Commensal intestinal microbiota regulates host luminal proteolytic activity and intestinal barrier integrity through β-glucuronidase activity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
TISSUE(S): Feces
DISEASE(S): Irritable Bowel Syndrome
PROVIDER: ST001718 | MetabolomicsWorkbench |
REPOSITORIES: MetabolomicsWorkbench
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| mwtab | Other |
Items per page: 5 1 - 1 of 1 |
Similar Datasets
Project description: Not available
| ST002094 | MetabolomicsWorkbench
Project description: Not available
| ST002090 | MetabolomicsWorkbench
Project description:BACKGROUND:Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale. RESULTS:We depleted the intestinal microbiota of hypercholesterolemic female Apoe-/- mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated to Betaproteobacteria, Alistipes, Bacteroides, and Barnesiella taxa. CONCLUSIONS:These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.
| S-EPMC6882370 | biostudies-literature
Project description:Low-molecular-weight metabolites produced by intestinal microbiota play a direct role in health and disease. In this study, we analyzed the colonic luminal metabolome using capillary electrophoresis mass spectrometry with time-of-flight (CE-TOFMS) -a novel technique for analyzing and differentially displaying metabolic profiles- in order to clarify the metabolite profiles in the intestinal lumen. CE-TOFMS identified 179 metabolites from the colonic luminal metabolome and 48 metabolites were present in significantly higher concentrations and/or incidence in the germ-free (GF) mice than in the Ex-GF mice (p < 0.05), 77 metabolites were present in significantly lower concentrations and/or incidence in the GF mice than in the Ex-GF mice (p < 0.05), and 56 metabolites showed no differences in the concentration or incidence between GF and Ex-GF mice. These indicate that intestinal microbiota highly influenced the colonic luminal metabolome and a comprehensive understanding of intestinal luminal metabolome is critical for clarifying host-intestinal bacterial interactions.
| S-EPMC3380406 | biostudies-literature
Project description:The intestinal tract contains many commensal bacteria that modulate various physiological host functions. Dysbiosis of commensal bacteria triggers dysfunction of the intestinal epithelial barrier, leading to the induction or aggravation of intestinal inflammation. To elucidate whether microRNA plays a role in commensal microbiome-dependent intestinal epithelial barrier regulation, we compared transcripts in intestinal epithelial cells (IECs) from conventional and germ-free mice and found that commensal bacteria induced the expression of miR-21-5p in IECs. miR-21-5p increased intestinal epithelial permeability and up-regulated ADP ribosylation factor 4 (ARF4), a small GTPase, in the IEC line Caco-2. We also found that ARF4 expression was up-regulated upon suppression of phosphatase and tensin homolog (PTEN) and programmed cell death 4 (PDCD4), which are known miR-21-5p targets, by RNAi. Furthermore, ARF4 expression in epithelial cells of the large intestine was higher in conventional mice than in germ-free mice. ARF4 suppression in the IEC line increased the expression of tight junction proteins and decreased intestinal epithelial permeability. These results indicate that commensal microbiome-dependent miR-21-5p expression in IECs regulates intestinal epithelial permeability via ARF4, which may therefore represent a target for preventing or managing dysfunction of the intestinal epithelial barrier.
| S-EPMC5602400 | biostudies-literature
Project description:Intestinal mucus forms the first line of defense against bacterial invasion while providing nutrition to support microbial symbiosis. How the host controls mucus barrier integrity and commensalism is unclear. We show that terminal sialylation of glycans on intestinal mucus by ST6GALNAC1 (ST6), the dominant sialyltransferase specifically expressed in goblet cells and induced by microbial pathogen-associated molecular patterns, is essential for mucus integrity and protecting against excessive bacterial proteolytic degradation. Glycoproteomic profiling and biochemical analysis of ST6 mutations identified in patients show that decreased sialylation causes defective mucus proteins and congenital inflammatory bowel disease (IBD). Mice harboring a patient ST6 mutation have compromised mucus barriers, dysbiosis, and susceptibility to intestinal inflammation. Based on our understanding of the ST6 regulatory network, we show that treatment with sialylated mucin or a Foxo3 inhibitor can ameliorate IBD.
