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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 26 Jul 2024 at 01:32 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: ( "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" ) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2024-07-23

Sun W, Reeves W, Fagan MM, et al (2024)

Evaluation of Brain Function Recovery After Traumatic Brain Injury Treatment in a Porcine Model by Cross-Group Temporal-Spatial Correlation Analysis.

Neurotrauma reports, 5(1):617-627.

Traumatic brain injury (TBI), a significant global health issue, is affecting ∼69 million annually. To better understand TBI's impact on brain function and assess the efficacy of treatments, this study uses a novel temporal-spatial cross-group approach with a porcine model, integrating resting-state functional magnetic resonance imaging (rs-fMRI) for temporal and arterial spin labeling for spatial information. Our research used 18 four-week-old pigs divided into three groups: TBI treated with saline (SLN, n = 6), TBI treated with fecal microbial transplant (FMT, n = 6), and a sham group (sham, n = 6) with only craniectomy surgery as the baseline. By applying machine learning techniques-specifically, independent component analysis and sparse dictionary learning-across seven identified resting-state networks, we assessed the temporal and spatial correlations indicative of treatment efficacy. Both temporal and spatial analyses revealed a consistent increase of correlation between the FMT and sham groups in the executive control and salience networks. Our results are further evidenced by a simulation study designed to mimic the progression of TBI severity through the introduction of variable Gaussian noise to an independent rs-fMRI dataset. The results demonstrate a decreasing temporal correlation between the sham and TBI groups with increasing injury severity, consistent with the experimental results. This study underscores the effectiveness of the methodology in evaluating post-TBI treatments such as the FMT. By presenting comprehensive experimental and simulated data, our research contributes significantly to the field and opens new paths for future investigations into TBI treatment evaluations.

RevDate: 2024-07-23

You M, Chen N, Yang Y, et al (2024)

The gut microbiota-brain axis in neurological disorders.

MedComm, 5(8):e656.

Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota-gut-brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe-based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.

RevDate: 2024-07-23

Lin Z, Jiang T, Chen M, et al (2024)

Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects.

Open life sciences, 19(1):20220910.

Sleep is crucial for wellness, and emerging research reveals a profound connection to gut microbiota. This review explores the bidirectional relationship between gut microbiota and sleep, exploring the mechanisms involved and the therapeutic opportunities it presents. The gut-brain axis serves as a conduit for the crosstalk between gut microbiota and the central nervous system, with dysbiosis in the microbiota impairing sleep quality and vice versa. Diet, circadian rhythms, and immune modulation all play a part. Specific gut bacteria, like Lactobacillus and Bifidobacterium, enhance sleep through serotonin and gamma-aminobutyric acid production, exemplifying direct microbiome influence. Conversely, sleep deprivation reduces beneficial bacteria, exacerbating dysbiosis. Probiotics, prebiotics, postbiotics, and fecal transplants show therapeutic potential, backed by animal and human research, yet require further study on safety and long-term effects. Unraveling this intricate link paves the way for tailored sleep therapies, utilizing microbiome manipulation to improve sleep and health. Accelerated research is essential to fully tap into this promising field for sleep disorder management.

RevDate: 2024-07-22
CmpDate: 2024-07-22

Krigul KL, Feeney RH, Wongkuna S, et al (2024)

A history of repeated antibiotic usage leads to microbiota-dependent mucus defects.

Gut microbes, 16(1):2377570.

Recent evidence indicates that repeated antibiotic usage lowers microbial diversity and ultimately changes the gut microbiota community. However, the physiological effects of repeated - but not recent - antibiotic usage on microbiota-mediated mucosal barrier function are largely unknown. By selecting human individuals from the deeply phenotyped Estonian Microbiome Cohort (EstMB), we here utilized human-to-mouse fecal microbiota transplantation to explore long-term impacts of repeated antibiotic use on intestinal mucus function. While a healthy mucus layer protects the intestinal epithelium against infection and inflammation, using ex vivo mucus function analyses of viable colonic tissue explants, we show that microbiota from humans with a history of repeated antibiotic use causes reduced mucus growth rate and increased mucus penetrability compared to healthy controls in the transplanted mice. Moreover, shotgun metagenomic sequencing identified a significantly altered microbiota composition in the antibiotic-shaped microbial community, with known mucus-utilizing bacteria, including Akkermansia muciniphila and Bacteroides fragilis, dominating in the gut. The altered microbiota composition was further characterized by a distinct metabolite profile, which may be caused by differential mucus degradation capacity. Consequently, our proof-of-concept study suggests that long-term antibiotic use in humans can result in an altered microbial community that has reduced capacity to maintain proper mucus function in the gut.

RevDate: 2024-07-21
CmpDate: 2024-07-21

Zhuang Y, Liu S, Gao D, et al (2024)

The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host.

NPJ biofilms and microbiomes, 10(1):59.

The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

RevDate: 2024-07-20

Zhang H, Hao Z, Zhang R, et al (2024)

Artemisia argyi polyphenols Attenuates DSS-induced colitis in mice by regulating the structural composition of gut microbiota.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 132:155897 pii:S0944-7113(24)00555-5 [Epub ahead of print].

BACKGROUND: Intestinal health is affected by heredity, lifestyle, and structure of gut microbiota. The imbalance of symbiotic and harmful bacteria in gut microbiota may increase the occurrence of colonic inflammation. Supplementary A. muciniphila can improve the survival rate of colitis mice, reduce colon tissue injury, and the expression of anti-inflammatory factors was upregulated. Artemisia argyi has been reported to have anti-inflammatory, antioxidant, bactericidal, and immunomodulatory effects. However, its anti-inflammatory effect and mechanism, and its influence on gut microbiota and metabolites are still unclear yet.

PURPOSE: To explore whether Artemisia argyi Polyphenols(AAPs) can alleviate ulcerative colitis (UC) by changing gut microbiota.

METHODS: The therapeutic effect of AAPs on colitis was investigated by inducing ulcerative colitis in mice using dextran sodium sulfate (DSS) and administering different doses of AAPs orally to mice. Exploring the levels of inflammatory proteins, oxidative stress proteins, and barrier proteins using western blotting and immunofluorescence, and explored the structural changes of gut microbiota and its metabolites. Meanwhile, in order to explore whether the role of AAPs in alleviating colitis is based on the regulation of gut microbiota structure, we conducted fecal microbiota transplantation (FMT).

RESULTS: It showed that AAPs and FMT trial alleviated DSS-induced colonic injury, including clinical parameters and pathological injury of colon tissue, reduction in the expression of inflammatory proteins: IL-6, TNF-α, p-p65, p-IκBα, and increase in the expression of antioxidant proteins: Nrf2, NQO-1 and HO-1 and barrier proteins: Claudin-1, Occludin, ZO-1 and MUC2. AAPs and FMT promoted the content of beneficial bacteria, such as Butyricimonas and Lactobacillus, and the content of beneficial metabolites for instance acetic acid, butyric acid, and valeric acid has also increased.

CONCLUSION: These results suggested that AAPs might improve DSS-induced colonic injury by changing the structural of gut microbiota while promoting the synthesis of fatty acids in the intestine, thereby providing a theoretical basis for using AAPs to treat ulcerative colitis.

RevDate: 2024-07-20

Koller T, Vrbova P, Kubanek N, et al (2024)

Assessment of intestinal inflammation via fecal calprotectin for early prediction of adverse outcomes in advanced chronic liver disease.

United European gastroenterology journal [Epub ahead of print].

BACKGROUND AND AIMS: Intestinal inflammation assessed by fecal calprotectin (F-CAL) in advanced chronic liver disease (ACLD) may represent an early sign of intestinal barrier dysfunction. We aimed to explore the usefulness of F-CAL testing in ACLD in the prediction of adverse outcomes (AO, death, or LT) and refinement of prognostic stratification.

PATIENTS AND METHODS: We explored the RH7 cirrhosis registry comprising consecutive hospitalized patients and a control group with data on disease phenotype, demographics, anthropometrics, prognostic indices, and medication. The F-CAL was evaluated on admission and reported in multiples of the upper limit of normal or terciles. Predictive power was tested in the Cox model for AO over 180 days. Additional risk refinement by F-CAL was tested for both groups.

RESULTS: We enrolled 263 cases in the study group with a median age of 57.2 years, M/F ratio 167/96, with alcohol, metabolic dysfunction-associated steatotic liver disease, MetALD, and viral etiologies in 72.2%, 9.1, 8.0, 3.4%. The median F-CAL was 3.92 × ULN. The control group comprised 108 cases. The adjusted Cox model confirmed F-CAL (hazard ratio [HR] = 1.05, p < 0.001) and F-CAL terciles (HR = 1.413, p = 0.009) as independent predictors of AO. F-CAL terciles had higher predictive accuracy in CLIF-C-AD<50 (HR = 2.49, p = 0.013) and Child stages A and B (HR = 1.706, p = 0.025), in whom high F-CAL (cut-off >11 × ULN) could identify patients having 2-3 times higher risk of AO. This approach has been validated in the control group.

CONCLUSION: Among hospitalized patients with ACLD, F-CAL values were independently proportional to the risk of AO, particularly in early disease stages when high F-CAL values could refine prognostic stratification.

RevDate: 2024-07-20

Dong Y, Dong J, Xiao H, et al (2024)

A gut microbial metabolite cocktail fights against obesity through modulating the gut microbiota and hepatic leptin signaling.

Journal of the science of food and agriculture [Epub ahead of print].

BACKGROUND: Excessive body weight and obesity elevate the risk of chronic non-communicable diseases. The judicious application of the gut microbiome, encompassing both microorganisms and their derived compounds, holds considerable promise in the treatment of obesity.

RESULTS: In this study, we showed that a cocktail of gut microbiota-derived metabolites, comprising indole 3-propionic acid (IPA), sodium butyrate (SB) and valeric acid (VA), alleviated various symptoms of obesity in both male and female mice subjected to a high-fat diet (HFD). The 16S ribosomal RNA (rRNA) sequencing revealed that administering the cocktail via oral gavage retained the gut microbiota composition in obese mice. Fecal microbiota transplantation using cocktail-treated mice as donors mitigated the obesity phenotype of HFD-fed mice. Transcriptomic sequencing analysis showed that the cocktail preserved the gene expression profile of hepatic tissues in obese mice, especially up-regulated the expression level of leptin receptor. Gene delivery via in vivo fluid dynamics further validated that the anti-obesity efficacy of the cocktail was dependent on leptin signaling at least partly. The cocktail also inhibited the expression of appetite stimulators in hypothalamus. Together, the metabolite cocktail combated adiposity by retaining the gut microbiota configuration and activating the hepatic leptin signaling pathway.

CONCLUSIONS: Our findings provide a sophisticated regulatory network between the gut microbiome and host, and highlight a cocktail of gut microbiota-derived metabolites, including IPA, SB, and VA, might be a prospective intervention for anti-obesity in a preclinical setting. © 2024 Society of Chemical Industry.

RevDate: 2024-07-19

Du HX, Yue SY, Niu D, et al (2024)

Alcohol intake exacerbates experimental autoimmune prostatitis through gut microbiota driving cholesterol biosynthesis-mediated Th17 differentiation.

International immunopharmacology, 139:112669 pii:S1567-5769(24)01190-1 [Epub ahead of print].

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process.

METHOD: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice.

RESULTS: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet.

CONCLUSION: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis.

RevDate: 2024-07-20

Li Y, Zhang B, Jiang L, et al (2024)

Gut microbiota plays pivotal roles in benign and malignant hematopoiesis.

Blood science (Baltimore, Md.), 6(4):e00200.

Accumulated evidence emerges that dynamic changes in human gut microbiota and microbial metabolites can alter the ecological balance of symbiotic hosts. The gut microbiota plays a role in various diseases through different mechanisms. More and more attention has been paid to the effects that human microbiota extends beyond the gut. This review summarized the current understanding of the roles that gut microbiota plays in hematopoietic regulation and the occurrence and development of benign and malignant hematologic diseases. The progress of the application of microbiota in treatment was discussed in order to provide new insights into clinical diagnosis and treatment in the future.

RevDate: 2024-07-20

Khaledi M, Sameni F, Gholipour A, et al (2024)

Potential role of gut microbiota in major depressive disorder: A review.

Heliyon, 10(12):e33157.

Interactions between the gut microbiota and host immunity are sophisticated, dynamic, and host-dependent. Scientists have recently conducted research showing that disturbances in the gut bacterial community can lead to a decrease in some metabolites and, consequently, to behaviors such as depression. Exposure to stressors dropped the relative abundance of bacteria in the genus Bacteroides while soaring the relative abundance of bacteria in the genus Clostridium, Coprococcus, Dialister, and Oscillibacter, which were also reduced in people with depression. Microbiota and innate immunity are in a bilateral relationship. The gut microbiota has been shown to induce the synthesis of antimicrobial proteins such as catalysidins, type C lectins, and defensins. Probiotic bacteria can modulate depressive behavior through GABA signaling. The gut microbiome produces essential metabolites such as neurotransmitters, tryptophan metabolites, and short-chain fatty acids (SCFAs) that can act on the CNS. In the case of dysbiosis, due to mucin changes, the ratio of intestinal-derived molecules may change and contribute to depression. Psychotropics, including Bifidobacterium longum NCC3001, Clostridium butyricum CBM588, and Lactobacillus acidophilus, have mental health benefits, and can have a positive effect on the host-brain relationship, and have antidepressant effects. This article reviews current studies on the association between gut microbiota dysbiosis and depression. Comprehensively, these findings could potentially lead to novel approaches to improving depressive symptoms via gut microbiota alterations, including probiotics, prebiotics, and fecal microbiota transplantation.

RevDate: 2024-07-20

Cui X, Wu Z, Zhou Y, et al (2024)

A bibliometric study of global trends in T1DM and intestinal flora research.

Frontiers in microbiology, 15:1403514.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that seriously jeopardizes human physical and mental health and reduces quality of life. Intestinal flora is one of the critical areas of exploration in T1DM research.

OBJECTIVE: This study aims to explore the research hotspot and development trend of T1DM and intestinal flora to provide research direction and ideas for researchers.

METHODS: We used the Web of Science (WOS) Core Collection and searched up to 18 November 2023, for articles on studies of the correlation between T1DM and intestinal flora. CiteSpace, VOSviewers and R package "bibliometrix" were used to conduct this bibliometric analysis.

RESULTS: Eventually, 534 documents met the requirements to be included, and as of 18 November 2023, there was an upward trend in the number of publications in the field, with a significant increase in the number of articles published after 2020. In summary, F Susan Wong (UK) was the author with the most publications (21), the USA was the country with the most publications (198), and the State University System of Florida (the United States) was the institution with the most publications (32). The keywords that appeared more frequently were T cells, fecal transplants, and short-chain fatty acids. The results of keywords with the most robust citation bursts suggest that Faecalibacterium prausnitzii and butyrate may become a focus of future research.

CONCLUSION: In the future, intestinal flora will remain a research focus in T1DM. Future research can start from Faecalibacterium prausnitzii and combine T cells, fecal bacteria transplantation, and short-chain fatty acids to explore the mechanism by which intestinal flora affects blood glucose in patients with T1DM, which may provide new ideas for the prevention and treatment of T1DM.

RevDate: 2024-07-20
CmpDate: 2024-07-19

Chen Y, Sun K, Qi Y, et al (2024)

L-valine derived from the gut microbiota protects sepsis-induced intestinal injury and negatively correlates with the severity of sepsis.

