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FEMS Microbiology Reviews Mar 2023Ruminococcus gnavus was first identified in 1974 as a strict anaerobe in the gut of healthy individuals, and for several decades, its study has been limited to specific... (Review)
Review
Ruminococcus gnavus was first identified in 1974 as a strict anaerobe in the gut of healthy individuals, and for several decades, its study has been limited to specific enzymes or bacteriocins. With the advent of metagenomics, R. gnavus has been associated both positively and negatively with an increasing number of intestinal and extraintestinal diseases from inflammatory bowel diseases to neurological disorders. This prompted renewed interest in understanding the adaptation mechanisms of R. gnavus to the gut, and the molecular mediators affecting its association with health and disease. From ca. 250 publications citing R. gnavus since 1990, 94% were published in the last 10 years. In this review, we describe the biological characterization of R. gnavus, its occurrence in the infant and adult gut microbiota and the factors influencing its colonization of the gastrointestinal tract; we also discuss the current state of our knowledge on its role in host health and disease. We highlight gaps in knowledge and discuss the hypothesis that differential health outcomes associated with R. gnavus in the gut are strain and niche specific.
Topics: Adult; Humans; Gastrointestinal Microbiome; Gastrointestinal Tract; Ruminococcus
PubMed: 37015876
DOI: 10.1093/femsre/fuad014 -
Nature Reviews. Microbiology Aug 2019Perturbations in the intestinal microbiome are implicated in inflammatory bowel disease (IBD). Studies of treatment-naive patients have identified microbial taxa... (Review)
Review
Perturbations in the intestinal microbiome are implicated in inflammatory bowel disease (IBD). Studies of treatment-naive patients have identified microbial taxa associated with disease course and treatment efficacy. To gain a mechanistic understanding of how the microbiome affects gastrointestinal health, we need to move from census to function. Bacteria, including those that adhere to epithelial cells as well as several Clostridium species, can alter differentiation of T helper 17 cells and regulatory T cells. Similarly, microbial products such as short-chain fatty acids and sphingolipids also influence immune responses. Metagenomics and culturomics have identified strains of Ruminococcus gnavus and adherent invasive Escherichia coli that are linked to IBD and gut inflammation. Integrated analysis of multiomics data, including metagenomics, metatranscriptomics and metabolomics, with measurements of host response and culturomics, have great potential in understanding the role of the microbiome in IBD. In this Review, we highlight current knowledge of gut microbial factors linked to IBD pathogenesis and discuss how multiomics data from large-scale population studies in health and disease have been used to identify specific microbial strains, transcriptional changes and metabolic alterations associated with IBD.
Topics: Bacterial Adhesion; Biological Factors; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Immunologic Factors; Inflammatory Bowel Diseases; Microbiota; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 31249397
DOI: 10.1038/s41579-019-0213-6 -
Journal of the International Society of... 2016Fatigue, mood disturbances, under performance and gastrointestinal distress are common among athletes during training and competition. The psychosocial and physical... (Review)
Review
Fatigue, mood disturbances, under performance and gastrointestinal distress are common among athletes during training and competition. The psychosocial and physical demands during intense exercise can initiate a stress response activating the sympathetic-adrenomedullary and hypothalamus-pituitary-adrenal (HPA) axes, resulting in the release of stress and catabolic hormones, inflammatory cytokines and microbial molecules. The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including metabolism, endocrine, neuronal and immune function. The gut microbiome and its influence on host behavior, intestinal barrier and immune function are believed to be a critical aspect of the brain-gut axis. Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition. For instance, induced exercise-stress decreased cecal levels of spp and increased which have well defined roles in intestinal mucus degradation and immune function. Diet is known to dramatically modulate the composition of the gut microbiota. Due to the considerable complexity of stress responses in elite athletes (from leaky gut to increased catabolism and depression), defining standard diet regimes is difficult. However, some preliminary experimental data obtained from studies using probiotics and prebiotics studies show some interesting results, indicating that the microbiota acts like an endocrine organ (e.g. secreting serotonin, dopamine or other neurotransmitters) and may control the HPA axis in athletes. What is troubling is that dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides, which is associated with reduced microbiota diversity and functionality (e.g. less synthesis of byproducts such as short chain fatty acids and neurotransmitters). As more elite athletes suffer from psychological and gastrointestinal conditions that can be linked to the gut, targeting the microbiota therapeutically may need to be incorporated in athletes' diets that take into consideration dietary fiber as well as microbial taxa not currently present in athlete's gut.
