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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 21 Aug 2025 at 01:52 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2025-08-20

Hyvönen S, Saarikivi A, Mälkönen J, et al (2025)

The association of maternal and infant early gut microbiota with respiratory infections in infants.

Pediatric research [Epub ahead of print].

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.

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.

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.

CONCLUSION: The maternal and early-life infant gut microbiota may play a role in predisposition to RTIs in infants.

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.

RevDate: 2025-08-20

Nguyen TT, Kim YK, Nguyen TVT, et al (2025)

Metabolic profiling and genetic tool development in the mucosal bacterium Selenomonas sputigena.

Genes & genomics [Epub ahead of print].

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.

OBJECTIVE: This study aimed to systematically characterize S. sputigena's metabolic capacity and develop genetic tools for functional studies.

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.

RESULTS: Selenomonas sputigena displayed glucose-preferential growth with rapid consumption (0.70 ± 0.05 mM h⁻[1]) and substantial acetate production (17.76 ± 2.05 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.

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.

RevDate: 2025-08-20

Qi Q, Gao C, Meng X, et al (2025)

Oral Microbiota Dynamics Across the Lifespan: Age, Sex, Race and Socioeconomic Influences in the US Population.

Journal of clinical periodontology [Epub ahead of print].

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.

MATERIALS AND METHODS: In this study, we analysed the oral microbiota of 9662 individuals aged 14-69 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.

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.

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.

RevDate: 2025-08-19

Davies RG, Wood LA, Hengist A, et al (2025)

Effects of a combined energy restriction and vigorous-intensity exercise intervention on the human gut microbiome: A randomised controlled trial.

The Journal of physiology [Epub ahead of print].

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.

RevDate: 2025-08-19

Caffrey EB, Olm MR, Kothe CI, et al (2025)

MiFoDB, a workflow for microbial food metagenomic characterization, enables high-resolution analysis of fermented food microbial dynamics.

mSystems [Epub ahead of print].

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.

RevDate: 2025-08-19

Allen JM (2025)

Rediscovering the wild: MiFoDB brings fermented food microbiomes into focus.

mSystems [Epub ahead of print].

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.

RevDate: 2025-08-18

Glowacki RW, Engelhart MJ, Till JM, et al (2025)

Identification of strain-specific cues that regulate biofilm formation in Bacteroides thetaiotaomicron.

Microbiology spectrum [Epub ahead of print].

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.

RevDate: 2025-08-16

Shah ND, HM Staudacher (2025)

Cultural competence in the delivery of nutrition and symptom care in irritable bowel syndrome.

The lancet. Gastroenterology & hepatology pii:S2468-1253(25)00236-5 [Epub ahead of print].

RevDate: 2025-08-18

Rakoff-Nahoum S, Debelius J, Valles-Colomer M, et al (2025)

A reconceptualized framework for human microbiome transmission in early life.

Nature communications, 16(1):7546.

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.

RevDate: 2025-08-12

Horvath M, Kang HG, Wu TC, et al (2025)

Host-specific bacterial modulation of airway gene expression and alternative splicing.

bioRxiv : the preprint server for biology pii:2025.07.18.665426.

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.

RevDate: 2025-07-13
CmpDate: 2025-07-13

Gupta R, S Gaur (2025)

Effect of diet and lifestyle on microbiome composition.

International review of cell and molecular biology, 395:157-174.

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.

RevDate: 2025-07-07
CmpDate: 2025-07-07

Agrawal P, Mendhey P, Kumar R, et al (2025)

Introduction to microbiomes in health and diseases.

International review of cell and molecular biology, 394:1-42.

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.

RevDate: 2025-07-24
CmpDate: 2025-07-22

Dason MS, Corà D, A Re (2025)

Sequence modeling tools to decode the biosynthetic diversity of the human microbiome.

mSystems, 10(7):e0033325.

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.

RevDate: 2025-08-15

Dash HR, NR Al-Snan (2025)

DNA forensics at forty: the way forward.

International journal of legal medicine, 139(5):2023-2046.

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.

RevDate: 2025-08-15

Dash HR, A Patel (2025)

Genealogically bewildered individuals and forensic identification: a review of current and emerging solutions.