Frontiers in immunology, 15:1424332.

BACKGROUND: The protective role of gut microbiota and its metabolites against intestinal damage in sepsis patients remain unclear.

METHODS: Fecal samples were acquired from patients categorized into sepsis and non-sepsis groups for analysis of microbial composition via 16S rRNA sequencing and untargeted metabolomics analysis. We assessed the impact of gut microbiota from sepsis patients on intestinal barriers in antibiotic-treated mice. Furthermore, We conducted spearman's correlation analysis to examine the relationship between metabolites and the severity of sepsis. Additionally, we performed animal experiments to validate the functionality of identified metabolites.

RESULTS: The diversity of intestinal flora is decreased in patients with sepsis compared to the control group. Through fecal microbiota transplantation experiments, it was discovered that the gut microbiota derived from sepsis patients could induce intestinal damage in antibiotic-treated mice. Metabolomics analysis of the microbiota revealed a significant enrichment of the Valine, leucine, and isoleucine biosynthesis pathway. Further analysis showed a significant decrease in the abundance of L-valine in sepsis patients, which was negatively correlated with APACHE-II and SOFA scores. In sepsis mouse experiments, it was found that L-valine could alleviate sepsis-induced intestinal damage.

CONCLUSION: Alterations in microbial and metabolic features in the gut can affect the severity of sepsis. Furthermore, L-valine can protect against sepsis-induced intestinal injury.

RevDate: 2024-07-20
CmpDate: 2024-07-19

Tian X, Li S, Wang C, et al (2024)

Gut virome-wide association analysis identifies cross-population viral signatures for inflammatory bowel disease.

Microbiome, 12(1):130.

BACKGROUND: The gut virome has been implicated in inflammatory bowel disease (IBD), yet a full understanding of the gut virome in IBD patients, especially across diverse geographic populations, is lacking.

RESULTS: In this study, we conducted a comprehensive gut virome-wide association study in a Chinese cohort of 71 IBD patients (15 with Crohn's disease and 56 with ulcerative colitis) and 77 healthy controls via viral-like particle (VLP) and bulk virome sequencing of their feces. By utilizing an integrated gut virus catalog tailored to the IBD virome, we revealed fundamental alterations in the gut virome in IBD patients. These characterized 139 differentially abundant viral signatures, including elevated phages predicted to infect Escherichia, Klebsiella, Enterococcus_B, Streptococcus, and Veillonella species, as well as IBD-depleted phages targeting Prevotella, Ruminococcus_E, Bifidobacterium, and Blautia species. Remarkably, these viral signatures demonstrated high consistency across diverse populations such as those in Europe and the USA, emphasizing their significance and broad relevance in the disease context. Furthermore, fecal virome transplantation experiments verified that the colonization of these IBD-characterized viruses can modulate experimental colitis in mouse models.

CONCLUSIONS: Building upon these insights into the IBD gut virome, we identified potential biomarkers for prognosis and therapy in IBD patients, laying the foundation for further exploration of viromes in related conditions. Video Abstract.

RevDate: 2024-07-18

Yirmiya K, Turjeman S, Shtossel O, et al (2024)

Microbiome signature of posttraumatic stress disorder and resilience in youth.

Psychological trauma : theory, research, practice and policy pii:2025-03751-001 [Epub ahead of print].

OBJECTIVE: Identifying biomarkers that can distinguish trauma-exposed youth at risk for developing posttraumatic pathology from resilient individuals is essential for targeted interventions. As trauma can alter the microbiome with lasting effects on the host, our longitudinal, multimeasure, cross-species study aimed to identify the microbial signature of posttraumatic stress disorder (PTSD).

METHOD: We followed children exposed to war-related trauma and matched controls from early childhood (Mage = 2.76 years, N = 232) to adolescence (Mage = 16.13 years, N = 84), repeatedly assessing posttraumatic symptomatology and maternal caregiving. In late adolescence, we collected fecal samples from mothers and youth and assessed microbiome composition, diversity, and mother-child microbial synchrony. We then transplanted adolescents' fecal samples into germ-free mice to determine if behavioral changes are observed.

RESULTS: Youth with PTSD exhibited a distinct gut microbiome profile and lower diversity compared to resilient individuals, and microbiome diversity mediated the continuity of posttraumatic symptomatology throughout development. Low microbiome diversity correlated with more posttraumatic symptoms in early childhood, more emotional and behavioral problems in adolescence, and poor maternal caregiving. Youth with PTSD demonstrated less mother-child microbial synchrony, suggesting that low microbial concordance between mother and child may indicate susceptibility to posttraumatic illness. Germ-free mice transplanted with microbiomes from individuals with PTSD displayed increased anxious behavior.

CONCLUSIONS: Our findings provide evidence that the trauma-associated microbiome profile is at least partially responsible for the anxiety component of the PTSD phenotype and highlight microbial underpinnings of resilience. Further, our results suggest that the microbiome may serve as additional biological memory of early life stress and underscore the potential for microbiome-related diagnosis and treatment following trauma. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

RevDate: 2024-07-19

Beyer BR, Sheppard C, Mullins J, et al (2024)

Campylobacter Infection Introduced Following Fecal Microbiota Transplantation.

Cureus, 16(6):e62541.

Fecal microbiota transplantation is an evidence-based therapeutic option for recurrent Clostridium difficile infection, involving the transfer of healthy donor fecal material to restore gut microbial balance. Despite meticulous donor screening, Campylobacter jejuni, a prevalent cause of bacterial gastroenteritis, is not routinely tested, potentially impacting fecal microbiota transplant safety. We present a case of a female with recurrent C. difficile infection treated with fecal microbiota transplantation, complicated by a subsequent C. jejuni infection. The emergence of Campylobacter post fecal microbiota transplantation underscores the importance of comprehensive donor screening protocols. Our case prompts a reevaluation of fecal microbiota transplantation safety measures and advocates for inclusive screening to enhance patient outcomes.

RevDate: 2024-07-19

Xu D, Ren L, Zhang W, et al (2024)

Therapeutic effects and mechanisms of fecal microbiota transplantation on EAE partly through HPA axis-mediated neuroendocrine regulation.

Heliyon, 10(12):e33214.

BACKGROUND: The pathogenesis of multiple sclerosis (MS) may be closely related to immune regulation and inflammatory cytokines induced by specific flora. Repairing the intestinal flora may alter the immune response in MS patients, thus opening up novel approaches for the treatment of MS.

OBJECTIVE: We aimed to test the therapeutic effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and the characteristics of intestinal microbiota composition changes, explore the potential mechanisms of FMT treatment.

METHODS: EAE animals were treated with FMT, with the therapeutic effects were evaluated by observing neurological scores and measuring serum levels of cortisol, IL-17, and TLR-2. Fecal microbiome 16S rRNA sequencing was used to profile changes in microbiota composition, and adrenalectomy pretreatment was used to test whether FMT effects were dependent on HPA axis function.

RESULTS: FMT improved neurological function and reduced serum IL-17 to levels that were close to the control group. FMT reestablished intestinal homeostasis by altering the structure of the intestinal flora, increasing the abundance of beneficial flora, and regulating intestinal metabolites. We found that the therapeutic effects of FMT depended partly on the efferent function of the HPA axis; surgical disruption of the HPA axis altered the abundance and diversity of the intestinal flora.

CONCLUSION: FMT showed a neuroprotective effect on EAE by increasing the abundance of the beneficial flora, rebuilding intestinal homeostasis, reducing IL-17 and cortisol serum levels, and promoting serum TLR-2; the therapeutic effect of FMT on EAE is partly dependent on the HPA axis.

RevDate: 2024-07-19

Xu J, Xu H, Yang F, et al (2024)

Different depths of food restriction and high-fat diet refeeding in mice impact host obesity and metabolic phenotypes with correlative changes in the gut microbiota.

MedComm, 5(8):e641.

Overweight and obesity affect almost 2 billion adults worldwide, and food restriction (FR) is commonly used to reduce body fat. Whether refeeding (Re) after FR at different ages and to different degrees leads to overweight and its possible mechanisms are uncertain. In this study, adult and young mice were both restricted to 15% and 40% of their casual food intake, and then were fed 60% high-fat chow (FR15%-Re, FR40%-Re), whereas the control groups(CON) consumed high-fat or normal food throughout, respectively. The results of the study suggest that mild FR-heavy feeding may lead to more significant abnormal fat accumulation, liver damage, and increased recruitment of intestinal inflammatory factors and immune cells in mice of different ages and involves multiple types of alterations in the gut microbiota. Further fecal transplantation experiments as well as serum and liver enzyme-linked immunosorbent assay experiments preliminarily suggest that the link between lipid metabolism and inflammatory responses and the gut microbiota may be related to the regulation of the gut and live by Lipopolysaccharides(LPS) and Peroxisome Proliferator-Activated Receptor-Alpha(PPAR-α). In addition, our study may also serve as a reference for studying obesity prevention and treatment programs at different ages.

RevDate: 2024-07-17

Rashidi A, Pidala J, Hamilton BK, et al (2024)

Oral and gut microbiome alterations in oral chronic graft-versus-host disease: results from Close Assessment and Testing for Chronic GVHD (CATCH study).

Clinical cancer research : an official journal of the American Association for Cancer Research pii:746452 [Epub ahead of print].

PURPOSE: Whether and how the oral microbiome and its changes in allogeneic hematopoietic cell transplantation (alloHCT) recipients may contribute to oral chronic graft-versus-host disease (cGVHD) pathogenesis is unknown. In addition, while the oral and colonic microbiota are distinct in healthy adults, whether oral microbes may ectopically colonize the gut in alloHCT patients is unknown.

EXPERIMENTAL DESIGN: To address these knowledge gaps, longitudinal oral and fecal samples were collected prospectively in the multicenter CATCH Study (Close Assessment and Testing for Chronic GVHD; NCT04188912). Through shotgun metagenomic sequencing of the samples collected at baseline, oral cGVHD onset, first post-cGVHD onset visit, and 1-year post-HCT timepoints in patients with oral cGVHD (cases; N = 29) or without any cGVHD (controls; N = 51), we examined whether (i) oral and/or gut microbiomes and their longitudinal trajectories differ between cases and controls, and (ii) oral and gut microbiomes overlap in alloHCT recipients, especially those developing cGVHD.

RESULTS: A total of 195 samples were analyzed. The onset of oral cGVHD was characterized by an expansion of Streptococcus salivarius and Veillonella parvula in the oral microbiome. High levels of oral/gut microbiota overlap were observed, particularly in patients with oral cGVHD, suggesting ectopic colonization of the gut by oral bacteria.

CONCLUSIONS: The unusual coalescence of two distant niches in these patients may have short- or long-term consequences for the host, a novel avenue for future research. In addition, this study suggests a contribution of the oral microbiome to oral cGVHD pathogenesis.

RevDate: 2024-07-20
CmpDate: 2024-07-20

Khalid A, Huang Z, Khan IM, et al (2024)

Improving broiler health through cecal microbiota transplantation: a comprehensive study on growth, immunity, and microbial diversity.

Journal of animal science, 102:.

Cecal microbiota has emerged as a prominent intervention target for improving the production and welfare of poultry. This is essential for the overall health and performance of broiler chickens. The current study focused on investigating the effect of cecal microbiota transplantation (CMT) from healthy donor chickens on the growth performance, immunity, and microbial composition of newly hatched chicks and evaluated the effect of sample storage on the microbial diversity of the cecal samples. A healthy "Wannan Yellow Chicken line" was selected as the donor, and 180 1-d-old chicks from the same line were used as recipients for a 60-d feed trial. The chicks were randomly allocated to three groups (60 birds per group) with three replicates in each group. The three treatment groups were CMT-0 (control, normal saline solution), CMT-I (1:12 cecal content, normal saline supplemented with 10% glycerol), and CMT-II (1:6 cecal content, normal saline supplemented with 10% glycerol). The results of weight gain and absolute organ weight showed significant improvements in the CMT-II group compared with the CMT-0 group. Serum IgG level was significantly improved (P < 0.05) in CMT-I compared with that in the CMT-0. However, IL-6 levels increased in CMT-I and then significantly decreased in CMT-II. The cecal microbial diversity of CMT treatment was compared between two groups, fresh samples (FS) and stored samples at-80 °C (SS). The results showed that beneficial taxa, such as Firmicutes and Verrucomicrobiota, were substantially more abundant in both CMT-I and CMT-II than in CMT-0 in both FS and SS. Microbial function analysis at levels 1, 2, and 3 showed improved metabolism, genetic information processing, cellular processes, environmental information processing, and organismal systems in CMT-I and CMT-II for both FS and SS groups. However, the SS group showed decreased microbial diversity and function. To conclude, cecal microbiota transplantation is a promising strategy for enhancing the productivity and health of broiler chickens.

RevDate: 2024-07-19
CmpDate: 2024-07-16

Zhao S, Zhang H, Zhu H, et al (2024)

Gut microbiota promotes macrophage M1 polarization in hepatic sinusoidal obstruction syndrome via regulating intestinal barrier function mediated by butyrate.

Gut microbes, 16(1):2377567.

BACKGROUND: The intestinal-liver axis is associated with various liver diseases. Here, we verified the role of the gut microbiota and macrophage activation in the progression of pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome (PA-HSOS), and explored the possible mechanisms and new treatment options.

METHODS: The HSOS murine model was induced by gavage of monocrotaline (MCT). An analysis of 16S ribosomal DNA (16S rDNA) of the feces was conducted to determine the composition of the fecal microbiota. Macrophage clearance, fecal microbiota transplantation (FMT), and butyrate supplementation experiments were used to assess the role of intestinal flora, gut barrier, and macrophage activation and to explore the relationships among these three variables.

RESULTS: Activated macrophages and low microflora diversity were observed in HSOS patients and murine models. Depletion of macrophages attenuated inflammatory reactions and apoptosis in the mouse liver. Moreover, compared with control-FMT mice, the exacerbation of severe liver injury was detected in HSOS-FMT mice. Specifically, butyrate fecal concentrations were significantly reduced in HSOS mice, and administration of butyrate could partially alleviated liver damage and improved the intestinal barrier in vitro and in vivo. Furthermore, elevated lipopolysaccharides in the portal vein and high proportions of M1 macrophages in the liver were also detected in HSOS-FMT mice and mice without butyrate treatment, which resulted in severe inflammatory responses and further accelerated HSOS progression.

CONCLUSIONS: These results suggested that the gut microbiota exacerbated HSOS progression by regulating macrophage M1 polarization via altered intestinal barrier function mediated by butyrate. Our study has identified new strategies for the clinical treatment of HSOS.

RevDate: 2024-07-16

Cheng CK, Gao J, Kang L, et al (2024)

Fecal Microbiota Transfer from Young Mice Reverts Vascular Aging Hallmarks and Metabolic Impairments in Aged Mice.

Aging and disease pii:AD.2024.0384 [Epub ahead of print].

