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Gut Microbes 2021is a genus of anaerobic bacteria with probiotic characteristics that occur widely in the feces and intestines of mammals. Based on phenotypic and phylogenetic analyses,... (Review)
Review
is a genus of anaerobic bacteria with probiotic characteristics that occur widely in the feces and intestines of mammals. Based on phenotypic and phylogenetic analyses, some species in the genera and have been reclassified as , so to date, there are 20 new species with valid published names in this genus. An extensive body of research has recently focused on the probiotic effects of this genus, such as biological transformation and its ability to regulate host health and alleviate metabolic syndrome. This article reviews the origin and biological characteristics of and the factors that affect its abundance and discusses its role in host health, thus laying a theoretical foundation for the development of new functional microorganisms with probiotic properties.
Topics: Animals; Biotransformation; Clostridiales; Gastrointestinal Microbiome; Genomics; Humans; Inflammation; Metabolic Syndrome; Phylogeny; Probiotics
PubMed: 33525961
DOI: 10.1080/19490976.2021.1875796 -
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 -
Biomedicines Feb 2022Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor... (Review)
Review
Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases. Emerging evidence shows that gut microbiota have significant roles in maintaining adequate concentrations of dopamine via intricate, bidirectional communication known as the microbiota-gut-brain axis. The vagus nerve, immune system, hypothalamus-pituitary-adrenal axis, and microbial metabolites serve as important mediators of the reciprocal microbiota-gut-brain signaling. Furthermore, gut microbiota contain intrinsic enzymatic activity that is highly involved in dopamine metabolism, facilitating dopamine synthesis as well as its metabolite breakdown. This review examines the relationship between key genera of gut microbiota such as and and their effects on dopamine. The effects of gut dysbiosis on dopamine bioavailability and the subsequent impact on dopamine-related pathological conditions such as Parkinson's disease are also discussed. Understanding the role of gut microbiota in modulating dopamine activity and bioavailability both in the periphery and in the central nervous system can help identify new therapeutic targets as well as optimize available methods to prevent, delay, or restore dopaminergic deficits in neurologic and metabolic disorders.
PubMed: 35203645
DOI: 10.3390/biomedicines10020436 -
BMC Cancer Dec 2022Recent studies have shown the relevance of gut microbiota in the occurrence and development of colorectal cancer (CRC), but the causal relationship remains unclear in...
Recent studies have shown the relevance of gut microbiota in the occurrence and development of colorectal cancer (CRC), but the causal relationship remains unclear in the human population. The present study aims to assess the causal relationship from the gut microbiota to CRC and to identify specific causal microbe taxa via genome-wide association study (GWAS) summary statistics based two-sample Mendelian randomization (MR) analyses. Microbiome GWAS (MGWAS) in the TwinsUK 1,126 twin pairs was used as discovery exposure sample, and MGWAS in 1,812 northern German participants was used as replication exposure sample. GWAS of CRC in 387,156 participants from the UK Biobank (UKB) was used as the outcome sample. Bacteria were grouped into taxa features at both family and genus levels. In the discovery sample, a total of 30 bacteria features including 15 families and 15 genera were analyzed. Five features, including 2 families (Verrucomicrobiaceae and Enterobacteriaceae) and 3 genera (Akkermansia, Blautia, and Ruminococcus), were nominally significant. In the replication sample, the genus Blautia (discovery beta=-0.01, P = 0.04) was successfully replicated (replication beta=-0.18, P = 0.01) with consistent effect direction. Our findings identified genus Blautia that was causally associated with CRC, thus offering novel insights into the microbiota-mediated CRC development mechanism.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Colorectal Neoplasms; Polymorphism, Single Nucleotide
PubMed: 36585646
DOI: 10.1186/s12885-022-10483-w -
Cell Metabolism Oct 2021Accumulating evidence suggests that the gut microbiota regulates obesity through metabolite-host interactions. However, the mechanisms underlying such interactions have...
Accumulating evidence suggests that the gut microbiota regulates obesity through metabolite-host interactions. However, the mechanisms underlying such interactions have been unclear. Here, we found that intestinal hypoxia-inducible factor 2α (HIF-2α) positively regulates gut lactate by controlling the expression of intestinal Ldha. Intestine-specific HIF-2α ablation in mice resulted in lower lactate levels, and less Bacteroides vulgatus and greater Ruminococcus torques abundance, respectively. Together, these changes resulted in elevated taurine-conjugated cholic acid (TCA) and deoxycholic acid (DCA) levels and activation of the adipose G-protein-coupled bile acid receptor, GPBAR1 (TGR5). This activation upregulated expression of uncoupling protein (UCP) 1 and mitochondrial creatine kinase (CKMT) 2, resulting in elevation of white adipose tissue thermogenesis. Administration of TCA and DCA mirrored these phenotypes, and colonization with B. vulgatus and R. torques inhibited and induced thermogenesis, respectively. This work deepens our understanding of how host genes regulate the microbiome and provides novel strategies for alleviating obesity.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Gastrointestinal Microbiome; Hypoxia; Lactic Acid; Mice; Mice, Inbred C57BL; Receptors, G-Protein-Coupled; Thermogenesis; Uncoupling Protein 1
PubMed: 34329568
DOI: 10.1016/j.cmet.2021.07.007 -
Cell Host & Microbe Apr 2020Secondary bile acids (SBAs) are derived from primary bile acids (PBAs) in a process reliant on biosynthetic capabilities possessed by few microbes. To evaluate the role...
