedicines}, volume = {10}, number = {2}, pages = {}, pmid = {35203519}, issn = {2227-9059}, abstract = {Diabetes mellitus is considered to be a global epidemic. The combination of genetic susceptibility and an unhealthy lifestyle is considered to be the main trigger of this metabolic disorder. Recently, there has been increased interest in the roles of gut microbiota as a new potential contributor to this epidemic. Research, in recent years, has contributed to an in-depth characterization of the human microbiome and its associations with various diseases, including metabolic diseases and diabetes mellitus. It is known that diet can change the composition of gut microbiota, but it is unclear how this, in turn, may influence metabolism. The main objective of this review is to evaluate the pathogenetic association between microbiota and diabetes and to explore any new therapeutic agents, including nutraceuticals that may modulate the microbiota. We also look at several mechanisms involved in this process. There is a clear, bidirectional relationship between microbiota and diabetes. Current treatments for diabetes influence microbiota in various ways, some beneficial, but others with still unclear effects. Microbiota-aimed treatments have seen no real-world significant effects on the progression of diabetes and its complications, with more studies needed in order to find a really beneficial agent.}, }
@article {pmid35202611, year = {2022}, author = {Jia, B and Kim, KH and Ruan, W and Kim, HM and Jeon, CO}, title = {Lantibiotic-encoding Streptococcus in the human microbiome are underlying risk factors for liver diseases.}, journal = {The Journal of infection}, volume = {84}, number = {5}, pages = {e70-e72}, doi = {10.1016/j.jinf.2022.02.020}, pmid = {35202611}, issn = {1532-2742}, mesh = {*Bacteriocins ; Humans ; Liver Cirrhosis ; *Liver Diseases ; *Microbiota ; Risk Factors ; Streptococcus ; }, }
@article {pmid35191218, year = {2022}, author = {Qu, D and Wang, Y and Xia, Q and Chang, J and Jiang, X and Zhang, H}, title = {Intratumoral Microbiome of Human Primary Liver Cancer.}, journal = {Hepatology communications}, volume = {6}, number = {7}, pages = {1741-1752}, pmid = {35191218}, issn = {2471-254X}, mesh = {Bacteria ; Humans ; Immunotherapy ; *Liver Neoplasms/therapy ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Tumor Microenvironment ; }, abstract = {Primary liver tumors (PLCs) and liver metastasis currently represent the leading cause of cancer-related deaths worldwide due to poor outcomes, high incidence, and postsurgical recurrence. Hence, novel diagnostic markers and therapeutic strategies for PLCs are urgently needed. The human microbiome can directly or indirectly impact cancer initiation, progression, and response to therapy, including cancer immunotherapy; however, the roles of the microbiota in the tumor microenvironment are not clear and require more investigation. Here, we investigated intratumoral microbial community profiling on formalin-fixed paraffin-embedded tissue samples of patients with PLC by 16S ribosomal RNA using the MiSeq platform. We characterized the microbial communities in different histopathological subtypes and in the different prognoses of patients with PLC. The study revealed microbial population differences not only in carcinoma tissue and the matched adjacent nontumor tissue but in different histopathological subtypes, even in patients with PLC with different prognoses. Interestingly, the abundance of certain bacteria that have antitumor effects at family and genus level, such as Pseudomonadaceae, decreased in tumor tissue and was linearly associated with prognosis of patients with PLC. Conclusion: We provide a potential novel diagnostic biomarker and therapeutic strategy for early clinical diagnosis and treatment of PLC.}, }
@article {pmid35190251, year = {2022}, author = {Moossavi, S and Arrieta, MC and Sanati-Nezhad, A and Bishehsari, F}, title = {Gut-on-chip for ecological and causal human gut microbiome research.}, journal = {Trends in microbiology}, volume = {30}, number = {8}, pages = {710-721}, doi = {10.1016/j.tim.2022.01.014}, pmid = {35190251}, issn = {1878-4380}, support = {//CIHR/Canada ; }, mesh = {Animals ; Diet ; *Gastrointestinal Microbiome/physiology ; Host Microbial Interactions ; Humans ; Mice ; *Microbiota ; }, abstract = {There is a growing interest to understand if and how the gut microbiome is causally linked to the pathogenesis and/or progression of diseases. While in vitro cell line models are commonly used for studying specific aspects of the host-microbe interaction, gnotobiotic murine models are considered the preferred platform for studying causality in microbiome research. Nevertheless, findings from animal studies provide limited opportunity for delineating various areas of interest to the human gut microbiome research. Gut-on-chips are biomimetics recapitulating intestinal physiology which enable investigation of bidirectional effects of the host and microbiome. We posit that they could advance causal and ecological gut microbiome research in three major areas: (i) diet-microbiome and drug-microbiome interaction; (ii) microbiome-targeted therapeutics pharmacoecology; and (iii) mechanistic studies of gut microbiome and microbiome-targeted intervention in extraintestinal pathologies.}, }
@article {pmid35186803, year = {2022}, author = {Manzanares-Leal, GL and Coronel-Martínez, JA and Rodríguez-Morales, M and Rangel-Cuevas, I and Bustamante-Montes, LP and Sandoval-Trujillo, H and Ramírez-Durán, N}, title = {Preliminary Identification of the Aerobic Cervicovaginal Microbiota in Mexican Women With Cervical Cancer as the First Step Towards Metagenomic Studies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {838491}, pmid = {35186803}, issn = {2235-2988}, mesh = {Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; *Microbiota/genetics ; Middle Aged ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; *Uterine Cervical Neoplasms ; Vagina/microbiology ; Young Adult ; }, abstract = {Cervical cancer (CC) is considered a public health problem. Recent studies have evaluated the possible relationship between the cervicovaginal microbiome and gynecologic cancer but have not studied the relationship between aerobic bacterial communities and neoplasia. The study aimed to identify the cultivable aerobic bacterial microbiota in women with cervical cancer as a preliminary approach to the metagenomic study of the cervicovaginal microbiome associated with cervical cancer in Mexican women. An observational cross-sectional study was conducted, including 120 women aged 21-71 years, divided into two study groups, women with locally advanced CC (n=60) and women without CC (n=60). Sociodemographic, gynecological-obstetric, sexual, and habit data were collected. Cervicovaginal samples were collected by swabbing, from which standard microbiological methods obtained culturable bacteria. The strains were genetically characterized by PCR-RFLP of the 16S rRNA gene and subsequently identified by sequencing the same gene. Variables regularly reported as risk factors for the disease were found in women with CC. Differences were found in the prevalence and number of species isolated in each study group. Bacteria commonly reported in women with aerobic vaginitis were identified. There were 12 species in women with CC, mainly Corynebacterium spp. and Staphylococcus spp.; we found 13 bacterial species in the group without cancer, mainly Enterococcus spp. and Escherichia spp. The advanced stages presented a more significant number of isolates and species. This study provided a preliminary test for cervicovaginal metagenomic analysis, demonstrating the presence of aerobic cervicovaginal dysbiosis in women with CC and the need for more in-depth studies.}, }
@article {pmid35185849, year = {2022}, author = {Mousa, WK and Chehadeh, F and Husband, S}, title = {Recent Advances in Understanding the Structure and Function of the Human Microbiome.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {825338}, pmid = {35185849}, issn = {1664-302X}, abstract = {Trillions of microbes live within our bodies in a deep symbiotic relationship. Microbial populations vary across body sites, driven by differences in the environment, immunological factors, and interactions between microbial species. Major advances in genome sequencing enable a better understanding of microbiome composition. However, most of the microbial taxa and species of the human microbiome are still unknown. Without revealing the identity of these microbes as a first step, we cannot appreciate their role in human health and diseases. A shift in the microbial balance, termed dysbiosis, is linked to a broad range of diseases from simple colitis and indigestion to cancer and dementia. The last decade has witnessed an explosion in microbiome research that led to a better understanding of the microbiome structure and function. This understanding leads to potential opportunities to develop next-generation microbiome-based drugs and diagnostic biomarkers. However, our understanding is limited given the highly personalized nature of the microbiome and its complex and multidirectional interactions with the host. In this review, we discuss: (1) our current knowledge of microbiome structure and factors that shape the microbial composition, (2) recent associations between microbiome dysbiosis and diseases, and (3) opportunities of new microbiome-based therapeutics. We analyze common themes, promises, gaps, and challenges of the microbiome research.}, }
@article {pmid35182101, year = {2022}, author = {Dhakal, S and Moazzami, Z and Perry, C and Dey, M}, title = {Effects of Lean Pork on Microbiota and Microbial-Metabolite Trimethylamine-N-Oxide: A Randomized Controlled Non-Inferiority Feeding Trial Based on the Dietary Guidelines for Americans.}, journal = {Molecular nutrition &amp; food research}, volume = {66}, number = {9}, pages = {e2101136}, doi = {10.1002/mnfr.202101136}, pmid = {35182101}, issn = {1613-4133}, support = {U2C ES030158/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Choline/metabolism ; *Gastrointestinal Microbiome ; Humans ; Methylamines ; *Microbiota ; Nutrition Policy ; Oxides ; *Pork Meat ; Poultry/metabolism ; *Red Meat ; Swine ; }, abstract = {SCOPE: Trimethylamine-N-oxide (TMAO) is a microbiota-dependent and primarily animal-protein-derived proatherogenic metabolite. The ecological impact of pork-the most popular animal protein worldwide-on the human microbiome, and in the physiological context of TMAO and other biogenic amines, remains unknown. Poultry being the recommended heart-healthier animal protein, we investigated-if pork intake results in inferior-to-chicken TMAO-response while consuming a diet based on the Dietary Guidelines for Americans (DGA).<br><br>METHODS AND RESULTS: In a randomized, controlled, all-food-provided, crossover, feeding trial, healthy adults consumed 156&#xa0;g day[-1] of lean-pork or chicken (active-control) as primary proteins. Mixed-effect modeling shows pork as noninferior to chicken for circulating TMAO response and microbiota-generated essential TMAO-precursor-trimethylamine (97.5% CI, n = 36/protein). Markers of lipid metabolism, inflammation and oxidative stress, serum levels of betaine, choline, L-carnitine, composition and functional-capability of the microbiota, and association of baseline TMAO-levels with TMAO-response (both, r > 0.6, p = 0.0001) are nondistinguishable between the protein groups. TMAO reduction and similar shifts in microbiota and biogenic-amine signatures postdiet in both groups indicate a background DGA-effect.<br><br>CONCLUSION: Unlike extrapolating negative results, this study presents noninferiority-testing based evidence. Consuming pork as a predominant protein within an omnivorous DGA-diet does not exacerbate TMAO-response. Results highlight the importance of understanding protein-TMAO interactions within dietary patterns.}, }
@article {pmid35181661, year = {2022}, author = {Johansen, J and Plichta, DR and Nissen, JN and Jespersen, ML and Shah, SA and Deng, L and Stokholm, J and Bisgaard, H and Nielsen, DS and Sørensen, SJ and Rasmussen, S}, title = {Genome binning of viral entities from bulk metagenomics data.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {965}, pmid = {35181661}, issn = {2041-1723}, mesh = {Bacteriophages/*classification/genetics ; Gastrointestinal Microbiome/*genetics/physiology ; Gastrointestinal Tract/*virology ; Genome, Viral/genetics ; Humans ; Metagenome/*genetics ; Metagenomics ; Virome/*genetics/physiology ; }, abstract = {Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal tract are not well understood. This is partly due to a paucity of whole-virome datasets and limitations in current approaches for identifying viral sequences in metagenomics data. Here, combining a deep-learning based metagenomics binning algorithm with paired metagenome and metavirome datasets, we develop Phages from Metagenomics Binning (PHAMB), an approach that allows the binning of thousands of viral genomes directly from bulk metagenomics data, while simultaneously enabling clustering of viral genomes into accurate taxonomic viral populations. When applied on the Human Microbiome Project 2 (HMP2) dataset, PHAMB recovered 6,077 high-quality genomes from 1,024 viral populations, and identified viral-microbial host interactions. PHAMB can be advantageously applied to existing and future metagenomes to illuminate viral ecological dynamics with other microbiome constituents.}, }
@article {pmid35177861, year = {2022}, author = {Blaak, EE and de Vos, WM}, title = {Before the heart attack.}, journal = {Nature medicine}, volume = {28}, number = {2}, pages = {237-238}, pmid = {35177861}, issn = {1546-170X}, mesh = {*Coronary Artery Disease ; Humans ; *Microbiota ; *Myocardial Infarction ; Risk Factors ; }, }
@article {pmid35176353, year = {2022}, author = {Mandal, S and Bandyopadhyay, S and Tyagi, K and Roy, A}, title = {Human microbial dysbiosis as driver of gynecological malignancies.}, journal = {Biochimie}, volume = {197}, number = {}, pages = {86-95}, doi = {10.1016/j.biochi.2022.02.005}, pmid = {35176353}, issn = {1638-6183}, mesh = {Biomarkers ; Dysbiosis/microbiology ; Female ; *Genital Neoplasms, Female ; Humans ; Lactobacillus ; *Microbiota ; }, abstract = {Gynecological cancers that affect female reproductive tract, remain at the top of the global cancer burden list with high relapse rate and mortality. Notwithstanding development of several novel therapeutic interventions including poly-ADP-ribose polymerase inhibitors, this family of malignancies remain deadly. The human microbiome project demonstrated that dysbiosis of health resident microflora is associated with several pathologies including malignancies of the female reproductive tract and detailed characterization of species variation and host-microbe interaction could provide clues for identification of early diagnostic biomarker, preventive and therapeutic interventions. Emerging evidence suggests that several microbial signatures are significantly associated with gynecological cancers. An increased population of Proteobacteria and Firmicutes followed by significantly reduced Lactobacilli are associated with lethal epithelial ovarian cancer. Similarly, a constant association of elevated level of Atopobium vaginae, Porphyromonas somerae, Micrococci and Gardnerella vaginalis are observed in endometrial and cervical cancers. Moreover, human papilloma virus infection significantly augments colonization of pathogenic microbes including Sneathia sanguinegens, Anaerococcus tetradius, and Peptostreptococcus anaerobius and drives carcinoma of the cervix. Interestingly, microbial dysbiosis in female reproductive tract modulates expression of several microbial and immune-responsive genes such as TLR-4, TLR-5, TLR-6 and NOD-1. Therefore, stringent investigation into the microbial dysbiosis and its underlying mechanism could provide valuable cues for identification of early diagnostic biomarker, preventive and therapeutic interventions against rogue gynecological malignancies.}, }
@article {pmid35170866, year = {2022}, author = {Falduto, M and Smedile, F and Zhang, M and Zheng, T and Zhu, J and Huang, Q and Weeks, R and Ermakov, AM and Chikindas, ML}, title = {Anti-obesity effects of Chenpi: an artificial gastrointestinal system study.}, journal = {Microbial biotechnology}, volume = {15}, number = {3}, pages = {874-885}, pmid = {35170866}, issn = {1751-7915}, mesh = {Aged ; Clostridiales ; *Drugs, Chinese Herbal ; Emulsions ; Humans ; *Microbiota ; Obesity ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The gut microbiota plays a significant role in human health; however, the complex relationship between gut microbial communities and host health is still to be thoroughly studied and understood. Microbes in the distal gut contribute to host health through the biosynthesis of vitamins and essential amino acids and the generation of important metabolic by-products from dietary components that are left undigested by the small intestine. Aged citrus peel (Chenpi) is used in traditional Chinese medicine to lower cholesterol, promote weight loss and treat various gastrointestinal symptoms. This study investigated how the microbial community changes during treatment with Chenpi using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Two preparations of Chenpi extract were tested: Chenpi suspended in oil only and Chenpi in a viscoelastic emulsion. Short-chain fatty acids (SCFAs) were measured during treatment to monitor changes in the microbial community of the colon presenting a decrease in production for acetic, propionic and butyric acid (ANOVA (P < 0.001) during the 15 days of treatment. 16S rRNA sequencing of microbial samples showed a clear difference between the two treatments at the different sampling times (ANOSIM P < 0.003; ADOSIM P < 0.002 [R[2] = 69%]). Beta diversity analysis by PcoA showed differences between the two Chenpi formulations for treatment day 6. These differences were no longer detectable as soon as the Chenpi treatment was stopped, showing a reversible effect of Chenpi on the human microbiome. 16S rRNA sequencing of microbial samples from the descending colon showed an increase in Firmicutes for the treatment with the viscoelastic emulsion. At the genus level, Roseburia, Blautia, Subdoligranulum and Eubacterium increased in numbers during the viscoelastic emulsion treatment. This study sheds light on the anti-obesity effect of a polymethoxyflavone (PMFs)-enriched Chenpi extract and creates a foundation for the identification of 'obesity-prevention' biomarkers in the gut microbiota.}, }
@article {pmid35167588, year = {2022}, author = {Abdill, RJ and Adamowicz, EM and Blekhman, R}, title = {Public human microbiome data are dominated by highly developed countries.}, journal = {PLoS biology}, volume = {20}, number = {2}, pages = {e3001536}, pmid = {35167588}, issn = {1545-7885}, support = {R35 GM128716/GM/NIGMS NIH HHS/United States ; }, mesh = {Asia ; Bangladesh ; Canada ; Developed Countries ; Europe ; Gastrointestinal Microbiome/*genetics ; Genomics/*methods/statistics &amp; numerical data ; Geography ; Humans ; India ; Metagenome/*genetics ; Metagenomics/*methods/statistics &amp; numerical data ; Microbiota/*genetics ; Pakistan ; United States ; }, abstract = {The importance of sampling from globally representative populations has been well established in human genomics. In human microbiome research, however, we lack a full understanding of the global distribution of sampling in research studies. This information is crucial to better understand global patterns of microbiome-associated diseases and to extend the health benefits of this research to all populations. Here, we analyze the country of origin of all 444,829 human microbiome samples that are available from the world's 3 largest genomic data repositories, including the Sequence Read Archive (SRA). The samples are from 2,592 studies of 19 body sites, including 220,017 samples of the gut microbiome. We show that more than 71% of samples with a known origin come from Europe, the United States, and Canada, including 46.8% from the US alone, despite the country representing only 4.3% of the global population. We also find that central and southern Asia is the most underrepresented region: Countries such as India, Pakistan, and Bangladesh account for more than a quarter of the world population but make up only 1.8% of human microbiome samples. These results demonstrate a critical need to ensure more global representation of participants in microbiome studies.}, }
@article {pmid35152186, year = {2022}, author = {Lim, H and Cankara, F and Tsai, CJ and Keskin, O and Nussinov, R and Gursoy, A}, title = {Artificial intelligence approaches to human-microbiome protein-protein interactions.}, journal = {Current opinion in structural biology}, volume = {73}, number = {}, pages = {102328}, doi = {10.1016/j.sbi.2022.102328}, pmid = {35152186}, issn = {1879-033X}, mesh = {*Artificial Intelligence ; Humans ; *Microbiota ; }, abstract = {Host-microbiome interactions play significant roles in human health and disease. Artificial intelligence approaches have been developed to better understand and predict the molecular interplay between the host and its microbiome. Here, we review recent advancements in computational methods to predict microbial effects on human cells with a special focus on protein-protein interactions. We categorize recent methods from traditional ones to more recent deep learning methods, followed by several challenges and potential solutions in structure-based approaches. This review serves as a brief guide to the current status and future directions in the field.}, }
@article {pmid35151278, year = {2022}, author = {Doocey, CM and Finn, K and Murphy, C and Guinane, CM}, title = {The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development.}, journal = {BMC microbiology}, volume = {22}, number = {1}, pages = {53}, pmid = {35151278}, issn = {1471-2180}, mesh = {Animals ; Bacteroides fragilis/genetics/pathogenicity ; Carcinogenesis/*genetics/pathology ; Colorectal Neoplasms/*therapy ; Fusobacterium nucleatum/genetics/pathogenicity ; Gastrointestinal Microbiome/genetics/physiology ; Humans ; Mice ; Microbiota/*genetics/physiology ; Probiotics ; Tumor Microenvironment ; Virulence Factors ; }, abstract = {BACKGROUND: Cancer impacts millions of lives globally each year, with approximately 10 million cancer-related deaths recorded worldwide in 2020. Mounting research has recognised the human microbiome as a key area of interest in the pathophysiology of various human diseases including cancer tumorigenesis, progression and in disease outcome. It is suggested that approximately 20% of human cancers may be linked to microbes. Certain residents of the human microbiome have been identified as potentially playing a role, including: Helicobacter pylori, Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis and Porphyromonas gingivalis.<br><br>MAIN BODY: In this review, we explore the current evidence that indicate a link between the human microbiome and cancer. Microbiome compositional changes have been well documented in cancer patients. Furthermore, pathogenic microbes harbouring specific virulence factors have been implicated in driving the carcinogenic activity of various malignancies including colorectal, gastric and pancreatic cancer. The associated genetic mechanisms with possible roles in cancer will be outlined. It will be indicated which microbes have a potential direct link with cancer cell proliferation, tumorigenesis and disease progression. Recent studies have also linked certain microbial cytotoxins and probiotic strains to cancer cell death, suggesting their potential to target the tumour microenvironment given that cancer cells are integral to its composition. Studies pertaining to such cytotoxic activity have suggested the benefit of microbial therapies in oncological treatment regimes. It is also apparent that bacterial pathogenic protein products encoded for by certain loci may have potential as oncogenic therapeutic targets given their possible role in tumorigenesis.<br><br>CONCLUSION: Research investigating the impact of the human microbiome in cancer has recently gathered pace. Vast amounts of evidence indicate the human microbiome as a potential player in tumorigenesis and progression. Promise in the development of cancer biomarkers and in targeted oncological therapies has also been demonstrated, although more studies are needed. Despite extensive in vitro and in vivo research, clinical studies involving large cohorts of human patients are lacking. The current literature suggests that further intensive research is necessary to validate both the role of the human microbiome in cancer, and the use of microbiome modification in cancer therapy.}, }
@article {pmid35147263, year = {2022}, author = {Wisgrill, L and Fyhrquist, N and Ndika, J and Paalanen, L and Berger, A and Laatikainen, T and Karisola, P and Haahtela, T and Alenius, H}, title = {Bet v 1 triggers antiviral-type immune signalling in birch-pollen-allergic individuals.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {52}, number = {8}, pages = {929-941}, pmid = {35147263}, issn = {1365-2222}, mesh = {Adolescent ; Allergens ; Antigens, Plant ; Antiviral Agents ; *Betula ; Humans ; *Hypersensitivity ; Immunoglobulin E ; Leukocytes, Mononuclear ; Plant Proteins ; Pollen ; }, abstract = {BACKGROUND: In allergic patients, clinical symptoms caused by pollen remind of symptoms triggered by viral respiratory infections, which are also the main cause of asthmatic exacerbations. In patients sensitized to birch pollen, Bet v 1 is the major symptom-causing allergen. Immune mechanisms driving Bet v 1-related responses of human blood cells have not been fully characterized.<br><br>OBJECTIVE: To characterize the immune response to Bet v 1 in peripheral blood in patients allergic to birch pollen.<br><br>METHODS: The peripheral blood mononuclear cells of birch-allergic (n&#xa0;=&#xa0;24) and non-allergic (n&#xa0;=&#xa0;47) adolescents were stimulated ex-vivo followed by transcriptomic profiling. Systems-biology approaches were employed to decipher disease-relevant gene networks and deconvolution of associated cell populations.<br><br>RESULTS: Solely in birch-allergic patients, co-expression analysis revealed activation of networks of innate immunity and antiviral signalling as the immediate response to Bet v 1&#xa0;stimulation. Toll-like receptors and signal transducer transcription were the main drivers of gene expression patterns. Macrophages and dendritic cells were the main cell subsets responding to Bet v 1.<br><br>In birch-pollen-allergic patients, the activated innate immune networks seem to be, in part, the same as those activated during viral infections. This tendency of the immune system to read pollens as viruses may provide new insight to allergy prevention and treatment.}, }
@article {pmid35145929, year = {2022}, author = {Gao, C and Guo, Y and Chen, F}, title = {Cross-Cohort Microbiome Analysis of Salivary Biomarkers in Patients With Type 2 Diabetes Mellitus.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {816526}, pmid = {35145929}, issn = {2235-2988}, mesh = {Biomarkers ; *Diabetes Mellitus, Type 2/microbiology ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; }, abstract = {Several studies have ascertained differences in salivary microbiota between patients with type 2 diabetes mellitus (T2DM) and healthy populations. However, the predictive accuracy and reproducibility of these 16S rRNA sequencing analyses when applied to other cohorts remain enigmatic. A comprehensive analysis was conducted on the included 470 samples from five researches in publicly available databases. The discrepancy and predictive accuracy of salivary microbiota between T2DM patients and healthy populations were evaluated from multiple perspectives, followed by the identification of salivary biomarkers for DM. Next, a classification model (areas under the curves = 0.92) was developed based on a large sample. The model could be used for clinical diagnosis and prognostic monitoring and as a basis for hypothesis-driven mechanistic researches. Furthermore, the research heterogeneity across geographic regions suggested that microbiological markers might not become a uniform clinical standard in human beings. They rather identify abnormal alterations under the microbiological characteristics of a specific population.}, }
@article {pmid35142027, year = {2022}, author = {Flach, M and Leu, C and Martinisi, A and Skachokova, Z and Frank, S and Tolnay, M and Stahlberg, H and Winkler, DT}, title = {Trans-seeding of Alzheimer-related tau protein by a yeast prion.}, journal = {Alzheimer's &amp; dementia : the journal of the Alzheimer's Association}, volume = {18}, number = {12}, pages = {2481-2492}, pmid = {35142027}, issn = {1552-5279}, mesh = {Mice ; Animals ; Humans ; tau Proteins/metabolism ; *Prions/metabolism ; *Alzheimer Disease/metabolism ; *Tauopathies/pathology ; Saccharomyces cerevisiae/metabolism ; Mice, Transgenic ; }, abstract = {Abnormal tau protein aggregates constitute a hallmark of Alzheimer's disease. The mechanisms underlying the initiation of tau aggregation in sporadic neurodegeneration remain unclear. Here we investigate whether a non-human prion can seed tau aggregation. Due to their structural similarity with tau aggregates, we chose Sup35NM yeast prion domain fibrils for explorative tau seedings. Upon in vitro incubation with tau monomers, Sup35NM fibrils promoted the formation of morphologically distinct tau fibril strains. In vivo, intrahippocampal inoculation of Sup35NM fibrils accentuated tau pathology in P301S tau transgenic mice. Thus, our results provide first in vivo evidence for heterotypic cross-species seeding of a neurodegenerative human prion-like protein by a yeast prion. This opens up the conceptual perspective that non-mammalian prions present in the human microbiome could be involved in the initiation of protein misfolding in neurodegenerative disorders, a mechanism for which we propose the term "trans-seeding."}, }
@article {pmid35140882, year = {2022}, author = {Junca, H and Pieper, DH and Medina, E}, title = {The emerging potential of microbiome transplantation on human health interventions.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {615-627}, pmid = {35140882}, issn = {2001-0370}, abstract = {The human microbiome has been the subject of intense research over the past few decades, in particular as a promising area for new clinical interventions. The microbiota colonizing the different body surfaces are of benefit for multiple physiological and metabolic processes of the human host and increasing evidence suggests an association between disturbances in the composition and functionality of the microbiota and several pathological conditions. This has provided a rationale for beneficial modulation of the microbiome. One approach being explored for modulating the microbiota in diseased individuals is transferring microbiota or microbiota constituents from healthy donors via microbiome transplantation. The great success of fecal microbiome transplantation for the treatment of Clostridioides difficile infections has encouraged the application of this procedure for the treatment of other diseases such as vaginal disorders via transplantation of vaginal microbiota, or of skin pathologies via the transplantation of skin microbiota. Microbiome modulation could even become a novel strategy for improving the efficacy of cancer therapies. This review discusses the principle, advantages and limitations of microbiome transplantation as well as different clinical contexts where microbiome transplantation has been applied.}, }
@article {pmid35136968, year = {2022}, author = {Jamrozik, E and Heriot, GS}, title = {Ethics and antibiotic resistance.}, journal = {British medical bulletin}, volume = {141}, number = {1}, pages = {4-14}, pmid = {35136968}, issn = {1471-8391}, support = {203132/WT_/Wellcome Trust/United Kingdom ; 221719/WT_/Wellcome Trust/United Kingdom ; 221719/Z/20/Z/WT_/Wellcome Trust/United Kingdom ; }, mesh = {*Anti-Bacterial Agents/therapeutic use ; Drug Resistance, Microbial ; Humans ; *Morals ; }, abstract = {INTRODUCTION OR BACKGROUND: Antibiotic resistance raises ethical issues due to the severe and inequitably distributed consequences caused by individual actions and policies.<br><br>SOURCES OF DATA: Synthesis of ethical, scientific and clinical literature.<br><br>AREAS OF AGREEMENT: Ethical analyses have focused on the moral responsibilities of patients to complete antibiotic courses, resistance as a tragedy of the commons and attempts to limit use through antibiotic stewardship.<br><br>AREAS OF CONTROVERSY: Each of these analyses has significant limitations and can result in self-defeating or overly narrow implications for policy.<br><br>GROWING POINTS: More complex analyses focus on ethical implications of ubiquitous asymptomatic carriage of resistant bacteria, non-linear outcomes within and between patients over time and global variation in resistant disease burdens.<br><br>Neglected topics include the harms of antibiotic use, including off-target effects on the human microbiome, and the lack of evidence guiding most antibiotic prescription decisions.}, }
@article {pmid35132375, year = {2022}, author = {Kozhakhmetov, S and Babenko, D and Kozhakhmetova, S and Tuyakova, A and Nurgaziyev, M and Nurgozhina, A and Muhanbetganov, N and Chulenbayeva, L and Sergazy, S and Gulyayev, A and Aljofan, M and Kushugulova, A}, title = {Therapeutic Potential of Metabolites from Lactobacillus rhamnosus and Mare's Milk in the Treatment of Dysbiosis.}, journal = {BioMed research international}, volume = {2022}, number = {}, pages = {3851478}, pmid = {35132375}, issn = {2314-6141}, mesh = {Animals ; Colitis, Ulcerative/*drug therapy/metabolism/microbiology ; Cytokines/metabolism ; Dextran Sulfate ; Disease Models, Animal ; Dysbiosis/*drug therapy ; Gastrointestinal Microbiome/*drug effects ; Horses ; Lacticaseibacillus rhamnosus/*metabolism ; Mesalamine/pharmacology ; Milk/*metabolism ; Rats ; Rats, Wistar ; }, abstract = {Ulcerative colitis is an inflammatory bowel disease that forms ulcerations in the mucous membrane of the colon and rectum, in which gut microbiota plays a pivotal role in its pathogenesis. Agents modulating microbial dysbiosis caused by colitis can help in the remission of this disease. The current study describes the potential therapeutic effects of active metabolites from Lactobacillus rhamnosus and mare's milk which have potential therapeutic values on the intestinal microbiota and proinflammatory cytokines. The analysis of the V1-V3 16S rDNA site revealed significant changes in the intestinal microbiome composition before and after treatment in the treated group compared to the positive control group that was treated with 5-aminosalicylic acid (5-ASA). So the effect of the study product on dextran sulfate sodium-induced dysbiosis was shown to be more potent than the positive control, 5-ASA. The level of proinflammatory cytokines also decreased under the influence of a biological product.}, }
@article {pmid35125119, year = {2022}, author = {Kuehnast, T and Abbott, C and Pausan, MR and Pearce, DA and Moissl-Eichinger, C and Mahnert, A}, title = {The crewed journey to Mars and its implications for the human microbiome.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {26}, pmid = {35125119}, issn = {2049-2618}, mesh = {Astronauts ; Confined Spaces ; Humans ; *Mars ; *Microbiota ; *Space Flight ; Spacecraft ; }, abstract = {A human spaceflight to Mars is scheduled for the next decade. In preparation for this unmatched endeavor, a plethora of challenges must be faced prior to the actual journey to Mars. Mission success will depend on the health of its crew and its working capacity. Hence, the journey to Mars will also depend on the microbiome and its far-reaching effects on individual crew health, the spaceship's integrity, and food supply. As human beings rely on their microbiome, these microbes are essential and should be managed to ensure their beneficial effects outweigh potential risks. In this commentary, we focus on the current state of knowledge regarding a healthy (gut) microbiome of space travelers based on research from the International Space Station and simulation experiments on Earth. We further indicate essential knowledge gaps of microbial conditions during long-term space missions in isolated confined space habitats or outposts and give detailed recommendations for microbial monitoring during pre-flight, in-flight, and post-flight. Finally, the conclusion outlines open questions and aspects of space traveler's health beyond the scope of this commentary. Video Abstract.}, }
@article {pmid35122129, year = {2022}, author = {Wang, Y and Wang, Y and Wang, J}, title = {A comprehensive analysis of intratumor microbiome in head and neck squamous cell carcinoma.}, journal = {European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery}, volume = {279}, number = {8}, pages = {4127-4136}, pmid = {35122129}, issn = {1434-4726}, support = {G2020KY0516//Fundamental Research Funds for the Central Universities of Northwestern Polytechnical University/ ; 2021SF-030//Shaanxi Provincial Key Research and Development Program/ ; }, mesh = {Biomarkers, Tumor/genetics ; *Head and Neck Neoplasms ; Humans ; *Microbiota ; Prognosis ; Squamous Cell Carcinoma of Head and Neck ; }, abstract = {PURPOSE: Human microbiome has been considered as the second genome of our body. The intratissue/intratumor microbiome analysis is a relatively new field and deserves more attention. In this study, we conducted a comprehensive analysis of microbiome signatures of head and neck squamous cell carcinoma (HNSC).<br><br>METHODS: The intratumor microbiome profiling and clinicopathological information about a total of 177 HNSC samples, including 155 tumors and 22 adjacent normal tissues, were obtained from The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA) databases. We identified the microbes that differed between tumors and normal tissues, and assessed their utility values as diagnostic biomarkers. The microbiome signatures under different conditions of clinicopathological parameters were also analyzed.<br><br>RESULTS: The intratissue microbiome profiles differed between tumor and normal samples of HNSC. The composition of four, six, and six microbes changed in tumors compared to normal tissues at the phylum, order, and genus levels, respectively (P&#x2009;<&#x2009;0.05). Eight of the differential microbes performed well in distinguishing tumors from normal tissues (AUC&#x2009;>&#x2009;0.7, P&#x2009;&#x2264;&#x2009;0.001). The microbiome signature was found to be associated with tumor&#xa0;clinicopathological&#xa0;characteristics such as host-gender, host-age, tumor stage, and neoplasm histologic grade.<br><br>CONCLUSION: Overall, our results revealed an intratissue microbiome signature of HNSC. We concluded that the intratumor microbiome signature may also reflect human biology in both healthy and disease status, and provide novel perspective for microbiota research about their roles in tumors.}, }
@article {pmid35118003, year = {2021}, author = {Abou Chacra, L and Fenollar, F and Diop, K}, title = {Bacterial Vaginosis: What Do We Currently Know?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {672429}, pmid = {35118003}, issn = {2235-2988}, mesh = {Ecosystem ; Female ; Gardnerella vaginalis ; Humans ; Lactobacillus ; Vagina/microbiology ; *Vaginosis, Bacterial/microbiology ; }, abstract = {The vaginal microbiome is a well-defined compartment of the human microbiome. It has unique conditions, characterized by the dominance of one bacterial species, the Lactobacilli. This microbiota manifests itself by a low degree of diversity and by a strong dynamic of change in its composition under the influence of various exogenous and endogenous factors. The increase in diversity may paradoxically be associated with dysbiosis, such as bacterial vaginosis (BV). BV is the result of a disturbance in the vaginal ecosystem; i.e., a sudden replacement of Lactobacilli by anaerobic bacteria such as Gardnerella vaginalis, Atopobium vaginae, Ureaplasma urealyticum, Mycoplasma hominis, and others. It is the most common cause of vaginal discharge in women of childbearing age, approximately 30% of all causes. The etiology of this dysbiosis remains unknown, but its health consequences are significant, including obstetrical complications, increased risk of sexually transmitted infections and urogenital infections. Its diagnosis is based on Amsel's clinical criteria and/or a gram stain based on the Nugent score. While both of these methods have been widely applied worldwide for approximately three decades, Nugent score are still considered the "gold standard" of BV diagnostic tools. Given the limitations of these tools, methods based on molecular biology have been developed as alternative rational strategies for the diagnosis of BV. The treatment of BV aims at restoring the balance of the vaginal flora to stop the proliferation of harmful microorganisms. Prescription of antibiotics such as metronidazole, clindamycin, etc. is recommended. Faced with the considerable uncertainty about the cause of BV, the high rate of recurrence, the unacceptable treatment options, and clinical management which is often insensitive and inconsistent, research on this topic is intensifying. Knowledge of its composition and its associated variations represents the key element in improving the therapeutic management of patients with the most suitable treatments possible.}, }
@article {pmid35111779, year = {2021}, author = {Wehedy, E and Shatat, IF and Al Khodor, S}, title = {The Human Microbiome in Chronic Kidney Disease: A Double-Edged Sword.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {790783}, pmid = {35111779}, issn = {2296-858X}, abstract = {Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin-angiotensin-aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis-a change in the microbial diversity-has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD.}, }
@article {pmid35107701, year = {2022}, author = {Vandamme, P and Peeters, C and Seth-Smith, HMB and Schmid, H and Cnockaert, M and Egli, A and Goldenberger, D}, title = {Description of Pseudoclavibacter triregionum sp. nov. from human blood and Pseudoclavibacter albus comb. nov., and revised classification of the genus Pseudoclavibacter: proposal of Caespitibacter gen. nov., with Caespitibacter soli comb. nov. and Caespitibacter caeni comb. nov.}, journal = {Antonie van Leeuwenhoek}, volume = {115}, number = {4}, pages = {461-472}, pmid = {35107701}, issn = {1572-9699}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/chemistry/genetics ; *Fatty Acids/analysis ; Humans ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {We present polyphasic taxonomic data to demonstrate that strain 125703-2019[T], a human blood isolate, represents a novel species within the genus Pseudoclavibacter, and to reclassify the illegitimate Zimmermannella alba Lin et al., 2004 as Pseudoclavibacter albus comb. nov. Upon primary isolation, strain 125703-2019[T] could not be identified reliably using MALDI-TOF mass spectrometry during routine diagnostic work, but partial 16S rRNA gene sequence analysis revealed that it belonged to the genus Pseudoclavibacter. Average nucleotide identity and digital DNA-DNA hybridisation analyses confirmed that it represented a novel species within this genus. A detailed physiological characterisation yielded differential tests between the novel species and its nearest neighbor taxa, which could also be differentiated using MALDI-TOF mass spectrometry. We propose to formally classify this strain into the novel species Pseudoclavibacter triregionum sp. nov., with strain 125703-2019[T] (= R-76471[T], LMG 31777[T], CCUG 74796[T]) as the type strain. The whole-genome assembly of strain 125703-2019[T] has a size of 2.4 Mb and a G + C content of 72.74%. A Pseudoclavibacter pangenome analysis revealed that 667 gene clusters were exclusively present in strain 125703-2019[T]. While these gene clusters were enriched in several COG functional categories, this analysis did not reveal functions that explained the occurrence of this species in human infection. Finally, several phylogenetic and phylogenomic analyses demonstrated that the genus Pseudoclavibacter is polyphyletic with Pseudoclavibacter soli and Pseudoclavibacter caeni representing a unique and deeply branching line of descent within the family Microbacteriaceae. We therefore also propose to reclassify both species into the novel genus Caespitibacter gen. nov. as Caespitibacter soli comb. nov. and Caespitibacter caeni comb. nov., respectively, and with C. soli comb. nov. as the type species.}, }
@article {pmid35105664, year = {2022}, author = {de Vos, WM and Tilg, H and Van Hul, M and Cani, PD}, title = {Gut microbiome and health: mechanistic insights.}, journal = {Gut}, volume = {71}, number = {5}, pages = {1020-1032}, pmid = {35105664}, issn = {1468-3288}, mesh = {Bacteria/metabolism ; Bile Acids and Salts/metabolism ; *Diabetes Mellitus, Type 2 ; Fatty Acids, Volatile/metabolism ; *Gastrointestinal Microbiome ; Humans ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metabolism are affected.In this review, specific attention is given to provide a critical evaluation of the current understanding in this field. Numerous molecular mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, short-chain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified molecular actors (ie, endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5).Altogether, understanding the complexity and the molecular aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.}, }
@article {pmid35103486, year = {2022}, author = {Shenhav, L and Azad, MB}, title = {Using Community Ecology Theory and Computational Microbiome Methods To Study Human Milk as a Biological System.}, journal = {mSystems}, volume = {7}, number = {1}, pages = {e0113221}, pmid = {35103486}, issn = {2379-5077}, mesh = {Infant ; Female ; Humans ; *Milk, Human ; Cross-Sectional Studies ; Lactation ; *Microbiota ; Breast Feeding ; }, abstract = {Human milk is a complex and dynamic biological system that has evolved to optimally nourish and protect human infants. Yet, according to a recent priority-setting review, "our current understanding of human milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation" (P. Christian et al., Am J Clin Nutr 113:1063-1072, 2021, https://doi.org/10.1093/ajcn/nqab075). We attribute this critical knowledge gap to three major reasons as follows. (i) Studies have typically examined each subsystem of the mother-milk-infant "triad" in isolation and often focus on a single element or component (e.g., maternal lactation physiology or milk microbiome or milk oligosaccharides or infant microbiome or infant gut physiology). This undermines our ability to develop comprehensive representations of the interactions between these elements and study their response to external perturbations. (ii) Multiomics studies are often cross-sectional, presenting a snapshot of milk composition, largely ignoring the temporal variability during lactation. The lack of temporal resolution precludes the characterization and inference of robust interactions between the dynamic subsystems of the triad. (iii) We lack computational methods to represent and decipher the complex ecosystem of the mother-milk-infant triad and its environment. In this review, we advocate for longitudinal multiomics data collection and demonstrate how incorporating knowledge gleaned from microbial community ecology and computational methods developed for microbiome research can serve as an anchor to advance the study of human milk and its many components as a "system within a system."}, }
@article {pmid35101562, year = {2022}, author = {Das, S and Goswami, AM and Saha, T}, title = {An insight into the role of protein kinases as virulent factors, regulating pathogenic attributes in Candida albicans.}, journal = {Microbial pathogenesis}, volume = {164}, number = {}, pages = {105418}, doi = {10.1016/j.micpath.2022.105418}, pmid = {35101562}, issn = {1096-1208}, mesh = {*Candida albicans ; *Candidiasis/pathology ; Fungal Proteins/metabolism ; Humans ; Protein Kinases ; Virulence ; Virulence Factors/metabolism ; }, abstract = {Candida albicans is a polymorphic, opportunistic pathogen, member of normal human microbiome causing candidiasis. It causes wide range of infections from superficial skin infections to life-threatening systemic infections. The pathogenicity in C. albicans attributes through several morphological characteristics and virulence factors. These morphological features are regulated by various molecules among which kinases are the most important. Several kinases and kinase signaling cascades play a well established role in Candidiasis. In this review we present an update on our current understanding of the pathogenicity attributes which is regulated by kinases as virulence factors.}, }
@article {pmid35101266, year = {2022}, author = {Kantele, A and Rombo, L and Vene, S and Kundi, M and Lindquist, L and Erra, EO}, title = {Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older: A single-centre, open-label, randomized controlled trial.}, journal = {Vaccine}, volume = {40}, number = {9}, pages = {1299-1305}, doi = {10.1016/j.vaccine.2022.01.022}, pmid = {35101266}, issn = {1873-2518}, mesh = {Adult ; Antibodies, Viral ; *Encephalitis Viruses, Tick-Borne ; *Encephalitis, Tick-Borne/prevention &amp; control ; Humans ; Immunization Schedule ; Middle Aged ; *Viral Vaccines ; }, abstract = {BACKGROUND: TBE vaccination failures among those past middle age have raised concern about immune response declining with age. We investigated immunogenicity of the TBE-vaccine FSME-Immun among those aged 50+ years using the standard three-dose primary series and alternative four-dose schedules.<br><br>METHODS: In this single-centre, open-label, randomized controlled trial, 200 TBE-naive Swedish adults were given primary TBE vaccination with FSME-Immun. Those aged 50+ years (n&#xa0;=&#xa0;150) were randomized to receive the standard three-dose (days 0-30-360) or one of two four-dose series (0-7-21-360; 0-30-90-360). For participants&#xa0;<&#xa0;50&#xa0;years (n&#xa0;=&#xa0;50) the standard three-dose schedule was used. Titres of neutralizing antibodies were determined on days 0, 60, 120, 360, and 400. The main outcome was the log titre of TBE virus-specific neutralizing antibodies on day 400.<br><br>RESULTS: The three-dose schedule yielded lower antibody titres among those aged 50+ years than the younger participants on day 400 (geometric mean titre 41 versus 74, p&#xa0;<&#xa0;0.05). The older group showed higher titres for the four-dose 0-7-21-360 than the standard three-dose schedule both on day 400 (103 versus 41, p&#xa0;<&#xa0;0.01; primary end point) and at the other testing points (days 60, 120, 360). Using the other four-dose schedule (0-30-90-360), no such difference was observed on day 400 (63 versus 41, NS).<br><br>CONCLUSION: Immune response to the TBE vaccine declined with age. A four-dose schedule (0-7-21-360) may benefit those aged 50&#xa0;years or older. This study is registered at ClinicalTrials.gov, NCT01361776.}, }
@article {pmid35096962, year = {2021}, author = {Zhang, Y and Zhou, L and Xia, J and Dong, C and Luo, X}, title = {Human Microbiome and Its Medical Applications.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {703585}, pmid = {35096962}, issn = {2296-889X}, abstract = {The commensal microbiome is essential for human health and is involved in many processes in the human body, such as the metabolism process and immune system activation. Emerging evidence implies that specific changes in the microbiome participate in the development of various diseases, including diabetes, liver diseases, tumors, and pathogen infections. Thus, intervention on the microbiome is becoming a novel and effective method to treat such diseases. Synthetic biology empowers researchers to create strains with unique and complex functions, making the use of engineered microbes for clinical applications attainable. The aim of this review is to summarize recent advances about the roles of the microbiome in certain diseases and the underlying mechanisms, as well as the use of engineered microbes in the prevention, detection, and treatment of various diseases.}, }
@article {pmid35094706, year = {2022}, author = {Alamri, A and AlKhater, SA}, title = {Evaluating the knowledge on microbiome and dysbiosis in allergic diseases among medical sciences students in Saudi Arabia.}, journal = {Clinical and molecular allergy : CMA}, volume = {20}, number = {1}, pages = {2}, pmid = {35094706}, issn = {1476-7961}, abstract = {BACKGROUND: Microbiome science deals with the development of diseases that are derived from the interaction between the host immune system and microbes. Microbiome disturbance or dysbiosis has been increasingly recognized as an important contributor to the pathogenesis of allergic diseases. Thus, this field is pivotal in the management of allergic disorders. Despite the increasing prevalence of allergic disorders in Saudi Arabia, medical students lack knowledge of microbiome science. Therefore, this study aimed to assess the level of knowledge of medical sciences students on the human microbiome, dysbiosis, and management of the impaired microbiome with a focus on allergic diseases and asthma.<br><br>METHODS: An online survey was designed, validated, and distributed to 100 final-year students and interns majoring in clinical nutrition, public health, and clinical laboratory sciences at a single university in Saudi Arabia. The study period was from November 2020 to January 2021.<br><br>RESULTS: The overall knowledge of the human microbiome was adequate among the participants, but their understanding of dysbiosis and management of the impaired microbiome was low to moderate. Knowledge of dysbiosis management was significantly higher in students majoring in clinical nutrition than in those majoring in public health and clinical laboratory sciences.<br><br>CONCLUSIONS: Collectively, this study provides the first evidence that knowledge of specific domains of microbiome science among a cohort of medical sciences students in Saudi Arabia is insufficient. Large-scale studies are warranted to confirm these observations at a national level, and specific curriculum modifications are necessary to improve the knowledge of future healthcare professionals about clinical applications of microbiome science.}, }
@article {pmid35093602, year = {2022}, author = {Zhang, X and Zhai, Q and Wang, J and Ma, X and Xing, B and Fan, H and Gao, Z and Zhao, F and Liu, W}, title = {Variation of the Vaginal Microbiome During and After Pregnancy in Chinese Women.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {20}, number = {2}, pages = {322-333}, pmid = {35093602}, issn = {2210-3244}, mesh = {Humans ; Infant, Newborn ; Pregnancy ; Female ; *Premature Birth/microbiology ; Vagina/microbiology ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Lactobacillus/genetics ; Bacteria/genetics ; China/epidemiology ; }, abstract = {A comprehensive profiling of the vaginal microbial communities and their variability enables an accurate description of the microbiome in women. However, there is a lack of studies available on Chinese women. In the present study, the composition of the vaginal microbiota during pregnancy and the 6-week postpartum period of 454 Chinese women was characterized by sequencing the V3-V4 region of the 16S ribosomal RNA (rRNA) gene. The vaginal microbiome showed variations during pregnancy and the postpartum period based on the abortion history, hypertensive disorders, delivery mode, and maternal age. Co-variation of 22 bacterial taxa, including the Lactobacillus genus and two of its species, may account for the common characteristics of the vaginal microbiome under scenarios of different medical histories and pregnancy outcomes. In contrast, discriminant bacterial species were significantly different between women who had preterm birth (PTB) with and without premature rupture of membranes (PROM), and the community state type (CST) IV-A without any predominant Lactobacillus species in the microbiota was more prevalent during pregnancy in the PROM-PTB cases, suggesting that specific bacterial species could be considered to distinguish between different types of PTB. By providing data on Chinese women, this study will enrich the knowledge of the human microbiome and contribute to a better understanding of the association between the vaginal microbiome and reproductive health.}, }
@article {pmid35092364, year = {2022}, author = {McClure, S and Enam, F and Arnold, J and Mimee, M}, title = {Proceedings from the 3rd International Conference on Microbiome Engineering.}, journal = {Biotechnology progress}, volume = {38}, number = {3}, pages = {e3241}, pmid = {35092364}, issn = {1520-6033}, mesh = {*Bacteriophages/genetics ; Bone and Bones/chemistry ; Humans ; *Microbiota/genetics ; Prebiotics/analysis ; *Probiotics/therapeutic use ; }, abstract = {The human microbiome has been inextricably linked to multiple facets of human physiology. From an engineering standpoint, the ability to precisely control the composition and activity of the microbiome holds great promise for furthering our understanding of disease etiology and for new avenues of therapeutic and diagnostic agents. While the field of microbiome research is still in its infancy, growing engineering efforts are emerging to enable new studies in the microbiome and to rapidly translate these findings to microbiome-based interventions. At the 3rd International Conference on Microbiome Engineering, leading experts in the field presented state-of-the-art work in microbiome engineering, discussing probiotics, prebiotics, engineered microbes, microbially derived biomolecules, and bacteriophage.}, }
@article {pmid35091681, year = {2022}, author = {Saliba, J and Coutaud, B and Makhani, K and Epstein Roth, N and Jackson, J and Park, JY and Gagnon, N and Costa, P and Jeyakumar, T and Bury, M and Beauchemin, N and Mann, KK and Blank, V}, title = {Loss of NFE2L3 protects against inflammation-induced colorectal cancer through modulation of the tumor microenvironment.}, journal = {Oncogene}, volume = {41}, number = {11}, pages = {1563-1575}, pmid = {35091681}, issn = {1476-5594}, support = {MOP-97932//CIHR/Canada ; PJT-152937//CIHR/Canada ; }, mesh = {Animals ; Basic-Leucine Zipper Transcription Factors/metabolism ; *Colorectal Neoplasms/genetics ; Forkhead Transcription Factors ; Humans ; Inflammation/genetics ; Interleukin-33 ; Mice ; T-Lymphocytes, Regulatory ; *Tumor Microenvironment/genetics ; }, abstract = {We investigated the role of the NFE2L3 transcription factor in inflammation-induced colorectal cancer. Our studies revealed that Nfe2l3[-/-] mice exhibit significantly less inflammation in the colon, reduced tumor size and numbers, and skewed localization of tumors with a more pronounced decrease of tumors in the distal colon. CIBERSORT analysis of RNA-seq data from normal and tumor tissue predicted a reduction in mast cells in Nfe2l3[-/-] animals, which was confirmed by toluidine blue staining. Concomitantly, the transcript levels of Il33 and Rab27a, both important regulators of mast cells, were reduced and increased, respectively, in the colorectal tumors of Nfe2l3[-/-] mice. Furthermore, we validated NFE2L3 binding to the regulatory sequences of the IL33 and RAB27A loci in human colorectal carcinoma cells. Using digital spatial profiling, we found that Nfe2l3[-/-] mice presented elevated FOXP3 and immune checkpoint markers CTLA4, TIM3, and LAG3, suggesting an increase in Treg counts. Staining for CD3 and FOXP3 confirmed a significant increase in immunosuppressive Tregs in the colon of Nfe2l3[-/-] animals. Also, Human Microbiome Project (HMP2) data showed that NFE2L3 transcript levels are higher in the rectum of ulcerative colitis patients. The observed changes in the tumor microenvironment provide new insights into the molecular differences regarding colon cancer sidedness. This may be exploited for the treatment of early-onset colorectal cancer as this emerging subtype primarily displays distal/left-sided tumors.}, }
@article {pmid35086550, year = {2022}, author = {Romito, I and Porru, M and Braghini, MR and Pompili, L and Panera, N and Crudele, A and Gnani, D and De Stefanis, C and Scarsella, M and Pomella, S and Mortera, SL and de Billy, E and Conti, AL and Marzano, V and Putignani, L and Vinciguerra, M and Balsano, C and Pastore, A and Rota, R and Tartaglia, M and Leonetti, C and Alisi, A}, title = {Correction to: Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {41}, number = {1}, pages = {40}, pmid = {35086550}, issn = {1756-9966}, }
@article {pmid35078284, year = {2022}, author = {Su, Z and Jia, X and Fan, Y and Zhao, F and Qiao, Y}, title = {[Progress of Research on the Relationship between Lung Microbiome and Lung Cancer].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {25}, number = {1}, pages = {40-45}, pmid = {35078284}, issn = {1999-6187}, mesh = {Humans ; Lung ; Lung Diseases ; *Lung Neoplasms ; *Microbiota ; Oncogenes ; }, abstract = {The microbiota plays an important role in the biological functions of the human body and is associated with various disease states such as inflammation (gastritis, hepatitis) and cancer (stomach, cervical, liver). The Human Microbiome Project painted a panorama of human microorganisms in its first phase, incorporating body parts such as the nasal cavity, oral cavity, intestine, vagina and skin, while the lungs were considered a sterile environment. However, studies in recent years have confirmed the presence of a rich microbial community in the lung, and the association of this lung microbiota with lung disease has become a hot topic of research. Current research has found that patients with lung cancer have a specific microbiota compared to healthy individuals or patients with lung disease. Even in patients with lung cancer, a lung microbiota specific to the tumor site is present. In addition, different pathological types and metastatic status of lung cancer can lead to differences in microbiota. Mechanistic studies have found that the lung microbiota may influence lung cancer development by affecting the immune response. Clinical studies on lung microbiota and immunotherapy are still in the preliminary stage. More relevant studies are needed in the future to provide high-quality evidence to further understand the oncogenic mechanisms of lung microbiota and provide new ideas for clinical treatment. This paper briefly reviews the progress of lung microbiota research in terms of its relevance to lung cancer, possible molecular mechanisms and applications in clinical treatment, and provides an outlook for future research. .}, }
@article {pmid35070166, year = {2022}, author = {Hou, Q and Pucci, F and Pan, F and Xue, F and Rooman, M and Feng, Q}, title = {Using metagenomic data to boost protein structure prediction and discovery.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {434-442}, pmid = {35070166}, issn = {2001-0370}, abstract = {Over the past decade, metagenomic sequencing approaches have been providing an ever-increasing amount of protein sequence data at an astonishing rate. These constitute an invaluable source of information which has been exploited in various research fields such as the study of the role of the gut microbiota in human diseases and aging. However, only a small fraction of all metagenomic sequences collected have been functionally or structurally characterized, leaving much of them completely unexplored. Here, we review how this information has been used in protein structure prediction and protein discovery. We begin by presenting some widely used metagenomic databases and analyze in detail how metagenomic data has contributed to the impressive improvement in the accuracy of structure prediction methods in recent years. We then examine how metagenomic information can be exploited to annotate protein sequences. More specifically, we focus on the role of metagenomes in the discovery of enzymes and new CRISPR-Cas systems, and in the identification of antibiotic resistance genes. With this review, we provide an overview of how metagenomic data is currently revolutionizing our understanding of protein science.}, }
@article {pmid35065652, year = {2022}, author = {Salachan, PV and Sørensen, KD}, title = {Dysbiotic microbes and how to find them: a review of microbiome profiling in prostate cancer.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {41}, number = {1}, pages = {31}, pmid = {35065652}, issn = {1756-9966}, mesh = {Dysbiosis/*physiopathology ; Humans ; Male ; Microbiota/*physiology ; Prostatic Neoplasms/*physiopathology ; }, abstract = {The role of the microbiota in human health and disease is well established, including its effects on several cancer types. However, the role of microbial dysbiosis in prostate cancer development, progression, and response to treatment is less well understood. This knowledge gap could perhaps be implicated in the lack of better risk stratification and prognostic tools that incorporate risk factors such as bacterial infections and inflammatory signatures. With over a decade's research investigating associations between microbiome and prostate carcinogenesis, we are ever closer to finding the crucial biological link between the two. Yet, definitive answers remain elusive, calling for continued research into this field. In this review, we outline the three frequently used NGS based analysis methodologies that are used for microbiome profiling, thereby serving as a quick guide for future microbiome research. We next provide a detailed overview of the current knowledge of the role of the human microbiome in prostate cancer development, progression, and treatment response. Finally, we describe proposed mechanisms of host-microbe interactions that could lead to prostate cancer development, progression or treatment response.}, }
@article {pmid35061732, year = {2022}, author = {Hyde, ER and Lozano, H and Cox, S}, title = {BIOME-Preserve: A novel storage and transport medium for preserving anaerobic microbiota samples for culture recovery.}, journal = {PloS one}, volume = {17}, number = {1}, pages = {e0261820}, pmid = {35061732}, issn = {1932-6203}, mesh = {Anaerobiosis ; *Bacteria/classification/genetics ; Feces/*microbiology ; Female ; Humans ; Male ; *Microbiota ; *Preservation, Biological ; *Specimen Handling ; }, abstract = {Sequencing-based protocols for studying the human microbiome have unearthed a wealth of information about the relationship between the microbiome and human health. But these microbes cannot be leveraged as therapeutic targets without culture-based studies to phenotype species of interest and to establish culture collections for use in animal models. Traditional sample collection protocols are focused on preserving nucleic acids and metabolites and are largely inappropriate for preserving sensitive anaerobic bacteria for later culture recovery. Here we introduce a novel microbiome preservation kit (BIOME-Preserve) that facilitates recovery of anaerobic bacteria from human stool. Using a combination of culture recovery and shallow whole-genome shotgun sequencing, we characterized the anaerobes cultured from fresh human stool and from human stool held at room temperature in BIOME-Preserve for up to 120 hours. We recovered several species of interest to microbiome researchers, including Bifidobacterium spp., Bacteroides spp., Blautia spp., Eubacterium halii (now Anaerobutyricum hallii), Akkermansia muciniphila, and Faecalibacterium prausnitzii. We also demonstrated that freezing at -80°C did not adversely affect our ability to culture organisms from BIOME-Preserve, suggesting that it is appropriate both as a transport medium and as a medium for longer-term ultra-cold storage. Together, our results suggest BIOME-Preserve is practical for the collection, transport, and culture of anaerobic bacteria from human samples and can help enable researchers to better understand the link between the microbiome and human health and how to leverage that link through novel microbiome-based therapeutics.}, }
@article {pmid35056496, year = {2021}, author = {Qiao, W and Liu, F and Wan, X and Qiao, Y and Li, R and Wu, Z and Saris, PEJ and Xu, H and Qiao, M}, title = {Genomic Features and Construction of Streamlined Genome Chassis of Nisin Z Producer Lactococcus lactis N8.}, journal = {Microorganisms}, volume = {10}, number = {1}, pages = {}, pmid = {35056496}, issn = {2076-2607}, support = {31770102//National Natural Science Foundation of China/ ; 200050//Jane and Aatos Erkko Foundation/ ; }, abstract = {Lactococcus lactis is a commonly used fermenting bacteria in cheese, beverages and meat products. Due to the lack of simplified chassis strains, it has not been widely used in the fields of synthetic biology. Thus, the construction of lactic acid bacteria chassis strains becomes more and more important. In this study, we performed whole genome sequencing, annotation and analysis of L. lactis N8. Based on the genome analysis, we found that L. lactis N8 contains two large plasmids, and the function prediction of the plasmids shows that some regions are related to carbohydrate transport/metabolism, multi-stress resistance and amino acid uptake. L. lactis N8 contains a total of seven prophage-related fragments and twelve genomic islands. A gene cluster encoding a hybrid NRPS-PKS system that was found in L. lactis N8 reveals that the strain has the potential to synthesize novel secondary metabolites. Furthermore, we have constructed a simplified genome chassis of L. lactis N8 and achieved the largest amount of deletion of L. lactis so far. Taken together, the present study offers further insights into the function and potential role of L. lactis N8 as a model strain of lactic acid bacteria and lays the foundation for its application in the field of synthetic biology.}, }
@article {pmid35054168, year = {2021}, author = {Gouello, A and Dunyach-Remy, C and Siatka, C and Lavigne, JP}, title = {Analysis of Microbial Communities: An Emerging Tool in Forensic Sciences.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {35054168}, issn = {2075-4418}, abstract = {The objective of forensic sciences is to find clues in a crime scene in order to reconstruct the scenario. Classical samples include DNA or fingerprints, but both have inherent limitations and can be uninformative. Another type of sample has emerged recently in the form of the microbiome. Supported by the Human Microbiome Project, the characteristics of the microbial communities provide real potential in forensics. They are highly specific and can be used to differentiate and classify the originating body site of a human biological trace. Skin microbiota is also highly specific and different between individuals, leading to its possibility as an identification tool. By extension, the possibilities of the microbial communities to be deposited on everyday objects has also been explored. Other uses include the determination of the post-mortem interval or the analysis of soil communities. One challenge is that the microbiome changes over time and can be influenced by many environmental and lifestyle factors. This review offers an overview of the main methods and applications to demonstrate the benefit of the microbiome to provide forensically relevant information.}, }
@article {pmid35053587, year = {2022}, author = {Kato, I and Zhang, J and Sun, J}, title = {Bacterial-Viral Interactions in Human Orodigestive and Female Genital Tract Cancers: A Summary of Epidemiologic and Laboratory Evidence.}, journal = {Cancers}, volume = {14}, number = {2}, pages = {}, pmid = {35053587}, issn = {2072-6694}, support = {R01 DK105118, R01DK114126/NH/NIH HHS/United States ; CDMRP BC191198//Department of Defence/ ; I01BX004824-01//Veterans for America/ ; }, abstract = {Infectious agents, including viruses, bacteria, fungi, and parasites, have been linked to pathogenesis of human cancers, whereas viruses and bacteria account for more than 99% of infection associated cancers. The human microbiome consists of not only bacteria, but also viruses and fungi. The microbiome co-residing in specific anatomic niches may modulate oncologic potentials of infectious agents in carcinogenesis. In this review, we focused on interactions between viruses and bacteria for cancers arising from the orodigestive tract and the female genital tract. We examined the interactions of these two different biological entities in the context of human carcinogenesis in the following three fashions: (1) direct interactions, (2) indirect interactions, and (3) no interaction between the two groups, but both acting on the same host carcinogenic pathways, yielding synergistic or additive effects in human cancers, e.g., head and neck cancer, liver cancer, colon cancer, gastric cancer, and cervical cancer. We discuss the progress in the current literature and summarize the mechanisms of host-viral-bacterial interactions in various human cancers. Our goal was to evaluate existing evidence and identify gaps in the knowledge for future directions in infection and cancer.}, }
@article {pmid35052575, year = {2021}, author = {Forero-Rodríguez, LJ and Josephs-Spaulding, J and Flor, S and Pinzón, A and Kaleta, C}, title = {Parkinson's Disease and the Metal-Microbiome-Gut-Brain Axis: A Systems Toxicology Approach.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, pmid = {35052575}, issn = {2076-3921}, support = {EXC 2167//Precision Medicine in Chronic Inflammation/ ; FOR5042//Research Unit miTarget/ ; }, abstract = {Parkinson's Disease (PD) is a neurodegenerative disease, leading to motor and non-motor complications. Autonomic alterations, including gastrointestinal symptoms, precede motor defects and act as early warning signs. Chronic exposure to dietary, environmental heavy metals impacts the gastrointestinal system and host-associated microbiome, eventually affecting the central nervous system. The correlation between dysbiosis and PD suggests a functional and bidirectional communication between the gut and the brain. The bioaccumulation of metals promotes stress mechanisms by increasing reactive oxygen species, likely altering the bidirectional gut-brain link. To better understand the differing molecular mechanisms underlying PD, integrative modeling approaches are necessary to connect multifactorial perturbations in this heterogeneous disorder. By exploring the effects of gut microbiota modulation on dietary heavy metal exposure in relation to PD onset, the modification of the host-associated microbiome to mitigate neurological stress may be a future treatment option against neurodegeneration through bioremediation. The progressive movement towards a systems toxicology framework for precision medicine can uncover molecular mechanisms underlying PD onset such as metal regulation and microbial community interactions by developing predictive models to better understand PD etiology to identify options for novel treatments and beyond. Several methodologies recently addressed the complexity of this interaction from different perspectives; however, to date, a comprehensive review of these approaches is still lacking. Therefore, our main aim through this manuscript is to fill this gap in the scientific literature by reviewing recently published papers to address the surrounding questions regarding the underlying molecular mechanisms between metals, microbiota, and the gut-brain-axis, as well as the regulation of this system to prevent neurodegeneration.}, }
@article {pmid35047812, year = {2022}, author = {Banerjee, K and Chen, J and Zhan, X}, title = {Adaptive and powerful microbiome multivariate association analysis via feature selection.}, journal = {NAR genomics and bioinformatics}, volume = {4}, number = {1}, pages = {lqab120}, pmid = {35047812}, issn = {2631-9268}, abstract = {The important role of human microbiome is being increasingly recognized in health and disease conditions. Since microbiome data is typically high dimensional, one popular mode of statistical association analysis for microbiome data is to pool individual microbial features into a group, and then conduct group-based multivariate association analysis. A corresponding challenge within this approach is to achieve adequate power to detect an association signal between a group of microbial features and the outcome of interest across a wide range of scenarios. Recognizing some existing methods' susceptibility to the adverse effects of noise accumulation, we introduce the Adaptive Microbiome Association Test (AMAT), a novel and powerful tool for multivariate microbiome association analysis, which unifies both blessings of feature selection in high-dimensional inference and robustness of adaptive statistical association testing. AMAT first alleviates the burden of noise accumulation via distance correlation learning, and then conducts a data-adaptive association test under the flexible generalized linear model framework. Extensive simulation studies and real data applications demonstrate that AMAT is highly robust and often more powerful than several existing methods, while preserving the correct type I error rate. A free implementation of AMAT in R computing environment is available at https://github.com/kzb193/AMAT.}, }
@article {pmid35046908, year = {2021}, author = {Hammerl, JA and Barac, A and Bienert, A and Demir, A and Drüke, N and Jäckel, C and Matthies, N and Jun, JW and Skurnik, M and Ulrich, J and Hertwig, S}, title = {Birds Kept in the German Zoo "Tierpark Berlin" Are a Common Source for Polyvalent Yersinia pseudotuberculosis Phages.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {634289}, pmid = {35046908}, issn = {1664-302X}, abstract = {Yersinia pseudotuberculosis is an important animal pathogen, particularly for birds, rodents, and monkeys, which is also able to infect humans. Indeed, an increasing number of reports have been published on zoo animals that were killed by this species. One option to treat diseased animals is the application of strictly lytic (virulent) phages. However, thus far relatively few phages infecting Y. pseudotuberculosis have been isolated and characterized. To determine the prevalence of Y. pseudotuberculosis phages in zoo animals, fecal samples of birds and some primates, maras, and peccaries kept in the Tierpark Berlin were analyzed. Seventeen out of 74 samples taken in 2013 and 2017 contained virulent phages. The isolated phages were analyzed in detail and could be allocated to three groups. The first group is composed of 10 T4-like phages (PYps2T taxon group: Myoviridae; Tevenvirinae; Tequatrovirus), the second group (PYps23T taxon group: Chaseviridae; Carltongylesvirus; Escherichia virus ST32) consists of five phages encoding a podovirus-like RNA polymerase that is related to an uncommon genus of myoviruses (e.g., Escherichia coli phage phiEcoM-GJ1), while the third group is comprised of two podoviruses (PYps50T taxon group: Autographiviridae; Studiervirinae; Berlinvirus) which are closely related to T7. The host range of the isolated phages differed significantly. Between 5.5 and 86.7% of 128 Y. pseudotuberculosis strains belonging to 20 serotypes were lysed by each phage. All phages were additionally able to lyse Y. enterocolitica B4/O:3 strains, when incubated at 37°C. Some phages also infected Y. pestis strains and even strains belonging to other genera of Enterobacteriaceae. A cocktail containing two of these phages would be able to lyse almost 93% of the tested Y. pseudotuberculosis strains. The study indicates that Y. pseudotuberculosis phages exhibiting a broad-host range can be isolated quite easily from zoo animals, particularly birds.}, }