As a major risk factor for cardiometabolic diseases, aging refers to a gradual decline in physiological function, characterized with 12 conspicuous hallmarks, like telomere attrition, chronic inflammation, and dysbiosis. Common vascular aging hallmarks include endothelial dysfunction, telomere dysfunction, and vascular inflammation. In this study, we sought to test the hypothesis that young-derived gut microbiota retards vascular aging hallmarks and metabolic impairments in aged hosts. We also aimed to study the therapeutic efficacy of young microbiota in hosts of different ages. Fecal microbiota transplantation (FMT) from young to aged or middle-aged C57BL/6 mice was conducted for 6 consecutive weeks after antibiotic pretreatment. Endothelium-dependent relaxations (EDRs) in mouse arteries were determined by wire myography. Inflammation and AMPK/SIRT1 signaling in mouse aortas and intestines were studied by biochemical assays. The telomere function of aortas and intestines, in terms of telomerase reverse transcriptase expression, telomerase activity, and relative telomere length, were also studied. FMT significantly reverted vascular dysfunction and metabolic impairments in middle-aged mice than in aged mice. Besides, FMT significantly reverted inflammation and telomere dysfunction in aortas and intestines of middle-aged mice. Improved intestinal barrier function and activated AMPK/SIRT1 signaling potentially underlie benefits of FMT. The findings imply gut-vascular connection as potential target against age-associated cardiometabolic disorders, highlight crosstalk among aging hallmarks, and suggest a critical timepoint for efficacy of anti-aging interventions.

RevDate: 2024-07-16

Tian YQ, Ren X, Wang J, et al (2024)

Berberine hydrochloride alleviates chronic prostatitis/chronic pelvic pain syndrome by modifying gut microbiome signaling.

Asian journal of andrology pii:00129336-990000000-00205 [Epub ahead of print].

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is highly prevalent worldwide and poses a significant threat to men's health, particularly affecting young men. However, the exact causes and mechanisms behind CP/CPPS remain unclear, leading to challenges in its treatment. In this research, a CP/CPPS rat model was established with complete Freund's adjuvant (CFA), and berberine hydrochloride was administered through daily gavage to assess its therapeutic effects. The alterations in the gut microbiome induced by CP/CPPS and berberine hydrochloride were investigated through 16S ribosomal RNA sequencing of cecum content and colonic epithelial cells. To investigate the impact of the gut microbiome on CP/CPPS, a pseudo germ-free rat model was established, and fecal microbiome transplantation (FMT) was performed on these rats. In all, berberine hydrochloride demonstrated effective reduction of inflammation and oxidative stress in the prostate, offering significant therapeutic advantages for CP/CPPS. Through analysis of the gut microbiome using 16S ribosome RNA sequencing, distinct differences were observed between CP/CPPS rats and control rats, and Clostridium butyricum was identified as a key bacteria. Pseudo germ-free rats that underwent FMT from CP/CPPS rats or rats treated with berberine hydrochloride displayed varying levels of inflammatory cytokine production, oxidative stress, and activity of associated signaling pathways. In conclusion, the therapeutic potential of berberine hydrochloride in addressing CP/CPPS is highly significant. The gut microbiome has emerged as a critical factor in the development of CP/CPPS and plays a pivotal role in mediating the therapeutic effects of berberine hydrochloride.

RevDate: 2024-07-17
CmpDate: 2024-07-15

Shoji F (2024)

[The Role of Gut Microbiota in Lung Carcinogenesis and Cancer Immunotherapy].

Gan to kagaku ryoho. Cancer & chemotherapy, 51(6):597-602.

In recent years, the human microbiota, especially the gut microbiota, has been attracting attention in various fields, and it is one of the topics in the field of oncology. The human microbiota is known to act directly or indirectly on host immunity, and the gut and lung microbiota influence each other through the"gut-lung axis". It has been suggested that dysbiosis, a condition in which the symbiosis of the human microbiota is disrupted, induces lung inflammation and various respiratory diseases, and is also implicated in the immune microenvironment of lung cancer. It is also widely known that the gut microbiota modulates the efficacy of cancer immunotherapy, a major pillar of lung cancer treatment, and many clinical trials targeting the gut microbiota, such as fecal microbiome transplantation and biotics intervention, are currently being conducted. In the future, research on lung carcinogenesis mechanisms and lung cancer treatment focusing on the human microbiota will become increasingly active.

RevDate: 2024-07-15

Réthi-Nagy Z, S Juhász (2024)

Microbiome's Universe: Impact on health, disease and cancer treatment.

Journal of biotechnology pii:S0168-1656(24)00189-5 [Epub ahead of print].

The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.

RevDate: 2024-07-16
CmpDate: 2024-07-15

Luo C, Li S, T Chen (2024)

Editorial: The role of probiotics, postbiotics, and microbial metabolites in preventing and treating chronic diseases, volume II.

Frontiers in cellular and infection microbiology, 14:1442855.

RevDate: 2024-07-16

Sanzone J, Life M, Reiss D, et al (2024)

Uses of Fecal Microbiota Transplantation in Neurodegenerative Disease: A Scoping Review.

Cureus, 16(6):e62265.

Fecal microbiota transplantation (FMT) is the administration of fecal bacteria from a healthy donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition and confer a health benefit. The relationship between the gut microbiome and the central nervous system, termed the gut-brain axis, has been a frequent topic of gut microbiome studies. Commensal gut bacteria communicate with the central nervous system through various hormones, cytokines, and neural pathways. Therefore, influencing the gut microbiome via FMT may have the potential in treating symptoms of neurodegenerative conditions. This study aims to identify current uses of FMT in treating neurodegenerative diseases and highlight areas of future investigation. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, a literature search was conducted of peer-reviewed sources on September 27, 2022, from Embase, MEDLINE, Web of Science, and Cochrane Central. Search terms were utilized that were related to the application of FMT and neurodegenerative disorders and limited those human studies, those that were published in English, and those that were published between 2017 and 2022. The initial search yielded 450 unique articles, and after the assessment of the title and abstract for inclusion and exclusion criteria, six articles were identified for full-text review. Studies that focused on either Parkinson's disease (PD) or multiple sclerosis (MS) demonstrated improvements in both motor symptoms and non-motor symptoms. FMT was also shown to provide significant relief of constipation and general gastrointestinal (GI) symptoms in all conditions studied. The studies related to MS showed the most mixed results with regard to symptomatic improvement. The data on the use of FMT as a treatment for neurodegenerative disorders is limited; however, studies have shown not only improvement in GI symptoms but also improvement in the cognitive symptoms of PD and dementia. The data on FMT as a treatment to improve the motor symptoms of PD is both more complete and more compelling than the data on the motor symptoms of MS. The studies that were reviewed showed no major adverse effects of FMT and generally promising results. There is a strong case to be made for larger, more well-controlled studies to be done on FMT and its potential use as a treatment not only for GI symptoms but for the motor and cognitive symptoms of neurodegenerative diseases.

RevDate: 2024-07-16

Lee CS, Lin CR, Chua HH, et al (2024)

Gut Bifidobacterium longum is associated with better native liver survival in patients with biliary atresia.

JHEP reports : innovation in hepatology, 6(7):101090.

BACKGROUND & AIMS: The gut microbiome plays an important role in liver diseases, but its specific impact on biliary atresia (BA) remains to be explored. We aimed to investigate the microbial signature in the early life of patients with BA and to analyze its influence on long-term outcomes.

METHODS: Fecal samples (n = 42) were collected from infants with BA before and after Kasai portoenterostomy (KPE). The stool microbiota was analyzed using 16S rRNA next-generation sequencing and compared with that of age-matched healthy controls (HCs). Shotgun metagenomic sequencing analysis was employed to confirm the bacterial composition in 10 fecal samples before KPE. The correlation of the microbiome signature with liver function and long-term outcomes was assessed.

RESULTS: In the 16S rRNA next-generation sequencing analysis of fecal microbiota, the alpha and beta diversity analyses revealed significant differences between HCs and patients with BA before and after KPE. The difference in microbial composition analyzed by linear discriminant analysis and random forest classification revealed that the abundance of Bifidobacterium longum (B. longum) was significantly lower in patients before and after KPE than in HCs. The abundance of B. longum was negatively correlated with the gamma-glutamyltransferase level after KPE (p <0.05). Patients with early detectable B. longum had significantly lower total and direct bilirubin 3 months after KPE (p <0.005) and had a significantly lower liver transplantation rate (hazard ratio: 0.16, 95% CI 0.03-0.83, p = 0.029). Shotgun metagenomic sequencing also revealed that patients with BA and detectable B. longum had reduced total and direct bilirubin after KPE.

CONCLUSION: The gut microbiome of patients with BA differed from that of HCs, with a notable abundance of B. longum in early infancy correlating with better long-term outcomes.

IMPACT AND IMPLICATIONS: Bifidobacterium longum (B. longum) is a beneficial bacterium commonly found in the human gut. It has been studied for its potential impacts on various health conditions. In patients with biliary atresia, we found that a greater abundance of B. longum in the fecal microbiome is associated with improved clinical outcomes. This suggests that early colonization and increasing B. longum levels in the gut could be a therapeutic strategy to improve the prognosis of patients with biliary atresia.

RevDate: 2024-07-16

Mao Q, Wang X, Cai H, et al (2024)

Research Progress on the Correlation of Atopic Dermatitis with Gut Microbiota.

Clinical, cosmetic and investigational dermatology, 17:1613-1619.

Atopic dermatitis (AD) is a common skin disease, the pathogenesis of which has not been fully elucidated. The gut microbiota is the largest micro-ecosystem in the human body that affects the immune system and skin barrier function. Recent studies have shown that in addition to the environmental factors, skin barrier, genetic factors and immune response, gut microbiota disturbance may also cause AD. This review described the correlation of AD with gut microbiota and existing research status of AD treatment via targeting gut microbiota.

RevDate: 2024-07-17
CmpDate: 2024-07-14

Schrock J, Yan M, Dolatyabi S, et al (2024)

Human Infant Fecal Microbiota Differentially Influences the Mucosal Immune Pathways Upon Influenza Infection in a Humanized Gnotobiotic Pig Model.

Current microbiology, 81(9):267.

In this study, we evaluated the impact of human gut microbiota on the immune pathways in the respiratory tract using a gnotobiotic (Gn) piglet model. We humanized piglets with rural and urban infant fecal microbiota (RIFM and UIFM, respectively) and then infected them with a H1N1 swine influenza virus. We analyzed the microbial diversity and structure of the intestinal and respiratory tracts of the piglets before and after the influenza virus infection and measured the viral load and immune responses. We found that the viral load in the upper respiratory tract of UIFM transplanted piglets was higher than their rural cohorts (RIFM), while virus-specific antibody responses were comparable. The relative cytokine gene expression in the tracheobronchial (respiratory tract) and mesenteric (gastrointestinal) lymph nodes, lungs, blood, and spleen of RIFM and UIFM piglets revealed a trend in reciprocal regulation of proinflammatory, innate, and adaptive immune-associated cytokines as well as the frequency of T-helper/memory cells, cytotoxic T cells, and myeloid immune cell subsets. We also observed different phylum-level shifts of the fecal microbiota in response to influenza virus infection between the two piglet groups, suggesting the potential impact of the gut microbiota on the immune responses to influenza virus infection and lung microbiota. In conclusion, Gn piglets humanized with diverse infant fecal microbiota had differential immune regulation, with UIFM favoring the activation of proinflammatory immune mediators following an influenza virus infection compared to their rural RIFM cohorts. Furthermore, Gn piglets can be a useful model in investigating the impact of diverse human microbiota of the gastrointestinal tract, probably also the respiratory tract, on respiratory health and testing specific probiotic- or prebiotic-based therapeutics.

RevDate: 2024-07-16

Liao L, Zhang L, Yang C, et al (2024)

Sotagliflozin attenuates cardiac dysfunction and depression-like behaviors in mice with myocardial infarction through the gut-heart-brain axis.

Neurobiology of disease, 199:106598 pii:S0969-9961(24)00198-0 [Epub ahead of print].

Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.

RevDate: 2024-07-15
CmpDate: 2024-07-13

Lin X, Han H, Wang N, et al (2024)

The Gut Microbial Regulation of Epigenetic Modification from a Metabolic Perspective.

International journal of molecular sciences, 25(13):.

Obesity is a global health challenge that has received increasing attention in contemporary research. The gut microbiota has been implicated in the development of obesity, primarily through its involvement in regulating various host metabolic processes. Recent research suggests that epigenetic modifications may serve as crucial pathways through which the gut microbiota and its metabolites contribute to the pathogenesis of obesity and other metabolic disorders. Hence, understanding the interplay between gut microbiota and epigenetic mechanisms is crucial for elucidating the impact of obesity on the host. This review primarily focuses on the understanding of the relationship between the gut microbiota and its metabolites with epigenetic mechanisms in several obesity-related pathogenic mechanisms, including energy dysregulation, metabolic inflammation, and maternal inheritance. These findings could serve as novel therapeutic targets for probiotics, prebiotics, and fecal microbiota transplantation tools in treating metabolic disruptions. It may also aid in developing therapeutic strategies that modulate the gut microbiota, thereby regulating the metabolic characteristics of obesity.

RevDate: 2024-07-16
CmpDate: 2024-07-13

Wu Y, Li Y, Zheng Q, et al (2024)

The Efficacy of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.

Nutrients, 16(13):.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with gut microbiota imbalance playing a significant role. There are increasing numbers of research studies exploring treatment options involving probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), but it is still uncertain which treatment option is superior. The research was conducted on various databases and unpublished trial data (up to February 2023). Randomized controlled trials (RCTs) were screened for adult patients with IBS comparing interventions with placebo. Probiotics, prebiotics, synbiotics, and FMT were assessed for their impact using mean difference and Bayesian network meta-analysis. Out of 6528 articles, 54 were included for probiotics, 7 for prebiotics/synbiotics, and 6 for FMT. Probiotics showed improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains. Prebiotics and synbiotics did not show significant improvement. Network meta-analysis indicated the favorable effects of probiotics (OR = 0.53, 95% CI, 0.48 to 0.59) and FMT (OR = 0.46, 95% CI, 0.33 to 0.64) on IBS, with no serious adverse events reported. In short, probiotics and FMT are effective for managing IBS, with Bifidobacterium and Lactobacillus being dominant strains. However, the most effective probiotic combination or strain remains unclear, while prebiotics and synbiotics did not show significant improvement.

RevDate: 2024-07-13

Gefen R, Strassmann V, Stefano Hernandez F, et al (2024)

Risk factors for complications following sacral neuromodulation for faecal incontinence: Long-term follow-up.

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland [Epub ahead of print].

AIM: Sacral neuromodulation (SNM) has become a standard surgical treatment for faecal incontinence (FI). Prior studies have reported various adverse events of SNM, including suboptimal therapeutic response, infection, pain, haematoma, and potential need for redo SNM. The aim of this study was to identify the risk factors associated with long-term complications of SNM.

METHOD: This retrospective cohort reviewed patients who underwent two-stage SNM for FI at our institution between 2011-2021. Preoperative baseline characteristics and follow-up were obtained from the medical record and/or by telephone interview. Management and outcome of each postoperative event were evaluated by univariate and multivariate regression analyses.

RESULTS: A total of 291 patients (85.2% female) were included in this study. Postoperative complications were recorded in 219 (75.2%) patients and 154 (52.9%) patients required surgical intervention to treat complications. The most common postoperative event was loss of efficacy (46.4%). Other common adverse events were problems at the implant site (pain, infection, etc.) in 16.5% and pain during stimulation in 11.7%. Previous vaginal delivery (OR 2.74, p = 0.003) and anal surgery (OR = 2.46, p = 0.039) were independent predictors for complications. Previous colorectal (OR = 2.04, p = 0.026) and anal (OR = 1.98, p = 0.022) surgery and history of irritable bowel syndrome (IBS) (OR = 3.49, p = 0.003) were independent predictors for loss of efficacy.