Secondary bile acids (SBAs) are derived from primary bile acids (PBAs) in a process reliant on biosynthetic capabilities possessed by few microbes. To evaluate the role of BAs in intestinal inflammation, we performed metabolomic, microbiome, metagenomic, and transcriptomic profiling of stool from ileal pouches (surgically created resevoirs) in colectomy-treated patients with ulcerative colitis (UC) versus controls (familial adenomatous polyposis [FAP]). We show that relative to FAP, UC pouches have reduced levels of lithocholic acid and deoxycholic acid (normally the most abundant gut SBAs), genes required to convert PBAs to SBAs, and Ruminococcaceae (one of few taxa known to include SBA-producing bacteria). In three murine colitis models, SBA supplementation reduces intestinal inflammation. This anti-inflammatory effect is in part dependent on the TGR5 bile acid receptor. These data suggest that dysbiosis induces SBA deficiency in inflammatory-prone UC patients, which promotes a pro-inflammatory state within the intestine that may be treated by SBA restoration.
Topics: Adenomatous Polyposis Coli; Animals; Bile Acids and Salts; Colitis; Colonic Pouches; Disease Models, Animal; Dysbiosis; Feces; Humans; Inflammation; Intestines; Metagenome; Mice; Microbiota; Receptors, G-Protein-Coupled; Ruminococcus; Transcriptome
PubMed: 32101703
DOI: 10.1016/j.chom.2020.01.021 -
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 -
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 -
European Journal of Nutrition Jun 2021Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to...
PURPOSE
Inulin is a type of fermentable dietary fiber, which is non-digestible, and can improve metabolic function by modulating intestinal microbiota. This study aimed to evaluate the role of inulin in hyperuricemia and microbial composition of the gut microbiota in a mouse model of hyperuricemia established through knockout of Uox (urate oxidase) gene.
METHODS
KO (Uox-knockout) and WT (wild-type) mice were given inulin or saline by gavage for 7 weeks. The effect of inulin to combat hyperuricemia was determined by assessing the changes in serum UA (uric acid) levels, inflammatory parameters, epithelial barrier integrity, fecal microbiota alterations, and SCFA (short-chain fatty acid) concentrations in KO mice.
RESULTS
Inulin supplementation can effectively alleviate hyperuricemia, increase the expressions of ABCG2 in intestine, and downregulate expression and activity of hepatic XOD (xanthine oxidase) in KO mice. It was revealed that the levels of inflammatory cytokines and the LPS (lipopolysaccharide) were remarkably higher in the KO group than those in the WT group, indicating systemic inflammation of hyperuricemic mice, but inulin treatment ameliorated inflammation in KO mice. Besides, inulin treatment repaired the intestinal epithelial barrier as evidenced by increased levels of intestinal TJ (tight junction) proteins [ZO-1 (zonula occludens-1) and occluding] in KO mice. Moreover, serum levels of uremic toxins, including IS (indoxyl sulfate) and PCS (p-cresol sulfate), were reduced in inulin-treated KO mice. Further investigation unveiled that inulin supplementation enhanced microbial diversity and raised the relative abundance of beneficial bacteria, involving SCFAs-producing bacteria (e.g., Akkermansia and Ruminococcus). Additionally, inulin treatment increased the production of gut microbiota-derived SCFAs (acetate, propionate and butyrate concentrations) in KO mice, which was positively correlated with the effectiveness of hyperuricemia relief.
CONCLUSIONS
Our findings showed that inulin may be a promising therapeutic candidate for the treatment of hyperuricemia. Moreover, alleviation of hyperuricemia by inulin supplementation was, at least, partially conciliated by modulation of gut microbiota and its metabolites.
Topics: Animals; Dietary Supplements; Gastrointestinal Microbiome; Hyperuricemia; Inulin; Mice; Mice, Knockout
PubMed: 33104864
DOI: 10.1007/s00394-020-02414-x -
ELife May 2021Culture-independent analyses of microbial communities have progressed dramatically in the last decade, particularly due to advances in methods for biological profiling...
Culture-independent analyses of microbial communities have progressed dramatically in the last decade, particularly due to advances in methods for biological profiling via shotgun metagenomics. Opportunities for improvement continue to accelerate, with greater access to multi-omics, microbial reference genomes, and strain-level diversity. To leverage these, we present bioBakery 3, a set of integrated, improved methods for taxonomic, strain-level, functional, and phylogenetic profiling of metagenomes newly developed to build on the largest set of reference sequences now available. Compared to current alternatives, MetaPhlAn 3 increases the accuracy of taxonomic profiling, and HUMAnN 3 improves that of functional potential and activity. These methods detected novel disease-microbiome links in applications to CRC (1262 metagenomes) and IBD (1635 metagenomes and 817 metatranscriptomes). Strain-level profiling of an additional 4077 metagenomes with StrainPhlAn 3 and PanPhlAn 3 unraveled the phylogenetic and functional structure of the common gut microbe , previously described by only 15 isolate genomes. With open-source implementations and cloud-deployable reproducible workflows, the bioBakery 3 platform can help researchers deepen the resolution, scale, and accuracy of multi-omic profiling for microbial community studies.
Topics: Bacteria; Computational Biology; Humans; Metagenome; Metagenomics; Microbiota; Phylogeny; Research Personnel; Ruminococcus; Workflow
PubMed: 33944776
DOI: 10.7554/eLife.65088