International journal of legal medicine, 139(5):2001-2021.

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.

RevDate: 2025-05-17

Gullo G, Satullo M, Billone V, et al (2025)

The Role of the Genital Tract Microbiome in Human Fertility: A Literature Review.

Journal of clinical medicine, 14(9):.

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.

RevDate: 2025-04-30
CmpDate: 2025-04-29

Pei X, Liu L, Y Han (2025)

Advances in human microbiome and prostate cancer research.

Frontiers in immunology, 16:1576679.

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.

RevDate: 2025-05-14

Walker AR, Pham DN, Noeparvar P, et al (2025)

FRUCTOSE ACTIVATES A STRESS RESPONSE SHARED BY METHYLGLYOXAL AND HYDROGEN PEROXIDE IN STREPTOCOCCUS MUTANS.

bioRxiv : the preprint server for biology pii:2024.10.26.620100.

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.

RevDate: 2025-08-15

Heidrich V, Valles-Colomer M, N Segata (2025)

Human microbiome acquisition and transmission.

Nature reviews. Microbiology, 23(9):568-584.

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.

RevDate: 2025-05-14
CmpDate: 2025-03-20

Vernon JJ (2025)

Modulation of the Human Microbiome: Probiotics, Prebiotics, and Microbial Transplants.

Advances in experimental medicine and biology, 1472:277-294.

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.

RevDate: 2025-08-15

Shah H, Patel P, Nath A, et al (2025)

Role of human microbiota in facilitating the metastatic journey of cancer cells.

Naunyn-Schmiedeberg's archives of pharmacology, 398(8):9767-9796.

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.

RevDate: 2024-10-31
CmpDate: 2024-10-13

Gordon JI, Barratt MJ, Hibberd MC, et al (2024)

Establishing human microbial observatory programs in low- and middle-income countries.

Annals of the New York Academy of Sciences, 1540(1):13-20.

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.

RevDate: 2024-09-03
CmpDate: 2024-08-31

Duller S, Vrbancic S, Szydłowski Ł, et al (2024)

Targeted isolation of Methanobrevibacter strains from fecal samples expands the cultivated human archaeome.

Nature communications, 15(1):7593.

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.

RevDate: 2024-09-09
CmpDate: 2024-09-09

Mohamed KA, Kruf S, C Büll (2024)

Putting a cap on the glycome: Dissecting human sialyltransferase functions.

Carbohydrate research, 544:109242.

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.

RevDate: 2024-09-21
CmpDate: 2024-09-17

de Palma TH, Powers C, McPartland MJ, et al (2024)

Essential genes for Haemophilus parainfluenzae survival and biofilm growth.

mSystems, 9(9):e0067424.

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.

RevDate: 2025-08-14
CmpDate: 2024-09-12

Etlin S, Rose J, Bielski L, et al (2024)

The human microbiome in space: parallels between Earth-based dysbiosis, implications for long-duration spaceflight, and possible mitigation strategies.

Clinical microbiology reviews, 37(3):e0016322.

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.

RevDate: 2025-08-14

Liu J, Zhang X, Lin T, et al (2024)

A New Paradigm for High-dimensional Data: Distance-Based Semiparametric Feature Aggregation Framework via Between-Subject Attributes.

Scandinavian journal of statistics, theory and applications, 51(2):672-696.

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.

RevDate: 2024-07-09

Castaño-Henao L, Mendez DFG, Egan S, et al (2024)

Changes in groundwater and surface water bacterial communities under disinfection processes: Chlorination, ozonization, photo-fenton and ultraviolet radiation.

Current research in microbial sciences, 7:100244.

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.

RevDate: 2025-05-30
CmpDate: 2024-06-08

Hoisington AJ, Stamper CE, Ellis JC, et al (2024)

Quantifying variation across 16S rRNA gene sequencing runs in human microbiome studies.

Applied microbiology and biotechnology, 108(1):367.

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.

RevDate: 2025-08-17
CmpDate: 2024-06-03

Kitsios GD, Sayed K, Fitch A, et al (2024)

Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure.

Nature communications, 15(1):4708.

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.