CONCLUSION: Postoperative adverse events are frequently recorded after SNM. Loss of efficacy is the most common. Previous colorectal or anal surgery, vaginal delivery, and IBS are independent risk factors for complications.

RevDate: 2024-07-12

Shao W, Pan B, Li Z, et al (2024)

Gut microbiota mediates ambient PM2.5 exposure-induced abnormal glucose metabolism via short-chain fatty acids.

Journal of hazardous materials, 476:135096 pii:S0304-3894(24)01675-3 [Epub ahead of print].

PM2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM2.5-induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM2.5-induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3β in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM2.5-exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM2.5-exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM2.5.

RevDate: 2024-07-12

Jiang ZM, Wang FF, Zhao YY, et al (2024)

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1β pathway.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 132:155847 pii:S0944-7113(24)00505-1 [Epub ahead of print].

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored.

PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL.

METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments.

RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1β pathway and increased proinflammatory IL1β in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1β pathway.

CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1β pathway, specifically by targeting AKK and tryptophan metabolites.

RevDate: 2024-07-14

Dela Cruz M, Lin H, Han J, et al (2023)

Reduced immunomodulatory metabolite concentrations in peri-transplant fecal samples from heart allograft recipients.

Frontiers in transplantation, 2:1182534.

BACKGROUND: Emerging evidence is revealing the impact of the gut microbiome on hematopoietic and solid organ transplantation. Prior studies postulate that this influence is mediated by bioactive metabolites produced by gut-dwelling commensal bacteria. However, gut microbial metabolite production has not previously been measured among heart transplant (HT) recipients.

METHODS: In order to investigate the potential influence of the gut microbiome and its metabolites on HT, we analyzed the composition and metabolite production of the fecal microbiome among 48 HT recipients at the time of HT.

RESULTS: Compared to 20 healthy donors, HT recipients have significantly reduced alpha, i.e. within-sample, microbiota diversity, with significantly lower abundances of key anaerobic commensal bacteria and higher abundances of potentially pathogenic taxa that have been correlated with adverse outcomes in other forms of transplantation. HT recipients have a wide range of microbiota-derived fecal metabolite concentrations, with significantly reduced levels of immune modulatory metabolites such as short chain fatty acids and secondary bile acids compared to healthy donors. These differences were likely due to disease severity and prior antibiotic exposures but were not explained by other demographic or clinical factors.

CONCLUSIONS: Key potentially immune modulatory gut microbial metabolites are quantifiable and significantly reduced among HT recipients compared to healthy donors. Further study is needed to understand whether this wide range of gut microbial dysbiosis and metabolite alterations impact clinical outcomes and if they can be used as predictive biomarkers or manipulated to improve transplant outcomes.

RevDate: 2024-07-14

Ge Y, Wang J, Wu L, et al (2024)

Gut microbiota: a potential new regulator of hypertension.

Frontiers in cardiovascular medicine, 11:1333005.

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases and has become a global public health concern. Although hypertension results from a combination of factors, the specific mechanism is still unclear. However, increasing evidence suggests that gut microbiota is closely associated with the development of hypertension. We provide a summary of the composition and physiological role of gut microbiota. We then delve into the mechanism of gut microbiota and its metabolites involved in the occurrence and development of hypertension. Finally, we review various regimens for better-controlling hypertension from the diet, exercise, drugs, antibiotics, probiotics, and fecal transplantation perspectives.

RevDate: 2024-07-11

Ananthakrishnan AN, Whelan K, Allegretti JR, et al (2024)

Diet and Microbiome-directed therapy 2.0 for IBD.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(24)00599-8 [Epub ahead of print].

Inflammatory bowel disease (IBD) are chronic and relapsing disorders of the gastrointestinal tract, characterized by dysregulated immune responses to the gut microbiome. The gut microbiome and diet are key environmental factors that influence the onset and progression of IBD and can be leveraged for treatment. In this review, we summarize the current evidence on the role of the gut microbiome and diet in IBD pathogenesis, and the potential of microbiome-directed therapies and dietary interventions and improve IBD outcomes. We discuss available data, the advantages and drawbacks of the different approaches to manipulate the gut microbiome, such as fecal microbiota transplantation, next-generation and conventional probiotics, and postbiotics. We also review the use of diet as a therapeutic tool in IBD, including the effects in induction and maintenance, special diets, and exclusive enteral nutrition. Finally, we highlight the challenges and opportunities for the translation of diet and microbiome interventions into clinical practice, such as the need for personalization, manufacturing and regulatory hurdles, and the specificity to take into account for clinical trial design.

RevDate: 2024-07-11

Ye XX, Jiang QY, Wu MJ, et al (2024)

Transplant of fecal microbiota from healthy young mice relieves cognitive defects in late-stage diabetic mice by reducing metabolic disorders and neuroinflammation.

Acta pharmacologica Sinica [Epub ahead of print].

Fecal microbiota transplant (FMT) is becoming as a promising area of interest for treating refractory diseases. In this study, we investigated the effects of FMT on diabetes-associated cognitive defects in mice as well as the underlying mechanisms. Fecal microbiota was prepared from 8-week-aged healthy mice. Late-stage type 1 diabetics (T1D) mice with a 30-week history of streptozotocin-induced diabetics were treated with antibiotics for 7 days, and then were transplanted with bacterial suspension (100 μL, i.g.) once a day for 14 days. We found that FMT from healthy young mice significantly alleviated cognitive defects of late-stage T1D mice assessed in Morris water maze test. We revealed that FMT significantly reduced the relative abundance of Gram-negative bacteria in the gut microbiota and enhanced intestinal barrier integrity, mitigating LPS translocation into the bloodstream and NLRP3 inflammasome activation in the hippocampus, thereby reducing T1D-induced neuronal loss and astrocytic proliferation. FMT also reshaped the metabolic phenotypes in the hippocampus of T1D mice especially for alanine, aspartate and glutamate metabolism. Moreover, we showed that application of aspartate (0.1 mM) significantly inhibited NLRP3 inflammasome activation and IL-1β production in BV2 cells under a HG/LPS condition. We conclude that FMT can effectively relieve T1D-associated cognitive decline via reducing the gut-brain metabolic disorders and neuroinflammation, providing a potential therapeutic approach for diabetes-related brain disorders in clinic.

RevDate: 2024-07-11

Wang Z, Li L, Li W, et al (2024)

Salidroside Alleviates Furan-Induced Impaired Gut Barrier and Inflammation via Gut Microbiota-SCFA-TLR4 Signaling.

Journal of agricultural and food chemistry [Epub ahead of print].

As a food contaminant that can be quickly absorbed through the gastrointestinal system, furan has been shown to disrupt the intestinal flora and barrier. Investigation of the intestinal toxicity mechanism of furan is of great significance to health. We previously identified the regulatory impact of salidroside (SAL) against furan-provoked intestinal damage, and the present work further explored whether the alleviating effect of SAL against furan-caused intestinal injury was based on the intestinal flora; three models, normal, pseudo-germ-free, and fecal microbiota transplantation (FMT), were established, and the changes in intestinal morphology, barrier, and inflammation were observed. Moreover, 16S rDNA sequencing observed the variation of the fecal flora associated with inflammation and short-chain fatty acids (SCFAs). Results obtained from the LC-MS/MS suggested that SAL increased furan-inhibited SCFA levels, activated the mRNA expressions of SCFA receptors (GPR41, GPR43, and GPR109A), and inhibited the furan-activated TLR4/MyD88/NF-κB signaling. Analysis of protein-protein interaction further confirmed the aforementioned effects of SAL, which inhibited furan-induced barrier damage and intestinal inflammation.

RevDate: 2024-07-11

Yang Y, Zhang Z, Wang Y, et al (2024)

Colonization of microbiota derived from Macaca fascicularis, Bama miniature pigs, beagle dogs, and C57BL/6J mice alleviates DSS-induced colitis in germ-free mice.

Microbiology spectrum [Epub ahead of print].

Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1β, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1β was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.

RevDate: 2024-07-11

Gu X, Yang Z, Kou Y, et al (2024)

Effects of Retrograde Colonic Enema Based Fecal Microbiota Transplantation in the Treatment of Childhood Constipation: A Randomized, Double-blind Controlled Trial.

The American journal of gastroenterology pii:00000434-990000000-01237 [Epub ahead of print].

OBJECTIVE: Management of intractable childhood constipation is still challenging. The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) in intractable childhood constipation has not been established although both have demonstrated potential in gastrointestinal diseases. The aim of the current study was to determine the safety and efficacy of RCE-based FMT in the treatment of intractable constipation in children.

METHODS: A randomized, double-blind, controlled trial with 110 children was conducted. The subjects were randomly assigned to the FMT with RCE group or the placebo with RCE group. All participants received a daily RCE followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. Spontaneous bowel movements (SBMs) ≥ 3 per week were the main outcomes and the risk ratio (RR) with 95% CI was calculated. Changes in the intestinal bacterial profile were analyzed by BOX-PCR-based DNA fingerprinting and sequencing. The adverse effects were assessed based on symptoms.

RESULTS: At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 SBMs per week (net difference = 21.8%, 95% CI: 13.2%-30.4%; RR: 1.364, 95% CI: 1.063-1.749; P<0.05). Both RCE and FMT enriched the intestinal bacterial diversity of patients with constipation. The adverse events were all mild self-limiting gastrointestinal symptoms.

CONCLUSIONS: FMT enhances the efficacy of RCE and the use of RCE-based FMT is a safe and effective method in the treatment of intractable constipation in children.

RevDate: 2024-07-11

Boyle BL, S Khanna (2024)

Fecal microbiota live - jslm (Rebyota™/RBL) for management of recurrent Clostridioides difficile infection.

Future microbiology [Epub ahead of print].

There is an unmet need for effective treatments of Clostridioides difficile infection, an emerging health crisis in the United States. The management of C. difficile infection should include treatment of active infection and a strategy to prevent recurrence. Current gold standard therapy includes oral antibiotics which predispose patients to gut dysbiosis and increase the risk of recurrent infection. Addressing dysbiosis via fecal microbiota transplantation is an active and promising area of research, but studies have lacked standardization which makes outcome and safety data difficult to interpret. Rebyota™, formerly known as RBX2660, is a live biotherapeutic product designed using a standardized protocol and manufacturing process that has been shown to be effective for preventing recurrent C. difficile infection.

RevDate: 2024-07-12

Peng Y, Huang Y, Li H, et al (2024)

Huangqin Qingre Chubi Capsule inhibits rheumatoid arthritis by regulating intestinal flora and improving intestinal barrier.

Frontiers in pharmacology, 15:1422245.

BACKGROUND: Changes in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified.

MATERIALS AND METHODS: In this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA.

RESULTS: Based on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-α, IL-1β and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology.

CONCLUSION: The dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA's new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.

RevDate: 2024-07-12
CmpDate: 2024-07-11

Sipos D, Varga A, Kappéter Á, et al (2024)

Encapsulation protocol for fecal microbiota transplantation.

Frontiers in cellular and infection microbiology, 14:1424376.

INTRODUCTION: Clostridioides difficile infections (CDI) continue to pose a challenge for clinicians. Fecal microbiota transplantation (FMT) is an effective treatment option in CDI. Furthermore, recent and ongoing studies suggest potential benefits of FMT in other diseases as well.

METHODS: We would like to present a novel protocol for encapsulation of lyophilized fecal material. Our method provides with better compliance as well as improved flexibility, storage and safety.

RESULTS: FMT was conducted in 28 patients with an overall success rate of 82,14% using apsules containing lyophilized stool. 16 of patients were given capsules with lessened bacteria counts. The success rate in this group was 93,75%.

DISCUSSION: The results highlight the still unanswered questions about the mechanism of action and contribute to a wider use of FMT in the clinical praxis and in research.

RevDate: 2024-07-10
CmpDate: 2024-07-11

Long AE, Pitta D, Hennessy M, et al (2024)

Assessment of fecal bacterial viability and diversity in fresh and frozen fecal microbiota transplant (FMT) product in horses.

BMC veterinary research, 20(1):306.

BACKGROUND: Currently, lack of standardization for fecal microbiota transplantation (FMT) in equine practice has resulted in highly variable techniques, and there is no data on the bacterial metabolic activity or viability of the administered product. The objectives of this study were to compare the total and potentially metabolically active bacterial populations in equine FMT, and assess the effect of different frozen storage times, buffers, and temperatures on an equine FMT product. Fresh feces collected from three healthy adult horses was subjected to different storage methods. This included different preservation solutions (saline plus glycerol or saline only), temperature (-20 °C or -80 °C), and time (fresh, 30, 60, or 90 days). Samples underwent DNA extraction to assess total bacterial populations (both live and dead combined) and RNA extraction followed by reverse transcription to cDNA as a proxy to assess viable bacteria, then 16s rRNA gene amplicon sequencing using the V1-V2 region.

RESULTS: The largest difference in population indices and taxonomic composition at the genus level was seen when evaluating the results of DNA-based (total) and cDNA-based (potentially metabolically active) extraction method. At the community level, alpha diversity (observed species, Shannon diversity) was significantly decreased in frozen samples for DNA-based analysis (P < 0.05), with less difference seen for cDNA-based sequencing. Using DNA-based analysis, length of storage had a significant impact (P < 0.05) on the bacterial community profiles. For potentially metabolically active populations, storage overall had less of an effect on the bacterial community composition, with a significant effect of buffer (P < 0.05). Individual horse had the most significant effect within both DNA and cDNA bacterial communities.

CONCLUSIONS: Frozen storage of equine FMT material can preserve potentially metabolically active bacteria of the equine fecal microbiome, with saline plus glycerol preservation more effective than saline alone. Larger studies are needed to determine if these findings apply to other individual horses. The ability to freeze FMT material for use in equine patients could allow for easier clinical use of fecal transplant in horses with disturbances in their intestinal microbiome.

RevDate: 2024-07-12
CmpDate: 2024-07-11

van Rossen TM, van Beurden YH, Bogaards JA, et al (2024)

Fecal microbiota composition is a better predictor of recurrent Clostridioides difficile infection than clinical factors in a prospective, multicentre cohort study.

BMC infectious diseases, 24(1):687.

INTRODUCTION: Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea. Fidaxomicin and fecal microbiota transplantation (FMT) are effective, but expensive therapies to treat recurrent CDI (reCDI). Our objective was to develop a prediction model for reCDI based on the gut microbiota composition and clinical characteristics, to identify patients who could benefit from early treatment with fidaxomicin or FMT.

METHODS: Multicentre, prospective, observational study in adult patients diagnosed with a primary episode of CDI. Fecal samples and clinical data were collected prior to, and after 5 days of CDI treatment. Follow-up duration was 8 weeks. Microbiota composition was analysed by IS-pro, a bacterial profiling technique based on phylum- and species-specific differences in the 16-23 S interspace regions of ribosomal DNA. Bayesian additive regression trees (BART) and adaptive group-regularized logistic ridge regression (AGRR) were used to construct prediction models for reCDI.

RESULTS: 209 patients were included, of which 25% developed reCDI. Variables related to microbiota composition provided better prediction of reCDI and were preferentially selected over clinical factors in joint prediction models. Bacteroidetes abundance and diversity after start of CDI treatment, and the increase in Proteobacteria diversity relative to baseline, were the most robust predictors of reCDI. The sensitivity and specificity of a BART model including these factors were 95% and 78%, but these dropped to 67% and 62% in out-of-sample prediction.

CONCLUSION: Early microbiota response to CDI treatment is a better predictor of reCDI than clinical prognostic factors, but not yet sufficient enough to predict reCDI in daily practice.

