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Diabetes, Metabolic Syndrome and... 2024( is a gram-positive anaerobe commonly resides in the human gut microbiota. The advent of metagenomics has linked with various diseases, including inflammatory bowel... (Review)
Review
( is a gram-positive anaerobe commonly resides in the human gut microbiota. The advent of metagenomics has linked with various diseases, including inflammatory bowel disease (IBD), obesity, and diabetes mellitus (DM), which has become a growing area of investigation. The initial focus of research primarily centered on assessing the abundance of and its potential association with disease presentation, taking into account variations in sample size, sequencing and analysis methods. However, recent investigations have shifted towards elucidating the underlying mechanistic pathways through which may contribute to disease manifestation. In this comprehensive review, we aim to provide an updated synthesis of the current literature on in the context of IBD, obesity, and DM. We critically analyze relevant studies and summarize the potential molecular mediators implicated in the association between and these diseases. Across numerous studies, various molecules such as methylation-controlled J (MCJ), glucopolysaccharides, ursodeoxycholic acid (UDCA), interleukin(IL)-10, IL-17, and capric acid have been proposed as potential contributors to the link between and IBD. Similarly, in the realm of obesity, molecules such as hydrogen peroxide, butyrate, and UDCA have been suggested as potential mediators, while glycine ursodeoxycholic acid (GUDCA) has been implicated in the connection between and DM. Furthermore, it is imperative to emphasize the necessity for additional studies to evaluate the potential efficacy of targeting pathways associated with as a viable strategy for managing these diseases. These findings have significantly expanded our understanding of the functional role of in the context of IBD, obesity, and DM. This review aims to offer updated insights into the role and potential mechanisms of , as well as potential strategies for the treatment of these diseases.
PubMed: 38496006
DOI: 10.2147/DMSO.S456173 -
Gut Microbes 2023is a prevalent gut microbe reported to occur in higher abundance among individuals with inflammatory bowel disease (IBD). This study reports the isolation and...
is a prevalent gut microbe reported to occur in higher abundance among individuals with inflammatory bowel disease (IBD). This study reports the isolation and characterization of six bacteriophages (phages) isolated from human fecal material and environmental samples that infect this species. Isolated phages have a siphovirus morphology, with genomes ranging between 36.5 and 37.8 kbp. Genome analysis indicates that the phages have a temperate lifestyle, which was confirmed by their ability to form lysogens on their host bacterial species. In contrast to the finding that phages lyse their host in liquid medium, results from a mouse trial indicate these phages can co-exist with the host bacterium in the gut without causing a significant reduction of . The bacterial counts in the feces of phage-treated mice did not significantly differ in the presence of phage. Furthermore, analysis of publicly available gut virome sequence data indicates a high abundance of these phages among individuals suffering from IBD. This work provides the first insight into how phages interact with in the human gut microbiome.
Topics: Humans; Mice; Animals; Bacteriophages; Mucins; Ruminococcus; Gastrointestinal Microbiome; Bacteria; Inflammatory Bowel Diseases
PubMed: 36994608
DOI: 10.1080/19490976.2023.2194794 -
Gastroenterology Jun 2024Chronic visceral pain is one of the most common reasons for patients with gastrointestinal disorders, such as inflammatory bowel disease or disorders of brain-gut... (Review)
Review
Chronic visceral pain is one of the most common reasons for patients with gastrointestinal disorders, such as inflammatory bowel disease or disorders of brain-gut interaction, to seek medical attention. It represents a substantial burden to patients and is associated with anxiety, depression, reductions in quality of life, and impaired social functioning, as well as increased direct and indirect health care costs to society. Unfortunately, the diagnosis and treatment of chronic visceral pain is difficult, in part because our understanding of the underlying pathophysiologic basis is incomplete. In this review, we highlight recent advances in peripheral pain signaling and specific physiologic and pathophysiologic preclinical mechanisms that result in the sensitization of peripheral pain pathways. We focus on preclinical mechanisms that have been translated into treatment approaches and summarize the current evidence base for directing treatment toward these mechanisms of chronic visceral pain derived from clinical trials. The effective management of chronic visceral pain remains of critical importance for the quality of life of suffers. A deeper understanding of peripheral pain mechanisms is necessary and may provide the basis for novel therapeutic interventions.
Topics: Humans; Visceral Pain; Chronic Pain; Animals; Quality of Life; Signal Transduction
PubMed: 38325759
DOI: 10.1053/j.gastro.2024.01.045 -
Internal and Emergency Medicine Aug 2023This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases... (Review)
Review
This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases involving the IL-17 and NF-κB signaling pathways. Inflammatory cytokines including TNF-α and Th17 cells in CD patients can induce activation of the ERK1/2, NF-κB and Bcl-2 pathways. Hub genes are involved in the generation of cancer stem cells (CSCs) and are related to inflammatory mediators, including CXCL8, IL1-β and PTGS2, which promote inflammation and breast cancer growth, metastasis, and development. CD activity is highly associated with altered intestinal microbiota processes, including secretion of complex glucose polysaccharides by Ruminococcus gnavus colonies; furthermore, γ-proteobacteria and Clostridium are associated with CD recurrence and active CD, while Ruminococcaceae, Faecococcus and Vibrio desulfuris are associated with CD remission. Intestinal microbiota disorder promotes breast cancer occurrence and development. Bacteroides fragilis can produce toxins that induce breast epithelial hyperplasia and breast cancer growth and metastasis. Gut microbiota regulation can also improve chemotherapy and immunotherapy efficacy in breast cancer treatment. Intestinal inflammation can affects the brain through the brain-gut axis, which activates the hypothalamic‒pituitary‒adrenal (HPA) axis to induce anxiety and depression in patients; these effects can inhibit the antitumor immune responses of the immune system and promote breast cancer occurrence in patients with CD. There are few studies on the treatment of patients with CD concomitant with breast cancer, but published studies show three main strategies: new biological agents combined with breast cancer treatment methods, intestinal fecal bacteria transplantation, and dietary treatment.