@article {pmid35042457, year = {2022}, author = {Latino, C and Gianatti, EJ and Mehta, S and Lo, J and Devine, A and Christophersen, C}, title = {Does a high dietary intake of resistant starch affect glycaemic control and alter the gut microbiome in women with gestational diabetes? A randomised control trial protocol.}, journal = {BMC pregnancy and childbirth}, volume = {22}, number = {1}, pages = {46}, pmid = {35042457}, issn = {1471-2393}, support = {Enabling Allied Health Research Capacity 2020//Department of Health, Government of Western Australia/ ; G1005941//Spinnaker Health Research Foundation/ ; }, mesh = {Adult ; Australia/epidemiology ; Diabetes, Gestational/blood/*diet therapy ; Dietary Fiber/*administration &amp; dosage ; Dietary Supplements ; Female ; Gastrointestinal Microbiome/*drug effects ; *Glycemic Control ; Humans ; Linear Models ; Pregnancy ; *Randomized Controlled Trials as Topic ; Resistant Starch/*administration &amp; dosage ; }, abstract = {BACKGROUND: Gestational Diabetes Mellitus (GDM) is prevalent with lasting health implications for the mother and offspring. Medical nutrition therapy is the foundation of GDM management yet achieving optimal glycaemic control often requires treatment with medications, like insulin. New dietary strategies to improve GDM management and outcomes are required. Gut dysbiosis is a feature of GDM pregnancies, therefore, dietary manipulation of the gut microbiota may offer a new avenue for management. Resistant starch is a fermentable dietary fibre known to alter the gut microbiota and enhance production of short-chain fatty acids. Evidence suggests that short-chain fatty acids improve glycaemia via multiple mechanisms, however, this has not been evaluated in GDM.<br><br>METHODS: An open-label, parallel-group design study will investigate whether a high dietary resistant starch intake or resistant starch supplement improves glycaemic control and changes the gut microbiome compared with standard dietary advice in women with newly diagnosed GDM. Ninety women will be randomised to one of three groups - standard dietary treatment for GDM (Control), a high resistant starch diet or a high resistant starch diet plus a 16&#x2009;g resistant starch supplement. Measurements taken at Baseline (24 to 30-weeks' gestation), Day 10 and Day 56 (approximately 36&#x2009;weeks' gestation) will include fasting plasma glucose levels, microbial composition and short-chain fatty acid concentrations in stool, 3-day dietary intake records and bowel symptoms questionnaires. One-week post-natal data collection will include microbial composition and short-chain fatty acid concentrations of maternal and neonatal stools, microbial composition of breastmilk, birthweight, maternal and neonatal outcomes. Mixed model analysis of variance will assess change in glycaemia and permutation-based multivariate analysis of variance will assess changes in microbial composition within and between intervention groups. Distance-based linear modelling will identify correlation between change in stool microbiota, short-chain fatty acids and measures of glycaemia.<br><br>DISCUSSION: To improve outcomes for GDM dyads, evaluation of a high dietary intake of resistant starch to improve glycaemia through the gut microbiome needs to be established. This will expand the dietary interventions available to manage GDM without medication.<br><br>TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry, ACTRN12620000968976p . Registered 28 September 2020.}, }
@article {pmid35042114, year = {2022}, author = {Ruiz-Rico, M and Renwick, S and Allen-Vercoe, E and Barat, JM}, title = {In vitro susceptibility of human gut microbes to potential food preservatives based on immobilized phenolic compounds.}, journal = {Food chemistry}, volume = {378}, number = {}, pages = {132136}, doi = {10.1016/j.foodchem.2022.132136}, pmid = {35042114}, issn = {1873-7072}, mesh = {*Actinobacteria/genetics ; Bacteroidetes/genetics ; Food Preservatives ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; RNA, Ribosomal, 16S ; }, abstract = {The development of novel food preservatives based on natural antimicrobials such as phenolic compounds is increasing, but their safety should be established before use, including evaluating their impact on the gut microbiota. This work explored the influence of antimicrobial phenolics presented in different forms on selected human gut microbiota members through in vitro susceptibility tests. The bacteria tested exhibited a wide range of susceptibilities to phenolics depending on the molecule structure and mode of administration. Agathobacter rectalis and Clostridium spiroforme, members of the phylum Firmicutes, were the most sensitive strains. Susceptibility was strain- and species-specific, suggesting that it may not be possible to easily extrapolate results across the human microbiome in general. Species of other phyla including Bacteroidetes, Actinobacteria, Proteobacteria and Verrucomicrobia were more resistant than Firmicutes, with growth of some strains even enhanced. Our results provide insights into the biocompatibility of free and immobilized phenolics as potential food additives.}, }
@article {pmid35040024, year = {2022}, author = {Mulpuru, V and Mishra, N}, title = {Antimicrobial Peptides from Human Microbiome Against Multidrug Efflux Pump of Pseudomonas aeruginosa: a Computational Study.}, journal = {Probiotics and antimicrobial proteins}, volume = {14}, number = {1}, pages = {180-188}, pmid = {35040024}, issn = {1867-1314}, mesh = {Anti-Bacterial Agents/metabolism/pharmacology ; Antimicrobial Peptides ; Bacterial Outer Membrane Proteins/metabolism ; Humans ; Membrane Transport Proteins/metabolism ; Microbial Sensitivity Tests ; *Microbiota ; *Pseudomonas aeruginosa/metabolism ; }, abstract = {The excess use of antibiotics has led to the evolution of multidrug-resistant pathogenic strains causing worldwide havoc. These multidrug-resistant strains require potent inhibitors. Pseudomonas aeruginosa is a lead cause of nosocomial infections and also feature in the critical priority list of the world health organization (WHO) for the development of new antibiotics against their antimicrobial resistance. Antimicrobial peptides (AMPs) found in almost every life form from microorganisms to humans are known to defend their hosts against various pathogens. Owing to the diversity of the human microbiome, in this study, we have identified the cell-penetrating AMPs from the human microbiome and studied their inhibitory activity against the outer membrane protein OprM of the MexAB-OprM, a constitutively expressed multidrug efflux pump of the Ps. aeruginosa. Screening of the AMPs from the human microbiome resulted in the identification of 147 cell-penetrating AMPs (CPAMPs). The virtual screening of these CPAMPs against the OprM protein showed significant inhibitory results with the top docked AMP showing binding affinity exceeding -30 kcal/mol. The molecular dynamic simulation determined the interaction stabilities between the AMPs and the OprM at the binding site. Further, the residue interaction networks (RINs) are analyses to identify the inhibitory patterns. Later, these patterns were confirmed by MM-PBSA analysis suggesting that the AMPs are majorly stabilized by electrostatic interactions at the binding site. Thus, the high binding affinity and insights from the molecular interaction signify that the identified CPAMPs from the human microbiome can be further explored as inhibitory agents against multidrug-resistant Ps. aeruginosa.}, }
@article {pmid35039534, year = {2022}, author = {Lee, SJ and Rho, M}, title = {Multimodal deep learning applied to classify healthy and disease states of human microbiome.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {824}, pmid = {35039534}, issn = {2045-2322}, support = {2017M3A9F3041232//National Research Foundation of Korea/ ; 2020-0-01373//Institute of Information &amp; Communications Technology Planning &amp; Evaluation (IITP)/ ; }, mesh = {Colorectal Neoplasms/diagnosis/*microbiology ; *Deep Learning ; Diabetes Mellitus, Type 2/diagnosis/*microbiology ; Genome, Microbial/*genetics ; *Healthy Volunteers ; Humans ; Inflammatory Bowel Diseases/diagnosis/*microbiology ; Liver Cirrhosis/diagnosis/*microbiology ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/*genetics ; }, abstract = {Metagenomic sequencing methods provide considerable genomic information regarding human microbiomes, enabling us to discover and understand microbial diseases. Compositional differences have been reported between patients and healthy people, which could be used in the diagnosis of patients. Despite significant progress in this regard, the accuracy of these tools needs to be improved for applications in diagnostics and therapeutics. MDL4Microbiome, the method developed herein, demonstrated high accuracy in predicting disease status by using various features from metagenome sequences and a multimodal deep learning model. We propose combining three different features, i.e., conventional taxonomic profiles, genome-level relative abundance, and metabolic functional characteristics, to enhance classification accuracy. This deep learning model enabled the construction of a classifier that combines these various modalities encoded in the human microbiome. We achieved accuracies of 0.98, 0.76, 0.84, and 0.97 for predicting patients with inflammatory bowel disease, type 2 diabetes, liver cirrhosis, and colorectal cancer, respectively; these are comparable or higher than classical machine learning methods. A deeper analysis was also performed on the resulting sets of selected features to understand the contribution of their different characteristics. MDL4Microbiome is a classifier with higher or comparable accuracy compared with other machine learning methods, which offers perspectives on feature generation with metagenome sequences in deep learning models and their advantages in the classification of host disease status.}, }
@article {pmid35024099, year = {2022}, author = {Pettersen, VK and Antunes, LCM and Dufour, A and Arrieta, MC}, title = {Inferring early-life host and microbiome functions by mass spectrometry-based metaproteomics and metabolomics.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {274-286}, pmid = {35024099}, issn = {2001-0370}, abstract = {Humans have a long-standing coexistence with microorganisms. In particular, the microbial community that populates the human gastrointestinal tract has emerged as a critical player in governing human health and disease. DNA and RNA sequencing techniques that map taxonomical composition and genomic potential of the gut community have become invaluable for microbiome research. However, deriving a biochemical understanding of how activities of the gut microbiome shape host development and physiology requires an expanded experimental design that goes beyond these approaches. In this review, we explore advances in high-throughput techniques based on liquid chromatography-mass spectrometry. These omics methods for the identification of proteins and metabolites have enabled direct characterisation of gut microbiome functions and the crosstalk with the host. We discuss current metaproteomics and metabolomics workflows for producing functional profiles, the existing methodological challenges and limitations, and recent studies utilising these techniques with a special focus on early life gut microbiome.}, }
@article {pmid35019670, year = {2022}, author = {Klopp, J and Ferretti, P and Meyer, CU and Hilbert, K and Haiß, A and Marißen, J and Henneke, P and Hudalla, H and Pirr, S and Viemann, D and Zemlin, M and Forslund, SK and Härtel, C and Bork, P and Gehring, S and Van Rossum, T and , }, title = {Meconium Microbiome of Very Preterm Infants across Germany.}, journal = {mSphere}, volume = {7}, number = {1}, pages = {e0080821}, pmid = {35019670}, issn = {2379-5042}, mesh = {Adult ; Bacteria/genetics ; Bifidobacterium/genetics ; Germany ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; *Meconium/microbiology ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Meconium constitutes infants' first bowel movements postnatally. The consistency and microbial load of meconium are different from infant and adult stool. While recent evidence suggests that meconium is sterile in utero, rapid colonization occurs after birth. The meconium microbiome has been associated with negative health outcomes, but its composition is not well described, especially in preterm infants. Here, we characterized the meconium microbiomes from 330 very preterm infants (gestational ages 28 to 32 weeks) from 15 hospitals in Germany and in fecal samples from a subset of their mothers (N = 217). Microbiome profiles were compiled using 16S rRNA gene sequencing with negative and positive controls. The meconium microbiome was dominated by Bifidobacterium, Staphylococcus, and Enterococcus spp. and was associated with gestational age at birth and age at sample collection. Bifidobacterial abundance was negatively correlated with potentially pathogenic genera. The amount of bacterial DNA in meconium samples varied greatly across samples and was associated with the time since birth but not with gestational age or hospital site. In samples with low bacterial load, human mitochondrial sequences were highly amplified using commonly used, bacterial-targeted 16S rRNA primers. Only half of the meconium samples contained sufficient bacterial material to study the microbiome using a standard approach. To facilitate future meconium studies, we present a five-level scoring system ("MecBac") that predicts the success of 16S rRNA bacterial sequencing for meconium samples. These findings provide a foundational characterization of an understudied portion of the human microbiome and will aid the design of future meconium microbiome studies. IMPORTANCE Meconium is present in the intestines of infants before and after birth and constitutes their first bowel movements postnatally. The consistency, composition and microbial load of meconium is largely different from infant and adult stool. While recent evidence suggests that meconium is sterile in utero, rapid colonization occurs after birth. The meconium microbiome has been associated with short-term and long-term negative health outcomes, but its composition is not yet well described, especially in preterm infants. We provide a characterization of the microbiome structure and composition of infant meconium and maternal feces from a large study cohort and propose a method to evaluate meconium samples for bacterial sequencing suitability. These findings provide a foundational characterization of an understudied portion of the human microbiome and will aid the design of future meconium microbiome studies.}, }
@article {pmid35017199, year = {2022}, author = {Chen, C and Liao, J and Xia, Y and Liu, X and Jones, R and Haran, J and McCormick, B and Sampson, TR and Alam, A and Ye, K}, title = {Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation.}, journal = {Gut}, volume = {71}, number = {11}, pages = {2233-2252}, pmid = {35017199}, issn = {1468-3288}, support = {P30 AG066511/AG/NIA NIH HHS/United States ; R01 AG065177/AG/NIA NIH HHS/United States ; RF1 AG067483/AG/NIA NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; K23 AG057790/AG/NIA NIH HHS/United States ; R56 DK136728/DK/NIDDK NIH HHS/United States ; K01 DK114391/DK/NIDDK NIH HHS/United States ; P20 GM130456/GM/NIGMS NIH HHS/United States ; }, mesh = {*Alzheimer Disease/metabolism ; Animals ; Cognition ; Disease Models, Animal ; Dysbiosis ; Fatty Acids, Unsaturated ; *Gastrointestinal Microbiome/physiology ; Humans ; Inflammation/metabolism ; Insulin-Like Growth Factor I ; *Insulins ; Mice ; Neuroinflammatory Diseases ; Plaque, Amyloid/pathology ; RNA, Ribosomal, 16S ; }, abstract = {OBJECTIVE: This study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer's disease (AD) pathogenesis.<br><br>DESIGN: We analysed the gut microbiota composition of 3&#xd7;Tg mice in an age-dependent manner. We generated germ-free 3&#xd7;Tg mice and recolonisation of germ-free 3&#xd7;Tg mice with fecal samples from both patients with AD and age-matched healthy donors.<br><br>RESULTS: Microbial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-&#x3b2; plaques and neurofibrillary tangles pathology in germ-free 3&#xd7;Tg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3&#xd7;Tg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients' gut microbiome exacerbated AD pathologies in 3&#xd7;Tg mice, associated with C/EBP&#x3b2;/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors' microbiota transplants.<br><br>CONCLUSIONS: These findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.}, }
@article {pmid35015907, year = {2022}, author = {Amar, Y and Schneider, E and Köberle, M and Seeholzer, T and Musiol, S and Hölge, IM and Gschwendtner, S and Krappmann, D and Steiger, K and Biedermann, T and Schmidt-Weber, CB and Alessandrini, F}, title = {Microbial dysbiosis in a mouse model of atopic dermatitis mimics shifts in human microbiome and correlates with the key pro-inflammatory cytokines IL-4, IL-33 and TSLP.}, journal = {Journal of the European Academy of Dermatology and Venereology : JEADV}, volume = {36}, number = {5}, pages = {705-716}, doi = {10.1111/jdv.17911}, pmid = {35015907}, issn = {1468-3083}, support = {22011215//Federal Ministry of Food and Agriculture/ ; //Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Bacteria ; Cytokines ; *Dermatitis, Atopic ; Disease Models, Animal ; Dysbiosis/chemically induced ; Humans ; Interleukin-33 ; Interleukin-4 ; Mice ; *Microbiota ; Oxazolone/adverse effects ; Skin ; }, abstract = {BACKGROUND: Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities.<br><br>OBJECTIVE: To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research.<br><br>METHODS: AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD.<br><br>RESULTS: We detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S.&#x2009;xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33.<br><br>CONCLUSIONS: In this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.}, }
@article {pmid35008909, year = {2022}, author = {Popkov, VA and Zharikova, AA and Demchenko, EA and Andrianova, NV and Zorov, DB and Plotnikov, EY}, title = {Gut Microbiota as a Source of Uremic Toxins.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008909}, issn = {1422-0067}, support = {21-75-30009//Russian Science Foundation/ ; }, mesh = {Animals ; Bacteria/metabolism ; Cluster Analysis ; Enzymes/metabolism ; *Gastrointestinal Microbiome ; Humans ; Metadata ; RNA, Messenger/genetics/metabolism ; Uremic Toxins/*metabolism ; }, abstract = {Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as "uremic toxins". The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.}, }
@article {pmid35008631, year = {2021}, author = {Wellington, VNA and Sundaram, VL and Singh, S and Sundaram, U}, title = {Dietary Supplementation with Vitamin D, Fish Oil or Resveratrol Modulates the Gut Microbiome in Inflammatory Bowel Disease.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008631}, issn = {1422-0067}, support = {DK108054/NH/NIH HHS/United States ; DK067420/NH/NIH HHS/United States ; P20GM121299/NH/NIH HHS/United States ; BX003443//United States Department of Veterans Affairs/ ; }, mesh = {Animals ; *Dietary Supplements ; Fish Oils/pharmacology/*therapeutic use ; *Gastrointestinal Microbiome/drug effects ; Humans ; Inflammatory Bowel Diseases/*drug therapy/*microbiology/pathology ; Resveratrol/pharmacology/*therapeutic use ; Vitamin D/pharmacology/*therapeutic use ; }, abstract = {Gastrointestinal health is influenced by the functional genes and metabolites generated by the human microbiome. As the volume of current biomedical and translational research indicates, the importance and impact of this ecosystem of microorganisms, especially those comprising the gut microbiome on human health, has become increasingly apparent. Changes to the gut microbiome are associated with inflammatory bowel disease (IBD), which is characterized by persistent intestinal inflammation. Furthermore, the lifetime dietary choices of their host may positively or negatively affect both the gut microbiome and its impact on IBD. As such, "anti-inflammatory" dietary supplements, their impact, and mechanisms in restoring gut microbiota homeostasis during IBD is an area of intensive research. Dietary supplementation may represent an important adjuvant treatment avenue for limiting intestinal inflammation in IBD. Overall, this review addresses the development of the gut microbiome, the significance of the gut microbiome in IBD, and the use of dietary supplements such as vitamin D, fish oil, and resveratrol in the mitigation of IBD-associated gut dysbiosis and intestinal inflammation.}, }
@article {pmid35008605, year = {2021}, author = {Vitale, SG and Ferrari, F and Ciebiera, M and Zgliczyńska, M and Rapisarda, AMC and Vecchio, GM and Pino, A and Angelico, G and Knafel, A and Riemma, G and De Franciscis, P and Cianci, S}, title = {The Role of Genital Tract Microbiome in Fertility: A Systematic Review.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008605}, issn = {1422-0067}, mesh = {Cervix Uteri/microbiology ; Endometrium/microbiology ; Female ; Genitalia, Female/*microbiology ; Humans ; Infertility, Female/*microbiology ; *Lactobacillus ; *Microbiota ; Vagina/microbiology ; }, abstract = {The human microbiome plays a crucial role in determining the health status of every human being, and the microbiome of the genital tract can affect the fertility potential before and during assisted reproductive treatments (ARTs). This review aims to identify and appraise studies investigating the correlation of genital microbiome to infertility. Publications up to February 2021 were identified by searching the electronic databases PubMed/MEDLINE, Scopus and Embase and bibliographies. Only full-text original research articles written in English were considered eligible for analysis, whereas reviews, editorials, opinions or letters, case studies, conference papers, and abstracts were excluded. Twenty-six articles were identified. The oldest studies adopted the exclusive culture-based technique, while in recent years PCR and RNA sequencing based on 16S rRNA were the most used technique. Regardless of the anatomical site under investigation, the Lactobacillus-dominated flora seems to play a pivotal role in determining fertility, and in particular Lactobacillus crispatus showed a central role. Nonetheless, the presence of pathogens in the genital tract, such as Chlamydia trachomatis, Gardnerella vaginalis, Ureaplasma species, and Gram-negative stains microorganism, affected fertility also in case of asymptomatic bacterial vaginosis (BV). We failed to identify descriptive or comparative studies regarding tubal microbiome. The microbiome of the genital tract plays a pivotal role in fertility, also in case of ARTs. The standardization of the sampling methods and investigations approaches is warranted to stratify the fertility potential and its subsequent treatment. Prospective tubal microbiome studies are warranted.}, }
@article {pmid34995772, year = {2022}, author = {Barlaam, A and Putignani, L and Pane, S and Bianchi, PM and Papini, RA and Giangaspero, A}, title = {What's in a child's ear? A case of otomyiasis by Sarcophaga argyrostoma (Diptera, Sarcophagidae).}, journal = {Parasitology international}, volume = {87}, number = {}, pages = {102537}, doi = {10.1016/j.parint.2022.102537}, pmid = {34995772}, issn = {1873-0329}, mesh = {Animals ; Female ; Humans ; Infant ; Larva ; Microscopy/methods ; Myiasis/diagnosis/*parasitology ; Otitis/diagnosis/*parasitology ; Sarcophagidae/*classification/genetics ; }, abstract = {A clinical report of otomyiasis in a 1-year-old girl is reported. A III instar larva of Sarcophaga sp. was microscopically identified and Sarcophaga (Liopygia) argyrostoma (Diptera, Sarcophagidae) was suspected. A molecular method targeting a fragment of the cox1 gene was used to confirm the identity of the specimen. Although myiases are not frequent manifestations in otolaryngology, they should arouse the attention of doctors, social workers and parents dealing with disabled people, the elderly and children. This contribution also highlights the need of combining microscopy and molecular tools to achieve a correct and reliable identification of the specimen/s.}, }
@article {pmid34995483, year = {2022}, author = {Conwill, A and Kuan, AC and Damerla, R and Poret, AJ and Baker, JS and Tripp, AD and Alm, EJ and Lieberman, TD}, title = {Anatomy promotes neutral coexistence of strains in the human skin microbiome.}, journal = {Cell host &amp; microbe}, volume = {30}, number = {2}, pages = {171-182.e7}, pmid = {34995483}, issn = {1934-6069}, support = {DP2 GM140922/GM/NIGMS NIH HHS/United States ; }, mesh = {*Acne Vulgaris/microbiology ; Humans ; *Microbiota ; Propionibacterium acnes/genetics ; Skin/microbiology ; Whole Genome Sequencing ; }, abstract = {What enables strains of the same species to coexist in a microbiome? Here, we investigate whether host anatomy can explain strain co-residence of Cutibacterium acnes, the most abundant species on human skin. We reconstruct on-person evolution and migration using whole-genome sequencing of C. acnes colonies acquired from healthy subjects, including from individual skin pores, and find considerable spatial structure at the level of pores. Although lineages (sets of colonies separated by <100 mutations) with in vitro fitness differences coexist within centimeter-scale regions, each pore is dominated by a single lineage. Moreover, colonies from a pore typically have identical genomes. An absence of adaptive signatures suggests a genotype-independent source of low within-pore diversity. We therefore propose that pore anatomy imposes random single-cell bottlenecks; the resulting population fragmentation reduces competition and promotes coexistence. Our findings suggest that therapeutic interventions involving pore-dwelling species might focus on removing resident populations over optimizing probiotic fitness.}, }
@article {pmid34994112, year = {2022}, author = {Basu, A and Singh, R and Gupta, S}, title = {Bacterial infections in cancer: A bilateral relationship.}, journal = {Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology}, volume = {14}, number = {3}, pages = {e1771}, doi = {10.1002/wnan.1771}, pmid = {34994112}, issn = {1939-0041}, mesh = {Bacteria ; *Bacterial Infections/drug therapy ; Drug Delivery Systems ; Drug Discovery ; Humans ; Nanomedicine ; Nanotechnology ; *Neoplasms/drug therapy ; Tumor Microenvironment ; }, abstract = {Bacteria share a long commensal relationship with the human body. New findings, however, continue to unravel many complexities associated with this old alliance. In the past decades, the dysbiosis of human microbiome has been linked to tumorigenesis, and more recently to spontaneous colonization of existing tumors. The topic, however, remains open for debate as the claims for causative-prevailing dual characteristics of bacteria are mostly based on epidemiological evidence rather than robust mechanistic models. There are also no reviews linking the collective impact of bacteria in tumor microenvironments to the efficacy of cancer drugs, mechanisms of pathogen-initiated cancer and bacterial colonization, personalized nanomedicine, nanotechnology, and antimicrobial resistance. In this review, we provide a holistic overview of the bilateral relationship between cancer and bacteria covering all these aspects. Our collated evidence from the literature does not merely categorize bacteria as cancer causative or prevailing agents, but also critically highlights the gaps in the literature where more detailed studies may be required to reach such a conclusion. Arguments are made in favor of dual drug therapies that can simultaneously co-target bacteria and cancer cells to overcome drug resistance. Also discussed are the opportunities for leveraging the natural colonization and remission power of bacteria for cancer treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.}, }
@article {pmid34992297, year = {2022}, author = {Pruss, KM and Enam, F and Battaglioli, E and DeFeo, M and Diaz, OR and Higginbottom, SK and Fischer, CR and Hryckowian, AJ and Van Treuren, W and Dodd, D and Kashyap, P and Sonnenburg, JL}, title = {Oxidative ornithine metabolism supports non-inflammatory C. difficile colonization.}, journal = {Nature metabolism}, volume = {4}, number = {1}, pages = {19-28}, pmid = {34992297}, issn = {2522-5812}, support = {K08 DK110335/DK/NIDDK NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Clostridioides difficile/*physiology ; Clostridium Infections/*metabolism/*microbiology ; Energy Metabolism ; Gastrointestinal Microbiome ; *Host-Pathogen Interactions ; Humans ; Metabolic Networks and Pathways ; Metabolome ; Metabolomics/methods ; Mice ; Nitric Oxide Synthase/metabolism ; Ornithine/*metabolism ; *Oxidation-Reduction ; Oxidative Stress ; }, abstract = {The enteric pathogen Clostridioides difficile (Cd) is responsible for a toxin-mediated infection that causes more than 200,000 recorded hospitalizations and 13,000 deaths in the United States every year[1]. However, Cd can colonize the gut in the absence of disease symptoms. Prevalence of asymptomatic colonization by toxigenic Cd in healthy populations is high; asymptomatic carriers are at increased risk of infection compared to noncolonized individuals and may be a reservoir for transmission of Cd infection[2,3]. Elucidating the molecular mechanisms by which Cd persists in the absence of disease is necessary for understanding pathogenesis and developing refined therapeutic strategies. Here, we show with gut microbiome metatranscriptomic analysis that mice recalcitrant to Cd infection and inflammation exhibit increased community-wide expression of arginine and ornithine metabolic pathways. To query Cd metabolism specifically, we leverage RNA sequencing in gnotobiotic mice infected with two wild-type strains (630 and R20291) and isogenic toxin-deficient mutants of these strains to differentiate inflammation-dependent versus -independent transcriptional states. A single operon encoding oxidative ornithine degradation is consistently upregulated across non-toxigenic Cd strains. Combining untargeted and targeted metabolomics with bacterial and host genetics, we demonstrate that both diet- and host-derived sources of ornithine provide a competitive advantage to Cd, suggesting a mechanism for Cd persistence within a non-inflammatory, healthy gut.}, }
@article {pmid34990774, year = {2022}, author = {Uzoukwu, EU and Phandanouvong-Lozano, V and Usman, H and Sfeir, CS and Niepa, THR}, title = {Droplet-based microsystems as novel assessment tools for oral microbial dynamics.}, journal = {Biotechnology advances}, volume = {55}, number = {}, pages = {107903}, doi = {10.1016/j.biotechadv.2021.107903}, pmid = {34990774}, issn = {1873-1899}, mesh = {Bacteria ; *Dental Caries ; Humans ; Microbial Interactions ; *Microbiota ; Mouth/microbiology ; }, abstract = {The human microbiome comprises thousands of microbial species that live in and on the body and play critical roles in human health and disease. Recent findings on the interplay among members of the oral microbiome, defined by a personalized set of microorganisms, have elucidated the role of bacteria and yeasts in oral health and diseases including dental caries, halitosis, and periodontal infections. However, the majority of these studies rely on traditional culturing methods which are limited in their ability of replicating the oral microenvironment, and therefore fail to evaluate key microbial interactions in microbiome dynamics. Novel culturing methods have emerged to address this shortcoming. Here, we reviewed the potential of droplet-based microfluidics as an alternative approach for culturing microorganisms and assessing the oral microbiome dynamics. We discussed the state of the art and recent progress in the field of oral microbiology. Although at its infancy, droplet-based microtechnology presents an interesting potential for elucidating oral microbial dynamics and pathophysiology. We highlight how new findings provided by current microfluidic-based methodologies could advance the investigation of the oral microbiome. We anticipate that our work involving the droplet-based microfluidic technique with a semipermeable membrane will lay the foundations for future microbial dynamics studies and further expand the knowledge of the oral microbiome and its implication in oral health.}, }
@article {pmid34989907, year = {2022}, author = {Filik, K and Szermer-Olearnik, B and Niedziółka-Jönson, J and Roźniecka, E and Ciekot, J and Pyra, A and Matyjaszczyk, I and Skurnik, M and Brzozowska, E}, title = {φYeO3-12 phage tail fiber Gp17 as a promising high specific tool for recognition of Yersinia enterocolitica pathogenic serotype O:3.}, journal = {AMB Express}, volume = {12}, number = {1}, pages = {1}, pmid = {34989907}, issn = {2191-0855}, support = {National Science Center//Narodowym Centrum Nauki/ ; Poland (Grant Numbers UMO-2017/26/E/NZ1/00249).//Narodowym Centrum Nauki/ ; }, abstract = {Yersiniosis is an infectious zoonotic disease caused by two enteropathogenic species of Gram-negative genus Yersinia: Yersinia enterocolitica and Yersinia pseudotuberculosis. Pigs and other wild and domestic animals are reservoirs for these bacteria. Infection is usually spread to humans by ingestion of contaminated food. Yersiniosis is considered a rare disease, but recent studies indicate that it is overlooked in the diagnostic process therefore the infections with this bacterium are not often identified. Reliable diagnosis of Yersiniosis by culturing is difficult due to the slow growth of the bacteria easily overgrown by other more rapidly growing microbes unless selec-tive growth media is used. Phage adhesins recognizing bacteria in a specific manner can be an excellent diagnostic tool, es-pecially in the diagnosis of pathogens difficult for culturing. In this study, it was shown that Gp17, the tail fiber protein (TFP) of phage φYeO3-12, specifically recognizes only the pathogenic Yersinia enterocolitica serotype O:3 (YeO:3) bacteria. The ELISA test used in this work confirmed the specific interaction of this protein with YeO:3 and demonstrated a promising tool for developing the pathogen recognition method based on phage adhesins.}, }
@article {pmid34985325, year = {2022}, author = {Sorboni, SG and Moghaddam, HS and Jafarzadeh-Esfehani, R and Soleimanpour, S}, title = {A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.}, journal = {Clinical microbiology reviews}, volume = {35}, number = {1}, pages = {e0033820}, pmid = {34985325}, issn = {1098-6618}, mesh = {Dysbiosis/metabolism/therapy ; *Gastrointestinal Microbiome/physiology ; Humans ; *Nervous System Diseases/therapy ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.}, }
@article {pmid34981957, year = {2022}, author = {Pavletić, B and Runzheimer, K and Siems, K and Koch, S and Cortesão, M and Ramos-Nascimento, A and Moeller, R}, title = {Spaceflight Virology: What Do We Know about Viral Threats in the Spaceflight Environment?.}, journal = {Astrobiology}, volume = {22}, number = {2}, pages = {210-224}, pmid = {34981957}, issn = {1557-8070}, mesh = {Astronauts ; Humans ; *Microbiota ; *Space Flight ; Spacecraft ; *Weightlessness ; }, abstract = {Viruses constitute a significant part of the human microbiome, so wherever humans go, viruses are brought with them, even on space missions. In this mini review, we focus on the International Space Station (ISS) as the only current human habitat in space that has a diverse range of viral genera that infect microorganisms from bacteria to eukaryotes. Thus, we have reviewed the literature on the physical conditions of space habitats that have an impact on both virus transmissibility and interaction with their host, which include UV radiation, ionizing radiation, humidity, and microgravity. Also, we briefly comment on the practices used on space missions that reduce virus spread, that is, use of antimicrobial surfaces, spacecraft sterilization practices, and air filtration. Finally, we turn our attention to the health threats that viruses pose to space travel. Overall, even though efforts are taken to ensure safe conditions during human space travel, for example, preflight quarantines of astronauts, we reflect on the potential risks humans might be exposed to and how those risks might be aggravated in extraterrestrial habitats.}, }
@article {pmid34978141, year = {2022}, author = {Michels, N and Zouiouich, S and Vanderbauwhede, B and Vanacker, J and Indave Ruiz, BI and Huybrechts, I}, title = {Human microbiome and metabolic health: An overview of systematic reviews.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {23}, number = {4}, pages = {e13409}, doi = {10.1111/obr.13409}, pmid = {34978141}, issn = {1467-789X}, support = {001/WHO_/World Health Organization/International ; }, mesh = {*Diabetes Mellitus, Type 2 ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Non-alcoholic Fatty Liver Disease ; Obesity ; *Probiotics ; Systematic Reviews as Topic ; }, abstract = {To summarize the microbiome's role in metabolic disorders (insulin resistance, hyperglycemia, type 2 diabetes, obesity, hyperlipidemia, hypertension, nonalcoholic fatty liver disease [NAFLD], and metabolic syndrome), systematic reviews on observational or interventional studies (prebiotics/probiotics/synbiotics/transplant) were searched in MEDLINE and Embase until September 2020. The 87 selected systematic reviews included 57 meta-analyses. Methodological quality (AMSTAR2) was moderate in 62%, 12% low, and 26% critically low. Observational studies on obesity (10 reviews) reported less gut bacterial diversity with higher Fusobacterium, Lactobacillus reuteri, Bacteroides fragilis, and Staphylococcus aureus, whereas lower Methanobrevibacter, Lactobacillus plantarum, Akkermansia muciniphila, and Bifidobacterium animalis compared with nonobese. For diabetes (n = 1), the same was found for Fusobacterium and A. muciniphila, whereas higher Ruminococcus and lower Faecalibacterium, Roseburia, Bacteroides vulgatus, and several Bifidobacterium spp. For NAFLD (n = 2), lower Firmicutes, Rikenellaceae, Ruminococcaceae, whereas higher Escherichia and Lactobacillus were detected. Discriminating bacteria overlapped between metabolic disorders, those with high abundance being often involved in inflammation, whereas those with low abundance being used as probiotics. Meta-analyses (n = 54) on interventional studies reported 522 associations: 54% was statistically significant with intermediate effect size and moderate between-study heterogeneity. Meta-evidence was highest for probiotics and lowest for fecal transplant. Future avenues include better methodological quality/comparability, testing functional differences, new intervention strategies, and considerating other body habitats and kingdoms.}, }
@article {pmid34978130, year = {2022}, author = {Feng, Y and Bui, TPN and Stams, AJM and Boeren, S and Sánchez-Andrea, I and de Vos, WM}, title = {Comparative genomics and proteomics of Eubacterium maltosivorans: functional identification of trimethylamine methyltransferases and bacterial microcompartments in a human intestinal bacterium with a versatile lifestyle.}, journal = {Environmental microbiology}, volume = {24}, number = {1}, pages = {517-534}, pmid = {34978130}, issn = {1462-2920}, mesh = {Eubacterium ; Humans ; Life Style ; Methylamines ; *Methyltransferases/genetics ; *Proteomics ; }, abstract = {Eubacterium maltosivorans YI[T] is a human intestinal isolate capable of acetogenic, propionogenic and butyrogenic growth. Its 4.3-Mb genome sequence contains coding sequences for 4227 proteins, including 41 different methyltransferases. Comparative proteomics of strain YI[T] showed the Wood-Ljungdahl pathway proteins to be actively produced during homoacetogenic growth on H2 and CO2 while butyrogenic growth on a mixture of lactate and acetate significantly upregulated the production of proteins encoded by the recently identified lctABCDEF cluster and accessory proteins. Growth on H2 and CO2 unexpectedly induced the production of two related trimethylamine methyltransferases. Moreover, a set of 16 different trimethylamine methyltransferases together with proteins for bacterial microcompartments were produced during growth and deamination of the quaternary amines, betaine, carnitine and choline. Growth of strain YI[T] on 1,2-propanediol generated propionate with propanol and induced the formation of bacterial microcompartments that were also prominently visible in betaine-grown cells. The present study demonstrates that E. maltosivorans is highly versatile in converting low-energy fermentation end-products in the human gut into butyrate and propionate whilst being capable of preventing the formation of the undesired trimethylamine by converting betaine and other quaternary amines in bacterial microcompartments into acetate and butyrate.}, }
@article {pmid34975829, year = {2021}, author = {Karisola, P and Palosuo, K and Hinkkanen, V and Wisgrill, L and Savinko, T and Fyhrquist, N and Alenius, H and Mäkelä, MJ}, title = {Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {704633}, pmid = {34975829}, issn = {1664-3224}, mesh = {Administration, Oral ; Adolescent ; Allergens/administration &amp; dosage/therapeutic use ; Antibody Specificity ; Child ; Cytokines/blood ; *Desensitization, Immunologic ; Dose-Response Relationship, Immunologic ; Egg Hypersensitivity/blood/genetics/immunology/*therapy ; Egg Proteins/administration &amp; dosage/adverse effects/*immunology/therapeutic use ; Female ; Gene Expression Regulation ; Gene Ontology ; Genomics/*methods ; Humans ; *Immunity, Innate ; Immunoglobulins/blood ; Inflammation/etiology/immunology/*prevention &amp; control ; Isoantibodies/blood/immunology ; Leukocytes, Mononuclear/*metabolism ; Lymphocyte Count ; Lymphocyte Subsets/immunology ; Male ; *Transcriptome ; Treatment Outcome ; }, abstract = {We previously reported the results of a randomized, open-label trial of egg oral immunotherapy (OIT) in 50 children where 44% were desensitized and 46% were partially desensitized after 8 months of treatment. Here we focus on cell-mediated molecular mechanisms driving desensitization during egg OIT. We sought to determine whether changes in genome-wide gene expression in blood cells during egg OIT correlate with humoral responses and the clinical outcome. The blood cell transcriptome of 50 children receiving egg OIT was profiled using peripheral blood mononuclear cell (PBMC) samples obtained at baseline and after 3 and 8 months of OIT. We identified 467 differentially expressed genes (DEGs) after 3 or 8 months of egg OIT. At 8 months, 86% of the DEGs were downregulated and played a role in the signaling of TREM1, IL-6, and IL-17. In correlation analyses, Gal d 1-4-specific IgG4 antibodies associated positively with DEGs playing a role in pathogen recognition and antigen presentation and negatively with DEGs playing a role in the signaling of IL-10, IL-6, and IL-17. Desensitized and partially desensitized patients had differences in their antibody responses, and although most of the transcriptomic changes were shared, both groups had also specific patterns, which suggest slower changes in partially desensitized and activation of NK cells in the desensitized group. OIT for egg allergy in children inhibits inflammation and activates innate immune responses regardless of the clinical outcome at 8 months. Changes in gene expression patterns first appear as posttranslational protein modifications, followed by more sustained epigenetic gene regulatory functions related to successful desensitization.}, }
@article {pmid34972816, year = {2022}, author = {Ryu, TY and Kim, K and Han, TS and Lee, MO and Lee, J and Choi, J and Jung, KB and Jeong, EJ and An, DM and Jung, CR and Lim, JH and Jung, J and Park, K and Lee, MS and Kim, MY and Oh, SJ and Hur, K and Hamamoto, R and Park, DS and Kim, DS and Son, MY and Cho, HS}, title = {Human gut-microbiome-derived propionate coordinates proteasomal degradation via HECTD2 upregulation to target EHMT2 in colorectal cancer.}, journal = {The ISME journal}, volume = {16}, number = {5}, pages = {1205-1221}, pmid = {34972816}, issn = {1751-7370}, mesh = {*Colorectal Neoplasms ; Histocompatibility Antigens/metabolism ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Humans ; *Microbiota ; Propionates ; Ubiquitin-Protein Ligases/*metabolism ; Up-Regulation ; }, abstract = {The human microbiome plays an essential role in the human immune system, food digestion, and protection from harmful bacteria by colonizing the human intestine. Recently, although the human microbiome affects colorectal cancer (CRC) treatment, the mode of action between the microbiome and CRC remains unclear. This study showed that propionate suppressed CRC growth by promoting the proteasomal degradation of euchromatic histone-lysine N-methyltransferase 2 (EHMT2) through HECT domain E3 ubiquitin protein ligase 2 (HECTD2) upregulation. In addition, EHMT2 downregulation reduced the H3K9me2 level on the promoter region of tumor necrosis factor α-induced protein 1 (TNFAIP1) as a novel direct target of EHMT2. Subsequently, TNFAIP1 upregulation induced the apoptosis of CRC cells. Furthermore, using Bacteroides thetaiotaomicron culture medium, we confirmed EHMT2 downregulation via upregulation of HECTD2 and TNFAIP1 upregulation. Finally, we observed the synergistic effect of propionate and an EHMT2 inhibitor (BIX01294) in 3D spheroid culture models. Thus, we suggest the anticancer effects of propionate and EHMT2 as therapeutic targets for colon cancer treatment and may provide the possibility for the synergistic effects of an EHMT2 inhibitor and microbiome in CRC treatment.}, }
@article {pmid37181836, year = {2022}, author = {Tochilina, AG and Belova, IV and Ilyicheva, TN and Marchenko, VY and Zhirnov, VA and Molodtsova, SB and Ikonnikov, AV and Muhkina, IV and Blagonravova, AS and Soloveva, IV}, title = {Genome Features of Probiotic Bifidobacteria Determining Their Strain-Specific Properties.}, journal = {Sovremennye tekhnologii v meditsine}, volume = {14}, number = {5}, pages = {36-43}, pmid = {37181836}, issn = {2309-995X}, mesh = {Animals ; Dogs ; Humans ; Bifidobacterium/genetics ; *Influenza A Virus, H1N1 Subtype ; *Influenza, Human ; Tryptophan ; *Probiotics/pharmacology ; *Bifidobacterium bifidum/physiology ; *Bacteriocins ; Antiviral Agents ; Folic Acid ; }, abstract = {UNLABELLED: The aim of the study was to analyze the genome features of the probiotic strains Bifidobacterium longum 379, Bifidobacterium bifidum 1, and Bifidobacterium bifidum 791 and study their antiviral activity.<br><br>MATERIALS AND METHODS: Whole genome sequencing of three strains of bifidobacteria was performed on the MiSeq platform (Illumina Inc., USA). The genomes were annotated using the Prokka v. 1.11 utility and RAST genomic server. The individual genetic determinants were searched using the ResFinder 3.2, PathogenFinder, PlasmidFinder, RAST, and Bagel 4 software. The antiviral activity of the strains against influenza A viruses was studied using MDCK cells (Madin-Darby canine kidney cells), the epidemic strain of influenza A/Lipetsk/1V/2018 (H1N1 pdm09) (EPI_ISL_332798), the highly pathogenic avian influenza virus A/common gull/Saratov/1676/2018 (H5N6) strain (EPI_ISL_336925), and neutral red vital dye.<br><br>RESULTS: The genomes of all studied strains contained determinants responsible for utilization of carbohydrates of plant origin; the genes of key enzymes for the synthesis of tryptophan and folic acid are present in the genomes of B. longum 379 and B. bifidum 791. A feature of the B. bifidum 791 genome is the presence of determinants responsible for the synthesis of thermostable type I bacteriocins - flavucin and lasso peptide. The B. bifidum 791 strain was found to show pronounced antiviral activity against both the strains of influenza A, the supernatant of which suppressed viral replication in vitro up to a dilution of 1:8, and the cells inhibited viral reproduction up to a concentration of 6&#xb7;106 CFU/ml.<br><br>CONCLUSION: The analysis of complete genomes of B. longum 379, B. bifidum 1, and B. bifidum 791 showed features that determine their strain-specific properties, the findings on which were previously made empirically based on indirect signs. In the genomes of B. longum 379 and B. bifidum 791 strains, in contrast to B. bifidum 1 strain, key enzymes for the synthesis of tryptophan and folic acid were found. These substances have an impact on the human body in many ways, including having a thymoleptic effect (reducing emotional stress, irritability, anxiety, eliminating lethargy, apathy, melancholy, anxiety) and regulating cognitive activity. The presence of determinants responsible for the synthesis of thermostable type I bacteriocins in the genome of B. bifidum 791 strain determines its pronounced antiviral activity.}, }
@article {pmid34970503, year = {2021}, author = {Cardile, S and Del Chierico, F and Candusso, M and Reddel, S and Bernaschi, P and Pietrobattista, A and Spada, M and Torre, G and Putignani, L}, title = {Impact of Two Antibiotic Therapies on Clinical Outcome and Gut Microbiota Profile in Liver Transplant Paediatric Candidates Colonized by Carbapenem-Resistant Klebsiella pneumoniae CR-KP.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {730904}, pmid = {34970503}, issn = {2235-2988}, mesh = {Anti-Bacterial Agents/therapeutic use ; Carbapenems/pharmacology ; Child ; *Gastrointestinal Microbiome ; Humans ; Klebsiella ; *Klebsiella Infections/drug therapy/prevention &amp; control ; Klebsiella pneumoniae/genetics ; *Liver Transplantation ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Colonization by multidrug-resistant (MDR) organisms in liver transplant (LT) candidates significantly affects the LT outcome. To date, consensus about patient management is lacking, including microbiological screening indications. This pilot study aimed to evaluate the impact of carbapenem-resistant Klebsiella pneumoniae (CR-KP) colonization in LT paediatric candidates to enable optimal prevention and therapeutic strategies that exploit both clinical and microbiological approaches. Seven paediatric patients colonized by CR-KP were evaluated before and until one-year post LT. At the time of the transplant, patients were stratified based on antibiotic (ATB) prophylaxis into two groups: 'standard ATB' (standard ATB prophylaxis), and 'targeted ATB' (MDR antibiogram-based ATB prophylaxis). Twenty-eight faecal samples were collected during follow-up and used for MDR screening and gut microbiota 16S rRNA-based profiling. Post-transplant hospitalization duration was comparable for both groups. With the exception of one patient, no serious infections and/or complications, nor deaths were recorded. A progressive MDR decontamination was registered. In the 'standard ATB' group, overall bacterial richness increased. Moreover, 6 months after LT, Lactobacillus and Bulleidia were increased and Enterobacteriaceae and Klebsiella spp. were reduced. In the 'targeted ATB' group Klebsiella spp., Ruminococcus gnavus, Erysipelotrichaceae, and Bifidobacterium spp. were increased 12 months after LT. In conclusion, both antibiotics prophylaxis do not affect nor LT outcomes or the risk of intestinal bacterial translocation. However, in the 'standard ATB' group, gut microbiota richness after LT was increased, with an increase of beneficial lactic acid- and short-chain fatty acids (SCFA)-producing bacteria and the reduction of harmful Enterobacteriaceae and Klebsiella spp. It could therefore be appropriate to administer standard prophylaxis, reserving the use of ATB-based molecules only in case of complications.}, }
@article {pmid34969973, year = {2022}, author = {Stankeviciute, G and Tang, P and Ashley, B and Chamberlain, JD and Hansen, MEB and Coleman, A and D'Emilia, R and Fu, L and Mohan, EC and Nguyen, H and Guan, Z and Campopiano, DJ and Klein, EA}, title = {Convergent evolution of bacterial ceramide synthesis.}, journal = {Nature chemical biology}, volume = {18}, number = {3}, pages = {305-312}, pmid = {34969973}, issn = {1552-4469}, support = {U54 GM069338/GM/NIGMS NIH HHS/United States ; R01 AI148366/AI/NIAID NIH HHS/United States ; BB/M010996/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/T016841/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacteria/genetics/metabolism ; Biosynthetic Pathways ; *Ceramides/chemistry/metabolism ; Humans ; Phylogeny ; *Sphingolipids/chemistry/metabolism ; }, abstract = {The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently.}, }
@article {pmid34969071, year = {2022}, author = {Clausen, DS and Willis, AD}, title = {Evaluating replicability in microbiome data.}, journal = {Biostatistics (Oxford, England)}, volume = {23}, number = {4}, pages = {1099-1114}, pmid = {34969071}, issn = {1468-4357}, support = {R35 GM133420/GM/NIGMS NIH HHS/United States ; T32 ES015459/ES/NIEHS NIH HHS/United States ; }, mesh = {High-Throughput Nucleotide Sequencing/methods ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {High-throughput sequencing is widely used to study microbial communities. However, choice of laboratory protocol is known to affect the resulting microbiome data, which has an unquantified impact on many comparisons between communities of scientific interest. We propose a novel approach to evaluating replicability in high-dimensional data and apply it to assess the cross-laboratory replicability of signals in microbiome data using the Microbiome Quality Control Project data set. We learn distinctions between samples as measured by a single laboratory and evaluate whether the same distinctions hold in data produced by other laboratories. While most sequencing laboratories can consistently distinguish between samples (median correct classification 87% on genus-level proportion data), these distinctions frequently fail to hold in data from other laboratories (median correct classification 55% across laboratory on genus-level proportion data). As identical samples processed by different laboratories generate substantively different quantitative results, we conclude that 16S sequencing does not reliably resolve differences in human microbiome samples. However, because we observe greater replicability under certain data transformations, our results inform the analysis of microbiome data.}, }
@article {pmid34965174, year = {2022}, author = {Hiippala, K and Khan, I and Ronkainen, A and Boulund, F and Vähä-Mäkilä, H and Suutarinen, M and Seifert, M and Engstrand, L and Satokari, R}, title = {Novel strain of Pseudoruminococcus massiliensis possesses traits important in gut adaptation and host-microbe interactions.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2013761}, pmid = {34965174}, issn = {1949-0984}, mesh = {Adaptation, Physiological ; Bacterial Proteins/genetics/metabolism ; Butyrates/metabolism ; Firmicutes/classification/genetics/*isolation &amp; purification/*physiology ; Gastrointestinal Microbiome ; Genome, Bacterial ; Glycoside Hydrolases/genetics/metabolism ; Host Microbial Interactions ; Humans ; Intestines/*microbiology ; }, abstract = {Fecal microbiota transplantation (FMT) is an efficient treatment for recurrent Clostridioides difficile infection and currently investigated as a treatment for other intestinal and systemic diseases. Better understanding of the species potentially transferred in FMT is needed. We isolated from a healthy fecal donor a novel strain E10-96H of Pseudoruminococcus massiliensis, a recently described strictly anaerobic species currently represented only by the type strain. The whole genome sequence of E10-96H had over 98% similarity with the type strain. E10-96H carries 20 glycoside hydrolase encoding genes, degrades starch in vitro and thus may contribute to fiber degradation, cross-feeding of other species and butyrate production in the intestinal ecosystem. The strain carries pilus-like structures, harbors pilin genes in its genome and adheres to enterocytes in vitro but does not provoke a proinflammatory response. P. massiliensis seems to have commensal behavior with the host epithelium, and its role in intestinal ecology should be studied further.}, }
@article {pmid34964289, year = {2021}, author = {Wise, NM and Wagner, SJ and Worst, TJ and Sprague, JE and Oechsle, CM}, title = {Comparison of swab types for collection and analysis of microorganisms.}, journal = {MicrobiologyOpen}, volume = {10}, number = {6}, pages = {e1244}, pmid = {34964289}, issn = {2045-8827}, mesh = {Bacteriological Techniques/*instrumentation ; DNA, Bacterial/*analysis/isolation &amp; purification ; Humans ; *Microbiota ; Proteus mirabilis/genetics/*isolation &amp; purification ; Real-Time Polymerase Chain Reaction ; Specimen Handling/*instrumentation ; }, abstract = {The human microbiome has begun to emerge as a potential forensic tool, with varied applications ranging from unique identification to investigative leads that link individuals and/or locations. The relative abundance of the combined DNA of the microbiome, compared to human nuclear DNA, may expand potential sources of biological evidence, especially in cases with transfer or low-copy number DNA samples. This work sought to determine the optimal swab type for the collection and analysis of microorganisms. A bacterium (Proteus mirabilis) was deposited by pipette onto four swab types (cotton, flocked, dental applicators, and dissolvable), and extraction and real-time PCR quantitation of the bacterial DNA were performed, which allowed for absolute microbial DNA recovery and comparison of yields across the four sampling substrates. Flocked swabs had the highest yield (~1240 ng) compared to the cotton swabs (~184 ng), dental applicators (~533 ng), and dissolvable swabs (~430 ng). The collection efficiency was further evaluated for cotton and flocked swabs using dried microbial samples spotted onto non-porous surfaces (treated wood, glass, plastic, and tile). Flocked swabs performed consistently better across wood, glass, and tile, but showed decreased recovery from plastic. The cotton swabs failed in the recovery of P. mirabilis DNA across all surfaces. Knowing the appropriate sampling substrate will be useful as others continue to investigate the use of the microbiome as a forensics tool.}, }
@article {pmid34963470, year = {2021}, author = {Jang, HJ and Choi, JY and Kim, K and Yong, SH and Kim, YW and Kim, SY and Kim, EY and Jung, JY and Kang, YA and Park, MS and Kim, YS and Cho, YJ and Lee, SH}, title = {Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer.}, journal = {Respiratory research}, volume = {22}, number = {1}, pages = {322}, pmid = {34963470}, issn = {1465-993X}, support = {2018R1C1B5043991//National Research Foundation of Korea/ ; 14-2016-011//Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital/ ; }, mesh = {Aged ; Antineoplastic Agents, Immunological ; B7-H1 Antigen/*biosynthesis/genetics ; Biomarkers, Tumor/biosynthesis/genetics ; Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/therapy ; Female ; Gene Expression Regulation, Neoplastic/*physiology ; Humans ; Immunotherapy/*methods ; Lung/metabolism/microbiology/pathology ; Lung Neoplasms/genetics/*metabolism/therapy ; Male ; Microbiota/*physiology ; Middle Aged ; Prospective Studies ; }, abstract = {BACKGROUND: Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the development of multiple diseases. Here, we investigated the differences in the lung microbiomes of patients with lung cancer.<br><br>METHODS: 16S rRNA sequencing was performed to evaluate the respiratory tract microbiome present in the bronchoalveolar lavage fluid. Patients were stratified based on programmed death-ligand 1 (PD-L1) expression levels and immunotherapy responses.<br><br>RESULTS: In total, 84 patients were prospectively analyzed, of which 59 showed low (<&#x2009;10%), and 25 showed high (&#x2265;&#x2009;10%) PD-L1 expression levels. The alpha and beta diversities did not significantly differ between the two groups. Veillonella dispar was dominant in the high-PD-L1 group; the population of Neisseria was significantly higher in the low-PD-L1 group than in the high-PD-L1 group. In the immunotherapy responder group, V. dispar was dominant, while Haemophilus influenzae and Neisseria perflava were dominant in the non-responder group.<br><br>CONCLUSION: The abundances of Neisseria and V. dispar differed significantly in relation to PD-L1 expression levels and immunotherapy responses.}, }
@article {pmid34963427, year = {2022}, author = {Fromentin, M and Bridier-Nahmias, A and Legoff, J and Mercier-Delarue, S and Ranger, N and Vuillard, C and Do Vale, J and Zucman, N and Alberdi, A and Ricard, JD and Roux, D}, title = {The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.}, journal = {Experimental lung research}, volume = {48}, number = {1}, pages = {23-34}, doi = {10.1080/01902148.2021.2021327}, pmid = {34963427}, issn = {1521-0499}, mesh = {Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lung ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; *Respiration, Artificial/adverse effects ; }, abstract = {Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. Materials and methods: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. "S-V4" for "Stringent V4" primer pair is used in two ongoing international projects "the Integrative Human microbiome project (iHMP)" and "the Earth microbiome project (EMP)." "R-V4" for "Relaxed V4" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. Results: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. "S-V4" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for "R-V4." The main difference related to poor Enterobacteriaceae detection with "R-V4" primers. Conclusions: Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R "S-V4" primer pair associated to Illumina® MiSeq paired-end sequencing.}, }
@article {pmid34960092, year = {2021}, author = {Fierro, V and Marzano, V and Monaci, L and Vernocchi, P and Mennini, M and Valluzzi, R and Levi Mortera, S and Pilolli, R and Dahdah, L and Calandrelli, V and Bracaglia, G and Arasi, S and Riccardi, C and Fiocchi, A and Putignani, L}, title = {Threshold of Reactivity and Tolerance to Precautionary Allergen-Labelled Biscuits of Baked Milk- and Egg-Allergic Children.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34960092}, issn = {2072-6643}, support = {Ricerca Corrente 2018//Ministero della Salute/ ; ad hoc//Galbusera/ ; }, mesh = {Adolescent ; Allergens/*analysis ; Child ; Child, Preschool ; Egg Hypersensitivity/etiology/*immunology/*prevention &amp; control ; Egg Proteins/analysis/immunology ; Female ; Food Analysis/methods ; *Food Labeling ; Humans ; Infant ; Male ; Mass Spectrometry ; Milk Hypersensitivity/etiology/*immunology/*prevention &amp; control ; Milk Proteins/analysis/immunology ; Patient Acuity ; Prospective Studies ; Proteomics/methods ; }, abstract = {Extremely sensitive food-allergic patients may react to very small amounts of allergenic foods. Precautionary allergen labelling (PAL) warns from possible allergenic contaminations. We evaluated by oral food challenge the reactivity to a brand of PAL-labelled milk- and egg-free biscuits of children with severe milk and egg allergy. We explored the ability of proteomic methods to identify minute amounts of milk/egg allergens in such biscuits. Traces of milk and/or egg allergens in biscuits were measured by two different liquid-chromatography-mass spectrometry methods. The binding of patient's serum with egg/milk proteins was assessed using immunoblotting. None of the patients reacted to biscuits. Egg and milk proteins were undetectable with a limit of detection of 0.6 µg/g for milk and egg (method A), and of 0.1 and 0.3 µg /g for milk and egg, respectively (method B). The immunoblots did not show milk/egg proteins in the studied biscuits. Milk/egg content of the biscuits is far lower than 4 µg of milk or egg protein per gram of product, the minimal doses considered theoretically capable of causing reactions. With high sensitivity, proteomic assessments predict the harmlessness of very small amount of allergens in foods, and can be used to help avoiding unnecessary PAL.}, }
@article {pmid34959740, year = {2021}, author = {Del Chierico, F and Trapani, V and Petito, V and Reddel, S and Pietropaolo, G and Graziani, C and Masi, L and Gasbarrini, A and Putignani, L and Scaldaferri, F and Wolf, FI}, title = {Dietary Magnesium Alleviates Experimental Murine Colitis through Modulation of Gut Microbiota.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, pmid = {34959740}, issn = {2072-6643}, support = {D.1.2017 and D.3.2.2015//Ministry of Education, Universities and Research/ ; }, mesh = {Animals ; Colitis/chemically induced/*microbiology/*therapy ; Dextran Sulfate ; Disease Models, Animal ; Dysbiosis/microbiology/therapy ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Magnesium/*pharmacology ; Magnesium Deficiency/microbiology/therapy ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; }, abstract = {Nutritional deficiencies are common in inflammatory bowel diseases (IBD). In patients, magnesium (Mg) deficiency is associated with disease severity, while in murine models, dietary Mg supplementation contributes to restoring mucosal function. Since Mg availability modulates key bacterial functions, including growth and virulence, we investigated whether the beneficial effects of Mg supplementation during colitis might be mediated by gut microbiota. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, and fecal consistency. Gut microbiota were analyzed by 16S-rRNA based profiling on fecal samples. Mg supplementation improved microbiota richness in colitic mice, increased abundance of Bifidobacterium and reduced Enterobacteriaceae. KEEG pathway analysis predicted an increase in biosynthetic metabolism, DNA repair and translation pathways during Mg supplementation and in the presence of colitis, while low Mg conditions favored catabolic processes. Thus, dietary Mg supplementation increases bacteria involved in intestinal health and metabolic homeostasis, and reduces bacteria involved in inflammation and associated with human diseases, such as IBD. These findings suggest that Mg supplementation may be a safe and cost-effective strategy to ameliorate disease symptoms and restore a beneficial intestinal flora in IBD patients.}, }
@article {pmid34959505, year = {2021}, author = {Pane, S and Ristori, MV and Gardini, S and Russo, A and Del Chierico, F and Putignani, L}, title = {Clinical Parasitology and Parasitome Maps as Old and New Tools to Improve Clinical Microbiomics.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, pmid = {34959505}, issn = {2076-0817}, support = {Ricerca Corrente 2020 and 2021//Italian Ministry of Health/ ; }, abstract = {A growing body of evidence shows that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, which reduces host damage. Herein, we discuss how diagnostic parasitology may contribute to designing clinical metagenomic pipelines and FMT programs, especially in pediatric subjects. The consequences of more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.}, }
@article {pmid34949230, year = {2021}, author = {Kurki, SN and Kantonen, J and Kaivola, K and Hokkanen, L and Mäyränpää, MI and Puttonen, H and ,  and Martola, J and Pöyhönen, M and Kero, M and Tuimala, J and Carpén, O and Kantele, A and Vapalahti, O and Tiainen, M and Tienari, PJ and Kaila, K and Hästbacka, J and Myllykangas, L}, title = {APOE ε4 associates with increased risk of severe COVID-19, cerebral microhaemorrhages and post-COVID mental fatigue: a Finnish biobank, autopsy and clinical study.}, journal = {Acta neuropathologica communications}, volume = {9}, number = {1}, pages = {199}, pmid = {34949230}, issn = {2051-5960}, support = {341007//Terveyden Tutkimuksen Toimikunta/ ; 336439//Terveyden Tutkimuksen Toimikunta/ ; 335527//Terveyden Tutkimuksen Toimikunta/ ; TYH2021310//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; }, mesh = {Adult ; Aged ; Apolipoprotein E4/*genetics ; Autopsy ; Biological Specimen Banks ; COVID-19/*complications/diagnosis/epidemiology/*genetics ; Cerebral Hemorrhage/diagnosis/epidemiology/*genetics ; Cohort Studies ; Female ; Finland/epidemiology ; Genetic Association Studies/methods ; Heterozygote ; Humans ; Male ; Mental Fatigue/diagnosis/epidemiology/*genetics ; Microvessels/pathology ; Middle Aged ; *Patient Acuity ; Prospective Studies ; Risk Factors ; Young Adult ; Post-Acute COVID-19 Syndrome ; }, abstract = {Apolipoprotein E ε4 allele (APOE4) has been shown to associate with increased susceptibility to SARS-CoV-2 infection and COVID-19 mortality in some previous genetic studies, but information on the role of APOE4 on the underlying pathology and parallel clinical manifestations is scarce. Here we studied the genetic association between APOE and COVID-19 in Finnish biobank, autopsy and prospective clinical cohort datasets. In line with previous work, our data on 2611 cases showed that APOE4 carriership associates with severe COVID-19 in intensive care patients compared with non-infected population controls after matching for age, sex and cardiovascular disease status. Histopathological examination of brain autopsy material of 21 COVID-19 cases provided evidence that perivascular microhaemorrhages are more prevalent in APOE4 carriers. Finally, our analysis of post-COVID fatigue in a prospective clinical cohort of 156 subjects revealed that APOE4 carriership independently associates with higher mental fatigue compared to non-carriers at six months after initial illness. In conclusion, the present data on Finns suggests that APOE4 is a risk factor for severe COVID-19 and post-COVID mental fatigue and provides the first indication that some of this effect could be mediated via increased cerebrovascular damage. Further studies in larger cohorts and animal models are warranted.}, }
@article {pmid34946243, year = {2021}, author = {Arbune, M and Iancu, AV and Lupasteanu, G and Vasile, MC and Stefanescu, V}, title = {A Challenge of COVID-19: Associated Infective Endocarditis with Streptococcus gordonii in a Young Immunocompetent Patient.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {57}, number = {12}, pages = {}, pmid = {34946243}, issn = {1648-9144}, mesh = {*COVID-19 ; *Endocarditis/diagnosis/drug therapy ; Female ; Humans ; Pandemics ; SARS-CoV-2 ; Streptococcus gordonii ; }, abstract = {The COVID-19 pandemic is a new challenge for the diagnosis and treatment of infective endocarditis (IE). Fever and other unspecific symptoms of coronaviral infection could be misleading or masking its manifestations. We present the case of a young patient admitted for persistent fever, profuse sweating, headache, articular pain, myalgias, and weight loss. She reported regression taste and smell disorders compared to a month earlier when diagnosed with moderate COVID-19 pneumonia. While the RT-PCR SARS-COV-2 test was positive, she was admitted to a COVID-19 ward. Investigations of febrile syndrome revealed two positive blood cultures with Streptococcus gordonii and the presence of vegetations on the aortic valve, supporting a certain diagnosis of IE. After six weeks of antibiotic treatment, the patient had clinical and biologic favorable outcomes. Streptococcus gordonii is a common commensal related to the dental biofilm, although there were no caries in our patient. The influence of COVID-19 infection on the human microbiome by modifying the virulence of some commensal germs may be a risk factor for IE pathogenesis on native valves and requires the vigilance of clinicians for suspicion of this disease.}, }
@article {pmid34943387, year = {2021}, author = {Sainz, T and Pignataro, V and Bonifazi, D and Ravera, S and Mellado, MJ and Pérez-Martínez, A and Escudero, A and Ceci, A and Calvo, C}, title = {Human Microbiome in Children, at the Crossroad of Social Determinants of Health and Personalized Medicine.}, journal = {Children (Basel, Switzerland)}, volume = {8}, number = {12}, pages = {}, pmid = {34943387}, issn = {2227-9067}, support = {777554//European Union- Horizon 2020/ ; }, abstract = {The evolving field of microbiome research offers an excellent opportunity for biomarker identification, understanding drug metabolization disparities, and improving personalized medicine. However, the complexities of host-microbe ecological interactions hinder clinical transferability. Among other factors, the microbiome is deeply influenced by age and social determinants of health, including environmental factors such as diet and lifestyle conditions. In this article, the bidirectionality of social and host-microorganism interactions in health will be discussed. While the field of microbiome-related personalized medicine evolves, it is clear that social determinants of health should be mitigated. Furthermore, microbiome research exemplifies the need for specific pediatric investigation plans to improve children's health.}, }
@article {pmid34942687, year = {2022}, author = {Jeong, S}, title = {Factors influencing development of the infant microbiota: from prenatal period to early infancy.}, journal = {Clinical and experimental pediatrics}, volume = {65}, number = {9}, pages = {439-447}, pmid = {34942687}, issn = {2713-4148}, abstract = {During early life, the gut microbial composition rapidly changes by maternal microbiota composition, delivery mode, infant feeding mode, antibiotic usage, and various environmental factors, such as the presence of pets and siblings. An integrative study on the diet, the microbiota, and genomic activity at the transcriptomic level may give an insight into the role of diet in shaping the human/microbiome relationship. Disruption in the gut microbiota (i.e., gut dysbiosis) has been linked to necrotizing enterocolitis in infancy, as well as some chronic diseases in later, including obesity, diabetes, inflammatory bowel disease, cancer, allergies, and asthma. Therefore, understanding the impact of maternal-to-infant transfer of dysbiotic microbes and then modifying infant early colonization or correcting early-life gut dysbiosis might be a potential strategy to overcome chronic health conditions.}, }
@article {pmid34940122, year = {2021}, author = {Ghannoum, MA and McCormick, TS and Retuerto, M and Bebek, G and Cousineau, S and Hartman, L and Barth, C and Schrom, K}, title = {Evaluation of Microbiome Alterations Following Consumption of BIOHM, a Novel Probiotic.}, journal = {Current issues in molecular biology}, volume = {43}, number = {3}, pages = {2135-2146}, pmid = {34940122}, issn = {1467-3045}, support = {R01 AI145289/AI/NIAID NIH HHS/United States ; AI145289//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Candida albicans ; Dysbiosis/*microbiology ; Healthy Volunteers ; Humans ; Metagenomics/methods ; Microbial Interactions ; *Microbiota ; Mycobiome ; Probiotics/*administration &amp; dosage ; RNA, Ribosomal, 16S ; }, abstract = {Gastrointestinal microbiome dysbiosis may result in harmful effects on the host, including those caused by inflammatory bowel diseases (IBD). The novel probiotic BIOHM, consisting of Bifidobacterium breve, Saccharomyces boulardii, Lactobacillus acidophilus, L. rhamnosus, and amylase, was developed to rebalance the bacterial-fungal gut microbiome, with the goal of reducing inflammation and maintaining a healthy gut population. To test the effect of BIOHM on human subjects, we enrolled a cohort of 49 volunteers in collaboration with the Fermentation Festival group (Santa Barbara, CA, USA). The profiles of gut bacterial and fungal communities were assessed via stool samples collected at baseline and following 4 weeks of once-a-day BIOHM consumption. Mycobiome analysis following probiotic consumption revealed an increase in Ascomycota levels in enrolled individuals and a reduction in Zygomycota levels (p value < 0.01). No statistically significant difference in Basidiomycota was detected between pre- and post-BIOHM samples and control abundance profiles (p > 0.05). BIOHM consumption led to a significant reduction in the abundance of Candida genus in tested subjects (p value < 0.013), while the abundance of C. albicans also trended lower than before BIOHM use, albeit not reaching statistical significance. A reduction in the abundance of Firmicutes at the phylum level was observed following BIOHM use, which approached levels reported for control individuals reported in the Human Microbiome Project data. The preliminary results from this clinical study suggest that BIOHM is capable of significantly rebalancing the bacteriome and mycobiome in the gut of healthy individuals, suggesting that further trials examining the utility of the BIOHM probiotic in individuals with gastrointestinal symptoms, where dysbiosis is considered a source driving pathogenesis, are warranted.}, }