RevDate: 2024-07-10

Fujimoto K, Hayashi T, Yamamoto M, et al (2024)

An enterococcal phage-derived enzyme suppresses graft-versus-host disease.

Nature [Epub ahead of print].

Changes in the gut microbiome have pivotal roles in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogenic haematopoietic cell transplantation (allo-HCT)[1-6]. However, effective methods for safely resolving gut dysbiosis have not yet been established. An expansion of the pathogen Enterococcus faecalis in the intestine, associated with dysbiosis, has been shown to be a risk factor for aGVHD[7-10]. Here we analyse the intestinal microbiome of patients with allo-HCT, and find that E. faecalis escapes elimination and proliferates in the intestine by forming biofilms, rather than by acquiring drug-resistance genes. We isolated cytolysin-positive highly pathogenic E. faecalis from faecal samples and identified an anti-E. faecalis enzyme derived from E. faecalis-specific bacteriophages by analysing bacterial whole-genome sequencing data. The antibacterial enzyme had lytic activity against the biofilm of E. faecalis in vitro and in vivo. Furthermore, in aGVHD-induced gnotobiotic mice that were colonized with E. faecalis or with patient faecal samples characterized by the domination of Enterococcus, levels of intestinal cytolysin-positive E. faecalis were decreased and survival was significantly increased in the group that was treated with the E. faecalis-specific enzyme, compared with controls. Thus, administration of a phage-derived antibacterial enzyme that is specific to biofilm-forming pathogenic E. faecalis-which is difficult to eliminate with existing antibiotics-might provide an approach to protect against aGVHD.

RevDate: 2024-07-10
CmpDate: 2024-07-10

Liow YJ, Kamimura I, Umezaki M, et al (2024)

Dietary fiber induces a fat preference associated with the gut microbiota.

PloS one, 19(7):e0305849.

Eating behavior is essential to human health. However, whether future eating behavior is subjected to the conditioning of preceding dietary composition is unknown. This study aimed to investigate the effect of dietary fiber consumption on subsequent nutrient-specific food preferences between palatable high-fat and high-sugar diets and explore its correlation with the gut microbiota. C57BL/6NJcl male mice were subjected to a 2-week dietary intervention and fed either a control (n = 6) or inulin (n = 6) diet. Afterward, all mice were subjected to a 3-day eating behavioral test to self-select from the simultaneously presented high-fat and high-sugar diets. The test diet feed intakes were recorded, and the mice's fecal samples were analyzed to evaluate the gut microbiota composition. The inulin-conditioned mice exhibited a preference for the high-fat diet over the high-sugar diet, associated with distinct gut microbiota composition profiles between the inulin-conditioned and control mice. The gut microbiota Oscillospiraceae sp., Bacteroides acidifaciens, and Clostridiales sp. positively correlated with a preference for fat. Further studies with fecal microbiota transplantation and eating behavior-related neurotransmitter analyses are warranted to establish the causal role of gut microbiota on host food preferences. Food preferences induced by dietary intervention are a novel observation, and the gut microbiome may be associated with this preference.

RevDate: 2024-07-10
CmpDate: 2024-07-10

Guzzardi MA, La Rosa F, Faita F, et al (2024)

The transfer of gut microbiota/metabolites from children to mice affects cardiometabolic development and induces sex-dimorphism in recipients.

Vascular pharmacology, 155:107325.

RevDate: 2024-07-10
CmpDate: 2024-07-10

Zhao JT, Zhang Y, Wang XW, et al (2024)

Long-term effects of fecal microbiota transplantation on gut microbiota after Helicobacter pylori eradication with bismuth quadruple therapy: A randomized controlled trial.

Helicobacter, 29(4):e13079.

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known.

MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment.

RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group.

CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.

RevDate: 2024-07-11
CmpDate: 2024-07-10

Ma BT, Sang LX, B Chang (2024)

Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.

World journal of gastroenterology, 30(24):3123-3125.

Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

RevDate: 2024-07-11
CmpDate: 2024-07-10

Zhang Q, Bi Y, Zhang B, et al (2024)

Current landscape of fecal microbiota transplantation in treating depression.

Frontiers in immunology, 15:1416961.

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.

RevDate: 2024-07-11

Azuma T, Sato Y, Chiba H, et al (2024)

Appendiceal goblet cell adenocarcinoma newly classified by WHO 5th edition: a case report (a secondary publication).

Surgical case reports, 10(1):168.

BACKGROUND: Appendiceal goblet cell adenocarcinoma (AGCA) is a newly proposed cancer type in the 5th edition of the WHO Classification of Tumours in 2019. We experienced this rare form of appendiceal primary neoplasm.

CASE PRESENTATION: An 85-year-old male presented a positive fecal occult blood test. A series of imagings revealed a type 1 tumor, located on the appendiceal orifice. The subsequent biopsy made the diagnosis of signet-ring cell carcinoma. Consequently, he underwent the laparoscopic-assisted ileocecal resection. Initially, the tumor was suspected to be a Goblet cell carcinoid (GCC). There was a discrepancy between the histological and immunostaining findings: the tumor cells exhibited morphological similarities to GCCs, however displayed limited staining upon immunostaining. Ultimately, we concluded that the tumor should be classified as AGCA, by following WHO 5th Edition. AGCA represents a newly categorized subtype of adenocarcinomas. Because of our preoperative suspicion of malignancy, we performed tumor resection with regional lymph node dissection, despite the fact that most appendiceal malignant tumors are typically identified after an appendectomy.

CONCLUSION: We experienced a case that provides valuable insights into the comprehension of AGCA, a recently established pathological entity in the WHO 5th Edition. This article is an acceptable secondary publication of a case report that appeared in Azuma et al. (J Jpn Surg Assoc 83:1103-1108, 2022).

RevDate: 2024-07-09

Yang Y, Chi L, Hsiao YC, et al (2024)

Sex-specific effects of gut microbiome on shaping bile acid metabolism.

bioRxiv : the preprint server for biology.

Gut microbiome is a group of microorganisms that plays important roles in contributing to health and diseases. These bacterial compositions have been demonstrated to impact bile acids (BAs) profiles, either by directly metabolizing primary BAs to secondary BAs or indirect ways through host metabolism by influencing BAs synthesis, transportation and conjugation in liver. It has been observed sexually dimorphic gut microbiome and bile acids composition, with variations in expression levels of bile acid metabolizing genes in the liver. However, associations betweensex-specific differences in gut microbiome and BAs profiles are not well understood. This study aimed to investigate whether gut microbiome could influence BAs profiles in host in a sex-specific manner. We transplanted cecum feces of male and female C57BL/6 mice to male mice and measured BAs concentrations in feces, serum and liver samples 7 days after fecal transplantation. We found different BAs profiles between mice with male and female gut microbiome, including altering levels and proportions of secondary BAs. We also observed varied expression levels of genes related to bile acid metabolism in the liver and distal ileum.Our results highlight sex-specific effects of gut microbiome on shaping bile acid metabolism through gut bacteria and regulation of host genes.

RevDate: 2024-07-10

He H, Li M, Qiu Y, et al (2024)

Washed microbiota transplantation improves sleep quality in patients with sleep disorder by the gut-brain axis.

Frontiers in neuroscience, 18:1415167.

BACKGROUND: The clinical impact of washed microbiota transplantation (WMT) from healthy donors in sleep disorder (SD) patients is unclear. This study aimed to investigate the effect of WMT in SD patients.

METHODS: The clinical data were collected from patients with different indications receiving 1-3 courses of WMT, divided into two groups by 7 points of PSQI scale. The score of PQSI and SF-36 scale was used to assess the improvement in sleep quality and life quality among patients with sleep disorders following WMT. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of patients with sleep disorders before and after WMT.

RESULTS: WMT significantly improved sleep quality in patients with sleep disorder in the short and medium term. WMT significantly improved sleep latency, sleep time and total score in the short term. WMT significantly improved sleep quality and total score in the medium term. In terms of sleep quality and sleep latency, the improvement value also increased with the increase of treatment course, and the improvement effect of multiple treatment course was better than that of single and double treatment course. In the total score, the improvement effect of double and multiple treatment was better than that of single treatment. WMT also improved quality of life in the sleep disorder group. WMT significantly improved general health, vitality, social function and mental health in the short term. WMT significantly improved role-physical, general health, vitality, and mental health in the medium term. WMT regulated the disturbed gut microbiota in patients with sleep disorders. In the normal sleep group, WMT had no effect on the decline of sleep quality in the short, medium and long term, and had an improving effect on the quality of life.

CONCLUSION: WMT could significantly improve sleep quality and life quality in patients with sleep disorders with no adverse events. The improvement in sleep quality resulting from WMT could lead to an overall enhancement in life quality. WMT could be a potentially effective treatment for patients with sleep disorders by regulating the gut microbiota.

RevDate: 2024-07-10

Watanangura A, Meller S, Farhat N, et al (2024)

Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: a pilot study of a novel therapeutic approach.

Frontiers in veterinary science, 11:1385469.

INTRODUCTION: Anxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy.

METHODS: Nine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification.

RESULTS: Following FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged.

DISCUSSION: Behavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT's potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.

RevDate: 2024-07-08
CmpDate: 2024-07-08

Vehreschild MJGT, Schreiber S, von Müller L, et al (2024)

[Need for improvement in the care of patients with Clostridioides difficile infections (CDI) - expert opinion in international comparison].

Zeitschrift fur Gastroenterologie, 62(7):1032-1041.

INTRODUCTION: Clostridioides difficile infection (CDI), as a nosocomial disease, is associated with high morbidity and mortality. Even though the incidence of CDI has been declining in Germany in recent years, the individual infection may pose a medical challenge despite therapeutic advances. The aim here is to clarify which gaps practitioners consider to be particularly serious in care and in the existing evidence base.

METHODS: In a moderated workshop of German CDI experts the topics considered as relevant were identified. A survey already conducted in five other countries (Australia, France, Great Britain, Canada, and Italy) was adapted and processed by 27 practitioners. During the evaluation, the topics perceived as particularly important were identified, the statements of the specialist groups were compared and changes in opinion were considered.

RESULTS: 27 fully completed questionnaires were evaluated. The need for improvement was primarily seen in the prevention of CDI recurrences (74.1%) and the treatment of recurrences (55.6%). Evidence deficits were noted in the treatment of recurrences (55.6%) and identification of risk factors for recurrences (48.1%). Improving care via fecal microbiota transfer (FMT) was named by 70.4%. For guidelines, more clarity (48.1%) and more regular updates (40.7%) were desired. For patients, better education on appropriate antibiotic use (52.0%) and choice of FMT were desired (48.1%).

SUMMARY: The German expert view and the international assessment is similar, when asked about the need for improvement in care and evidence gaps in the treatment of patients with CDI: The focus is on prevention and therapy of recurrent CDI. The problem of access to FMT is a German peculiarity that seems to need improvement.

RevDate: 2024-07-08
CmpDate: 2024-07-08

Fang L, J Ning (2024)

Gut virome and diabetes: discovering links, exploring therapies.

Archives of microbiology, 206(8):346.

This review offers a comprehensive analysis of the intricate relationship between the gut virome and diabetes, elucidating the mechanisms by which the virome engages with both human cells and the intestinal bacteriome. By examining a decade of scientific literature, we provide a detailed account of the distinct viral variations observed in type 1 diabetes (T1D) and type 2 diabetes (T2D). Our synthesis reveals that the gut virome significantly influences the development of both diabetes types through its interactions, which indirectly modulate immune and inflammatory responses. In T1D, the focus is on eukaryotic viruses that stimulate the host's immune system, whereas T2D is characterized by a broader spectrum of altered phage diversities. Promisingly, in vitro and animal studies suggest fecal virome transplantation as a potential therapeutic strategy to alleviate symptoms of T2D and obesity. This study pioneers a holistic overview of the gut virome's role in T1D and T2D, its interplay with host immunity, and the innovative potential of fecal transplantation therapy in clinical diabetes management.

RevDate: 2024-07-09

Mehta N, Goodenough D, Gupta NK, et al (2024)

Recurrent Clostridioides difficile Infection and Outcome of Fecal Microbiota Transplantation Use: A Population-Based Assessment.

Open forum infectious diseases, 11(7):ofae309.

BACKGROUND: Fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection (rCDI). In the current study, we evaluated rates of rCDI and subsequent FMT in a large metropolitan area. We compared demographic and clinical differences in FMT recipients and nonrecipients and quantified differences in outcomes based on treatment modality.

METHODS: A retrospective community-wide cohort study was conducted using surveillance data from the Georgia Emerging Infections Program, the Georgia Discharge Data System, and locally maintained lists of FMTs completed across multiple institutions to evaluate all episodes of C. difficile infection (CDI) in this region between 2016 and 2019. Cases were limited to patients with rCDI and ≥1 documented hospitalization. A propensity-matched cohort was created to compare rates of recurrence and mortality among matched patients based on FMT receipt.

RESULTS: A total of 3038 (22%) of 13 852 patients with CDI had rCDI during this period. In a propensity-matched cohort, patients who received an FMT had lower rates of rCDI (odds ratio, 0.6 [95% confidence interval, .38-.96) and a lower mortality rate (0.26 [.08-.82]). Of patients with rCDI, only 6% had received FMT. Recipients were more likely to be young, white, and female and less likely to have renal disease, diabetes, or liver disease, though these chronic illnesses were associated with higher rates of rCDI.

CONCLUSIONS: These data suggest FMT has been underused in a population-based assessment and that FMT substantially reduced risk of recurrence and death.

RevDate: 2024-07-09

Benvenuti L, Di Salvo C, Bellini G, et al (2024)

Gut-directed therapy in Parkinson's disease.

Frontiers in pharmacology, 15:1407925.

Parkinson's disease (PD) is a common and slow-progressing neurodegenerative disorder characterized by motor and non-motor symptoms, including gastrointestinal (GI) dysfunctions. Over the last years, the microbiota-gut-brain (MGB) axis is emerging as a bacterial-neuro-immune ascending pathway that contributes to the progression of PD. Indeed, PD patients are characterized by changes in gut microbiota composition, alterations of intestinal epithelial barrier (IEB) and enteric neurogenic/inflammatory responses that, besides determining intestinal disturbances, contribute to brain pathology. In this context, despite the causal relationship between gut dysbiosis, impaired MGB axis and PD remains to be elucidated, emerging evidence shows that MGB axis modulation can represent a suitable therapeutical strategy for the treatment of PD. This review provides an overview of the available knowledge about the beneficial effects of gut-directed therapies, including dietary interventions, prebiotics, probiotics, synbiotics and fecal microbiota transplantation (FMT), in both PD patients and animal models. In this context, particular attention has been devoted to the mechanisms by which the modulation of MGB axis could halt or slow down PD pathology and, most importantly, how these approaches can be included in the clinical practice.

RevDate: 2024-07-09

Li Y, Zhou Z, Liang X, et al (2024)

Gut Microbiota Disorder Contributes to the Production of IL-17A That Exerts Chemotaxis via Binding to IL-17RA in Endometriosis.

Journal of inflammation research, 17:4199-4217.

INTRODUCTION: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized.

METHODS: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry.

RESULTS: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects.

DISCUSSION: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.

RevDate: 2024-07-10

Kim NH, Hamadani M, S Abedin (2024)

New investigational drugs for steroid-refractory acute graft-versus-host disease: a review of the literature.

Expert opinion on investigational drugs [Epub ahead of print].