Topics: Athletes; Athletic Performance; Brain; Diet; Food; Gastrointestinal Microbiome; Gastrointestinal Tract; Hormones; Humans; Probiotics; Sports Nutritional Physiological Phenomena; Stress, Psychological
PubMed: 27924137
DOI: 10.1186/s12970-016-0155-6 -
Journal of Affective Disorders Jun 2019Depression is the leading cause of disability worldwide; with evidence suggesting that decreased gut barrier function and inflammation are correlated with depressive... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Depression is the leading cause of disability worldwide; with evidence suggesting that decreased gut barrier function and inflammation are correlated with depressive symptoms. We conducted a clinical trial to determine the effect of consumption of probiotic supplements (Winclove's Ecologic® Barrier) on depressive symptoms in a sample of participants with mild to severe depression.
METHOD
71 participants were randomly allocated to either probiotic or placebo, which was, consumed daily over eight weeks. Pre- and post-intervention measures of symptoms and vulnerability markers of depression as well as gut microbiota composition were compared. Clinical trial participants were also compared on psychological variables and gut microbiota composition to a non-depressed group (n = 20).
RESULTS
All clinical trial participants demonstrated improvement in symptoms, suggesting non-specific therapeutic effects associated with weekly monitoring visits. Participants in the probiotic group demonstrated a significantly greater reduction in cognitive reactivity compared with the placebo group, particularly in the mild/moderate subgroup. Probiotics did not significantly alter the microbiota of depressed individuals, however, a significant correlation was found between Ruminococcus gnavus and one depression metric.
LIMITATIONS
There was a high attrition rate, which may be attributed to weekly monitoring visits. Additionally, modulation of the gut microbiota may need more specific testing to distinguish subtle changes.
CONCLUSIONS
While microbiota composition was similar between all groups, probiotics did affect a psychological variable associated with susceptibility to depression. Further research is needed to investigate how probiotics can be utilised to modify mental wellbeing, and whether they can act as an adjunct to existing treatments.
Topics: Adult; Depression; Dietary Supplements; Female; Gastrointestinal Microbiome; Humans; Male; Placebos; Probiotics; Research Design
PubMed: 31078831
DOI: 10.1016/j.jad.2019.04.097 -
Cell Sep 2020The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to...
The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.
Topics: Animals; Bile Acids and Salts; Biopsy; Butyrates; Chromatography, Liquid; Cross-Sectional Studies; Epigenomics; Feces; Female; Gastrointestinal Microbiome; Gene Expression Regulation; Host Microbial Interactions; Humans; Hypoxanthine; Irritable Bowel Syndrome; Longitudinal Studies; Male; Metabolome; Mice; Observational Studies as Topic; Prospective Studies; Purines; Software; Tandem Mass Spectrometry; Transcriptome
PubMed: 32916129
DOI: 10.1016/j.cell.2020.08.007 -
Cell Host & Microbe Jan 2023Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that...
Diarrhea-predominant irritable bowel syndrome (IBS-D), a globally prevalent functional gastrointestinal (GI) disorder, is associated with elevated serotonin that increases gut motility. While anecdotal evidence suggests that the gut microbiota contributes to serotonin biosynthesis, mechanistic insights are limited. We determined that the bacterium Ruminococcus gnavus plays a pathogenic role in IBS-D. Monocolonization of germ-free mice with R. gnavus induced IBS-D-like symptoms, including increased GI transit and colonic secretion, by stimulating the production of peripheral serotonin. R. gnavus-mediated catabolism of dietary phenylalanine and tryptophan generated phenethylamine and tryptamine that directly stimulated serotonin biosynthesis in intestinal enterochromaffin cells via a mechanism involving activation of trace amine-associated receptor 1 (TAAR1). This R. gnavus-driven increase in serotonin levels elevated GI transit and colonic secretion but was abrogated upon TAAR1 inhibition. Collectively, our study provides molecular and pathogenetic insights into how gut microbial metabolites derived from dietary essential amino acids affect serotonin-dependent control of gut motility.