RevDate: 2025-08-15

Jain R, Hadjigeorgiou A, Harkos C, et al (2023)

Dissecting the Impact of the Gut Microbiome on Cancer Immunotherapy.

Research square.

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.

RevDate: 2024-09-30

Li W, Mirone J, Prasad A, et al (2023)

Orthogonal outlier detection and dimension estimation for improved MDS embedding of biological datasets.

Frontiers in bioinformatics, 3:1211819.

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.

RevDate: 2023-07-18
CmpDate: 2023-07-18

Lugones-Sánchez C, Santos-Mínguez S, Salvado R, et al (2023)

Lifestyles, arterial aging, and its relationship with the intestinal and oral microbiota (MIVAS III study): a research protocol for a cross-sectional multicenter study.

Frontiers in public health, 11:1164453.

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.

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[®]) 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 α and β diversity, conducting abundance profiling, and performing clustering analysis.

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.

TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT04924907, ClinicalTrials.gov, identifier: NCT04924907. Registered on 21 April 2021.

RevDate: 2023-02-27
CmpDate: 2023-01-03

Villemin C, Six A, Neville BA, et al (2023)

The heightened importance of the microbiome in cancer immunotherapy.

Trends in immunology, 44(1):44-59.

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.

RevDate: 2022-11-02
CmpDate: 2022-10-25

Mahapatra S, Mohanty S, Mishra R, et al (2022)

An overview of cancer and the human microbiome.

Progress in molecular biology and translational science, 191(1):83-139.

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.

RevDate: 2022-12-22
CmpDate: 2022-09-19

Roussel C, Anunciação Braga Guebara S, Plante PL, et al (2022)

Short-term supplementation with ω-3 polyunsaturated fatty acids modulates primarily mucolytic species from the gut luminal mucin niche in a human fermentation system.

Gut microbes, 14(1):2120344.

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.

RevDate: 2025-07-28
CmpDate: 2022-09-08

Ke S, Weiss ST, YY Liu (2022)

Dissecting the role of the human microbiome in COVID-19 via metagenome-assembled genomes.

Nature communications, 13(1):5235.

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.

RevDate: 2025-07-28
CmpDate: 2022-08-29

Lane MM, Lotfaliany M, Forbes M, et al (2022)

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.

Nutrients, 14(16):.

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.

RevDate: 2024-09-03
CmpDate: 2022-12-23

Kitrinos C, Bell RB, Bradley BJ, et al (2022)

Hair Microbiome Diversity within and across Primate Species.

mSystems, 7(4):e0047822.

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.

RevDate: 2022-07-16
CmpDate: 2022-06-30

Oliver A, Xue Z, Villanueva YT, et al (2022)

Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults.

mBio, 13(3):e0010122.

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.

RevDate: 2023-11-08

McGee JS, C Huttenhower (2021)

Of mice and men and women: Sexual dimorphism of the gut microbiome.

International journal of women's dermatology, 7(5Part A):533-538.

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.

RevDate: 2023-11-07
CmpDate: 2021-09-17

Wang C, Hu J, Blaser MJ, et al (2021)

Microbial trend analysis for common dynamic trend, group comparison, and classification in longitudinal microbiome study.

BMC genomics, 22(1):667.

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.

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.

CONCLUSIONS: The proposed MTA framework is an attractive and effective tool in investigating dynamic microbial pattern from longitudinal microbiome studies.

RevDate: 2024-10-28
CmpDate: 2021-05-26

Classen AY, Henze L, von Lilienfeld-Toal M, et al (2021)

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).

Annals of hematology, 100(6):1603-1620.

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.

RevDate: 2023-11-10
CmpDate: 2021-04-06

Blaustein RA, Michelitsch LM, Glawe AJ, et al (2021)

Toothbrush microbiomes feature a meeting ground for human oral and environmental microbiota.

Microbiome, 9(1):32.

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.

RESULTS: Toothbrush microbiomes often comprised a dominant subset of human oral taxa and less abundant or 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.

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.

RevDate: 2023-11-10
CmpDate: 2021-03-10

Silverstein RB, IU Mysorekar (2021)

Group therapy on in utero colonization: seeking common truths and a way forward.

Microbiome, 9(1):7.

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.