INTRODUCTION: Steroid-refractory acute graft-versus-host disease (SR-aGVHD) remains a formidable obstacle in the field of allogeneic hematopoietic cell transplantation (allo-HCT), significantly contributing to patient morbidity and mortality. The current therapeutic landscape for SR-aGVHD is limited, often yielding suboptimal results, thereby emphasizing the urgent need for innovative and effective treatments.

AREAS COVERED: In light of the pivotal REACH2 trial, ruxolitinib phosphate, a Janus kinase inhibitor, has gained prominence as the standard treatment for SR-aGVHD. Nevertheless, a considerable number of patients either do not respond to or cannot tolerate this therapy. This review delves into emerging treatments for SR-aGVHD, including mesenchymal stromal cells (MSCs), fecal microbiota transplantation (FMT), CD3/CD7 blockade, neihulizumab, begelomab, tocilizumab, and vedolizumab. While some of these agents have shown encouraging results in early-phase trials, issues such as treatment-related toxicities and inconsistent responses in larger studies highlight the necessity for ongoing research.

EXPERT OPINION: Current trials exploring new agents and combination therapies offer hope for fulfilling the unmet clinical needs in SR-aGVHD, potentially leading to more effective and precise treatment strategies.

RevDate: 2024-07-08

Khalaf R, Sciberras M, P Ellul (2024)

The role of the fecal microbiota in inflammatory bowel disease.

European journal of gastroenterology & hepatology pii:00042737-990000000-00382 [Epub ahead of print].

The understanding of the potential role of the microbiota in the pathogenesis of inflammatory bowel disease (IBD) is ever-evolving. Traditionally, the management of IBD has involved medical therapy and/or surgical intervention. IBD can be characterized by gut microbiome alterations through various pathological processes. Various studies delve into nontraditional methods such as probiotics and fecal microbiota transplant and their potential therapeutic effects. Fecal microbiota transplant involves the delivery of a balanced composition of gut microorganisms into an affected patient via multiple possible routes and methods, while probiotics consist of live microorganisms given via the oral route. At present, neither method is considered first-line treatment, however, fecal microbiota transplant has shown potential success in inducing and maintaining remission in ulcerative colitis. In a study by Kruis and colleagues, Escherichia coli Nissle 1917 was considered to be equivalent to mesalamine in mild ulcerative colitis. Alteration of the microbiome in the management of Crohn's disease is less well defined. Furthermore, variation in the clinical usefulness of 5-aminosalicylic acid medication has been attributed, in part, to its acetylation and inactivation by gut microbes. In summary, our understanding of the microbiome's role is continually advancing, with the possibility of paving the way for personalized medicine based on the microbiome.

RevDate: 2024-07-08
CmpDate: 2024-07-08

Sui Y, Feng X, Ma Y, et al (2024)

BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.

CNS neuroscience & therapeutics, 30(7):e14840.

BACKGROUND: Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. β-Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti-inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms.

METHODS: An in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS-induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH-DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents.

RESULTS: Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF-α, IL-1β, and IL-6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti-inflammatory cytokines (IL-10), while also inhibiting HS-induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF-α and IL-1β) in mouse BV2 cells.

CONCLUSION: β-Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut-brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota.

RevDate: 2024-07-06

Tang L, Zhang X, Zhang B, et al (2024)

Electroacupuncture remodels gut microbiota and metabolites in mice with perioperative neurocognitive impairment.

Experimental gerontology pii:S0531-5565(24)00149-9 [Epub ahead of print].

Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100β, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice.

RevDate: 2024-07-06

Zeng C, Wan SR, Guo M, et al (2024)

Fecal virome transplantation: A promising strategy for the treatment of metabolic diseases.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 177:117065 pii:S0753-3322(24)00949-1 [Epub ahead of print].

Metabolic diseases are a group of disorders caused by metabolic abnormalities, including obesity, diabetes, non-alcoholic fatty liver disease, and more. Increasing research indicates that, beyond inherent metabolic irregularities, the onset and progression of metabolic diseases are closely linked to alterations in the gut microbiota, particularly gut bacteria. Additionally, fecal microbiota transplantation (FMT) has demonstrated effectiveness in clinically treating metabolic diseases, notably diabetes. Recent attention has also focused on the role of gut viruses in disease onset. This review first introduces the characteristics and influencing factors of gut viruses, then summarizes their potential mechanisms in disease development, highlighting their impact on gut bacteria and regulation of host immunity. We also compare FMT, fecal filtrate transplantation (FFT), washed microbiota transplantation (WMT), and fecal virome transplantation (FVT). Finally, we review the current understanding of gut viruses in metabolic diseases and the application of FVT in treating these conditions. In conclusion, FVT may provide a novel and promising treatment approach for metabolic diseases, warranting further validation through basic and clinical research.

RevDate: 2024-07-08
CmpDate: 2024-07-06

Zuppi M, Vatanen T, Wilson BC, et al (2024)

Fecal microbiota transplantation alters gut phage communities in a clinical trial for obesity.

Microbiome, 12(1):122.

BACKGROUND: Fecal microbiota transplantation (FMT) is a therapeutic intervention used to treat diseases associated with the gut microbiome. In the human gut microbiome, phages have been implicated in influencing human health, with successful engraftment of donor phages correlated with FMT treatment efficacy. The impact that gastrointestinal phages exert on human health has primarily been connected to their ability to modulate the bacterial communities in the gut. Nonetheless, how FMT affects recipients' phage populations, and in turn, how this influences the gut environment, is not yet fully understood. In this study, we investigated the effects of FMT on the phageome composition of participants within the Gut Bugs Trial (GBT), a double-blind, randomized, placebo-controlled trial that investigated the efficacy of FMT in treating obesity and comorbidities in adolescents. Stool samples collected from donors at the time of treatment and recipients at four time points (i.e., baseline and 6 weeks, 12 weeks, and 26 weeks post-intervention), underwent shotgun metagenomic sequencing. Phage sequences were identified and characterized in silico to examine evidence of phage engraftment and to assess the extent of FMT-induced alterations in the recipients' phageome composition.

RESULTS: Donor phages engrafted stably in recipients following FMT, composing a significant proportion of their phageome for the entire course of the study (33.8 ± 1.2% in females and 33.9 ± 3.7% in males). Phage engraftment varied between donors and donor engraftment efficacy was positively correlated with their phageome alpha diversity. FMT caused a shift in recipients' phageome toward the donors' composition and increased phageome alpha diversity and variability over time.

CONCLUSIONS: FMT significantly altered recipients' phage and, overall, microbial populations. The increase in microbial diversity and variability is consistent with a shift in microbial population dynamics. This proposes that phages play a critical role in modulating the gut environment and suggests novel approaches to understanding the efficacy of FMT in altering the recipient's microbiome.

TRIAL REGISTRATION: The Gut Bugs Trial was registered with the Australian New Zealand Clinical Trials Registry (ACTR N12615001351505). Trial protocol: the trial protocol is available at https://bmjopen.bmj.com/content/9/4/e026174 . Video Abstract.

RevDate: 2024-07-08
CmpDate: 2024-07-05

Wang Y, Hu Y, P Shi (2024)

A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome.

BMC gastroenterology, 24(1):217.

OBJECTIVE: Multiple randomized controlled trials (RCTs) have investigated the efficacy of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), but have yielded inconsistent results. We updated the short-term and long-term efficacy of FMT in treating IBS, and performed a first-of-its-kind exploration of the relationship between gut microbiota and emotions.

METHODS: We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library using various search strategies to identify all eligible studies. The inclusion criteria for data extraction were randomized controlled trials (RCTs) that investigated the efficacy of fecal microbiota transplantation (FMT) compared to placebo in adult patients (≥ 18 years old) with irritable bowel syndrome (IBS). A meta-analysis was then performed to assess the summary relative risk (RR) and corresponding 95% confidence intervals (CIs).

RESULTS: Out of 3,065 potentially relevant records, a total of 10 randomized controlled trials (RCTs) involving 573 subjects met the eligibility criteria for inclusion in the meta-analysis. The meta-analyses revealed no significant differences in short-term (12 weeks) (RR 0.20, 95% CI -0.04 to 0.44), long-term (52 weeks) global improvement (RR 1.38, 95% CI 0.87 to 2.21), besides short-term (12 weeks) (SMD - 48.16, 95% CI -102.13 to 5.81, I[2] = 90%) and long-term (24 weeks) (SMD 2.16, 95% CI -60.52 to 64.83, I[2] = 68%) IBS-SSS. There was statistically significant difference in short-term improvement of IBS-QoL (SMD 10.11, 95% CI 0.71 to 19.51, I[2] = 82%), although there was a high risk of bias. In terms of long-term improvement (24 weeks and 54 weeks), there were no significant differences between the FMT and placebo groups (SMD 7.56, 95% CI 1.60 to 13.52, I[2] = 0%; SMD 6.62, 95% CI -0.85 to 14.08, I[2] = 0%). Sensitivity analysis indicated that there were visible significant effects observed when the criteria were based on Rome IV criteria (RR 16.48, 95% CI 7.22 to 37.62) and Gastroscopy (RR 3.25, 95%CI 2.37 to 4.47), Colonoscopy (RR 1.42, 95% CI 0.98 to 2.05). when using mixed stool FMT based on data from two RCTs, no significant difference was observed (RR 0.94, 95% CI 0.66 to -1.34). The remission of depression exhibited no significant difference between the FMT and placebo groups at the 12-week mark (SMD - 0.26, 95% CI -3.09 to 2.58), and at 24 weeks (SMD - 2.26, 95% CI -12.96 to 8.45). Furthermore, major adverse events associated with FMT were transient and self-limiting.

DISCUSSION: Based on the available randomized controlled trials (RCTs), the current evidence does not support the efficacy of FMT in improving global IBS symptoms in the long term. The differential results observed in subgroup analyses raise questions about the accurate identification of suitable populations for FMT. Further investigation is needed to better understand the reasons behind these inconsistent findings and to determine the true potential of FMT as a treatment for IBS.

RevDate: 2024-07-05

Yu J, Chen X, Yang X, et al (2024)

Understanding gut dysbiosis for hepatocellular carcinoma diagnosis and treatment.

Trends in endocrinology and metabolism: TEM pii:S1043-2760(24)00163-2 [Epub ahead of print].

The gut microbiome can play a crucial role in hepatocellular carcinoma (HCC) progression through the enterohepatic circulation, primarily acting via metabolic reprogramming and alterations in the hepatic immune microenvironment triggered by microbe-associated molecular patterns (MAMPs), metabolites, and fungi. In addition, the gut microbiome shows potential as a biomarker for early HCC diagnosis and for assessing the efficacy of immunotherapy in unresectable HCC. This review examines how gut microbiota dysbiosis, with varied functional profiles, contributes to HCCs of different etiologies. We discuss therapeutic strategies to modulate the gut microbiome including diets, antibiotics, probiotics, fecal microbiota transplantation, and nano-delivery systems, and underscore their potential as an adjunctive treatment modality for HCC.

RevDate: 2024-07-05

Li X, Shang S, Wu M, et al (2024)

Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis.

Cancer letters pii:S0304-3835(24)00491-9 [Epub ahead of print].

Metabolic derivatives of numerous microorganisms inhabiting the human gut can participate in physiological activities and immune status of the lungs through the gut-lung axis. The current well-established microbial metabolites include short-chain fatty acids (SCFAs), tryptophan and its derivatives, polyamines (PAs), secondary bile acids (SBAs), etc. As the study continues to deepen, the critical function of microbial metabolites in the occurrence and treatment of lung cancer has gradually been revealed. Microbial derivates can enter the circulation system to modulate the immune microenvironment of lung cancer. Mechanistically, oncometabolites damage host DNA and promote the occurrence of lung cancer, while tumor-suppresive metabolites directly affect the immune system to combat the malignant properties of cancer cells and even show considerable application potential in improving the efficacy of lung cancer immunotherapy. Considering the crosstalk along the gut-lung axis, in-depth exploration of microbial metabolites in patients' feces or serum will provide novel guidance for lung cancer diagnosis and treatment selection strategies. In addition, targeted therapeutics on microbial metabolites are expected to overcome the bottleneck of lung cancer immunotherapy and alleviate adverse reactions, including fecal microbiota transplantation, microecological preparations, metabolite synthesis and drugs targeting metabolic pathways. In summary, this review provides novel insights and explanations on the intricate interplay between gut microbial metabolites and lung cancer development, and immunotherapy through the lens of the gut-lung axis, which further confirms the possible translational potential of the microbiome metabolome in lung cancer treatment.

RevDate: 2024-07-05

Cheng Z, Yang L, H Chu (2024)

The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD.

Journal of advanced research pii:S2090-1232(24)00268-6 [Epub ahead of print].

BACKGROUND: The liver disorders caused by alcohol abuse are termed alcoholic-related liver disease (ALD), including alcoholic steatosis, alcoholic steatohepatitis alcoholic hepatitis, and alcoholic cirrhosis, posing a significant threat to human health. Currently, ALD pathogenesis has not been completely clarified, which is likely to be related to the direct damage caused by alcohol and its metabolic products, oxidative stress, gut dysbiosis, and exosomes.

AIMS: The existing studies suggest that both the gut microbiota and exosomes contribute to the development of ALD. Moreover, there exists an interaction between the gut microbiota and exosomes. We discuss whether this interaction plays a role in the pathogenesis of ALD and whether it can be a potential therapeutic target for ALD treatment.

Chronic alcohol intake alters the diversity and composition of gut microbiota, which greatly contributes to ALD's progression. Some approaches targeting the gut microbiota, including probiotics, fecal microbiota transplantation, and phage therapy, have been confirmed to effectively ameliorate ALD in many animal experiments and/or several clinical trials. In ALD, the levels of exosomes and the expression profile of microRNA have also changed, which affects the pathogenesis of ALD. Moreover, there is an interplay between exosomes and the gut microbiota, which also putatively acts as a pathogenic factor of ALD.

RevDate: 2024-07-06

Bai X, Duan Z, Deng J, et al (2024)

Ginsenoside Rh4 inhibits colorectal cancer via the modulation of gut microbiota-mediated bile acid metabolism.

Journal of advanced research pii:S2090-1232(24)00265-0 [Epub ahead of print].

INTRODUCTION: Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored.

OBJECTIVES: We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota.

METHODS: We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC.

RESULTS: Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila (A. muciniphila), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila-mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC.

CONCLUSION: Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.

RevDate: 2024-07-05

Beckers M, Coburn B, Kalia LV, et al (2024)

A Randomized Controlled Trial of Fecal Microbiota Transplantation for Parkinson's Disease: Getting it right, if not PARFECT.

RevDate: 2024-07-08
CmpDate: 2024-07-05

Zhang R, Yan Z, Zhong H, et al (2024)

Gut microbial metabolites in MASLD: Implications of mitochondrial dysfunction in the pathogenesis and treatment.

Hepatology communications, 8(7):.

With an increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health problem. MASLD is well-known as a multifactorial disease. Mitochondrial dysfunction and alterations in the gut bacteria are 2 vital events in MASLD. Recent studies have highlighted the cross-talk between microbiota and mitochondria, and mitochondria are recognized as pivotal targets of the gut microbiota to modulate the host's physiological state. Mitochondrial dysfunction plays a vital role in MASLD and is associated with multiple pathological changes, including hepatocyte steatosis, oxidative stress, inflammation, and fibrosis. Metabolites are crucial mediators of the gut microbiota that influence extraintestinal organs. Additionally, regulation of the composition of gut bacteria may serve as a promising therapeutic strategy for MASLD. This study reviewed the potential roles of several common metabolites in MASLD, emphasizing their impact on mitochondrial function. Finally, we discuss the current treatments for MASLD, including probiotics, prebiotics, antibiotics, and fecal microbiota transplantation. These methods concentrate on restoring the gut microbiota to promote host health.