@article {pmid34935428, year = {2021}, author = {Zhang, RM and Sun, J and Sun, RY and Wang, MG and Cui, CY and Fang, LX and Liao, MN and Lu, XQ and Liu, YX and Liao, XP and Liu, YH}, title = {Source Tracking and Global Distribution of the Tigecycline Non-Susceptible tet(X).}, journal = {Microbiology spectrum}, volume = {9}, number = {3}, pages = {e0116421}, pmid = {34935428}, issn = {2165-0497}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/*genetics/metabolism ; Bacteroidaceae/drug effects/*genetics/metabolism ; DNA Transposable Elements ; Drug Resistance, Bacterial ; Escherichia coli/drug effects/*genetics/metabolism ; Flavobacteriaceae/drug effects/*genetics/metabolism ; Gene Transfer, Horizontal ; Humans ; Microbial Sensitivity Tests ; Plasmids/genetics/metabolism ; Riemerella/drug effects/*genetics/metabolism ; Tigecycline/*pharmacology ; }, abstract = {The emergence of tet(X) genes has compromised the clinical use of the last-line antibiotic tigecycline. We identified 322 (1.21%) tet(X) positive samples from 12,829 human microbiome samples distributed in four continents (Asia, Europe, North America, and South America) using retrospective data from worldwide. These tet(X) genes were dominated by tet(X2)-like orthologs but we also identified 12 samples carrying novel tet(X) genes, designed tet(X45), tet(X46), and tet(X47), were resistant to tigecycline. The metagenomic analysis indicated these tet(X) genes distributed in anaerobes dominated by Bacteroidaceae (78.89%) of human-gut origin. Two mobile elements ISBf11 and IS4351 were most likely to promote the transmission of these tet(X2)-like orthologs between Bacteroidaceae and Riemerella anatipestifer. tet(X2)-like orthologs was also developed during transmission by mutation to high-level tigecycline resistant genes tet(X45), tet(X46), and tet(X47). Further tracing these tet(X) in single bacterial isolate from public repository indicated tet(X) genes were present as early as 1960s in R. anatipestifer that was the primary tet(X) carrier at early stage (before 2000). The tet(X2) and non-tet(X2) orthologs were primarily distributed in humans and food animals respectively, and non-tet(X2) were dominated by tet(X3) and tet(X4). Genomic comparison indicated these tet(X) genes were likely to be generated during tet(X) transmission between Flavobacteriaceae and E. coli/Acinetobacter spp., and ISCR2 played a key role in the transmission. These results suggest R. anatipestifer was the potential ancestral source of tet(X). In addition, Bacteroidaceae of human-gut origin was an important hidden reservoir and mutational incubator for the mobile tet(X) genes that enabled spread to facultative anaerobes and aerobes. IMPORTANCE The emergence of the tigecycline resistance gene tet(X) has posed a severe threat to public health. However, reports of its origin and distribution in human remain rare. Here, we explore the origin and distribution of tet(X) from large-scale metagenomic data of human-gut origin and public repository. This study revealed the emergency of tet(X) gene in 1960s, which has refreshed a previous standpoint that the earliest presence of tet(X) was in 1980s. The metagenomic analysis from data mining covered the unculturable bacteria, which has overcome the traditional bacteria isolating and purificating technologies, and the analysis indicated that the Bacteroidaceae of human-gut origin was an important hidden reservoir for tet(X) that enabled spread to facultative anaerobes and aerobes. The continuous monitoring of mobile tigecycline resistance determinants from both culturable and unculturable microorganisms is imperative for understanding and tackling the dissemination of tet(X) genes in both the health care and agricultural sectors.}, }
@article {pmid34929293, year = {2022}, author = {Nel Van Zyl, K and Matukane, SR and Hamman, BL and Whitelaw, AC and Newton-Foot, M}, title = {Effect of antibiotics on the human microbiome: a systematic review.}, journal = {International journal of antimicrobial agents}, volume = {59}, number = {2}, pages = {106502}, doi = {10.1016/j.ijantimicag.2021.106502}, pmid = {34929293}, issn = {1872-7913}, mesh = {Anti-Bacterial Agents/adverse effects ; Child ; Dysbiosis/chemically induced ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Global antibiotic use has been increasing for decades. The gut microbiome, a key contributor to health, can be altered by antibiotics, which have been associated with both short- and long-term effects on the intestinal microbiome. The aim of this study was to summarize the effects of antibiotics on the diversity and composition of the human microbiota at different anatomical sites.<br><br>METHODS: A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus and Web of Science online databases were searched for studies that described the microbiome of any human bodily site pre- and post-antibiotic treatment using 16S rRNA gene sequencing. Increases or decreases in diversity, dissimilarity of microbial communities, and changes in taxonomic composition following antibiotic treatment were recorded as outcome measures.<br><br>RESULTS: The review identified consistent changes in the microbiota following quinolone and metronidazole treatment, and showed that combination treatment may result in longer-term dysbiosis. The importance of longitudinal analysis, and a lack of studies in paediatric populations was highlighted. Heterogeneity in the methodology of included studies could have contributed to the inconsistent findings regarding the effect of most antibiotic classes on the microbiome.<br><br>CONCLUSIONS: It is recommended that studies investigating the effect of antibiotics on the microbiome need to exclude participants exposed to antibiotics within 4 months preceding collection and analysis of baseline samples, and to include longitudinal analysis, particularly in the longer term. Further explorations need to be made into the functional implications of antibiotic-induced dysbiosis in the microbiome.<br><br>PROSPERO (https://www.crd.york.ac.uk/prospero; Registration:CRD42020168991).}, }
@article {pmid34928256, year = {2022}, author = {Verstraelen, H and Vieira-Baptista, P and De Seta, F and Ventolini, G and Lonnee-Hoffmann, R and Lev-Sagie, A}, title = {The Vaginal Microbiome: I. Research Development, Lexicon, Defining "Normal" and the Dynamics Throughout Women's Lives.}, journal = {Journal of lower genital tract disease}, volume = {26}, number = {1}, pages = {73-78}, pmid = {34928256}, issn = {1526-0976}, mesh = {Adolescent ; Bacteria ; Female ; Humans ; Infant, Newborn ; Menopause ; *Microbiota ; Research ; Vagina ; }, abstract = {OBJECTIVE: This series of articles, titled The Vaginal Microbiome, written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the current findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders.<br><br>MATERIALS AND METHODS: A database search of PubMed was performed, using the search terms "vaginal microbiome" (VMB) with "research," "normal," "neonate," "puberty," "adolescent," "menopause," and "ethnicities," as well as "human microbiome project." Full article texts were reviewed. Reference lists were screened for additional articles.<br><br>RESULTS: In the last 2 decades, many studies applying molecular techniques were performed, intending to characterize the vaginal microbiota. These studies advanced our understanding of how vaginal health is defined. The first article in this series focuses on the advancement of VMB research, technical definitions, the definition of "normal" VMB, and the dynamics of VMB throughout women's lives.<br><br>CONCLUSIONS: Understanding how microorganisms inhabiting the vagina interact with each other and with the host is important for a more complete understanding of vaginal health. The clinical application of microbial community sequencing is in its beginning, and its interpretation regarding practical clinical aspects is yet to be determined.}, }
@article {pmid34917651, year = {2021}, author = {Parolin, C and Zhu, W and Zhu, J}, title = {Editorial: Metabolomics of Human Microbiome Studies: Recent Advances in Methods and Applications.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {800337}, pmid = {34917651}, issn = {2296-889X}, }
@article {pmid34917047, year = {2021}, author = {Lin, S and Zhang, H and Wang, X and Lin, T and Chen, Z and Liu, J and Wang, J}, title = {Abundance of Lipopolysaccharide Heptosyltransferase I in Human Gut Microbiome and Its Association With Cardiovascular Disease and Liver Cirrhosis.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {756976}, pmid = {34917047}, issn = {1664-302X}, abstract = {Lipopolysaccharide (LPS) is a potent endotoxin on the outer membrane of gram-negative bacteria. Heptosyltransferase I (HpeI) takes part in the synthesis of LPS. In this study, we first collected the protein sequences of HpeI homologs from the human microbiome. The collected HpeI sequences was classified based on sequence similarity, and seven clusters of HpeI were obtained. Among these clusters, proteins from Cluster 3 were abundant in the human mouth, while Clusters 1, 6, and 7 were abundant in the human gut. In addition, proteins from Cluster 1 were mainly from the order of Enterobacterales, while Cluster 6 and 7 were from Burkholderiales. The correlation analysis indicated that the total abundance of HpeIs was increased in patients with cardiovascular disease and liver cirrhosis, and HpeI in Cluster 1 contributed to this increase. These data suggest that HpeI homologs in Cluster 1 can be recognized as biomarkers for cardiovascular disease and liver cirrhosis, and that reducing the bacterial load in Cluster 1 may contribute to disease therapy.}, }
@article {pmid34911583, year = {2021}, author = {Allali, I and Abotsi, RE and Tow, LA and Thabane, L and Zar, HJ and Mulder, NM and Nicol, MP}, title = {Human microbiota research in Africa: a systematic review reveals gaps and priorities for future research.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {241}, pmid = {34911583}, issn = {2049-2618}, support = {U54 HG009824/HG/NHGRI NIH HHS/United States ; U41 HG006941/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; Mass Screening ; *Microbiota ; Public Health ; South Africa ; Uganda ; }, abstract = {BACKGROUND: The role of the human microbiome in health and disease is an emerging and important area of research; however, there is a concern that African populations are under-represented in human microbiome studies. We, therefore, conducted a systematic survey of African human microbiome studies to provide an overview and identify research gaps. Our secondary objectives were: (i) to determine the number of peer-reviewed publications; (ii) to identify the extent to which the researches focused on diseases identified by the World Health Organization [WHO] State of Health in the African Region Report as being the leading causes of morbidity and mortality in 2018; (iii) to describe the extent and pattern of collaborations between researchers in Africa and the rest of the world; and (iv) to identify leadership and funders of the studies.<br><br>METHODOLOGY: We systematically searched Medline via PubMed, Scopus, CINAHL, Academic Search Premier, Africa-Wide Information through EBSCOhost, and Web of Science from inception through to 1st April 2020. We included studies that characterized samples from African populations using next-generation sequencing approaches. Two reviewers independently conducted the literature search, title and abstract, and full-text screening, as well as data extraction.<br><br>RESULTS: We included 168 studies out of 5515 records retrieved. Most studies were published in PLoS One (13%; 22/168), and samples were collected from 33 of the 54 African countries. The country where most studies were conducted was South Africa (27/168), followed by Kenya (23/168) and Uganda (18/168). 26.8% (45/168) focused on diseases of significant public health concern in Africa. Collaboration between scientists from the United States of America and Africa was most common (96/168). The first and/or last authors of 79.8% of studies were not affiliated with institutions in Africa. Major funders were the United States of America National Institutes of Health (45.2%; 76/168), Bill and Melinda Gates Foundation (17.8%; 30/168), and the European Union (11.9%; 20/168).<br><br>CONCLUSIONS: There are significant gaps in microbiome research in Africa, especially those focusing on diseases of public health importance. There is a need for local leadership, capacity building, intra-continental collaboration, and national government investment in microbiome research within Africa. Video Abstract.}, }
@article {pmid34900793, year = {2021}, author = {Mane, S and Dixit, KK and Lathwal, N and Dhotre, D and Kadus, P and Shouche, YS and Bhalerao, S}, title = {Rectal administration of buttermilk processed with medicinal plants alters gut microbiome in obese individuals.}, journal = {Journal of diabetes and metabolic disorders}, volume = {20}, number = {2}, pages = {1415-1427}, pmid = {34900793}, issn = {2251-6581}, abstract = {OBJECTIVE: To evaluate the effect of rectal administration of buttermilk processed with medicinal plants on gut microbial composition and thereby on weight in obese individuals.<br><br>METHODS: With ethics&#xa0;committee approval, 16 obese individuals in the age group 20-50&#xa0;years (BMI &#x2265;30&#xa0;kg/m[2]) were recruited who received a course of 15-enemas over 15-days. Of these, 1st, 8th and 15th enemas were of sesame-oil administered after food, while other enemas were of buttermilk processed with medicinal plants administered before food. Outcome variables viz. anthropometry, body composition, blood glucose, insulin and lipid profile were evaluated on day 0, 16 and 45. Also,&#xa0;microbial composition of buttermilk preparation and faecal samples of patients collected on day 0, 16 and 45 were studied with the help of 16S rRNA gene sequencing.<br><br>RESULTS: The circumferential measures and skinfold-thickness showed a decrease on day 16, which remained lower as compared to baseline till day 45. A gradual decrease in blood-glucose was seen, which was statistically significant on day 45, while insulin levels increased on day 16 and fell to baseline on day 45. There was an overall increase in bacterial diversity on day 16 that settled back to its original composition by day 45.<br><br>CONCLUSION: Our findings suggest that buttermilk administration per rectum is effective for a specific period and may have to be repeated for sustained benefits.<br><br>SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00879-z.}, }
@article {pmid34900137, year = {2021}, author = {Narayana, JK and Mac Aogáin, M and Goh, WWB and Xia, K and Tsaneva-Atanasova, K and Chotirmall, SH}, title = {Mathematical-based microbiome analytics for clinical translation.}, journal = {Computational and structural biotechnology journal}, volume = {19}, number = {}, pages = {6272-6281}, pmid = {34900137}, issn = {2001-0370}, abstract = {Traditionally, human microbiology has been strongly built on the laboratory focused culture of microbes isolated from human specimens in patients with acute or chronic infection. These approaches primarily view human disease through the lens of a single species and its relevant clinical setting however such approaches fail to account for the surrounding environment and wide microbial diversity that exists in vivo. Given the emergence of next generation sequencing technologies and advancing bioinformatic pipelines, researchers now have unprecedented capabilities to characterise the human microbiome in terms of its taxonomy, function, antibiotic resistance and even bacteriophages. Despite this, an analysis of microbial communities has largely been restricted to ordination, ecological measures, and discriminant taxa analysis. This is predominantly due to a lack of suitable computational tools to facilitate microbiome analytics. In this review, we first evaluate the key concerns related to the inherent structure of microbiome datasets which include its compositionality and batch effects. We describe the available and emerging analytical techniques including integrative analysis, machine learning, microbial association networks, topological data analysis (TDA) and mathematical modelling. We also present how these methods may translate to clinical settings including tools for implementation. Mathematical based analytics for microbiome analysis represents a promising avenue for clinical translation across a range of acute and chronic disease states.}, }
@article {pmid34896087, year = {2022}, author = {Naspolini, NF and Meyer, A and Moreira, JC and Sun, H and Froes-Asmus, CIR and Dominguez-Bello, MG}, title = {Environmental pollutant exposure associated with altered early-life gut microbiome: Results from a birth cohort study.}, journal = {Environmental research}, volume = {205}, number = {}, pages = {112545}, doi = {10.1016/j.envres.2021.112545}, pmid = {34896087}, issn = {1096-0953}, support = {P30 ES005022/ES/NIEHS NIH HHS/United States ; }, mesh = {Birth Cohort ; Cohort Studies ; *Environmental Pollutants/toxicity ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Emerging evidence shows that the gut microbiota interacts with environmental pollutants, but the effect of early exposure on the neonatal microbiome remains unknown. We investigated the association between maternal exposure to environmental pollutants and changes in early-life gut microbiome development. We surveyed 16S rRNA gene on meconium and fecal samples (at 1, 3, and 6 months) from the Brazilian birth cohort, and associated with levels of metals, perfluoroalkyl chemicals (PFAS), and pesticides in maternal and umbilical cord blood. The results indicate that the magnitude of the microbiome changes associated with increasing pollutant exposure was bigger in cesarean-section (CS) born and CS-born-preterm babies, in relation to vaginally (VG) delivered infants. Breastfeeding was associated with a stronger pollutant-associated effect on the infant feces, suggesting that the exposure source could be maternal milk. Differences in microbiome effects associated with maternal or cord blood pollutant concentrations suggest that fetal exposure time - intrauterine or perinatal - may matter. Finally, despite the high developmental microbiota variability, specific microbionts were consistently affected across all pollutants, with taxa clusters found in samples from infants exposed to the highest toxicant exposure. The results evidence that perinatal exposure to environmental pollutants is associated with alterations in gut microbiome development which may have health significance.}, }
@article {pmid34896030, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Ufimtseva, A and Poluektova, E}, title = {Two consecutive attacks of diarrhea in 15 COVID-19 patients: An antibiotic-associated one following the viral one.}, journal = {Revista de gastroenterologia de Mexico (English)}, volume = {87}, number = {1}, pages = {59-62}, pmid = {34896030}, issn = {2255-534X}, mesh = {Anti-Bacterial Agents/adverse effects ; *COVID-19 ; Diarrhea/chemically induced ; Female ; Humans ; Intensive Care Units ; Middle Aged ; SARS-CoV-2 ; }, abstract = {Of the 971 patients admitted to our Clinic with suspected COVID-19, 15 (1.5%) presented with two consecutive attacks of diarrhea. One of those patients (a 47-year-old woman) required admission to the intensive care unit and mechanical ventilation. She died on the 11th day of hospitalization (18th day of illness). The first attack of diarrhea in those patients occurred on the 6th (4th-7th) day of disease and lasted 3 (3-5) days. The second attack of diarrhea developed 11 (8-12) days after the initial onset of diarrhea. Despite the existing trend, the difference in the duration of the diarrhea and the maximum number of bowel movements per day between the first and second attacks was not statistically significant (p = 0.130; p = 0.328). There was no significant difference between the patients with a double attack of diarrhea and those with no diarrhea, regarding the results of the complete blood count, biochemical blood tests, and inflammation biomarkers.}, }
@article {pmid34888397, year = {2021}, author = {Presti, RM and Yeh, E and Williams, B and Landay, A and Jacobson, JM and Wilson, C and Fichtenbaum, CJ and Utay, NS and Dube, MP and Klingman, KL and Estes, JD and Flynn, JK and Loftin, A and Brenchley, JM and Andrade, A and Kitch, DW and Overton, ET}, title = {A Randomized, Placebo-Controlled Trial Assessing the Effect of VISBIOME ES Probiotic in People With HIV on Antiretroviral Therapy.}, journal = {Open forum infectious diseases}, volume = {8}, number = {12}, pages = {ofab550}, pmid = {34888397}, issn = {2328-8957}, support = {UM1 AI069494/AI/NIAID NIH HHS/United States ; UM1 AI069501/AI/NIAID NIH HHS/United States ; UM1 AI069432/AI/NIAID NIH HHS/United States ; UM1 AI069439/AI/NIAID NIH HHS/United States ; UM1 AI068634/AI/NIAID NIH HHS/United States ; UM1 AI069481/AI/NIAID NIH HHS/United States ; U01 AI069432/AI/NIAID NIH HHS/United States ; UM1 AI106701/AI/NIAID NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; UM1 AI069419/AI/NIAID NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; UM1 AI069452/AI/NIAID NIH HHS/United States ; UM1 AI069496/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function.<br><br>METHODS: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample t test with equal variance or the Wilcoxon rank-sum test. For safety, the highest graded adverse events (AEs) were compared between arms using the Fisher exact test.<br><br>RESULTS: Overall, 93 participants enrolled: 86% male, median age 51 years, median CD4 count 712 cells/mm3. Visbiome ES was safe and well tolerated. There was no difference in mean change in sCD14 from baseline to week 25/26 between placebo (mean change, 92.3 &#xb5;g/L; 95% CI, -48.5 to 233 &#xb5;g/L) and Visbiome ES (mean change, 41.0 &#xb5;g/L; 95% CI, -94.1 to 176.2 &#xb5;g/L; P=.60). Similarly, no statistically significant differences between arms in inflammatory marker changes were identified. In substudy participants, no statistical differences between arms for change in cellular marker expression or gut permeability were observed (P>.05 for all). The microbiome demonstrated increased probiotic species and a significant decrease in Gammaproteobacteria (P=.044) in the Visbiome ES arm.<br><br>CONCLUSIONS: Visbiome ES was safe and altered the microbiome but demonstrated no effect on systemic inflammatory markers, pathology, or gut permeability in antiretroviral therapy-treated people with HIV.}, }
@article {pmid34886156, year = {2021}, author = {Fischer, JAJ and Karakochuk, CD}, title = {Feasibility of an At-Home Adult Stool Specimen Collection Method in Rural Cambodia.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {23}, pages = {}, pmid = {34886156}, issn = {1660-4601}, support = {ID400771//CIHR/Canada ; }, mesh = {Adult ; Cambodia ; Feasibility Studies ; Feces ; Female ; Humans ; *Microbiota ; Specimen Handling ; }, abstract = {The human microbiome has received significant attention over the past decade regarding its potential impact on health. Epidemiological and intervention studies often rely on at-home stool collection methods designed for high-resource settings, such as access to an improved toilet with a modern toilet seat. However, this is not always appropriate or applicable to low-resource settings. Therefore, the design of a user-friendly stool collection kit for low-resource rural settings is needed. We describe the development, assembly, and user experience of a simple and low-cost at-home stool collection kit for women living in rural Cambodia as part of a randomized controlled trial in 2020. Participants were provided with the stool collection kit and detailed verbal instruction. Enrolled women (n = 480) provided two stool specimens (at the start of the trial and after 12 weeks) at their home and brought them to the health centre that morning in a sterile collection container. User specimen collection compliance was high, with 90% (n = 434) of women providing a stool specimen at the end of the trial (after 12 weeks). This feasible and straightforward method has strong potential for similar or adapted use among adults residing in other rural or low-resource contexts.}, }
@article {pmid34885015, year = {2021}, author = {Gugnacki, P and Sierko, E}, title = {Is There an Interplay between Oral Microbiome, Head and Neck Carcinoma and Radiation-Induced Oral Mucositis?.}, journal = {Cancers}, volume = {13}, number = {23}, pages = {}, pmid = {34885015}, issn = {2072-6694}, abstract = {Head and neck carcinoma is one of the most common human malignancy types and it ranks as the sixth most common cancer worldwide. Nowadays, a great potential of microbiome research is observed in oncology-investigating the effect of oral microbiome in oncogenesis, occurrence of treatment side effects and response to anticancer therapies. The microbiome is a unique collection of microorganisms and their genetic material, interactions and products residing within the mucous membranes. The aim of this paper is to summarize current research on the oral microbiome and its impact on the development of head and neck cancer and radiation-induced oral mucositis. Human microbiome might determine an oncogenic effect by, among other things, inducing chronic inflammatory response, instigating cellular antiapoptotic signals, modulation of anticancer immunity or influencing xenobiotic metabolism. Influence of oral microbiome on radiation-induced oral mucositis is expressed by the production of additional inflammatory cytokines and facilitates progression and aggravation of mucositis. Exacerbated acute radiation reaction and bacterial superinfections lead to the deterioration of the patient's condition and worsening of the quality of life. Simultaneously, positive effects of probiotics on the course of radiation-induced oral mucositis have been observed. Understanding the impact on the emerging acute radiation reaction on the composition of the microflora can be helpful in developing a multifactorial model to forecast the course of radiation-induced oral mucositis. Investigating these processes will allow us to create optimized and personalized preventive measures and treatment aimed at their formation mechanism. Further studies are needed to better establish the structure of the oral microbiome as well as the dynamics of its changes before and after therapy. It will help to expand the understanding of the biological function of commensal and pathogenic oral microbiota in HNC carcinogenesis and the development of radiation-induced oral mucositis.}, }
@article {pmid34884776, year = {2021}, author = {Sammallahti, H and Kokkola, A and Rezasoltani, S and Ghanbari, R and Asadzadeh Aghdaei, H and Knuutila, S and Puolakkainen, P and Sarhadi, VK}, title = {Microbiota Alterations and Their Association with Oncogenomic Changes in Pancreatic Cancer Patients.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884776}, issn = {1422-0067}, mesh = {Carcinoma, Pancreatic Ductal/*microbiology/pathology/therapy ; Cell Transformation, Neoplastic/pathology ; Dysbiosis/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mouth/microbiology ; Pancreas/*microbiology/pathology ; Pancreatic Neoplasms/*microbiology/pathology/therapy ; }, abstract = {Pancreatic cancer (PC) is an aggressive disease with a high mortality and poor prognosis. The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and PC development are not completely clear. Herein, we review the complex interactions between PC tumorigenesis and the microbiota, and especially the question, whether and how an altered microbiota induces oncogenomic changes, or vice versa, whether cancer mutations have an impact on microbiota composition. In addition, the role of the microbiota in drug efficacy in PC chemo- and immunotherapies is discussed. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.}, }
@article {pmid34884466, year = {2021}, author = {Yu, D and Meng, X and de Vos, WM and Wu, H and Fang, X and Maiti, AK}, title = {Implications of Gut Microbiota in Complex Human Diseases.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, pmid = {34884466}, issn = {1422-0067}, support = {YDZJ202101ZYTS080//Jilin Province Science and Technology Department/ ; }, mesh = {Anti-Bacterial Agents/adverse effects ; Diet/*adverse effects ; Dysbiosis/etiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Prebiotics/adverse effects ; Probiotics/adverse effects ; }, abstract = {Humans, throughout the life cycle, from birth to death, are accompanied by the presence of gut microbes. Environmental factors, lifestyle, age and other factors can affect the balance of intestinal microbiota and their impact on human health. A large amount of data show that dietary, prebiotics, antibiotics can regulate various diseases through gut microbes. In this review, we focus on the role of gut microbes in the development of metabolic, gastrointestinal, neurological, immune diseases and, cancer. We also discuss the interaction between gut microbes and the host with respect to their beneficial and harmful effects, including their metabolites, microbial enzymes, small molecules and inflammatory molecules. More specifically, we evaluate the potential ability of gut microbes to cure diseases through Fecal Microbial Transplantation (FMT), which is expected to become a new type of clinical strategy for the treatment of various diseases.}, }
@article {pmid34884327, year = {2021}, author = {Daniluk, J and Daniluk, U and Rogalski, P and Dabrowski, A and Swidnicka-Siergiejko, A}, title = {Microbiome-Friend or Foe of Pancreatic Cancer?.}, journal = {Journal of clinical medicine}, volume = {10}, number = {23}, pages = {}, pmid = {34884327}, issn = {2077-0383}, support = {2017/27/B/NZ5/02904//National Science Center/ ; }, abstract = {Pancreatic ductal adenocarcinoma is one of the deadliest human neoplasms. Despite the development of new surgical and adjuvant therapies, the prognosis remains very poor, with the overall survival rate not exceeding 9%. There is now increasing evidence that the human microbiome, which is involved in many physiological functions, including the regulation of metabolic processes and the modulation of the immune system, is possibly linked to pancreatic oncogenesis. However, the exact mechanisms of action are poorly understood. Our review summarizes the current understanding of how the microbiome affects pancreatic cancer development and progression. We discuss potential pathways of microbe translocation to the pancreas, as well as the mechanism of their action. We describe the role of the microbiome as a potential marker of pancreatic cancer diagnosis, progression, and survival. Finally, we discuss the possibilities of modifying the microbiome to improve treatment effectiveness for this deadly disease.}, }
@article {pmid34880965, year = {2022}, author = {Barb, JJ and Maki, KA and Kazmi, N and Meeks, BK and Krumlauf, M and Tuason, RT and Brooks, AT and Ames, NJ and Goldman, D and Wallen, GR}, title = {The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment.}, journal = {Journal of oral microbiology}, volume = {14}, number = {1}, pages = {2004790}, pmid = {34880965}, issn = {2000-2297}, abstract = {BACKGROUND: Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome.<br><br>AIM: To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD.<br><br>METHODS: Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing.<br><br>RESULTS: Alpha diversity decreased linearly during treatment across the entire cohort (P =&#xa0;0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella.<br><br>CONCLUSION: The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.}, }
@article {pmid34879270, year = {2021}, author = {Daisley, BA and Koenig, D and Engelbrecht, K and Doney, L and Hards, K and Al, KF and Reid, G and Burton, JP}, title = {Emerging connections between gut microbiome bioenergetics and chronic metabolic diseases.}, journal = {Cell reports}, volume = {37}, number = {10}, pages = {110087}, doi = {10.1016/j.celrep.2021.110087}, pmid = {34879270}, issn = {2211-1247}, mesh = {Animals ; Bacteria/growth &amp; development/*metabolism ; Chronic Disease ; Dysbiosis ; *Energy Metabolism ; Fatty Acids, Volatile/*metabolism ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Metabolic Diseases/metabolism/*microbiology ; Symbiosis ; }, abstract = {The conventional viewpoint of single-celled microbial metabolism fails to adequately depict energy flow at the systems level in host-adapted microbial communities. Emerging paradigms instead support that distinct microbiomes develop interconnected and interdependent electron transport chains that rely on cooperative production and sharing of bioenergetic machinery (i.e., directly involved in generating ATP) in the extracellular space. These communal resources represent an important subset of the microbial metabolome, designated here as the "pantryome" (i.e., pantry or external storage compartment), that critically supports microbiome function and can exert multifunctional effects on host physiology. We review these interactions as they relate to human health by detailing the genomic-based sharing potential of gut-derived bacterial and archaeal reference strains. Aromatic amino acids, metabolic cofactors (B vitamins), menaquinones (vitamin K2), hemes, and short-chain fatty acids (with specific emphasis on acetate as a central regulator of symbiosis) are discussed in depth regarding their role in microbiome-related metabolic diseases.}, }
@article {pmid34867436, year = {2021}, author = {Rao, B and Ren, T and Wang, X and Wang, H and Zou, Y and Sun, Y and Liu, S and Ren, Z and Yu, Z}, title = {Dysbiosis in the Human Microbiome of Cholangiocarcinoma.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {715536}, pmid = {34867436}, issn = {1664-042X}, abstract = {Cholangiocarcinoma (CCA) is the most common malignant tumor of the biliary system with a very poor prognosis. The human microbiome, which is the sum of the genetic information of human microorganisms, plays an important role in regulating the digestion, absorption, immune response, and metabolism of the host. Increasing evidence indicates a close relationship between CCA and the human microbiome. Specific alterations occur in the human microbiome of patients with CCA. Therefore, in this review, we aimed to summarize the recent evidence on dysbiosis in the human microbiome of CCA. Then, we generalized the effect of Helicobacter pylori on CCA. Additionally, the potential mechanism of human microbial dysbiosis promoted the progress of CCA, and its precancerous disease was also explored. Furthermore, the possibility of the human microbiome as a diagnostic and therapeutic target of CCA was discussed.}, }
@article {pmid34866471, year = {2022}, author = {Chen, B and Xu, W}, title = {Functional response regression model on correlated longitudinal microbiome sequencing data.}, journal = {Statistical methods in medical research}, volume = {31}, number = {2}, pages = {361-371}, pmid = {34866471}, issn = {1477-0334}, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; Least-Squares Analysis ; *Microbiota/genetics ; Research Design ; }, abstract = {Functional regression has been widely used on longitudinal data, but it is not clear how to apply functional regression to microbiome sequencing data. We propose a novel functional response regression model analyzing correlated longitudinal microbiome sequencing data, which extends the classic functional response regression model only working for independent functional responses. We derive the theory of generalized least squares estimators for predictors' effects when functional responses are correlated, and develop a data transformation technique to solve the computational challenge for analyzing correlated functional response data using existing functional regression method. We show by extensive simulations that our proposed method provides unbiased estimations for predictors' effect, and our model has accurate type I error and power performance for correlated functional response data, compared with classic functional response regression model. Finally we implement our method to a real infant gut microbiome study to evaluate the relationship of clinical factors to predominant taxa along time.}, }
@article {pmid34857814, year = {2021}, author = {Korpela, K and Kallio, S and Salonen, A and Hero, M and Kukkonen, AK and Miettinen, PJ and Savilahti, E and Kohva, E and Kariola, L and Suutela, M and Tarkkanen, A and de Vos, WM and Raivio, T and Kuitunen, M}, title = {Gut microbiota develop towards an adult profile in a sex-specific manner during puberty.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {23297}, pmid = {34857814}, issn = {2045-2322}, mesh = {Adolescent ; Clostridiaceae ; Cohort Studies ; Estrogens/metabolism ; Feces/microbiology ; Female ; Finland ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; Puberty/*physiology ; Ruminococcus ; *Sex Characteristics ; Surveys and Questionnaires ; }, abstract = {Accumulating evidence indicates that gut microbiota may regulate sex-hormone levels in the host, with effects on reproductive health. Very little is known about the development of intestinal microbiota during puberty in humans. To assess the connection between pubertal timing and fecal microbiota, and to assess how fecal microbiota develop during puberty in comparison with adult microbiota, we utilized a Finnish allergy-prevention-trial cohort (Flora). Data collected at 13-year follow-up were compared with adult data from a different Finnish cohort. Among the 13-year-old participants we collected questionnaire information, growth data from school-health-system records and fecal samples from 148 participants. Reference adult fecal samples were received from the Health and Early Life Microbiota (HELMi) cohort (n = 840). Fecal microbiota were analyzed using 16S rRNA gene amplicon sequencing; the data were correlated with pubertal timing and compared with data on adult microbiota. Probiotic intervention in the allergy-prevention-trial cohort was considered as a confounding factor only. The main outcome was composition of the microbiota in relation to pubertal timing (time to/from peak growth velocity) in both sexes separately, and similarity to adult microbiota. In girls, fecal microbiota became more adult-like with pubertal progression (p = 0.009). No such development was observed in boys (p = 0.9). Both sexes showed a trend towards increasing relative abundance of estrogen-metabolizing Clostridia and decreasing Bacteroidia with pubertal development, but this was statistically significant in girls only (p = 0.03). In girls, pubertal timing was associated positively with exposure to cephalosporins prior to the age of 10. Our data support the hypothesis that gut microbiota, particularly members of Ruminococcaceae, may affect pubertal timing, possibly via regulating host sex-hormone levels.Trial registration The registration number for the allergy-prevention-trial cohort: ClinicalTrials.gov, NCT00298337, registered 1 March 2006-Retrospectively registered, https://clinicaltrials.gov/show/NCT00298337 . The adult-comparison cohort (HELMi) is NCT03996304.}, }
@article {pmid34856363, year = {2022}, author = {Morikawa, A and Kawabata, A and Shirahige, K and Akiyama, T and Okamoto, A and Sutani, T}, title = {Altered cervicovaginal microbiota in premenopausal ovarian cancer patients.}, journal = {Gene}, volume = {811}, number = {}, pages = {146083}, doi = {10.1016/j.gene.2021.146083}, pmid = {34856363}, issn = {1879-0038}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacterial Typing Techniques/methods ; Biomarkers ; Carcinoma, Ovarian Epithelial/*microbiology ; Case-Control Studies ; Cervix Uteri/*microbiology ; DNA, Bacterial ; Female ; Humans ; Japan ; Lactobacillus/classification/genetics ; Metagenome ; *Microbiota ; Middle Aged ; Ovarian Neoplasms/*microbiology ; Postmenopause ; Premenopause ; RNA, Ribosomal, 16S ; Vagina/*microbiology ; Young Adult ; }, abstract = {Nearly three hundred thousand female patients are diagnosed with ovarian cancer in the world annually, and this number shows an increasing trend. However, characteristic symptoms caused by ovarian cancer are so few that early diagnosis remains challenging, and an effective screening method has not yet been established. Here, we conducted a case-control study in Japan to analyze the association between cervicovaginal microbiome and ovarian cancer, using 16S rRNA amplicon sequencing. Analysis of DNA extracted from cervical smear samples revealed Lactobacillus-dominant and Lactobacillus-deficient, highly-diversified bacterial communities in premenopausal and postmenopausal healthy controls, respectively, as reported for vaginal microbiota previously. We found that cervicovaginal microbiota in ovarian cancer patients, regardless of their menopausal status, were frequently a diversified community and similar to those in healthy subjects at postmenopausal ages. The diverse microbiota was associated with the major histotypes of epithelial ovarian cancer, including serous ovarian cancer and ovarian clear cell cancer. The present study implies the potential of a cervicovaginal microbiome biomarker in screening ovarian cancer in premenopausal women.}, }
@article {pmid34853760, year = {2021}, author = {Mamgain, G and Patra, P and Naithani, M and Nath, UK}, title = {The Role of Microbiota in the Development of Cancer Tumour Cells and Lymphoma of B and T Cells.}, journal = {Cureus}, volume = {13}, number = {10}, pages = {e19047}, pmid = {34853760}, issn = {2168-8184}, abstract = {Human body harbours enormous numbers of microbial organisms, including bacteria, viruses, and fungi which have a momentous role in well-being and illness in humans. Immune system shelters us from pathogenic bacteria, microorganisms found in human tissues have many benefits related to the functional movement of the host by regulating important procedures such as immunity, signalling, and breakdown. Lymphocytes assume a significant part in the reaction to bacterial colonization, primarily by prompting a safe reaction to obstruction or initiation. Most immunologically occupant cells have a place with the mucosal invulnerable framework and are continually motioned by dendritic cells or other Antigen introducing cells that gather intestinal samples. Thus, Microbiome is a key contributor to developing lymphoma and specific alterations to microbiome composition could attenuate the risk. There is an indication that microbial morphology can affect and control humanoids. The difference in the composition of these microorganisms is associated with tumour development. With the increased knowledge of the connection among the human microbiome and carcinogenesis, the use of these findings to prevent, predict or diagnose of lymphomas has attracted a great attention. In this article, we explored current knowledge of various microbial ecosystems, their connection with carcinogens and the potential for useful microorganisms to control and prevent B and T cell lymphoma.}, }
@article {pmid34851166, year = {2021}, author = {Piscotta, FJ and Hoffmann, HH and Choi, YJ and Small, GI and Ashbrook, AW and Koirala, B and Campbell, EA and Darst, SA and Rice, CM and Brady, SF}, title = {Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals.}, journal = {mSphere}, volume = {6}, number = {6}, pages = {e0071121}, pmid = {34851166}, issn = {2379-5042}, support = {T32 GM066699/GM/NIGMS NIH HHS/United States ; R01 GM114450/GM/NIGMS NIH HHS/United States ; R35 GM118130/GM/NIGMS NIH HHS/United States ; R01 AT009562/AT/NCCIH NIH HHS/United States ; R01 AI161278/AI/NIAID NIH HHS/United States ; }, mesh = {Antiviral Agents/*pharmacology ; Bacteria/chemistry/classification/growth &amp; development/*metabolism ; Biological Assay ; Cell Line, Tumor ; Culture Media/*chemistry/pharmacology ; Humans ; *Metabolic Networks and Pathways ; Microbiota/*physiology ; Molecular Docking Simulation ; Protease Inhibitors/pharmacology ; Protein Binding ; SARS-CoV-2/*drug effects ; Symbiosis/*physiology ; }, abstract = {The COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities, their antiviral properties remain poorly explored. Using a cell-based SARS-CoV-2 infection assay, we screened culture broth extracts from a collection of phylogenetically diverse human-associated bacteria for the production of small molecules with antiviral activity. Bioassay-guided fractionation uncovered three bacterial metabolites capable of inhibiting SARS-CoV-2 infection. This included the nucleoside analogue N6-(Δ[2]-isopentenyl)adenosine, the 5-hydroxytryptamine receptor agonist tryptamine, and the pyrazine 2,5-bis(3-indolylmethyl)pyrazine. The most potent of these, N6-(Δ[2]-isopentenyl)adenosine, had a 50% inhibitory concentration (IC50) of 2 μM. These natural antiviral compounds exhibit structural and functional similarities to synthetic drugs that have been clinically examined for use against COVID-19. Our discovery of structurally diverse metabolites with anti-SARS-CoV-2 activity from screening a small fraction of the bacteria reported to be associated with the human microbiome suggests that continued exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections. IMPORTANCE The continued prevalence of COVID-19 and the emergence of new variants has once again put the spotlight on the need for the identification of SARS-CoV-2 antivirals. The human microbiome produces an array of small molecules with bioactivities (e.g., host receptor ligands), but its ability to produce antiviral small molecules is relatively underexplored. Here, using a cell-based screening platform, we describe the isolation of three microbiome-derived metabolites that are able to prevent SARS-CoV-2 infection in vitro. These molecules display structural similarities to synthetic drugs that have been explored for the treatment of COVID-19, and these results suggest that the microbiome may be a fruitful source of the discovery of small molecules with antiviral activities.}, }
@article {pmid34850062, year = {2022}, author = {DiMaio, D and Emu, B and Goodman, AL and Mothes, W and Justice, A}, title = {Cancer Microbiology.}, journal = {Journal of the National Cancer Institute}, volume = {114}, number = {5}, pages = {651-663}, pmid = {34850062}, issn = {1460-2105}, support = {P30CA016359/NH/NIH HHS/United States ; U10 AA013566/AA/NIAAA NIH HHS/United States ; R01 AI150897/AI/NIAID NIH HHS/United States ; P50 CA196530/CA/NCI NIH HHS/United States ; R35 CA242462/CA/NCI NIH HHS/United States ; R01 CA206465/NH/NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Carcinogens ; Delivery of Health Care ; Humans ; *Microbiota ; *Neoplasms/prevention &amp; control ; }, abstract = {Microbes play important roles in cancer from direct carcinogenic effects to their use in treatment. Cancers caused by microorganisms account for approximately 15% of cancers, primarily in low- and middle-income countries. Unique features of infectious carcinogens include their transmissibility, mutability, and specific immune interactions, which provide challenges and opportunities for cancer prevention and treatment. For these agents, infection control through exposure reduction, antivirals, antibiotics, and vaccines is cancer control. In addition, developing evidence suggests that microorganisms including the human microbiome can indirectly modulate cancer formation and influence the effectiveness and toxicity of cancer treatments. Finally, microorganisms themselves can be used to prevent or treat cancer. The convergence of these factors signals the emergence of a new field, cancer microbiology. Recognition of cancer microbiology will spur research, stimulate cross-disciplinary training, inform drug development, and improve public health.}, }
@article {pmid34841785, year = {2021}, author = {Liu, H and Xu, X and Ling, K and Zou, X}, title = {[Vaginal microbiome: community characteristics and disease intervention].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3801-3811}, doi = {10.13345/j.cjb.210204}, pmid = {34841785}, issn = {1872-2075}, mesh = {Female ; Humans ; *Microbiota ; *Probiotics ; Vagina ; }, abstract = {The application of high-throughput sequencing technologies has greatly enhanced our understanding to the human microbiome. The causal relations between human microbiome and diseases have become a critical issue to elucidate disease development and develop precision medicine. Recently, the study about vaginal microbiome (the microbial flora that inhabits the female vagina) has received wide interests. It has been shown that dysbiosis of vaginal microbiome was closely related to the development of genital tract diseases. This article summarizes the interaction between vaginal microbiome and disease and the treatment for the dysbiosis of vaginal microbiome. The culturomics of virginal microbiome, engineered probiotics and synthetic microbiome were also proposed.}, }
@article {pmid34841779, year = {2021}, author = {Yin, Y and Yu, R and Chen, H}, title = {[Shotgun metagenome sequencing of Chinese gut microbiota: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3717-3733}, doi = {10.13345/j.cjb.210556}, pmid = {34841779}, issn = {1872-2075}, mesh = {China ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {The research on the relationship between gut microbiota and human health continues to be a hot topic in the field of life science. Culture independent 16S rRNA gene high-throughput sequencing is the current main research method. However, with the reduction of sequencing cost and the maturity of data analysis methods, shotgun metagenome sequencing is gradually becoming an important method for the study of gut microbiome due to its advantages of obtaining more information. With the support from the human microbiome project, 30 805 metagenome samples were sequenced in the United States. By searching NCBI PubMed and SRA databases, it was found that 72 studies collecting about 10 000 Chinese intestinal samples were used for metagenome sequencing. To date, only 56 studies were published, including 16 related to metabolic diseases, 16 related to infectious and immune diseases, and 12 related to cardiovascular and cerebrovascular diseases. The samples were mainly collected in Beijing, Guangzhou, Shanghai and other cosmopolitan cities, where great differences exist in sequencing platforms and methods. The outcome of most studies are based on correlation analysis, which has little practical value in guiding the diagnosis and treatment of clinical diseases. Standardizing sampling methods, sequencing platform and data analysis process, and carrying out multi center parallel research will contribute to data integration and comparative analysis. Moreover, insights into the functional verification and molecular mechanism by using the combination of transcriptomics, proteomics and culturomics will enable the gut microbiota research to better serve the clinical diagnosis and treatment.}, }
@article {pmid34841778, year = {2021}, author = {Wang, J and Wang, J and Deng, Z}, title = {[Preface for special issue on microbiome and human health].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3711-3716}, doi = {10.13345/j.cjb.210789}, pmid = {34841778}, issn = {1872-2075}, mesh = {China ; Humans ; Intestines ; Lung ; *Microbiota ; *Neoplasms ; }, abstract = {Human microbiome is comprised of symbiotic microorganisms in the human body, whose dynamic balance is closely related to human health, and is recognized as important "organs" that can regulate immunity, metabolism and other aspects in human body, and is associated with functions of many organs including lung, intestine, vagina and brain, becoming a potential target for the treatment of cancer, coronary heart disease, neurological diseases and other difficult diseases. In recent years, with the rapid development of microbiome sequencing and analysis technology, it has become an international focus and forefront to discover the relationship between human microorganisms and many diseases, as well as target for new treatment methods. Thus, we organized this special issue and publish reviews on study methodology, human disease and microbiome as well as therapeutic strategies, and provide important information to advance microbiome research in China.}, }
@article {pmid34839034, year = {2021}, author = {Sahni, V}, title = {The oral microbiome and vaccine efficacy.}, journal = {Medical hypotheses}, volume = {158}, number = {}, pages = {110732}, doi = {10.1016/j.mehy.2021.110732}, pmid = {34839034}, issn = {1532-2777}, abstract = {The immune response elicited by vaccines is crucial in determining their eventual efficacy. The human microbiome, in particular, that of the gut has been demonstrated to influence the immunogenicity of vaccines delivered by both the oral and non-oral routes. There is a significant overlap between the microflora of the mouth and that recovered from the gut, with certain periodontopathogens playing key roles in influencing the gut microflora. The present paper hypothesized that the oral microflora may play a role in the eventual immunogenicity and efficacy of vaccines.}, }
@article {pmid34834977, year = {2021}, author = {Happonen, LJ and Pajunen, MI and Jun, JW and Skurnik, M}, title = {BtuB-Dependent Infection of the T5-like Yersinia Phage ϕR2-01.}, journal = {Viruses}, volume = {13}, number = {11}, pages = {}, pmid = {34834977}, issn = {1999-4915}, mesh = {Bacterial Outer Membrane Proteins/*metabolism ; Bacterial Proteins/*metabolism ; Bacteriophages/classification/genetics/isolation &amp; purification/physiology ; Genome, Viral ; Membrane Transport Proteins/*metabolism ; Proteomics ; Siphoviridae/classification/genetics/isolation &amp; purification/*physiology ; Yersinia/genetics/*virology ; Yersinia enterocolitica/virology ; }, abstract = {Yersinia enterocolitica is a food-borne Gram-negative pathogen responsible for several gastrointestinal disorders. Host-specific lytic bacteriophages have been increasingly used recently as an alternative or complementary treatment to combat bacterial infections, especially when antibiotics fail. Here, we describe the proteogenomic characterization and host receptor identification of the siphovirus vB_YenS_ϕR2-01 (in short, ϕR2-01) that infects strains of several Yersinia enterocolitica serotypes. The ϕR2-01 genome contains 154 predicted genes, 117 of which encode products that are homologous to those of Escherichia bacteriophage T5. The ϕR2-01 and T5 genomes are largely syntenic, with the major differences residing in areas encoding hypothetical ϕR2-01 proteins. Label-free mass-spectrometry-based proteomics confirmed the expression of 90 of the ϕR2-01 genes, with 88 of these being either phage particle structural or phage-particle-associated proteins. In vitro transposon-based host mutagenesis and ϕR2-01 adsorption experiments identified the outer membrane vitamin B12 receptor BtuB as the host receptor. This study provides a proteogenomic characterization of a T5-type bacteriophage and identifies specific Y. enterocolitica strains sensitive to infection with possible future applications of ϕR2-01 as a food biocontrol or phage therapy agent.}, }
@article {pmid34833893, year = {2021}, author = {Guan, ZW and Yu, EZ and Feng, Q}, title = {Soluble Dietary Fiber, One of the Most Important Nutrients for the Gut Microbiota.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {22}, pages = {}, pmid = {34833893}, issn = {1420-3049}, support = {81630072//National Natural Science Foundation of China/ ; 82071122//National Natural Science Foundation of China/ ; }, mesh = {Dietary Fiber/*administration &amp; dosage/analysis/*metabolism ; Energy Intake ; Gastrointestinal Microbiome/*physiology ; Histone Deacetylase Inhibitors/administration &amp; dosage/chemistry/metabolism ; Humans ; Intestinal Absorption ; Ligands ; Molecular Structure ; Polysaccharides/administration &amp; dosage/chemistry/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Satiation ; Solubility ; }, abstract = {Dietary fiber is a widely recognized nutrient for human health. Previous studies proved that dietary fiber has significant implications for gastrointestinal health by regulating the gut microbiota. Moreover, mechanistic research showed that the physiological functions of different dietary fibers depend to a great extent on their physicochemical characteristics, one of which is solubility. Compared with insoluble dietary fiber, soluble dietary fiber can be easily accessed and metabolized by fiber-degrading microorganisms in the intestine and produce a series of beneficial and functional metabolites. In this review, we outlined the structures, characteristics, and physiological functions of soluble dietary fibers as important nutrients. We particularly focused on the effects of soluble dietary fiber on human health via regulating the gut microbiota and reviewed their effects on dietary and clinical interventions.}, }
@article {pmid34833140, year = {2021}, author = {Salabura, A and Łuniewski, A and Kucharska, M and Myszak, D and Dołęgowska, B and Ciechanowski, K and Kędzierska-Kapuza, K and Wojciuk, B}, title = {Urinary Tract Virome as an Urgent Target for Metagenomics.}, journal = {Life (Basel, Switzerland)}, volume = {11}, number = {11}, pages = {}, pmid = {34833140}, issn = {2075-1729}, abstract = {Virome-a part of a microbiome-is a term used to describe all viruses found in the specific organism or system. Recently, as new technologies emerged, it has been confirmed that kidneys and the lower urinary tract are colonized not only by the previously described viruses, but also completely novel species. Viruses can be both pathogenic and protective, as they often carry important virulence factors, while at the same time represent anti-inflammatory functions. This paper aims to show and compare the viral species detected in various, specific clinical conditions. Because of the unique characteristics of viruses, new sequencing techniques and databases had to be developed to conduct research on the urinary virome. The dynamic development of research on the human microbiome suggests that the detailed studies on the urinary system virome will provide answers to many questions about the risk factors for civilization, cancer, and autoimmune diseases.}, }
@article {pmid34830161, year = {2021}, author = {Puebla-Barragan, S and Akouris, PP and Al, KF and Carr, C and Lamb, B and Sumarah, M and van der Veer, C and Kort, R and Burton, J and Reid, G}, title = {The Two-Way Interaction between the Molecules That Cause Vaginal Malodour and Lactobacilli: An Opportunity for Probiotics.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830161}, issn = {1422-0067}, support = {692895//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; }, mesh = {Dysbiosis/drug therapy/*immunology ; Female ; Humans ; *Lactobacillus/classification/growth &amp; development/isolation &amp; purification ; Probiotics/therapeutic use ; Vagina/*microbiology ; Vaginosis, Bacterial/drug therapy/*microbiology ; }, abstract = {Vaginal malodour is a sign of dysbiosis. The biogenic amines (BAs) cadaverine, putrescine and tyramine are known to be causative compounds. Recent reports suggest these compounds produced by pathogens might have a role beyond causing malodour; namely inhibiting the growth of lactobacilli bacteria that are crucial in the maintenance of vaginal homeostasis. The aim of this study was to identify whether certain lactobacilli strains could reduce BAs and to evaluate how Lactobacillus species were affected by these compounds. Using LC-MS and HPLC-UV, five Lactobacillus crispatus strains were identified as being capable of significantly reducing BAs from the media under in vitro conditions. Through 16S rRNA gene sequencing of vaginal swabs exposed to Bas, cadaverine was found to reduce the relative abundance of lactobacilli. When L. crispatus was exposed to media supplemented with BAs with an HCl adjusted lower pH, its growth was enhanced, demonstrating the relevance of the maintenance of an acidic vaginal environment. If strains are to be developed for probiotic application to alleviate bacterial vaginosis and other conditions affecting large numbers of women worldwide, their ability to adapt to Bas and regulate pH should be part of the experimentation.}, }
@article {pmid34827311, year = {2021}, author = {D'Angeli, F and Guadagni, F and Genovese, C and Nicolosi, D and Trovato Salinaro, A and Spampinato, M and Mannino, G and Lo Furno, D and Petronio Petronio, G and Ronsisvalle, S and Sipala, F and Falzone, L and Calabrese, V}, title = {Anti-Candidal Activity of the Parasitic Plant Orobanche crenata Forssk.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {10}, number = {11}, pages = {}, pmid = {34827311}, issn = {2079-6382}, support = {CUP B66G18000220005//European Social Fund, PNR 2015-2020 ARS01_01163 PerMedNet under the Italian Ministries of Education, University and Research/ ; CUP G88I18000710007//PO FESR 2014-2020 Sicily Region Action 1.1.5, NUVACAL BC/ ; }, abstract = {Candida albicans (C. albicans) and Candida glabrata (C. glabrata) are part of the human microbiome. However, they possess numerous virulence factors, which confer them the ability to cause both local and systemic infections. Candidiasis can involve multiple organs, including the eye. In the present study, we investigated the anti-candidal activity and the re-epithelizing effect of Orobanche crenata leaf extract (OCLE). By the microdilution method, we demonstrated an inhibitory effect of OCLE on both C. albicans and C. glabrata growth. By crystal violet and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of OCLE to inhibit the biofilm formation and the viability of yeast cells, respectively. By germ tube and adhesion assays, we proved the capacity of OCLE to affect the morphological transition of C. albicans and the adhesion of both pathogens to human retinal pigment epithelial cells (ARPE-19), respectively. Besides, by MTT and wound healing assay, we evaluated the cytotoxic and re-epithelizing effects of OCLE on ARPE-19. Finally, the Folin-Ciocalteu and the ultra-performance liquid chromatography-tandem mass spectrometry revealed a high content of phenols and the presence of several bioactive molecules in the extract. Our results highlighted new properties of O. crenata, useful in the control of Candida infections.}, }
@article {pmid34821456, year = {2022}, author = {Diotallevi, C and Fontana, M and Latimer, C and Ternan, NG and Pourshahidi, LK and Lawther, R and O'Connor, G and Conterno, L and Gasperotti, M and Angeli, A and Lotti, C and Bianchi, M and Vrhovsek, U and Fava, F and Gobbetti, M and Gill, CIR and Tuohy, KM}, title = {Ex Vivo Fecal Fermentation of Human Ileal Fluid Collected After Wild Strawberry Consumption Modulates Human Microbiome Community Structure and Metabolic Output and Protects Against DNA Damage in Colonic Epithelial Cells.}, journal = {Molecular nutrition &amp; food research}, volume = {66}, number = {3}, pages = {e2100405}, doi = {10.1002/mnfr.202100405}, pmid = {34821456}, issn = {1613-4133}, mesh = {Colon/metabolism ; DNA Damage ; Epithelial Cells ; Fermentation ; *Fragaria/chemistry ; Fruit/chemistry ; *Gastrointestinal Microbiome ; Humans ; Kinetics ; }, abstract = {SCOPE: Wild strawberries (Fragaria vesca) are richer in (poly)phenols than common commercial strawberry varieties, e.g., Fragaria × ananassa. (Poly)phenols and their microbiota-derived metabolites are hypothesized to exert bioactivity within the human gut mucosa. To address this, the effects of wild strawberries are investigated with respect to their bioactivity and microbiota-modulating capacity using both in vitro and ex vivo approaches.<br><br>METHODS AND RESULTS: Ileal fluids collected pre- (0h) and post-consumption (8h) of 225&#xa0;g wild strawberries by ileostomates (n = 5) and also in vitro digested strawberry varieties (Fragaria vesca and Fragaria &#xd7; ananassa Duchesne) supernatants are collected. Subsequent fermentation of these supernatants using an in vitro batch culture proximal colon model reveals significant treatment-specific changes in microbiome community structure in terms of alpha but not beta diversity at 24 h. Nutri-kinetic analysis reveals a significant increase in the concentration of gut microbiota catabolites, including 3-(4hydroxyphenyl)propionic acid, 3-(3-hydroxyphenyl)propanoic acid, and benzoic acid. Furthermore, post-berry ileal fermentates (24 h) significantly (p&#xa0;< 0.01) decrease DNA damage (% Tail DNA, COMET assay) in both HT29 cells (&#x223c;45%) and CCD 841 CoN cells (&#x223c;25%) compared to untreated controls.<br><br>CONCLUSIONS: Post berry consumption fermentates exhibit increased overall levels of (poly)phenolic metabolites, which retains their bioactivity, reducing DNA damage in colonocytes.}, }
@article {pmid34820530, year = {2021}, author = {Liang, G}, title = {Altered gut bacterial and metabolic signatures and their interaction in inflammatory bowel disease.}, journal = {Synthetic and systems biotechnology}, volume = {6}, number = {4}, pages = {377-383}, pmid = {34820530}, issn = {2405-805X}, abstract = {Dysregulation of the gut microbiome has been implicated in the progression of many diseases. This study explored the role of microbial and metabolic signatures, and their interaction between the Human inflammatory bowel disease (IBD) and healthy controls (HCs) based on the combination of machine learning and traditional statistical analysis, using data collected from the Human Microbiome Project (HMP) and the Integrative Human Microbiome Project (iHMP). It was showed that the microbial and metabolic signatures of IBD patients were significantly different from those of HCs. Compared to HCs, IBD subjects were characterized by 25 enriched species and 6 depleted species. Furthermore, a total of 17 discriminative pathways were identified between the IBD and HC groups. Those differential pathways were mainly involved in amino acid, nucleotide biosynthesis, and carbohydrate degradation. Notably, co-occurrence network analysis revealed that non-predominant bacteria Ruminococcus_obeum and predominant bacteria Faecalibacterium_prausnitzii formed the same broad and strong co-occurring relationships with pathways. Moreover, the essay identified a combinatorial marker panel that could distinguish IBD from HCs. Receiver Operating Characteristic (ROC) and Decision Curve Analysis (DCA) confirmed the high accuracy (AUC = 0.966) and effectiveness of the model. Meanwhile, an independent cohort used for external validation also showed the identical high efficacy (AUC = 0.835). These findings showed that the gut microbes may be relevant to the pathogenesis and pathophysiology, and offer universal utility as a non-invasive diagnostic test in IBD.}, }
@article {pmid34819672, year = {2021}, author = {Balaich, J and Estrella, M and Wu, G and Jeffrey, PD and Biswas, A and Zhao, L and Korennykh, A and Donia, MS}, title = {The human microbiome encodes resistance to the antidiabetic drug acarbose.}, journal = {Nature}, volume = {600}, number = {7887}, pages = {110-115}, pmid = {34819672}, issn = {1476-4687}, support = {R01 GM110161/GM/NIGMS NIH HHS/United States ; DP2 AI124441/AI/NIAID NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; T32 GM007388/GM/NIGMS NIH HHS/United States ; P41 GM111244/GM/NIGMS NIH HHS/United States ; 1013579/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Acarbose/metabolism/*pharmacology ; Amylases/metabolism ; Animals ; Drug Resistance, Bacterial/*drug effects ; Gastrointestinal Microbiome/*drug effects ; Humans ; Hypoglycemic Agents/metabolism/*pharmacology ; *Inactivation, Metabolic ; Metagenome/drug effects/*genetics ; Models, Molecular ; Mouth/drug effects/*microbiology ; Phosphotransferases (Alcohol Group Acceptor)/chemistry/*genetics/metabolism ; }, abstract = {The human microbiome encodes a large repertoire of biochemical enzymes and pathways, most of which remain uncharacterized. Here, using a metagenomics-based search strategy, we discovered that bacterial members of the human gut and oral microbiome encode enzymes that selectively phosphorylate a clinically used antidiabetic drug, acarbose[1,2], resulting in its inactivation. Acarbose is an inhibitor of both human and bacterial α-glucosidases[3], limiting the ability of the target organism to metabolize complex carbohydrates. Using biochemical assays, X-ray crystallography and metagenomic analyses, we show that microbiome-derived acarbose kinases are specific for acarbose, provide their harbouring organism with a protective advantage against the activity of acarbose, and are widespread in the microbiomes of western and non-western human populations. These results provide an example of widespread microbiome resistance to a non-antibiotic drug, and suggest that acarbose resistance has disseminated in the human microbiome as a defensive strategy against a potential endogenous producer of a closely related molecule.}, }
@article {pmid34819600, year = {2021}, author = {Tozzi, AE and Del Chierico, F and Pandolfi, E and Reddel, S and Gesualdo, F and Gardini, S and Guarrasi, V and Russo, L and Croci, I and Campagna, I and Linardos, G and Concato, C and Villani, A and Putignani, L}, title = {Nasopharyngeal microbiota in hospitalized children with Bordetella pertussis and Rhinovirus infection.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {22858}, pmid = {34819600}, issn = {2045-2322}, mesh = {Bordetella Infections/diagnosis/*microbiology ; Bordetella pertussis/*isolation &amp; purification ; *Coinfection ; Dysbiosis ; Female ; *Hospitalization ; Host-Pathogen Interactions ; Humans ; Infant ; Male ; Metagenome ; Metagenomics ; Microbiota ; Nasopharynx/*microbiology/*virology ; Picornaviridae Infections/diagnosis/*virology ; Rhinovirus/*isolation &amp; purification ; Ribotyping ; }, abstract = {Despite great advances in describing Bordetella pertussis infection, the role of the host microbiota in pertussis pathogenesis remains unexplored. Indeed, the microbiota plays important role in defending against bacterial and viral respiratory infections. We investigated the nasopharyngeal microbiota in infants infected by B. pertussis (Bp), Rhinovirus (Rv) and simultaneously by both infectious agents (Bp + Rv). We demonstrated a specific nasopharyngeal microbiome profiles for Bp group, compared to Rv and Bp + Rv groups, and a reduction of microbial richness during coinfection compared to the single infections. The comparison amongst the three groups showed the increase of Alcaligenaceae and Achromobacter in Bp and Moraxellaceae and Moraxella in Rv group. Furthermore, correlation analysis between patients' features and nasopharyngeal microbiota profile highlighted a link between delivery and feeding modality, antibiotic administration and B. pertussis infection. A model classification demonstrated a microbiota fingerprinting specific of Bp and Rv infections. In conclusion, external factors since the first moments of life contribute to the alteration of nasopharyngeal microbiota, indeed increasing the susceptibility of the host to the pathogens' infections. When the infection is triggered, the presence of infectious agents modifies the microbiota favoring the overgrowth of commensal bacteria that turn in pathobionts, hence contributing to the disease severity.}, }
@article {pmid34812271, year = {2021}, author = {Wang, Y and Sun, M and Duan, Y}, title = {Metagenomic Sequencing Analysis for Acne Using Machine Learning Methods Adapted to Single or Multiple Data.}, journal = {Computational and mathematical methods in medicine}, volume = {2021}, number = {}, pages = {8008731}, pmid = {34812271}, issn = {1748-6718}, mesh = {Acne Vulgaris/*genetics/metabolism/*microbiology ; Canonical Correlation Analysis ; Case-Control Studies ; Computational Biology ; Face/microbiology ; Humans ; Lipids/analysis/genetics ; *Machine Learning ; *Metagenome ; Metagenomics/statistics &amp; numerical data ; Microbiota/genetics ; Principal Component Analysis ; Skin/chemistry/microbiology ; }, abstract = {The human health status can be assessed by the means of research and analysis of the human microbiome. Acne is a common skin disease whose morbidity increases year by year. The lipids which influence acne to a large extent are studied by metagenomic methods in recent years. In this paper, machine learning methods are used to analyze metagenomic sequencing data of acne, i.e., all kinds of lipids in the face skin. Firstly, lipids data of the diseased skin (DS) samples and the healthy skin (HS) samples of acne patients and the normal control (NC) samples of healthy person are, respectively, analyzed by using principal component analysis (PCA) and kernel principal component analysis (KPCA). Then, the lipids which have main influence on each kind of sample are obtained. In addition, a multiset canonical correlation analysis (MCCA) is utilized to get lipids which can differentiate the face skins of the above three samples. The experimental results show the machine learning methods can effectively analyze metagenomic sequencing data of acne. According to the results, lipids which only influence one of the three samples or the lipids which simultaneously have different degree of influence on these three samples can be used as indicators to judge skin statuses.}, }
@article {pmid34812127, year = {2021}, author = {Depommier, C and Everard, A and Druart, C and Maiter, D and Thissen, JP and Loumaye, A and Hermans, MP and Delzenne, NM and de Vos, WM and Cani, PD}, title = {Serum metabolite profiling yields insights into health promoting effect of A. muciniphila in human volunteers with a metabolic syndrome.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1994270}, pmid = {34812127}, issn = {1949-0984}, mesh = {Adolescent ; Adult ; Aged ; Akkermansia/physiology ; Amino Acids/metabolism ; Carnitine/analogs &amp; derivatives/metabolism ; Glycolysis/drug effects ; Humans ; Insulin Resistance ; Ketone Bodies/metabolism ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Metabolic Syndrome/blood/*diet therapy ; Metabolome/*drug effects ; Middle Aged ; Probiotics/administration &amp; dosage/*pharmacology ; Young Adult ; }, abstract = {Reduction of A. muciniphila relative abundance in the gut microbiota is a widely accepted signature associated with obesity-related metabolic disorders. Using untargeted metabolomics profiling of fasting plasma, our study aimed at identifying metabolic signatures associated with beneficial properties of alive and pasteurized A. muciniphila when administrated to a cohort of insulin-resistant individuals with metabolic syndrome. Our data highlighted either shared or specific alterations in the metabolome according to the form of A. muciniphila administered with respect to a control group. Common responses encompassed modulation of amino acid metabolism, characterized by reduced levels of arginine and alanine, alongside several intermediates of tyrosine, phenylalanine, tryptophan, and glutathione metabolism. The global increase in levels of acylcarnitines together with specific modulation of acetoacetate also suggested induction of ketogenesis through enhanced β-oxidation. Moreover, our data pinpointed some metabolites of interest considering their emergence as substantial compounds pertaining to health and diseases in the more recent literature.}, }
@article {pmid34806323, year = {2022}, author = {Allen, NG and Edupuganti, L and Edwards, DJ and Jimenez, NR and Buck, GA and Jefferson, KK and Strauss, JF and ,  and Wickham, EP and Fettweis, JM}, title = {The vaginal microbiome in women of reproductive age with healthy weight versus overweight/obesity.}, journal = {Obesity (Silver Spring, Md.)}, volume = {30}, number = {1}, pages = {142-152}, pmid = {34806323}, issn = {1930-739X}, support = {UH3AI083263//Foundation for the National Institutes of Health/ ; R21 HD092965/HD/NICHD NIH HHS/United States ; R21HD092965//Foundation for the National Institutes of Health/ ; UH3 AI083263/AI/NIAID NIH HHS/United States ; R25 GM090084/GM/NIGMS NIH HHS/United States ; UL1 TR002649/TR/NCATS NIH HHS/United States ; R25GM090084//Foundation for the National Institutes of Health/ ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54HD080784//Foundation for the National Institutes of Health/ ; }, mesh = {Adult ; Case-Control Studies ; Female ; Humans ; Infant, Newborn ; *Microbiota ; Obesity ; Overweight ; *Premature Birth ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the differences between the vaginal microbiome of reproductive-aged women with overweight and obesity (Ow/Ob) compared with healthy weight (HW).<br><br>METHODS: In this case-control study, a cohort of 367 nonpregnant women (18 to 40 years) with Ow/Ob (BMI &#x2265;25 kg/m[2]) was case-matched with 367 women with HW (BMI 18.0 to 24.9 kg/m[2]). The study was a secondary analysis of 16S rRNA vaginal microbiome surveys through the Vaginal Human Microbiome Study (VaHMP).&#xa0;Groups were matched on age, race/ethnicity, income, and nulliparity status.<br><br>RESULTS: Mean age and BMI of Ow/Ob and HW groups were 26.8 versus 26.7 years and 37.0 versus 22.1 kg/m[2] , respectively. The overall vaginal microbiome composition differed between&#xa0;groups (PERMANOVA, p = 0.035). Women with Ow/Ob had higher alpha diversity compared with women with HW (Wilcoxon test, Shannon index p = 0.025; inverse Simpson index p = 0.026). Lactobacillus&#xa0;dominance (&#x2265;30% proportional abundance) was observed in a greater proportion of women with HW (48.7%) compared with Ow/Ob (40.1%; p = 0.026).<br><br>CONCLUSIONS: The vaginal microbiome differs in reproductive-aged women with Ow/Ob compared with women with HW, with increased alpha diversity and decreased predominance of Lactobacillus. Observed differences in the vaginal microbiome may partially explain differences in preterm birth and bacterial vaginosis risk between these populations.}, }
@article {pmid34803517, year = {2021}, author = {Amedei, A and Capasso, C and Nannini, G and Supuran, CT}, title = {Microbiota, Bacterial Carbonic Anhydrases, and Modulators of Their Activity: Links to Human Diseases?.}, journal = {Mediators of inflammation}, volume = {2021}, number = {}, pages = {6926082}, pmid = {34803517}, issn = {1466-1861}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/*enzymology ; Carbonic Anhydrase Inhibitors/pharmacology ; Carbonic Anhydrases/*physiology ; Dysbiosis/etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Prebiotics ; Probiotics/pharmacology ; Synbiotics ; }, abstract = {The involvement of the human microbiome is crucial for different host functions such as protection, metabolism, reproduction, and especially immunity. However, both endogenous and exogenous factors can affect the balance of the microbiota, creating a state of dysbiosis, which can start various gastrointestinal or systemic diseases. The challenge of future medicine is to remodel the intestinal microbiota to bring it back to healthy equilibrium (eubiosis) and, thus, counteract its negative role in the diseases' onset. The shaping of the microbiota is currently practiced in different ways ranging from diet (or use of prebiotics, probiotics, and synbiotics) to phage therapy and antibiotics, including microbiota fecal transplantation. Furthermore, because microbiota modulation is a capillary process, and because many microbiota bacteria (both beneficial and pathogenic) have carbonic anhydrases (specifically the four classes α, β, γ, and ι), we believe that the use of CA inhibitors and activators can open up new therapeutic strategies for many diseases associated with microbial dysbiosis, such as the various gastrointestinal disorders and the same colorectal cancer.}, }