RevDate: 2023-11-10
CmpDate: 2021-11-30

Utter DR, Borisy GG, Eren AM, et al (2020)

Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity.

Genome biology, 21(1):293.

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.

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.

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.

RevDate: 2021-06-21
CmpDate: 2021-06-21

Gosens R, Hiemstra PS, Adcock IM, et al (2020)

Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease.

The European respiratory journal, 56(2):.

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.

RevDate: 2020-09-28

Wang C, Li P, Yan Q, et al (2019)

Characterization of the Pig Gut Microbiome and Antibiotic Resistome in Industrialized Feedlots in China.

mSystems, 4(6):.

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.

RevDate: 2019-12-17
CmpDate: 2019-12-06

Lew KN, Starkweather A, Cong X, et al (2019)

A Mechanistic Model of Gut-Brain Axis Perturbation and High-Fat Diet Pathways to Gut Microbiome Homeostatic Disruption, Systemic Inflammation, and Type 2 Diabetes.

Biological research for nursing, 21(4):384-399.

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.

RevDate: 2020-11-06

Vlasova AN, Rajashekara G, LJ Saif (2018)

Interactions between human microbiome, diet, enteric viruses and immune system: Novel insights from gnotobiotic pig research.

Drug discovery today. Disease models, 28:95-103.

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.

RevDate: 2018-04-24
CmpDate: 2018-04-24

Wagner Mackenzie B, Waite DW, Hoggard M, et al (2017)

Moving beyond descriptions of diversity: clinical and research implications of bacterial imbalance in chronic rhinosinusitis.

Rhinology, 55(4):291-297.

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.

RevDate: 2023-11-10
CmpDate: 2015-03-10

Bawa M, VA Saraswat (2013)

Gut-liver axis: role of inflammasomes.

Journal of clinical and experimental hepatology, 3(2):141-149.

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.

RevDate: 2025-08-17

H L, L T, J L, et al (2025)

Ketogenic diet influences the renin-angiotensin-aldosterone system components in the healthy and inflamed intestine of male mice.

The Journal of nutritional biochemistry pii:S0955-2863(25)00241-4 [Epub ahead of print].

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.

RevDate: 2025-08-15

Wang X, Liang T, Liang Z, et al (2025)

Increased vaginal Gardnerella vaginalis abundance and reduced D-galactose metabolism are associated with preterm birth in older mothers with columnar ectopy in South China.

mSystems [Epub ahead of print].

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.

RevDate: 2025-08-13

West SR, Adekoya AE, Arriaga SK, et al (2025)

Genomic analysis of eight clinical Rothia isolates.

Microbiology resource announcements [Epub ahead of print].

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.

RevDate: 2025-08-11

Nooij S, Sanders IMJG, Schout L, et al (2025)

Draft and complete genome sequences of 17 Streptococcus species.

Microbiology resource announcements [Epub ahead of print].

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.

RevDate: 2025-08-13
CmpDate: 2025-08-13

Zhang Z, Zhao Z, Huang X, et al (2025)

Galectin-3-integrin α5β1 phase separation disrupted by advanced glycation end-products impairs diabetic wound healing in rodents.

Nature communications, 16(1):7287.

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.

RevDate: 2025-08-09
CmpDate: 2025-08-07

Myers T, Song SJ, Chen Y, et al (2025)

Chronological age estimation from human microbiomes with transformer-based Robust Principal Component Analysis.

Communications biology, 8(1):1159.

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.

RevDate: 2025-08-08

Kim BR, Rha MS, Cho HJ, et al (2025)

Spatiotemporal regulation by downstream genes of Prok2 in the olfactory system: from development to function.

Frontiers in cell and developmental biology, 13:1550845.

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.

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.

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.

DISCUSSION: Overall, these findings reveal the role of Prok2 in olfactory system organization and elucidate how olfactory development defects translate to olfactory function.

RevDate: 2025-08-12

Ho PY, KC Huang (2025)

Challenges in interpreting functional redundancy and quantifying functional selection in microbial communities.

Cell systems pii:S2405-4712(25)00183-8 [Epub ahead of print].

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.

RevDate: 2025-08-05

do Carmo Greier M, BG Hofauer (2025)

[Prebiotics, probiotics and postbiotics-An introduction].