RevDate: 2024-07-06

Lin L, Tang R, Liu Y, et al (2024)

Research on the anti-aging mechanisms of Panax ginseng extract in mice: a gut microbiome and metabolomics approach.

Frontiers in pharmacology, 15:1415844.

Introduction: Aged-related brain damage and gut microbiome disruption are common. Research affirms that modulating the microbiota-gut-brain axis can help reduce age-related brain damage. Methods: Ginseng, esteemed in traditional Chinese medicine, is recognized for its anti-aging capabilities. However, previous Ginseng anti-aging studies have largely focused on diseased animal models. To this end, efforts were hereby made to explore the potential neuroprotective effects of fecal microbiota transplantation (FMT) from Ginseng-supplemented aged mice to those pre-treated with antibiotics. Results: As a result, FMT with specific modifications in natural aging mice improved animal weight gain, extended the telomere length, anti-oxidative stress in brain tissue, regulated the serum levels of cytokine, and balanced the proportion of Treg cells. Besides, FMT increased the abundance of beneficial bacteria of Lachnospiraceae, Dubosiella, Bacteroides, etc. and decreased the levels of potential pathogenic bacteria of Helicobacter and Lachnoclostridium in the fecal samples of natural aged mice. This revealed that FMT remarkably reshaped gut microbiome. Additionally, FMT-treated aged mice showed increased levels of metabolites of Ursolic acid, β-carotene, S-Adenosylmethionine, Spermidine, Guanosine, Celecoxib, Linoleic acid, etc., which were significantly positively correlated with critical beneficial bacteria above. Additionally, these identified critical microbiota and metabolites were mainly enriched in the pathways of Amino acid metabolism, Lipid metabolism, Nucleotide metabolism, etc. Furthermore, FMT downregulated p53/p21/Rb signaling and upregulated p16/p14, ATM/synapsin I/synaptophysin/PSD95, CREB/ERK/AKT signaling in brain damage following natural aging. Discussion: Overall, the study demonstrates that reprogramming of gut microbiota by FMT impedes brain damage in the natural aging process, possibly through the regulation of microbiota-gut-brain axis.

RevDate: 2024-07-06

Tominaga K, Kojima Y, Kawata Y, et al (2024)

An updated review on the treatment for diversion colitis and pouchitis, with a focus on the utility of autologous fecal microbiota transplantation and its relationship with the intestinal microbiota.

Bioscience of microbiota, food and health, 43(3):162-169.

Diversion colitis (DC) is characterized by mucosal inflammation in the defunctioned segment of the colon following a colostomy or ileostomy. The major causes of DC are an increase in the number of aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon. However, its exact pathogenesis remains unknown. Various treatment strategies for DC have been explored, although none have been definitively established. Treatment approaches such as SCFAs, 5-aminosalicylic acid enemas, steroid enemas, and irrigation with fibers have been attempted, yielding various degrees of efficacies in mitigating mucosal inflammation. However, only individual case reports demonstrating the limited effect of the following therapies have been published: leukocytapheresis, dextrose (hypertonic glucose) spray, infliximab, an elemental diet, and coconut oil. The usefulness of probiotics for treating DC has recently been reported. Furthermore, fecal microbiota transplantation (FMT) has emerged as a promising treatment for DC. This review provides an update on the treatment strategies of DC, with a particular focus on FMT and its relationship with the intestinal microbiota. FMT may become the first choice of treatment for some patients in the future because of its low medical costs, ease of use, and minimal side effects. Furthermore, FMT can also be used for postoperative DC prophylaxis.

RevDate: 2024-07-04

Drew L (2024)

Faecal transplants can treat some cancers - but probably won't ever be widely used.

RevDate: 2024-07-04

Zhu Y, Self WK, DM Holtzman (2024)

An emerging role for the gut microbiome in tauopathy.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics pii:S1878-7479(24)00109-0 [Epub ahead of print].

Tauopathies constitute a group of neurodegenerative diseases characterized by abnormal aggregation of the protein tau, progressive neuronal and synaptic loss, and eventual cognitive and motor impairment. In this review, we will highlight the latest efforts investigating the intricate interplay between the gut microbiome and tauopathies. We discuss the physiological interactions between the microbiome and the brain as well as clinical and experimental evidence that suggests that the presence of tauopathy alters the composition of gut microbiota. We explore both animal and human studies that define causative relationships between the gut microbiome and tauopathy by directly manipulating or transferring gut microbiota. This review highlights future directions into identifying and mechanistically elucidating microbial species causally linked to tauopathies, with an ultimate goal of devising therapeutic targets towards the gut microbiome to treat tauopathies.

RevDate: 2024-07-05

Davido B, Watson AR, de Truchis P, et al (2024)

Bacterial diversity and specific taxa are associated with decolonization of carbapenemase-producing enterobacterales after fecal microbiota transplantation.

The Journal of infection, 89(2):106216 pii:S0163-4453(24)00150-6 [Epub ahead of print].

OBJECTIVES: We evaluated the effect of fecal microbiota transplantation (FMT) on the clearance of carbapenemase-producing Enterobacterales (CPE) carriage.

METHODS: We performed a prospective, multi-center study, conducted among patients who received a single dose of FMT from one of four healthy donors. The primary endpoint was complete clearance of CPE carriage two weeks after FMT with a secondary endpoint at three months. Shotgun metagenomic sequencing was performed to assess gut microbiota composition of donors and recipients before and after FMT.

RESULTS: Twenty CPE-colonized patients were included in the study, where post-FMT 20% (n = 4/20) of patients met the primary endpoint and 40% (n = 8/20) of patients met the secondary endpoint. Kaplan-Meier curves between patients with FMT intervention and the control group (n = 82) revealed a similar rate of decolonization between groups. Microbiota composition analyses revealed that response to FMT was not donor-dependent. Responders had a significantly lower relative abundance of CPE species pre-FMT than non-responders, and 14 days post-FMT responders had significantly higher bacterial species richness and alpha diversity compared to non-responders (p < 0.05). Responder fecal samples were also enriched in specific species, with significantly higher relative abundances of Faecalibacterium prausnitzii, Parabacteroides distasonis, Collinsella aerofaciens, Alistipes finegoldii and Blautia_A sp900066335 (q<0.01) compared to non-responders.

CONCLUSION: FMT administration using the proposed regimen did not achieve statistical significance for complete CPE decolonization but was correlated with the relative abundance of specific bacterial taxa, including CPE species.

RevDate: 2024-07-04

Chen S, Liu H, Yan C, et al (2024)

Fecal microbiota transplantation provides insights into the consequences of transcriptome profiles and cell energy in response to circadian misalignment of chickens.

Poultry science, 103(9):103926 pii:S0032-5791(24)00505-4 [Epub ahead of print].

The circadian misalignment (CM) disordered circadian rhythms exert adverse effects on animals. Poultry as one of animals suffers health and welfare problems due to long-term lighting photoperiods caused by CM. However, the roles of CM on organ development, cell growth, metabolism and immune are still unclear in chickens. In this study, a Chinese dual-purpose native breed, was used to explore the effects of CM on transcriptomic pattern of brain and cell energy biogenesis, and further fecal microbiota transplantation (FMT) was applied to investigate its "therapy" effect from CM suffering. Our results showed that the CM led to stunting in brain and small intestine of chicken. CM decreased of cell proliferation, and energy production, mtDNA copies and expression of genes related to cell cycle or mitochondrial biogenetics, while it upregulated the reactive oxygen species (ROS) level and the sensitivity to inflammation. Interestingly, FMT rescued the organ developmental defects and cell dysfunctions induced by CM. Circadian misalignment brought about abnormal tissue and cell developments, energy biogenesis, and immune response in birds. This study provided a comprehensive perspective on understanding the regulation of CM and FMT on bird development and welfare.

RevDate: 2024-07-04

Xiong Y, Pu YN, Li LY, et al (2024)

Gut microbiota-derived metabolite trimethylamine N-oxide aggravates cognitive dysfunction induced by femoral fracture operation in mice.

The Kaohsiung journal of medical sciences [Epub ahead of print].

An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N-oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO-induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ-free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO-related POCD and improving the quality of life for elderly patients.

RevDate: 2024-07-05

Zou S, Li Y, Zou Q, et al (2024)

Gut microbiota and serum metabolomic alterations in modulating the impact of fecal microbiota transplantation on ciprofloxacin-induced seizure susceptibility.

Frontiers in microbiology, 15:1403892.

INTRODUCTION: The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear.

METHODS: We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models.

RESULTS: We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation.

CONCLUSION: In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy.

RevDate: 2024-07-04
CmpDate: 2024-07-04

Mehra P, A Kumar (2024)

Emerging importance of stool preservation methods in OMICS studies with special focus on cancer biology.

Cell biochemistry and function, 42(5):e4063.

The intricate consortium of microorganisms in the human gut plays a crucial role in different physiological functions. The complex known-unknown elements of the gut microbiome are perplexing and the absence of standardized procedures for collecting and preserving samples has hindered continuous research in comprehending it. The technological bias produced because of lack of standard protocols has affected the reproducibility of results. The complex nature of diseases like colorectal cancer, gastric cancer, hepatocellular carcinoma and breast cancer require a thorough understanding of its etiology for an efficient and timely diagnosis. The designated protocols for collection and preservation of stool specimens have great variance, hence generate inconsistencies in OMICS studies. Due to the complications associated to the nature of sample, it is important to preserve the sample to be studied later in a laboratory or to be used in the future research purpose. Stool preservation is gaining importance due to the increased use of treatment options like fecal microbiota transplantation to cure conditions like recurrent Clostridium difficile infections and for OMICS studies including metagenomics, metabolomics and culturomics. This review provides an insight into the importance of omics studies for the identification and development of novel biomarkers for quick and noninvasive diagnosis of various diseases.

RevDate: 2024-07-03
CmpDate: 2024-07-03

Wang B, Qiu Y, Xie M, et al (2024)

Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses.

BMC microbiology, 24(1):237.

OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer.

METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms.

RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4[+]T and CD8[+]T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group.

CONCLUSION: P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

RevDate: 2024-07-03

Bum Lee J, Huang Y, Oya Y, et al (2024)

Modulating the gut microbiome in non-small cell lung cancer: Challenges and opportunities.

Lung cancer (Amsterdam, Netherlands), 194:107862 pii:S0169-5002(24)00396-9 [Epub ahead of print].

Despite the efficacy of immunotherapy in non-small cell lung cancer (NSCLC), the majority of the patients experience relapse with limited subsequent treatment options. Preclinical studies of various epithelial tumors, such as melanoma and NSCLC, have shown that harnessing the gut microbiome resulted in improvement of therapeutic responses to immunotherapy. Is this review, we summarize the role of microbiome, including lung and gut microbiome in the context of NSCLC, provide overview of the mechanisms of microbiome in efficacy and toxicity of chemotherapies and immunotherapies, and address current ongoing clinical trials for NSCLC including fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs).

RevDate: 2024-07-03

Cheng X, Hu Y, Kuang J, et al (2024)

Berberine alleviates high-energy and low-protein diet-induced fatty liver hemorrhagic syndrome in laying hens: insights from microbiome and metabolomics.

Poultry science, 103(8):103968 pii:S0032-5791(24)00547-9 [Epub ahead of print].

Berberine (BBR), a well-known quaternary ammonium alkaloid, is recognized for its ability to prevent and alleviate metabolic disorders because of its anti-oxidative and anti-inflammatory properties. However, the underlying mechanisms of BBR to mitigate fatty liver hemorrhagic syndrome (FLHS) through the modulation of gut microbiota and their metabolism remained unclear. The results revealed that BBR ameliorates lipid metabolism disorder in high-energy and low-protein (HELP) diet-induced FLHS laying hens, as evidenced by improved liver function and lipid deposition of the liver, reduced blood lipids, and the expression of liver lipid synthesis-related factors. Moreover, BBR alleviated HELP diet-induced barrier dysfunction, increased microbial population, and dysregulated lipid metabolism in the ileum. BBR reshaped the HELP-perturbed gut microbiota, particularly declining the abundance of Desulfovibrio_piger and elevating the abundance of Bacteroides_salanitronis_DSM_18170. Meanwhile, metabolomic profiling analysis revealed that BBR reshaped microbial metabolism and function, particularly by reducing the levels of hydrocinnamic acid, dehydroanonaine, and leucinic acid. Furthermore, fecal microbiota transplantation (FMT) experiments revealed that BBR-enriched gut microbiota alleviated hepatic lipid deposition and intestinal inflammation compared with those chicks that received a gut microbiota by HELP. Collectively, our study provided evidence that BBR effectively alleviated FLHS induced by HELP by reshaping the microbial and metabolic homeostasis within the liver-gut axis.

RevDate: 2024-07-04
CmpDate: 2024-07-03

Chen J, Zhang C, Yang Z, et al (2024)

Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury.

Parasites & vectors, 17(1):284.

BACKGROUND: Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. gondii infection, disruption of gut microbiota further exacerbates the damage to intestinal and brain barriers. Therefore, identifying imbalanced probiotics during infection and restoring their equilibrium can regulate the balance of gut microbiota metabolites, thereby alleviating tissue damage.

METHODS: Vimentin gene knockout (vim-/-) mice were employed as an immunocompromised model to evaluate the influence of host immune responses on gut microbiota balance during T. gondii infection. Behavioral experiments were performed to assess changes in cognitive levels and depressive tendencies between chronically infected vim-/- and wild-type (WT) mice. Fecal samples were subjected to 16S ribosomal RNA (rRNA) sequencing, and serum metabolites were analyzed to identify potential gut probiotics and their metabolites for the treatment of T. gondii infection.

RESULTS: Compared to the immunocompetent WT sv129 mice, the immunocompromised mice exhibited lower levels of neuronal apoptosis and fewer neurobehavioral abnormalities during chronic infection. 16S rRNA sequencing revealed a significant decrease in the abundance of probiotics, including several species of Lactobacillus, in WT mice. Restoring this balance through the administration of Lactobacillus murinus and Lactobacillus gasseri significantly suppressed the T. gondii burden in the intestine, liver, and brain. Moreover, transplantation of these two Lactobacillus spp. significantly improved intestinal barrier damage and alleviated inflammation and neuronal apoptosis in the central nervous system. Metabolite detection studies revealed that the levels of various Lactobacillus-related metabolites, including indole-3-lactic acid (ILA) in serum, decreased significantly after T. gondii infection. We confirmed that L. gasseri secreted much more ILA than L. murinus. Notably, ILA can activate the aromatic hydrocarbon receptor signaling pathway in intestinal epithelial cells, promoting the activation of CD8[+] T cells and the secretion of interferon-gamma.

CONCLUSION: Our study revealed that host immune responses against T. gondii infection severely disrupted the balance of gut microbiota, resulting in intestinal and brain damage. Lactobacillus spp. play a crucial role in immune regulation, and the metabolite ILA is a promising therapeutic compound for efficient and safe treatment of T. gondii infection.

RevDate: 2024-07-02

Swarte JC, Zhang S, Nieuwenhuis LM, et al (2024)

Multiple indicators of gut dysbiosis predict all-cause and cause-specific mortality in solid organ transplant recipients.