@article {pmid34796006, year = {2021}, author = {Belova, IV and Khrulev, AE and Tochilina, AG and Khruleva, NS and Lobanova, NA and Zhirnov, VA and Molodtsova, SB and Lobanov, VN and Solovieva, IV}, title = {Colon Microbiocenosis and Its Correction in Patients Receiving Programmed Hemodialysis.}, journal = {Sovremennye tekhnologii v meditsine}, volume = {12}, number = {5}, pages = {62-68}, pmid = {34796006}, issn = {2309-995X}, mesh = {Colon/microbiology ; Dysbiosis/microbiology ; Humans ; *Quality of Life ; Renal Dialysis/adverse effects ; *Synbiotics ; }, abstract = {UNLABELLED: The aim of the investigation was to study the species composition of colon microbiocenosis in patients with chronic kidney disease receiving programmed hemodialysis treatment and to evaluate the efficacy of its correction using a new immobilized synbiotic.<br><br>MATERIALS AND METHODS: Samples of colon microbiota from 62 patients undergoing programmed hemodialysis were studied before and after a course of diet therapy that included probiotic components, in particular, the immobilized synbiotic LB-complex L. Isolation of microorganisms was carried out according to our original method; for bacteria identification, a MALDI-TOF Autoflex speed mass spectrometer (Bruker Daltonik, Germany) was used in the Biotyper program mode. The results were assessed using the criteria proposed by the authors and based on the OST 91500.11.0004-2003. The efficacy of the immobilized synbiotic was determined based on the clinical data, questionnaires, and bacteriological tests.<br><br>RESULTS: In patients receiving programmed hemodialysis (before the start of the diet therapy), chronic moderate inflammation and azotemia were found. Dysbiotic changes in microbiocenosis were revealed in all the examined patients; in the absence or suppression of lacto- and bifidoflora, the number and diversity of Bacteroides spp., Clostridium spp., Collinsella spp., Eggerthella spp. and other bacteria increased, which was consistent with the theory of functional redundancy of gut microbiota. From the answers to the questionnaires, a decrease in the quality of life was found (up to 70 points out of 100) according to six of the eight scales used. After the combined therapy using the synbiotic LB-complex L in the study group, 56% of the examined patients showed their microbiocenosis restored to normal; no grade III dysbiosis was detected in any patient. There was a significant decrease in CRP and ESR in these patients and an improvement in the quality of life by criteria reflecting physical health.<br><br>CONCLUSION: In patients receiving programmed hemodialysis, the addition of a probiotic component in the diet therapy restores the evolutionarily determined structure of the microbiocenosis, normalizes its functions, and leads to an overall improvement in health and quality of life.}, }
@article {pmid34789871, year = {2021}, author = {Mirzayi, C and Renson, A and ,  and ,  and Zohra, F and Elsafoury, S and Geistlinger, L and Kasselman, LJ and Eckenrode, K and van de Wijgert, J and Loughman, A and Marques, FZ and MacIntyre, DA and Arumugam, M and Azhar, R and Beghini, F and Bergstrom, K and Bhatt, A and Bisanz, JE and Braun, J and Bravo, HC and Buck, GA and Bushman, F and Casero, D and Clarke, G and Collado, MC and Cotter, PD and Cryan, JF and Demmer, RT and Devkota, S and Elinav, E and Escobar, JS and Fettweis, J and Finn, RD and Fodor, AA and Forslund, S and Franke, A and Furlanello, C and Gilbert, J and Grice, E and Haibe-Kains, B and Handley, S and Herd, P and Holmes, S and Jacobs, JP and Karstens, L and Knight, R and Knights, D and Koren, O and Kwon, DS and Langille, M and Lindsay, B and McGovern, D and McHardy, AC and McWeeney, S and Mueller, NT and Nezi, L and Olm, M and Palm, N and Pasolli, E and Raes, J and Redinbo, MR and Rühlemann, M and Balfour Sartor, R and Schloss, PD and Schriml, L and Segal, E and Shardell, M and Sharpton, T and Smirnova, E and Sokol, H and Sonnenburg, JL and Srinivasan, S and Thingholm, LB and Turnbaugh, PJ and Upadhyay, V and Walls, RL and Wilmes, P and Yamada, T and Zeller, G and Zhang, M and Zhao, N and Zhao, L and Bao, W and Culhane, A and Devanarayan, V and Dopazo, J and Fan, X and Fischer, M and Jones, W and Kusko, R and Mason, CE and Mercer, TR and Sansone, SA and Scherer, A and Shi, L and Thakkar, S and Tong, W and Wolfinger, R and Hunter, C and Segata, N and Huttenhower, C and Dowd, JB and Jones, HE and Waldron, L}, title = {Reporting guidelines for human microbiome research: the STORMS checklist.}, journal = {Nature medicine}, volume = {27}, number = {11}, pages = {1885-1892}, pmid = {34789871}, issn = {1546-170X}, support = {R01 GM135218/GM/NIGMS NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; P30 ES005022/ES/NIEHS NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 CA230551/CA/NCI NIH HHS/United States ; U01 CA230551/CA/NCI NIH HHS/United States ; BB/E025080/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Computational Biology/*methods ; Dysbiosis/*microbiology ; Humans ; Microbiota/*physiology ; Observational Studies as Topic/*methods ; *Research Design ; Translational Science, Biomedical ; }, abstract = {The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies. The resulting tool, called 'Strengthening The Organization and Reporting of Microbiome Studies' (STORMS), is composed of a 17-item checklist organized into six sections that correspond to the typical sections of a scientific publication, presented as an editable table for inclusion in supplementary materials. The STORMS checklist provides guidance for concise and complete reporting of microbiome studies that will facilitate manuscript preparation, peer review, and reader comprehension of publications and comparative analysis of published results.}, }
@article {pmid34785217, year = {2022}, author = {Mousavi, SE and Delgado-Saborit, JM and Adivi, A and Pauwels, S and Godderis, L}, title = {Air pollution and endocrine disruptors induce human microbiome imbalances: A systematic review of recent evidence and possible biological mechanisms.}, journal = {The Science of the total environment}, volume = {816}, number = {}, pages = {151654}, doi = {10.1016/j.scitotenv.2021.151654}, pmid = {34785217}, issn = {1879-1026}, support = {MR/S019669/1/MRC_/Medical Research Council/United Kingdom ; }, mesh = {*Air Pollution/statistics &amp; numerical data ; Dysbiosis ; *Endocrine Disruptors/toxicity ; Female ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {A rich body of literature indicates that environmental factors interact with the human microbiome and influence its composition and functions contributing to the pathogenesis of diseases in distal sites of the body. This systematic review examines the scientific evidence on the effect of environmental toxicants, air pollutants and endocrine disruptors (EDCs), on compositional and diversity of human microbiota. Articles from PubMed, Embase, WoS and Google Scholar where included if they focused on human populations or the SHIME® model, and assessed the effects of air pollutants and EDCs on human microbiome. Non-human studies, not written in English and not displaying original research were excluded. The Newcastle-Ottawa Scale was used to assess the quality of individual studies. Results were extracted and presented in tables. 31 studies were selected, including 24 related to air pollutants, 5 related to EDCs, and 2 related to EDC using the SHIME® model. 19 studies focussed on the respiratory system (19), gut (8), skin (2), vaginal (1) and mammary (1) microbiomes. No sufficient number of studies are available to observe a consistent trend for most of the microbiota, except for streptococcus and veillionellales for which 9 out of 10, and 3 out of 4 studies suggest an increase of abundance with exposure to air pollution. A limitation of the evidence reviewed is the scarcity of existing studies assessing microbiomes from individual systems. Growing evidence suggests that exposure to environmental contaminants could change the diversity and abundance of resident microbiota, e.g. in the upper and lower respiratory, gastrointestinal, and female reproductive system. Microbial dysbiosis might lead to colonization of pathogens and outgrowth of pathobionts facilitating infectious diseases. It also might prime metabolic dysfunctions disrupting the production of beneficial metabolites. Further studies should elucidate the role of environmental pollutants in the development of dysbiosis and dysregulation of microbiota-related immunological processes.}, }
@article {pmid34784956, year = {2021}, author = {Romito, I and Porru, M and Braghini, MR and Pompili, L and Panera, N and Crudele, A and Gnani, D and De Stefanis, C and Scarsella, M and Pomella, S and Levi Mortera, S and de Billy, E and Conti, AL and Marzano, V and Putignani, L and Vinciguerra, M and Balsano, C and Pastore, A and Rota, R and Tartaglia, M and Leonetti, C and Alisi, A}, title = {Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {40}, number = {1}, pages = {364}, pmid = {34784956}, issn = {1756-9966}, support = {MFAG12936//Associazione Italiana per la Ricerca sul Cancro/ ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/pharmacology/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy ; Cell Line, Tumor ; Cell Proliferation ; Epigenesis, Genetic/*genetics ; Humans ; Liver Neoplasms/*drug therapy ; Male ; Mice ; Mice, Inbred NOD ; Morpholines/pharmacology/*therapeutic use ; Sorafenib/pharmacology/*therapeutic use ; }, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumours worldwide. Sorafenib (SOR) is one of the most effective single-drug systemic therapy against advanced HCC, but the identification of novel combination regimens for a continued improvement in overall survival is a big challenge. Recent studies highlighted the crucial role of focal adhesion kinase (FAK) in HCC growth. The aim of this study was to investigate the antitumor effects of three different FAK inhibitors (FAKi), alone or in combination with SOR, using in vitro and in vivo models of HCC.<br><br>METHODS: The effect of PND1186, PF431396, TAE226 on cell viability was compared to SOR. Among them TAE226, emerging as the most effective FAKi, was tested alone or in combination with SOR using 2D/3D human HCC cell line cultures and HCC xenograft murine models. The mechanisms of action were assessed by gene/protein expression and imaging approaches, combined with high-throughput methods.<br><br>RESULTS: TAE226 was the more effective FAKi to be combined with SOR against HCC. Combined TAE226 and SOR treatment reduced HCC growth both in vitro and in vivo by affecting tumour-promoting gene expression and inducing epigenetic changes via dysregulation of FAK nuclear interactome. We characterized a novel nuclear functional interaction between FAK and the NuRD complex. TAE226-mediated FAK depletion and SOR-promoted MAPK down-modulation caused a decrease in the nuclear amount of HDAC1/2 and a consequent increase of the histone H3 lysine 27 acetylation, thus counteracting histone H3 lysine 27 trimethylation.<br><br>CONCLUSIONS: Altogether, our findings provide the first evidence that TAE226 combined with SOR efficiently reduces HCC growth in vitro and in vivo. Also, our data highlight that deep analysis of FAK nuclear interactome may lead to the identification of new promising targets for HCC therapy.}, }
@article {pmid34784344, year = {2021}, author = {Mallick, H and Rahnavard, A and McIver, LJ and Ma, S and Zhang, Y and Nguyen, LH and Tickle, TL and Weingart, G and Ren, B and Schwager, EH and Chatterjee, S and Thompson, KN and Wilkinson, JE and Subramanian, A and Lu, Y and Waldron, L and Paulson, JN and Franzosa, EA and Bravo, HC and Huttenhower, C}, title = {Multivariable association discovery in population-scale meta-omics studies.}, journal = {PLoS computational biology}, volume = {17}, number = {11}, pages = {e1009442}, pmid = {34784344}, issn = {1553-7358}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U19 AI110820/AI/NIAID NIH HHS/United States ; R01 HG005220/HG/NHGRI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {*Computational Biology ; Computer Simulation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism/pathology ; *Multivariate Analysis ; }, abstract = {It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses generalized linear and mixed models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g., counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2's linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel diseases (IBD) across multiple time points and omics profiles.}, }
@article {pmid34778069, year = {2021}, author = {Wang, Y and Guo, H and Gao, X and Wang, J}, title = {The Intratumor Microbiota Signatures Associate With Subtype, Tumor Stage, and Survival Status of Esophageal Carcinoma.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {754788}, pmid = {34778069}, issn = {2234-943X}, abstract = {Altered human microbiome characteristic has been linked with esophageal carcinoma (ESCA), analysis of microbial profiling directly derived from ESCA tumor tissue is beneficial for studying the microbial functions in tumorigenesis and development of ESCA. In this study, we identified the intratumor microbiome signature and investigated the correlation between microbes and clinical characteristics of patients with ESCA, on the basis of data and information obtained from The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA) databases. A total of 82 samples were analyzed for microbial composition at various taxonomic levels, including 40 tumor samples of esophageal squamous cell carcinoma (ESCC), 20 tumor samples of esophageal adenocarcinoma (EAD), and 22 adjacent normal samples. The results showed that the relative abundance of several microbes changed in tumors compared to their paired normal tissues, such as Firmicutes increased significantly while Proteobacteria decreased in tumor samples. We also identified a microbial signature composed of ten microbes that may help in the classification of ESCC and EAD, the two subtypes of ESCA. Correlation analysis demonstrated that compositions of microbes Fusobacteria/Fusobacteriia/Fusobacteriales, Lactobacillales/Lactobacillaceae/Lactobacillus, Clostridia/Clostridiales, Proteobacteria, and Negativicutes were correlated with the clinical characteristics of ESCA patients. In summary, this study supports the feasibility of detecting intratumor microbial composition derived from tumor sequencing data, and it provides novel insights into the roles of microbiota in tumors. Ultimately, as the second genome of human body, microbiome signature analysis may help to add more information to the blueprint of human biology.}, }
@article {pmid34771614, year = {2021}, author = {Amatya, SB and Salmi, S and Kainulainen, V and Karihtala, P and Reunanen, J}, title = {Bacterial Extracellular Vesicles in Gastrointestinal Tract Cancer: An Unexplored Territory.}, journal = {Cancers}, volume = {13}, number = {21}, pages = {}, pmid = {34771614}, issn = {2072-6694}, abstract = {Bacterial extracellular vesicles are membrane-enclosed, lipid bi-layer nanostructures that carry different classes of biomolecules, such as nucleic acids, lipids, proteins, and diverse types of small molecular metabolites, as their cargo. Almost all of the bacteria in the gut secrete extracellular vesicles to assist them in competition, survival, material exchange, host immune modulation, infection, and invasion. The role of gut microbiota in the development, progression, and pathogenesis of gastrointestinal tract (GIT) cancer has been well documented. However, the possible involvement of bacterial extracellular vesicles (bEVs) in GIT cancer pathophysiology has not been given due attention. Studies have illustrated the ability of bEVs to cross physiological barriers, selectively accumulate near tumor cells, and possibly alter the tumor microenvironment (TME). A systematic search of original published works related to bacterial extracellular vesicles on gastrointestinal cancer was performed for this review. The current systemic review outlines the possible impact of gut microbiota derived bEVs in GIT cancer in light of present-day understanding. The necessity of using advanced sequencing technologies, such as genetic, proteomic, and metabolomic investigation methodologies, to facilitate an understanding of the interrelationship between cancer-associated bacterial vesicles and gastrointestinal cancer is also emphasized. We further discuss the clinical and pharmaceutical potential of bEVs, along with future efforts needed to understand the mechanism of interaction of bEVs in GIT cancer pathogenesis.}, }
@article {pmid34768350, year = {2021}, author = {Tourelle, KM and Boutin, S and Weigand, MA and Schmitt, FCF}, title = {Sepsis and the Human Microbiome. Just Another Kind of Organ Failure? A Review.}, journal = {Journal of clinical medicine}, volume = {10}, number = {21}, pages = {}, pmid = {34768350}, issn = {2077-0383}, abstract = {Next-generation sequencing (NGS) has been further optimised during the last years and has given us new insights into the human microbiome. The 16S rDNA sequencing, especially, is a cheap, fast, and reliable method that can reveal significantly more microorganisms compared to culture-based diagnostics. It might be a useful method for patients suffering from severe sepsis and at risk of organ failure because early detection and differentiation between healthy and harmful microorganisms are essential for effective therapy. In particular, the gut and lung microbiome in critically ill patients have been probed by NGS. For this review, an iterative approach was used. Current data suggest that an altered microbiome with a decreased alpha-diversity compared to healthy individuals could negatively influence the individual patient's outcome. In the future, NGS may not only contribute to the diagnosis of complications. Patients at risk could also be identified before surgery or even during their stay in an intensive care unit. Unfortunately, there is still a lack of knowledge to make precise statements about what constitutes a healthy microbiome, which patients exactly have an increased perioperative risk, and what could be a possible therapy to strengthen the microbiome. This work is an iterative review that presents the current state of knowledge in this field.}, }
@article {pmid34763095, year = {2022}, author = {Levi Mortera, S and Vernocchi, P and Basadonne, I and Zandonà, A and Chierici, M and Durighello, M and Marzano, V and Gardini, S and Gasbarrini, A and Urbani, A and Vicari, S and Roncada, P and Furlanello, C and Venuti, P and Putignani, L}, title = {A metaproteomic-based gut microbiota profiling in children affected by autism spectrum disorders.}, journal = {Journal of proteomics}, volume = {251}, number = {}, pages = {104407}, doi = {10.1016/j.jprot.2021.104407}, pmid = {34763095}, issn = {1876-7737}, mesh = {Aged ; *Autism Spectrum Disorder/complications/metabolism ; Child ; Chromatography, Liquid ; *Gastrointestinal Microbiome/physiology ; Humans ; RNA, Ribosomal, 16S/genetics ; Tandem Mass Spectrometry ; }, abstract = {During the last decade, the evidences on the relationship between neurodevelopmental disorders and the microbial communities of the intestinal tract have considerably grown. Particularly, the role of gut microbiota (GM) ecology and predicted functions in Autism Spectrum Disorders (ASD) has been especially investigated by 16S rRNA targeted and shotgun metagenomics, trying to assess disease signature and their correlation with cognitive impairment or gastrointestinal (GI) manifestations of the disease. Herein we present a metaproteomic approach to point out the microbial gene expression profiles, their functional annotations, and the taxonomic distribution of gut microbial communities in ASD children. We pursued a LC-MS/MS based investigation, to compare the GM profiles of patients with those of their respective relatives and aged-matched controls, providing a quantitative evaluation of bacterial metaproteins by SWATH analysis. All data were managed by a multiple step bioinformatic pipeline, including network analysis. In particular, comparing ASD subjects with CTRLs, up-regulation was found for some metaproteins associated with Clostridia and with carbohydrate metabolism (glyceraldehyde-3-phosphate and glutamate dehydrogenases), while down-regulation was observed for others associated with Bacteroidia (SusC and SusD family together with the TonB dependent receptor). Moreover, network analysis highlighted specific microbial correlations among ASD subgroups characterized by different functioning levels and GI symptoms. SIGNIFICANCE: To the best of our knowledge, this study represents the first metaproteomic investigation on the gut microbiota of ASD children compared with relatives and age-matched CTRLs. Remarkably, the applied SWATH methodology allowed the attribution of differentially regulated functions to specific microbial taxa, offering a novel and complementary point of view with respect to previous studies.}, }
@article {pmid34754133, year = {2022}, author = {Maslennikov, R and Ivashkin, V and Ufimtseva, A and Poluektova, E}, title = {[Two consecutive attacks of diarrhea in 15 COVID-19 patients: An antibiotic-associated one following the viral one].}, journal = {Revista de gastroenterologia de Mexico}, volume = {87}, number = {1}, pages = {59-62}, pmid = {34754133}, issn = {0375-0906}, abstract = {Of the 971 patients admitted to our Clinic with suspected COVID-19, 15 (1.5%) presented with two consecutive attacks of diarrhea. One of those patients (a 47-year-old woman) required admission to the intensive care unit and mechanical ventilation. She died on the 11th day of hospitalization (18th day of illness). The first attack of diarrhea in those patients occurred on the 6 th (4th-7th) day of disease and lasted 3 (3-5) days. The second attack of diarrhea developed 11 (8-12) days after the initial onset of diarrhea. Despite the existing trend, the difference in the duration of the diarrhea and the maximum number of bowel movements per day between the first and second attacks was not statistically significant (p = 0.130; p = 0.328). There was no significant difference between the patients with a double attack of diarrhea and those with no diarrhea, regarding the results of the complete blood count, biochemical blood tests, and inflammation biomarkers.}, }
@article {pmid34752448, year = {2021}, author = {Devlin, SM and Martin, A and Ostrovnaya, I}, title = {Identifying prognostic pairwise relationships among bacterial species in microbiome studies.}, journal = {PLoS computational biology}, volume = {17}, number = {11}, pages = {e1009501}, pmid = {34752448}, issn = {1553-7358}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Algorithms ; Bacteria/classification/*genetics/isolation &amp; purification ; Case-Control Studies ; Computational Biology ; Computer Simulation ; Databases, Genetic ; Host Microbial Interactions/genetics/physiology ; Humans ; Logistic Models ; Microbiota/*genetics/*physiology ; Mouth Neoplasms/microbiology ; Prognosis ; RNA, Ribosomal, 16S/genetics ; Software ; Species Specificity ; }, abstract = {In recent literature, the human microbiome has been shown to have a major influence on human health. To investigate this impact, scientists study the composition and abundance of bacterial species, commonly using 16S rRNA gene sequencing, among patients with and without a disease or condition. Methods for such investigations to date have focused on the association between individual bacterium and an outcome, and higher-order pairwise relationships or interactions among bacteria are often avoided due to the substantial increase in dimension and the potential for spurious correlations. However, overlooking such relationships ignores the environment of the microbiome, where there is dynamic cooperation and competition among bacteria. We present a method for identifying and ranking pairs of bacteria that have a differential dichotomized relationship across outcomes. Our approach, implemented in an R package PairSeek, uses the stability selection framework with data-driven dichotomized forms of the pairwise relationships. We illustrate the properties of the proposed method using a published oral cancer data set and a simulation study.}, }
@article {pmid34747338, year = {2021}, author = {van der Vossen, EWJ and Bastos, D and Stols-Gonçalves, D and de Goffau, MC and Davids, M and Pereira, JPB and Li Yim, AYF and Henneman, P and Netea, MG and de Vos, WM and de Jonge, W and Groen, AK and Nieuwdorp, M and Levin, E}, title = {Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1993513}, pmid = {34747338}, issn = {1949-0984}, mesh = {Adult ; Aged ; DNA Methylation ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Male ; Metabolic Syndrome/genetics/metabolism/microbiology/*therapy ; Microfilament Proteins/genetics/metabolism ; Middle Aged ; Young Adult ; }, abstract = {Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.}, }
@article {pmid34742104, year = {2022}, author = {Yan, Y and Li, H and Fayyaz, A and Gai, Y}, title = {Metagenomic and network analysis revealed wide distribution of antibiotic resistance genes in monkey gut microbiota.}, journal = {Microbiological research}, volume = {254}, number = {}, pages = {126895}, doi = {10.1016/j.micres.2021.126895}, pmid = {34742104}, issn = {1618-0623}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; *Drug Resistance, Microbial/genetics ; *Gastrointestinal Microbiome/drug effects/genetics ; *Haplorhini/microbiology ; Metagenomics ; }, abstract = {The emergence and spread of drug-resistant microorganisms that have acquired new resistance mechanisms, leading to antibiotic resistance, continue to threaten the health of humans and animals worldwide. Non-human primates (NHPs), as close living relatives of human beings in the world, have a high degree of genetic and physiological similarity to humans. However, despite its importance, we lack a comprehensive characterization or understanding of the similarities and differences of the antibiotic resistance genes of the gut microbiome carried by non-human primates and humans. In the present study, the diversity and abundance of antibiotic resistance genes carried by the gut microbiota of cynomolgus monkeys (Macaca fascicularis) were investigated by metagenomic analysis. In total, 60 resistance types conferring resistance to 11 categories of antibiotics were identified in the gut microbiome of cynomolgus monkeys. Interestingly, the composition and abundance of ARGs carried by the gut microbiota of cynomolgus monkeys can be significantly affected by dietary changes. Moreover, we found that all ARG types carried by humans are also present in cynomolgus monkeys. The tetracycline resistance gene tet(37) is evolutionarily conserved and highly homologous. Taken together, our study provides a comprehensive overview of the diversity and richness of ARGs in the gut microbiota of cynomolgus monkeys and underlines the potentially crucial role of diet in the gut health of monkeys and humans.}, }
@article {pmid34742094, year = {2022}, author = {Díez López, C and Vidaki, A and Kayser, M}, title = {Integrating the human microbiome in the forensic toolkit: Current bottlenecks and future solutions.}, journal = {Forensic science international. Genetics}, volume = {56}, number = {}, pages = {102627}, doi = {10.1016/j.fsigen.2021.102627}, pmid = {34742094}, issn = {1878-0326}, mesh = {Computational Biology ; DNA/genetics ; Forensic Medicine ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; }, abstract = {Over the last few years, advances in massively parallel sequencing technologies (also referred to next generation sequencing) and bioinformatics analysis tools have boosted our knowledge on the human microbiome. Such insights have brought new perspectives and possibilities to apply human microbiome analysis in many areas, particularly in medicine. In the forensic field, the use of microbial DNA obtained from human materials is still in its infancy but has been suggested as a potential alternative in situations when other human (non-microbial) approaches present limitations. More specifically, DNA analysis of a wide variety of microorganisms that live in and on the human body offers promises to answer various forensically relevant questions, such as post-mortem interval estimation, individual identification, and tissue/body fluid identification, among others. However, human microbiome analysis currently faces significant challenges that need to be considered and overcome via future forensically oriented human microbiome research to provide the necessary solutions. In this perspective article, we discuss the most relevant biological, technical and data-related issues and propose future solutions that will pave the way towards the integration of human microbiome analysis in the forensic toolkit.}, }
@article {pmid34742036, year = {2021}, author = {Stockdale, SR and Hill, C}, title = {Progress and prospects of the healthy human gut virome.}, journal = {Current opinion in virology}, volume = {51}, number = {}, pages = {164-171}, doi = {10.1016/j.coviro.2021.10.001}, pmid = {34742036}, issn = {1879-6265}, mesh = {*Health ; Humans ; Intestines/*virology ; Metagenomics ; *Virome/genetics ; Viruses/genetics/*isolation &amp; purification ; }, abstract = {Not all viruses associated with humans cause disease. Non-pathogenic human-infecting viruses are predicted as important for immune system induction and preparation. Phages that infect bacteria are the most abundant predators of the human microbial ecosystem, promoting and maintaining bacterial diversity. Metagenomic analyses of the human gut virome and microbiome are unravelling the intricate predator-prey dynamics of phage-bacteria co-existence, co-evolution, and their interplay with the human host. While most adults harbour a distinctly individualistic and persistent community of virulent phages, new-borns are dominated by temperate phages heavily influenced by environmental exposures. The future development of microbiome-based interventions, therapeutics, and manipulation, will require a greater understanding of the human microbiome and the virome.}, }
@article {pmid34735597, year = {2022}, author = {Regel, A and Föll, D and Kriegel, MA}, title = {[Still's syndrome-similarities and differences between the juvenile and adult forms].}, journal = {Zeitschrift fur Rheumatologie}, volume = {81}, number = {1}, pages = {22-27}, pmid = {34735597}, issn = {1435-1250}, support = {R01 AI118855/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; *Arthritis, Juvenile/diagnosis ; Child ; Cytokines ; Humans ; Joints ; *Macrophage Activation Syndrome/diagnosis/therapy ; *Still's Disease, Adult-Onset/diagnosis/therapy ; }, abstract = {Still's syndrome includes systemic juvenile idiopathic arthritis (sJIA) and the adult form of Still's disease (adult-onset Still's disease, AOSD). Except for age, there are many similarities between sJIA and AOSD. A biphasic disease model is currently put forth. At disease onset, autoinflammation predominates, which is caused by dysregulation of the innate immune system. Later on, the disease can progress to a chronic-articular form, which is predominantly mediated by the adaptive immune system and is consequently due to autoimmunity. The "window-of-opportunity" hypothesis is based on this biphasic model and supports the assumption that an early, targeted therapy with cytokine blockade can prevent disease progression to chronic destructive arthritis. Macrophage activation syndrome (MAS) is a serious complication of the so-called cytokine storm during the systemic phase of the disease. Clinically, there are many similarities between sJIA and AOSD. Recurrent fever, a fleeting, salmon-colored rash, and arthralgia/arthritis are common signs and symptoms of both sJIA and AOSD. The few differences are mainly related to the therapies and their side effects in children versus adults. In addition, the contribution of genetics to pathogenesis is more pronounced in sJIA compared to AOSD, but there are also smooth transitions in this respect and both diseases are heavily influenced by exogenous factors such as microbial triggers. Future research aspects could include additional investigation of these triggers such as viruses, bacteria, or dysbiosis of the human microbiome.}, }
@article {pmid34731631, year = {2021}, author = {Lam, KN and Spanogiannopoulos, P and Soto-Perez, P and Alexander, M and Nalley, MJ and Bisanz, JE and Nayak, RR and Weakley, AM and Yu, FB and Turnbaugh, PJ}, title = {Phage-delivered CRISPR-Cas9 for strain-specific depletion and genomic deletions in the gut microbiome.}, journal = {Cell reports}, volume = {37}, number = {5}, pages = {109930}, pmid = {34731631}, issn = {2211-1247}, support = {T32 GM007810/GM/NIGMS NIH HHS/United States ; T32 AI060537/AI/NIAID NIH HHS/United States ; R01 AT011117/AT/NCCIH NIH HHS/United States ; K08 AR073930/AR/NIAMS NIH HHS/United States ; //CIHR/Canada ; P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; F32 AI147456/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteriophage M13/*genetics ; CRISPR-Associated Protein 9/*genetics/metabolism ; *CRISPR-Cas Systems ; *Chromosome Deletion ; *Chromosomes, Bacterial ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Escherichia coli/*genetics/growth &amp; development ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; *Gene Editing ; Gene Expression Regulation, Bacterial ; Mice, Inbred BALB C ; Mice, Transgenic ; Proof of Concept Study ; Mice ; }, abstract = {Mechanistic insights into the role of the human microbiome in the predisposition to and treatment of disease are limited by the lack of methods to precisely add or remove microbial strains or genes from complex communities. Here, we demonstrate that engineered bacteriophage M13 can be used to deliver DNA to Escherichia coli within the mouse gastrointestinal (GI) tract. Delivery of a programmable exogenous CRISPR-Cas9 system enables the strain-specific depletion of fluorescently marked isogenic strains during competitive colonization and genomic deletions that encompass the target gene in mice colonized with a single strain. Multiple mechanisms allow E. coli to escape targeting, including loss of the CRISPR array or even the entire CRISPR-Cas9 system. These results provide a robust and experimentally tractable platform for microbiome editing, a foundation for the refinement of this approach to increase targeting efficiency, and a proof of concept for the extension to other phage-bacterial pairs of interest.}, }
@article {pmid34731146, year = {2021}, author = {Maslennikov, R and Svistunov, A and Ivashkin, V and Ufimtseva, A and Poluektova, E and Efremova, I and Ulyanin, A and Okhlobystin, A and Kardasheva, S and Kurbatova, A and Levshina, A and Grigoriadis, D and Magomedov, S and Dzhakhaya, N and Shifrin, O and Zharkova, M and Yuryeva, E and Kokina, N and Shirtladze, M and Kiseleva, O}, title = {Early viral versus late antibiotic-associated diarrhea in novel coronavirus infection.}, journal = {Medicine}, volume = {100}, number = {41}, pages = {e27528}, pmid = {34731146}, issn = {1536-5964}, mesh = {Aged ; Anti-Bacterial Agents/*adverse effects ; COVID-19/*epidemiology ; Diarrhea/*chemically induced/classification/epidemiology/*virology ; Humans ; Length of Stay ; Middle Aged ; Pandemics ; Retrospective Studies ; Risk Factors ; SARS-CoV-2 ; }, abstract = {Diarrhea is one of the manifestations of the novel coronavirus disease (COVID-19), but it also develops as a complication of massive antibiotic therapy in this disease. This study aimed to compare these types of diarrhea.We included patients with COVID-19 in a cohort study and excluded patients with chronic diarrhea, laxative use, and those who died during the first day of hospitalization.There were 89 (9.3%), 161 (16.7%), and 731 (75.7%) patients with early viral, late antibiotic-associated, and without diarrhea, respectively. Late diarrhea lasted longer (6 [4-10] vs 5 [3-7] days, P < .001) and was more severe. Clostridioides difficile was found in 70.5% of tested patients with late diarrhea and in none with early diarrhea. Presence of late diarrhea was associated with an increased risk of death after 20 days of disease (P = .009; hazard ratio = 4.7). Patients with late diarrhea had a longer hospital stay and total disease duration, and a higher proportion of these patients required intensive care unit admission. Oral amoxicillin/clavulanate (odds ratio [OR] = 2.23), oral clarithromycin (OR = 3.79), and glucocorticoids (OR = 4.41) use was a risk factor for the development of late diarrhea, while ceftriaxone use (OR = 0.35) had a protective effect. Before the development of late diarrhea, decrease in C-reactive protein levels and increase in lymphocyte count stopped but the white blood cell and neutrophil count increased. An increase in neutrophils by >0.6 × 109 cells/L predicted the development of late diarrhea in the coming days (sensitivity 82.0%, specificity 70.8%, area under the curve = 0.791 [0.710-0.872]).Diarrhea in COVID-19 is heterogeneous, and different types of diarrhea require different management.}, }
@article {pmid34718406, year = {2022}, author = {Liu, T and Xu, P and Du, Y and Lu, H and Zhao, H and Wang, T}, title = {MZINBVA: variational approximation for multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys.}, journal = {Briefings in bioinformatics}, volume = {23}, number = {1}, pages = {}, doi = {10.1093/bib/bbab443}, pmid = {34718406}, issn = {1477-4054}, mesh = {Computer Simulation ; Humans ; *Microbiota ; Models, Statistical ; Research Design ; }, abstract = {As our understanding of the microbiome has expanded, so has the recognition of its critical role in human health and disease, thereby emphasizing the importance of testing whether microbes are associated with environmental factors or clinical outcomes. However, many of the fundamental challenges that concern microbiome surveys arise from statistical and experimental design issues, such as the sparse and overdispersed nature of microbiome count data and the complex correlation structure among samples. For example, in the human microbiome project (HMP) dataset, the repeated observations across time points (level 1) are nested within body sites (level 2), which are further nested within subjects (level 3). Therefore, there is a great need for the development of specialized and sophisticated statistical tests. In this paper, we propose multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys. We develop a variational approximation method for maximum likelihood estimation and inference. It uses optimization, rather than sampling, to approximate the log-likelihood and compute parameter estimates, provides a robust estimate of the covariance of parameter estimates and constructs a Wald-type test statistic for association testing. We evaluate and demonstrate the performance of our method using extensive simulation studies and an application to the HMP dataset. We have developed an R package MZINBVA to implement the proposed method, which is available from the GitHub repository https://github.com/liudoubletian/MZINBVA.}, }
@article {pmid34715771, year = {2021}, author = {Geerlings, SY and Ouwerkerk, JP and Koehorst, JJ and Ritari, J and Aalvink, S and Stecher, B and Schaap, PJ and Paulin, L and de Vos, WM and Belzer, C}, title = {Genomic convergence between Akkermansia muciniphila in different mammalian hosts.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {298}, pmid = {34715771}, issn = {1471-2180}, mesh = {Akkermansia/classification/genetics/isolation &amp; purification/metabolism ; Animals ; Feces/microbiology ; Gastrointestinal Tract/microbiology ; Genetic Variation ; Genome, Bacterial/*genetics ; Genomics ; Humans ; Mammals/classification/*microbiology ; Mice ; Mucins/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Verrucomicrobia/classification/genetics/isolation &amp; purification ; }, abstract = {BACKGROUND: Akkermansia muciniphila is a member of the human gut microbiota where it resides in the mucus layer and uses mucin as the sole carbon, nitrogen and energy source. A. muciniphila is the only representative of the Verrucomicrobia phylum in the human gut. However, A. muciniphila 16S rRNA gene sequences have also been found in the intestines of many vertebrates.<br><br>RESULTS: We detected A. muciniphila-like bacteria in the intestines of animals belonging to 15 out of 16 mammalian orders. In addition, other species belonging to the Verrucomicrobia phylum were detected in fecal samples. We isolated 10 new A. muciniphila strains from the feces of chimpanzee, siamang, mouse, pig, reindeer, horse and elephant. The physiology and genome of these strains were highly similar in comparison to the type strain A. muciniphila Muc[T]. Overall, the genomes of the new strains showed high average nucleotide identity (93.9 to 99.7%). In these genomes, we detected considerable conservation of at least 75 of the 78 mucin degradation genes that were previously detected in the genome of the type strain Muc[T].<br><br>CONCLUSIONS: The low genomic divergence observed in the new strains may indicate that A. muciniphila favors mucosal colonization independent of the differences in hosts. In addition, the conserved mucus degradation capability points towards a similar beneficial role of the new strains in regulating host metabolic health.}, }
@article {pmid34715674, year = {2021}, author = {Han, S and Ellberg, CC and Olomu, IN and Vyas, AK}, title = {Gestational microbiome: metabolic perturbations and developmental programming.}, journal = {Reproduction (Cambridge, England)}, volume = {162}, number = {6}, pages = {R85-R98}, doi = {10.1530/REP-21-0241}, pmid = {34715674}, issn = {1741-7899}, mesh = {*Diabetes Mellitus, Type 2 ; *Diabetes, Gestational/metabolism ; Female ; Humans ; *Microbiota ; Obesity/metabolism ; Pregnancy ; *Prenatal Exposure Delayed Effects/metabolism ; }, abstract = {A growing body of research suggests that alterations to the human microbiome are associated with disease states, including obesity and diabetes. During pregnancy, these disease states are associated with maternal microbial dysbiosis. This review discusses the current literature regarding the typical maternal and offspring microbiome as well as alterations to the microbiome in the context of obesity, type 2 diabetes mellitus, and gestational diabetes mellitus. Furthermore, this review outlines the proposed mechanisms linking associations between the maternal microbiome in the aforementioned disease states and offspring microbiome. Additionally, this review highlights associations between alterations in offspring microbiome and postnatal health outcomes.}, }
@article {pmid34704787, year = {2021}, author = {Stubbendieck, RM and Zelasko, SE and Safdar, N and Currie, CR}, title = {Biogeography of Bacterial Communities and Specialized Metabolism in Human Aerodigestive Tract Microbiomes.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0166921}, pmid = {34704787}, issn = {2165-0497}, support = {TL1 TR002375/TR/NCATS NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; T32 GM140935/GM/NIGMS NIH HHS/United States ; U01 AI125053/AI/NIAID NIH HHS/United States ; U19 AI142720/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/*isolation &amp; purification/*metabolism ; Bacterial Proteins/genetics/metabolism ; Biosynthetic Pathways ; Cheek/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial ; Humans ; Microbiota ; Mouth/microbiology ; Nasal Cavity/microbiology ; Phylogeny ; }, abstract = {The aerodigestive tract (ADT) is the primary portal through which pathogens and other invading microbes enter the body. As the direct interface with the environment, we hypothesize that the ADT microbiota possess biosynthetic gene clusters (BGCs) for antibiotics and other specialized metabolites to compete with both endogenous and exogenous microbes. From 1,214 bacterial genomes, representing 136 genera and 387 species that colonize the ADT, we identified 3,895 BGCs. To determine the distribution of BGCs and bacteria in different ADT sites, we aligned 1,424 metagenomes, from nine different ADT sites, onto the predicted BGCs. We show that alpha diversity varies across the ADT and that each site is associated with distinct bacterial communities and BGCs. We identify specific BGC families enriched in the buccal mucosa, external naris, gingiva, and tongue dorsum despite these sites harboring closely related bacteria. We reveal BGC enrichment patterns indicative of the ecology at each site. For instance, aryl polyene and resorcinol BGCs are enriched in the gingiva and tongue, which are colonized by many anaerobes. In addition, we find that streptococci colonizing the tongue and cheek possess different ribosomally synthesized and posttranslationally modified peptide BGCs. Finally, we highlight bacterial genera with BGCs but are underexplored for specialized metabolism and demonstrate the bioactivity of Actinomyces against other bacteria, including human pathogens. Together, our results demonstrate that specialized metabolism in the ADT is extensive and that by exploring these microbiomes further, we will better understand the ecology and biogeography of this system and identify new bioactive natural products. IMPORTANCE Bacteria produce specialized metabolites to compete with other microbes. Though the biological activities of many specialized metabolites have been determined, our understanding of their ecology is limited, particularly within the human microbiome. As the aerodigestive tract (ADT) faces the external environment, bacteria colonizing this tract must compete both among themselves and with invading microbes, including human pathogens. We analyzed the genomes of ADT bacteria to identify biosynthetic gene clusters (BGCs) for specialized metabolites. We found that the majority of ADT BGCs are uncharacterized and the metabolites they encode are unknown. We mapped the distribution of BGCs across the ADT and determined that each site is associated with its own distinct bacterial community and BGCs. By further characterizing these BGCs, we will inform our understanding of ecology and biogeography across the ADT, and we may uncover new specialized metabolites, including antibiotics.}, }
@article {pmid34699641, year = {2021}, author = {Swanson, BA and Carson, MD and Hathaway-Schrader, JD and Warner, AJ and Kirkpatrick, JE and Corker, A and Alekseyenko, AV and Westwater, C and Aguirre, JI and Novince, CM}, title = {Antimicrobial-induced oral dysbiosis exacerbates naturally occurring alveolar bone loss.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {11}, pages = {e22015}, pmid = {34699641}, issn = {1530-6860}, support = {P30 DK123704/DK/NIDDK NIH HHS/United States ; T32 GM132055/GM/NIGMS NIH HHS/United States ; K08 DE025337/DE/NIDCR NIH HHS/United States ; R25 GM113278/GM/NIGMS NIH HHS/United States ; P20 GM130457/GM/NIGMS NIH HHS/United States ; R21 TR002513/TR/NCATS NIH HHS/United States ; R01 DE023783/DE/NIDCR NIH HHS/United States ; T32 DE017551/DE/NIDCR NIH HHS/United States ; P20 GM121342/GM/NIGMS NIH HHS/United States ; R01 LM012517/LM/NLM NIH HHS/United States ; R01 DE029637/DE/NIDCR NIH HHS/United States ; }, mesh = {Alveolar Bone Loss/*microbiology ; Animals ; Anti-Bacterial Agents/*adverse effects ; Dysbiosis/*microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; *Host Microbial Interactions ; Male ; Mice ; Mice, Inbred C57BL ; }, abstract = {Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6- to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline- versus vehicle-treated germ-free mice had similar alveolar bone loss outcomes, implying that antimicrobial-driven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring alveolar bone loss in SPF mice. Chlorhexidine further disrupted the oral bacteriome and worsened alveolar bone loss in minocycline-treated SPF mice, validating that antimicrobial-induced oral dysbiosis has deleterious effects on alveolar bone. Minocycline enhanced osteoclast size and interface with alveolar bone in SPF mice. Neutrophils and plasmacytoid dendritic cells were upregulated in cervical lymph nodes of minocycline-treated SPF mice. Paralleling the upregulated proinflammatory innate immune cells, minocycline therapy increased TH 1 and TH 17 cells that have known pro-osteoclastic actions in the alveolar bone. This report reveals that antimicrobial perturbation of the commensal microbiota induces a proinflammatory oral dysbiotic state that exacerbates naturally occurring alveolar bone loss.}, }
@article {pmid34697034, year = {2022}, author = {Koopen, A and Witjes, J and Wortelboer, K and Majait, S and Prodan, A and Levin, E and Herrema, H and Winkelmeijer, M and Aalvink, S and Bergman, JJGHM and Havik, S and Hartmann, B and Levels, H and Bergh, PO and van Son, J and Balvers, M and Bastos, DM and Stroes, E and Groen, AK and Henricsson, M and Kemper, EM and Holst, J and Strauch, CM and Hazen, SL and Bäckhed, F and De Vos, WM and Nieuwdorp, M and Rampanelli, E}, title = {Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study.}, journal = {Gut}, volume = {71}, number = {8}, pages = {1577-1587}, pmid = {34697034}, issn = {1468-3288}, mesh = {Blood Glucose/metabolism ; Blood Glucose Self-Monitoring ; Clostridiales ; Cross-Over Studies ; *Diabetes Mellitus, Type 2/drug therapy ; Double-Blind Method ; Glucagon-Like Peptide 1/metabolism ; Glycemic Control ; Humans ; Insulin/metabolism ; *Insulin Resistance ; Male ; *Metabolic Syndrome/genetics ; Transcriptome ; }, abstract = {OBJECTIVE: Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS.<br><br>DESIGN: In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6&#x2009;hours postinfusion) and 24-hour continuous glucose monitoring.<br><br>RESULTS: A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated.<br><br>CONCLUSIONS: A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.<br><br>TRIAL REGISTRATION NUMBER: NTR-NL6630.}, }
@article {pmid34696318, year = {2021}, author = {Tuomala, H and Verkola, M and Meller, A and Van der Auwera, J and Patpatia, S and Järvinen, A and Skurnik, M and Heikinheimo, A and Kiljunen, S}, title = {Phage Treatment Trial to Eradicate LA-MRSA from Healthy Carrier Pigs.}, journal = {Viruses}, volume = {13}, number = {10}, pages = {}, pmid = {34696318}, issn = {1999-4915}, mesh = {Animals ; Carrier State/microbiology/*veterinary ; Farms ; Livestock/microbiology ; Methicillin-Resistant Staphylococcus aureus/*physiology ; Nasal Cavity/microbiology ; Phage Therapy/*methods/*veterinary ; Staphylococcal Infections/*therapy/*veterinary ; Swine ; Swine Diseases/microbiology/*therapy ; }, abstract = {The increase of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) causes a threat to human health. LA-MRSA can be transmitted from animals to animal caretakers, which may further spread MRSA to communities and health care facilities. The objective of this work was to study the efficacy of phage treatment in the eradication of LA-MRSA from healthy carrier pigs. A total of 19 MRSA -positive weanling pigs were assigned to a test (n = 10) and a control group (n = 9). A phage cocktail containing three Staphylococcus phages, or a control buffer was administered to the nares and skin of the pigs three times every two days, after which the phage and MRSA levels in nasal and skin swab samples were monitored for a three-week period. The sensitivity of the strains isolated during the follow-up period to the phage cocktail and each phage individually was analyzed and the pig sera were tested for antibodies against the phages used in the cocktail. The phage treatment did not cause any side effects to the pigs. Phages were found in the skin and nasal samples on the days following the phage applications, but there was no reduction in the MRSA levels in the sampled animals. Phage-resistant strains or phage-specific antibodies were not detected during the experiment. The MRSA load in these healthy carrier animals was only 10-100 CFU/swab or nasal sample, which was likely below the replication threshold of phages. The effectiveness of phage treatment to eradicate MRSA from the pigs could thus not be (reliably) determined.}, }
@article {pmid34696185, year = {2021}, author = {Mintoff, D and Borg, I and Pace, NP}, title = {The Clinical Relevance of the Microbiome in Hidradenitis Suppurativa: A Systematic Review.}, journal = {Vaccines}, volume = {9}, number = {10}, pages = {}, pmid = {34696185}, issn = {2076-393X}, abstract = {Hidradenitis suppurativa is a chronic disease of the pilosebaceous unit. The name of the condition is a testament to the presumed relationship between the disease and the microbiome. The pathophysiology of hidradenitis suppurativa is, however, complex and believed to be the product of a multifactorial interplay between the interfollicular epithelium, pilosebaceous unit, microbiome, as well as genetic and environmental factors. In this review we assimilate the existing literature regarding the role played by the human microbiome in HS in various contexts of the disease, including the pathophysiologic, therapeutic, and potentially, diagnostic as well prognostic. In conclusion, the role played by the microbiome in HS is extensive and relevant and can have bench-to-bedside applications.}, }
@article {pmid34693388, year = {2021}, author = {Baunwall, SMD and Terveer, EM and Dahlerup, JF and Erikstrup, C and Arkkila, P and Vehreschild, MJ and Ianiro, G and Gasbarrini, A and Sokol, H and Kump, PK and Satokari, R and De Looze, D and Vermeire, S and Nakov, R and Brezina, J and Helms, M and Kjeldsen, J and Rode, AA and Kousgaard, SJ and Alric, L and Trang-Poisson, C and Scanzi, J and Link, A and Stallmach, A and Kupcinskas, J and Johnsen, PH and Garborg, K and Rodríguez, ES and Serrander, L and Brummer, RJ and Galpérine, KT and Goldenberg, SD and Mullish, BH and Williams, HR and Iqbal, TH and Ponsioen, C and Kuijper, EJ and Cammarota, G and Keller, JJ and Hvas, CL}, title = {The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.}, journal = {The Lancet regional health. Europe}, volume = {9}, number = {}, pages = {100181}, pmid = {34693388}, issn = {2666-7762}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe.<br><br>METHODS: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT.<br><br>FINDINGS: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0&#x2022;3%) unaccounted for. Adjusted to population size, 0&#x2022;257 per 100,000 population received FMT for CDI and 0&#x2022;189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres.<br><br>INTERPRETATION: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need.<br><br>FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).}, }
@article {pmid34692558, year = {2021}, author = {Li, RJ and Jie, ZY and Feng, Q and Fang, RL and Li, F and Gao, Y and Xia, HH and Zhong, HZ and Tong, B and Madsen, L and Zhang, JH and Liu, CL and Xu, ZG and Wang, J and Yang, HM and Xu, X and Hou, Y and Brix, S and Kristiansen, K and Yu, XL and Jia, HJ and He, KL}, title = {Network of Interactions Between Gut Microbiome, Host Biomarkers, and Urine Metabolome in Carotid Atherosclerosis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {708088}, pmid = {34692558}, issn = {2235-2988}, mesh = {Biomarkers ; *Carotid Artery Diseases ; Clostridiales ; *Gastrointestinal Microbiome ; Humans ; Metabolome ; Metabolomics ; }, abstract = {Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.}, }
@article {pmid34691000, year = {2021}, author = {Mancabelli, L and Milani, C and Anzalone, R and Alessandri, G and Lugli, GA and Tarracchini, C and Fontana, F and Turroni, F and Ventura, M}, title = {Free DNA and Metagenomics Analyses: Evaluation of Free DNA Inactivation Protocols for Shotgun Metagenomics Analysis of Human Biological Matrices.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {749373}, pmid = {34691000}, issn = {1664-302X}, abstract = {Culture-independent approaches now represent the gold standard for the investigation of both environmental and host-associated complex microbial communities. Nevertheless, despite the great advantages offered by these novel methodologies based on the use of next-generation DNA sequencing approaches, a number of bias sources have been identified. Among the latter, free DNA contained in biological matrices is one of the main sources of inaccuracy in reconstructing the resident microbial population of viable cells. For this reason, the photoreactive DNA-binding dye propidium monoazide (PMAxx[™]) has been developed by improving standard PMA. This compound binds and inactivates free DNA, thus preventing its amplification and sequencing. While the performances of PMA have been previously investigated, the efficiency with PMAxx[™] has been tested mainly for amplicon-based profiling approaches on a limited number of biological matrices. In this study, we validated the performance of PMAxx[™] for shotgun metagenomics approaches employing various human-associated matrices. Notably, results revealed that the effectiveness of PMAxx[™] in inactivating free DNA of prokaryotes and eukaryotes tends to vary significantly based on the biological matrices analyzed.}, }
@article {pmid34683389, year = {2021}, author = {Parkin, K and Christophersen, CT and Verhasselt, V and Cooper, MN and Martino, D}, title = {Risk Factors for Gut Dysbiosis in Early Life.}, journal = {Microorganisms}, volume = {9}, number = {10}, pages = {}, pmid = {34683389}, issn = {2076-2607}, abstract = {Dysbiosis refers to a reduction in microbial diversity, combined with a loss of beneficial taxa, and an increase in pathogenic microorganisms. Dysbiosis of the intestinal microbiota can have a substantial effect on the nervous and immune systems, contributing to the onset of several inflammatory diseases. Epidemiological studies provided insight in how changes in the living environment have contributed to an overall loss of diversity and key taxa in the gut microbiome, coinciding with increased reports of atopy and allergic diseases. The gut microbiome begins development at birth, with major transition periods occurring around the commencement of breastfeeding, and the introduction of solid foods. As such, the development of the gut microbiome remains highly plastic and easily influenced by environmental factors until around three years of age. Developing a diverse and rich gut microbiome during this sensitive period is crucial to setting up a stable gut microbiome into adulthood and to prevent gut dysbiosis. Currently, the delivery route, antibiotic exposure, and diet are the best studied drivers of gut microbiome development, as well as risk factors of gut dysbiosis during infancy. This review focuses on recent evidence regarding key environmental factors that contribute to promoting gut dysbiosis.}, }
@article {pmid34682761, year = {2021}, author = {Dinis-Oliveira, RJ}, title = {The Auto-Brewery Syndrome: A Perfect Metabolic "Storm" with Clinical and Forensic Implications.}, journal = {Journal of clinical medicine}, volume = {10}, number = {20}, pages = {}, pmid = {34682761}, issn = {2077-0383}, abstract = {Auto-brewery syndrome (ABS) is a rare, unstudied, unknown, and underreported phenomenon in modern medicine. Patients with this syndrome become inebriated and may suffer the medical and social implications of alcoholism, including arrest for inebriated driving. The pathophysiology of ABS is reportedly due to a fungal type dysbiosis of the gut that ferments some carbohydrates into ethanol and may mimic a food allergy or intolerance. This syndrome should be considered in patients with chronic obstruction or hypomotility presenting with elevated breath and blood alcohol concentrations, especially after a high carbohydrate intake. A glucose challenge test should be performed as the confirmatory test. Treatment typically includes antifungal drugs combined with changes in lifestyle and nutrition. Additional studies are particularly needed on the human microbiome to shed light on how imbalances of commensal bacteria in the gut allow yeast to colonize on a pathological level.}, }
@article {pmid34677583, year = {2022}, author = {Pärnänen, KMM and Hultman, J and Markkanen, M and Satokari, R and Rautava, S and Lamendella, R and Wright, J and McLimans, CJ and Kelleher, SL and Virta, MP}, title = {Early-life formula feeding is associated with infant gut microbiota alterations and an increased antibiotic resistance load.}, journal = {The American journal of clinical nutrition}, volume = {115}, number = {2}, pages = {407-421}, pmid = {34677583}, issn = {1938-3207}, mesh = {Bacterial Proteins/*metabolism ; Cross-Sectional Studies ; Drug Resistance, Microbial/*genetics ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Infant Formula/*microbiology ; *Infant Nutritional Physiological Phenomena ; Infant, Newborn ; Infant, Premature ; Linear Models ; Male ; }, abstract = {BACKGROUND: Infants are at a high risk of acquiring fatal infections, and their treatment relies on functioning antibiotics. Antibiotic resistance genes (ARGs) are present in high numbers in antibiotic-naive infants' gut microbiomes, and infant mortality caused by resistant infections is high. The role of antibiotics in shaping the infant resistome has been studied, but there is limited knowledge on other factors that affect the antibiotic resistance burden of the infant gut.<br><br>OBJECTIVES: Our objectives were to determine the impact of early exposure to formula on the ARG load in neonates and infants born either preterm or full term. Our hypotheses were that diet causes a selective pressure that influences the microbial community of the infant gut, and formula exposure would increase the abundance of taxa that carry ARGs.<br><br>METHODS: Cross-sectionally sampled gut metagenomes of 46 neonates were used to build a generalized linear model to determine the impact of diet on ARG loads in neonates. The model was cross-validated using neonate metagenomes gathered from public databases using our custom statistical pipeline for cross-validation.<br><br>RESULTS: Formula-fed neonates had higher relative abundances of opportunistic pathogens such as Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Klebsiella oxytoca, and Clostridioides difficile. The relative abundance of ARGs carried by gut bacteria was 69% higher in the formula-receiving group (fold change, 1.69; 95% CI: 1.12-2.55; P&#xa0;=&#xa0;0.013; n&#xa0;=&#xa0;180) compared to exclusively human milk-fed infants. The formula-fed infants also had significantly less typical infant bacteria, such as Bifidobacteria, that have potential health benefits.<br><br>CONCLUSIONS: The novel finding that formula exposure is correlated with a higher neonatal ARG burden lays the foundation that clinicians should consider feeding mode in addition to antibiotic use during the first months of life to minimize the proliferation of antibiotic-resistant gut bacteria in infants.}, }
@article {pmid34671696, year = {2021}, author = {Zhao, Y and Jaber, V and Lukiw, WJ}, title = {Gastrointestinal Tract Microbiome-Derived Pro-inflammatory Neurotoxins in Alzheimer's Disease.}, journal = {Journal of aging science}, volume = {9}, number = {Suppl 5}, pages = {}, pmid = {34671696}, issn = {2329-8847}, support = {R01 EY006311/EY/NEI NIH HHS/United States ; R01 AG018031/AG/NIA NIH HHS/United States ; P50 AG016573/AG/NIA NIH HHS/United States ; R01 AG038834/AG/NIA NIH HHS/United States ; P30 GM103340/GM/NIGMS NIH HHS/United States ; }, abstract = {The microbiome contained within the human gastrointestinal (GI)-tract constitutes a highly complex, dynamic and interactive internal prokaryotic ecosystem that possesses a staggering diversity, speciation and complexity. This repository of microbes comprises the largest interactive source and highest density of microbes anywhere in nature, collectively constituting the largest 'diffuse organ system' in the human body. Through the extracellular fluid (ECF), cerebrospinal fluid (CSF), lymphatic and glymphatic circulation, endocrine, systemic and neurovascular circulation and/or central and peripheral nervous systems (CNS, PNS) microbiome-derived signaling strongly impacts the health, well-being and vitality of the human host. Recent data from the Human Microbiome Initiative (HMI) and the Unified Human Gastrointestinal Genome (UHGG) consortium have classified over [~]200 thousand diverse, non-redundant prokaryotic genomes in the human GI-tract microbiome involving about [~]5 thousand different GI-tract microbes that all together encode almost [~]200 million different protein sequences. While the largest proportion of different microbiome-derived proteins, lipoproteins and nucleic acids provide essential microorganism-specific gene products necessary to support microbial structure, function and viability, many of these same components are also shed from the outer cell wall of different Gram-negative bacterial species into surrounding biofluids which eventually enter the systemic circulation. Several of these microbial-derived secreted molecular species represent some of the most pro-inflammatory and noxious neurotoxins known. These neurotoxins disrupt cell-cell adhesion and easily translocate across aged or damaged plasma membranes and into the systemic circulation, brain, and CNS and PNS compartments. For example, microbial lipoprotein glycoconjugates such as Gram-negative bacteria-derived lipopolysaccharide (LPS), bacterial amyloids and more recently small non-coding RNA (sncRNA) microbial-derived neurotoxins have been found by many independent research groups to reside within the brain cells and CNS tissues of aged patients affected with Alzheimer's disease (AD). This 'Commentary' will highlight the most recent findings on these microbial-derived secreted toxins, their neurotropic properties and the potential contribution of these neurotoxic and pro-inflammatory microbial exudates to age-related inflammatory neurodegeneration, with specific reference to the human GI-tract abundant Gram-negative anaerobe Bacteroides fragilis and to AD wherever possible.}, }
@article {pmid34671642, year = {2021}, author = {Conta, G and Del Chierico, F and Reddel, S and Marini, F and Sciubba, F and Capuani, G and Tomassini, A and Di Cocco, ME and Laforgia, N and Baldassarre, ME and Putignani, L and Miccheli, A}, title = {Longitudinal Multi-Omics Study of a Mother-Infant Dyad from Breastfeeding to Weaning: An Individualized Approach to Understand the Interactions Among Diet, Fecal Metabolome and Microbiota Composition.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {688440}, pmid = {34671642}, issn = {2296-889X}, abstract = {The development of the human gut microbiota is characterized by a dynamic sequence of events from birth to adulthood, which make the gut microbiota unique for everyone. Its composition and metabolism may play a critical role in the intestinal homeostasis and health. We propose a study on a single mother-infant dyad to follow the dynamics of an infant fecal microbiota and metabolome changes in relation to breast milk composition during the lactation period and evaluate the changes induced by introduction of complementary food during the weaning period. Nuclear Magnetic Resonance (NMR)-based metabolomics was performed on breast milk and, together with 16S RNA targeted-metagenomics analysis, also on infant stool samples of a mother-infant dyad collected over a period running from the exclusive breastfeeding diet to weaning. Breast milk samples and neonatal stool samples were collected from the 4th to the 10th month of life. Both specimens were collected from day 103 to day 175, while from day 219-268 only stool samples were examined. An exploratory and a predictive analysis were carried out by means of Common component and specific weight analysis and multi-block partial least squares discriminant analysis, respectively. Stools collected during breastfeeding and during a mixed fruit/breastfeeding diet were characterized by high levels of fucosyl-oligosaccharides and glycolysis intermediates, including succinate and formate. The transition to a semi-solid food diet was characterized by several changes in fecal parameters: increase in short-chain fatty acids (SCFAs) levels, including acetate, propionate and butyrate, dissapearance of HMOs and the shift in the community composition, mainly occurring within the Firmicutes phylum. The variations in the fecal metabolome reflected the infant's diet transition, while the composition of the microbiota followed a more complex and still unstable behavior.}, }
@article {pmid34670249, year = {2021}, author = {Li, S and Su, B and He, QS and Wu, H and Zhang, T}, title = {Alterations in the oral microbiome in HIV infection: causes, effects and potential interventions.}, journal = {Chinese medical journal}, volume = {134}, number = {23}, pages = {2788-2798}, pmid = {34670249}, issn = {2542-5641}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; *HIV Infections/drug therapy ; Humans ; *Microbiota ; Mouth ; }, abstract = {A massive depletion of CD4+ T lymphocytes has been described in early and acute human immunodeficiency virus (HIV) infection, leading to an imbalance between the human microbiome and immune responses. In recent years, a growing interest in the alterations in gut microbiota in HIV infection has led to many studies; however, only few studies have been conducted to explore the importance of oral microbiome in HIV-infected individuals. Evidence has indicated the dysbiosis of oral microbiota in people living with HIV (PLWH). Potential mechanisms might be related to the immunodeficiency in the oral cavity of HIV-infected individuals, including changes in secretory components such as reduced levels of enzymes and proteins in saliva and altered cellular components involved in the reduction and dysfunction of innate and adaptive immune cells. As a result, disrupted oral immunity in HIV-infected individuals leads to an imbalance between the oral microbiome and local immune responses, which may contribute to the development of HIV-related diseases and HIV-associated non-acquired immunodeficiency syndrome comorbidities. Although the introduction of antiretroviral therapy (ART) has led to a significant decrease in occurrence of the opportunistic oral infections in HIV-infected individuals, the dysbiosis in oral microbiome persists. Furthermore, several studies with the aim to investigate the ability of probiotics to regulate the dysbiosis of oral microbiota in HIV-infected individuals are ongoing. However, the effects of ART and probiotics on oral microbiome in HIV-infected individuals remain unclear. In this article, we review the composition of the oral microbiome in healthy and HIV-infected individuals and the possible effect of oral microbiome on HIV-associated oral diseases. We also discuss how ART and probiotics influence the oral microbiome in HIV infection. We believe that a deeper understanding of composition and function of the oral microbiome is critical for the development of effective preventive and therapeutic strategies for HIV infection.}, }
@article {pmid34669983, year = {2022}, author = {Karimova, M and Moyes, D and Ide, M and Setterfield, JF}, title = {The human microbiome in immunobullous disorders and lichen planus.}, journal = {Clinical and experimental dermatology}, volume = {47}, number = {3}, pages = {522-528}, doi = {10.1111/ced.14987}, pmid = {34669983}, issn = {1365-2230}, mesh = {Humans ; Immunosenescence ; Lichen Planus/*immunology/*microbiology ; *Microbiota ; Molecular Mimicry ; Mouth/microbiology ; Mouth Diseases/immunology/microbiology ; Skin Diseases, Vesiculobullous/*immunology/*microbiology ; }, abstract = {For several decades, there has been a significant growth in the incidence of autoimmune diseases. Studies indicate that genetic factors may not be the only trigger for disease development and that dysbiosis of the microbiome may be another mechanism involved in the pathogenesis of autoimmune diseases. The role of the microbiome in the development of common skin disorders such as psoriasis, atopic dermatitis, acne and rosacea is increasingly well understood. However, few studies have focused on lichen planus and the rare acquired immunobullous diseases, both mucocutaneous groups of disorders linked to skin, oral and gut microbiomes. This review provides an insight into the current understanding of how the microbiome may contribute to the development of autoimmunity and to the maintenance and exacerbation of acquired immunobullous and lichenoid diseases. These mechanisms may have implications for future preventive and therapeutic approaches.}, }
@article {pmid34662348, year = {2021}, author = {Earle, SG and Lobanovska, M and Lavender, H and Tang, C and Exley, RM and Ramos-Sevillano, E and Browning, DF and Kostiou, V and Harrison, OB and Bratcher, HB and Varani, G and Tang, CM and Wilson, DJ and Maiden, MCJ}, title = {Genome-wide association studies reveal the role of polymorphisms affecting factor H binding protein expression in host invasion by Neisseria meningitidis.}, journal = {PLoS pathogens}, volume = {17}, number = {10}, pages = {e1009992}, pmid = {34662348}, issn = {1553-7374}, support = {R35 GM126942/GM/NIGMS NIH HHS/United States ; 102908/Z/13/Z/WT_/Wellcome Trust/United Kingdom ; 218205/Z/19/Z/WT_/Wellcome Trust/United Kingdom ; 101237/Z/13/B/WT_/Wellcome Trust/United Kingdom ; 087622/Z/08/Z/WT_/Wellcome Trust/United Kingdom ; 203141/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; /DH_/Department of Health/United Kingdom ; }, mesh = {Antigens, Bacterial/*genetics ; Bacterial Proteins/*genetics ; Genome-Wide Association Study ; Humans ; Meningococcal Infections/*genetics ; Neisseria meningitidis/*genetics/*pathogenicity ; Polymorphism, Single Nucleotide ; }, abstract = {Many invasive bacterial diseases are caused by organisms that are ordinarily harmless components of the human microbiome. Effective interventions against these microbes require an understanding of the processes whereby symbiotic or commensal relationships transition into pathology. Here, we describe bacterial genome-wide association studies (GWAS) of Neisseria meningitidis, a common commensal of the human respiratory tract that is nevertheless a leading cause of meningitis and sepsis. An initial GWAS discovered bacterial genetic variants, including single nucleotide polymorphisms (SNPs), associated with invasive meningococcal disease (IMD) versus carriage in several loci across the meningococcal genome, encoding antigens and other extracellular components, confirming the polygenic nature of the invasive phenotype. In particular, there was a significant peak of association around the fHbp locus, encoding factor H binding protein (fHbp), which promotes bacterial immune evasion of human complement by recruiting complement factor H (CFH) to the meningococcal surface. The association around fHbp with IMD was confirmed by a validation GWAS, and we found that the SNPs identified in the validation affected the 5' region of fHbp mRNA, altering secondary RNA structures, thereby increasing fHbp expression and enhancing bacterial escape from complement-mediated killing. This finding is consistent with the known link between complement deficiencies and CFH variation with human susceptibility to IMD. These observations demonstrate the importance of human and bacterial genetic variation across the fHbp:CFH interface in determining IMD susceptibility, the transition from carriage to disease.}, }
@article {pmid34656848, year = {2021}, author = {Tan-Torres, AL and Brooks, JP and Singh, B and Seashols-Williams, S}, title = {Machine learning clustering and classification of human microbiome source body sites.}, journal = {Forensic science international}, volume = {328}, number = {}, pages = {111008}, doi = {10.1016/j.forsciint.2021.111008}, pmid = {34656848}, issn = {1872-6283}, mesh = {Algorithms ; Cluster Analysis ; Humans ; Machine Learning ; Metagenomics ; *Microbiota ; }, abstract = {Distinct microbial signatures associated with specific human body sites can play a role in the identification of biological materials recovered from the crime scene, but at present, methods that have capability to predict origin of biological materials based on such signatures are limited. Metagenomic sequencing and machine learning (ML) offer a promising enhancement to current identification protocols. We use ML for forensic source body site identification using shotgun metagenomic sequenced data to verify the presence of microbiomic signatures capable of discriminating between source body sites and then show that accurate prediction is possible. The consistency between cluster membership and actual source body site (purity) exceeded 99% at the genus taxonomy using off-the-shelf ML clustering algorithms. Similar results were obtained at the family level. Accurate predictions were observed for genus, family, and order taxonomies, as well as with a core set of 51 genera. The accurate outcomes from our replicable process should encourage forensic scientists to seriously consider integrating ML predictors into their source body site identification protocols.}, }
@article {pmid34650058, year = {2021}, author = {Ji, X and Sun, T and Xie, S and Qian, H and Song, L and Wang, L and Liu, H and Feng, Q}, title = {Upregulation of CPNE7 in mesenchymal stromal cells promotes oral squamous cell carcinoma metastasis through the NF-κB pathway.}, journal = {Cell death discovery}, volume = {7}, number = {1}, pages = {294}, pmid = {34650058}, issn = {2058-7716}, abstract = {A remarkable shift in Mesenchymal stromal cells (MSCs) plays an important role in cancer metastasis, but the molecular mechanism is still unclear. CPNE7, a calcium-dependent phospholipid-binding protein, mediates signal transduction and metastasis in many tumours. Here, we demonstrated that MSCs derived from OSCC (OSCC-MSCs) promoted the metastasis of OSCC cells by transwell assay and animal models through epithelial to mesenchymal transition (EMT) (p < 0.05). RNA-sequencing, ELISA, neutralizing antibody and CXCR2 inhibitor assay confirmed that CXCL8 secreted by OSCC-MSCs was associated with the upregulated expression of CPNE7 by immunohistochemical and western blotting (p < 0.05). This is mechanistically linked to the activation of CPNE7 to NF-κB pathway-induced metastasis, including phosphorylated p65 and IκBa. CPNE7 silencing inhibited metastatic abilities and the expression of CXCL8, phosphorylated p65, IκBa, and p65 nuclear translocation by western blotting and immunofluorescence, while CPNE7 overexpression markedly promoted these events (p < 0.05). We also identified that Nucleolin could be bind CPNE7 and IκBa by co-immunoprecipitation. Together, our results suggest that upregulation of CPNE7 in MSCs interacted with surface receptor -Nucleolin and then combined with IκBa to promoted phosphorylated IκBa and p65 nuclear translocation to active NF-κB pathway, and then regulates CXCL8 secretion to promote the metastasis of OSCC cells. Therefore, CPNE7 in MSCs could be promising therapeutic targets in OSCC.}, }