Topics: Humans; Female; Crohn Disease; NF-kappa B; Breast Neoplasms; Intestinal Mucosa; Neoplasm Recurrence, Local; Inflammation
PubMed: 37138170
DOI: 10.1007/s11739-023-03281-0 -
Frontiers in Microbiology 2018Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the...
Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities. Here, we focused on two major human gut symbionts, the mucin-degrader ATCC 29149, and L2-63, a keystone species for the degradation of resistant starch (RS) in human colon. Using anaerobic individual and co-cultures of and grown on mucin or starch as sole carbon source, we showed that starch degradation by supported the growth of whereas did not benefit from mucin degradation by . Further we analyzed the growth (quantitative PCR), metabolite production (H NMR analysis), and bacterial transcriptional response (RNA-Seq) of cultured with RS or soluble starch (SS) in the presence or absence of . In co-culture fermentations on starch, H NMR analysis showed that benefits from transient glucose and malto-oligosaccharides released by upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products. Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of induced changes in transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of to utilize starch degradation products. In the RS co-culture, showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of . Together this study showed a direct competition between and on RS, suggesting that , the population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
PubMed: 30455672
DOI: 10.3389/fmicb.2018.02558 -
BMC Microbiology Apr 2024Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional... (Meta-Analysis)
Meta-Analysis
Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.
Topics: Humans; Gastrointestinal Microbiome; Metagenome; Obesity; Bacteria; Feces; Clostridiales; Akkermansia
PubMed: 38580930
DOI: 10.1186/s12866-024-03278-5 -
Translational Psychiatry Nov 2023Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently...
Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.
Topics: Adult; Humans; Microbiota; Stress Disorders, Post-Traumatic; Gastrointestinal Microbiome; Feces; Biological Availability
PubMed: 37980332
DOI: 10.1038/s41398-023-02643-8 -
Pharmacological Research Mar 2023The gut microbiome is closely shaped by host genetic and dietary factors to regulate metabolic health and disease. However, the signaling mechanisms underlying such...
The gut microbiome is closely shaped by host genetic and dietary factors to regulate metabolic health and disease. However, the signaling mechanisms underlying such interactions have been largely unclear. Here we identify G protein-coupled receptor 35 (Gpr35) as a regulator of gut microbial ecology and the susceptibility to obesity and hepatic steatosis in mice. Both global and intestinal epithelia specific ablation of Gpr35 aggravated high-fat diet (HFD)-induced metabolic disturbance and hepatic steatosis in mice. Gpr35 deficiency induced a remarkable loss of goblet cells and an extensive remodeling of the gut microbiome, featuring enrichment of the Bacteroides and Ruminococcus genera. Antibiotics treatment and co-housing alleviated the metabolic disturbance markers in Gpr35 deficient mice. Spatiotemporal profiling and mono-colonization screening revealed that Ruminococcus gnavus synergized with HFD to promote hepatic steatosis possibly via tryptophan and phenylalanine pathway metabolites. Our results provide mechanistic insights into a genetic-diet-microbe interplay that dictates susceptibility to metabolic disorder.
Topics: Mice; Animals; Gastrointestinal Microbiome; Fatty Liver; Receptors, G-Protein-Coupled; Obesity; Diet, High-Fat; Mice, Inbred C57BL; Liver
PubMed: 36758734
DOI: 10.1016/j.phrs.2023.106690 -
BMC Microbiology Oct 2023The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and...
BACKGROUND
The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP.
METHODS
We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites.
RESULTS
An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP.
CONCLUSIONS
Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.
Topics: Humans; Female; Pregnancy; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Feces; Bile Acids and Salts; Hypoxanthines
PubMed: 37784030
DOI: 10.1186/s12866-023-02983-x -
Access Microbiology 2023, a Gram-positive anaerobic coccus, is a common constituent of the human gut microbiota but rarely causes any disease in humans. Herein, we report a case of...
, a Gram-positive anaerobic coccus, is a common constituent of the human gut microbiota but rarely causes any disease in humans. Herein, we report a case of bacteraemia in an immunocompromised 73-year-old man with sigmoid colon perforation. is usually reported as Gram-positive diplococci or short chains on Gram staining; however, in our patient, a blood isolate showed Gram-positive cocci in long chains, and organisms from an anaerobic subculture showed morphological diversity. This case provides insight into the morphological diversity of , which might help with the recognition of these bacteria in the preliminary identification stage on Gram staining.
PubMed: 37424554
DOI: 10.1099/acmi.0.000442