Topics: Animals; Mice; Irritable Bowel Syndrome; Serotonin; Diarrhea
PubMed: 36495868
DOI: 10.1016/j.chom.2022.11.006 -
Cell Host & Microbe Mar 2023The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune...
The intestinal microbiota plays an important role in colorectal cancer (CRC) progression. However, the effect of tissue-resident commensal bacteria on CRC immune surveillance remains poorly understood. Here, we analyzed the intratissue bacteria from CRC patient colon tissues. We found that the commensal bacteria belonging to the Lachnospiraceae family, including Ruminococcus gnavus (Rg), Blautia producta (Bp), and Dorea formicigenerans (Df), were enriched in normal tissues, while Fusobacterium nucleatum (Fn) and Peptostreptococcus anaerobius (Pa) were abundant in tumor tissues. Tissue-resident Rg and Bp reduced colon tumor growth and promoted the activation of CD8 T cells in immunocompetent mice. Mechanistically, intratissue Rg and Bp degraded lyso-glycerophospholipids that inhibited CD8 T cell activity and maintained the immune surveillance function of CD8 T cells. Lyso-glycerophospholipids alone promoted tumor growth that was abrogated with Rg and Bp injection. Collectively, intratissue Lachnospiraceae family bacteria facilitate the immune surveillance function of CD8 T cells and control colorectal cancer progression.
Topics: Animals; Mice; Colorectal Neoplasms; CD8-Positive T-Lymphocytes; Carcinogenesis; Colonic Neoplasms; Fusobacterium nucleatum
PubMed: 36893736
DOI: 10.1016/j.chom.2023.01.013 -
Gut Mar 2022Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear.
BACKGROUND
Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear.
OBJECTIVE
To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus.
METHODS
We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months.
RESULTS
At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of , and lower levels of . Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including and (all p<0.05). Butyrate-producing bacteria, including and showed the largest inverse correlations with PACS at 6 months.
CONCLUSION
These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.
Topics: COVID-19; Follow-Up Studies; Gastrointestinal Microbiome; Humans; Metagenomics; Prospective Studies; SARS-CoV-2; Severity of Illness Index; Post-Acute COVID-19 Syndrome
PubMed: 35082169
DOI: 10.1136/gutjnl-2021-325989 -
Journal of Affective Disorders May 2023Several studies have linked gut microbiota to human brain activity. This study used Mendelian randomization (MR) to investigate the causal relationship between gut...
BACKGROUND
Several studies have linked gut microbiota to human brain activity. This study used Mendelian randomization (MR) to investigate the causal relationship between gut microbes and delirium.
METHODS
MR was used to select SNPs from large-scale GWAS summary data on 211 gut microbiota taxa and delirium. Inverse variance weighting (IVW), weighted median, and MR-Egger methods were used for statistical analyses. Outliers were assessed using the leave-one-out method. To avoid horizontal pleiotropy, we performed the MR-PRESSO and MR-Egger intercept tests. Cochran's Q and I values for IVW and MR-Egger were used to assess heterogeneity.
RESULTS
IVW suggested that genetic prediction of the family Desulfovibrionaceae (1.784 (1.267-2.512), P = 0.001), order Desulfovibrionales (1.501 (1.058-2.128), P = 0.023), and genus Candidatus Soleaferrea (1.322 (1.052-1.659), P = 0.016) increased the risk of delirium, but the family Oxalobacteraceae (0.841 (0.722-0.981), P = 0.027), and genera Holdemania (0.766 (0.620-0.946), P = 0.013), Ruminococcus gnavus (0.806 (0.661-0.982), P = 0.033), and Eggerthella (0.815 (0.667-0.997), P = 0.047) reduced the risk of delirium.