@article {pmid34647264, year = {2021}, author = {Elton, S}, title = {Intimate ecosystems: the microbiome and the ecological determinants of health.}, journal = {Canadian journal of public health = Revue canadienne de sante publique}, volume = {112}, number = {6}, pages = {1004-1007}, pmid = {34647264}, issn = {1920-7476}, mesh = {Ecosystem ; *Health Equity ; Humans ; *Microbiota ; }, abstract = {The ecological determinants of health make explicit the ways in which human health and well-being depend on the biosphere and its systems. Water, oxygen, and food are listed along with soil systems, water systems, material for shelter, energy, the ozone layer and a stable climate. Research in the sciences is uncovering the critical role that the earth microbiome, including the human microbiome, plays in human health. The relationship between commensal microbiota and the systems of the human body, as well as the ways in which these systems are interdependent with other ecosystems such as food systems, invites revisiting the ecological determinants of health. In this commentary, I argue that microbiota, including the human microbiome, should be considered ecological determinants of health. Such a characterization would recognize the importance of the microbiome to human health. It would also frame this as a public health issue and raise questions about health equity, including who benefits from the knowledge produced through biomedical research.}, }
@article {pmid37440868, year = {2021}, author = {Shuler, K and Verbanic, S and Chen, IA and Lee, J}, title = {A Bayesian nonparametric analysis for zero-inflated multivariate count data with application to microbiome study.}, journal = {Journal of the Royal Statistical Society. Series C, Applied statistics}, volume = {70}, number = {4}, pages = {961-979}, pmid = {37440868}, issn = {0035-9254}, support = {DP2 GM123457/GM/NIGMS NIH HHS/United States ; }, abstract = {High-throughput sequencing technology has enabled researchers to profile microbial communities from a variety of environments, but analysis of multivariate taxon count data remains challenging. We develop a Bayesian nonparametric (BNP) regression model with zero inflation to analyse multivariate count data from microbiome studies. A BNP approach flexibly models microbial associations with covariates, such as environmental factors and clinical characteristics. The model produces estimates for probability distributions which relate microbial diversity and differential abundance to covariates, and facilitates community comparisons beyond those provided by simple statistical tests. We compare the model to simpler models and popular alternatives in simulation studies, showing, in addition to these additional community-level insights, it yields superior parameter estimates and model fit in various settings. The model's utility is demonstrated by applying it to a chronic wound microbiome data set and a Human Microbiome Project data set, where it is used to compare microbial communities present in different environments.}, }
@article {pmid36398283, year = {2021}, author = {Jeganathan, P and Holmes, SP}, title = {A Statistical Perspective on the Challenges in Molecular Microbial Biology.}, journal = {Journal of agricultural, biological, and environmental statistics}, volume = {26}, number = {2}, pages = {131-160}, pmid = {36398283}, issn = {1085-7117}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; }, abstract = {High throughput sequencing (HTS)-based technology enables identifying and quantifying non-culturable microbial organisms in all environments. Microbial sequences have enhanced our understanding of the human microbiome, the soil and plant environment, and the marine environment. All molecular microbial data pose statistical challenges due to contamination sequences from reagents, batch effects, unequal sampling, and undetected taxa. Technical biases and heteroscedasticity have the strongest effects, but different strains across subjects and environments also make direct differential abundance testing unwieldy. We provide an introduction to a few statistical tools that can overcome some of these difficulties and demonstrate those tools on an example. We show how standard statistical methods, such as simple hierarchical mixture and topic models, can facilitate inferences on latent microbial communities. We also review some nonparametric Bayesian approaches that combine visualization and uncertainty quantification. The intersection of molecular microbial biology and statistics is an exciting new venue. Finally, we list some of the important open problems that would benefit from more careful statistical method development.}, }
@article {pmid35936977, year = {2021}, author = {Adade, EE and Al Lakhen, K and Lemus, AA and Valm, AM}, title = {Recent progress in analyzing the spatial structure of the human microbiome: distinguishing biogeography and architecture in the oral and gut communities.}, journal = {Current opinion in endocrine and metabolic research}, volume = {18}, number = {}, pages = {275-283}, pmid = {35936977}, issn = {2451-9650}, support = {R03 DE028042/DE/NIDCR NIH HHS/United States ; }, abstract = {Fueled by technological advances in methods for sample collection and preservation in sequencing studies, and in advances in computational analyses of high content image data, the spatial structure of the human microbiome is coming to light. In this mini-review, we summarize recent developments in our understanding of the structure of two human microbiomes: the lower gut and the oral cavity. We focus on only the most recent literature and we make an important distinction between two forms of spatial structure, governed by scale: biogeography and architecture. By segmenting the study of microbiome spatial structure into two categories, we demonstrate the potential to greatly advance our understanding of the mechanistic principles that link structure and function in the microbiome.}, }
@article {pmid35492394, year = {2021}, author = {Marshall, EA and Telkar, N and Lam, WL}, title = {Functional role of the cancer microbiome in the solid tumour niche.}, journal = {Current research in immunology}, volume = {2}, number = {}, pages = {1-6}, pmid = {35492394}, issn = {2590-2555}, abstract = {The importance of gut microbiome to cancer therapy and response cannot be overstated, however the contribution of the bacterial population to the local solid tumour ecosystem is often overlooked. Seminal studies of tumour-resident microbiomes have shown that relative abundances of specific bacteria in the tumour correlate with survival metrics, implicating the microbiome in patient outcome. Similarly, patterns of microbiome community shifts between tumour-bearing and unaffected organs suggests a role for the tumour microbiome niche in contributing to tumour biology and behaviour. Recent reports of the detection of bacteria in solid tumours of diverse human organs have provided a strong rationale for deciphering the role of the solid-tumour microbiome across all human-host anatomic and physiologic niches, as the microbiome is ubiquitously present throughout the human body. Here, we review the role of the human microbiome in mediating response to therapies, as well as the differences between tumour and non-malignant-resident communities. We discuss the ability of the tumour microbiome to interact with the host, thereby influencing host cell behaviour and cancer-associated processes. Further, we evaluate recent technological advances that allow us to actively quantify these populations and the relationships between cell types. Finally, we suggest how these dynamic interactions can be harnessed for therapeutic benefit in the treatment of cancer.}, }
@article {pmid35695645, year = {2021}, author = {Swafford, AD and Khandelwal, S and Bhute, S}, title = {Potential Immune-Microbiome Interactions in Breast Cancer May Advance Treatment: What's Holding Us Back?.}, journal = {Critical reviews in immunology}, volume = {41}, number = {6}, pages = {27-42}, doi = {10.1615/CritRevImmunol.2022043153}, pmid = {35695645}, issn = {1040-8401}, mesh = {*Breast Neoplasms/therapy ; Dysbiosis ; Female ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy ; *Microbiota ; Tumor Microenvironment ; }, abstract = {The impact of the human microbiome, the diverse collection of microorganisms that inhabit nearly every niche in the human body, in shaping the immune response to dysbiotic events is apparent if poorly understood, particularly in complex, evolving disease states such as breast cancer. The impacts can be both indirect via metabolites and immune-interactions along the skin, gut, and oral cavities where the microbial communities are most abundant, or direct in the tumor microenvironment where microbial activities can promote growth or clearance of cancerous cells. Based on reports of using gut microbial signatures to predict therapeutic efficacy, the role that gut microbes and their metabolites may play in shaping the success or failure of immunotherapy has been extensively reviewed. In this review, we dissect the evidence for the direct and distal impact of microbes on oncogenesis, tumor growth and the immune responses to combat or promote tolerance of breast cancer tumors. Implementation of robust, valid analyses and methods are lacking in the field, and we provide recommendations for researchers and clinicians to work together to characterize the micro-biome-immune-breast cancer interactions that will hopefully enable the next generation of biomarkers and targets for improving disease outcomes.}, }
@article {pmid35695644, year = {2021}, author = {Maslinska, M and Kostyra-Grabczak, K and Królicki, L and Kwiatkowska, B}, title = {The Role of the Microbiome in Sjogren's Syndrome.}, journal = {Critical reviews in immunology}, volume = {41}, number = {6}, pages = {13-26}, doi = {10.1615/CritRevImmunol.2022043083}, pmid = {35695644}, issn = {1040-8401}, mesh = {Autoantigens ; *Autoimmune Diseases ; Dysbiosis ; Humans ; *Microbiota ; *Sjogren's Syndrome/diagnosis ; }, abstract = {The human microbiome is a living ecosystem existing within the host organism, determined by a balance between pathogenic microorganisms, symbionts, and commensals. The disturbance of microbiome composition-dysbiosis-often resulting in the excess of commensal numbers, may push the immune system towards activation of inflammatory and autoimmune processes. Changes in the microbiome of gut, eyes, and mouth may play a significant role in the development and course of autoimmune diseases, including primary Sjogren's syndrome. This autoimmune disease is associated with changes in the protective barrier of the epithelium, which is an important part of the antimicrobial defense. The development of pSS may be influenced by a mechanism of molecular mimicry between microbial antigens and self antigens leading to the initiation of anti-Ro60 antibody response. The knowledge of the influence of the state of microbiome on pSS may translate into the prophylaxis of the progression of dryness symptoms. The aim of this review is to present various aspects related to the human microbiome and Sjogren's syndrome.}, }
@article {pmid35695642, year = {2021}, author = {Passos, GA and Chaturvedi, VK}, title = {Preface Special Issue: Microbiome-Immune System Interactions.}, journal = {Critical reviews in immunology}, volume = {41}, number = {6}, pages = {v}, doi = {10.1615/CritRevImmunol.2022043499}, pmid = {35695642}, issn = {1040-8401}, mesh = {Autoimmunity ; *Gastrointestinal Microbiome ; Humans ; IgA Deficiency ; Immune System ; *Microbiota ; }, abstract = {Body homeostasis, immune response to microbial infections or vaccination, control of cancer onset or autoimmune or inflammatory diseases, as well as autism or other behavioral disorders, among other examples, are now recognized to be associated with the complex constitution of the body's microbiome. Recent findings demonstrate that the microbial composition, i.e., pathogenic, symbionts, and commensal viruses, bacteria, or yeast mainly in the gut, is strongly associated with susceptibility/resistance to several classes of diseases or its therapeutic response. This Special Issue focuses on the processes that link the human microbiome to three classes of diseases; immunodeficiency, autoimmunity, and cancer. Review articles cover aspects of the recent progress in selective immunoglobulin A (IgA) deficiency, Sjörgren's syndrome, breast cancer.}, }
@article {pmid35423066, year = {2020}, author = {Frateloreto, F and Capocasa, G and Olivo, G and Abdel Hady, K and Sappino, C and Di Berto Mancini, M and Levi Mortera, S and Lanzalunga, O and Di Stefano, S}, title = {Increasing the steric hindrance around the catalytic core of a self-assembled imine-based non-heme iron catalyst for C-H oxidation.}, journal = {RSC advances}, volume = {11}, number = {1}, pages = {537-542}, pmid = {35423066}, issn = {2046-2069}, abstract = {Sterically hindered imine-based non-heme complexes 4 and 5 rapidly self-assemble in acetonitrile at 25 °C, when the corresponding building blocks are added in solution in the proper ratios. Such complexes are investigated as catalysts for the H2O2 oxidation of a series of substrates in order to ascertain the role and the importance of the ligand steric hindrance on the action of the catalytic core 1, previously shown to be an efficient catalyst for aliphatic and aromatic C-H bond oxidation. The study reveals a modest dependence of the output of the oxidation reactions on the presence of bulky substituents in the backbone of the catalyst, both in terms of activity and selectivity. This result supports a previously hypothesized catalytic mechanism, which is based on the hemi-lability of the metal complex. In the active form of the catalyst, one of the pyridine arms temporarily leaves the iron centre, freeing up a lot of room for the access of the substrate.}, }
@article {pmid35846090, year = {2021}, author = {Ludwig, H and Hausmann, B and Schreder, M and Pönisch, W and Zojer, N and Knop, S and Gunsilius, E and Egle, A and Petzer, A and Einsele, H and Hajek, R and Weisel, K and Krenosz, KJ and Lang, A and Lechner, D and Greil, R and Berry, D}, title = {Reduced alpha diversity of the oral microbiome correlates with short progression-free survival in patients with relapsed/refractory multiple myeloma treated with ixazomib-based therapy (AGMT MM 1, phase II trial).}, journal = {EJHaem}, volume = {2}, number = {1}, pages = {99-103}, pmid = {35846090}, issn = {2688-6146}, abstract = {Alterations in the human microbiome have been linked to several malignant diseases. Here, we investigated the oral microbiome of 79 patients with relapsed/refractory multiple myeloma (MM) treated with ixazomib-thalidomide-dexamethasone. Increased alpha diversity (Shannon index) at the phylum level was associated with longer progression-free survival (PFS) (10.2 vs 8.5 months, P = .04), particularly in patients with very long (>75% quartile) PFS . Additionally, alpha diversity was lower in patients with progressive disease (P < .05). These findings suggest an interrelationship between the oral microbiome and outcome in patients with MM and encourage a novel direction for diagnostic and/or therapeutic strategies.}, }
@article {pmid37333953, year = {2020}, author = {Wilcox, H and Carr, C and Seney, S and Reid, G and Burton, JP}, title = {Expired probiotics: what is really in your cabinet?.}, journal = {FEMS microbes}, volume = {1}, number = {1}, pages = {xtaa007}, pmid = {37333953}, issn = {2633-6685}, abstract = {The popularity of using probiotics has surged, since they became widely accepted as safe and help improve general health. Inevitably, some of these products are used after expiration when microbial cell viability is below the recommended effective dose. Given that probiotics must be live microorganisms administered in adequate amounts, the aim of this study was to measure viability in expired products and assess how packaging and storage conditions impact efficacy, if at all. Thirty-three expired probiotic products were evaluated, of which 26 were stored in conditions recommended by the manufacturer. The viable microbial cells were enumerated and representative isolates identified by 16S and internally transcribed spacer rRNA gene sequencing. While the products had a mean past expiration time of 11.32 (1-22) years, 22 still had viable contents, and 5 were within or above the original product cell count claim. Product formulation and the number of species present did not appear to impact the stability of the products. However, overall packaging type, storage conditions and time since expiry were found to affect viability. All products with viable cells had the strain stipulated on the label. Despite some selected probiotic products retaining viability past their expiry date (indicating long-term storage is possible), the total counts were mostly well below that required for efficacious use as recommended by the manufacturer. Consuming expired probiotics may not yield the benefits for which they were designed.}, }
@article {pmid35117679, year = {2020}, author = {Mallika, L and Augustine, D and Rao, RS and Patil, S and Alamir, AWH and Awan, KH and Sowmya, SV and Haragannavar, VC and Prasad, K}, title = {Does microbiome shift play a role in carcinogenesis? A systematic review.}, journal = {Translational cancer research}, volume = {9}, number = {4}, pages = {3153-3166}, pmid = {35117679}, issn = {2219-6803}, abstract = {Recent scientific advances have presented substantial evidence that there is a multifaceted relationship between the microbiome and cancer. Humans are hosts to multifarious microbial communities, and these resident microbes contribute to both health and disease. Circulating toxic metabolites from these resident microbes may contribute to the development and progression of cancer. The aim of this systematic review was to evaluate microbiome and microbial shift contribution to the development and progression of cancer. This systematic review provides an analytical presentation of the evidence linking various parts of the microbiota to cancer. Searches were performed in databases such as PubMed, Google Scholar, Scopus, EBSCO, E-Journals and Science Direct from the time of their establishment until May 2018 with the following search terms: cancer or human microbe or cancer and human microbiome AND shift in microbes in cancer. The merged data were assessed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane's Risk of Bias Tool was used to assess the bias. Initially, 2,691 articles were identified, out of which 60 full-text articles were screened and re-evaluated. Among them, 14 were excluded based on inclusion/exclusion criteria; eventually, 46 articles were included in the systematic review. The reports of 46 articles revealed that microbial shift involving Candida species, Fusobacterium nucleatum, Porphyromonas gingivalis, Helicobacter pylori and Human papilloma virus (HPV) 16 &amp; 18 were most commonly involved in various human cancers. In particular, organisms, such as Candida albicans, Fusobacterium nucleatum, Porphyromonas gingivalis and HPV-16 were found to be more prevalent in oral cancer. The present systematic review emphasizes that the role and diverse contributions of the microbiome in carcinogenesis will provide opportunities for the development of effective diagnostic and preventive methods.}, }
@article {pmid35117578, year = {2020}, author = {Li, J and Chu, R and Wang, C and Li, Y and Wu, B and Wan, J}, title = {Microbiome characteristics and Bifidobacterium longum in colorectal cancer patients pre- and post-chemotherapy.}, journal = {Translational cancer research}, volume = {9}, number = {4}, pages = {2178-2190}, pmid = {35117578}, issn = {2219-6803}, abstract = {BACKGROUND: With the development of next generation sequencing technology, a lot of research has focused on the role of human microbiome in regulating immunity. The present study evaluated microbiome changes of colorectal cancer patients who received XELOX regimen (capecitabine plus oxaliplatin) without requiring antimicrobials.<br><br>METHODS: Stool samples from 7 patients (3 females/4 males) after screening of 11 patients before and after XELOX chemotherapy were subjected to 16S ribosomal RNA (rRNA) sequencing and flora dynamics compared at baseline and after 8 weeks of chemotherapy. Enrolled patients were newly diagnosed with stage IV colorectal cancer and had not received antimicrobial therapy or surgery. XELOX was administered for 2 cycles or 2-weekly treatments for 3 cycles.<br><br>RESULTS: The patterns of relative abundance of all bacteria isolated from stool samples before or after chemotherapy treatment appeared to be different, but there were no significant differences in the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolism pathway between the two groups. The top five pathways in patients were the two-component system, phenylalanine metabolism, degradation of aromatic compounds, beta-lactam resistance and folate biosynthesis. More than 99.6% intestinal flora isolates were bacteria, <0.4% were viruses and Archaea. The relative abundances of the 5 most common bacterial phyla in fecal samples before chemotherapy were Bacteroides, Firmicutes, Proteobacteria, Actinobacteria and Verrucomicrobia. The abundance of Actinomycetes in stools after chemotherapy was increased to 2.5 fold higher than before chemotherapy. Bifidobacterium longum species were significantly elevated in stools after chemotherapy (P<0.05), and changes of relative abundance of Bifidobacterium longum species after chemotherapy from baseline in favorable outcome population (stable disease) was significant higher than them in unfavorable outcome population (progressive disease, PD) (P=0.023).<br><br>CONCLUSIONS: The results indicated that Actinomyces in the gut might have a positive clinical outcome for colorectal cancer patients. This idea needs further studies to examine the actions of Actinomyces on inhibition of tumor growth.}, }
@article {pmid34917757, year = {2019}, author = {Grenga, L and Pible, O and Armengaud, J}, title = {Pathogen proteotyping: A rapidly developing application of mass spectrometry to address clinical concerns.}, journal = {Clinical mass spectrometry (Del Mar, Calif.)}, volume = {14 Pt A}, number = {}, pages = {9-17}, pmid = {34917757}, issn = {2376-9998}, abstract = {For the rapid and reliable differentiation of clinically-relevant bacterial species, mass spectrometry-based methods have emerged in recent years as valid alternatives to existing techniques. Mass profiles generated by whole-cell Matrix-Assisted Laser Desorption Ionization-Time of Flight mass spectrometry have revolutionized microorganism identification and proven their potential for proteotyping at the species level. Indeed, the methodology has been widely deployed in clinical settings. However, the low resolution and dynamic range of the methodology has limited its capacity to distinguish between subspecies. This discrimination capacity is pivotal in cases where certain strains display virulence or antibiotic resistance, and for epidemiologic analyses. Moreover, sensitivity and specificity are both key parameters when attempting to discriminate between microorganisms present in complex multi-pathogenic samples. These two parameters are also essential to meet the growing interest in the characterization of microorganisms contained within even more complex samples, such as the human microbiome. Tandem mass spectrometry, with its high resolution, holds great potential for use in the real-time direct analysis of pathogens at the most relevant taxonomic rank in routine clinical practice. This review explores the numerous benefits and challenges of implementing advanced proteotyping methods, based on tandem mass spectrometry, in clinical laboratories. We provide an overview of the current applications and methodologies, while also discussing recent improvements and potential new approaches for typing, as well as their future applications.}, }
@article {pmid35415428, year = {2019}, author = {Chandrababu, S and Bastola, D}, title = {An Integrated Approach to Recognize Potential Protective Effects of Culinary Herbs Against Chronic Diseases.}, journal = {Journal of healthcare informatics research}, volume = {3}, number = {2}, pages = {184-199}, pmid = {35415428}, issn = {2509-4971}, abstract = {Secondary metabolites in plants have been of interest to humans for their wide variety of functions, including its use as dye, drugs, or perfumes. They are increasingly recognized as potential sources of new natural drugs and antibiotics. More recently, gut-associated microbes have been found to fulfill important functions in human health. However, our knowledge about the impact of secondary metabolites from culinary herbs on gut microbiome is limited. The present study was conducted to access the availability of computational resources relating to secondary metabolites and bioactive compounds in culinary herbs. A graph-based database HerbMicrobeDataBase (HMDB) was developed using Neo4j framework. It integrates knowledge from key biological entities associated in maintaining gut health and provides efficient storage/retrieval and graphical presentation of botanical, biochemical, and pharmacological data for culinary herbs and the human microbiome. We demonstrate the utility of this resource in understanding the molecular mechanism of metabolite production as well as their therapeutic or toxicological effects on gut microbes.}, }
@article {pmid36119463, year = {2015}, author = {Darling, KW and Boyce, AM and Cho, MK and Sankar, PL}, title = {"What is the FDA Going to Think?": Negotiating Values through Reflective and Strategic Category Work in Microbiome Science.}, journal = {Science, technology &amp; human values}, volume = {40}, number = {1}, pages = {71-95}, pmid = {36119463}, issn = {0162-2439}, support = {P50 HG003389/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; }, abstract = {The US National Institute of Health's Human Microbiome Project aims to use genomic techniques to understand the microbial communities that live on the human body. The emergent field of microbiome science brought together diverse disciplinary perspectives and technologies, thus facilitating the negotiation of differing values. Here, we describe how values are conceptualized and negotiated within microbiome research. Analyzing discussions from a series of interdisciplinary workshops conducted with microbiome researchers, we argue that negotiations of epistemic, social, and institutional values were inextricable from the reflective and strategic category work (i.e., the work of anticipating and strategizing around divergent sets of institutional categories) that defined and organized the microbiome as an object of study and a potential future site of biomedical intervention. Negotiating the divergence or tension between emerging scientific and regulatory classifications also activated "values levers" and opened up reflective discussions of how classifications embody values and how these values might differ across domains. These data suggest that scholars at the intersections of science and technology studies, ethics, and policy could leverage such openings to identify and intervene in the ways that ethical/regulatory and scientific/technical practices are coproduced within unfolding research.}, }
@article {pmid34646255, year = {2021}, author = {Glowacki, RWP and Engelhart, MJ and Ahern, PP}, title = {Controlled Complexity: Optimized Systems to Study the Role of the Gut Microbiome in Host Physiology.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {735562}, pmid = {34646255}, issn = {1664-302X}, abstract = {The profound impact of the gut microbiome on host health has led to a revolution in biomedical research, motivating researchers from disparate fields to define the specific molecular mechanisms that mediate host-beneficial effects. The advent of genomic technologies allied to the use of model microbiomes in gnotobiotic mouse models has transformed our understanding of intestinal microbial ecology and the impact of the microbiome on the host. However, despite incredible advances, our understanding of the host-microbiome dialogue that shapes host physiology is still in its infancy. Progress has been limited by challenges associated with developing model systems that are both tractable enough to provide key mechanistic insights while also reflecting the enormous complexity of the gut ecosystem. Simplified model microbiomes have facilitated detailed interrogation of transcriptional and metabolic functions of the microbiome but do not recapitulate the interactions seen in complex communities. Conversely, intact complex communities from mice or humans provide a more physiologically relevant community type, but can limit our ability to uncover high-resolution insights into microbiome function. Moreover, complex microbiomes from lab-derived mice or humans often do not readily imprint human-like phenotypes. Therefore, improved model microbiomes that are highly defined and tractable, but that more accurately recapitulate human microbiome-induced phenotypic variation are required to improve understanding of fundamental processes governing host-microbiome mutualism. This improved understanding will enhance the translational relevance of studies that address how the microbiome promotes host health and influences disease states. Microbial exposures in wild mice, both symbiotic and infectious in nature, have recently been established to more readily recapitulate human-like phenotypes. The development of synthetic model communities from such "wild mice" therefore represents an attractive strategy to overcome the limitations of current approaches. Advances in microbial culturing approaches that allow for the generation of large and diverse libraries of isolates, coupled to ever more affordable large-scale genomic sequencing, mean that we are now ideally positioned to develop such systems. Furthermore, the development of sophisticated in vitro systems is allowing for detailed insights into host-microbiome interactions to be obtained. Here we discuss the need to leverage such approaches and highlight key challenges that remain to be addressed.}, }
@article {pmid34643888, year = {2023}, author = {Ivashkin, V and Fomin, V and Moiseev, S and Brovko, M and Maslennikov, R and Ulyanin, A and Sholomova, V and Vasilyeva, M and Trush, E and Shifrin, O and Poluektova, E}, title = {Efficacy of a Probiotic Consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the Treatment of Hospitalized Patients with COVID-19: a Randomized Controlled Trial.}, journal = {Probiotics and antimicrobial proteins}, volume = {15}, number = {3}, pages = {460-468}, pmid = {34643888}, issn = {1867-1314}, mesh = {Humans ; Aged ; *Bifidobacterium bifidum ; *Lacticaseibacillus rhamnosus ; Lacticaseibacillus ; *COVID-19/therapy ; *Probiotics/therapeutic use ; Diarrhea/prevention &amp; control ; Bifidobacterium longum subspecies infantis ; Anti-Bacterial Agents/therapeutic use ; }, abstract = {The treatment of coronavirus disease (COVID-19) and COVID-19-associated diarrhea remains challenging. This study aimed to evaluate the efficacy of a multi-strain probiotic in the treatment of COVID-19. This was a randomized, controlled, single-center, open-label trial (NCT04854941). Inpatients with confirmed COVID-19 and pneumonia were randomly assigned to a group that received a multi-strain probiotic (PRO group) or to the control group (CON group). There were 99 and 101 patients in the PRO and CON groups, respectively. No significant differences in mortality, total duration of disease and hospital stay, incidence of intensive care unit admission, need for mechanical ventilation or oxygen support, liver injury development, and changes in inflammatory biomarker levels were observed between the PRO and CON groups among all included patients as well as among subgroups delineated based on age younger or older than 65 years, and subgroups with chronic cardiovascular diseases and diabetes. Diarrhea on admission was observed in 11.5% of patients; it resolved earlier in the PRO group than in the CON group (2 [1-4] vs. 4 [3-6] days; p = 0.049). Hospital-acquired diarrhea developed less frequently in the PRO group than in the CON group among patients who received a single antibiotic (0% vs. 12.5%; p = 0.023) unlike among those who received > 1 antibiotic (10.5% vs. 13.3%; p = 0.696). The studied probiotic had no significant effect on mortality and changes in most biomarkers in COVID-19. However, it was effective in treating diarrhea associated with COVID-19 and in preventing hospital-acquired diarrhea in patients who received a single antibiotic.}, }
@article {pmid34642755, year = {2022}, author = {Vanhaecke, T and Bretin, O and Poirel, M and Tap, J}, title = {Drinking Water Source and Intake Are Associated with Distinct Gut Microbiota Signatures in US and UK Populations.}, journal = {The Journal of nutrition}, volume = {152}, number = {1}, pages = {171-182}, pmid = {34642755}, issn = {1541-6100}, mesh = {*Drinking Water ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S ; United Kingdom ; }, abstract = {BACKGROUND: The microbiome of the digestive tract exerts fundamental roles in host physiology. Extrinsic factors including lifestyle and diet are widely recognized as key drivers of gut and oral microbiome compositions. Although drinking water is among the food items consumed in the largest amount, little is known about its potential impact on the microbiome.<br><br>OBJECTIVES: We explored the associations of plain drinking water source and intake with gut and oral microbiota compositions in a population-based cohort.<br><br>METHODS: Microbiota, health, lifestyle, and food intake data were extracted from the American Gut Project public database. Associations of drinking water source (bottled, tap, filtered, or well water) and intake with global microbiota composition were evaluated using linear and logistic models adjusted for anthropometric, diet, and lifestyle factors in 3413 and 3794 individuals, respectively (fecal samples; 56% female, median [IQR] age: 48 [36-59] y; median [IQR] BMI: 23.3 [20.9-26.3] kg/m2), and in 283 and 309 individuals, respectively (oral samples).<br><br>RESULTS: Drinking water source ranked among the key contributing factors explaining the gut microbiota variation, accounting for 13% [Faith's phylogenetic diversity (Faith's PD)] and 47% (Bray-Curtis dissimilarity) of the age effect size. Drinking water source was associated with differences in gut microbiota signatures, as revealed by &#x3b2; diversity analyses (P&#xa0;<&#xa0;0.05; Bray-Curtis dissimilarity, weighted UniFrac distance). Subjects drinking mostly well water had higher fecal &#x3b1; diversity (P&#xa0;<&#xa0;0.05; Faith's PD, observed amplicon sequence variants), higher Dorea, and lower Bacteroides, Odoribacter, and Streptococcus than the other groups. Low water drinkers also exhibited gut microbiota differences compared with high water drinkers (P&#xa0;<&#xa0;0.05; Bray-Curtis dissimilarity, unweighted UniFrac distance) and a higher abundance of Campylobacter. No associations were found between oral microbiota composition and drinking water consumption.<br><br>CONCLUSIONS: Our results indicate that drinking water may be an important factor in shaping the human gut microbiome and that integrating drinking water source and intake as covariates in future microbiome analyses is warranted.}, }
@article {pmid34641955, year = {2021}, author = {Arikawa, K and Ide, K and Kogawa, M and Saeki, T and Yoda, T and Endoh, T and Matsuhashi, A and Takeyama, H and Hosokawa, M}, title = {Recovery of strain-resolved genomes from human microbiome through an integration framework of single-cell genomics and metagenomics.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {202}, pmid = {34641955}, issn = {2049-2618}, mesh = {Genome, Microbial ; Humans ; Metagenome ; *Metagenomics ; *Microbiota/genetics ; Phylogeny ; }, abstract = {BACKGROUND: Obtaining high-quality (HQ) reference genomes from microbial communities is crucial for understanding the phylogeny and function of uncultured microbes in complex microbial ecosystems. Despite improvements in bioinformatic approaches to generate curated metagenome-assembled genomes (MAGs), existing metagenome binners obtain population consensus genomes but they are nowhere comparable to genomes sequenced from isolates in terms of strain level resolution. Here, we present a framework for the integration of single-cell genomics and metagenomics, referred to as single-cell (sc) metagenomics, to reconstruct strain-resolved genomes from microbial communities at once.<br><br>RESULTS: Our sc-metagenomics integration framework, termed SMAGLinker, uses single-cell amplified genomes (SAGs) generated using microfluidic technology as binning guides and integrates them with metagenome-assembled genomes (MAGs) to recover improved draft genomes. We compared sc-metagenomics with the metagenomics-alone approach using conventional metagenome binners. The sc-metagenomics approach showed precise contig binning and higher recovery rates (>97%) of rRNA and plasmids than conventional metagenomics in genome reconstruction from the cell mock community. In human microbiota samples, sc-metagenomics recovered the largest number of genomes with a total of 103 gut microbial genomes (21 HQ, with 65 showing >90% completeness) and 45 skin microbial genomes (10 HQ, with 40 showing >90% completeness), respectively. Conventional metagenomics recovered one Staphylococcus hominis genome, whereas sc-metagenomics recovered two S. hominis genomes from identical skin microbiota sample. Single-cell sequencing revealed that these S. hominis genomes were derived from two distinct strains harboring specifically different plasmids. We found that all conventional S. hominis MAGs had a substantial lack or excess of genome sequences and contamination from other Staphylococcus species (S. epidermidis).<br><br>CONCLUSIONS: SMAGLinker enabled us to obtain strain-resolved genomes in the mock community and human microbiota samples by assigning metagenomic sequences correctly and covering both highly conserved genes such as rRNA genes and unique extrachromosomal elements, including plasmids. SMAGLinker will provide HQ genomes that are difficult to obtain using metagenomics alone and will facilitate the understanding of microbial ecosystems by elucidating detailed metabolic pathways and horizontal gene transfer networks. SMAGLinker is available at https://github.com/kojiari/smaglinker . Video abstract.}, }
@article {pmid34641521, year = {2021}, author = {Dohnálek, J and Dušková, J and Tishchenko, G and Kolenko, P and Skálová, T and Novák, P and Fejfarová, K and Šimůnek, J}, title = {Chitinase Chit62J4 Essential for Chitin Processing by Human Microbiome Bacterium Clostridium paraputrificum J4.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {19}, pages = {}, pmid = {34641521}, issn = {1420-3049}, support = {LM2015043, LM2018127//Ministry of Education, Youth and Sports of the Czech Republic/ ; CZ.1.05/1.1.00/02.0109//European Regional Development Fund/ ; CZ.02.1.01/0.0/0.0/15_003/0000447//European Regional Development Fund/ ; 86652036//Czech Academy of Sciences/ ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Catalytic Domain ; Chitin/*metabolism ; Chitinases/chemistry/genetics/*metabolism ; Clostridium/growth &amp; development/isolation &amp; purification/*metabolism ; Gastrointestinal Microbiome ; Humans ; Hydrogen-Ion Concentration ; Recombinant Proteins/genetics/metabolism ; }, abstract = {Commensal bacterium Clostridium paraputrificum J4 produces several extracellular chitinolytic enzymes including a 62 kDa chitinase Chit62J4 active toward 4-nitrophenyl N,N'-diacetyl-β-d-chitobioside (pNGG). We characterized the crude enzyme from bacterial culture fluid, recombinant enzyme rChit62J4, and its catalytic domain rChit62J4cat. This major chitinase, securing nutrition of the bacterium in the human intestinal tract when supplied with chitin, has a pH optimum of 5.5 and processes pNGG with Km = 0.24 mM and kcat = 30.0 s[-1]. Sequence comparison of the amino acid sequence of Chit62J4, determined during bacterial genome sequencing, characterizes the enzyme as a family 18 glycosyl hydrolase with a four-domain structure. The catalytic domain has the typical TIM barrel structure and the accessory domains-2x Fn3/Big3 and a carbohydrate binding module-that likely supports enzyme activity on chitin fibers. The catalytic domain is highly homologous to a single-domain chitinase of Bacillus cereus NCTU2. However, the catalytic profiles significantly differ between the two enzymes despite almost identical catalytic sites. The shift of pI and pH optimum of the commensal enzyme toward acidic values compared to the soil bacterium is the likely environmental adaptation that provides C. paraputrificum J4 a competitive advantage over other commensal bacteria.}, }
@article {pmid34639020, year = {2021}, author = {Suojalehto, H and Ndika, J and Lindström, I and Airaksinen, L and Karvala, K and Kauppi, P and Lauerma, A and Toppila-Salmi, S and Karisola, P and Alenius, H}, title = {Transcriptomic Profiling of Adult-Onset Asthma Related to Damp and Moldy Buildings and Idiopathic Environmental Intolerance.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34639020}, issn = {1422-0067}, support = {114350//The Finnish Work Environment Fund/ ; }, mesh = {Adult ; *Air Pollution, Indoor ; Asthma/*etiology ; Blood Cells/immunology/metabolism ; Case-Control Studies ; Cytokines/metabolism ; *Disease Susceptibility ; Environmental Exposure/*adverse effects ; Female ; *Fungi ; *Gene Expression Profiling ; Humans ; Immunophenotyping ; Macrophages/immunology/metabolism ; Male ; Middle Aged ; Risk Factors ; *Transcriptome ; }, abstract = {A subset of adult-onset asthma patients attribute their symptoms to damp and moldy buildings. Symptoms of idiopathic environmental intolerance (IEI) may resemble asthma and these two entities overlap. We aimed to evaluate if a distinct clinical subtype of asthma related to damp and moldy buildings can be identified, to unravel its corresponding pathomechanistic gene signatures, and to investigate potential molecular similarities with IEI. Fifty female adult-onset asthma patients were categorized based on exposure to building dampness and molds during disease initiation. IEI patients (n = 17) and healthy subjects (n = 21) were also included yielding 88 study subjects. IEI was scored with the Quick Environmental Exposure and Sensitivity Inventory (QEESI) questionnaire. Inflammation was evaluated by blood cell type profiling and cytokine measurements. Disease mechanisms were investigated via gene set variation analysis of RNA from nasal biopsies and peripheral blood mononuclear cells. Nasal biopsy gene expression and plasma cytokine profiles suggested airway and systemic inflammation in asthma without exposure to dampness (AND). Similar evidence of inflammation was absent in patients with dampness-and-mold-related asthma (AAD). Gene expression signatures revealed a greater degree of similarity between IEI and dampness-related asthma than between IEI patients and asthma not associated to dampness and mold. Blood cell transcriptome of IEI subjects showed strong suppression of immune cell activation, migration, and movement. QEESI scores correlated to blood cell gene expression of all study subjects. Transcriptomic analysis revealed clear pathomechanisms for AND but not AAD patients. Furthermore, we found a distinct molecular pathological profile in nasal and blood immune cells of IEI subjects, including several differentially expressed genes that were also identified in AAD samples, suggesting IEI-type mechanisms.}, }
@article {pmid34638770, year = {2021}, author = {Georgiou, K and Marinov, B and Farooqi, AA and Gazouli, M}, title = {Gut Microbiota in Lung Cancer: Where Do We Stand?.}, journal = {International journal of molecular sciences}, volume = {22}, number = {19}, pages = {}, pmid = {34638770}, issn = {1422-0067}, mesh = {*Carcinoma, Non-Small-Cell Lung/immunology/microbiology/therapy ; Gastrointestinal Microbiome/*immunology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; *Lung Neoplasms/immunology/microbiology/therapy ; T-Lymphocytes, Regulatory/*immunology/pathology ; }, abstract = {The gut microbiota (GM) is considered to constitute a powerful "organ" capable of influencing the majority of the metabolic, nutritional, physiological, and immunological processes of the human body. To date, five microbial-mediated mechanisms have been revealed that either endorse or inhibit tumorigenesis. Although the gastrointestinal and respiratory tracts are distant physically, they have common embryonic origin and similarity in structure. The lung microbiota is far less understood, and it is suggested that the crosslink between the human microbiome and lung cancer is a complex, multifactorial relationship. Several pathways linking their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Regarding implications of specific GM in lung cancer therapy, a few studies showed that the GM considerably affects immune checkpoint inhibitor (ICI) therapy by altering the differentiation of regulatory T cells and thus resulting in changes in immunomodulation mechanisms, as discovered by assessing drug metabolism directly and by assessing the host immune modulation response. Additionally, the GM may increase the efficacy of chemotherapeutic treatment in lung cancer. The mechanism underlying the role of the GLA in the pathogenesis and progression of lung cancer and its capability for diagnosis, manipulation, and treatment need to be further explored.}, }
@article {pmid34637779, year = {2021}, author = {Chipashvili, O and Utter, DR and Bedree, JK and Ma, Y and Schulte, F and Mascarin, G and Alayyoubi, Y and Chouhan, D and Hardt, M and Bidlack, F and Hasturk, H and He, X and McLean, JS and Bor, B}, title = {Episymbiotic Saccharibacteria suppresses gingival inflammation and bone loss in mice through host bacterial modulation.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {11}, pages = {1649-1662.e7}, pmid = {34637779}, issn = {1934-6069}, support = {K99 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE020102/DE/NIDCR NIH HHS/United States ; R01 DE031274/DE/NIDCR NIH HHS/United States ; R21 DE027199/DE/NIDCR NIH HHS/United States ; R00 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; R01 GM095373/GM/NIGMS NIH HHS/United States ; F31 DE026057/DE/NIDCR NIH HHS/United States ; }, mesh = {Actinobacteria/genetics/isolation &amp; purification/*pathogenicity/physiology ; Actinomyces/genetics/isolation &amp; purification/pathogenicity/physiology ; Alveolar Bone Loss/*microbiology/prevention &amp; control ; Animals ; Bacteria/classification/isolation &amp; purification/pathogenicity ; Bacterial Infections/microbiology/prevention &amp; control ; *Bacterial Physiological Phenomena ; Collagen/metabolism ; Dental Plaque/microbiology ; Down-Regulation ; Genes, Bacterial ; Gingivitis/*microbiology/prevention &amp; control ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Microbiota ; N-Acetylneuraminic Acid/metabolism ; Periodontitis/*microbiology/prevention &amp; control ; Propionibacteriaceae/genetics/isolation &amp; purification/pathogenicity/physiology ; *Symbiosis ; Virulence ; }, abstract = {Saccharibacteria (TM7) are obligate epibionts living on the surface of their host bacteria and are strongly correlated with dysbiotic microbiomes during periodontitis and other inflammatory diseases, suggesting they are putative pathogens. However, due to the recalcitrance of TM7 cultivation, causal research to investigate their role in inflammatory diseases is lacking. Here, we isolated multiple TM7 species on their host bacteria from periodontitis patients. These TM7 species reduce inflammation and consequential bone loss by modulating host bacterial pathogenicity in a mouse ligature-induced periodontitis model. Two host bacterial functions involved in collagen binding and utilization of eukaryotic sialic acid are required for inducing bone loss and are altered by TM7 association. This TM7-mediated downregulation of host bacterial pathogenicity is shown for multiple TM7/host bacteria pairs, suggesting that, in contrast to their suspected pathogenic role, TM7 could protect mammalian hosts from inflammatory damage induced by their host bacteria.}, }
@article {pmid34636673, year = {2021}, author = {De Wolfe, TJ and Arefin, MR and Benezra, A and Rebolleda Gómez, M}, title = {Chasing Ghosts: Race, Racism, and the Future of Microbiome Research.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0060421}, pmid = {34636673}, issn = {2379-5077}, support = {RT-2020-04-64//Michael Smith Foundation for Health Research (MSFHR)/ ; }, abstract = {In this article, we argue that a careful examination of human microbiome science's relationship with race and racism is necessary to foster equitable social and ecological relations in the field. We point to the origins and evolution of the problematic use of race in microbiome literature by demonstrating the increased usage of race both explicitly and implicitly in and beyond the human microbiome sciences. We demonstrate how these uses limit the future of rigorous and just microbiome research. We conclude with an outline of alternative actionable ways to build a more effective, antiracist microbiome science.}, }
@article {pmid34628621, year = {2021}, author = {Giraldo, PC and Sanches, JM and Sparvolli, LG and Amaral, R and Migliorini, I and Gil, CD and Taddei, CR and Witkin, SS and Discacciati, MG}, title = {Relationship between Papillomavirus vaccine, vaginal microbiome, and local cytokine response: an exploratory research.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {52}, number = {4}, pages = {2363-2371}, pmid = {34628621}, issn = {1678-4405}, support = {2016/08392-3//FAPESP/ ; }, mesh = {Adult ; *Bacteria/drug effects/genetics ; *Cytokines/immunology ; Female ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; *Microbiota/drug effects/genetics ; *Papillomavirus Infections/prevention &amp; control ; *Papillomavirus Vaccines/pharmacology ; RNA, Ribosomal, 16S/genetics ; *Vagina/microbiology ; Young Adult ; }, abstract = {INTRODUCTION: The influence of vaccination on composition of the human microbiome at distinct sites has been recognized as an essential component in the development of new vaccine strategies. The HPV vaccine is widely used to prevent cervical cancer; however, the influence of HPV vaccine on the vaginal microbiota has not been previously investigated. In his study, we performed an initial characterization of the microbiome and cytokine composition in the vagina following administration of the bivalent vaccine against HPV 16/18.<br><br>MATERIAL AND METHODS: In this exploratory study, fifteen women between 18 and 40&#xa0;years received three doses of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix&#xae;). Cervicovaginal samples were collected before the first dose and 30&#xa0;days after the third dose. HPV genotyping was performed by the XGEN Flow Chip technique. The cytokines IFN-&#x3b3;, IL-2, IL-12p70, TNF-&#x3b1;, GM-CSF, IL-4, IL-5, IL-10, and IL-13 were quantitated by multiplex immunoassay. The vaginal microbiome was identified by analysis of the V3/V4 region of the bacterial 16S rRNA gene.<br><br>RESULTS: The most abundant bacterial species in the vaginal microbiome was Lactobacillus crispatus, followed by L. iners. Bacterial diversity and dominant organisms were unchanged following vaccination. Small decreases in levels of pro and anti-inflammatory cytokines were observed following HPV vaccination, but there was no association between vaginal cytokine levels and microbiome composition.<br><br>CONCLUSION: Vaginal microbiome is not altered following administration of the standard three-dose HPV-16/18 AS04-adjuvanted (Cervarix&#xae;) vaccine.}, }
@article {pmid34616771, year = {2021}, author = {Medeiros Filho, F and do Nascimento, APB and Costa, MOCE and Merigueti, TC and de Menezes, MA and Nicolás, MF and Dos Santos, MT and Carvalho-Assef, APD and da Silva, FAB}, title = {A Systematic Strategy to Find Potential Therapeutic Targets for Pseudomonas aeruginosa Using Integrated Computational Models.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {728129}, pmid = {34616771}, issn = {2296-889X}, abstract = {Pseudomonas aeruginosa is an opportunistic human pathogen that has been a constant global health problem due to its ability to cause infection at different body sites and its resistance to a broad spectrum of clinically available antibiotics. The World Health Organization classified multidrug-resistant Pseudomonas aeruginosa among the top-ranked organisms that require urgent research and development of effective therapeutic options. Several approaches have been taken to achieve these goals, but they all depend on discovering potential drug targets. The large amount of data obtained from sequencing technologies has been used to create computational models of organisms, which provide a powerful tool for better understanding their biological behavior. In the present work, we applied a method to integrate transcriptome data with genome-scale metabolic networks of Pseudomonas aeruginosa. We submitted both metabolic and integrated models to dynamic simulations and compared their performance with published in vitro growth curves. In addition, we used these models to identify potential therapeutic targets and compared the results to analyze the assumption that computational models enriched with biological measurements can provide more selective and (or) specific predictions. Our results demonstrate that dynamic simulations from integrated models result in more accurate growth curves and flux distribution more coherent with biological observations. Moreover, identifying drug targets from integrated models is more selective as the predicted genes were a subset of those found in the metabolic models. Our analysis resulted in the identification of 26 non-host homologous targets. Among them, we highlighted five top-ranked genes based on lesser conservation with the human microbiome. Overall, some of the genes identified in this work have already been proposed by different approaches and (or) are already investigated as targets to antimicrobial compounds, reinforcing the benefit of using integrated models as a starting point to selecting biologically relevant therapeutic targets.}, }
@article {pmid34616291, year = {2021}, author = {Sergazy, S and Gulyayev, A and Amangeldiyeva, A and Nurgozhina, A and Nurgaziyev, M and Shulgau, Z and Chulenbayeva, L and Khassenbekova, Z and Kushugulova, A and Aljofan, M}, title = {Antiradical and Cytoprotective Properties of Allium nutans L. Honey Against CCL4-Induced Liver Damage in Rats.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {687763}, pmid = {34616291}, issn = {1663-9812}, abstract = {The aim of this study is determine the in vitro and in vivo antiradical properties and the cytoprotective activity of Allium nutans L. honey extract. The antiradical properties of the extracts were investigated in rabbit alveolar macrophages and human foreskin fibroblast (hFFs) cells in the presence of doxorubicin, a cytotoxic substance using DPPH and ABTS assays. The cytoprotective activities were determined using 18 Wistar rats divided into three different groups, a negative control, and two other groups with experimentally induced hepatotoxicity by a single intraperitoneal injection of 50% carbon tetrachloride (CCl4) oil solution. A positive control group, received drinking water only and an experimental group that was treated with Allium nutans L. honey extracts for 7 days. In vitro treatment with Allium nutans L. honey extracts resulted in 78% reduction in radical activity in DPPH and 91.6% inhibition using the ABTS. Also, honey extracts were able to preserve 100% of cell viability in the presence of the cytotoxic, doxorubicin. Furthermore, the treatment with honey extracts resulted in a significant reduction in damage to the structure of liver tissue, as well significant reduction in the levels of ALT and AST in the experimental group compared to the control group.}, }
@article {pmid34615932, year = {2021}, author = {Morrow, JD and Castaldi, PJ and Chase, RP and Yun, JH and Lee, S and Liu, YY and Hersh, CP}, title = {Peripheral blood microbial signatures in current and former smokers.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {19875}, pmid = {34615932}, issn = {2045-2322}, support = {R01 HL130512/HL/NHLBI NIH HHS/United States ; U01 HL089897/HL/NHLBI NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 HL147326/HL/NHLBI NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; K25 HL136846/HL/NHLBI NIH HHS/United States ; R01 HL124233/HL/NHLBI NIH HHS/United States ; K08 HL146972/HL/NHLBI NIH HHS/United States ; R01 HL125583/HL/NHLBI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Disease Susceptibility ; Follow-Up Studies ; Genetic Predisposition to Disease ; Host Microbial Interactions ; Host-Pathogen Interactions ; Lung/microbiology ; *Microbiota ; Pulmonary Disease, Chronic Obstructive/complications/diagnosis/etiology ; Respiratory Function Tests ; *Sepsis/diagnosis/etiology/microbiology ; *Smokers ; Smoking/adverse effects ; }, abstract = {The human microbiome has a role in the development of multiple diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. We hypothesize the blood microbiome signature may be a surrogate for some lung microbial characteristics. We sought associations between the blood microbiome signature and lung-relevant host factors. Based on reads not mapped to the human genome, we detected microbial nucleic acids through secondary use of peripheral blood RNA-sequencing from 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the Genome Analysis Toolkit (GATK) microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways. We replicated our analyses using a second independent set of blood RNA-seq data from 1,065 COPDGene study subjects and performed a meta-analysis across the two studies. The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. In our meta-analysis, we observed associations (q-value < 0.05) between Acinetobacter, Serratia, Streptococcus and Bacillus inferred abundances and Modified Medical Research Council (mMRC) dyspnea score. Current smoking status was associated (q < 0.05) with Acinetobacter, Serratia and Cutibacterium abundance. All 12 taxa investigated were associated with at least one white blood cell distribution variable. Abundance for nine of the 12 taxa was associated with sex, and seven of the 12 taxa were associated with race. Host-microbiome interaction analysis revealed clustering of genera associated with mMRC dyspnea score and smoking status, through shared links to several host pathways. This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between systemic microbial signatures and lung-related phenotypes may inform novel interventions and aid understanding of the systemic effects of smoking.}, }
@article {pmid34612695, year = {2021}, author = {Gierse, LC and Meene, A and Schultz, D and Schwaiger, T and Schröder, C and Mücke, P and Zühlke, D and Hinzke, T and Wang, H and Methling, K and Kreikemeyer, B and Bernhardt, J and Becher, D and Mettenleiter, TC and Lalk, M and Urich, T and Riedel, K}, title = {Influenza A H1N1 Induced Disturbance of the Respiratory and Fecal Microbiome of German Landrace Pigs - a Multi-Omics Characterization.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0018221}, pmid = {34612695}, issn = {2165-0497}, mesh = {Animals ; Bacteria/*classification/genetics/*isolation &amp; purification ; Disease Models, Animal ; Fatty Acids, Volatile/biosynthesis ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Gene Expression Profiling ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Male ; Orthomyxoviridae Infections/*pathology ; Proteomics ; RNA, Ribosomal, 16S/genetics ; Respiratory System/*microbiology ; Swine ; }, abstract = {Seasonal influenza outbreaks represent a large burden for the health care system as well as the economy. While the role of the microbiome has been elucidated in the context of various diseases, the impact of respiratory viral infections on the human microbiome is largely unknown. In this study, swine was used as an animal model to characterize the temporal dynamics of the respiratory and gastrointestinal microbiome in response to an influenza A virus (IAV) infection. A multi-omics approach was applied on fecal samples to identify alterations in microbiome composition and function during IAV infection. We observed significantly altered microbial richness and diversity in the gastrointestinal microbiome after IAV infection. In particular, increased abundances of Prevotellaceae were detected, while Clostridiaceae and Lachnospiraceae decreased. Moreover, our metaproteomics data indicated that the functional composition of the microbiome was heavily affected by the influenza infection. For instance, we identified decreased amounts of flagellin, correlating with reduced abundances of Lachnospiraceae and Clostridiaceae, possibly indicating involvement of a direct immune response toward flagellated Clostridia during IAV infection. Furthermore, enzymes involved in short-chain fatty acid (SCFA) synthesis were identified in higher abundances, while metabolome analyses revealed rather stable concentrations of SCFAs. In addition, 16S rRNA gene sequencing was used to characterize effects on the composition and natural development of the upper respiratory tract microbiome. Our results showed that IAV infection resulted in significant changes in the abundance of Moraxellaceae and Pasteurellaceae in the upper respiratory tract. Surprisingly, temporal development of the respiratory microbiome structure was not affected. IMPORTANCE Here, we used swine as a biomedical model to elucidate the impact of influenza A H1N1 infection on structure and function of the respiratory and gastrointestinal tract microbiome by employing a multi-omics analytical approach. To our knowledge, this is the first study to investigate the temporal development of the porcine microbiome and to provide insights into the functional capacity of the gastrointestinal microbiome during influenza A virus infection.}, }
@article {pmid34611047, year = {2022}, author = {Lv, S and Wang, Y and Zhang, W and Shang, H}, title = {Trimethylamine oxide: a potential target for heart failure therapy.}, journal = {Heart (British Cardiac Society)}, volume = {108}, number = {12}, pages = {917-922}, doi = {10.1136/heartjnl-2021-320054}, pmid = {34611047}, issn = {1468-201X}, mesh = {Cardiotonic Agents ; Carnitine/metabolism ; Choline/metabolism ; Diuretics ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/drug therapy ; Humans ; Methylamines ; }, abstract = {Heart failure (HF) is a clinical syndrome in the late stage of cardiovascular disease and is associated with high prevalence, mortality and rehospitalisation rate. The pathophysiological mechanisms of HF have experienced the initial 'water-sodium retention' mode to 'abnormal hemodynamics' mode, and subsequent to 'abnormal activation of neuroendocrine' mode, which has extensively promoted the reform of HF treatment and updated the treatment concept. Since the Human Microbiome Project commencement, the study on intestinal microecology has swiftly developed, providing a new direction to reveal the occurrence of diseases and the mechanisms behind drug effects. Intestinal microecology comprises the gastrointestinal lumen, epithelial secretion, food entering the intestine, intestinal flora and metabolites. Choline and L-carnitine in the diet are metabolised to trimethylamine (TMA) by the intestinal micro-organisms, with TMA being absorbed into the blood. TMA then enters the liver through the portal vein circulation and is oxidised to trimethylamine oxide (TMAO) by the hepatic flavin-containing mono-oxygenase (FMO) family, especially FMO3. The circulating TMAO levels are associated with adverse outcomes in HF (mortality and readmission), and lower TMAO levels indicate better prognosis. As HF progresses, the concentration of TMAO in patients gradually increases. Whether the circulating TMAO level can be decreased by intervening with the intestinal microflora or relevant enzymes, thereby affecting the prognosis of patients with HF, has become a research hotspot. Therefore, based on the HF intestinal hypothesis, exploring the treatment strategy for HF targeting the TMAO metabolite of the intestinal flora may update the treatment concept in HF and improve its therapeutic effect.}, }
@article {pmid34609165, year = {2021}, author = {Boix-Amorós, A and Piras, E and Bu, K and Wallach, D and Stapylton, M and Fernández-Sesma, A and Malaspina, D and Clemente, JC}, title = {Viral Inactivation Impacts Microbiome Estimates in a Tissue-Specific Manner.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0067421}, pmid = {34609165}, issn = {2379-5077}, support = {R01 MH110418/MH/NIMH NIH HHS/United States ; 5R01MH110418//HHS | National Institutes of Health (NIH)/ ; }, abstract = {The global emergence of novel pathogenic viruses presents an important challenge for research, as high biosafety levels are required to process samples. While inactivation of infectious agents facilitates the use of less stringent safety conditions, its effect on other biological entities of interest present in the sample is generally unknown. Here, we analyzed the effect of five inactivation methods (heat, ethanol, formaldehyde, psoralen, and TRIzol) on microbiome composition and diversity in samples collected from four different body sites (gut, nasal, oral, and skin) and compared them against untreated samples from the same tissues. We performed 16S rRNA gene sequencing and estimated abundance and diversity of bacterial taxa present in all samples. Nasal and skin samples were the most affected by inactivation, with ethanol and TRIzol inducing the largest changes in composition, and heat, formaldehyde, TRIzol, and psoralen inducing the largest changes in diversity. Oral and stool microbiomes were more robust to inactivation, with no significant changes in diversity and only moderate changes in composition. Firmicutes was the taxonomic group least affected by inactivation, while Bacteroidetes had a notable enrichment in nasal samples and moderate enrichment in fecal and oral samples. Actinobacteria were more notably depleted in fecal and skin samples, and Proteobacteria exhibited a more variable behavior depending on sample type and inactivation method. Overall, our results demonstrate that inactivation methods can alter the microbiome in a tissue-specific manner and that careful consideration should be given to the choice of method based on the sample type under study. IMPORTANCE Understanding how viral infections impact and are modulated by the microbiome is an important problem in basic research but is also of high clinical relevance under the current pandemic. To facilitate the study of interactions between microbial communities and pathogenic viruses under safe conditions, the infectious agent is generally inactivated prior to processing samples. The effect of this inactivation process in the microbiome is, however, unknown. Further, it is unclear whether biases introduced by inactivation methods are dependent on the sample type under study. Estimating the magnitude and nature of the changes induced by different methods in samples collected from various body sites thus provides important information for current and future studies that require inactivation of pathogenic agents.}, }
@article {pmid34596014, year = {2021}, author = {Kajova, M and Khawaja, T and Kangas, J and Mäkinen, H and Kantele, A}, title = {Import of multidrug-resistant bacteria from abroad through interhospital transfers, Finland, 2010-2019.}, journal = {Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin}, volume = {26}, number = {39}, pages = {}, pmid = {34596014}, issn = {1560-7917}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Drug Resistance, Multiple, Bacterial ; Enterobacteriaceae ; Finland/epidemiology ; Hospitals, University ; Humans ; *Methicillin-Resistant Staphylococcus aureus/genetics ; beta-Lactamases/genetics ; }, abstract = {BackgroundWhile 20-80% of regular visitors to (sub)tropical regions become colonised by extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE), those hospitalised abroad often also carry other multidrug-resistant (MDR) bacteria on return; the rates are presumed to be highest for interhospital transfers.AimThis observational study assessed MDR bacterial colonisation among patients transferred directly from hospitals abroad to Helsinki University Hospital. We investigated predisposing factors, clinical infections and associated fatalities.MethodsData were derived from screening and from diagnostic samples collected between 2010 and 2019. Risk factors of colonisation were identified by multivariable analysis. Microbiologically verified symptomatic infections and infection-related mortality were recorded during post-transfer hospitalisation.ResultsColonisation rates proved highest for transfers from Asia (69/96; 71.9%) and lowest for those within Europe (99/524; 18.9%). Of all 698 patients, 208 (29.8%) were colonised; among those, 163 (78.4%) carried ESBL-PE, 28 (13.5%) MDR Acinetobacter species, 25 (12.0%) meticillin-resistant Staphylococcus aureus, 25 (12.0%) vancomycin-resistant Enterococcus, 14 (6.7%) carbapenemase-producing Enterobacteriaceae, and 12 (5.8%) MDR Pseudomonas aeruginosa; 46 strains tested carbapenemase gene-positive. In multivariable analysis, geographical region, intensive care unit (ICU) treatment and antibiotic use abroad proved to be risk factors for colonisation. Clinical MDR infections, two of them fatal (1.0%), were recorded for 22 of 208 (10.6%) MDR carriers.ConclusionsColonisation by MDR bacteria was common among patients transferred from foreign hospitals. Region of hospitalisation, ICU treatment and antibiotic use were identified as predisposing factors. Within 30 days after transfer, MDR colonisation manifested as clinical infection in more than 10% of the carriers.}, }
@article {pmid34594028, year = {2021}, author = {Toni, T and Alverdy, J and Gershuni, V}, title = {Re-examining chemically defined liquid diets through the lens of the microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {18}, number = {12}, pages = {903-911}, pmid = {34594028}, issn = {1759-5053}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; }, mesh = {Critical Care/*history/methods ; Critical Illness/therapy ; Diet/adverse effects/*history/methods ; Dietary Fiber/microbiology/therapeutic use ; Food, Formulated/adverse effects/*history ; *Gastrointestinal Microbiome ; History, 20th Century ; Humans ; Malnutrition/diet therapy/history/microbiology ; Nutritional Support/*history/methods ; Parenteral Nutrition, Total/adverse effects/history/methods ; Perioperative Care/adverse effects/*history/methods ; United States ; }, abstract = {Trends in nutritional science are rapidly shifting as information regarding the value of eating unprocessed foods and its salutary effect on the human microbiome emerge. Unravelling the evolution and ecology by which humans have harboured a microbiome that participates in every facet of health and disease is daunting. Most strikingly, the host habitat has sought out naturally occurring foodstuff that can fulfil its own metabolic needs and also the needs of its microbiota, each of which remain inexorably connected to one another. With the introduction of modern medicine and complexities of critical care, came the assumption that the best way to feed a critically ill patient is by delivering fibre-free chemically defined sterile liquid foods (that is, total enteral nutrition). In this Perspective, we uncover the potential flaws in this assumption and discuss how emerging technology in microbiome sciences might inform the best method of feeding malnourished and critically ill patients.}, }
@article {pmid34589068, year = {2021}, author = {Buckel, W}, title = {Energy Conservation in Fermentations of Anaerobic Bacteria.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {703525}, pmid = {34589068}, issn = {1664-302X}, abstract = {Anaerobic bacteria ferment carbohydrates and amino acids to obtain energy for growth. Due to the absence of oxygen and other inorganic electron acceptors, the substrate of a fermentation has to serve as electron donor as well as acceptor, which results in low free energies as compared to that of aerobic oxidations. Until about 10 years ago, anaerobes were thought to exclusively use substrate level phosphorylation (SLP), by which only part of the available energy could be conserved. Therefore, anaerobes were regarded as unproductive and inefficient energy conservers. The discovery of electrochemical Na[+] gradients generated by biotin-dependent decarboxylations or by reduction of NAD[+] with ferredoxin changed this view. Reduced ferredoxin is provided by oxidative decarboxylation of 2-oxoacids and the recently discovered flavin based electron bifurcation (FBEB). In this review, the two different fermentation pathways of glutamate to ammonia, CO2, acetate, butyrate and H2 via 3-methylaspartate or via 2-hydroxyglutarate by members of the Firmicutes are discussed as prototypical examples in which all processes characteristic for fermentations occur. Though the fermentations proceed on two entirely different pathways, the maximum theoretical amount of ATP is conserved in each pathway. The occurrence of the 3-methylaspartate pathway in clostridia from soil and the 2-hydroxyglutarate pathway in the human microbiome of the large intestine is traced back to the oxygen-sensitivity of the radical enzymes. The coenzyme B12-dependent glutamate mutase in the 3-methylaspartate pathway tolerates oxygen, whereas 2-hydroxyglutaryl-CoA dehydratase is extremely oxygen-sensitive and can only survive in the gut, where the combustion of butyrate produced by the microbiome consumes the oxygen and provides a strict anaerobic environment. Examples of coenzyme B12-dependent eliminases are given, which in the gut are replaced by simpler extremely oxygen sensitive glycyl radical enzymes.}, }
@article {pmid34588993, year = {2021}, author = {Montanari, C and Parolisi, S and Borghi, E and Putignani, L and Bassanini, G and Zuvadelli, J and Bonfanti, C and Tummolo, A and Dionisi Vici, C and Biasucci, G and Burlina, A and Carbone, MT and Verduci, E}, title = {Dysbiosis, Host Metabolism, and Non-communicable Diseases: Trialogue in the Inborn Errors of Metabolism.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {716520}, pmid = {34588993}, issn = {1664-042X}, abstract = {Inborn errors of metabolism (IEMs) represent a complex system model, in need of a shift of approach exploring the main factors mediating the regulation of the system, internal or external and overcoming the traditional concept of biochemical and genetic defects. In this context, among the established factors influencing the metabolic flux, i.e., diet, lifestyle, antibiotics, xenobiotics, infectious agents, also the individual gut microbiota should be considered. A healthy gut microbiota contributes in maintaining human health by providing unique metabolic functions to the human host. Many patients with IEMs are on special diets, the main treatment for these diseases. Hence, IEMs represent a good model to evaluate how specific dietary patterns, in terms of macronutrients composition and quality of nutrients, can be related to a characteristic microbiota associated with a specific clinical phenotype ("enterophenotype"). In the present review, we aim at reporting the possible links existing between dysbiosis, a condition reported in IEMs patients, and a pro-inflammatory status, through an altered "gut-liver" cross-talk network and a major oxidative stress, with a repercussion on the health status of the patient, increasing the risk of non-communicable diseases (NCDs). On this basis, more attention should be paid to the nutritional status assessment and the clinical and biochemical signs of possible onset of comorbidities, with the goal of improving the long-term wellbeing in IEMs. A balanced intestinal ecosystem has been shown to positively contribute to patient health and its perturbation may influence the clinical spectrum of individuals with IEMs. For this, reaching eubiosis through the improvement of the quality of dietary products and mixtures, the use of pre-, pro- and postbiotics, could represent both a preventive and therapeutic strategy in these complex diseases.}, }
@article {pmid34588273, year = {2021}, author = {Kussmann, M and Obermueller, M and Spettel, K and Winkler, S and Aletaha, D}, title = {In vitro evaluation of disease-modifying antirheumatic drugs against rheumatoid arthritis associated pathogens of the oral microflora.}, journal = {RMD open}, volume = {7}, number = {3}, pages = {}, pmid = {34588273}, issn = {2056-5933}, mesh = {*Antirheumatic Agents/pharmacology/therapeutic use ; *Arthritis, Rheumatoid/drug therapy ; Humans ; Methotrexate/pharmacology/therapeutic use ; *Microbiota ; Sulfasalazine/pharmacology/therapeutic use ; }, abstract = {OBJECTIVES: In the past, the human microbiome has consistently been associated with rheumatoid arthritis (RA) and disease activity. Here, we investigate the antimicrobial activity of disease-modifying antirheumatic drugs (DMARDs) against typical representatives of the oral microflora that have been associated with RA.<br><br>METHODS: DMARDs were screened for antimicrobial activity against bacteria that are associated with the pathogenesis of the disease and/or frequently isolated from the oral microflora of patients with RA. Screening was done by an agar diffusion assay and minimum inhibitory concentrations (MICs) of antimicrobial active substances were then determined by broth dilution.<br><br>RESULTS: Aurothiomalate and sulfasalazine demonstrated broad-spectrum antimicrobial activity, but with MICs ranging from 18 to >280 &#xb5;g/mL and 150 to >600 &#xb5;g/mL, respectively, only at supratherapeutic concentrations. Methotrexate showed antimicrobial activity only against Fusobacterium nucleatum and Viridans streptococci. The corresponding MICs were 3.75 to >30 &#xb5;g/mL and 0.5-15 &#xb5;g/mL, respectively, thus at least for streptococci, within the therapeutically achievable range. No other DMARD tested showed antimicrobial activity in the agar diffusion screening assay.<br><br>CONCLUSION: Methotrexate, sulfasalazine and aurothiomalate showed antimicrobial activity against a broad spectrum of RA associated pathogens of the oral microflora. While methotrexate showed relevant antimicrobial activity, and to a more limited extent aurothiomalate, sulfasalazine was active only at far supratherapeutic systemic concentrations. Nevertheless, given the highly species-dependent antimicrobial activity and the multiple ways it can affect the human microbiome, our results suggest a link between antimicrobially active antirheumatic drugs and their potential effect in the treatment of RA.}, }