HNO [Epub ahead of print].

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.

RevDate: 2025-08-04

Blaser MJ, MG Dominguez-Bello (2025)

The Invisible Extinction.

Annual review of microbiology [Epub ahead of print].

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.

RevDate: 2025-08-04

Adekoya AE, West SR, Arriaga SK, et al (2025)

Infections as ecosystems: community metabolic interactions in microbial pathogenesis.

Infection and immunity [Epub ahead of print].

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.

RevDate: 2025-08-02

Sendo S, Vela AJ, Ro M, et al (2025)

Interaction between haploinsufficiency of PTPN2 and patient microbiome promotes autoimmune arthritis in mice.

Journal of autoimmunity, 156:103452 pii:S0896-8411(25)00097-6 [Epub ahead of print].

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.

RevDate: 2025-08-02

Malik YS, Pathania A, De UK, et al (2025)

Exploring the Therapeutic Landscape of Probiotics in Enteric and Respiratory Viral Infections.

Probiotics and antimicrobial proteins [Epub ahead of print].

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.

RevDate: 2025-08-04

Caminero A, Tropini C, Valles-Colomer M, et al (2025)

Credible inferences in microbiome research: ensuring rigour, reproducibility and relevance in the era of AI.

Nature reviews. Gastroenterology & hepatology [Epub ahead of print].

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.

RevDate: 2025-08-05

Tang G, Carr AV, Perez C, et al (2025)

Metagenomic estimation of absolute bacterial biomass in the mammalian gut through host-derived read normalization.

mSystems [Epub ahead of print].

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.

RevDate: 2025-08-03
CmpDate: 2025-07-31

Tao R, Wang X, Zhen X, et al (2025)

Skin Microbiome alterations in heroin users revealed by full-length 16S rRNA sequencing.

BMC microbiology, 25(1):461.

BACKGROUND: Identifying key characteristics of unknown suspects, such as age, height, and drug use, is essential for advancing forensic investigations.

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.

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.

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.

RevDate: 2025-07-30

Carter MM, Demis D, Perelman D, et al (2025)

A human milk oligosaccharide alters the microbiome, circulating hormones, and metabolites in a randomized controlled trial of older adults.

Cell reports. Medicine pii:S2666-3791(25)00329-5 [Epub ahead of print].

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).

RevDate: 2025-07-30

Liang C, Zhou Z, Li P, et al (2025)

The role of Gram-positive cocci in cancer initiation, progression, and its application in therapy.

International journal of cancer [Epub ahead of print].

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.

RevDate: 2025-07-31
CmpDate: 2025-07-29

Anholt H (2025)

The association between Toxoplasma gondii infection and asthma in the United States: A cross-sectional survey analysis.

PloS one, 20(7):e0304044.

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.

RevDate: 2025-07-30

Qi H, Gao H, Li M, et al (2025)

Author Correction: Parvimonas micra promotes oral squamous cell carcinoma metastasis through TmpC-CKAP4 axis.

Nature communications, 16(1):6856 pii:10.1038/s41467-025-62180-4.

RevDate: 2025-07-27

Verma B, Kumar N, Ashique S, et al (2025)

Probiotics: An adjuvant treatment strategy for chronic respiratory diseases.

Respiratory medicine, 247:108268 pii:S0954-6111(25)00331-2 [Epub ahead of print].

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.

RevDate: 2025-07-24
CmpDate: 2025-07-24

Zhao Y, Liu X, Song P, et al (2025)

Advances in the Relationship Between Skin Tumor Occurrence, Development, Prognosis, and the Human Microbiome.

Current microbiology, 82(9):408.

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.

RevDate: 2025-07-31
CmpDate: 2025-07-24

Männistö SA, Muotka J, Suojanen LU, et al (2025)

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.

JMIR mental health, 12:e66518.

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.

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.

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).

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.

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.

RevDate: 2025-07-25
CmpDate: 2025-07-24

Xiao YY, Ma YY, Zhang YB, et al (2025)

Advances in Influencing Mechanisms and Therapeutic Effects of Bacteriophages on Cancer.

Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae, 47(3):470-477.

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.