LIMITATIONS
(1) Limited sample size, (2) inability to assess gut microbiota interactions, and (3) limited to European populations.
CONCLUSION
Our results suggest that presence of the microbial family Desulfovibrionaceae, order Desulfovibrionales, and genus Candidatus Soleaferrea increased the risk of delirium, whereas the Oxalobacteraceae family, and the genera Holdemania, Ruminococcus gnavus, and Eggerthella decreased the risk of delirium. However, the potential of gut probiotic interventions in the prevention of perioperative delirium should be emphasized.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Causality; Delirium; Genome-Wide Association Study
PubMed: 36842654
DOI: 10.1016/j.jad.2023.02.078 -
Alzheimer's Research & Therapy May 2023Increasing evidence links the gut microbiota (GM) to Alzheimer's disease (AD) but the mechanisms through which gut bacteria influence the brain are still unclear. This...
BACKGROUND
Increasing evidence links the gut microbiota (GM) to Alzheimer's disease (AD) but the mechanisms through which gut bacteria influence the brain are still unclear. This study tests the hypothesis that GM and mediators of the microbiota-gut-brain axis (MGBA) are associated with the amyloid cascade in sporadic AD.
METHODS
We included 34 patients with cognitive impairment due to AD (CI-AD), 37 patients with cognitive impairment not due to AD (CI-NAD), and 13 cognitively unimpaired persons (CU). We studied the following systems: (1) fecal GM, with 16S rRNA sequencing; (2) a panel of putative MGBA mediators in the blood including immune and endothelial markers as bacterial products (i.e., lipopolysaccharide, LPS), cell adhesion molecules (CAMs) indicative of endothelial dysfunction (VCAM-1, PECAM-1), vascular changes (P-, E-Selectin), and upregulated after infections (NCAM, ICAM-1), as well as pro- (IL1β, IL6, TNFα, IL18) and anti- (IL10) inflammatory cytokines; (3) the amyloid cascade with amyloid PET, plasma phosphorylated tau (pTau-181, for tau pathology), neurofilament light chain (NfL, for neurodegeneration), and global cognition measured using MMSE and ADAScog. We performed 3-group comparisons of markers in the 3 systems and calculated correlation matrices for the pooled group of CI-AD and CU as well as CI-NAD and CU. Patterns of associations based on Spearman's rho were used to validate the study hypothesis.
RESULTS
CI-AD were characterized by (1) higher abundance of Clostridia_UCG-014 and decreased abundance of Moryella and Blautia (p < .04); (2) elevated levels of LPS (p < .03), upregulation of CAMs, Il1β, IL6, and TNFα, and downregulation of IL10 (p < .05); (3) increased brain amyloid, plasma pTau-181, and NfL (p < 0.004) compared with the other groups. CI-NAD showed (1) higher abundance of [Eubacterium] coprostanoligenes group and Collinsella and decreased abundance of Lachnospiraceae_ND3007_group, [Ruminococcus]_gnavus_group and Oscillibacter (p < .03); (2) upregulation of PECAM-1 and TNFα (p < .03); (4) increased plasma levels of NfL (p < .02) compared with CU. Different GM genera were associated with immune and endothelial markers in both CI-NAD and CI-AD but these mediators were widely related to amyloid cascade markers only in CI-AD.
CONCLUSIONS
Specific bacterial genera are associated with immune and endothelial MGBA mediators, and these are associated with amyloid cascade markers in sporadic AD. The physiological mechanisms linking the GM to the amyloid cascade should be further investigated to elucidate their potential therapeutic implications.
Topics: Humans; Alzheimer Disease; Tumor Necrosis Factor-alpha; Brain-Gut Axis; Lipopolysaccharides; Platelet Endothelial Cell Adhesion Molecule-1; RNA, Ribosomal, 16S; Interleukin-10; Interleukin-6; NAD; Biomarkers; Amyloid beta-Peptides
PubMed: 37254223
DOI: 10.1186/s13195-023-01218-5