@article {pmid34587184, year = {2021}, author = {Chen, X and Liu, L and Chu, Q and Sun, S and Wu, Y and Tong, Z and Fang, W and Timko, MP and Fan, L}, title = {Large-scale identification of extracellular plant miRNAs in mammals implicates their dietary intake.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0257878}, pmid = {34587184}, issn = {1932-6203}, mesh = {Animal Feed/analysis ; Animals ; Brain Chemistry ; Carnivora/genetics ; Computational Biology/*methods ; Diet ; Female ; Herbivory/genetics ; Humans ; MicroRNAs/*genetics ; Milk, Human/chemistry ; Organ Specificity ; Plants/*genetics ; RNA, Plant/genetics ; Sample Size ; Sequence Analysis, RNA/*methods ; }, abstract = {Extracellular microRNAs (miRNAs) have been proposed to function in cross-kingdom gene regulation. Among these, plant-derived miRNAs of dietary origin have been reported to survive the harsh conditions of the human digestive system, enter the circulatory system, and regulate gene expression and metabolic function. However, definitive evidence supporting the presence of plant-derived miRNAs of dietary origin in mammals has been difficult to obtain due to limited sample sizes. We have developed a bioinformatics pipeline (ePmiRNA_finder) that provides strident miRNA classification and applied it to analyze 421 small RNA sequencing data sets from 10 types of human body fluids and tissues and comparative samples from carnivores and herbivores. A total of 35 miRNAs were identified that map to plants typically found in the human diet and these miRNAs were found in at least one human blood sample and their abundance was significantly different when compared to samples from human microbiome or cow. The plant-derived miRNA profiles were body fluid/tissue-specific and highly abundant in the brain and the breast milk samples, indicating selective absorption and/or the ability to be transported across tissue/organ barriers. Our data provide conclusive evidence for the presence of plant-derived miRNAs as a consequence of dietary intake and their cross-kingdom regulatory function within human circulating system.}, }
@article {pmid34587158, year = {2021}, author = {Mero, S and Timonen, S and Lääveri, T and Løfberg, S and Kirveskari, J and Ursing, J and Rombo, L and Kofoed, PE and Kantele, A}, title = {Prevalence of diarrhoeal pathogens among children under five years of age with and without diarrhoea in Guinea-Bissau.}, journal = {PLoS neglected tropical diseases}, volume = {15}, number = {9}, pages = {e0009709}, pmid = {34587158}, issn = {1935-2735}, mesh = {Bacteria/classification/genetics/*isolation &amp; purification ; Bacterial Infections/epidemiology/*microbiology ; Child, Preschool ; Diarrhea/epidemiology/*microbiology/*virology ; Feces/microbiology/virology ; Female ; Guinea-Bissau/epidemiology ; Humans ; Infant ; Male ; Virus Diseases/epidemiology/*virology ; Viruses/classification/genetics/*isolation &amp; purification ; }, abstract = {BACKGROUND: Childhood diarrhoea, a major cause of morbidity and mortality in low-income regions, remains scarcely studied in many countries, such as Guinea-Bissau. Stool sample drying enables later qPCR analyses of pathogens without concern about electricity shortages.<br><br>METHODS: Dried stool samples of children under five years treated at the Bandim Health Centre in Bissau, Guinea-Bissau were screened by qPCR for nine enteric bacteria, five viruses, and four parasites. The findings of children having and not having diarrhoea were compared in age groups 0-11 and 12-59 months.<br><br>RESULTS: Of the 429 children- 228 with and 201 without diarrhoea- 96.9% and 93.5% had bacterial, 62.7% and 44.3% viral, and 52.6% and 48.3% parasitic pathogen findings, respectively. Enteroaggregarive Escherichia coli (EAEC; 60.5% versus 66.7%), enteropathogenic E. coli (EPEC; 61.4% versus 62.7%), Campylobacter (53.2% versus 51.8%), and enterotoxigenic E. coli (ETEC; 54.4% versus 44.3%) were the most common bacterial pathogens. Diarrhoea was associated with enteroinvasive E. coli (EIEC)/Shigella (63.3%), ETEC (54.4%), astrovirus (75.0%), norovirus GII (72.6%) and Cryptosporidium (71.2%). The only pathogen associated with severe diarrhoea was EIEC/Shigella (p<0.001). EAEC was found more frequent among the infants, and EIEC/Shigella, Giardia duodenalis and Dientamoeba fragilis among the older children.<br><br>CONCLUSIONS: Stool pathogens proved common among all the children regardless of them having diarrhoea or not.}, }
@article {pmid34581596, year = {2021}, author = {Huus, KE and Ley, RE}, title = {Blowing Hot and Cold: Body Temperature and the Microbiome.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0070721}, pmid = {34581596}, issn = {2379-5077}, support = {//Max Planck Society/ ; //Max Planck Society/ ; }, abstract = {The intestinal microbiome influences host health, and its responsiveness to diet and disease is increasingly well studied. However, our understanding of the factors driving microbiome variation remain limited. Temperature is a core factor that controls microbial growth, but its impact on the microbiome remains to be fully explored. Although commonly assumed to be a constant 37°C, normal body temperatures vary across the animal kingdom, while individual body temperature is affected by multiple factors, including circadian rhythm, age, environmental temperature stress, and immune activation. Changes in body temperature via hypo- and hyperthermia have been shown to influence the gut microbiota in a variety of animals, with consistent effects on community diversity and stability. It is known that temperature directly modulates the growth and virulence of gastrointestinal pathogens; however, the effect of temperature on gut commensals is not well studied. Further, body temperature can influence other host factors, such as appetite and immunity, with indirect effects on the microbiome. In this minireview, we discuss the evidence linking body temperature and the intestinal microbiome and their implications for microbiome function during hypothermia, heat stress, and fever.}, }
@article {pmid34580445, year = {2021}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {6}, number = {10}, pages = {1309-1318}, pmid = {34580445}, issn = {2058-5276}, support = {R01 DK123749/DK/NIDDK NIH HHS/United States ; U24 CA224319/CA/NCI NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/classification/genetics/*isolation &amp; purification ; Benchmarking ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Metagenome/genetics ; Recurrence ; Tissue Donors ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has been successfully applied to treat recurrent Clostridium difficile infection in humans, but a precise method to measure which bacterial strains stably engraft in recipients and evaluate their association with clinical outcomes is lacking. We assembled a collection of >1,000 different bacterial strains that were cultured from the fecal samples of 22 FMT donors and recipients. Using our strain collection combined with metagenomic sequencing data from the same samples, we developed a statistical approach named Strainer for the detection and tracking of bacterial strains from metagenomic sequencing data. We applied Strainer to evaluate a cohort of 13 FMT longitudinal clinical interventions and detected stable engraftment of 71% of donor microbiota strains in recipients up to 5 years post-FMT. We found that 80% of recipient gut bacterial strains pre-FMT were eliminated by FMT and that post-FMT the strains present persisted up to 5 years later, together with environmentally acquired strains. Quantification of donor bacterial strain engraftment in recipients independently explained (precision 100%, recall 95%) the clinical outcomes (relapse or success) after initial and repeat FMT. We report a compendium of bacterial species and strains that consistently engraft in recipients over time that could be used in defined live biotherapeutic products as an alternative to FMT. Our analytical framework and Strainer can be applied to systematically evaluate either FMT or defined live bacterial therapeutic studies by quantification of strain engraftment in recipients.}, }
@article {pmid34572284, year = {2021}, author = {Dietert, RR}, title = {Microbiome First Medicine in Health and Safety.}, journal = {Biomedicines}, volume = {9}, number = {9}, pages = {}, pmid = {34572284}, issn = {2227-9059}, abstract = {Microbiome First Medicine is a suggested 21st century healthcare paradigm that prioritizes the entire human, the human superorganism, beginning with the microbiome. To date, much of medicine has protected and treated patients as if they were a single species. This has resulted in unintended damage to the microbiome and an epidemic of chronic disorders [e.g., noncommunicable diseases and conditions (NCDs)]. Along with NCDs came loss of colonization resistance, increased susceptibility to infectious diseases, and increasing multimorbidity and polypharmacy over the life course. To move toward sustainable healthcare, the human microbiome needs to be front and center. This paper presents microbiome-human physiology from the view of systems biology regulation. It also details the ongoing NCD epidemic including the role of existing drugs and other factors that damage the human microbiome. Examples are provided for two entryway NCDs, asthma and obesity, regarding their extensive network of comorbid NCDs. Finally, the challenges of ensuring safety for the microbiome are detailed. Under Microbiome-First Medicine and considering the importance of keystone bacteria and critical windows of development, changes in even a few microbiota-prioritized medical decisions could make a significant difference in health across the life course.}, }
@article {pmid34566921, year = {2021}, author = {Jaakkola, K and Virtanen, K and Lahti, P and Keto-Timonen, R and Lindström, M and Korkeala, H}, title = {Comparative Genome Analysis and Spore Heat Resistance Assay Reveal a New Component to Population Structure and Genome Epidemiology Within Clostridium perfringens Enterotoxin-Carrying Isolates.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {717176}, pmid = {34566921}, issn = {1664-302X}, abstract = {Clostridium perfringens causes a variety of human and animal enteric diseases including food poisoning, antibiotic-associated diarrhea, and necrotic enteritis. Yet, the reservoirs of enteropathogenic enterotoxin-producing strains remain unknown. We conducted a genomic comparison of 290 strains and a heat resistance phenotyping of 30 C. perfringens strains to elucidate the population structure and ecology of this pathogen. C. perfringens genomes shared a conserved genetic backbone with more than half of the genes of an average genome conserved in >95% of strains. The cpe-carrying isolates were found to share genetic context: the cpe-carrying plasmids had different distribution patterns within the genetic lineages and the estimated pan genome of cpe-carrying isolates had a larger core genome and a smaller accessory genome compared to that of 290 strains. We characterize cpe-negative strains related to chromosomal cpe-carrying strains elucidating the origin of these strains and disclose two distinct groups of chromosomal cpe-carrying strains with different virulence characteristics, spore heat resistance properties, and, presumably, ecological niche. Finally, an antibiotic-associated diarrhea isolate carrying two copies of the enterotoxin cpe gene and the associated genetic lineage with the potential for the emergence of similar strains are outlined. With C. perfringens as an example, implications of input genome quality for pan genome analysis are discussed. Our study furthers the understanding of genome epidemiology and population structure of enteropathogenic C. perfringens and brings new insight into this important pathogen and its reservoirs.}, }
@article {pmid34566693, year = {2021}, author = {Busing, JD and Buendia, M and Choksi, Y and Hiremath, G and Das, SR}, title = {Microbiome in Eosinophilic Esophagitis-Metagenomic, Metatranscriptomic, and Metabolomic Changes: A Systematic Review.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {731034}, pmid = {34566693}, issn = {1664-042X}, support = {IK2 BX004648/BX/BLRD VA/United States ; }, abstract = {Background: Our understanding of human gut microbiota has expanded in recent years with the introduction of high-throughput sequencing methods. These technologies allow for the study of metagenomic, metatranscriptomic, and metabolomic bacterial alterations as they relate to human disease. Work in this area has described the human gut microbiome in both healthy individuals and those with chronic gastrointestinal diseases, such as eosinophilic esophagitis (EoE). Objectives: A systematic review of the current available literature on metagenomic, metatranscriptomic, and metabolomic changes in EoE was performed. Methods: This review was performed following the PRISMA guidelines for reporting systematic reviews and meta-analyses. All relevant publications up to March 2021 were retrieved using the search engines PubMed, Google Scholar, and Web of Science. They were then extracted, assessed, and reviewed. Only original studies published in English were included. Results: A total of 46 potential manuscripts were identified for review. Twelve met criteria for further review based on relevance screening and 9 met criteria for inclusion, including 6 studies describing the microbiome in EoE and 3 detailing metabolomic/tissue biochemistry alterations in EoE. No published studies examined metatranscriptomic changes. Samples for microbiome analysis were obtained via esophageal biopsy (n = 3), esophageal string test (n = 1), salivary sampling (n = 1), or stool specimen (n = 1). Samples analyzing tissue biochemistry were obtained via esophageal biopsy (n = 2) and blood plasma (n = 1). There were notable differences in how samples were collected and analyzed. Metabolomic and tissue biochemical alterations were described using Raman spectroscopy, which demonstrated distinct differences in the spectral intensities of glycogen, lipid, and protein content compared to controls. Finally, research in proteomics identified an increase in the pro-fibrotic protein thrombospondin-1 in patients with EoE compared with controls. Conclusions: While there are notable changes in the microbiome, these differ with the collection technique and method of analysis utilized. Techniques characterizing metabolomics and tissue biochemistry are now being utilized to further study patients with EoE. The lack of published data related to the human microbiome, metagenome, metatranscriptome, and metabolome in patients with EoE highlights the need for further research in these areas.}, }
@article {pmid34560884, year = {2021}, author = {Kumpitsch, C and Fischmeister, FPS and Mahnert, A and Lackner, S and Wilding, M and Sturm, C and Springer, A and Madl, T and Holasek, S and Högenauer, C and Berg, IA and Schoepf, V and Moissl-Eichinger, C}, title = {Reduced B12 uptake and increased gastrointestinal formate are associated with archaeome-mediated breath methane emission in humans.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {193}, pmid = {34560884}, issn = {2049-2618}, support = {I 3792/FWF_/Austrian Science Fund FWF/Austria ; P 28854/FWF_/Austrian Science Fund FWF/Austria ; W 1226/FWF_/Austrian Science Fund FWF/Austria ; }, mesh = {Adult ; Animals ; Female ; Formates ; Gastrointestinal Tract ; Humans ; Male ; Metagenomics ; *Methane ; *Methanobrevibacter/genetics ; Rumen ; Young Adult ; }, abstract = {BACKGROUND: Methane is an end product of microbial fermentation in the human gastrointestinal tract. This gas is solely produced by an archaeal subpopulation of the human microbiome. Increased methane production has been associated with abdominal pain, bloating, constipation, IBD, CRC or other conditions. Twenty percent of the (healthy) Western populations innately exhale substantially higher amounts (>5 ppm) of this gas. The underlying principle for differential methane emission and its effect on human health is not sufficiently understood.<br><br>RESULTS: We assessed the breath methane content,&#xa0;the gastrointestinal microbiome,&#xa0;its function&#xa0;and metabolome, and dietary intake of one-hundred healthy young adults (female: n = 52, male: n = 48; mean age =24.1). On the basis of the amount of methane emitted, participants were grouped into high methane emitters (CH4 breath content 5-75 ppm) and low emitters (CH4 < 5 ppm). The microbiomes of high methane emitters were characterized by a 1000-fold increase in Methanobrevibacter smithii. This archaeon co-occurred with a bacterial community specialized on dietary fibre degradation, which included members of Ruminococcaceae and Christensenellaceae. As confirmed by metagenomics and metabolomics, the biology of high methane producers was further characterized by increased formate and acetate levels in the gut. These metabolites were strongly correlated with dietary habits, such as vitamin, fat and fibre intake, and microbiome function, altogether driving archaeal methanogenesis.<br><br>CONCLUSIONS: This study enlightens the complex, multi-level interplay of host diet, genetics and microbiome composition/function leading to two fundamentally different gastrointestinal phenotypes and identifies novel points of therapeutic action in methane-associated disorders. Video Abstract.}, }
@article {pmid34559283, year = {2021}, author = {Bajerski, F and Nagel, M and Overmann, J}, title = {Microbial occurrence in liquid nitrogen storage tanks: a challenge for cryobanking?.}, journal = {Applied microbiology and biotechnology}, volume = {105}, number = {20}, pages = {7635-7650}, pmid = {34559283}, issn = {1432-0614}, mesh = {*Cryopreservation ; Gases ; Humans ; *Nitrogen ; Temperature ; }, abstract = {Modern biobanks maintain valuable living materials for medical diagnostics, reproduction medicine, and conservation purposes. To guarantee high quality during long-term storage and to avoid metabolic activities, cryostorage is often conducted in the N2 vapour phase or in liquid nitrogen (LN) at temperatures below - 150 °C. One potential risk of cryostorage is microbial cross contamination in the LN storage tanks. The current review summarises data on the occurrence of microorganisms that may compromise the safety and quality of biological materials during long-term storage. We assess the potential for the microbial contamination of LN in storage tanks holding different biological materials based on the detection by culture-based and molecular approaches. The samples themselves, the LN, the human microbiome, and the surrounding environment are possible routes of contamination and can cause cross contaminations via the LN phase. In general, the results showed that LN is typically not the source of major contaminations and only a few studies provided evidence for a risk of microbial cross contamination. So far, culture-based and culture-independent techniques detected only low amounts of microbial cells, indicating that cross contamination may occur at a very low frequency. To further minimise the potential risk of microbial cross contaminations, we recommend reducing the formation of ice crystals in cryotanks that can entrap environmental microorganisms and using sealed or second sample packing. A short survey demonstrated the awareness for microbial contaminations of storage containers among different culture collections. Although most participants consider the risk of cross contaminations in LN storage tanks as low, they prevent potential contaminations by using sealed devices and - 150 °C freezers. It is concluded that the overall risk for cross contaminations in biobanks is relatively low when following standard operating procedures (SOPs). We evaluated the potential sources in detail and summarised our results in a risk assessment spreadsheet which can be used for the quality management of biobanks. KEY POINTS: • Identification of potential contaminants and their sources in LN storage tanks. • Recommendations to reduce this risk of LN storage tank contamination. • Development of a risk assessment spreadsheet to support quality management.}, }
@article {pmid34559210, year = {2021}, author = {Klein, K and Garkov, D and Rütschlin, S and Böttcher, T and Schreiber, F}, title = {QSDB-a graphical Quorum Sensing Database.}, journal = {Database : the journal of biological databases and curation}, volume = {2021}, number = {}, pages = {}, pmid = {34559210}, issn = {1758-0463}, mesh = {Humans ; *Microbiota ; *Quorum Sensing ; }, abstract = {The human microbiome is largely shaped by the chemical interactions of its microbial members, which includes cross-talk via shared signals or quenching of the signalling of other species. Quorum sensing is a process that allows microbes to coordinate their behaviour in dependence of their population density and to adjust gene expression accordingly. We present the Quorum Sensing Database (QSDB), a comprehensive database of all published sensing and quenching relations between organisms and signalling molecules of the human microbiome, as well as an interactive web interface that allows browsing the database, provides graphical depictions of sensing mechanisms as Systems Biology Graphical Notation diagrams and links to other databases. Database URL: QSDB (Quorum Sensing DataBase) is freely available via an interactive web interface and as a downloadable csv file at http://qsdb.org.}, }
@article {pmid34555832, year = {2022}, author = {Zafar, H and Saier, MH}, title = {Comparative Analyses of the Transport Proteins Encoded within the Genomes of nine Bifidobacterium Species.}, journal = {Microbial physiology}, volume = {32}, number = {1-2}, pages = {30-44}, pmid = {34555832}, issn = {2673-1673}, support = {R01 GM077402/GM/NIGMS NIH HHS/United States ; }, mesh = {Bifidobacterium/genetics ; *Bifidobacterium bifidum ; Carrier Proteins/metabolism ; *Gastrointestinal Microbiome/genetics ; Humans ; Infant, Newborn ; *Probiotics ; }, abstract = {The human microbiome influences human health in both negative and positive ways. Studies on the transportomes of these organisms yield information that may be utilized for various purposes, including the identification of novel drug targets and the manufacture of improved probiotic strains. Moreover, these genomic analyses help to improve our understanding of the physiology and metabolic capabilities of these organisms. The present study is a continuation of our studies on the transport proteins of the major gut microbes. Bifidobacterium species are essential members of the human gut microbiome, and they initiate colonization of the gut at birth, providing health benefits that last a lifetime. In this study we analyze the transportomes of nine bifidobacterial species: B. adolescentis, B. animalis, B. bifidum, B. breve, B. catenulatum, B. dentium, B. longum subsp. infantis, B. longum subsp. longum, and B. pseudocatenulatum. All of these species have proven probiotic characteristics and exert beneficial effects on human health. Surprisingly, we found that all nine of these species have similar pore-forming toxins and drug exporters that may play roles in pathogenesis. These species have transporters for amino acids, carbohydrates, and proteins, essential for their organismal lifestyles and adaption to their respective ecological niches. The strictly probiotic species, B. bifidum, however, contains fewer such transporters, thus indicative of limited interactions with host cells and other gut microbial counterparts. The results of this study were compared with those of our previous studies on the transportomes of multiple species of Bacteroides, Escherichia coli/Salmonella, and Lactobacillus. Overall, bifidobacteria have larger transportomes (based on percentages of total proteins) than the previously examined groups of bacterial species, with a preference for primary active transport systems over secondary carriers. Taken together, these results provide useful information about the physiologies and pathogenic potentials of these probiotic organisms as reflected by their transportomes.}, }
@article {pmid34554215, year = {2022}, author = {Bodein, A and Scott-Boyer, MP and Perin, O and Lê Cao, KA and Droit, A}, title = {timeOmics: an R package for longitudinal multi-omics data integration.}, journal = {Bioinformatics (Oxford, England)}, volume = {38}, number = {2}, pages = {577-579}, doi = {10.1093/bioinformatics/btab664}, pmid = {34554215}, issn = {1367-4811}, support = {//Research and Innovation chair L'Or&#xe9;al in Digital Biology/ ; GNT1159458//National Health and Medical Research Council (NHMRC) Career Development fellowship/ ; }, mesh = {Humans ; *Genomics/methods ; *Multiomics ; Cluster Analysis ; }, abstract = {MOTIVATION: Multi-omics data integration enables the global analysis of biological systems and discovery of new biological insights. Multi-omics experimental designs have been further extended with a longitudinal dimension to study dynamic relationships between molecules. However, methods that integrate longitudinal multi-omics data are still in their infancy.<br><br>RESULTS: We introduce the R package timeOmics, a generic analytical framework for the integration of longitudinal multi-omics data. The framework includes pre-processing, modeling and clustering to identify molecular features strongly associated with time. We illustrate this framework in a case study to detect seasonal patterns of mRNA, metabolites, gut taxa and clinical variables in patients with diabetes mellitus from the integrative Human Microbiome Project.<br><br>timeOmics is available on Bioconductor and github.com/abodein/timeOmics.<br><br>SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid34546072, year = {2021}, author = {Flores Ramos, S and Brugger, SD and Escapa, IF and Skeete, CA and Cotton, SL and Eslami, SM and Gao, W and Bomar, L and Tran, TH and Jones, DS and Minot, S and Roberts, RJ and Johnston, CD and Lemon, KP}, title = {Genomic Stability and Genetic Defense Systems in Dolosigranulum pigrum, a Candidate Beneficial Bacterium from the Human Microbiome.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0042521}, pmid = {34546072}, issn = {2379-5077}, support = {R01 DE027850/DE/NIDCR NIH HHS/United States ; R01 GM117174/GM/NIGMS NIH HHS/United States ; Stimulus Pilot Grant//The Forsyth Institute/ ; P3SMP3_155315//Swiss National Science Foundation and Swiss Foundation for Grants in Biology and Medicine/ ; R01 DE027850/DE/NIDCR NIH HHS/United States ; R01 GM117174/GM/NIGMS NIH HHS/United States ; 16B065//Novartis Stiftung&#xa0;f&#xfc;r&#xa0;Medizinisch-Biologische Forschung (Novartis Foundation for Medical-Biological Research)/ ; 1449/M//Promedica Stiftung/ ; }, abstract = {Dolosigranulum pigrum is positively associated with indicators of health in multiple epidemiological studies of human nasal microbiota. Knowledge of the basic biology of D. pigrum is a prerequisite for evaluating its potential for future therapeutic use; however, such data are very limited. To gain insight into D. pigrum's chromosomal structure, pangenome, and genomic stability, we compared the genomes of 28 D. pigrum strains that were collected across 20 years. Phylogenomic analysis showed closely related strains circulating over this period and closure of 19 genomes revealed highly conserved chromosomal synteny. Gene clusters involved in the mobilome and in defense against mobile genetic elements (MGEs) were enriched in the accessory genome versus the core genome. A systematic analysis for MGEs identified the first candidate D. pigrum prophage and insertion sequence. A systematic analysis for genetic elements that limit the spread of MGEs, including restriction modification (RM), CRISPR-Cas, and deity-named defense systems, revealed strain-level diversity in host defense systems that localized to specific genomic sites, including one RM system hot spot. Analysis of CRISPR spacers pointed to a wealth of MGEs against which D. pigrum defends itself. These results reveal a role for horizontal gene transfer and mobile genetic elements in strain diversification while highlighting that in D. pigrum this occurs within the context of a highly stable chromosomal organization protected by a variety of defense mechanisms. IMPORTANCE Dolosigranulum pigrum is a candidate beneficial bacterium with potential for future therapeutic use. This is based on its positive associations with characteristics of health in multiple studies of human nasal microbiota across the span of human life. For example, high levels of D. pigrum nasal colonization in adults predicts the absence of Staphylococcus aureus nasal colonization. Also, D. pigrum nasal colonization in young children is associated with healthy control groups in studies of middle ear infections. Our analysis of 28 genomes revealed a remarkable stability of D. pigrum strains colonizing people in the United States across a 20-year span. We subsequently identified factors that can influence this stability, including genomic stability, phage predators, the role of MGEs in strain-level variation, and defenses against MGEs. Finally, these D. pigrum strains also lacked predicted virulence factors. Overall, these findings add additional support to the potential for D. pigrum as a therapeutic bacterium.}, }
@article {pmid34545840, year = {2021}, author = {Dery, KJ and Kupiec-Weglinski, JW and Dong, TS}, title = {The human microbiome in transplantation: the past, present, and future.}, journal = {Current opinion in organ transplantation}, volume = {26}, number = {6}, pages = {595-602}, doi = {10.1097/MOT.0000000000000922}, pmid = {34545840}, issn = {1531-7013}, mesh = {High-Throughput Nucleotide Sequencing ; Humans ; *Metagenomics ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: Over the past 20 years, DNA sequencing technology has transformed human microbiome research from identity characterizations to metagenomics approaches that reveal how microbials correlate with human health and disease. New studies are showing unprecedented opportunity for deep characterization of the human microbial ecosystem, with benefits to the field of organ transplantation.<br><br>RECENT FINDINGS: In the present review, we focus on past milestones of human-associated microbiota research, paying homage to microbiota pioneers. We highlight the role of sequencing efforts to provide insights beyond taxonomic identification. Recent advances in microbiome technology is now integrating high-throughput datasets, giving rise to multi'omics - a comprehensive assessment modeling dynamic biologic networks. Studies that show benefits and mechanisms in peritransplant antibiotic (Abx)-conditioned recipients are reviewed. We describe how next-generation microbial sequencing has the potential to combine with new technologies like phage therapy (PT) to translate into life-saving therapeutics.<br><br>SUMMARY: The study of the microbiome is advancing the field of transplantation by enhancing our knowledge of precision medicine. Sequencing technology has allowed the use of the microbiome as a biomarker to risk stratify patients. Further research is needed to better understand how microbiomes shape transplantation outcomes while informing immune cell - tissue crosstalk platforms.}, }
@article {pmid34536920, year = {2022}, author = {Samarrai, R and Frank, S and Lum, A and Woodis, K and Weinstock, G and Roberts, D}, title = {Defining the microbiome of the head and neck: A contemporary review.}, journal = {American journal of otolaryngology}, volume = {43}, number = {1}, pages = {103224}, doi = {10.1016/j.amjoto.2021.103224}, pmid = {34536920}, issn = {1532-818X}, mesh = {Anti-Bacterial Agents/therapeutic use ; Dysbiosis/microbiology ; Ear/*microbiology ; Head/*microbiology ; Humans ; *Microbiota ; Neck/*microbiology ; }, abstract = {OBJECTIVE: The purpose of this paper is to define the microbiome of the head and neck by characterizing and distinguishing the commensal bacteria from pathogenic species.<br><br>STUDY DESIGN: Literature review.<br><br>METHODS: Pubmed and Google scholar databases were queried for relevant articles. Keywords such as "middle ear microbiome", "outer ear microbiome", "sinonasal microbiome", "tonsil microbiome", and "laryngeal microbiome" were utilized separately to identify articles pertaining to each topic of study. All applicable abstracts were chosen for initial review and relevant abstracts were then selected for review of the full texts. Articles that did not study the human microbiome, those not written primarily in English, those that were not readily available for full review, and case reports were excluded from the study.<br><br>RESULTS: Limited studies that investigate the microbial environments of isolated anatomic subsites in the head and neck exist, however the comprehensive microbiome of the head and neck has yet to be completely defined. Based on this review, various studies of the ears, larynx, tonsils and sinus microbiomes exist and yield valuable information, however they are limited in scope and anatomic subsite. In this literature review, these studies are compiled in order to create a comprehensive text inclusive of the known microbial elements of the major anatomic subsites of the head and neck, namely the tonsils, larynx, sinus, outer ear and middle ear.<br><br>CONCLUSIONS: The significance of the human microbiome in identifying and preventing disease has been established in various physiologic systems, however there is limited research on the microbiome of the head and neck. Understanding the microbiome of the head and neck can help differentiate disease-prone patients from normal patients and guide treatment regimens and antibiotic usage, to aid in resistance control and limit adverse effects of antibiotic overuse. Understanding the elements that lead to dysbiosis can help treat and even prevent common conditions as tonsillitis and rhinosinusitis. In this review, we provide a comprehensive review to serve as an initial background for future studies to define the head and neck microbiome distinguished by all relevant subsites.}, }
@article {pmid34531833, year = {2021}, author = {Ezzamouri, B and Shoaie, S and Ledesma-Amaro, R}, title = {Synergies of Systems Biology and Synthetic Biology in Human Microbiome Studies.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {681982}, pmid = {34531833}, issn = {1664-302X}, abstract = {A number of studies have shown that the microbial communities of the human body are integral for the maintenance of human health. Advances in next-generation sequencing have enabled rapid and large-scale quantification of the composition of microbial communities in health and disease. Microorganisms mediate diverse host responses including metabolic pathways and immune responses. Using a system biology approach to further understand the underlying alterations of the microbiota in physiological and pathological states can help reveal potential novel therapeutic and diagnostic interventions within the field of synthetic biology. Tools such as biosensors, memory arrays, and engineered bacteria can rewire the microbiome environment. In this article, we review the computational tools used to study microbiome communities and the current limitations of these methods. We evaluate how genome-scale metabolic models (GEMs) can advance our understanding of the microbe-microbe and microbe-host interactions. Moreover, we present how synergies between these system biology approaches and synthetic biology can be harnessed in human microbiome studies to improve future therapeutics and diagnostics and highlight important knowledge gaps for future research in these rapidly evolving fields.}, }
@article {pmid34531252, year = {2022}, author = {Pinto, D and Trink, A and Giuliani, G and Rinaldi, F}, title = {Protective effects of sunscreen (50+) and octatrienoic acid 0.1% in actinic keratosis and UV damages.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {70}, number = {1}, pages = {92-98}, pmid = {34531252}, issn = {1708-8267}, mesh = {Humans ; *Keratosis, Actinic/prevention &amp; control ; Skin ; Sun Protection Factor ; Sunburn/*drug therapy/prevention &amp; control ; Sunscreening Agents/*pharmacology/therapeutic use ; Ultraviolet Rays/*adverse effects ; }, abstract = {Actinic keratosis is a form of dysplastic epidermal lesion resulting from chronic and excessive UV exposure with a certain risk of becoming cancerous. Current guidelines advocated the use of sunscreens to prevent photodamage. An efficient photoprotection must involve both primary protective factors such as UV filters and secondary factors (eg, antioxidants) able to disrupt the photochemical and genetic cascade triggered by UVs. An in vitro model of human skin (Phenion FT) was used to assess the photoprotective potential of a sunscreen containing inorganic sun-filters (50+ SPF) and 0.1% octatrienoic acid (KERA'+) after UVA (10 J/cm[2]) and UVB (25 mJ/cm[2]) by means of evaluation of the number of sunburn cells (SBCs) and apoptotic keratinocytes. Also resulting alterations in the gene expression of markers involved in apoptosis (Tumor protein 53), inflammation/immunosuppression (IL-6 and IL-8), oxidative stress (oxidative stress response enzyme heme oxygenase 1), remodeling (metalloproteinase 1) and cell-cell adhesion (E-cadherin) were investigated. Gene expression was investigated using quantitative real-time PCR. This work demonstrated that the sunscreen preparations under study (with and without 0.1% octatrienoic acid, respectively) can be distinguished about their ability to prevent UVs-induced damage. Synergism between the inorganic filters and 0.1% octatrienoic acid was found (KERA'+) on all end points analyzed and this effect was found to be statistically significant (p<0.05). Our data revealed that topical application of a sunscreen containing inorganic filters (50+SPF) and 0.1% octatrienoic acid can protect from SBC formation, reduce the number of apoptotic keratinocytes and protect from the main molecular alterations caused by UV radiations.}, }
@article {pmid34525400, year = {2021}, author = {Giufrè, M and Mazzolini, E and Cerquetti, M and Brusaferro, S and , }, title = {Extended-spectrum β-lactamase-producing Escherichia coli from extraintestinal infections in humans and from food-producing animals in Italy: a 'One Health' study.}, journal = {International journal of antimicrobial agents}, volume = {58}, number = {5}, pages = {106433}, doi = {10.1016/j.ijantimicag.2021.106433}, pmid = {34525400}, issn = {1872-7913}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/*genetics ; Cattle ; Cross-Sectional Studies ; Drug Resistance, Multiple, Bacterial/*genetics ; Escherichia coli/drug effects/*genetics/isolation &amp; purification ; Escherichia coli Infections/*veterinary ; Escherichia coli Proteins/genetics ; Humans ; Italy ; Microbial Sensitivity Tests ; Molecular Epidemiology ; Multilocus Sequence Typing ; Poultry/microbiology ; Swine/microbiology ; beta-Lactamases/*genetics ; }, abstract = {Recently, Escherichia coli producing extended-spectrum β-lactamases (ESBLs) have become a serious public-health problem, and food-producing animals (FPAs) have been suggested as a potential reservoir/source. This study aimed to compare ESBL-producing E. coli isolates from different sources. ESBL-producing E. coli isolates were collected from humans (n = 480) and FPAs (n = 445) in Italy (2016-2017). Isolates were screened for the presence of ESBL and carbapenemase genes and were classified according to phylogenetic group and MLST genotyping. The genes mcr-1 to -5 were searched for in colistin-resistant isolates. CTX-M was the most frequent ESBL type both in human and animal isolates. CTX-M-15 prevailed in humans (75.0%) and cattle (51.1%) but not in poultry (36.6%). CTX-M-1 was common (58.3%) in pigs. SHV-type and CMY-2-like were found in FPAs, especially in poultry (17.0% and 29.9%, respectively). Additionally, 29 isolates were mcr-1 carriers (3 from humans and 26 from FPAs). No carbapenemase genes were detected. Human isolates mostly belonged to phylogroup B2 (76.5%). Animal isolates were distributed among groups A (35.7%), B1 (26.1%) and C (12.4%). Few animal isolates (almost all from poultry) were classified into group B2 (4.3%). Most human isolates (83.4%) belonged to the pandemic ST131 clone and frequently carried CTX-M-15 (75.9%). ST131 was rarely detected in FPAs (three isolates from poultry). Nineteen STs were shared in both sources, with ST10, ST410 and ST69 being more frequently detected. Potential exchange of ESBL genes from animals to humans is feasible, underlying the need for strict monitoring based on a 'One Health' approach.}, }
@article {pmid34524796, year = {2021}, author = {Wernke, KM and Tirla, A and Xue, M and Surovtseva, YV and Menges, FS and Herzon, SB}, title = {Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure-Activity Relationships and Facilitates Mechanism of Action Studies.}, journal = {Journal of the American Chemical Society}, volume = {143}, number = {38}, pages = {15824-15833}, doi = {10.1021/jacs.1c07559}, pmid = {34524796}, issn = {1520-5126}, support = {T32 GM067543/GM/NIGMS NIH HHS/United States ; R01 CA215553/CA/NCI NIH HHS/United States ; }, mesh = {DNA/chemistry ; Escherichia coli/genetics ; Escherichia coli Proteins/*chemical synthesis ; Humans ; Microbiota/genetics ; Molecular Conformation ; Multigene Family ; Mutagens/metabolism ; Mutation ; Oxidation-Reduction ; Peptides/*chemical synthesis ; Phenotype ; Polyketides/*chemical synthesis ; Protein Binding ; Structure-Activity Relationship ; }, abstract = {Colibactin is a genotoxic metabolite produced by commensal-pathogenic members of the human microbiome that possess the clb (aka pks) biosynthetic gene cluster. clb[+] bacteria induce tumorigenesis in models of intestinal inflammation and have been causally linked to oncogenesis in humans. While colibactin is believed underlie these effects, it has not been possible to study the molecule directly due to its instability. Herein, we report the synthesis and biological studies of colibactin 742 (4), a stable colibactin derivative. We show that colibactin 742 (4) induces DNA interstrand-cross-links, activation of the Fanconi Anemia DNA repair pathway, and G2/M arrest in a manner similar to clb[+]E. coli. The linear precursor 9, which mimics the biosynthetic precursor to colibactin, also recapitulates the bacterial phenotype. In the course of this work, we discovered a novel cyclization pathway that was previously undetected in MS-based studies of colibactin, suggesting a refinement to the natural product structure and its mode of DNA binding. Colibactin 742 (4) and its precursor 9 will allow researchers to study colibactin's genotoxic effects independent of the producing organism for the first time.}, }
@article {pmid34523995, year = {2021}, author = {Brycki, JD and Chen See, JR and Letson, GR and Emlet, CS and Unverdorben, LV and Heibeck, NS and Brislawn, CJ and Buonaccorsi, VP and Chan, JP and Lamendella, R}, title = {Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0049821}, pmid = {34523995}, issn = {2165-0497}, support = {R15 AG052933/AG/NIA NIH HHS/United States ; R15 AG063103/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*genetics/metabolism ; Animals ; Caenorhabditis elegans/genetics/growth &amp; development/metabolism/*microbiology ; Disease Models, Animal ; Escherichia coli/*genetics/metabolism ; Escherichia coli Proteins/*genetics/metabolism ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Transcriptome ; }, abstract = {Host-bacterial interactions over the course of aging are understudied due to complexities of the human microbiome and challenges of collecting samples that span a lifetime. To investigate the role of host-microbial interactions in aging, we performed transcriptomics using wild-type Caenorhabditis elegans (N2) and three long-lived mutants (daf-2, eat-2, and asm-3) fed Escherichia coli OP50 and sampled at days 5, 7.5, and 10 of adulthood. We found host age is a better predictor of the E. coli expression profiles than host genotype. Specifically, host age was associated with clustering (permutational multivariate analysis of variance [PERMANOVA], P = 0.001) and variation (Adonis, P = 0.001, R[2] = 11.5%) among E. coli expression profiles, whereas host genotype was not (PERMANOVA, P > 0.05; Adonis, P > 0.05, R[2] = 5.9%). Differential analysis of the E. coli transcriptome yielded 22 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 100 KEGG genes enriched when samples were grouped by time point [LDA, linear discriminant analysis; log(LDA), ≥2; P ≤ 0.05], including several involved in biofilm formation. Coexpression analysis of host and bacterial genes yielded six modules of C. elegans genes that were coexpressed with one bacterial regulator gene over time. The three most significant bacterial regulators included genes relating to biofilm formation, lipopolysaccharide production, and thiamine biosynthesis. Age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, building on a growing literature of host-microbial interactions. IMPORTANCE Previous research has reported effects of the microbiome on health span and life span of Caenorhabditis elegans, including interactions with evolutionarily conserved pathways in humans. We build on this literature by reporting the gene expression of Escherichia coli OP50 in wild-type (N2) and three long-lived mutants of C. elegans. The manuscript represents the first study, to our knowledge, to perform temporal host-microbial transcriptomics in the model organism C. elegans. Understanding changes to the microbial transcriptome over time is an important step toward elucidating host-microbial interactions and their potential relationship to aging. We found that age was significantly associated with clustering and variation among transcriptomic samples, supporting the idea that microbes are active and plastic within C. elegans throughout life. Coexpression analysis further revealed interactions between E. coli and C. elegans that occurred over time, which contributes to our growing knowledge about host-microbial interactions.}, }
@article {pmid34522484, year = {2021}, author = {Patel, P and Poudel, A and Kafle, S and Thapa Magar, M and Cancarevic, I}, title = {Influence of Microbiome and Antibiotics on the Efficacy of Immune Checkpoint Inhibitors.}, journal = {Cureus}, volume = {13}, number = {8}, pages = {e16829}, pmid = {34522484}, issn = {2168-8184}, abstract = {The human microbiome mainly consists of bacteria and interacts closely with the immune system. Immune checkpoint inhibitors (ICI) are used to treat several types of cancers. Recently, it has been identified that the gut microbiome plays a role in the effectiveness of immunotherapy. This study aims to analyze the effect of microbiome and antibiotics on the effectiveness of ICI in cancer patients and the measures to improve efficacy based on that. A detailed review was conducted on articles published in PubMed and Science Direct in the last five years i.e., 2016 to 2021. A total of 16 articles involving 1293 patients with cancer who were receiving immunotherapy, were deemed eligible to be included in the final review. Data were extracted from the eligible articles and were checked for quality appraisal. All 16 articles revealed the effect of either gut microbiome or antibiotics or both on ICI. Based on our findings, we found that the microbiome enriched in different microorganisms responded differently to the ICI and that antibiotics negatively impacted the effectiveness of ICI. The time at which patients receiving ICI were prescribed antibiotics influenced the effect of ICI. Antibiotics and different microbiome also affected progression-free survival (PFS) and overall survival (OS).}, }
@article {pmid34520499, year = {2021}, author = {Carr, C and Wilcox, H and Burton, JP and Menon, S and Al, KF and O'Gorman, D and Lanting, BA and Vasarhelyi, EM and Neufeld, M and Teeter, MG}, title = {Deciphering the low abundance microbiota of presumed aseptic hip and knee implants.}, journal = {PloS one}, volume = {16}, number = {9}, pages = {e0257471}, pmid = {34520499}, issn = {1932-6203}, mesh = {Adult ; Aged ; Arthroplasty, Replacement, Hip ; Arthroplasty, Replacement, Knee ; Artifacts ; Bacteria/genetics/*isolation &amp; purification ; Female ; Hip Joint/microbiology ; Humans ; Knee Joint/microbiology ; Male ; *Microbiota ; Middle Aged ; Polymerase Chain Reaction ; Prosthesis-Related Infections/*microbiology/pathology ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Sequence Analysis, DNA ; }, abstract = {16S rRNA gene sequencing of DNA extracted from clinically uninfected hip and knee implant samples has revealed polymicrobial populations. However, previous studies assessed 16S rRNA gene sequencing as a technique for the diagnosis of periprosthetic joint infections, leaving the microbiota of presumed aseptic hip and knee implants largely unstudied. These communities of microorganisms might play important roles in aspects of host health, such as aseptic loosening. Therefore, this study sought to characterize the bacterial composition of presumed aseptic joint implant microbiota using next generation 16S rRNA gene sequencing, and it evaluated this method for future investigations. 248 samples were collected from implants of 41 patients undergoing total hip or knee arthroplasty revision for presumed aseptic failure. DNA was extracted using two methodologies-one optimized for high throughput and the other for human samples-and amplicons of the V4 region of the 16S rRNA gene were sequenced. Sequencing data were analyzed and compared with ancillary specific PCR and microbiological culture. Computational tools (SourceTracker and decontam) were used to detect and compensate for environmental and processing contaminants. Microbial diversity of patient samples was higher than that of open-air controls and differentially abundant taxa were detected between these conditions, possibly reflecting a true microbiota that is present in clinically uninfected joint implants. However, positive control-associated artifacts and DNA extraction methodology significantly affected sequencing results. As well, sequencing failed to identify Cutibacterium acnes in most culture- and PCR-positive samples. These challenges limited characterization of bacteria in presumed aseptic implants, but genera were identified for further investigation. In all, we provide further support for the hypothesis that there is likely a microbiota present in clinically uninfected joint implants, and we show that methods other than 16S rRNA gene sequencing may be ideal for its characterization. This work has illuminated the importance of further study of microbiota of clinically uninfected joint implants with novel molecular and computational tools to further eliminate contaminants and artifacts that arise in low bacterial abundance samples.}, }
@article {pmid34519530, year = {2021}, author = {Leclerc, M and Bedu-Ferrari, C and Etienne-Mesmin, L and Mariadassou, M and Lebreuilly, L and Tran, SL and Brazeau, L and Mayeur, C and Delmas, J and Rué, O and Denis, S and Blanquet-Diot, S and Ramarao, N}, title = {Nitric Oxide Impacts Human Gut Microbiota Diversity and Functionalities.}, journal = {mSystems}, volume = {6}, number = {5}, pages = {e0055821}, pmid = {34519530}, issn = {2379-5077}, support = {MICA-MEM//Institut National de la Recherche Agronomique (INRA)/ ; }, abstract = {The disruption of gut microbiota homeostasis has been associated with numerous diseases and with a disproportionate inflammatory response, including overproduction of nitric oxide (NO) in the intestinal lumen. However, the influence of NO on the human gut microbiota has not been well characterized yet. We used in vitro fermentation systems inoculated with human fecal samples to monitor the effect of repetitive NO pulses on the gut microbiota. NO exposure increased the redox potential and modified the fermentation profile and gas production. The overall metabolome was modified, reflecting less strict anaerobic conditions and shifts in amino acid and nitrogen metabolism. NO exposure led to a microbial shift in diversity with a decrease in Clostridium leptum group and Faecalibacterium prausnitzii biomass and an increased abundance of the Dialister genus. Escherichia coli, Enterococcus faecalis, and Proteus mirabilis operational taxonomic unit abundance increased, and strains from those species isolated after NO stress showed resistance to high NO concentrations. As a whole, NO quickly changed microbial fermentations, functions, and composition in a pulse- and dose-dependent manner. NO could shift, over time, the trophic chain to conditions that are unfavorable for strict anaerobic microbial processes, implying that a prolonged or uncontrolled inflammation has detrimental and irreversible consequences on the human microbiome. IMPORTANCE Gut microbiota dysbiosis has been associated with inflammatory diseases. The human inflammatory response leads to an overproduction of nitric oxide (NO) in the gut. However, so far, the influence of NO on the human gut microbiota has not been characterized. In this study, we used in vitro fermentation systems with human fecal samples to understand the effect of NO on the microbiota: NO modified the microbial composition and its functionality. High NO concentration depleted the microbiota of beneficial butyrate-producing species and favored potentially deleterious species (E. coli, E. faecalis, and P. mirabilis), which we showed can sustain high NO concentrations. Our work shows that NO may participate in the vicious circle of inflammation, leading to detrimental and irreversible consequences on human health.}, }
@article {pmid34517942, year = {2021}, author = {Smith, DR and Temime, L and Opatowski, L}, title = {Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: A modeling study applied to nosocomial pathogen control.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34517942}, issn = {2050-084X}, support = {164263//CIHR/Canada ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Cross Infection/*epidemiology/microbiology/*prevention &amp; control ; Drug Resistance, Microbial/drug effects/*physiology ; Humans ; Microbiota/drug effects/*physiology ; Models, Theoretical ; }, abstract = {The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modeling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens (Clostridioides difficile, methicillin-resistant Staphylococcus aureus, multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.}, }
@article {pmid34515049, year = {2021}, author = {Korpela, K}, title = {Impact of Delivery Mode on Infant Gut Microbiota.}, journal = {Annals of nutrition &amp; metabolism}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000518498}, pmid = {34515049}, issn = {1421-9697}, abstract = {Microbial colonization of the neonate is an important feature of normal birth. The gut microbiota has a central role in the programming of the host's metabolism and immune function, with both immediate and long-term health consequences. During vaginal birth, the infant is exposed to diverse maternal microbes, of which specific faecal microbes colonize the infant's gut. C-section eliminates the infant's contact with maternal microbes, preventing vertical transmission of gut microbes. Consequently, infants are colonized by bacteria from the environment, including potential pathogens from the hospital environment. Recent studies have shown that intrapartum antibiotic exposure has a C-section-like effect on the infant gut microbiota. While the composition of the gut microbiota largely normalizes during the first year of life, epidemiological studies suggest that the aberrant early microbial exposures have long-term immunological and metabolic consequences. Because of the high prevalence of procedures that prevent normal gut microbiota development, effective methods to normalize the gut microbiota of neonates are urgently needed. Even more importantly, attention should be paid to the microbiota imbalance in C-section-born and antibiotic-exposed infants in clinical practice. Breastfeeding and probiotics are particularly important for infants with disrupted gut colonization.}, }
@article {pmid34509994, year = {2021}, author = {Houf, J}, title = {Faecal microbiota transplants: towards a healthy disgust scepticism.}, journal = {Medical humanities}, volume = {47}, number = {4}, pages = {407-416}, doi = {10.1136/medhum-2020-012135}, pmid = {34509994}, issn = {1473-4265}, mesh = {*Disgust ; Emotions ; Humans ; *Microbiota ; Morals ; }, abstract = {This paper engages with the obstacle of disgust surrounding the use of faecal microbiota transplants (FMT). In discourse about the human microbiome and microbiota-based therapies (like FMT), disgust has become an unavoidable emotion for physicians, patients and caregivers interested in these therapies. Additionally, microbiota therapies and microbiomes are challenging our conception of an individual biological self. As these two discourses converge with FMT, it becomes necessary to understand how they are working together. To do this, this paper explores the way disgust functions in the formation of subjects. Scholarship about disgust can be categorised into two approaches: disgust as a deep wisdom or disgust scepticism. The former approach focuses on the physiological, embodied aspects of our disgust reactions as evidence of 'truth' in disgusting encounters, and the latter recognises the way disgust is culturally contingent and adapted for use in moral and social determinations of good and bad. However, both positions accept the use of disgust as a defence against 'toxins and diseases'. Yet, as this paper argues, we should take the sceptical approach further. The disgust sceptical approach, particularly as developed by Sarah Ahmed, does more than just challenge disgust's role in moral deliberations. It also demands sceptical reflection on disgust as a universal defence against 'toxins and diseases'. Much as disgust can be co-opted to support oppression, it too can be co-opted to reconstitute a false vision of human subjectivity-the coherent, contained and exceptional human subject situated above the natural world. The human microbiome, faecal therapeutics and being disgusted give us an opportunity to recognise ourselves as more-than-human subjects.}, }
@article {pmid34506740, year = {2021}, author = {Cullin, N and Azevedo Antunes, C and Straussman, R and Stein-Thoeringer, CK and Elinav, E}, title = {Microbiome and cancer.}, journal = {Cancer cell}, volume = {39}, number = {10}, pages = {1317-1341}, doi = {10.1016/j.ccell.2021.08.006}, pmid = {34506740}, issn = {1878-3686}, mesh = {Humans ; Microbiota/*immunology ; Neoplasms/*immunology ; }, abstract = {The human microbiome constitutes a complex multikingdom community that symbiotically interacts with the host across multiple body sites. Host-microbiome interactions impact multiple physiological processes and a variety of multifactorial disease conditions. In the past decade, microbiome communities have been suggested to influence the development, progression, metastasis formation, and treatment response of multiple cancer types. While causal evidence of microbial impacts on cancer biology is only beginning to be unraveled, enhanced molecular understanding of such cancer-modulating interactions and impacts on cancer treatment are considered of major scientific importance and clinical relevance. In this review, we describe the molecular pathogenic mechanisms shared throughout microbial niches that contribute to the initiation and progression of cancer. We highlight advances, limitations, challenges, and prospects in understanding how the microbiome may causally impact cancer and its treatment responsiveness, and how microorganisms or their secreted bioactive metabolites may be potentially harnessed and targeted as precision cancer therapeutics.}, }
@article {pmid34502031, year = {2021}, author = {Bron, PA and Catalayud, M and Marzorati, M and Pane, M and Kartal, E and Dhir, R and Reid, G}, title = {Delivery of Metabolically Neuroactive Probiotics to the Human Gut.}, journal = {International journal of molecular sciences}, volume = {22}, number = {17}, pages = {}, pmid = {34502031}, issn = {1422-0067}, mesh = {*Gastrointestinal Microbiome ; Genomics ; Humans ; Limosilactobacillus reuteri/*metabolism ; Probiotics/*administration &amp; dosage ; Sequence Analysis, DNA ; Vitamin B 12/*biosynthesis ; }, abstract = {The human microbiome is a rich factory for metabolite production and emerging data has led to the concept that orally administered microbial strains can synthesize metabolites with neuroactive potential. Recent research from ex vivo and murine models suggests translational potential for microbes to regulate anxiety and depression through the gut-brain axis. However, so far, less emphasis has been placed on the selection of specific microbial strains known to produce the required key metabolites and the formulation in which microbial compositions are delivered to the gut. Here, we describe a double-capsule technology to deliver high numbers of metabolically active cells derived from the 24-strain probiotic product SH-DS01 to the gastrointestinal tract, including the small intestine, where immune responses and adsorption of metabolites into the bloodstream occur. Based on its genome sequence, Limosilactobacillus reuteri SD-LRE2-IT was predicted to have the genetic capacity to de novo produce a specific metabolite of interest to brain health, vitamin B12, which could be confirmed in vitro. Taken together, our data conceptualizes the importance of rationally defined microbial strain characterization based on genomics and metabolomics data, combined with carefully designed capsule technology for delivery of live cells and concomitant functionality in and beyond the gut ecosystem.}, }
@article {pmid34499859, year = {2021}, author = {Allen-Vercoe, E}, title = {Commensals make the most of their hosts.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {9}, pages = {1337-1339}, doi = {10.1016/j.chom.2021.08.007}, pmid = {34499859}, issn = {1934-6069}, mesh = {ADP Ribose Transferases ; Humans ; *Microbiota ; *Symbiosis ; }, abstract = {In this issue of Cell Host &amp; Microbe, Brown et al. reveal a large group of genes within the human microbiome that code for ADP-ribosyltransferases that are predicted to manipulate host cells. Previously studied for pathogens, these host modification mechanisms may also be common properties of commensals.}, }
@article {pmid34494564, year = {2021}, author = {Wiqoyah, N and Mertaniasih, NM and Artama, WT and Matsumoto, S}, title = {Microbiome in sputum as a potential biomarker of chronicity in pulmonary resistant to rifampicin-tuberculosis and multidrug-resistant-tuberculosis patients.}, journal = {International journal of mycobacteriology}, volume = {10}, number = {3}, pages = {260-267}, doi = {10.4103/ijmy.ijmy_132_21}, pmid = {34494564}, issn = {2212-554X}, mesh = {Antitubercular Agents/therapeutic use ; Biomarkers ; Humans ; *Microbiota ; *Mycobacterium tuberculosis/genetics ; Rifampin ; Sputum ; *Tuberculosis, Multidrug-Resistant/drug therapy ; }, abstract = {BACKGROUND: Cases of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) in South-east Asia including Indonesia are still high. The presence of mixed infections in TB cases has been reported. Several studies revealed the role of the human microbiome in TB. This study purposes to characterize microbiome which can be a potential biomarker of chronicity in TB or MDR-TB.<br><br>METHODS: Sputum samples of pulmonary TB patients confirmed MDR-TB and resistant to rifampicin TB (RR-TB) were conducted Metagenomic next-generation sequencing. Principal coordinate analysis of UniFrac's showing the community structure of microbiome in MDR-TB comorbid diabetes mellitus (DM) is different from RR-TB noncomorbid DM (P = 0.003).<br><br>RESULTS: Proteobacteria microbiome in MDR-TB comorbid DM was more abundant than in RR-TB noncomorbid DM. Actinobacteria found in the small quantity in RR-TB and MDR-TB. Diversity of microbiome genera was greater in RR-TB. The linear discriminant analysis effect size analysis represents a genus biomarker whose abundance shows significant differences between groups, genus Rothia as a potential biomarker for RR-TB noncomorbid DM.<br><br>CONCLUSIONS: Interesting findings is the community structure of microbiome in MDR-TB and RR-TB. In chronic TB such as recurrent, associated MDR-TB should attention to the findings of a small number of Actinobacteria could be a biomarker of TB which is also a determinant in patient taking combined anti-TB drugs of choice.}, }
@article {pmid34490420, year = {2021}, author = {Lymberopoulos, E and Gentili, GI and Alomari, M and Sharma, N}, title = {Topological Data Analysis Highlights Novel Geographical Signatures of the Human Gut Microbiome.}, journal = {Frontiers in artificial intelligence}, volume = {4}, number = {}, pages = {680564}, pmid = {34490420}, issn = {2624-8212}, abstract = {Background: There is growing interest in the connection between the gut microbiome and human health and disease. Conventional approaches to analyse microbiome data typically entail dimensionality reduction and assume linearity of the observed relationships, however, the microbiome is a highly complex ecosystem marked by non-linear relationships. In this study, we use topological data analysis (TDA) to explore differences and similarities between the gut microbiome across several countries. Methods: We used curated adult microbiome data at the genus level from the GMrepo database. The dataset contains OTU and demographical data of over 4,400 samples from 19 studies, spanning 12 countries. We analysed the data with tmap, an integrative framework for TDA specifically designed for stratification and enrichment analysis of population-based gut microbiome datasets. Results: We find associations between specific microbial genera and groups of countries. Specifically, both the USA and UK were significantly co-enriched with the proinflammatory genera Lachnoclostridium and Ruminiclostridium, while France and New Zealand were co-enriched with other, butyrate-producing, taxa of the order Clostridiales. Conclusion: The TDA approach demonstrates the overlap and distinctions of microbiome composition between and within countries. This yields unique insights into complex associations in the dataset, a finding not possible with conventional approaches. It highlights the potential utility of TDA as a complementary tool in microbiome research, particularly for large population-scale datasets, and suggests further analysis on the effects of diet and other regionally varying factors.}, }
@article {pmid34489882, year = {2021}, author = {Qin, J and Shi, X and Xu, J and Yuan, S and Zheng, B and Zhang, E and Huang, G and Li, G and Jiang, G and Gao, S and Tian, C and Guo, R and Fu, Z and Huang, Q and Yang, R and Zhang, W and Li, S and Wu, S}, title = {Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {673969}, pmid = {34489882}, issn = {1664-302X}, abstract = {Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including Prevotella, Streptococcus, Lactobacillus, Gardnerella, Escherichia-Shigella, and Veillonella, and 131 low-abundance genera (0.01-5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by Acinetobacter, Corynebacterium, Staphylococcus, or Sphingomonas. Peptoniphilus, Ezakiella, and Porphyromonas were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.}, }
@article {pmid34480670, year = {2021}, author = {Vandamme, P and Peeters, C and Seth-Smith, HMB and Graf, L and Cnockaert, M and Egli, A and Goldenberger, D}, title = {Gulosibacter hominis sp. nov.: a novel human microbiome bacterium that may cause opportunistic infections.}, journal = {Antonie van Leeuwenhoek}, volume = {114}, number = {11}, pages = {1841-1854}, pmid = {34480670}, issn = {1572-9699}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Fatty Acids/analysis ; Humans ; *Microbiota ; Nucleic Acid Hybridization ; *Opportunistic Infections ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {We present genomic, phylogenomic, and phenotypic taxonomic data to demonstrate that three human ear isolates represent a novel species within the genus Gulosibacter. These isolates could not be identified reliably using MALDI-TOF mass spectrometry during routine diagnostic work, but partial 16S rRNA gene sequence analysis revealed that they belonged to the genus Gulosibacter. Overall genomic relatedness indices between the draft genome sequences of the three isolates and of the type strains of established Gulosibacter species confirmed that the three isolates represented a single novel Gulosibacter species. A biochemical characterisation yielded differential tests between the novel and established Gulosibacter species, which could also be differentiated using MALDI-TOF mass spectrometry. We propose to formally classify these three isolates into Gulosibacter hominis sp. nov., with 401352-2018[ T] (= LMG 31778[ T], CCUG 74795[ T]) as the type strain. The whole-genome sequence of strain 401352-2018[ T] has a size of 2,340,181 bp and a G+C content of 62.04 mol%. A Gulosibacter pangenome analysis revealed 467 gene clusters that were exclusively present in G. hominis genomes. While these G. hominis specific gene clusters were enriched in several COG functional categories, this analysis did not reveal functions that suggested a role in the human microbiome, nor did it explain the occurrence of G. hominis in ear infections. The absence of acquired antimicrobial resistance determinants and virulence factors in the G. hominis genomes, and an analysis of publicly available 16S rRNA gene sequences and 16S rRNA amplicon sequencing data sets suggested that G. hominis is a member of the human skin microbiota that may occasionally be involved in opportunistic infections.}, }
@article {pmid34476756, year = {2021}, author = {Babino, G and Caccavale, S and Pinto, D and Trink, A and Giuliani, G and Rinaldi, F and Argenziano, G}, title = {A Randomized Double-Blind Parallel-Group Study to Evaluate the Long-Term Effects of a Medical Device Containing 0.3% Octatrienoic Acid in the Treatment of Grade III Actinic Keratosis.}, journal = {Dermatology and therapy}, volume = {11}, number = {5}, pages = {1751-1762}, pmid = {34476756}, issn = {2193-8210}, abstract = {INTRODUCTION: Actinic keratosis (AK) consists of skin lesions with a milder degree of keratinocytic atypia. It can be also referred to as "field of cancerization," which can potentially evolve to cutaneous squamous cell carcinoma (SCC). Several therapeutic options are currently available, but not all are indicated on hyperkeratotic lesions. This study aimed to test the efficacy and tolerability of a medical device containing 2,4,6-octatrienoic acid and urea for the treatment of hyperkeratotic AK lesions.<br><br>METHODS: Seventy male and female subjects with grade III AK were enrolled in this randomized double-blind parallel-group study. The product was applied once daily for three consecutive months. The primary efficacy endpoint was the reduction in the mean number of AK lesions per subject from baseline (T0) to the end of the trial (T1) and 3&#xa0;months after the end of the treatment period (T2). Therefore, clearance of target AK lesions at the end of the treatment period and local skin reaction score (LSR) versus baseline were evaluated.<br><br>RESULTS: There was a decrease of mean values from baseline to visit T2 in both treatment groups, but the decrease (versus baseline values) was more evident in the Ker&#xe0; K2 group than in the placebo group (-42.78, SD 26.53, versus -6.20, SD 31.57), and the difference was statistically significant (p&#x2009;<&#x2009;0.001). For 70 subjects (56.7%) in the Ker&#xe0; K2 group and 3 (11.54%) in the placebo group, a significant (p&#x2009;<&#x2009;0.005) partial clearance was evidenced. The product was well tolerated, and no serious adverse events were reported during the duration of the trial. Subject self-assessment of acceptability, local tolerability, and the cosmetic result was good at both T1 and T2 for both groups.<br><br>CONCLUSIONS: The medical device has demonstrated good efficacy in the reduction of visible AKs, encouraging its use.}, }
@article {pmid34471732, year = {2021}, author = {D'Huys, L and Vitale, R and Ruppeka-Rupeika, E and Goyvaerts, V and Ruckebusch, C and Hofkens, J}, title = {Assessing the Resolution of Methyltransferase-Mediated DNA Optical Mapping.}, journal = {ACS omega}, volume = {6}, number = {33}, pages = {21276-21283}, pmid = {34471732}, issn = {2470-1343}, abstract = {Interest in the human microbiome is growing and has been, for the past decade, leading to new insights into disease etiology and general human biology. Stimulated by these advances and in a parallel trend, new DNA sequencing platforms have been developed, radically expanding the possibilities in microbiome research. While DNA sequencing plays a pivotal role in this field, there are some technological hurdles that are yet to be overcome. Targeting of the 16S rRNA gene with amplicon sequencing, for instance, is frequently used for sample composition profiling due to its short sample-to-result time and low cost, which counterbalance its low resolution (genus to species level). On the other hand, more comprehensive methods, namely, whole-genome sequencing (WGS) and shallow shotgun sequencing, are capable of yielding single-gene- and functional-level resolution at a higher cost and much higher sample processing time. It goes without saying that the existing gap between these two types of approaches still calls for the development of a fast, robust, and low-cost analytical platform. In search of the latter, we investigated the taxonomic resolution of methyltransferase-mediated DNA optical mapping and found that strain-level identification can be achieved with both global and whole-genome analyses as well as using a unique identifier (UI) database. In addition, we demonstrated that UI selection in DNA optical mapping, unlike variable region selection in 16S amplicon sequencing, is not limited to any genomic location, explaining the increase in resolution. This latter aspect was highlighted by SCCmec typing in methicillin-resistant Staphylococcus aureus (MRSA) using a simulated data set. In conclusion, we propose DNA optical mapping as a method that has the potential to be highly complementary to current sequencing platforms.}, }
@article {pmid34465175, year = {2021}, author = {Zhang, Y and Thompson, KN and Branck, T and Yan Yan,  and Nguyen, LH and Franzosa, EA and Huttenhower, C}, title = {Metatranscriptomics for the Human Microbiome and Microbial Community Functional Profiling.}, journal = {Annual review of biomedical data science}, volume = {4}, number = {}, pages = {279-311}, doi = {10.1146/annurev-biodatasci-031121-103035}, pmid = {34465175}, issn = {2574-3414}, support = {K23 DK125838/DK/NIDDK NIH HHS/United States ; R39789/VAC_/Versus Arthritis/United Kingdom ; R24 DK110499/DK/NIDDK NIH HHS/United States ; C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {Host Microbial Interactions ; Humans ; *Metagenomics ; *Microbiota/genetics ; Sequence Analysis, RNA ; Transcriptome ; }, abstract = {Shotgun metatranscriptomics (MTX) is an increasingly practical way to survey microbial community gene function and regulation at scale. This review begins by summarizing the motivations for community transcriptomics and the history of the field. We then explore the principles, best practices, and challenges of contemporary MTX workflows: beginning with laboratory methods for isolation and sequencing of community RNA, followed by informatics methods for quantifying RNA features, and finally statistical methods for detecting differential expression in a community context. In thesecond half of the review, we survey important biological findings from the MTX literature, drawing examples from the human microbiome, other (nonhuman) host-associated microbiomes, and the environment. Across these examples, MTX methods prove invaluable for probing microbe-microbe and host-microbe interactions, the dynamics of energy harvest and chemical cycling, and responses to environmental stresses. We conclude with a review of open challenges in the MTX field, including making assays and analyses more robust, accessible, and adaptable to new technologies; deciphering roles for millions of uncharacterized microbial transcripts; and solving applied problems such as biomarker discovery and development of microbial therapeutics.}, }
@article {pmid34461180, year = {2021}, author = {Chen, H and Ma, Y and Liu, Z and Li, J and Li, X and Yang, F and Qiu, M}, title = {Circulating microbiome DNA: An emerging paradigm for cancer liquid biopsy.}, journal = {Cancer letters}, volume = {521}, number = {}, pages = {82-87}, doi = {10.1016/j.canlet.2021.08.036}, pmid = {34461180}, issn = {1872-7980}, abstract = {Dysbiosis of the human microbiome has long been reported to be closely associated with various cancers. Accumulating studies have shown that microbial dysbiosis can accelerate tumorigenesis through tumor-promoting inflammation, DNA damage, and inducing immune evasion. Differential composition of microbiome could be novel biomarkers for cancer detection or biomarkers of successful immunotherapy. More importantly, emerging evidence demonstrates that alterations of circulating microbiome DNA (cmDNA) could serve as promising noninvasive biomarkers for cancer detection. It has been reported that distinct circulating bacterial DNA could distinguish prostate cancer, lung cancer, and melanoma patients from healthy populations. Therefore, in this review, we summarized current literature on microbial biomarkers for cancer detection and unraveled the potential of cmDNA as a promising cancer detection tool.}, }
@article {pmid34460287, year = {2021}, author = {Ancona, G and Alagna, L and Lombardi, A and Palomba, E and Castelli, V and Renisi, G and Dondossola, D and Iavarone, M and Muscatello, A and Gori, A and Bandera, A}, title = {The Interplay between Gut Microbiota and the Immune System in Liver Transplant Recipients and Its Role in Infections.}, journal = {Infection and immunity}, volume = {89}, number = {11}, pages = {e0037621}, pmid = {34460287}, issn = {1098-5522}, mesh = {Bacterial Infections/*etiology/immunology ; Drug Resistance, Multiple, Bacterial ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions ; Humans ; Immune System/*physiology ; Liver Cirrhosis/complications/microbiology ; Liver Transplantation/*adverse effects ; Severity of Illness Index ; }, abstract = {Liver transplantation (LT) is a life-saving strategy for patients with end-stage liver disease, hepatocellular carcinoma, and acute liver failure. LT success can be hampered by several short-term and long-term complications. Among them, bacterial infections, especially those due to multidrug-resistant germs, are particularly frequent, with a prevalence between 19 and 33% in the first 100 days after transplantation. In the last decades, a number of studies have highlighted how the gut microbiota (GM) is involved in several essential functions to ensure intestinal homeostasis, becoming one of the most important virtual metabolic organs. The GM works through different axes with other organs, and the gut-liver axis is among the most relevant and investigated ones. Any alteration or disruption of the GM is defined as dysbiosis. Peculiar phenotypes of GM dysbiosis have been associated with several liver conditions and complications, such as chronic hepatitis, fatty liver disease, cirrhosis, and hepatocellular carcinoma. Moreover, there is growing evidence of the crucial role of the GM in shaping the immune response, both locally and systemically, against pathogens. This paves the way to the manipulation of the GM as a therapeutic instrument to modulate infectious risk and outcome. In this minireview, we provide an overview of the current understanding of the interplay between the gut microbiota and the immune system in liver transplant recipients and the role of the former in infections.}, }
@article {pmid34458160, year = {2021}, author = {Cho, HW and Eom, YB}, title = {Forensic Analysis of Human Microbiome in Skin and Body Fluids Based on Geographic Location.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {695191}, pmid = {34458160}, issn = {2235-2988}, mesh = {*Body Fluids/microbiology ; Female ; Forensic Sciences ; Geography ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Saliva ; Skin/*microbiology ; }, abstract = {High-throughput DNA sequencing technologies have facilitated the in silico forensic analysis of human microbiome. Specific microbial species or communities obtained from the crime scene provide evidence of human contacts and their body fluids. The microbial community is influenced by geographic, ethnic, lifestyle, and environmental factors such as urbanization. An understanding of the effects of these external stressors on the human microbiome and determination of stable and changing elements are important in selecting appropriate targets for investigation. In this study, the Forensic Microbiome Database (FMD) (http://www.fmd.jcvi.org) containing the microbiome data of various locations in the human body in 35 countries was used. We focused on skin, saliva, vaginal fluid, and stool and found that the microbiome distribution differed according to the body part as well as the geographic location. In the case of skin samples, Staphylococcus species were higher than Corynebacterium species among Asians compared with Americans. Holdemanella and Fusobacterium were specific in the saliva of Koreans and Japanese populations. Lactobacillus was found in the vaginal fluids of individuals in all countries, whereas Serratia and Enterobacter were endemic to Bolivia and Congo, respectively. This study is the first attempt to collate and describe the observed variation in microbiomes from the forensic microbiome database. As additional microbiome databases are reported by studies worldwide, the diversity of the applications may exceed and expand beyond the initial identification of the host.}, }
@article {pmid34458156, year = {2021}, author = {Vork, L and Penders, J and Jalanka, J and Bojic, S and van Kuijk, SMJ and Salonen, A and de Vos, WM and Rajilic-Stojanovic, M and Weerts, ZZRM and Masclee, AAM and Pozuelo, M and Manichanh, C and Jonkers, DMAE}, title = {Does Day-to-Day Variability in Stool Consistency Link to the Fecal Microbiota Composition?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {639667}, pmid = {34458156}, issn = {2235-2988}, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; }, abstract = {INTRODUCTION: Stool consistency has been associated with fecal microbial composition. Stool consistency often varies over time, in subjects with and without gastrointestinal disorders, raising the question whether variability in the microbial composition should be considered in microbiota studies. We evaluated within-subject day-to-day variability in stool consistency and the association with the fecal microbiota in irritable bowel syndrome (IBS) and healthy subjects, over seven days.<br><br>METHODS: Twelve IBS patients and 12 healthy subjects collected fecal samples during seven consecutive days. Stool consistency was determined by the patient-reported Bristol Stool Scale (BSS) and fecal dry weight percentage. 16S rRNA V4 gene sequencing was performed and microbial richness (alpha diversity; Chao1 index, observed number of species, effective Shannon index) and microbial community structure (beta diversity; Bray-Curtis distance, generalized UniFrac, and taxa abundance on family level) were determined.<br><br>RESULTS: Linear mixed-effects models showed significant associations between stool consistency and microbial richness, but no time effect. This implies that between-subject but not within-subject variation in microbiota over time can partially be explained by variation in stool consistency. Redundancy analysis showed a significant association between stool consistency and microbial community structure, but additional linear mixed-effects models did not demonstrate a time effect on this.<br><br>CONCLUSION: This study supports an association between stool consistency and fecal microbiota, but no effect of day-to-day fluctuations in stool consistency within seven days. This consolidates the importance of considering stool consistency in gut microbiota research, though confirms the validity of single fecal sampling to represent an individual's microbiota at a given time point. NCT00775060.}, }
@article {pmid34455517, year = {2021}, author = {Li, JJ and Zhu, M and Kashyap, PC and Chia, N and Tran, NH and McWilliams, RR and Bekaii-Saab, TS and Ma, WW}, title = {The role of microbiome in pancreatic cancer.}, journal = {Cancer metastasis reviews}, volume = {40}, number = {3}, pages = {777-789}, pmid = {34455517}, issn = {1573-7233}, support = {R01 CA179243/CA/NCI NIH HHS/United States ; }, mesh = {*Carcinoma, Pancreatic Ductal/therapy ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; *Pancreatic Neoplasms/therapy ; *Probiotics/therapeutic use ; Tumor Microenvironment ; }, abstract = {Recent studies of the human microbiome have offered new insights into how the microbiome can impact cancer development and treatment. Specifically, in pancreatic ductal adenocarcinoma (PDAC), the microbiota has been shown to modulate PDAC risk, contribute to tumorigenesis, impact the tumor microenvironment, and alter treatment response. These findings provide rationale for further investigations into leveraging the microbiome to develop new strategies to diagnose and treat PDAC patients. There is growing evidence that microbiome analyses have the potential to become easily performed, non-invasive diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. More excitingly, there is now emerging interest in developing interventions based on the modulation of microbiota. Fecal microbiota transplantation, probiotics, dietary changes, and antibiotics are all potential strategies to augment the efficacy of current therapeutics and reduce toxicities. While there are still challenges to overcome, this is a rapidly growing field that holds promise for translation into clinical practice and provides a new approach to improving patient outcomes.}, }
@article {pmid34451527, year = {2021}, author = {Javelle, E and Mayet, A and Million, M and Levasseur, A and Allodji, RS and Marimoutou, C and Lavagna, C and Desplans, J and Fournier, PE and Raoult, D and Texier, G}, title = {Gut Microbiota in Military International Travelers with Doxycycline Malaria Prophylaxis: Towards the Risk of a Simpson Paradox in the Human Microbiome Field.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {8}, pages = {}, pmid = {34451527}, issn = {2076-0817}, abstract = {Dysbiosis, developed upon antibiotic administration, results in loss of diversity and shifts in the abundance of gut microbes. Doxycycline is a tetracycline antibiotic widely used for malaria prophylaxis in travelers. We prospectively studied changes in the fecal microbiota of 15 French soldiers after a 4-month mission to Mali with doxycycline malaria prophylaxis, compared to changes in the microbiota of 28 soldiers deployed to Iraq and Lebanon without doxycycline. Stool samples were collected with clinical data before and after missions, and 16S rRNA sequenced on MiSeq targeting the V3-V4 region. Doxycycline exposure resulted in increased alpha-biodiversity and no significant beta-dissimilarities. It led to expansion in Bacteroides, with a reduction in Bifidobacterium and Lactobacillus, as in the group deployed without doxycycline. Doxycycline did not alter the community structure and was specifically associated with a reduction in Escherichia and expression of Rothia. Differences in the microbiota existed at baseline between military units but not within the studied groups. This group-effect highlighted the risk of a Simpson paradox in microbiome studies.}, }
@article {pmid34448860, year = {2021}, author = {Dalal, P and Sharma, D}, title = {Microbe defines the efficacy of chemotherapeutic drug: a complete paradigm.}, journal = {FEMS microbiology letters}, volume = {368}, number = {17}, pages = {}, doi = {10.1093/femsle/fnab116}, pmid = {34448860}, issn = {1574-6968}, mesh = {Drug Therapy/standards ; Humans ; *Microbiota ; *Pharmaceutical Preparations ; }, abstract = {The human body harbors a diverse microbiome that regulates host physiology and disease development. Several studies have also been reported where the human microbiome interferes with the efficacy of chemotherapeutics. Reports have also suggested the use of microbes in specific targeting and drug delivery. This review mainly focuses on the alteration in the efficacy of the drug by human microbiota. We have also discussed how the diversity in microbes can determine the therapeutic outcomes of a particular drug. The pathways involved in the alteration are also focused, with some highlights on microbes being used in cancer therapy.}, }
@article {pmid34445114, year = {2021}, author = {Kouvela, A and Zaravinos, A and Stamatopoulou, V}, title = {Adaptor Molecules Epitranscriptome Reprograms Bacterial Pathogenicity.}, journal = {International journal of molecular sciences}, volume = {22}, number = {16}, pages = {}, pmid = {34445114}, issn = {1422-0067}, support = {81344//Research Committee of the University of Patras via "C. CARATHEODORI" program/ ; }, mesh = {Anticodon/genetics ; Bacteria/*genetics/*pathogenicity ; Humans ; Nucleosides/genetics ; Protein Biosynthesis/genetics ; RNA Processing, Post-Transcriptional/genetics ; RNA, Transfer/genetics ; Transcriptome/*genetics ; Virulence/genetics ; }, abstract = {The strong decoration of tRNAs with post-transcriptional modifications provides an unprecedented adaptability of this class of non-coding RNAs leading to the regulation of bacterial growth and pathogenicity. Accumulating data indicate that tRNA post-transcriptional modifications possess a central role in both the formation of bacterial cell wall and the modulation of transcription and translation fidelity, but also in the expression of virulence factors. Evolutionary conserved modifications in tRNA nucleosides ensure the proper folding and stability redounding to a totally functional molecule. However, environmental factors including stress conditions can cause various alterations in tRNA modifications, disturbing the pathogen homeostasis. Post-transcriptional modifications adjacent to the anticodon stem-loop, for instance, have been tightly linked to bacterial infectivity. Currently, advances in high throughput methodologies have facilitated the identification and functional investigation of such tRNA modifications offering a broader pool of putative alternative molecular targets and therapeutic avenues against bacterial infections. Herein, we focus on tRNA epitranscriptome shaping regarding modifications with a key role in bacterial infectivity including opportunistic pathogens of the human microbiome.}, }
@article {pmid34442842, year = {2021}, author = {Yano, Y and Etemadi, A and Abnet, CC}, title = {Microbiome and Cancers of the Esophagus: A Review.}, journal = {Microorganisms}, volume = {9}, number = {8}, pages = {}, pmid = {34442842}, issn = {2076-2607}, support = {Intramural Research Program/CA/NCI NIH HHS/United States ; }, abstract = {Esophageal cancer (EC) is an aggressive malignant disease ranking amongst the leading causes of cancer deaths in the world. The two main histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and temporal patterns and risk factor profiles. Despite decades of research, the factors underlying these geo-temporal patterns are still not fully understood. The human microbiome has recently been implicated in various health conditions and disease, and it is possible that the microbiome may play an important role in the etiology of EC. Although studies of the microbiome and EC are still in their early stages, we review our current understanding of the potential links between ESCC, EAC, and bacterial communities in the oral cavity and esophagus. We also provide a summary of the epidemiology of EC and highlight some key challenges and future directions.}, }
@article {pmid34437713, year = {2022}, author = {Insolia, L and Kenney, A and Chiaromonte, F and Felici, G}, title = {Simultaneous feature selection and outlier detection with optimality guarantees.}, journal = {Biometrics}, volume = {78}, number = {4}, pages = {1592-1603}, pmid = {34437713}, issn = {1541-0420}, support = {T32 LM012415/LM/NLM NIH HHS/United States ; 5T32LM012415-03/NH/NIH HHS/United States ; }, mesh = {Child ; Humans ; *Pediatric Obesity ; Algorithms ; Sample Size ; Probability ; }, abstract = {Biomedical research is increasingly data rich, with studies comprising ever growing numbers of features. The larger a study, the higher the likelihood that a substantial portion of the features may be redundant and/or contain contamination (outlying values). This poses serious challenges, which are exacerbated in cases where the sample sizes are relatively small. Effective and efficient approaches to perform sparse estimation in the presence of outliers are critical for these studies, and have received considerable attention in the last decade. We contribute to this area considering high-dimensional regressions contaminated by multiple mean-shift outliers affecting both the response and the design matrix. We develop a general framework and use mixed-integer programming to simultaneously perform feature selection and outlier detection with provably optimal guarantees. We prove theoretical properties for our approach, that is, a necessary and sufficient condition for the robustly strong oracle property, where the number of features can increase exponentially with the sample size; the optimal estimation of parameters; and the breakdown point of the resulting estimates. Moreover, we provide computationally efficient procedures to tune integer constraints and warm-start the algorithm. We show the superior performance of our proposal compared to existing heuristic methods through simulations and use it to study the relationships between childhood obesity and the human microbiome.}, }
@article {pmid34437668, year = {2021}, author = {Wilson, M and Mello, MJ and Gruppuso, PA}, title = {Antibiotics and the Human Microbiome: A Survey of Prescribing Clinicians' Knowledge and Opinions Regarding the Link between Antibiotic-Induced Dysbiosis and Immune-Mediated Disease.}, journal = {Rhode Island medical journal (2013)}, volume = {104}, number = {7}, pages = {59-63}, pmid = {34437668}, issn = {2327-2228}, mesh = {Anti-Bacterial Agents/adverse effects ; *Dysbiosis/chemically induced/drug therapy ; Humans ; *Microbiota ; Rhode Island ; }, abstract = {Altered composition or function of the human micro- biome, termed dysbiosis, has been associated with a variety of immune-mediated diseases. Antibiotic use is a well-studied cause of dysbiosis. We conducted an electronic survey of 351 antibiotic-prescribing clinicians in Rhode Island to evaluate antibiotic prescription patterns, knowledge and opinions regarding the importance of the human microbiome and its relation to antibiotics and the immune system. We found that clinicians view the health of the human microbiome as important when prescribing antibiotics; however, they do not feel well-informed or confident in their knowledge about the microbiome or its relevance to patient health. A higher level of self- reported knowledge about the microbiome was associated with increased importance placed on the microbiome and its relevance to medical practice. Our results indicate that clinicians may benefit from continuing medical education on the link between antibiotic-induced dysbiosis and immune-mediated disease.}, }
@article {pmid34430543, year = {2021}, author = {Gabaldón, T}, title = {Roles of the human microbiome in cancer.}, journal = {Hepatobiliary surgery and nutrition}, volume = {10}, number = {4}, pages = {558-560}, pmid = {34430543}, issn = {2304-3881}, }
@article {pmid34427674, year = {2021}, author = {Mejía-Caballero, A and Salas-Villagrán, VA and Jiménez-Serna, A and Farrés, A}, title = {Challenges in the production and use of probiotics as therapeuticals in cancer treatment or prevention.}, journal = {Journal of industrial microbiology &amp; biotechnology}, volume = {48}, number = {9-10}, pages = {}, pmid = {34427674}, issn = {1476-5535}, support = {//UNAM/ ; //CONACYT/ ; }, mesh = {Humans ; *Neoplasms/prevention &amp; control ; *Probiotics/therapeutic use ; }, abstract = {Probiotics were defined as microbial strains that confer health benefits to their consumers. The concept has evolved during the last 20 years, and today metabolites produced by the strains, known as postbiotics, and even dead cells, known as paraprobiotics, are closely associated to them. The isolation of commensal strains from human microbiome has led to the development of next generation probiotics. This review aims to present an overview of the developments in the area of cancer prevention and treatment, intimately related to advances in the knowledge of the microbiome role in its genesis and therapy. Strain identification and characterization, production processes, delivery strategies, and clinical evaluation are crucial to translate results into the market with solid scientific support. Examples of recent tools in isolation, strain typification, quality control, and development of new probiotic strains are described. Probiotics market and regulation were originally developed in the food sector, but these new strategies will impact the pharmaceutical and health sectors, requiring new considerations in regulatory frameworks.}, }
@article {pmid34427527, year = {2021}, author = {Ammer-Herrmenau, C and Pfisterer, N and van den Berg, T and Gavrilova, I and Amanzada, A and Singh, SK and Khalil, A and Alili, R and Belda, E and Clement, K and Abd El Wahed, A and Gady, EE and Haubrock, M and Beißbarth, T and Ellenrieder, V and Neesse, A}, title = {Comprehensive Wet-Bench and Bioinformatics Workflow for Complex Microbiota Using Oxford Nanopore Technologies.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0075021}, pmid = {34427527}, issn = {2379-5077}, support = {404935781//Deutsche Forschungsgemeinschaft (DFG)/ ; 404935781//Deutsche Forschungsgemeinschaft (DFG)/ ; 404935781//Deutsche Forschungsgemeinschaft (DFG)/ ; }, abstract = {The advent of high-throughput sequencing techniques has recently provided an astonishing insight into the composition and function of the human microbiome. Next-generation sequencing (NGS) has become the gold standard for advanced microbiome analysis; however, 3rd generation real-time sequencing, such as Oxford Nanopore Technologies (ONT), enables rapid sequencing from several kilobases to >2 Mb with high resolution. Despite the wide availability and the enormous potential for clinical and translational applications, ONT is poorly standardized in terms of sampling and storage conditions, DNA extraction, library creation, and bioinformatic classification. Here, we present a comprehensive analysis pipeline with sampling, storage, DNA extraction, library preparation, and bioinformatic evaluation for complex microbiomes sequenced with ONT. Our findings from buccal and rectal swabs and DNA extraction experiments indicate that methods that were approved for NGS microbiome analysis cannot be simply adapted to ONT. We recommend using swabs and DNA extractions protocols with extended washing steps. Both 16S rRNA and metagenomic sequencing achieved reliable and reproducible results. Our benchmarking experiments reveal thresholds for analysis parameters that achieved excellent precision, recall, and area under the precision recall values and is superior to existing classifiers (Kraken2, Kaiju, and MetaMaps). Hence, our workflow provides an experimental and bioinformatic pipeline to perform a highly accurate analysis of complex microbial structures from buccal and rectal swabs. IMPORTANCE Advanced microbiome analysis relies on sequencing of short DNA fragments from microorganisms like bacteria, fungi, and viruses. More recently, long fragment DNA sequencing of 3rd generation sequencing has gained increasing importance and can be rapidly conducted within a few hours due to its potential real-time sequencing. However, the analysis and correct identification of the microbiome relies on a multitude of factors, such as the method of sampling, DNA extraction, sequencing, and bioinformatic analysis. Scientists have used different protocols in the past that do not allow us to compare results across different studies and research fields. Here, we provide a comprehensive workflow from DNA extraction, sequencing, and bioinformatic workflow that allows rapid and accurate analysis of human buccal and rectal swabs with reproducible protocols. This workflow can be readily applied by many scientists from various research fields that aim to use long-fragment microbiome sequencing.}, }
@article {pmid34422393, year = {2021}, author = {Grover, K and Gregory, S and Gibbs, JF and Emenaker, NJ}, title = {A discussion of the gut microbiome's development, determinants, and dysbiosis in cancers of the esophagus and stomach.}, journal = {Journal of gastrointestinal oncology}, volume = {12}, number = {Suppl 2}, pages = {S290-S300}, pmid = {34422393}, issn = {2078-6891}, abstract = {The microbiome refers to a population of microbes that colonize the skin, nasopharynx, oral cavity, gastrointestinal tract, and urogenital tract. The human microbiome consists of bacteria, archaea, fungi, viruses, and phages. Recent advances in genomic sequencing have catalyzed a deeper understanding of complex microbe-microbe and host-microbe interactions. Dysregulation of these interactions, or dysbiosis of the gastrointestinal tract, has been implicated in a growing list of pathologies including nonalcoholic fatty liver disease, cardiovascular disease, obesity, diabetes, depression, Parkinson's disease, autism, and various gastrointestinal cancers. Gastric and esophageal cancer, for example, continue to remain as two of the most common causes of cancer-related deaths worldwide, therefore there is an increased emphasis on investigating the role of dysbiosis on these cancers. In this review, we discuss the development and structure of the gut microbiome, its homeostatic and dysbiotic mechanisms, and the key microbes in esophageal and gastric carcinogenesis with a focus on bacterial biology. Further clarification of these pathways and discovery of diagnostic or therapeutic targets could have broad impacts on global subpopulations. It is important to understand the nature of the gastrointestinal tract microbiome and its potentional risk factors for dysbiosis in order to tailor its application to the individual patient and create an era of highly personalized, precision medicine.}, }
@article {pmid34419057, year = {2021}, author = {Chuzel, L and Fossa, SL and Boisvert, ML and Cajic, S and Hennig, R and Ganatra, MB and Reichl, U and Rapp, E and Taron, CH}, title = {Combining functional metagenomics and glycoanalytics to identify enzymes that facilitate structural characterization of sulfated N-glycans.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {162}, pmid = {34419057}, issn = {1475-2859}, mesh = {Acetylglucosamine/*metabolism ; Enzymes/genetics/*isolation &amp; purification/*metabolism ; Kinetics ; Metagenomics/*methods ; Polysaccharides/*chemistry/*metabolism ; Sulfates/chemistry/*metabolism ; }, abstract = {BACKGROUND: Sulfate modification of N-glycans is important for several biological functions such as clearance of pituitary hormones or immunoregulation. Yet, the prevalence of this N-glycan modification and its functions remain largely unexplored. Characterization of N-glycans bearing sulfate modifications is hampered in part by a lack of enzymes that enable site-specific detection of N-glycan sulfation. In this study, we used functional metagenomic screening to identify enzymes that act upon sulfated N-acetylglucosamine (GlcNAc). Using multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (xCGE-LIF) -based glycoanalysis we proved their ability to act upon GlcNAc-6-SO4 on N-glycans.<br><br>RESULTS: Our screen identified a sugar-specific sulfatase that specifically removes sulfate from GlcNAc-6-SO4 when it is in a terminal position on an N-glycan. Additionally, in the absence of calcium, this sulfatase binds to the sulfated glycan but does not remove the sulfate group, suggesting it could be used for selective isolation of sulfated N-glycans. Further, we describe isolation of a sulfate-dependent hexosaminidase that removes intact GlcNAc-6-SO4 (but not asulfated GlcNAc) from a terminal position on N-glycans. Finally, the use of these enzymes to detect the presence of sulfated N-glycans by xCGE-LIF is demonstrated.<br><br>CONCLUSION: The present study demonstrates the feasibility of using functional metagenomic screening combined with glycoanalytics to discover enzymes that act upon chemical modifications of glycans. The discovered enzymes represent new specificities that can help resolve the presence of GlcNAc-6-SO4 in N-glycan structural analyses.}, }
@article {pmid34416161, year = {2021}, author = {Li, W and Hang, S and Fang, Y and Bae, S and Zhang, Y and Zhang, M and Wang, G and McCurry, MD and Bae, M and Paik, D and Franzosa, EA and Rastinejad, F and Huttenhower, C and Yao, L and Devlin, AS and Huh, JR}, title = {A bacterial bile acid metabolite modulates Treg activity through the nuclear hormone receptor NR4A1.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {9}, pages = {1366-1377.e9}, pmid = {34416161}, issn = {1934-6069}, support = {210664/Z/18/Z/WT_/Wellcome Trust/United Kingdom ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 DK110559/DK/NIDDK NIH HHS/United States ; R35 GM128618/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteroidetes/*metabolism ; Bile Acids and Salts/*metabolism ; Cell Differentiation/physiology ; Chromatin/metabolism ; Forkhead Transcription Factors/genetics ; Humans ; Inflammatory Bowel Diseases/pathology ; Multigene Family/genetics ; Nuclear Receptor Subfamily 4, Group A, Member 1/*metabolism ; Phenanthrenes/*metabolism ; Promoter Regions, Genetic/genetics ; Signal Transduction/physiology ; T-Lymphocyte Subsets/cytology/immunology ; T-Lymphocytes, Regulatory/cytology/*immunology ; }, abstract = {Bile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4[+] T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (Treg cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes. We also show that the nuclear hormone receptor NR4A1 is required for the effect of isoalloLCA on Treg cells. Moreover, the levels of isoalloLCA and its biosynthetic genes are significantly reduced in patients with inflammatory bowel diseases, suggesting that isoalloLCA and its bacterial producers may play a critical role in maintaining immune homeostasis in humans.}, }
@article {pmid34412621, year = {2021}, author = {Yu, ZK and Xie, RL and You, R and Liu, YP and Chen, XY and Chen, MY and Huang, PY}, title = {The role of the bacterial microbiome in the treatment of cancer.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {934}, pmid = {34412621}, issn = {1471-2407}, support = {No.2018015//Program of Sun Yat-Sen University for Clinical Research 5010 Program(CN)/ ; No.2018029;No.201310//Program of Sun Yat-Sen University for Clinical Research 5010 Program(CN)/ ; No.81772895//National Natural Science Foundation of China/ ; No.81874134//National Natural Science Foundation of China/ ; No.2020B1111190001//Key-Area Research and Development of Guangdong Province(CN)/ ; No.2017B020226004//Guangdong Province Science and Technology Development Special Funds(CN)/ ; No.Y-JS2019-002//CSCO-JunShi Cancer Immunotherapy Clinical Research Fund(CN)/ ; }, mesh = {Animals ; Bacteria/*immunology ; *Gastrointestinal Microbiome ; Humans ; Immune System/*immunology ; Immunotherapy/*methods ; Neoplasms/immunology/microbiology/*therapy ; Probiotics/*therapeutic use ; }, abstract = {The human microbiome is defined as the microorganisms that reside in or on the human body, such as bacteria, viruses, fungi, and protozoa, and their genomes. The human microbiome participates in the modulation of human metabolism by influencing several intricate pathways. The association between specific bacteria or viruses and the efficacy of cancer treatments and the occurrence of treatment-related toxicity in cancer patients has been reported. However, the understanding of the interaction between the host microbiome and the cancer treatment response is limited, and the microbiome potentially plays a greater role in the treatment of cancer than reported to date. Here, we provide a thorough review of the potential role of the gut and locally resident bacterial microbiota in modulating responses to different cancer therapeutics to demonstrate the association between the gut or locally resident bacterial microbiota and cancer therapy. Probable mechanisms, such as metabolism, the immune response and the translocation of microbiome constituents, are discussed to promote future research into the association between the microbiome and other types of cancer. We conclude that the interaction between the host immune system and the microbiome may be the basis of the role of the microbiome in cancer therapies. Future research on the association between host immunity and the microbiome may improve the efficacy of several cancer treatments and provide insights into the cause of treatment-related side effects.}, }
@article {pmid34410636, year = {2021}, author = {Gopinath, D and Menon, RK}, title = {Increasing Reproducibility in Oral Microbiome Research.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2327}, number = {}, pages = {1-15}, pmid = {34410636}, issn = {1940-6029}, mesh = {*Microbiota ; Mouth ; RNA, Ribosomal, 16S ; Reproducibility of Results ; Specimen Handling ; }, abstract = {Evidence on the role of the oral microbiome in health and disease is changing the way we understand, diagnose, and treat ailments. Numerous studies on diseases affecting the oral cavity have revealed a large amount of data that is invaluable for the advancements in diagnosing and treating these diseases. However, the clinical translation of most of these exploratory data is stalled by variable methodology between studies and non-uniform reporting of the data.Understanding the key areas that are gateways to bias in microbiome studies is imperative to overcome this challenge faced by oral microbiome research. Bias can be multifactorial and may be introduced in a microbiome research study during the formulation of the study design, sample collection and storage, or the sample processing protocols before sequencing. This chapter summarizes the recommendations from literature to eliminate bias in the microbiome research studies and to ensure the reproducibility of the microbiome research data.}, }
@article {pmid34409655, year = {2021}, author = {Huck, O and Mulhall, H and Rubin, G and Kizelnik, Z and Iyer, R and Perpich, JD and Haque, N and Cani, PD and de Vos, WM and Amar, S}, title = {Authors' Response: "Akkermansia muciniphila reduces Porphyromonas gingivalis induced inflammation and periodontal bone destruction".}, journal = {Journal of clinical periodontology}, volume = {48}, number = {11}, pages = {1493-1494}, doi = {10.1111/jcpe.13539}, pmid = {34409655}, issn = {1600-051X}, support = {RO1HL076801/HL/NHLBI NIH HHS/United States ; RO1DE014079/DE/NIDCR NIH HHS/United States ; }, mesh = {Akkermansia ; *Alveolar Bone Loss/prevention &amp; control ; Humans ; Inflammation ; *Porphyromonas gingivalis ; }, }
@article {pmid34408590, year = {2021}, author = {Mazur, M and Tomczak, H and Lodyga, M and Czajkowski, R and Żaba, R and Adamski, Z}, title = {The microbiome of the human skin and its variability in psoriasis and atopic dermatitis.}, journal = {Postepy dermatologii i alergologii}, volume = {38}, number = {2}, pages = {205-209}, pmid = {34408590}, issn = {1642-395X}, abstract = {The human organism is inhabited by very diverse microorganisms, which constitute the so-called human microbiome and are necessary for the proper functioning of the macroorganism. The correct microbiome ensures homeostasis of the body. A disturbance in its homeostasis leads to dysbiosis. Such deviations may also be related to the development of inflammatory skin diseases, including atopic dermatitis and psoriasis. This review aims to analyse the most current published data on the microbiome of the human skin and examine its role in cutaneous skin diseases, such as atopic dermatitis and psoriasis. This review was compiled by collaborating dermatologists specializing in atopic dermatitis and psoriasis. A comprehensive review of current literature was done using PubMed and limited to relevant case reports and original papers on the skin microbiome in atopic dermatitis and/or psoriasis. It has not been yet established whether changes in the microbiome are the cause or consequence of disease (atopic dermatitis/psoriasis). However, it was found that in the cases where pathological microflora predominated, an intensification of lesion severity is observed, while with clinical improvement, commensal microflora is restored. Modification of the composition of the microflora may lead to changes in the activation of the immune system and eventually to the development of inflammatory diseases. Adverse effects on the microbiome may include antibiotics, poor diet, stress and adverse environmental conditions. However, more research is needed to identify exact details and mechanisms.}, }
@article {pmid34407780, year = {2021}, author = {Kværner, AS and Birkeland, E and Bucher-Johannessen, C and Vinberg, E and Nordby, JI and Kangas, H and Bemanian, V and Ellonen, P and Botteri, E and Natvig, E and Rognes, T and Hovig, E and Lyle, R and Ambur, OH and de Vos, WM and Bultman, S and Hjartåker, A and Landberg, R and Song, M and Blix, HS and Ursin, G and Randel, KR and de Lange, T and Hoff, G and Holme, &#xd8; and Berstad, P and Rounge, TB}, title = {The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants.}, journal = {BMC cancer}, volume = {21}, number = {1}, pages = {930}, pmid = {34407780}, issn = {1471-2407}, mesh = {Aged ; Case-Control Studies ; Colonoscopy ; Colorectal Neoplasms/*diagnosis/epidemiology/microbiology ; Early Detection of Cancer/*methods ; Female ; Follow-Up Studies ; *Gastrointestinal Microbiome ; Humans ; Incidence ; *Life Style ; Male ; Middle Aged ; Norway/epidemiology ; Occult Blood ; Prognosis ; Prospective Studies ; ROC Curve ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.<br><br>METHODS: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74&#x2009;years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12&#x2009;months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10&#x2009;year follow-up period.<br><br>DISCUSSION: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01538550 .}, }
@article {pmid34402650, year = {2021}, author = {Adriaenssens, EM}, title = {Phage Diversity in the Human Gut Microbiome: a Taxonomist's Perspective.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0079921}, pmid = {34402650}, issn = {2379-5077}, support = {BBS/E/F/000PR10353/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490/1//UKRI | Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, abstract = {Bacteriophages (phages) have been known for over a century, but only in the last 2 decades have we really come to appreciate how abundant and diverse they are. With that realization, research groups across the globe have shown the importance of phage-based processes in a myriad of environments, including the global oceans and soils, and as part of the human microbiome. Through advances in sequencing technology, genomics, and bioinformatics, we know that the morphological diversity of bacteriophages originally used for taxonomy is eclipsed by their genomic diversity. Because we currently do not have a complete taxonomic framework or naming scheme to describe this diversity, crucial information from virome and microbiome studies is being lost. In this commentary, I will discuss recent advances in taxonomy and its importance for studies of the microbiome with examples of the human gut phageome and make recommendations for future analyses.}, }
@article {pmid34402617, year = {2021}, author = {Esvap, E and Ulgen, KO}, title = {Advances in Genome-Scale Metabolic Modeling toward Microbial Community Analysis of the Human Microbiome.}, journal = {ACS synthetic biology}, volume = {10}, number = {9}, pages = {2121-2137}, doi = {10.1021/acssynbio.1c00140}, pmid = {34402617}, issn = {2161-5063}, mesh = {Gastrointestinal Microbiome ; *Genomics ; Humans ; Inflammatory Bowel Diseases/microbiology/pathology ; Machine Learning ; Metabolic Networks and Pathways/genetics ; Microbiota/*genetics/physiology ; Models, Biological ; Parkinson Disease/microbiology/pathology ; Precision Medicine ; }, abstract = {A genome-scale metabolic model (GEM) represents metabolic pathways of an organism in a mathematical form and can be built using biochemistry and genome annotation data. GEMs are invaluable for understanding organisms since they analyze the metabolic capabilities and behaviors quantitatively and can predict phenotypes. The development of high-throughput data collection techniques led to an immense increase in omics data such as metagenomics, which expand our knowledge on the human microbiome, but this also created a need for systematic analysis of these data. In recent years, GEMs have also been reconstructed for microbial species, including human gut microbiota, and methods for the analysis of microbial communities have been developed to examine the interaction between the organisms or the host. The purpose of this review is to provide a comprehensive guide for the applications of GEMs in microbial community analysis. Starting with GEM repositories, automatic GEM reconstruction tools, and quality control of models, this review will give insights into microbe-microbe and microbe-host interaction predictions and optimization of microbial community models. Recent studies that utilize microbial GEMs and personalized models to infer the influence of microbiota on human diseases such as inflammatory bowel diseases (IBD) or Parkinson's disease are exemplified. Being powerful system biology tools for both species-level and community-level analysis of microbes, GEMs integrated with omics data and machine learning techniques will be indispensable for studying the microbiome and their effects on human physiology as well as for deciphering the mechanisms behind human diseases.}, }
@article {pmid34400408, year = {2021}, author = {Knippel, RJ and Drewes, JL and Sears, CL}, title = {The Cancer Microbiome: Recent Highlights and Knowledge Gaps.}, journal = {Cancer discovery}, volume = {11}, number = {10}, pages = {2378-2395}, pmid = {34400408}, issn = {2159-8290}, support = {R00 CA230192/CA/NCI NIH HHS/United States ; R01 CA196845/CA/NCI NIH HHS/United States ; T32 CA009110/CA/NCI NIH HHS/United States ; C10674/A27140/CRUK_/Cancer Research UK/United Kingdom ; }, mesh = {*Cell Transformation, Neoplastic ; Humans ; *Microbiota ; *Neoplasms ; }, abstract = {Knowledge of the human microbiome, which is likely a critical factor in the initiation, progression, and prognosis of multiple forms of cancer, is rapidly expanding. In this review, we focus on recent investigations to discern putative, causative microbial species and the microbiome composition and structure currently associated with procarcinogenesis and tumorigenesis at select body sites. We specifically highlight forms of cancer, gastrointestinal and nongastrointestinal, that have significant bacterial associations and well-defined experimental evidence with the aim of generating directions for future experimental and translational investigations to develop a clearer understanding of the multifaceted mechanisms by which microbiota affect cancer formation. SIGNIFICANCE: Emerging and, for some cancers, strong experimental and translational data support the contribution of the microbiome to cancer biology and disease progression. Disrupting microbiome features and pathways contributing to cancer may provide new approaches to improving cancer outcomes in patients.}, }
@article {pmid34399524, year = {2021}, author = {van Dongen, KCW and Linkens, AMA and Wetzels, SMW and Wouters, K and Vanmierlo, T and van de Waarenburg, MPH and Scheijen, JLJM and de Vos, WM and Belzer, C and Schalkwijk, CG}, title = {Dietary advanced glycation endproducts (AGEs) increase their concentration in plasma and tissues, result in inflammation and modulate gut microbial composition in mice; evidence for reversibility.}, journal = {Food research international (Ottawa, Ont.)}, volume = {147}, number = {}, pages = {110547}, doi = {10.1016/j.foodres.2021.110547}, pmid = {34399524}, issn = {1873-7145}, mesh = {Animals ; Diet ; *Gastrointestinal Microbiome ; *Glycation End Products, Advanced ; Inflammation ; Mice ; Mice, Inbred C57BL ; }, abstract = {SCOPE: Dietary advanced glycation endproducts (AGEs) are associated with negative biological effects, possibly due to accumulation in plasma and tissues and through modulation of inflammation and gut microbiota. Whether these biological consequences are reversible by limiting dietary AGE intake is unknown.<br><br>METHODS AND RESULTS: Young healthy C57BL/6 mice were fed a standard chow (n&#xa0;=&#xa0;10) or a baked chow high AGE-diet (n&#xa0;=&#xa0;10) (~1.8-6.9 fold increased protein-bound N&#x3b5;-(carboxymethyl)lysine (CML), N&#x3b5;-(1-carboxyethyl)lysine (CEL), and N&#x3b4;-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)) for 10&#xa0;weeks or a switch diet with baked chow for 5&#xa0;weeks followed by 5&#xa0;weeks of standard chow (n&#xa0;=&#xa0;10). We assessed accumulation of AGEs in plasma, kidney, and liver and measured inflammatory markers and gut microbial composition. After 10&#xa0;weeks of baked chow, a substantial panel of AGEs were increased in plasma, liver, and kidney. These increases were normalized after the switch diet. The inflammatory z-score increased after the baked chow diet. Gut microbial composition differed significantly between groups, with enriched Dubosiella spp. dominating these alterations.<br><br>CONCLUSION: A high AGE-diet led to an increase of AGEs in plasma, kidney, and liver and to more inflammation and modification of the gut microbiota. These effects were reversed or discontinued by a diet lower in AGEs.}, }
@article {pmid34387406, year = {2021}, author = {Alenius, H and Sinkko, H and Moitinho-Silva, L and Rodriguez, E and Broderick, C and Alexander, H and Reiger, M and Hjelmsø, MH and Fyhrquist, N and Olah, P and Bryce, P and Smith, C and Koning, F and Eyerich, K and Greco, D and van den Bogaard, EH and Neumann, AU and Traidl-Hoffmann, C and Homey, B and Flohr, C and Bønnelykke, K and Stokholm, J and Weidinger, S}, title = {The power and potential of BIOMAP to elucidate host-microbiome interplay in skin inflammatory diseases.}, journal = {Experimental dermatology}, volume = {30}, number = {10}, pages = {1517-1531}, doi = {10.1111/exd.14446}, pmid = {34387406}, issn = {1600-0625}, mesh = {Dermatitis, Atopic/*immunology/*microbiology ; Humans ; Microbiota/*immunology ; Psoriasis/*immunology/*microbiology ; Skin/*immunology/*microbiology ; }, abstract = {The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time point for intervention are as yet unknown. The BIOMAP project is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome. The consortium includes 7 large pharmaceutical companies and 25 non-industry partners including academia. Since there is mounting evidence supporting an important role for microbial exposures and our microbiota as factors mediating immune polarization and AD and psoriasis pathogenesis, an entire work package is dedicated to the investigation of skin and gut microbiome linked to AD or psoriasis. The large collaborative BIOMAP project will enable the integration of patient cohorts, data and knowledge in unprecedented proportions. The project has a unique opportunity with a potential to bridge and fill the gaps between current problems and solutions. This review highlights the power and potential of the BIOMAP project in the investigation of microbe-host interplay in AD and psoriasis.}, }
@article {pmid34386513, year = {2021}, author = {Jana, UK and Kango, N and Pletschke, B}, title = {Hemicellulose-Derived Oligosaccharides: Emerging Prebiotics in Disease Alleviation.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {670817}, pmid = {34386513}, issn = {2296-861X}, abstract = {The gut microbiota in the human body is an important component that plays a pivotal role in the ability of the host to prevent diseases and recover from these diseases. If the human microbiome changes for any reason, it affects the overall functioning of the host. Healthy and vigorous gut microbiota require dietary fiber supplementation. Recently, oligosaccharides have been found to play a significant role in the modulation of microbiota. Several such oligosaccharides, i.e., xylooligosaccharides (XOS), mannooligosaccharides (MOS), and arabino-xylooligosaccharides (AXOS), are derived from hemicellulosic macromolecules such as xylan, mannan, and arabino-xylan, respectively. These oligosaccharides serve as substrates for the probiotic production of health-promoting substances (short-chain fatty acids, branched chain amino acids etc.), which confer a variety of health benefits, including the prevention of some dreaded diseases. Among hemicellulose-derived oligosaccharides (HDOs), XOS have been largely explored, whereas, studies on MOS and AXOS are currently underway. HDOs, upon ingestion, help reduce morbidities by lowering populations of harmful or pathogenic bacteria. The ATP-binding cassette (ABC) transporters are mainly utilized for the uptake of oligosaccharides in probiotics. Butyrate generated by the selective fermentation of oligosaccharides, along with other short-chain fatty acids, reduces gut inflammation. Overall, oligosaccharides derived from hemicelluloses show a similar potential as conventional prebiotics and can be supplemented as functional foods. This review summarizes the role of HDOs in the alleviation of autoimmune diseases (inflammatory bowel disease, Crohn's disease), diabetes, urinary tract infection, cardiovascular diseases, and antimicrobial resistance (AMR) through the modulation of the gut microbiota. The mechanism of oligosaccharide utilization and disease mitigation is also explained.}, }
@article {pmid34381207, year = {2021}, author = {Fremin, BJ and Nicolaou, C and Bhatt, AS}, title = {Simultaneous ribosome profiling of hundreds of microbes from the human microbiome.}, journal = {Nature protocols}, volume = {16}, number = {10}, pages = {4676-4691}, pmid = {34381207}, issn = {1750-2799}, support = {R01 AI148623/AI/NIAID NIH HHS/United States ; U24 AG021886/AG/NIA NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; P30 AG047366//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; P30 AG066515/AG/NIA NIH HHS/United States ; }, mesh = {Humans ; *Ribosomes/metabolism/genetics ; *Feces/microbiology ; *Microbiota/genetics ; Metagenomics/methods ; Metagenome ; Bacteria/genetics/classification ; High-Throughput Nucleotide Sequencing/methods ; Gastrointestinal Microbiome/genetics ; Ribosome Profiling ; }, abstract = {Ribosome profiling enables sequencing of ribosome-bound fragments of RNA, revealing which transcripts are being translated as well as the position of ribosomes along mRNAs. Although ribosome profiling has been applied to cultured bacterial isolates, its application to uncultured, mixed communities has been challenging. We present MetaRibo-Seq, a protocol that enables the application of ribosome profiling directly to the human fecal microbiome. MetaRibo-Seq is a benchmarked method that includes several modifications to existing ribosome profiling protocols, specifically addressing challenges involving fecal sample storage, purity and input requirements. We also provide a computational workflow to quality control and trim reads, de novo assemble a reference metagenome with metagenomic reads, align MetaRibo-Seq reads to the reference, and assess MetaRibo-Seq library quality (https://github.com/bhattlab/bhattlab_workflows/tree/master/metariboseq). This MetaRibo-Seq protocol enables researchers in standard molecular biology laboratories to study translation in the fecal microbiome in ~5 d.}, }
@article {pmid34379050, year = {2022}, author = {Ahmed, E and Hens, K}, title = {Microbiome in Precision Psychiatry: An Overview of the Ethical Challenges Regarding Microbiome Big Data and Microbiome-Based Interventions.}, journal = {AJOB neuroscience}, volume = {13}, number = {4}, pages = {270-286}, doi = {10.1080/21507740.2021.1958096}, pmid = {34379050}, issn = {2150-7759}, mesh = {Humans ; Big Data ; *Psychiatry ; *Mental Disorders/therapy ; *Microbiota/genetics ; Mental Health ; }, abstract = {There has been a spurt in both fundamental and translational research that examines the underlying mechanisms of the human microbiome in psychiatric disorders. The personalized and dynamic features of the human microbiome suggest the potential of its manipulation for precision psychiatry in ways to improve mental health and avoid disease. However, findings in the field of microbiome also raise philosophical and ethical questions. From a philosophical point of view, they may yet be another attempt at providing a biological cause for phenomena that ultimately cannot be so easily localized. From an ethical point of view, it is relevant that the human gut microbiome comprises data on the individual's lifestyle, disease history, previous medications, and mental health. Massive datasets of microbiome sequences are collected to facilitate comparative studies to identify specific links between the microbiome and mental health. Although this emerging research domain may show promise for psychiatric patients, it is surrounded by ethical challenges regarding patient privacy, health risks, effects on personal identity, and concerns about responsibility. This narrative overview displays the roles and advances of microbiome research in psychiatry and discusses the philosophical and ethical implications of microbiome big data and microbiome-based interventions for psychiatric patients. We also investigate whether these issues are really "new," or "old wine in new bottles."}, }
@article {pmid34376656, year = {2021}, author = {Bui, TPN and Mannerås-Holm, L and Puschmann, R and Wu, H and Troise, AD and Nijsse, B and Boeren, S and Bäckhed, F and Fiedler, D and deVos, WM}, title = {Conversion of dietary inositol into propionate and acetate by commensal Anaerostipes associates with host health.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4798}, pmid = {34376656}, issn = {2041-1723}, mesh = {Acetates/*metabolism ; Animals ; Clostridiales/classification/*metabolism/physiology ; Diet ; Feces/microbiology ; Host Microbial Interactions ; Humans ; Inositol/*metabolism ; Intestines/*chemistry/microbiology ; Magnetic Resonance Spectroscopy/methods ; Male ; Mice, Inbred C57BL ; Phytic Acid/metabolism ; Propionates/*metabolism ; Tandem Mass Spectrometry/methods ; Mice ; }, abstract = {We describe the anaerobic conversion of inositol stereoisomers to propionate and acetate by the abundant intestinal genus Anaerostipes. A inositol pathway was elucidated by nuclear magnetic resonance using [[13]C]-inositols, mass spectrometry and proteogenomic analyses in A. rhamnosivorans, identifying 3-oxoacid CoA transferase as a key enzyme involved in both 3-oxopropionyl-CoA and propionate formation. This pathway also allowed conversion of phytate-derived inositol into propionate as shown with [[13]C]-phytate in fecal samples amended with A. rhamnosivorans. Metabolic and (meta)genomic analyses explained the adaptation of Anaerostipes spp. to inositol-containing substrates and identified a propionate-production gene cluster to be inversely associated with metabolic biomarkers in (pre)diabetes cohorts. Co-administration of myo-inositol with live A. rhamnosivorans in western-diet fed mice reduced fasting-glucose levels comparing to heat-killed A. rhamnosivorans after 6-weeks treatment. Altogether, these data suggest a potential beneficial role for intestinal Anaerostipes spp. in promoting host health.}, }
@article {pmid34372590, year = {2021}, author = {Skurnik, M and Jaakkola, S and Mattinen, L and von Ossowski, L and Nawaz, A and Pajunen, MI and Happonen, LJ}, title = {Bacteriophages fEV-1 and fD1 Infect Yersinia pestis.}, journal = {Viruses}, volume = {13}, number = {7}, pages = {}, pmid = {34372590}, issn = {1999-4915}, mesh = {Bacteriophages/*genetics/*physiology/ultrastructure ; Finland ; *Genome, Viral ; Host Specificity ; Microscopy, Electron, Transmission ; *Proteome ; Sewage ; Yersinia pestis/classification/*virology ; }, abstract = {Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1.}, }
@article {pmid34368762, year = {2021}, author = {Puca, P and Petito, V and Laterza, L and Lopetuso, LR and Neri, M and Del Chierico, F and Boskoski, I and Gasbarrini, A and Scaldaferri, F}, title = {Bariatric procedures and microbiota: patient selection and outcome prediction.}, journal = {Therapeutic advances in gastrointestinal endoscopy}, volume = {14}, number = {}, pages = {26317745211014746}, pmid = {34368762}, issn = {2631-7745}, abstract = {Obesity is a major health issue throughout the world and bariatric surgery plays a key role in its management and treatment. The role of microbiota in determining the pathogenesis of obesity has been widely studied, while its role in determining the outcome of bariatric surgery is an emerging issue that will be an outcome in near future studies. Studies on mice first showed the key role of microbiota in determining obesity, highlighting the fat mass increase in mice transplanted with microbiota from fat individuals, as well as the different microbiota composition between mice undergone to low-fat or high-fat diets. This led to characterize the asset of microbiota composition in obesity: increased abundance of Firmicutes, reduced abundance of Bacteroidetes and other taxonomical features. Variations on the composition of gut microbiome have been detected in patients undergone to diet and/or bariatric surgery procedures. Patients undergone to restricting diets showed lower level of trimethylamine N-oxide and other metabolites strictly associated to microbiome, as well as patients treated with bariatric surgery showed, after the procedure, changes in the relative abundance of Bacteroidetes, Firmicutes and other phyla with a role in the pathogenesis of obesity. Eventually, studies have been led about the effects that the modification of microbiota could have on obesity itself, mainly focusing on elements like fecal microbiota transplantation and probiotics such as inulin. This series of studies and considerations represent the first step in order to select patients eligible to bariatric surgery and to predict their outcome.}, }
@article {pmid34368008, year = {2021}, author = {Josephs-Spaulding, J and Krogh, TJ and Rettig, HC and Lyng, M and Chkonia, M and Waschina, S and Graspeuntner, S and Rupp, J and Møller-Jensen, J and Kaleta, C}, title = {Recurrent Urinary Tract Infections: Unraveling the Complicated Environment of Uncomplicated rUTIs.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {562525}, pmid = {34368008}, issn = {2235-2988}, mesh = {Anti-Bacterial Agents/therapeutic use ; Humans ; Inflammation/drug therapy ; Urinary Bladder ; *Urinary Tract Infections ; }, abstract = {Urinary tract infections (UTIs) are frequent in humans, affecting the upper and lower urinary tract. Present diagnosis relies on the positive culture of uropathogenic bacteria from urine and clinical markers of inflammation of the urinary tract. The bladder is constantly challenged by adverse environmental stimuli which influence urinary tract physiology, contributing to a dysbiotic environment. Simultaneously, pathogens are primed by environmental stressors such as antibiotics, favoring recurrent UTIs (rUTIs), resulting in chronic illness. Due to different confounders for UTI onset, a greater understanding of the fundamental environmental mechanisms and microbial ecology of the human urinary tract is required. Such advancements could promote the tandem translation of bench and computational studies for precision treatments and clinical management of UTIs. Therefore, there is an urgent need to understand the ecological interactions of the human urogenital microbial communities which precede rUTIs. This review aims to outline the mechanistic aspects of rUTI ecology underlying dysbiosis between both the human microbiome and host physiology which predisposes humans to rUTIs. By assessing the applications of next generation and systems level methods, we also recommend novel approaches to elucidate the systemic consequences of rUTIs which requires an integrated approach for successful treatment. To this end, we will provide an outlook towards the so-called 'uncomplicated environment of UTIs', a holistic and systems view that applies ecological principles to define patient-specific UTIs. This perspective illustrates the need to withdraw from traditional reductionist perspectives in infection biology and instead, a move towards a systems-view revolving around patient-specific pathophysiology during UTIs.}, }
@article {pmid34367159, year = {2021}, author = {de Jong, E and Lauzon-Joset, JF and Leffler, J and Serralha, M and Larcombe, AN and Christophersen, CT and Holt, PG and Strickland, DH and Bosco, A}, title = {IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {699633}, pmid = {34367159}, issn = {1664-3224}, mesh = {Allergens/*immunology ; Animals ; Asthma/etiology/*immunology ; Cardiovirus Infections/*immunology ; Cell Extracts/*pharmacology ; Immunophenotyping ; Interferon Regulatory Factor-7/*immunology ; Male ; Rats ; }, abstract = {High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high (BN) versus low susceptibility (PVG) to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype. We also investigated potential risk mitigation via pretreatment with the immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resulted in rapid and transient airways inflammation alongside IRF7 gene network formation. In contrast, responses in high-risk BN rats were characterized by severe airways eosinophilia and exaggerated proinflammatory responses that failed to resolve, and complete absence of IRF7 gene networks. OM-85 had more profound effects in high-risk BN rats, inducing immune-related gene expression changes in lung at baseline and reducing exaggerated airway inflammatory responses to virus/allergen coexposure. In low-risk PVG rats, OM-85 boosted IRF7 gene networks in the lung but did not alter baseline gene expression or cellular influx. Distinct IRF7-associated asthma risk immunophenotypes have dichotomous responses to virus/allergen coexposure and respond differentially to OM-85 pretreatment. Extrapolating to humans, our findings suggest that the beneficial effects OM-85 pretreatment may preferentially target those in high-risk subgroups.}, }
@article {pmid34367134, year = {2021}, author = {Hetemäki, I and Jian, C and Laakso, S and Mäkitie, O and Pajari, AM and de Vos, WM and Arstila, TP and Salonen, A}, title = {Fecal Bacteria Implicated in Biofilm Production Are Enriched and Associate to Gastrointestinal Symptoms in Patients With APECED - A Pilot Study.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {668219}, pmid = {34367134}, issn = {1664-3224}, mesh = {Adult ; Aged ; Antibodies, Fungal/metabolism ; Bacteria/genetics/*growth &amp; development/immunology/metabolism ; Biofilms/*growth &amp; development ; Case-Control Studies ; Dysbiosis ; Feces/*microbiology ; Female ; Finland ; Gastrointestinal Diseases/diagnosis/immunology/metabolism/*microbiology ; *Gastrointestinal Microbiome ; Genetic Predisposition to Disease ; Host-Pathogen Interactions ; Humans ; Immunoglobulin G/metabolism ; Intestines/*microbiology ; Lipopolysaccharides/metabolism ; Male ; Metagenome ; Middle Aged ; *Mutation ; Pilot Projects ; Polyendocrinopathies, Autoimmune/complications/diagnosis/genetics/immunology ; Saccharomyces cerevisiae/genetics/immunology ; Transcription Factors/*genetics ; Young Adult ; AIRE Protein ; }, abstract = {BACKGROUNDS AND AIMS: APECED is a rare autoimmune disease caused by mutations in the Autoimmune Regulator gene. A significant proportion of patients also have gastrointestinal symptoms, including malabsorption, chronic diarrhea, and obstipation. The pathological background of the gastrointestinal symptoms remains incompletely understood and involves multiple factors, with autoimmunity being the most common underlying cause. Patients with APECED have increased immune responses against gut commensals. Our objective was to evaluate whether the intestinal microbiota composition, predicted functions or fungal abundance differ between Finnish patients with APECED and healthy controls, and whether these associate to the patients' clinical phenotype and gastrointestinal symptoms.<br><br>METHODS: DNA was isolated from fecal samples from 15 patients with APECED (median age 46.4 years) together with 15 samples from body mass index matched healthy controls. DNA samples were subjected to analysis of the gut microbiota using 16S rRNA gene amplicon sequencing, imputed metagenomics using the PICRUSt2 algorithm, and quantitative PCR for fungi. Extensive correlations of the microbiota with patient characteristics were determined.<br><br>RESULTS: Analysis of gut microbiota indicated that both alpha- and beta-diversity were altered in patients with APECED compared to healthy controls. The fraction of Faecalibacterium was reduced in patients with APECED while that of Atopobium spp. and several gram-negative genera previously implicated in biofilm formation, e.g. Veillonella, Prevotella, Megasphaera and Heamophilus, were increased in parallel to lipopolysaccharide (LPS) synthesis in imputed metagenomics. The differences in gut microbiota were linked to patient characteristics, especially the presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and severity of gastrointestinal symptoms.<br><br>CONCLUSIONS: Gut microbiota of patients with APECED is altered and enriched with predominantly gram-negative bacterial taxa that may promote biofilm formation and lead to increased exposure to LPS in the patients. The most pronounced alterations in the microbiota were associated with more severe gastrointestinal symptoms.}, }
@article {pmid34365823, year = {2021}, author = {Thiele-Bruhn, S}, title = {The role of soils in provision of genetic, medicinal and biochemical resources.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {376}, number = {1834}, pages = {20200183}, pmid = {34365823}, issn = {1471-2970}, mesh = {*Biodiversity ; Conservation of Natural Resources ; *Ecosystem ; Humans ; *Microbiota ; Mycorrhizae ; Soil/*chemistry ; *Soil Microbiology ; }, abstract = {Intact, 'healthy' soils provide indispensable ecosystem services that largely depend on the biotic activity. Soil health is connected with human health, yet, knowledge of the underlying soil functioning remains incomplete. This review highlights selected services, i.e. (i) soil as a genetic resource and hotspot of biodiversity, forming the basis for providing (ii) biochemical resources and (iii) medicinal services and goods. Soils harbour an unrivalled biodiversity of organisms, especially microorganisms. Some of the abilities of autochthonous microorganisms and their relevant enzymes serve (i) to improve natural soil functions and in particular plant growth, e.g. through beneficial plant growth-promoting, symbiotic and mycorrhizal microorganisms, (ii) to act as biopesticides, (iii) to facilitate biodegradation of pollutants for soil bioremediation and (iv) to yield enzymes or chemicals for industrial use. Soils also exert direct effects on human health. Contact with soil enriches the human microbiome, affords protection against allergies and promotes emotional well-being. Medicinally relevant are soil substrates such as loams, clays and various minerals with curative effects as well as pharmaceutically active organic chemicals like antibiotics that are formed by soil microorganisms. By contrast, irritating minerals, soil dust inhalation and misguided soil ingestion may adversely affect humans. This article is part of the theme issue 'The role of soils in delivering Nature's Contributions to People.}, }
@article {pmid34365651, year = {2021}, author = {Dwivedi, M and Powali, S and Rastogi, S and Singh, A and Gupta, DK}, title = {Microbial community in human gut: a therapeutic prospect and implication in health and diseases.}, journal = {Letters in applied microbiology}, volume = {73}, number = {5}, pages = {553-568}, doi = {10.1111/lam.13549}, pmid = {34365651}, issn = {1472-765X}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {The interest in the working and functionality of the human gut microbiome has increased drastically over the years. Though the existence of gut microbes has long been speculated for long over the last few decades, a lot of research has sprung up in studying and understanding the role of gut microbes in the human digestive tract. The microbes present in the gut are highly instrumental in maintaining the metabolism in the body. Further research is going on in this field to understand how gut microbes can be employed as potential sources of novel therapeutics; moreover, probiotics have also elucidated their significant place in this direction. As regards the clinical perspective, microbes can be engineered to afford defence mechanisms while interacting with foreign pathogenic bodies. More investigations in this field may assist us to evaluate and understand how these cells communicate with human cells and promote immune interactions. Here we elaborate on the possible implication of human gut microbiota into the immune system as well as explore the probiotics in the various human ailments. Comprehensive information on the human gut microbiome at the same platform may contribute effectively to our understanding of the human microbiome and possible mechanisms of associated human diseases.}, }
@article {pmid34364710, year = {2021}, author = {Kanangat, S and Skaljic, I}, title = {Microbiome analysis, the immune response and transplantation in the era of next generation sequencing.}, journal = {Human immunology}, volume = {82}, number = {11}, pages = {883-901}, doi = {10.1016/j.humimm.2021.07.009}, pmid = {34364710}, issn = {1879-1166}, mesh = {Computational Biology ; Dysbiosis/*diagnosis/immunology/microbiology ; Graft Rejection/immunology/prevention &amp; control ; HLA Antigens/genetics ; *High-Throughput Nucleotide Sequencing ; Histocompatibility Testing/methods ; Host Microbial Interactions/genetics/*immunology ; Humans ; Microbiota/*genetics/immunology ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA/methods ; Transplantation, Homologous/adverse effects ; }, abstract = {The human gastrointestinal tract, skin and mucosal surfaces are inhabited by a complex system of bacteria, viruses, fungi, archaea, protists, and eukaryotic parasites with predominance of bacteria and bacterial viruses (bacteriophages). Collectively these microbes form the microbiota of the microecosystem of humans. Recent advancement in technologies for nucleic acid isolation from various environmental samples, feces and body secretions and advancements in shotgun throughput massive parallel DNA and RNA sequencing along with 16S ribosomal gene sequencing have unraveled the identity of otherwise unknown microbial entities constituting the human microecosystem. The improved transcriptome analysis, technological developments in biochemical analytical methods and availability of complex bioinformatics tools have allowed us to begin to understand the metabolome of the microbiome and the biochemical pathways and potential signal transduction pathways in human cells in response to microbial infections and their products. Also, developments in human whole genome sequencing, targeted gene sequencing of histocompatibility genes and other immune response associated genes by Next Generation Sequencing (NGS) have allowed us to have a better conceptualization of immune responses, and alloimmune responses. These modern technologies have enabled us to dive into the intricate relationship between commensal symbiotic and pathogenic microbiome and immune system. For the most part, the commensal symbiotic microbiota helps to maintain normal immune homeostasis besides providing healthy nutrients, facilitating digestion, and protecting the skin, mucosal and intestinal barriers. However, changes in diets, administration of therapeutic agents like antibiotics, chemotherapeutic agents, immunosuppressants etc. along with certain host factors including human histocompatibility antigens may alter the microbial ecosystem balance by causing changes in microbial constituents, hierarchy of microbial species and even dysbiosis. Such alterations may cause immune dysregulation, breach of barrier protection and lead to immunopathogenesis rather than immune homeostasis. The effects of human microbiome on immunity, health and disease are currently under intense research with cutting edge technologies in molecular biology, biochemistry, and bioinformatics along with tremendous ability to characterize immune response at single cell level. This review will discuss the contemporary status on human microbiome immune system interactions and their potential effects on health, immune homeostasis and allograft transplantation.}, }
@article {pmid34361885, year = {2021}, author = {Kim, JC and Park, MJ and Park, S and Lee, ES}, title = {Alteration of the Fecal but Not Salivary Microbiome in Patients with Behçet's Disease According to Disease Activity Shift.}, journal = {Microorganisms}, volume = {9}, number = {7}, pages = {}, pmid = {34361885}, issn = {2076-2607}, abstract = {The human microbiome plays an important role in various diseases, including Behçet's disease (BD). However, the effects of disease activity and covariates influencing the microbial composition have not yet been investigated. Therefore, we investigated the fecal and salivary microbiomes of BD patients compared to those of recurrent aphthous ulcer (RAU) patients, as well as dietary habit-matched healthy controls (HCs) selected from immediate family members using 16S rRNA gene sequencing. The fecal microbiome alpha diversity of BD patients was not different from that of their matched HCs, although it was higher than that of unrelated HCs and decreased in BD patients with disease activity. A tendency toward clustering in the beta diversity of the fecal microbiome was observed between the active BD patients and their matched HCs. Active BD patients had a significantly higher abundance of fecal Bacteroides uniformis than their matched HCs and patients with the disease in an inactive state (p = 0.038). The abundance of salivary Rothia mucilaginosa group was higher in BD patients than in RAUs patients. BD patients with uveitis had different abundances of various taxa, compared to those without uveitis. Our results showed an association of fecal microbiome composition with BD disease activity and symptoms, suggesting the possible role of the gut microbiome in BD pathogenesis.}, }
@article {pmid34361691, year = {2021}, author = {Puebla-Barragan, S and Watson, E and van der Veer, C and Chmiel, JA and Carr, C and Burton, JP and Sumarah, M and Kort, R and Reid, G}, title = {Interstrain Variability of Human Vaginal Lactobacillus crispatus for Metabolism of Biogenic Amines and Antimicrobial Activity against Urogenital Pathogens.}, journal = {Molecules (Basel, Switzerland)}, volume = {26}, number = {15}, pages = {}, pmid = {34361691}, issn = {1420-3049}, support = {692895//Consejo Nacional de Ciencia y Tecnolog&#xed;a/ ; }, mesh = {Anti-Infective Agents/*metabolism ; Biogenic Amines/*metabolism ; Candida albicans/metabolism ; Dysbiosis/metabolism/microbiology ; Enterococcus faecium/metabolism ; Escherichia coli/metabolism ; Female ; Female Urogenital Diseases/*metabolism/*microbiology ; Genomics/methods ; Humans ; Lactobacillus crispatus/classification/genetics/*metabolism ; Metabolome ; Metabolomics/methods ; *Microbiota ; Phylogeny ; Prevotella/metabolism ; Probiotics/metabolism ; Vagina/*microbiology ; }, abstract = {Lactobacillus crispatus is the dominant species in the vagina of many women. With the potential for strains of this species to be used as a probiotic to help prevent and treat dysbiosis, we investigated isolates from vaginal swabs with Lactobacillus-dominated and a dysbiotic microbiota. A comparative genome analysis led to the identification of metabolic pathways for synthesis and degradation of three major biogenic amines in most strains. However, targeted metabolomic analysis of the production and degradation of biogenic amines showed that certain strains have either the ability to produce or to degrade these compounds. Notably, six strains produced cadaverine, one produced putrescine, and two produced tyramine. These biogenic amines are known to raise vaginal pH, cause malodour, and make the environment more favourable to vaginal pathogens. In vitro experiments confirmed that strains isolated from women with a dysbiotic vaginal microbiota have higher antimicrobial effects against the common urogenital pathogens Escherichia coli and Enterococcus faecium. The results indicate that not all L. crispatus vaginal strains appear suitable for probiotic application and the basis for selection should not be only the overall composition of the vaginal microbiota of the host from which they came, but specific biochemical and genetic traits.}, }
@article {pmid34358008, year = {2021}, author = {Chow, EWL and Pang, LM and Wang, Y}, title = {From Jekyll to Hyde: The Yeast-Hyphal Transition of Candida albicans.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {34358008}, issn = {2076-0817}, support = {NMRC/OFIRG/0072/2018 and NMRC/OFIRG/0055/2019//National Medical Research Council of Singapore/ ; NRF2019-NRF-ISF003-3039//National Research Foundation of Singapore/ ; }, abstract = {Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people. Under constant exposure to highly dynamic environmental cues in diverse host niches, C. albicans has successfully evolved to adapt to both commensal and pathogenic lifestyles. The ability of C. albicans to undergo a reversible morphological transition from yeast to filamentous forms is a well-established virulent trait. Over the past few decades, a significant amount of research has been carried out to understand the underlying regulatory mechanisms, signaling pathways, and transcription factors that govern the C. albicans yeast-to-hyphal transition. This review will summarize our current understanding of well-elucidated signal transduction pathways that activate C. albicans hyphal morphogenesis in response to various environmental cues and the cell cycle machinery involved in the subsequent regulation and maintenance of hyphal morphogenesis.}, }
@article {pmid34355132, year = {2021}, author = {Barton, W and Cronin, O and Garcia-Perez, I and Whiston, R and Holmes, E and Woods, T and Molloy, CB and Molloy, MG and Shanahan, F and Cotter, PD and O'Sullivan, O}, title = {The effects of sustained fitness improvement on the gut microbiome: A longitudinal, repeated measures case-study approach.}, journal = {Translational sports medicine}, volume = {4}, number = {2}, pages = {174-192}, pmid = {34355132}, issn = {2573-8488}, support = {CDF-2017-10-032/DH_/Department of Health/United Kingdom ; PDF-2012-05-456/DH_/Department of Health/United Kingdom ; }, abstract = {The athlete gut microbiome differs from that of non-athletes in its composition and metabolic function. Short-term fitness improvement in sedentary adults does not replicate the microbiome characteristics of athletes. The objective of this study was to investigate whether sustained fitness improvement leads to pronounced alterations in the gut microbiome. This was achieved using a repeated-measures, case-study approach that examined the gut microbiome of two initially unfit volunteers undertaking progressive exercise training over a 6-month period. Samples were collected every two weeks, and microbiome, metabolome, diet, body composition, and cardiorespiratory fitness data were recorded. Training culminated in both participants completing their respective goals (a marathon or Olympic-distance triathlon) with improved body composition and fitness parameters. Increases in gut microbiota α-diversity occurred with sustained training and fluctuations occurred in response to training events (eg, injury, illness, and training peaks). Participants' BMI reduced during the study and was significantly associated with increased urinary measurements of N-methyl nicotinate and hippurate, and decreased phenylacetylglutamine. These results suggest that sustained fitness improvements support alterations to gut microbiota and physiologically-relevant metabolites. This study provides longitudinal analysis of the gut microbiome response to real-world events during progressive fitness training, including intercurrent illness and injury.}, }