RevDate: 2025-08-13

Aro T, Häkkinen TA, Holmberg V, et al (2025)

War on antimicrobial resistance: high carriage rates of multidrug-resistant bacteria among war-injured Ukrainian refugees.

RevDate: 2025-07-24

Sun H, Finlay B, Azad MB, et al (2025)

The human milk bacteriome and mycobiome and their inter-kingdom interactions viewed across geography.

Frontiers in nutrition, 12:1610346.

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.

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.

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.

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.

RevDate: 2025-07-24
CmpDate: 2025-07-22

Mun S, Jo H, Heo YM, et al (2025)

Skin microbiome-biophysical association: a first integrative approach to classifying Korean skin types and aging groups.

Frontiers in cellular and infection microbiology, 15:1561590.

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.

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.

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.

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.

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.

RevDate: 2025-07-28
CmpDate: 2025-07-19

Pianka ML, Werba A, Zimmermann S, et al (2025)

The role of the MicroBiome in PANCreatic cancer and its precursors- the study protocol of the MiBiPanc systematic review and meta-analysis.

Systematic reviews, 14(1):150.

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.

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.

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.

PROSPERO CRD42023487995.

RevDate: 2025-07-18

Searle T, Al-Niaimi F, FR Ali (2025)

Modulation of the microbiome: a paradigm shift in the treatment of acne.

Clinical and experimental dermatology pii:8206091 [Epub ahead of print].

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.

RevDate: 2025-07-18

Parks ST, Marchesani A, C Taylor (2025)

Scaffolding of assignments and grading to promote STEM literacy in a human microbiome course.

Journal of microbiology & biology education [Epub ahead of print].

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.

RevDate: 2025-07-17

Zhang J, Dong H, Liang L, et al (2025)

Targeting gut microbiota and arginase boosts MEK inhibitors' enhancement of antitumour immunity via MHC-I upregulation in colorectal cancer.

British journal of cancer [Epub ahead of print].

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.

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.

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.

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.

RevDate: 2025-07-20
CmpDate: 2025-07-17

Serna C, Matamoros BR, Pulido-Vadillo M, et al (2025)

Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria.

Nature communications, 16(1):6360.

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.

RevDate: 2025-08-07
CmpDate: 2025-07-30

Saarimäki LA, Fratello M, Del Giudice G, et al (2025)

Wisdom of Crowds for Supporting the Safety Evaluation of Nanomaterials.

Environmental science & technology, 59(29):14969-14980.

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.

RevDate: 2025-07-18
CmpDate: 2025-07-17

Whitaker WR, Russ ZN, Stanley Shepherd E, et al (2025)

Controlled colonization of the human gut with a genetically engineered microbial therapeutic.

Science (New York, N.Y.), 389(6757):303-308.

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.

RevDate: 2025-07-25
CmpDate: 2025-07-16

Omary L, Canfora EE, Puhlmann ML, et al (2025)

Intrinsic chicory root fibers modulate colonic microbial butyrate-producing pathways and improve insulin sensitivity in individuals with obesity.

Cell reports. Medicine, 6(7):102237.

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).

RevDate: 2025-07-18

Lei S, Wang J, Zhang M, et al (2025)

The Succession of Cervical Canal Microbiota in Endometrial Cancer and Cervical Cancer: A Clinical Metagenomics Study.

International journal of women's health, 17:2039-2050.

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.

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.

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.

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.

RevDate: 2025-07-17
CmpDate: 2025-07-15

Ji X, Zhi M, Gu X, et al (2025)

DnaK of Parvimonas micra extracellular vesicles interacts with the host fibroblasts BAG3-IKK-γ axis to accelerate TNF-α secretion in oral lichen planus.

Microbiome, 13(1):164.

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.

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-κB pathway linked to TNF-α. Co-culturing of P. micra or its extracellular vesicles (EVs) with fibroblasts showed that P. micra and EVs could activate the NF-κB 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-κB pathway and decreased autophagy flux. Additionally, we identified that IKK-γ was the key downstream protein that could bind with DnaK-BAG3, thereby inhibiting autophagy and promoting TNF-α secretion.