| S-EPMC9088855 | biostudies-literature
Project description:The intestinal microbiome produces various metabolites that may harm or benefit the host. However, the production pathways of these metabolites have not been well characterised. The polyamines putrescine and spermidine required for physiological process are also produced by intestinal microbiome. The production and release of these polyamines by microbiome are poorly understood, though we have confirmed that intestinal bacteria produced putrescine from arginine. In this study, we characterised polyamine synthesis by analysing the collective metabolic functions of the intestinal microbiome. In particular, we analysed polyamines and their intermediates in faecal cultures, as well as the colonic contents of rats injected with isotope-labelled arginine through a colon catheter, using mass spectrometry. Isotope-labelled putrescine was detected in faecal cultures and colonic contents of rats injected with isotope-labelled arginine. Putrescine is produced through multiple pathways, and its extracellular intermediates are exchanged between bacterial species. Additionally, we demonstrated that the collective metabolic pathway depends on a complex exchange of metabolites released into the colonic lumen. This study demonstrates the existence of putrescine biosynthetic pathways based on the collective metabolic functions of the intestinal microbial community. Our findings provide knowledge to manipulate the levels of intestinal microbial products, including polyamines, that may modulate host health.
| S-EPMC6546329 | biostudies-literature
Project description:Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory disorders of the gastrointestinal tract with complex etiology and no strategies for complete cure. IBD are often complicated by mental disorders like anxiety and depression, indicating substantial shifts in the microbiota gut-brain axis. However, the mechanisms connecting IBD to mental diseases are still under debate. Here we use Muc2 knockout mouse model of chronic colitis to uncouple the effects of the intestinal microbiota on host behavior from chronic inflammation in the gut. Muc2 knockout male mice exhibit high exploratory activity, reduced anxiety-related behaviors, impaired sensorimotor gating, and altered social preference towards males and females. Microbial transfer to wild-type mice via littermate co-housing shows that colitis-associated microbiota rather than inflammation per se defines behavioral features in Muc2 colitis model. Metagenomic profiling and combination of antibiotic treatments revealed that bacterial species Akkermansia muciniphila is associated with the behavioral phenotype in mutants, and that its intestinal abundance correlates with social preference towards males. Metabolomic analysis together with pharmacological inhibition of Gly and NMDA receptors helped us to determine that brain glycine is responsible for the behavioral phenotype in Muc2 mice. Blood and brain metabolic profiles suggest that microbiota-dependent changes in choline metabolism might be involved in regulation of central glycine neurotransmission. Taken together, our data demonstrates that colitis-associated microbiota controls anxiety, sensorimotor gating and social behavior via metabolic regulation of the brain glycinergic system, providing new venues to combat neurological complications of IBD.
| S-EPMC9522854 | biostudies-literature
Project description:The epidermis forms a barrier that defends the body from desiccation and entry of harmful substances, while also sensing and integrating environmental signals. The tightly orchestrated cellular changes needed for the formation and maintenance of this epidermal barrier occur in the context of the skin microbiome. Using germ-free mice, we demonstrate the microbiota is necessary for proper differentiation and repair of the epidermal barrier. These effects are mediated by microbiota signaling through the aryl hydrocarbon receptor (AHR) in keratinocytes, a xenobiotic receptor also implicated in epidermal differentiation. Mice lacking keratinocyte AHR are more susceptible to barrier damage and infection, during steady-state and epicutaneous sensitization. Colonization with a defined consortium of human skin isolates restored barrier competence in an AHR-dependent manner. We reveal a fundamental mechanism whereby the microbiota regulates skin barrier formation and repair, which has far-reaching implications for the numerous skin disorders characterized by epidermal barrier dysfunction.
| S-EPMC8364505 | biostudies-literature
Project description:Melatonin has various physiological effects, such as the maintenance of circadian rhythms, anti-inflammatory functions, and regulation of intestinal barriers. The regulatory functions of melatonin in gut microbiota remodeling have also been well clarified; however, the role of gut microbiota in regulating host melatonin production remains poorly understood. To address this, we studied the contribution of gut microbiota to host melatonin production using gut microbiota-perturbed models. We demonstrated that antibiotic-treated and germ-free mice possessed diminished melatonin levels in the serum and elevated melatonin levels in the colon. The influence of the intestinal microbiota on host melatonin production was further confirmed by fecal microbiota transplantation. Notably, Lactobacillus reuteri (L. R) and Escherichia coli (E. coli) recapitulated the effects of gut microbiota on host melatonin production. Mechanistically, L. R and E. coli activated the TLR2/4/MyD88/NF-κB signaling pathway to promote expression of arylalkylamine N-acetyltransferase (AANAT, a rate-limiting enzyme for melatonin production), and MyD88 deficiency in colonic epithelial cells abolished the influence of intestinal microbiota on colonic melatonin production. Collectively, we revealed a specific underlying mechanism of gut microbiota to modulate host melatonin production, which might provide novel therapeutic ideas for melatonin-related diseases.
| S-EPMC10868534 | biostudies-literature