@article {pmid34350192, year = {2021}, author = {De Vincentis, A and Santonico, M and Del Chierico, F and Altomare, A and Marigliano, B and Laudisio, A and Reddel, S and Grasso, S and Zompanti, A and Pennazza, G and Putignani, L and Guarino, MPL and Cicala, M and Antonelli Incalzi, R}, title = {Gut Microbiota and Related Electronic Multisensorial System Changes in Subjects With Symptomatic Uncomplicated Diverticular Disease Undergoing Rifaximin Therapy.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {655474}, pmid = {34350192}, issn = {2296-858X}, abstract = {Background: Intestinal dysbiosis might play a pathogenetic role in subjects with symptomatic uncomplicated diverticular disease (SUDD), but the effect of rifaximin therapy has been scantly explored with regard to gut microbiota variations in patients with SUDD. Aims: To verify to which extent rifaximin treatment affects the gut microbiota and whether an electronic multisensorial assessment of stools and breath has the potential for detecting these changes. Methods: Breath and stool samples were collected from consecutive patients with SUDD before and after a 7 days' therapy with rifaximin. Stool microbiota was assessed, and the electronic multisensorial assessment was carried out by means of the BIONOTE electronic (e-)tongue in stools and (e-)nose in breath. Results: Forty-three subjects (female 60%, median age 66 years) were included, and 20 (47%) reported clinical improvement after rifaximin therapy. Alpha and beta diversity of stool microbiota did not significantly change after treatment, while a significant variation of selected taxa was shown (i.e., Citrobacter, Coprococcus, Anaerotruncus, Blautia, Eggerthella lenta, Dehalobacterium, SMB53, and Haemophilus parainfluenzae). Overall, the electronic multisensorial system suboptimally mirrored microbiota changes, but it was able to efficiently predict patients' clinical improvement after rifaximin with accuracies ranging from 0.81 to 0.98. Conclusions: In patients with SUDD, rifaximin administration is associated with significant variation of selected taxa. While inaccurate in predicting gut microbiota change, an electronic multisensorial system, made up of e-tongue and e-nose, was able to predict clinical improvement, thus potentially qualifying as an easy and cheap tool to forecast subjects taking most likely benefit from rifaximin therapy.}, }
@article {pmid34348558, year = {2022}, author = {Bajinka, O and Simbilyabo, L and Tan, Y and Jabang, J and Saleem, SA}, title = {Lung-brain axis.}, journal = {Critical reviews in microbiology}, volume = {48}, number = {3}, pages = {257-269}, doi = {10.1080/1040841X.2021.1960483}, pmid = {34348558}, issn = {1549-7828}, mesh = {Animals ; Brain ; *Gastrointestinal Microbiome ; Lung ; *Neurodegenerative Diseases ; Prospective Studies ; *Respiratory Tract Infections ; }, abstract = {The appreciation of human microbiome is gaining strong grounds in biomedical research. In addition to gut-brain axis, is the lung-brain axis, which is hypothesised to link pulmonary microbes to neurodegenerative disorders and behavioural changes. There is a need for analysis based on emerging studies to map out the prospects for lung-brain axis. In this review, relevant English literature and researches in the field of 'lung-brain axis' is reported. We recommend all the highlighted prospective studies to be integrated with an interdisciplinary approach. This might require conceptual research approaches based on physiology and pathophysiology. Multimodal aspects should include experimental animal units, while exploring the research gaps and making reference to the already existing human data. The overall microbiome medicine is gaining more ground. Aetiological paths and experimental recommendations as per prospective studies in this review will be an important guideline to develop effective treatments for any lung induced neurodegenerative diseases. An in-depth knowledge of the bi-directional communication between host and microbiome in the lung could help treatment to respiratory infections, alleviate stress, anxiety and enhanced neurological effects. The timely prevention and treatment of neurodegenerative diseases requires paradigm shift of the aetiology and more innovative experimentation.Impact statementThe overall microbiome medicine is gaining more ground. An in-depth knowledge of the bi-directional communication between host and microbiome in the lung could confer treatment to respiratory infections, alleviate stress, anxiety and enhanced neurological effects. Based on this review, we recommend all the highlighted prospective studies to be integrated and be given an interdisciplinary approach. This might require conceptual research approaches based on physiology and pathophysiology. Multimodal aspects should include experimental animal units; while exploring the research gaps and making reference to the already existing human data.}, }
@article {pmid34348151, year = {2021}, author = {Kieft, K and Breister, AM and Huss, P and Linz, AM and Zanetakos, E and Zhou, Z and Rahlff, J and Esser, SP and Probst, AJ and Raman, S and Roux, S and Anantharaman, K}, title = {Virus-associated organosulfur metabolism in human and environmental systems.}, journal = {Cell reports}, volume = {36}, number = {5}, pages = {109471}, doi = {10.1016/j.celrep.2021.109471}, pmid = {34348151}, issn = {2211-1247}, mesh = {*Environment ; Gastrointestinal Microbiome ; Genes, Viral ; Genetic Variation ; Genomics ; Humans ; Metabolic Networks and Pathways/genetics ; Microbiota ; Organic Chemicals/*metabolism ; Phylogeny ; Recombination, Genetic/genetics ; Sulfides/metabolism ; Sulfur/*metabolism ; Viruses/genetics/*metabolism ; }, abstract = {Viruses influence the fate of nutrients and human health by killing microorganisms and altering metabolic processes. Organosulfur metabolism and biologically derived hydrogen sulfide play dynamic roles in manifestation of diseases, infrastructure degradation, and essential biological processes. Although microbial organosulfur metabolism is well studied, the role of viruses in organosulfur metabolism is unknown. Here, we report the discovery of 39 gene families involved in organosulfur metabolism encoded by 3,749 viruses from diverse ecosystems, including human microbiomes. The viruses infect organisms from all three domains of life. Six gene families encode for enzymes that degrade organosulfur compounds into sulfide, whereas others manipulate organosulfur compounds and may influence sulfide production. We show that viral metabolic genes encode key enzymatic domains, are translated into protein, and are maintained after recombination, and sulfide provides a fitness advantage to viruses. Our results reveal viruses as drivers of organosulfur metabolism with important implications for human and environmental health.}, }
@article {pmid34348027, year = {2021}, author = {Britton, GJ and Faith, JJ}, title = {Causative Microbes in Host-Microbiome Interactions.}, journal = {Annual review of microbiology}, volume = {75}, number = {}, pages = {223-242}, doi = {10.1146/annurev-micro-041321-042402}, pmid = {34348027}, issn = {1545-3251}, mesh = {Animals ; Host Microbial Interactions ; *Microbiota ; Symbiosis ; }, abstract = {Despite identification of numerous associations between microbiomes and diseases, the complexity of the human microbiome has hindered identification of individual species and strains that are causative in host phenotype or disease. Uncovering causative microbes is vital to fully understand disease processes and to harness the potential therapeutic benefits of microbiota manipulation. Developments in sequencing technology, animal models, and bacterial culturing have facilitated the discovery of specific microbes that impact the host and are beginning to advance the characterization of host-microbiome interaction mechanisms. We summarize the historical and contemporary experimental approaches taken to uncover microbes from the microbiota that affect host biology and describe examples of commensals that have specific effects on the immune system, inflammation, and metabolism. There is still much to learn, and we lay out challenges faced by the field and suggest potential remedies for common pitfalls encountered in the hunt for causative commensal microbes.}, }
@article {pmid34342530, year = {2021}, author = {Kuthyar, S and Reese, AT}, title = {Variation in Microbial Exposure at the Human-Animal Interface and the Implications for Microbiome-Mediated Health Outcome.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0056721}, pmid = {34342530}, issn = {2379-5077}, support = {T32 GM127235/GM/NIGMS NIH HHS/United States ; }, abstract = {The human gut microbiome varies between populations, largely reflecting ecological differences. One ecological variable that is rarely considered but may contribute substantially to microbiome variation is the multifaceted nature of human-animal interfaces. We present the hypothesis that different interactions with animals contribute to shaping the human microbiome globally. We utilize a One Health framework to explore how changes in microbial exposure from human-animal interfaces shape the microbiome and, in turn, contribute to differential human health across populations, focusing on commensal and pathogen exposure, changes in colonization resistance and immune system training, and the potential for other functional shifts. Although human-animal interfaces are known to underlie human health and particularly infectious disease disparities, since their impact on the human microbiome remains woefully understudied, we propose foci for future research. We believe it will be crucial to understand this critical aspect of biology and its impacts on human health around the globe.}, }
@article {pmid34335499, year = {2021}, author = {Peterson, D and Bonham, KS and Rowland, S and Pattanayak, CW and ,  and Klepac-Ceraj, V}, title = {Comparative Analysis of 16S rRNA Gene and Metagenome Sequencing in Pediatric Gut Microbiomes.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {670336}, pmid = {34335499}, issn = {1664-302X}, abstract = {The colonization of the human gut microbiome begins at birth, and over time, these microbial communities become increasingly complex. Most of what we currently know about the human microbiome, especially in early stages of development, was described using culture-independent sequencing methods that allow us to identify the taxonomic composition of microbial communities using genomic techniques, such as amplicon or shotgun metagenomic sequencing. Each method has distinct tradeoffs, but there has not been a direct comparison of the utility of these methods in stool samples from very young children, which have different features than those of adults. We compared the effects of profiling the human infant gut microbiome with 16S rRNA amplicon vs. shotgun metagenomic sequencing techniques in 338 fecal samples; younger than 15, 15-30, and older than 30 months of age. We demonstrate that observed changes in alpha-diversity and beta-diversity with age occur to similar extents using both profiling methods. We also show that 16S rRNA profiling identified a larger number of genera and we find several genera that are missed or underrepresented by each profiling method. We present the link between alpha diversity and shotgun metagenomic sequencing depth for children of different ages. These findings provide a guide for selecting an appropriate method and sequencing depth for the three studied age groups.}, }
@article {pmid34332502, year = {2021}, author = {Moeller, AH}, title = {Genomic Expansions in the Human Gut Microbiome.}, journal = {Genome biology and evolution}, volume = {13}, number = {7}, pages = {}, pmid = {34332502}, issn = {1759-6653}, support = {R35 GM138284/GM/NIGMS NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/genetics ; Genome, Bacterial ; Genomics ; Humans ; Metagenome ; *Microbiota ; }, abstract = {Bacteria inhabiting the human body vary in genome size by over an order of magnitude, but the processes that generate this diversity are poorly understood. Here, we show that evolutionary forces drive divergence in genome size between bacterial lineages in the gut and their closest relatives in other body sites. Analyses of thousands of reference bacterial isolate genomes and metagenome-assembled genomes from the human microbiome indicated that transitions into the gut from other body sites have promoted genomic expansions, whereas the opposite transitions have promoted genomic contractions. Bacterial genomes in the gut are on average ∼127 kb larger than their closest congeneric relatives from other body sites. Moreover, genome size and relative abundance are positively associated within the gut but negatively associated at other body sites. These results indicate that the gut microbiome promotes expansions of bacterial genomes relative to other body sites.}, }
@article {pmid34331994, year = {2021}, author = {Suojalehto, H and Ndika, J and Lindström, I and Airaksinen, L and Karisola, P and Alenius, H}, title = {Endotyping asthma related to 3 different work exposures.}, journal = {The Journal of allergy and clinical immunology}, volume = {148}, number = {4}, pages = {1072-1080}, doi = {10.1016/j.jaci.2021.07.019}, pmid = {34331994}, issn = {1097-6825}, mesh = {Adult ; Air Pollutants, Occupational/*adverse effects ; Asthma, Occupational/blood/*genetics/immunology/physiopathology ; Biomarkers ; Biopsy ; Cell Movement ; Cytokines/blood ; Flour/*adverse effects ; Gene Expression Profiling ; Humans ; Immunoglobulin E/blood ; Inhalation Exposure/*adverse effects ; Isocyanates/*adverse effects ; Leukocytes/immunology ; Male ; Middle Aged ; Nasal Mucosa/pathology ; Nitric Oxide/metabolism ; Occupational Exposure/*adverse effects ; Respiratory Function Tests ; *Welding ; }, abstract = {BACKGROUND: Work exposures play a significant role in adult-onset asthma, but the mechanisms of work-related asthma are not fully elucidated.<br><br>OBJECTIVE: We aimed to reveal the molecular mechanisms of work-related asthma associated with exposure to flour (flour asthma), isocyanate (isocyanate asthma), or welding fumes (welding asthma) and identify potential biomarkers that distinguish these groups from each other.<br><br>METHODS: We used a combination of clinical tests, transcriptomic analysis, and associated pathway analyses to investigate the underlying disease mechanisms of the blood immune cells and the airway epithelium of 61 men.<br><br>RESULTS: Compared with the healthy controls, the welding asthma patients had more differentially expressed genes than the flour asthma and isocyanate asthma patients, both in the airway epithelia and in the blood immune cells. In the airway epithelia, active inflammation was detected only in welding asthma patients. In contrast, many differentially expressed genes were detected in blood cells in all 3 asthma groups. Disease-related immune functions in blood cells, including leukocyte migration and inflammatory responses, and decreased expression of upstream cytokines such as TNF and IFN-&#x3b3; were suppressed in all the asthma groups. In transcriptome-phenotype correlations, hyperresponsiveness (R &#x223c; |0.6|) had the highest clinical relevance and was associated with a set of exposure group-specific genes. Finally, biomarker subsets of only 5&#xa0;genes&#xa0;specifically distinguished each of the asthma exposure groups.<br><br>CONCLUSIONS: This study provides novel data on the molecular mechanisms underlying work-related asthma. We identified a set of 5 promising biomarkers in asthma related to flour, isocyanate, and welding fume exposure to be tested and clinically validated in future studies.}, }
@article {pmid34330476, year = {2021}, author = {Varsha, KK and Maheshwari, AP and Nampoothiri, KM}, title = {Accomplishment of probiotics in human health pertaining to immunoregulation and disease control.}, journal = {Clinical nutrition ESPEN}, volume = {44}, number = {}, pages = {26-37}, doi = {10.1016/j.clnesp.2021.06.020}, pmid = {34330476}, issn = {2405-4577}, mesh = {Dietary Supplements ; *Gastrointestinal Microbiome ; Humans ; *Intestinal Diseases ; *Probiotics ; }, abstract = {It is a well-established fact that the microbiome harboring the human body plays a critical role in maintaining human health and can influence treatments against various ailments. Human microbiome-based research contemplates the possibility of selecting and administering specific commensal bacterial strains to modulate the gut microbiota to attain favorable outcomes to the therapies. Consumption of probiotics and probiotic-based dietary supplements as functional foods has been a promising treatment strategy against various diseases. Clinical studies demonstrate that probiotic administration alters gut microbiota composition and instigates immune modulation in the host. The benefits of probiotics are reported to be strain-specific and depend on the host's baseline immune competence. This review explores the role of probiotics in alleviating symptoms of allergy, cancer, cardio vascular (CV) diseases, diabetes mellitus (DM), bowel diseases (IBD and IBS), periodontal disease, diseases affecting liver and kidney, neuroinflammatory diseases, and viral infections. Also, it surveyed the broad spectrum bioactive compounds produced by probiotics and possible mechanisms that trigger the immune system.}, }
@article {pmid34329771, year = {2021}, author = {Avis, T and Wilson, FX and Khan, N and Mason, CS and Powell, DJ}, title = {Targeted microbiome-sparing antibiotics.}, journal = {Drug discovery today}, volume = {26}, number = {9}, pages = {2198-2203}, doi = {10.1016/j.drudis.2021.07.016}, pmid = {34329771}, issn = {1878-5832}, support = {/WT_/Wellcome Trust/United Kingdom ; }, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/diagnosis/drug therapy/microbiology ; Dysbiosis/*prevention &amp; control ; Humans ; Microbiota/*drug effects ; }, abstract = {A factor in our inability to meet the challenge of clinical antibiotic resistance has been the low productivity of research and development (R&amp;D) efforts, with only incremental improvements on existing broad-spectrum classes coming into clinical use recently. The disappointing returns from this approach have focussed attention on narrower-spectrum antibiotics; such new agents are directed against the pathogen of relevance with the additional benefit of preserving the human microbiome(s). Our knowledge of the gut microbiome and its contribution to health homeostasis increases yearly and suggests that broad-spectrum treatments incur health costs beyond the initial infection. Improved diagnostics, antibiotic stewardship, and the crucial role of the gut microbiome in health indicate targeted agents as a more viable approach for future antibiotic R&amp;D.}, }
@article {pmid34329170, year = {2022}, author = {Ko, YJ and Kim, S and Pan, CH and Park, K}, title = {Identification of Functional Microbial Modules Through Network-Based Analysis of Meta-Microbial Features Using Matrix Factorization.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {19}, number = {5}, pages = {2851-2862}, doi = {10.1109/TCBB.2021.3100893}, pmid = {34329170}, issn = {1557-9964}, mesh = {*Algorithms ; Humans ; *Microbiota/genetics ; }, abstract = {As the microbiome is composed of a variety of microbial interactions, it is imperative in microbiome research to identify a microbial sub-community that collectively conducts a specific function. However, current methodologies have been highly limited to analyzing conditional abundance changes of individual microorganisms without considering group-wise collective microbial features. To overcome this limitation, we developed a network-based method using nonnegative matrix factorization (NMF) to identify functional meta-microbial features (MMFs) that, as a group, better discriminate specific environmental conditions of samples using microbiome data. As proof of concept, large-scale human microbiome data collected from different body sites were used to identify body site-specific MMFs by applying NMF. The statistical test for MMFs led us to identify highly discriminative MMFs on sample classes, called synergistic MMFs (SYMMFs). Finally, we constructed a SYMMF-based microbial interaction network (SYMMF-net) by integrating all of the SYMMF information. Network analysis revealed core microbial modules closely related to critical sample properties. Similar results were also found when the method was applied to various disease-associated microbiome data. The developed method interprets high-dimensional microbiome data by identifying functional microbial modules on sample properties and intuitively representing their systematic relationships via a microbial network.}, }
@article {pmid34319607, year = {2021}, author = {Briana, DD and Papaevangelou, V and Malamitsi-Puchner, A}, title = {The jury is still out on the existence of a placental microbiome.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {110}, number = {11}, pages = {2958-2963}, doi = {10.1111/apa.16048}, pmid = {34319607}, issn = {1651-2227}, mesh = {Bacteria ; Female ; Fetus ; Humans ; *Infertility ; *Microbiota ; Placenta ; Pregnancy ; }, abstract = {The human microbiome is crucial for regulating normal development, but the exact point when it is established remains unknown. A sterile placenta was traditionally considered a prerequisite for a healthy pregnancy, but studies have revealed that the placenta harbours microbial communities, even under normal conditions. However, reports have failed to provide evidence for the consistent presence of bacteria in the normal human placenta, challenging the in utero colonisation hypothesis. This mini review examines our understanding of the potential placental microbial colonisation in normal healthy pregnancies. This may impact the metabolic and immune functions of the growing foetus and have long-term consequences.}, }
@article {pmid34319583, year = {2022}, author = {Aronson, MR and Ali Akbari Ghavimi, S and Gehret, PM and Jacobs, IN and Gottardi, R}, title = {Drug-Eluting Endotracheal Tubes for Preventing Bacterial Inflammation in Subglottic Stenosis.}, journal = {The Laryngoscope}, volume = {132}, number = {7}, pages = {1356-1363}, doi = {10.1002/lary.29769}, pmid = {34319583}, issn = {1531-4995}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria ; Constriction, Pathologic/complications ; Humans ; Inflammation ; Intubation, Intratracheal/adverse effects ; *Laryngostenosis/etiology/prevention &amp; control ; }, abstract = {OBJECTIVES/HYPOTHESIS: Subglottic stenosis (SGS) results from dysregulated extracellular matrix deposition by laryngotracheal fibroblasts causing scar tissue formation following intubation. Recent work has highlighted a relationship between this inflammatory state and imbalances in the upper airway microbiome. Herein, we engineer novel drug-eluting endotracheal (ET) tubes to deliver a model antimicrobial peptide Lasioglossin-III (Lasio) for the local modulation of the microbiome during intubation.<br><br>STUDY DESIGN: Controlled in vitro study.<br><br>METHODS: ET tubes were coated with a water-in-oil (w/o) emulsion of Lasio in poly(d,l-lactide-co-glycolide) (PLGA) by dipping thrice. Peptide release was quantified over 2&#x2009;weeks via fluorometric peptide assays. The antibacterial activity was tested against airway microbes (Staphylococcus epidermidis, Streptococcus pneumoniae, and pooled human microbiome samples) by placing Lasio/PLGA-coated tubes and appropriate controls in 48 well plates with diluted bacteria. Bacterial inhibition and tube adhesion were tested by measuring optical density and colony formation after tube culture, respectively. Biocompatibility was tested against laryngotracheal fibroblasts and lung epithelial cells.<br><br>RESULTS: We achieved a homogeneous coating of ET tubes with Lasio in a PLGA matrix that yields a prolonged, linear release over 1&#x2009;week (typical timeframe before the ET tube is changed). We observed significant antibacterial activity against S. epidermidis, S. pneumoniae, and human microbiome samples, and prevention of bacterial adherence to the tube. Additionally, the released Lasio did not cause any cytotoxicity toward laryngotracheal fibroblasts or lung epithelial cells in vitro.<br><br>CONCLUSION: Overall, we demonstrate the design of an effective-eluting ET tube to modulate upper-airway bacterial infections during intubation which could be deployed to help prevent SGS.<br><br>LEVEL OF EVIDENCE: NA Laryngoscope, 132:1356-1363, 2022.}, }
@article {pmid34315165, year = {2022}, author = {Bernard, R and Fazili, I and Rajagopala, SV and Das, SR and Hiremath, G}, title = {Association between Oral Microbiome and Esophageal Diseases: A State-of-the-Art Review.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {40}, number = {3}, pages = {345-354}, pmid = {34315165}, issn = {1421-9875}, support = {K12 HD087023/HD/NICHD NIH HHS/United States ; R21 AI149262/AI/NIAID NIH HHS/United States ; T32 HD060554/HD/NICHD NIH HHS/United States ; P30 AI110527/AI/NIAID NIH HHS/United States ; U19 AI095227/AI/NIAID NIH HHS/United States ; R01 HL146401/HL/NHLBI NIH HHS/United States ; R21 AI142321/AI/NIAID NIH HHS/United States ; R21 AI154016/AI/NIAID NIH HHS/United States ; }, mesh = {*Barrett Esophagus/pathology ; *Esophageal Diseases/complications ; *Esophageal Neoplasms/pathology ; Humans ; *Microbiota ; *Precancerous Conditions/pathology ; }, abstract = {BACKGROUND: Esophageal conditions result in significant morbidity and mortality worldwide. There is growing enthusiasm for discerning the role of microbiome in esophageal diseases. Conceivably, the focus has been on examining the role of local microbiome in esophageal diseases although this is somewhat limited by the invasive approach required to sample the esophageal tissue. Given the ease of sampling the oral cavity combined with the advances in genomic techniques, there is immense interest in discovering the role of the oral microbiome in esophageal conditions.<br><br>SUMMARY: In this review, we aim to discuss the current evidence highlighting the association between the oral microbiome and esophageal diseases. In particular, we have focused on summarizing the alterations in oral microbiome associated with malignant, premalignant, and benign esophageal cancers, inflammatory and infectious conditions, and esophageal dysmotility diseases. Identifying alterations in the oral microbiome is a key to advancing our understanding of the etiopathogenesis and progression of esophageal diseases, promoting novel diagnostics, and laying the foundation for personalized treatment approaches.<br><br>KEY MESSAGES: Further studies are needed to unravel the mechanisms by which the oral microbiome influences the development and progression of esophageal diseases, as well as to investigate whether alterations in the oral microbiome can impact the natural history of various esophageal diseases.}, }
@article {pmid34314593, year = {2021}, author = {Heinken, A and Basile, A and Hertel, J and Thinnes, C and Thiele, I}, title = {Genome-Scale Metabolic Modeling of the Human Microbiome in the Era of Personalized Medicine.}, journal = {Annual review of microbiology}, volume = {75}, number = {}, pages = {199-222}, doi = {10.1146/annurev-micro-060221-012134}, pmid = {34314593}, issn = {1545-3251}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Microbiota ; Precision Medicine ; }, abstract = {The human microbiome plays an important role in human health and disease. Meta-omics analyses provide indispensable data for linking changes in microbiome composition and function to disease etiology. Yet, the lack of a mechanistic understanding of, e.g., microbiome-metabolome links hampers the translation of these findings into effective, novel therapeutics. Here, we propose metabolic modeling of microbial communities through constraint-based reconstruction and analysis (COBRA) as a complementary approach to meta-omics analyses. First, we highlight the importance of microbial metabolism in cardiometabolic diseases, inflammatory bowel disease, colorectal cancer, Alzheimer disease, and Parkinson disease. Next, we demonstrate that microbial community modeling can stratify patients and controls, mechanistically link microbes with fecal metabolites altered in disease, and identify host pathways affected by the microbiome. Finally, we outline our vision for COBRA modeling combined with meta-omics analyses and multivariate statistical analyses to inform and guide clinical trials, yield testable hypotheses, and ultimately propose novel dietary and therapeutic interventions.}, }
@article {pmid34313463, year = {2021}, author = {Lichtenstein, M and Turjerman, S and Pinto, JM and Barash, O and Koren, O}, title = {Pathophysiology of SARS-CoV-2 Infection in the Upper Respiratory Tract and Its Relation to Breath Volatile Organic Compounds.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0010421}, pmid = {34313463}, issn = {2379-5077}, abstract = {Among the many products of metabolic processes are volatile organic compounds (VOCs). In the airways, these volatile metabolites are emitted through breathing and thus are easily sampled for analysis. Recent work has connected the functions and structure of the human microbiome with health and disease. Alteration in microbial function in this context can result in differences in metabolite composition, including that of VOCs, presenting the possibility of a new noninvasive method for clinical diagnosis. Screening methods that assess VOCs arising from changes in the airway microbiome could be highly useful in diagnosing viral upper respiratory tract infections (URTIs), e.g., COVID-19, which are highly contagious and have an enormous public health impact worldwide. A rapid noninvasive screening test for URTIs would pose major advantages in containing the disease. As early evidence shows that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the human microbiome (both in the gut and the respiratory tract), we propose that detection of a VOC signature of an altered nasal microbiome could be fruitful as a rapid noninvasive measure of URTI in general and of SARS-CoV-2 in particular.}, }
@article {pmid34306841, year = {2021}, author = {Sumibcay, TJ and Lee-Jayaram, JJ and Yamamoto, LG}, title = {Reducing Broad-Spectrum Antibiotic Treatment of Simple Group A Streptococcal Infections to Reduce Harm to the Microbiome.}, journal = {Cureus}, volume = {13}, number = {6}, pages = {e15629}, pmid = {34306841}, issn = {2168-8184}, abstract = {Background Broad-spectrum antibiotics disrupt the human microbiome resulting in a greater risk of harmful, long-term conditions that impact human health. Group A streptococcal (GAS) infections can be treated with penicillin. Objective We examined the treatment of simple GAS infections to assess the use of broad-spectrum antibiotics. Methods Smart relational database extraction queries from January 1, 2016 to July 10, 2019 (3.6 years) of patients less than 22 years old in a 4-hospital system electronic medical record (EMR). Results We found 1778 non-ED outpatients and 873 ED patients with simple GAS infections who were not allergic to penicillin. A total of 75% and 44% of non-ED and ED patients were treated with broad-spectrum antibiotics, respectively (p < 0.001). Older patients were treated with penicillin alone more frequently than younger age groups (p < 0.001). Conclusion These findings highlight opportunities for clinicians to reduce the utilization of broad-spectrum antibiotics for the treatment of simple GAS infections to reduce harm to the microbiome.}, }
@article {pmid34302622, year = {2021}, author = {Hyun, DW and Lee, JY and Kim, MS and Shin, NR and Whon, TW and Kim, KH and Kim, PS and Tak, EJ and Jung, MJ and Lee, JY and Kim, HS and Kang, W and Sung, H and Jeon, CO and Bae, JW}, title = {Pathogenomics of Streptococcus ilei sp. nov., a newly identified pathogen ubiquitous in human microbiome.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {59}, number = {8}, pages = {792-806}, pmid = {34302622}, issn = {1976-3794}, mesh = {Adult ; Animals ; Gastrointestinal Microbiome ; Humans ; Ileostomy ; Male ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Phylogeny ; Streptococcal Infections/*microbiology ; Streptococcus/classification/genetics/*isolation &amp; purification/*pathogenicity ; Virulence ; }, abstract = {Viridans group streptococci are a serious health concern because most of these bacteria cause life-threatening infections, especially in immunocompromised and hospitalized individuals. We focused on two alpha-hemolytic Streptococcus strains (I-G2 and I-P16) newly isolated from an ileostomy effluent of a colorectal cancer patient. We examined their pathogenic potential by investigating their prevalence in human and assessing their pathogenicity in a mouse model. We also predicted their virulence factors and pathogenic features by using comparative genomic analysis and in vitro tests. Using polyphasic and systematic approaches, we identified the isolates as belonging to a novel Streptococcus species and designated it as Streptococcus ilei. Metagenomic survey based on taxonomic assignment of datasets from the Human Microbiome Project revealed that S. ilei is present in most human population and at various body sites but is especially abundant in the oral cavity. Intraperitoneal injection of S. ilei was lethal to otherwise healthy C57BL/6J mice. Pathogenomics and in vitro assays revealed that S. ilei possesses a unique set of virulence factors. In agreement with the in vivo and in vitro data, which indicated that S. ilei strain I-G2 is more pathogenic than strain I-P16, only the former displayed the streptococcal group A antigen. We here newly identified S. ilei sp. nov., and described its prevalence in human, virulence factors, and pathogenicity. This will help to prevent S. ilei strain misidentification in the future, and improve the understanding and management of streptococcal infections.}, }
@article {pmid34296826, year = {2021}, author = {Gawlik, A and Salonen, A and Jian, C and Yanover, C and Antosz, A and Shmoish, M and Wasniewska, M and Bereket, A and Wudy, SA and Hartmann, MF and Thivel, D and Matusik, P and Weghuber, D and Hochberg, Z}, title = {Personalized approach to childhood obesity: Lessons from gut microbiota and omics studies. Narrative review and insights from the 29th European childhood obesity congress.}, journal = {Pediatric obesity}, volume = {16}, number = {10}, pages = {e12835}, doi = {10.1111/ijpo.12835}, pmid = {34296826}, issn = {2047-6310}, mesh = {Child ; Data Collection ; *Gastrointestinal Microbiome ; Humans ; Metabolomics ; *Pediatric Obesity/prevention &amp; control ; }, abstract = {The traditional approach to childhood obesity prevention and treatment should fit most patients, but misdiagnosis and treatment failure could be observed in some cases that lie away from average as part of individual variation or misclassification. Here, we reflect on the contributions that high-throughput technologies such as next-generation sequencing, mass spectrometry-based metabolomics and microbiome analysis make towards a personalized medicine approach to childhood obesity. We hypothesize that diagnosing a child as someone with obesity captures only part of the phenotype; and that metabolomics, genomics, transcriptomics and analyses of the gut microbiome, could add precision to the term "obese," providing novel corresponding biomarkers. Identifying a cluster -omic signature in a given child can thus facilitate the development of personalized prognostic, diagnostic, and therapeutic approaches. It can also be applied to the monitoring of symptoms/signs evolution, treatment choices and efficacy, predisposition to drug-related side effects and potential relapse. This article is a narrative review of the literature and summary of the main observations, conclusions and perspectives raised during the annual meeting of the European Childhood Obesity Group. Authors discuss some recent advances and future perspectives on utilizing a systems approach to understanding and managing childhood obesity in the context of the existing omics data.}, }
@article {pmid34294041, year = {2021}, author = {Andrade, BGN and Goris, T and Afli, H and Coutinho, FH and Dávila, AMR and Cuadrat, RRC}, title = {Putative mobilized colistin resistance genes in the human gut microbiome.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {220}, pmid = {34294041}, issn = {1471-2180}, mesh = {Colistin/*pharmacology ; Computational Biology ; Drug Resistance, Bacterial/*genetics ; Gene Transfer, Horizontal ; Genes, Bacterial/*genetics ; Genetic Variation ; Humans ; Microbiota/*drug effects/*genetics ; }, abstract = {BACKGROUND: The high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin, caused by mobilized colistin resistance (mcr) genes, poses an unprecedented threat to human health. Understanding the spread, evolution, and distribution of such genes among human populations will help in the development of strategies to diminish their occurrence. To tackle this problem, we investigated the distribution and prevalence of potential mcr genes in the human gut microbiome using a set of bioinformatics tools to screen the Unified Human Gastrointestinal Genome (UHGG) collection for the presence, synteny and phylogeny of putative mcr genes, and co-located antibiotic resistance genes.<br><br>RESULTS: A total of 2079 antibiotic resistance genes (ARGs) were classified as mcr genes in 2046 metagenome assembled genomes (MAGs), distributed across 1596 individuals from 41 countries, of which 215 were identified in plasmidial contigs. The genera that presented the largest number of mcr-like genes were Suterella and Parasuterella. Other potential pathogens carrying mcr genes belonged to the genus Vibrio, Escherichia and Campylobacter. Finally, we identified a total of 22,746 ARGs belonging to 21 different classes in the same 2046 MAGs, suggesting multi-resistance potential in the corresponding bacterial strains, increasing the concern of ARGs impact in the clinical settings.<br><br>CONCLUSION: This study uncovers the diversity of mcr-like genes in the human gut microbiome. We demonstrated the cosmopolitan distribution of these genes in individuals worldwide and the co-presence of other antibiotic resistance genes, including Extended-spectrum Beta-Lactamases (ESBL). Also, we described mcr-like genes fused to a PAP2-like domain in S. wadsworthensis. These novel sequences increase our knowledge about the diversity and evolution of mcr-like genes. Future research should focus on activity, genetic mobility and a potential colistin resistance in the corresponding strains to experimentally validate those findings.}, }
@article {pmid34289377, year = {2021}, author = {Zhang, XS and Yin, YS and Wang, J and Battaglia, T and Krautkramer, K and Li, WV and Li, J and Brown, M and Zhang, M and Badri, MH and Armstrong, AJS and Strauch, CM and Wang, Z and Nemet, I and Altomare, N and Devlin, JC and He, L and Morton, JT and Chalk, JA and Needles, K and Liao, V and Mount, J and Li, H and Ruggles, KV and Bonneau, RA and Dominguez-Bello, MG and Bäckhed, F and Hazen, SL and Blaser, MJ}, title = {Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {8}, pages = {1249-1265.e9}, pmid = {34289377}, issn = {1934-6069}, support = {R01 DK120679/DK/NIDDK NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R35 GM139655/GM/NIGMS NIH HHS/United States ; R01 GM128955/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Autoimmune Diseases ; Bacteria/classification/drug effects ; Cecum/*immunology/*microbiology ; Diabetes Mellitus, Type 1/*immunology ; Disease Models, Animal ; Female ; Gastrointestinal Microbiome/*drug effects/*physiology ; Gene Expression ; Histone Code ; Intestines/immunology ; Male ; Metabolic Networks and Pathways ; Metagenome ; Mice ; Mice, Inbred NOD ; MicroRNAs ; }, abstract = {Early-life antibiotic exposure perturbs the intestinal microbiota and accelerates type 1 diabetes (T1D) development in the NOD mouse model. Here, we found that maternal cecal microbiota transfer (CMT) to NOD mice after early-life antibiotic perturbation largely rescued the induced T1D enhancement. Restoration of the intestinal microbiome was significant and persistent, remediating the antibiotic-depleted diversity, relative abundance of particular taxa, and metabolic pathways. CMT also protected against perturbed metabolites and normalized innate and adaptive immune effectors. CMT restored major patterns of ileal microRNA and histone regulation of gene expression. Further experiments suggest a gut-microbiota-regulated T1D protection mechanism centered on Reg3γ, in an innate intestinal immune network involving CD44, TLR2, and Reg3γ. This regulation affects downstream immunological tone, which may lead to protection against tissue-specific T1D injury.}, }
@article {pmid34282932, year = {2021}, author = {Brubaker, L and Gourdine, JF and Siddiqui, NY and Holland, A and Halverson, T and Limeria, R and Pride, D and Ackerman, L and Forster, CS and Jacobs, KM and Thomas-White, KJ and Putonti, C and Dong, Q and Weinstein, M and Lukacz, ES and Karstens, L and Wolfe, AJ}, title = {Forming Consensus To Advance Urobiome Research.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0137120}, pmid = {34282932}, issn = {2379-5077}, support = {K01 DK116706/DK/NIDDK NIH HHS/United States ; R13 DK120286/DK/NIDDK NIH HHS/United States ; }, abstract = {Urobiome research has the potential to advance the understanding of a wide range of diseases, including lower urinary tract symptoms and kidney disease. Many scientific areas have benefited from early research method consensus to facilitate the greater, common good. This consensus document, developed by a group of expert investigators currently engaged in urobiome research (UROBIOME 2020 conference participants), aims to promote standardization and advances in this field by the adoption of common core research practices. We propose a standardized nomenclature as well as considerations for specimen collection, preservation, storage, and processing. Best practices for urobiome study design include our proposal for standard metadata elements as part of core metadata collection. Although it is impractical to follow fixed analytical procedures when analyzing urobiome data, we propose guidelines to document and report data originating from urobiome studies. We offer this first consensus document with every expectation of subsequent revision as our field progresses.}, }
@article {pmid34282723, year = {2021}, author = {Diebold, PJ and New, FN and Hovan, M and Satlin, MJ and Brito, IL}, title = {Linking plasmid-based beta-lactamases to their bacterial hosts using single-cell fusion PCR.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {34282723}, issn = {2050-084X}, support = {DP2 HL141007/HL/NHLBI NIH HHS/United States ; K23 AI114994/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Cell Fusion/*methods ; Chickens/microbiology ; Clostridiales/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Feces/microbiology ; Gene Transfer, Horizontal ; Humans ; Klebsiella pneumoniae/genetics ; Microbiota/genetics ; Plasmids/*genetics ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S ; beta-Lactamases/*genetics/metabolism ; }, abstract = {The horizonal transfer of plasmid-encoded genes allows bacteria to adapt to constantly shifting environmental pressures, bestowing functional advantages to their bacterial hosts such as antibiotic resistance, metal resistance, virulence factors, and polysaccharide utilization. However, common molecular methods such as short- and long-read sequencing of microbiomes cannot associate extrachromosomal plasmids with the genome of the host bacterium. Alternative methods to link plasmids to host bacteria are either laborious, expensive, or prone to contamination. Here we present the One-step Isolation and Lysis PCR (OIL-PCR) method, which molecularly links plasmid-encoded genes with the bacterial 16S rRNA gene via fusion PCR performed within an emulsion. After validating this method, we apply it to identify the bacterial hosts of three clinically relevant beta-lactamases within the gut microbiomes of neutropenic patients, as they are particularly vulnerable multidrug-resistant infections. We successfully detect the known association of a multi-drug resistant plasmid with Klebsiella pneumoniae, as well as the novel associations of two low-abundance genera, Romboutsia and Agathobacter. Further investigation with OIL-PCR confirmed that our detection of Romboutsia is due to its physical association with Klebsiella as opposed to directly harboring the beta-lactamase genes. Here we put forth a robust, accessible, and high-throughput platform for sensitively surveying the bacterial hosts of mobile genes, as well as detecting physical bacterial associations such as those occurring within biofilms and complex microbial communities.}, }
@article {pmid34281323, year = {2021}, author = {Gargiulo Isacco, C and Inchingolo, AD and Nguyen Cao, KD and Malcangi, G and Paduanelli, G and Pham Hung, V and Tran Cong, T and Bordea, IR and Scarano, A and Laforgia, A and Marinelli, G and Limongelli, L and Inchingolo, F and Lorusso, F and Inchingolo, AM and Dipalma, G}, title = {The bad relationship, osteo-decay and diabetes type 2 searching for a link: a literature review.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {35}, number = {2 Suppl. 1}, pages = {253-269}, doi = {10.23812/21-2supp1-26}, pmid = {34281323}, issn = {0393-974X}, mesh = {Bone and Bones ; *Diabetes Mellitus, Type 2 ; *Gastrointestinal Microbiome ; Hematopoiesis ; Humans ; *Metabolic Diseases ; }, abstract = {The diabetes and osteoporotic metabolic diseases are characterized by a wide prevalence of the population worldwide and correlated to alteration of the bone tissues. Several cofactors could influence the clinical course and the biochemistry of the pathologies such as human microbiome, nutrition characteristics, gut microbiota activity and interactions with vitamin K and D across IGF/GH and TP53 signaling pathways and the glucose/energy as mechanism for bone tissue health. Moreover, also the calories and sugar consumption seem to be correlated to an increased inflammatory state with several consequences for hematopoiesis and host tissues response. The aim of the present literature review was to highlight the role of osteoporotic diseases and diabetes type 2 link for the bone metabolism. The literature cases showed that a correlation between bone-gut-kidney-heart-CNS-Immunity crosstalk seems to be linked with bone metabolism and health regulation. Moreover, also the aging process could represent a valuable co-factor for the sustaining of the metabolic disorders upon a multi-systemic level.}, }
@article {pmid34272085, year = {2021}, author = {Hammond, AM and Monir, RL and Schoch, JJ}, title = {The role of the pediatric cutaneous and gut microbiomes in childhood disease: A review.}, journal = {Seminars in perinatology}, volume = {45}, number = {6}, pages = {151452}, doi = {10.1016/j.semperi.2021.151452}, pmid = {34272085}, issn = {1558-075X}, mesh = {Child ; Child, Preschool ; *Dermatitis, Atopic ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Skin ; }, abstract = {OBJECTIVE: Infancy and early childhood are crucial periods in the development of the human microbiome and shape the trajectory of microbial colonization, immune system development, and systemic disease. We review the development of the skin and gut microbiomes, their connection to the immune system, and their relevance to common pediatric pathologies.<br><br>FINDINGS: Beginning after birth, and likely even in utero, colonization of the skin and the gut occur in parallel, influenced by external factors. This colonization, in turn, dictates maturation of the immune system and contributes to conditions from atopic dermatitis to sepsis. Emerging literature is identifying links between the gut and skin microbiomes.<br><br>CONCLUSION: The gut and skin microbiomes are associated with pediatric disease states. Immune and microbial plasticity make this unique period an ideal target for intervention. Investigating the purposeful manipulation of the pediatric microbiome may lead to novel treatment and prevention strategies.}, }
@article {pmid34269346, year = {2021}, author = {Bai, J and Zhang, W and Amirkhanzadeh Barandouzir, Z}, title = {Human Microbiome: Understanding the Role of the Gut Microbiome and Implications for Oncology Nursing Care.}, journal = {Clinical journal of oncology nursing}, volume = {25}, number = {4}, pages = {383-387}, pmid = {34269346}, issn = {1538-067X}, support = {K99 NR017897/NR/NINR NIH HHS/United States ; R00 NR017897/NR/NINR NIH HHS/United States ; R25 CA203650/CA/NCI NIH HHS/United States ; }, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Neoplasms ; Oncology Nursing ; }, abstract = {By understanding the human microbiome and its influencing factors, oncology nurses in clinical practice can educate, screen, and monitor patients with cancer who have a higher risk of gut microbiome dysbiosis. Knowledge of the gut microbiome and its impact on cancer outcomes can help oncology nurses interpret associations between the gut microbiome and treatment- related toxicities and symptoms. Oncology nurses can guide patients to build a healthy gut microbiome across the trajectory of cancer treatment and survivorship.}, }
@article {pmid34267333, year = {2022}, author = {Javier-DesLoges, J and McKay, RR and Swafford, AD and Sepich-Poore, GD and Knight, R and Parsons, JK}, title = {The microbiome and prostate cancer.}, journal = {Prostate cancer and prostatic diseases}, volume = {25}, number = {2}, pages = {159-164}, pmid = {34267333}, issn = {1476-5608}, support = {F30 CA243480/CA/NCI NIH HHS/United States ; R01 CA241728/CA/NCI NIH HHS/United States ; U24 CA248454/CA/NCI NIH HHS/United States ; }, mesh = {Feces ; Humans ; Male ; *Microbiota ; Prostate ; *Prostatic Neoplasms/diagnosis/therapy ; }, abstract = {There is growing evidence that the microbiome is involved in development and treatment of many human diseases, including prostate cancer. There are several potential pathways for microbiome-based mechanisms for the development of prostate cancer: direct impacts of microbes or microbial products in the prostate or the urine, and indirect impacts from microbes or microbial products in the gastrointestinal tract. Unique microbial signatures have been identified within the stool, oral cavity, tissue, urine, and blood of prostate cancer patients, but studies vary in their findings. Recent studies describe potential diagnostic and therapeutic applications of the microbiome, but further clinical investigation is needed. In this review, we explore the existing literature on the discovery of the human microbiome and its relationship to prostate cancer.}, }
@article {pmid34262212, year = {2021}, author = {Han, S and Van Treuren, W and Fischer, CR and Merrill, BD and DeFelice, BC and Sanchez, JM and Higginbottom, SK and Guthrie, L and Fall, LA and Dodd, D and Fischbach, MA and Sonnenburg, JL}, title = {A metabolomics pipeline for the mechanistic interrogation of the gut microbiome.}, journal = {Nature}, volume = {595}, number = {7867}, pages = {415-420}, pmid = {34262212}, issn = {1476-4687}, support = {R01 DK101674/DK/NIDDK NIH HHS/United States ; DP1 AT009892/AT/NCCIH NIH HHS/United States ; K08 DK110335/DK/NIDDK NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; F32 AG062119/AG/NIA NIH HHS/United States ; DP1 DK113598/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; 5T32 AI007328-32/NH/NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/*metabolism ; Bacteroides/genetics/metabolism ; *Gastrointestinal Microbiome ; Genes, Bacterial/genetics ; Genomics ; Host Microbial Interactions ; Humans ; Male ; *Metabolome ; Metabolomics/*methods ; Mice ; Nitrogen/metabolism ; Phenotype ; Phylogeny ; }, abstract = {Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules[1-3], yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites in diverse sample types. We report the metabolic profiles of 178 gut microorganism strains using our library of 833 metabolites. Using this metabolomics resource, we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover a previously undescribed type of metabolism in Bacteroides, and reveal candidate biochemical pathways using comparative genomics. Microbiota-dependent metabolites can be detected in diverse biological fluids from gnotobiotic and conventionally colonized mice and traced back to the corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microorganisms and interactions between microorganisms and their host.}, }
@article {pmid34261503, year = {2021}, author = {Karcher, N and Nigro, E and Punčochář, M and Blanco-Míguez, A and Ciciani, M and Manghi, P and Zolfo, M and Cumbo, F and Manara, S and Golzato, D and Cereseto, A and Arumugam, M and Bui, TPN and Tytgat, HLP and Valles-Colomer, M and de Vos, WM and Segata, N}, title = {Genomic diversity and ecology of human-associated Akkermansia species in the gut microbiome revealed by extensive metagenomic assembly.}, journal = {Genome biology}, volume = {22}, number = {1}, pages = {209}, pmid = {34261503}, issn = {1474-760X}, support = {U01 CA230551/CA/NCI NIH HHS/United States ; }, mesh = {Akkermansia/classification/genetics/metabolism/virology ; Animals ; Bacteriophages/growth &amp; development ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; *Genome, Bacterial ; Humans ; *Metagenome ; Mice ; Operon ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Akkermansia muciniphila is a human gut microbe with a key role in the physiology of the intestinal mucus layer and reported associations with decreased body mass and increased gut barrier function and health. Despite its biomedical relevance, the genomic diversity of A. muciniphila remains understudied and that of closely related species, except for A. glycaniphila, unexplored.<br><br>RESULTS: We present a large-scale population genomics analysis of the Akkermansia genus using 188 isolate genomes and 2226 genomes assembled from 18,600 metagenomes from humans and other animals. While we do not detect A. glycaniphila, the Akkermansia strains in the human gut can be grouped into five distinct candidate species, including A. muciniphila, that show remarkable whole-genome divergence despite surprisingly similar 16S rRNA gene sequences. These candidate species are likely human-specific, as they are detected in mice and non-human primates almost exclusively when kept in captivity. In humans, Akkermansia candidate species display ecological co-exclusion, diversified functional capabilities, and distinct patterns of associations with host body mass. Analysis of CRISPR-Cas loci reveals new variants and spacers targeting newly discovered putative bacteriophages. Remarkably, we observe an increased relative abundance of Akkermansia when cognate predicted bacteriophages are present, suggesting ecological interactions. A. muciniphila further exhibits subspecies-level genetic stratification with associated functional differences such as a putative exo/lipopolysaccharide operon.<br><br>CONCLUSIONS: We uncover a large phylogenetic and functional diversity of the Akkermansia genus in humans. This variability should be considered in the ongoing experimental and metagenomic efforts to characterize the health-associated properties of A. muciniphila and related bacteria.}, }
@article {pmid34260950, year = {2022}, author = {McCoubrey, LE and Gaisford, S and Orlu, M and Basit, AW}, title = {Predicting drug-microbiome interactions with machine learning.}, journal = {Biotechnology advances}, volume = {54}, number = {}, pages = {107797}, doi = {10.1016/j.biotechadv.2021.107797}, pmid = {34260950}, issn = {1873-1899}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Machine Learning ; *Microbiota ; }, abstract = {Pivotal work in recent years has cast light on the importance of the human microbiome in maintenance of health and physiological response to drugs. It is now clear that gastrointestinal microbiota have the metabolic power to promote, inactivate, or even toxify the efficacy of a drug to a level of clinically relevant significance. At the same time, it appears that drug intake has the propensity to alter gut microbiome composition, potentially affecting health and response to other drugs. Since the precise composition of an individual's microbiome is unique, one's drug-microbiome relationship is similarly unique. Thus, in the age of evermore personalised medicine, the ability to predict individuals' drug-microbiome interactions is highly sought. Machine learning (ML) offers a powerful toolkit capable of characterising and predicting drug-microbiota interactions at the individual patient level. ML techniques have the potential to learn the mechanisms operating drug-microbiome activities and measure patients' risk of such occurrences. This review will outline current knowledge at the drug-microbiota interface, and present ML as a technique for examining and forecasting personalised drug-microbiome interactions. When harnessed effectively, ML could alter how the pharmaceutical industry and healthcare professionals consider the drug-microbiome axis in patient care.}, }
@article {pmid34256346, year = {2021}, author = {Jian, C and Carpén, N and Helve, O and de Vos, WM and Korpela, K and Salonen, A}, title = {Early-life gut microbiota and its connection to metabolic health in children: Perspective on ecological drivers and need for quantitative approach.}, journal = {EBioMedicine}, volume = {69}, number = {}, pages = {103475}, pmid = {34256346}, issn = {2352-3964}, mesh = {Child ; Environment ; *Gastrointestinal Microbiome ; Humans ; Metabolic Diseases/epidemiology/*microbiology ; }, abstract = {The colonisation and development of the gut microbiota has been implicated in paediatric metabolic disorders via its powerful effect on host metabolic and immune homeostasis. Here we summarise the evidence from human studies on the early gut microbiota and paediatric overweight and obesity. Manipulation of the early gut microbiota may represent a promising target for countering the burgeoning metabolic disorders in the paediatric population, provided the assembly patterns of microbiota and their health consequences can be decoded. Therefore, in this review, we pay particular attention to the important ecological drivers affecting the community dynamics of the early gut microbiota. We then discuss the knowledge gaps in commonly studied exposures linking the gut microbiota to metabolic disorders, especially regarding maternal factors and antibiotic use. This review also attempts to give directions for future studies aiming to identify predictive and corrective measures for paediatric metabolic disorders based on the gut microbiota. Gut microbiota; Metabolism; Paediatric overweight and obesity; Ecological driver; Dynamics; Infants.}, }
@article {pmid34256014, year = {2021}, author = {Wastyk, HC and Fragiadakis, GK and Perelman, D and Dahan, D and Merrill, BD and Yu, FB and Topf, M and Gonzalez, CG and Van Treuren, W and Han, S and Robinson, JL and Elias, JE and Sonnenburg, ED and Gardner, CD and Sonnenburg, JL}, title = {Gut-microbiota-targeted diets modulate human immune status.}, journal = {Cell}, volume = {184}, number = {16}, pages = {4137-4153.e14}, pmid = {34256014}, issn = {1097-4172}, support = {F32 AG062119/AG/NIA NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; }, mesh = {Biodiversity ; *Diet ; Dietary Fiber/pharmacology ; Feeding Behavior ; Female ; Fermented Foods ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Immunity ; Inflammation/pathology ; Male ; Middle Aged ; Signal Transduction/drug effects ; }, abstract = {Diet modulates the gut microbiome, which in turn can impact the immune system. Here, we determined how two microbiota-targeted dietary interventions, plant-based fiber and fermented foods, influence the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study (n = 18/arm) combined with -omics measurements of microbiome and host, including extensive immune profiling, we found diet-specific effects. The high-fiber diet increased microbiome-encoded glycan-degrading carbohydrate active enzymes (CAZymes) despite stable microbial community diversity. Although cytokine response score (primary outcome) was unchanged, three distinct immunological trajectories in high-fiber consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented-food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in industrialized society.}, }
@article {pmid34248864, year = {2021}, author = {Kostopoulos, I and Aalvink, S and Kovatcheva-Datchary, P and Nijsse, B and Bäckhed, F and Knol, J and de Vos, WM and Belzer, C}, title = {A Continuous Battle for Host-Derived Glycans Between a Mucus Specialist and a Glycan Generalist in vitro and in vivo.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {632454}, pmid = {34248864}, issn = {1664-302X}, abstract = {The human gastrointestinal tract is colonized by a diverse microbial community, which plays a crucial role in human health. In the gut, a protective mucus layer that consists of glycan structures separates the bacteria from the host epithelial cells. These host-derived glycans are utilized by bacteria that have adapted to this specific compound in the gastrointestinal tract. Our study investigated the close interaction between two distinct gut microbiota members known to use mucus glycans, the generalist Bacteroides thetaiotaomicron and the specialist Akkermansia muciniphila in vitro and in vivo. The in vitro study, in which mucin was the only nutrient source, indicated that B. thetaiotaomicron significantly upregulated genes coding for Glycoside Hydrolases (GHs) and mucin degradation activity when cultured in the presence of A. muciniphila. Furthermore, B. thetaiotaomicron significantly upregulated the expression of a gene encoding for membrane attack complex/perforin (MACPF) domain in co-culture. The transcriptome analysis also indicated that A. muciniphila was less affected by the environmental changes and was able to sustain its abundance in the presence of B. thetaiotaomicron while increasing the expression of LPS core biosynthesis activity encoding genes (O-antigen ligase, Lipid A and Glycosyl transferases) as well as ABC transporters. Using germ-free mice colonized with B. thetaiotaomicron and/or A. muciniphila, we observed a more general glycan degrading profile in B. thetaiotaomicron while the expression profile of A. muciniphila was not significantly affected when colonizing together, indicating that two different nutritional niches were established in mice gut. Thus, our results indicate that a mucin degrading generalist adapts to its changing environment, depending on available carbohydrates while a mucin degrading specialist adapts by coping with competing microorganism through upregulation of defense related genes.}, }
@article {pmid34244284, year = {2021}, author = {Koskenvuo, L and Lunkka, P and Varpe, P and Hyöty, M and Satokari, R and Haapamäki, C and Lepistö, A and Sallinen, V}, title = {Mechanical bowel preparation and oral antibiotics versus mechanical bowel preparation only prior rectal surgery (MOBILE2): a multicentre, double-blinded, randomised controlled trial-study protocol.}, journal = {BMJ open}, volume = {11}, number = {7}, pages = {e051269}, pmid = {34244284}, issn = {2044-6055}, mesh = {*Anti-Bacterial Agents/therapeutic use ; Colon/surgery ; Humans ; Multicenter Studies as Topic ; Preoperative Care ; Randomized Controlled Trials as Topic ; Rectum/surgery ; Retrospective Studies ; *Surgical Wound Infection/prevention &amp; control ; }, abstract = {INTRODUCTION: Mechanical bowel preparation (MBP) prior to rectal surgery is widely used. Based on retrospective data many guidelines recommend mechanical and oral antibiotic bowel preparation (MOABP) to reduce postoperative complications and specifically surgical site infections (SSIs). The primary aim of this study is to examine whether MOABP reduces complications of rectal surgery.<br><br>METHODS AND ANALYSIS: The MOBILE2 (Mechanical Bowel Preparation and Oral Antibiotics vs Mechanical Bowel Preparation Only Prior Rectal Surgery) trial is a multicentre, double-blinded, parallel group, superiority, randomised controlled trial comparing MOABP to MBP among patients scheduled for rectal surgery with colorectal or coloanal anastomosis. The patients randomised to the MOABP group receive 1&#x2009;g neomycin and 1&#x2009;g metronidazole two times on a day prior to surgery and patients randomised to the MBP group receive identical placebo. Based on power calculations, 604 patients will be enrolled in the study. The primary outcome is Comprehensive Complication Index within 30 days after surgery. Secondary outcomes are SSIs within 30 days after surgery, the number and classification of anastomosis dehiscences, the length of hospital stay, mortality within 90 days after surgery and the number of patients who received adjuvant treatment if needed. Tertiary outcomes are overall survival, disease-specific survival, recurrence-free survival and difference in quality-of-life before and 1&#x2009;year after surgery. In addition, the microbiota differences in colon mucosa are analysed.<br><br>ETHICS AND DISSEMINATION: The Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals.<br><br>TRIAL REGISTRATION NUMBER: NCT04281667.}, }
@article {pmid34242413, year = {2021}, author = {Tuganbaev, T and Honda, K}, title = {Non-zero-sum microbiome immune system interactions.}, journal = {European journal of immunology}, volume = {51}, number = {9}, pages = {2120-2136}, pmid = {34242413}, issn = {1521-4141}, mesh = {Adaptive Immunity/immunology ; Enteric Nervous System/*physiology ; Gastrointestinal Microbiome/*immunology ; Gastrointestinal Tract/*immunology/innervation/*microbiology/physiology ; Humans ; Immunity, Innate/immunology ; Symbiosis/immunology ; }, abstract = {Fundamental asymmetries between the host and its microbiome in enzymatic activities and nutrient storage capabilities have promoted mutualistic adaptations on both sides. As a result, the enteric immune system has evolved so as not to cause a zero-sum sterilization of non-self, but rather achieve a non-zero-sum self-reinforcing cooperation with its evolutionary partner the microbiome. In this review, we attempt to integrate the accumulated knowledge of immune-microbiome interactions into an evolutionary framework and trace the pattern of positive immune-microbiome feedback loops across epithelial, enteric nervous system, innate, and adaptive immune circuits. Indeed, the immune system requires commensal signals for its development and function, and reciprocally protects the microbiome from nutrient shortage and pathogen outgrowth. In turn, a healthy microbiome is the result of immune system curatorship as well as microbial ecology. The paradigms of host-microbiome asymmetry and the cooperative nature of their interactions identified in the gut are applicable across all tissues influenced by microbial activities. Incorporation of immune system influences into models of microbiome ecology will be a step forward toward defining what constitutes a healthy human microbiome and guide discoveries of novel host-microbiome mutualistic adaptations that may be harnessed for the promotion of human health.}, }
@article {pmid34239510, year = {2021}, author = {Young, RB and Marcelino, VR and Chonwerawong, M and Gulliver, EL and Forster, SC}, title = {Key Technologies for Progressing Discovery of Microbiome-Based Medicines.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {685935}, pmid = {34239510}, issn = {1664-302X}, abstract = {A growing number of experimental and computational approaches are illuminating the "microbial dark matter" and uncovering the integral role of commensal microbes in human health. Through this work, it is now clear that the human microbiome presents great potential as a therapeutic target for a plethora of diseases, including inflammatory bowel disease, diabetes and obesity. The development of more efficacious and targeted treatments relies on identification of causal links between the microbiome and disease; with future progress dependent on effective links between state-of-the-art sequencing approaches, computational analyses and experimental assays. We argue determining causation is essential, which can be attained by generating hypotheses using multi-omic functional analyses and validating these hypotheses in complex, biologically relevant experimental models. In this review we discuss existing analysis and validation methods, and propose best-practice approaches required to enable the next phase of microbiome research.}, }
@article {pmid34237996, year = {2021}, author = {Paglia, L}, title = {From native core micriobiome to milk-oriented microbiome.}, journal = {European journal of paediatric dentistry}, volume = {22}, number = {2}, pages = {89}, doi = {10.23804/ejpd.2021.22.02.1}, pmid = {34237996}, issn = {2035-648X}, mesh = {Breast Feeding ; Child ; Female ; Humans ; Infant ; Infant, Newborn ; *Microbiota ; Milk, Human ; Mothers ; Pregnancy ; }, abstract = {The human microbiome is the full set of microorganisms (microbiota) present on and in our body. Its importance is such that the human being has been defined as a holobiont, that is, a superorganism made up of human eukaryotic cells and microbial cells. A balanced microbiota (eubiosis) is a prerequisite for health and well-being; on the contrary, an altered microbiota (dysbiosis) is the cause of pathological conditions. This concept is the cornerstone of the "microbiota revolution": Currently there is no disease that cannot be re- interpreted as a function of microbiome. While all human beings have similar DNA, it is the microbiome that make every person genetically unique; therefore the microbiome is the variable component of the genome which characterises each one of us. About one third of the microbiome is common to all individuals, while two thirds are specific to each subject and constitute a sort of fingerprint that forms and stabilises in the first 2-3 years of life. This timeframe is extremely important since it has been shown that the structure of the microbiome is already acquired in the embryonic-fetal period, it is completed within 3 years and lasts a lifetime. The native core microbiome is the first microbiota and characterises individuals for their whole life. It is affected by four main variables: The quality of family and social life of the mother-to-be, the intake of drugs during pregnancy, as well as the type of birth and breastfeeding. It is renowned that breast milk is a complex, unique and essential food for the growth of the child, but one of its functions - which is still under investigation today - is to feed and guide the formation of the microbiome of the newborn even after the introduction of solid foods, during the first 3 years of life. This function is carried out by the over one hundred different types of oligosaccharides that are present in breast milk, which is why these days we talk about the so-called MOM (milk-oriented microbiome). The correct formation of the microbiome affects the entire life of an individual. This is a more than valid reason to promote breastfeeding even after eruption of baby teeth and throughout the weaning period. The role of pediatric dentists, together with hygienists and pediatricians, is to spread and stress out the importance of oral hygiene so that breastfeeding can only bring benefits and not carious lesions!}, }
@article {pmid34234185, year = {2021}, author = {Jones, J and Reinke, SN and Ali, A and Palmer, DJ and Christophersen, CT}, title = {Fecal sample collection methods and time of day impact microbiome composition and short chain fatty acid concentrations.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {13964}, pmid = {34234185}, issn = {2045-2322}, mesh = {Biodiversity ; Cluster Analysis ; Fatty Acids, Volatile/analysis/*metabolism ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenome ; Metagenomics/methods ; Microbial Viability ; Specimen Handling/*methods ; }, abstract = {Associations between the human gut microbiome and health outcomes continues to be of great interest, although fecal sample collection methods which impact microbiome studies are sometimes neglected. Here, we expand on previous work in sample optimization, to promote high quality microbiome data. To compare fecal sample collection methods, amplicons from the bacterial 16S rRNA gene (V4) and fungal (ITS2) region, as well as short chain fatty acid (SCFA) concentrations were determined in fecal material over three timepoints. We demonstrated that spot sampling of stool results in variable detection of some microbial members, and inconsistent levels of SCFA; therefore, sample homogenization prior to subsequent analysis or subsampling is recommended. We also identify a trend in microbial and metabolite composition that shifts over two consecutive stool collections less than 25 h apart. Lastly, we show significant differences in bacterial composition that result from collecting stool samples in OMNIgene·Gut tube (DNA Genotec) or Stool Nucleic Acid Collection and Preservation Tube (NORGEN) compared to immediate freezing. To assist with planning fecal sample collection and storage procedures for microbiome investigations with multiple analyses, we recommend participants to collect the first full bowel movement of the day and freeze the sample immediately after collection.}, }
@article {pmid34233595, year = {2021}, author = {Liao, B and Ye, X and Chen, X and Zhou, Y and Cheng, L and Zhou, X and Ren, B}, title = {The two-component signal transduction system and its regulation in Candida albicans.}, journal = {Virulence}, volume = {12}, number = {1}, pages = {1884-1899}, pmid = {34233595}, issn = {2150-5608}, mesh = {Antifungal Agents/pharmacology ; *Candida albicans/genetics/metabolism ; *Fungal Proteins/genetics/metabolism ; Humans ; *Signal Transduction ; Virulence ; }, abstract = {Candida albicans, which can cause superficial and life-threatening systemic infections, is the most common opportunistic fungal pathogen in the human microbiome. The two-component system is one of the most important C. albicans signal transduction pathways, regulating the response to oxidative and osmotic stresses, adhesion, morphogenesis, cell wall synthesis, virulence, drug resistance, and the host-pathogen interactions. Notably, some components of this signaling pathway have not been found in the human genome, indicating that the two-component system of C. albicans can be a potential target for new antifungal agents. Here, we summarize the composition, signal transduction, and regulation of the two-component system of C. albicans to emphasize its essential roles in the pathogenesis of C. albicans and the new therapeutic target for antifungal drugs.}, }
@article {pmid34228753, year = {2021}, author = {Cabrera, LE and Pekkarinen, PT and Alander, M and Nowlan, KHA and Nguyen, NA and Jokiranta, S and Kuivanen, S and Patjas, A and Mero, S and Pakkanen, SH and Heinonen, S and Kantele, A and Vapalahti, O and Kekäläinen, E and Strandin, T}, title = {Characterization of low-density granulocytes in COVID-19.}, journal = {PLoS pathogens}, volume = {17}, number = {7}, pages = {e1009721}, pmid = {34228753}, issn = {1553-7374}, mesh = {Acute Disease ; Adult ; Aged ; COVID-19/blood/*immunology ; Case-Control Studies ; Cohort Studies ; Convalescence ; Disease Progression ; Female ; Follow-Up Studies ; Granulocytes/*classification/cytology ; Humans ; Immune Tolerance/immunology ; Male ; Middle Aged ; Scavenger Receptors, Class E/analysis ; Severity of Illness Index ; }, abstract = {Severe COVID-19 is characterized by extensive pulmonary complications, to which host immune responses are believed to play a role. As the major arm of innate immunity, neutrophils are one of the first cells recruited to the site of infection where their excessive activation can contribute to lung pathology. Low-density granulocytes (LDGs) are circulating neutrophils, whose numbers increase in some autoimmune diseases and cancer, but are poorly characterized in acute viral infections. Using flow cytometry, we detected a significant increase of LDGs in the blood of acute COVID-19 patients, compared to healthy controls. Based on their surface marker expression, COVID-19-related LDGs exhibit four different populations, which display distinctive stages of granulocytic development and most likely reflect emergency myelopoiesis. Moreover, COVID-19 LDGs show a link with an elevated recruitment and activation of neutrophils. Functional assays demonstrated the immunosuppressive capacities of these cells, which might contribute to impaired lymphocyte responses during acute disease. Taken together, our data confirms a significant granulocyte activation during COVID-19 and suggests that granulocytes of lower density play a role in disease progression.}, }
@article {pmid34228203, year = {2022}, author = {Schwierzeck, V and Hülpüsch, C and Reiger, M}, title = {Microbiome of Barrier Organs in Allergy: Who Runs the World? Germs!.}, journal = {Handbook of experimental pharmacology}, volume = {268}, number = {}, pages = {53-65}, pmid = {34228203}, issn = {0171-2004}, mesh = {*Dermatitis, Atopic ; Dysbiosis ; *Food Hypersensitivity ; Humans ; *Microbiota ; *Rhinitis, Allergic ; }, abstract = {Over the last few decades, allergic diseases have been steadily increasing worldwide, a phenomenon that is not yet completely understood. Recent evidence, however, suggests that alterations in the microbiome may be a contributing factor. The microbiome refers to all microorganisms in a habitat including bacteria, fungi, and viruses. Using modern sequencing technologies, we are now capable of detecting and analyzing the human microbiome in more detail than ever before. Epidemiological and experimental studies have indicated that a complex intestinal microbiome supports the development of the immune system during childhood, thus providing protection from allergic diseases, including food allergy. The microbiome becomes an important part of human physiology and forms dynamic relationships with our various barrier systems. For example, bacterial dysbiosis is a hallmark of atopic eczema and correlates with disease progression. Similarly, the lung and nasopharyngeal microbiome is altered in patients with asthma and allergic rhinitis. While these results are interesting, the underlying mechanisms are still unclear and need to be investigated with functional studies. This review gives a short overview of the terminology and methods used in microbiome research before highlighting results concerning the lung, skin, and intestinal microbiome in allergic diseases.}, }
@article {pmid34224290, year = {2021}, author = {Saha, D and Ota, MOC and Pereira, P and Buchy, P and Badur, S}, title = {Rotavirus vaccines performance: dynamic interdependence of host, pathogen and environment.}, journal = {Expert review of vaccines}, volume = {20}, number = {8}, pages = {945-957}, doi = {10.1080/147605