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-α secretion in OLP fibroblasts via the DnaK-BAG3-IKK-γ axis. This study offers novel insights into the pathogenic mechanisms underlying OLP. Video Abstract.

RevDate: 2025-07-16

Robinson JM, Crino OL, Camargo A, et al (2025)

Does a microbial-endocrine interplay shape love-associated emotions in humans? A hypothesis.

mSystems [Epub ahead of print].

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.

RevDate: 2025-07-16
CmpDate: 2025-07-14

Pena-Amelunxen G, Asghari M, Khatri K, et al (2025)

Pre-clinical allergenicity assessment of IgE epitope-targeted Der p 2 mutants demonstrate potential as hypoallergenic AIT candidates.

Frontiers in immunology, 16:1623920.

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.

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.

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.

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.

RevDate: 2025-07-13
CmpDate: 2025-07-13

Sarath Krishnan MP, Goyal B, Nampui L, et al (2025)

The role of microbiome in gastrointestinal cancer.

International review of cell and molecular biology, 395:67-98.

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.

RevDate: 2025-07-16

Palkovsky M, Modrackova N, Neuzil-Bunesova V, et al (2025)

Role of Human Microbiome in Development and Management of Head and Neck Squamous Cell Carcinoma.

Cancers, 17(13):.

Despite decades of research, cancer remains a major global health problem [...].

RevDate: 2025-08-01
CmpDate: 2025-07-30

Seekatz AM (2025)

Straining to define a healthy microbiome.

mSphere, 10(7):e0079724.

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.

RevDate: 2025-08-07
CmpDate: 2025-08-06

Qi X, Zhang M, Wei T, et al (2025)

LorDist: a novel method for calculating the distance based on functional data analysis with application to longitudinal microbial data.

Microbiology spectrum, 13(8):e0154225.

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.

RevDate: 2025-07-12
CmpDate: 2025-07-11

Jasemi SK, Faridafshar H, Amin MN, et al (2025)

NO: a key player in microbiome dynamics and cancer pathogenesis.

Frontiers in cellular and infection microbiology, 15:1532255.

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.

RevDate: 2025-08-06
CmpDate: 2025-08-06

Dasgupta S (2025)

Unraveling the Microbiome-Asthma Axis: Metagenomic Insights from Airway and Gut Microbial Communities.

Omics : a journal of integrative biology, 29(8):374-383.

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.

RevDate: 2025-07-10

Hyvönen S, Solasaari T, Pokka T, et al (2025)

Maternal Prenatal and Postnatal Stress and Infections in Infancy.

Acta paediatrica (Oslo, Norway : 1992) [Epub ahead of print].

AIM: To study maternal stress as a possible risk factor for early infections in infants in a well-characterised, prospective infant HELMi cohort.

METHODS: We measured maternal stress during the last trimester with questionnaires (4 items, scales 0-100) and breastmilk cortisol levels at 3 months. We compared maternal stress between infants with several infections (n = 125) and infants with no infections (n = 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.

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 = 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 nmol/L [IQR 4.8-8.8] and 6.2 nmol/L [4.5-8.4], respectively; p = 0.12).

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.

RevDate: 2025-07-08

Wan H, Weng J, Cai J, et al (2025)

Nodal Downstaging in Rectal Cancer Patients: Survival is Promising if YpN0 is Achieved.

Diseases of the colon and rectum pii:00003453-990000000-00997 [Epub ahead of print].

BACKGROUND: Locally advanced rectal cancer is a critical health concern, with neoadjuvant therapy emerging as a pivotal strategy to enhance survival rates.

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.

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.

SETTINGS: The multicenter, randomized phase III FOWARC trial was conducted across 15 hospitals in China, adhering to ethical standards.

PATIENTS: Our cohort included 449 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision.

INTERVENTIONS: Neoadjuvant chemoradiotherapy followed by total mesorectal excision.

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.

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.

LIMITATIONS: The study's retrospective design may introduce potential biases in patient selection and preoperative staging.

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.

RevDate: 2025-07-29
CmpDate: 2025-07-08

Sequoia JA, Haddock NL, Gay PM, et al (2025)

Identification of bacteriophage DNA in human umbilical cord blood.

JCI insight, 10(13):.

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.

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In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

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