Gut pii:gutjnl-2023-331441 [Epub ahead of print].

OBJECTIVE: Gut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in the general population, the relationship with overall survival in specific diseases has not been extensively studied. In the current study, we present results from an in-depth analysis of the relationship between gut dysbiosis and all-cause and cause-specific mortality in the setting of solid organ transplant recipients (SOTR).

DESIGN: We analysed 1337 metagenomes derived from faecal samples of 766 kidney, 334 liver, 170 lung and 67 heart transplant recipients part of the TransplantLines Biobank and Cohort-a prospective cohort study including extensive phenotype data with 6.5 years of follow-up. To analyze gut dysbiosis, we included an additional 8208 metagenomes from the general population of the same geographical area (northern Netherlands). Multivariable Cox regression and a machine learning algorithm were used to analyse the association between multiple indicators of gut dysbiosis, including individual species abundances, and all-cause and cause-specific mortality.

RESULTS: We identified two patterns representing overall microbiome community variation that were associated with both all-cause and cause-specific mortality. The gut microbiome distance between each transplantation recipient to the average of the general population was associated with all-cause mortality and death from infection, malignancy and cardiovascular disease. A multivariable Cox regression on individual species abundances identified 23 bacterial species that were associated with all-cause mortality, and by applying a machine learning algorithm, we identified a balance (a type of log-ratio) consisting of 19 out of the 23 species that were associated with all-cause mortality.

CONCLUSION: Gut dysbiosis is consistently associated with mortality in SOTR. Our results support the observations that gut dysbiosis is associated with long-term survival. Since our data do not allow us to infer causality, more preclinical research is needed to understand mechanisms before we can determine whether gut microbiome-directed therapies may be designed to improve long-term outcomes.

RevDate: 2024-07-04
CmpDate: 2024-07-02

Rasmussen TS, Mao X, Forster S, et al (2024)

Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments.

Microbiome, 12(1):119.

BACKGROUND: Fecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases.

METHODS: To overcome these challenges, we developed methods to broaden FVT's clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline.

RESULTS: FVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy.

CONCLUSIONS: This proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches. Video Abstract.

RevDate: 2024-07-01

Ngo VL, Wang Y, Shi Z, et al (2024)

Gut-resident C. perfringens impedes rotavirus vaccine efficacy.

bioRxiv : the preprint server for biology pii:2024.06.17.599343.

BACKGROUND & AIMS: The extent to which live orally-administered rotavirus (RV) vaccines elicit protective immunity is highly heterogeneous. We hypothesized microbiota composition might influence vaccine efficacy.

METHODS: We tested this concept by examining extent to which colonizing mice with segmented filamentous bacteria (SFB) influenced RV vaccine efficacy.Influence of human microbiomes on RV vaccination was studied via administering germ-free mice fecal microbial transplants (FMT) from children with robust or minimal RV vaccine responsiveness. Post-FMT, mice were subjected to vaccination and challenge doses of RV.

RESULTS: SFB administration resulted in a phenotype reminiscent of RV vaccine failure, i.e. minimal generation of RV antigens and, consequently, lack of anti-RV antibodies resulting in proneness to RV challenge once SFB levels diminished. Transplant of microbiomes from children to mice recapitulated donor vaccination phenotype. Specifically, mice receiving FMT from high-responding children exhibited high levels of fecal RV antigen shedding and RV antibodies in response to RV vaccination and, concomitantly, were impervious to RV challenge. In contrast, mice receiving FMT from children who had not responded to RV vaccination exhibited only modest responses to RV challenge and, accordingly, remained prone to RV challenge. Microbiome analysis ruled out a role for SFB but suggested that RV vaccine failure might involve Clostridium perfringens . Oral administration of cultured C. perfringens to gnotobiotic mice partially recapitulated the RV vaccine non-responder phenotype. Analysis of previously-reported microbiome data found C. perfringens abundance in children associated with RV vaccine failure.

CONCLUSION: Microbiota composition influences RV vaccine virus infection and, consequently, protective immunity. C. perfringens may be one, perhaps of many, bacterial species harbored in the intestine of RV-vaccine non-responders that influences RV vaccine outcomes.

RevDate: 2024-07-02
CmpDate: 2024-07-01

Yan J, Zhang X, Zhu K, et al (2024)

Sleep deprivation causes gut dysbiosis impacting on systemic metabolomics leading to premature ovarian insufficiency in adolescent mice.

Theranostics, 14(9):3760-3776.

Rationale: Currently, there are occasional reports of health problems caused by sleep deprivation (SD). However, to date, there remains a lack of in-depth research regarding the effects of SD on the growth and development of oocytes in females. The present work aimed to investigate whether SD influences ovarian folliculogenesis in adolescent female mice. Methods: Using a dedicated device, SD conditions were established in 3-week old female mice (a critical stage of follicular development) for 6 weeks and gut microbiota and systemic metabolomics were analyzed. Analyses were related to parameters of folliculogenesis and reproductive performance of SD females. Results: We found that the gut microbiota and systemic metabolomics were severely altered in SD females and that these were associated with parameters of premature ovarian insufficiency (POI). These included increased granulosa cell apoptosis, reduced numbers of primordial follicles (PmFs), correlation with decreased AMH, E2, and increased LH in blood serum, and a parallel increased number of growing follicles and changes in protein expression compatible with PmF activation. SD also reduced oocyte maturation and reproductive performance. Notably, fecal microbial transplantation from SD females into normal females induced POI parameters in the latter while niacinamide (NAM) supplementation alleviated such symptoms in SD females. Conclusion: Gut microbiota and alterations in systemic metabolomics caused by SD induced POI features in juvenile females that could be counteracted with NAM supplementation.

RevDate: 2024-06-28

Dhanda AD, Allgar V, Bhala N, et al (2024)

Breaking down barriers between liver, addiction, and mental health services for people with alcohol-related liver disease.

The lancet. Gastroenterology & hepatology pii:S2468-1253(24)00189-4 [Epub ahead of print].

RevDate: 2024-06-28

Teng M, Sun J, Zhao L, et al (2024)

Effects of BBIBP-CorV vaccine on gut microbiota and short-chain fatty acids in mice exposed to bis (2-ethylhexyl) phthalate and dioctyl terephthalate.

Environment international, 190:108851 pii:S0160-4120(24)00437-9 [Epub ahead of print].

As the COVID-19 pandemic has progressed, increasing evidences suggest that the gut microbiota may play a crucial role in the effectiveness of SARS-CoV-2 vaccine. Thus, this study was aimed at investigating the influence of SARS-CoV-2 vaccine on the gut microbiota and short-chain fatty acids (SCFAs) of organisms exposed to environmental contaminants, i.e., plasticizers: phthalate esters. We found that in mice, exposure to dioctyl terephthalate (DOTP) and bis -2-ethylhexyl phthalate (DEHP) decreased the blood glucose level and white fat weight, induced inflammatory responses, caused damage to liver and intestinal tissues, and disrupted the gut microbiota composition and SCFAs metabolism. Specifically, the Bacteroidetes phylum was positively correlated with BBIBP-CorV vaccine, while acetic acid was negatively associated with the vaccine. Interestingly, the BBIBP-CorV vaccine somewhat alleviated tissue inflammation and reduced the contents of acetic acid and propionic acid in mice exposed to DEHP and DOTP. These findings were confirmed by a fecal microbiota transplantation assay. Overall, this study revealed that exposure to DEHP and DOTP adversely affects the gut microbiota and SCFAs, while the BBIBP-CorV vaccine can protect mice against these effects. This work highlighted the relationship between BBIBP-CorV vaccination, gut microbiome composition, and responses to plasticizers, which may facilitate the development and risk assessment of SARS-CoV-2 vaccines and environmental contaminants on microbiota health.

RevDate: 2024-06-28

Yang S, Wei Z, Luo J, et al (2024)

Integrated bioinformatics and multiomics reveal Liupao tea extract alleviating NAFLD via regulating hepatic lipid metabolism and gut microbiota.

Phytomedicine : international journal of phytotherapy and phytopharmacology, 132:155834 pii:S0944-7113(24)00492-6 [Epub ahead of print].

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) poses a significant global public health concern. Liupao tea (LPT) is a Chinese national geographical indication product renowned for its lipid-lowering properties. However, the precise mechanisms and active constituents contributing to the efficacy of LPT against NAFLD remain unclear.

PURPOSE: This study aims to comprehensively explore the therapeutic potential of Liupao tea extract (LPTE) in alleviating NAFLD through an integrated strategy.

METHODS: Initially, network pharmacology analysis was conducted based on LPTE chemical ingredient analysis, identifying core targets and key components. Potential active ingredients were validated through chemical standards based on LC-MS/MS. To confirm the pharmacological efficacy of LPTE in NAFLD, NAFLD mice models were employed. Alterations in hepatic lipid metabolism were comprehensively elucidated through integration of metabolomics, lipidomics, network pharmacology analysis, and real-time PCR analysis. To further explore the binding interactions between key components and core targets, molecular docking and microscale thermophoresis (MST) analysis were employed. Furthermore, to investigate LPTE administration effectiveness on gut microbiota in NAFLD mice, a comprehensive approach was employed. This included Metorigin analysis, 16S rRNA sequencing, molecular docking, and fecal microbiome transplantation (FMT).

RESULTS: Study identified naringenin, quercetin, luteolin, and kaempferol as the potential active ingredients of LPTE. These compounds exhibited therapeutic potential for NAFLD by targeting key proteins such as PTGS2, CYP3A4, and ACHE, which are involved in the metabolic pathways of hepatic linoleic acid (LA) and glycerophospholipid (GP) metabolism. The therapeutic effectiveness of LPTE was observed to be comparable to that of simvastatin. Furthermore, LPTE exhibited notable efficacy in alleviating NAFLD by influencing alterations in gut microbiota composition (Proteobacteria phylum, Lactobacillus and Dubosiella genus) that perhaps impact LA and GP metabolic pathways.

CONCLUSION: LPTE could be effective in preventing high-fat diet (HFD)-induced NAFLD by modulating hepatic lipid metabolism and gut microbiota. This study firstly integrated bioinformatics and multi-omics technologies to identify the potential active components and key microbiota associated with LPTE's effects, while also primally elucidating the action mechanisms of LPTE in alleviating NAFLD. The findings offer a conceptual basis for LPTE's potential transformation into an innovative pharmaceutical agent for NAFLD prevention.

RevDate: 2024-07-03
CmpDate: 2024-06-28

Zhong HJ, Zhuang YP, Xie X, et al (2024)

Washed microbiota transplantation promotes homing of group 3 innate lymphoid cells to the liver via the CXCL16/CXCR6 axis: a potential treatment for metabolic-associated fatty liver disease.

Gut microbes, 16(1):2372881.

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.

RevDate: 2024-06-28
CmpDate: 2024-06-28

Li Y, Fang Y, Wang H, et al (2024)

Balancing Act: Exploring the Gut Microbiota-Brown Adipose Tissue Axis in PCOS Pathogenesis and Therapeutic Frontiers.

Frontiers in bioscience (Landmark edition), 29(6):208.

Polycystic ovary syndrome (PCOS) is a prevalent reproductive, endocrine, and metabolic disease that affects 5-18% of women worldwide, with a rising incidence. Hyperandrogenemia and insulin resistance are two key pathophysiological factors that contribute to PCOS, both of which contribute to a variety of health issues such as menstrual irregularities, obesity, dysfunctional glucose and lipid homeostasis, infertility, mental disorders, and cardiovascular and cerebrovascular diseases. Despite ongoing studies, the origin and pathogenesis of PCOS remain elusive; there is also a clinical need for simpler, more effective, longer lasting, and more comprehensive treatments for women with PCOS. The gut-fat axis, a critical regulatory route for metabolism, endocrine function, and immune response, has received considerable interest in recent years in the research of the etiology and treatment of metabolic illnesses such as type 2 diabetes mellitus and non-alcoholic fatty liver disease. The latest research in PCOS has revealed significant alterations in the homogeneity and phylogenetic diversity of the gut microbiota. Animal research using fecal microbiota transplantation has confirmed the importance of gut microbiota in regulating insulin sensitivity and sex hormone balance in PCOS. Furthermore, studies have shown a decrease in the volume and/or activity of brown adipose tissue (BAT) in PCOS patients, a change that alters adipokine release, leading to insulin resistance and hyperandrogenemia, aggravating PCOS progression. Given the function of BAT in increasing energy expenditure and alleviating metabolic parameters, efforts to activate BAT or induce browning of white adipose tissue have emerged as possible treatments for PCOS. Recent research has suggested that the gut microbiota can influence BAT creation and activity via metabolites such as short-chain fatty acids and bile acids, as well as the gut-brain axis. Cold exposure, healthy dieting, metformin, bariatric surgery, glucagon-like peptide 1 receptor agonists and melatonin have all been shown in basic and clinical studies to modulate BAT activity by influencing the gut microbiota, demonstrating significant clinical potential. However, more studies into the regulation mechanisms of the gut-BAT axis are required to produce more effective, comfortable, and safe tailored therapeutics for PCOS.

RevDate: 2024-07-03
CmpDate: 2024-06-28

Wu Y, Gu D, Li J, et al (2024)

Role of the gut microbiota in cefoperazone/sulbactam-induced epilepsy in mice with chronic renal failure.

Renal failure, 46(2):2371551.

OBJECTIVES: The mechanism of cefoperazone/sulbactam-induced epilepsy in chronic kidney disease (CKD) patients is not yet clear. We hypothesized that cefoperazone/sulbactam-induced epilepsy could be based on two main factors: neurotoxicity caused by drug accumulation after renal failure and an abnormal gut microbiota (GM).

METHODS: A chronic renal failure (CRF) model in mice was established, and then different doses of cefoperazone/sulbactam were injected to induce epilepsy in mice. Normal mouse feces for fecal microbiota transplantation (FMT) were collected. We observed the changes in feces, mental state, and activity of each group of mice. After killing, we collected kidneys and colon for H&E staining. We collected mouse feces for the 16S RNA sequencing of bacteria.

RESULTS: All CRF mice injected with different concentrations of cefoperazone/sulbactam experienced grade-V seizures and eventually died, whereas normal control mice did not. However, after FMT intervention, the time of epilepsy onset and death in mice was delayed. Early FMT intervention resulted in more mice surviving (p = .0359). Moreover, the villi in the mucosal of group-CS layer fell off, goblet cells missed, and crypts disappeared. The mucosal layer and submucosa were clearly separated. The morphology of intestinal tissue of the CFS and FS group was improved. After FMT, the changes of the GM were observed.

CONCLUSIONS: The GM may be involved in the epilepsy induced by cefoperazone/sulbactam in CRF mice. FMT can delay the onset of epilepsy in CRF mice induced by cefoperazone/sulbactam, and the earlier the intervention, the better the effect.

RevDate: 2024-06-27

Sun J, Teng M, Zhu W, et al (2024)

MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.

ACS nano [Epub ahead of print].

Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F0 and F1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F0 and F1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.

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Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
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E-mail: RJR8222 @ gmail.com

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin and even a collection of poetry — Chicago Poems by Carl Sandburg.

Timelines

ESP now offers a large collection of user-selected side-by-side timelines (e.g., all science vs. all other categories, or arts and culture vs. world history), designed to provide a comparative context for appreciating world events.

Biographies

Biographical information about many key scientists (e.g., Walter Sutton).

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )