Mouse gut metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1322462 | ENA |
REPOSITORIES: ENA
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Project description:The intestinal mucus layer produced by goblet cells is a critical component of innate immunity. The key host factors and regulatory mechanisms controlling goblet cell function in mucus layer formation remain poorly understood. This study identifies a function for the microprotein FXYD domain-containing transport regulator 3 (FXYD3) in goblet cells in regulating mucus layer formation to maintain intestinal homeostasis. Deficiency of FXYD3 in mouse intestinal epithelial cellsresults in a damaged mucus barrier, leading to microbiota dysbiosis and increased susceptibility to colitis. Mechanistically, FXYD3 interacts with endoplasmic reticulum Ca2+-ATPase SERCA2 to enhances its pump activity. FXYD3 deficiency causes defects in ER Ca2+ homeostasis and mucin glycosylation, impairing mucus layer integrity. Furthermore, metabolites of gut microbiota, propionate and butyrate promoteFXYD3 expression. In ulcerative colitis (UC) patients, FXYD3 expression is significantly downregulated and correlats with disease severity. These findings indicat FXYD3 is a key mediator of host-microbiota interactions for intestinal health.
2025-09-25 | GSE309210 | GEO
Project description:Inflammatory bowel disease (IBD) is characterised by chronic intestinal inflammation, epithelial barrier dysfunction, and maladaptive stromal remodelling that can progress to fibrosis. Current therapies primarily target inflammatory pathways and rarely achieve durable remission or structural disease modification, highlighting a major unmet clinical need. Here, we evaluated the therapeutic potential of YUQ-A1007, an orally active, gut-enriched small-molecule aryl hydrocarbon receptor (AhR) agonist, across multiple translational models of colitis. The anti-inflammatory, barrier-restorative, and anti-fibrotic effects of YUQ-A1007 were assessed using in vitro cell systems, patient-derived colonic biopsies and organoids, permeability assays, and three murine colitis models. YUQ-A1007 partially activated AhR signalling, suppressed pro-inflammatory cytokine production, enhanced regulatory T cell differentiation, increased tight junction protein expression, and inhibited fibrotic gene programs. In vivo, oral YUQ-A1007 administration reduced disease severity, restored epithelial barrier integrity, and broadly downregulated inflammatory cytokines, chemokines, fibrosis-associated genes, pro-inflammatory mesenchymal stromal cell biomarkers, and matrix metalloproteinases. In ulcerative colitis patient-derived colonic explants, YUQ-A1007 dose-dependently reduced inflammatory mediator secretion while preserving barrier function. Collectively, these findings support further development of YUQ-A1007 as a gut-targeted AhR therapeutic for ulcerative colitis and broader inflammatory bowel disease.
2026-07-17 | GSE338894 | GEO
Project description:Dietary components and their metabolites produced by intestinal bacteria play a crucial role in maintaining intestinal epithelial integrity. Disrupted epithelial integrity can lead to increased permeability and chronic inflammation in the colon, known as ulcerative colitis (UC), in genetically predisposed individuals. Our data identified 3-aminobenzoic acid (3-ABA) as a key metabolite that reduces epithelial permeability and enhances barrier integrity in Caco2 cells by modulating the tight junctional regulatory pathway. Attenuated experimental colitis in mice treated with 3-ABA and decreased fecal 3-ABA in patients with UC implied the potential usefulness of 3-ABA as a novel treatment target for UC.
2025-05-01 | GSE270624 | GEO
Project description:Hsa_circ_0001021 regulates intestinal epithelial barrier function via sponging miR-224-5p in ulcerative colitis
| PRJNA740289 | ENA
Project description:Offspring born to mothers with colitis exhibited gut microbial dysbiosis, impaired barrier function, low-grade intestinal inflammation, compromised Wnt signaling and reduced crypt cell proliferation, which collectively increased their susceptibility to colitis in adulthood.
2026-02-18 | GSE298759 | GEO
Project description:Malnutrition is a major global health challenge that increases intestinal permeability and susceptibility to sepsis, yet the mechanisms driving barrier dysfunction remain poorly defined. We aimed to identify how the gut microbiome and microbiota-derived metabolites regulate intestinal barrier integrity during malnutrition. We used a low-protein, low-fat diet (LPLFD) to induce malnutrition in specific pathogen-free (SPF) and germ-free (GF) mice. Colonic permeability and mucus thickness were quantified. Metabolomics identified microbiota-derived metabolites altered by malnutrition. Human colonoids were used to test mechanistic effects of candidate metabolites. Barrier restoration was evaluated following colonic administration of isovalerate or oral supplementation with its precursor amino acid, leucine. LPLFD-induced malnutrition increased colonic permeability and reduced mucus thickness in male, but not female, SPF mice. These defects were absent in malnourished GF mice, indicating a microbiota-dependent and sexually dimorphic mechanism of barrier disruption. Metabolomic analysis revealed reduced colonic levels of branched-chain fatty acids (BCFAs) in malnourished mice. Supplementation of human colonoids with the BCFA isovalerate improved barrier function and altered expression of genes associated with epithelial junctional complexes. Restoring isovalerate levels, either directly via colonic administration or indirectly through oral leucine supplementation, partially rescued barrier defects in malnourished male mice. These findings identify BCFAs, particularly isovalerate, as essential microbiota-derived regulators of intestinal barrier integrity during malnutrition. This work reveals a sex-specific, microbiota-dependent pathway of barrier dysfunction and highlights microbial metabolites as promising therapeutic targets for mitigating sepsis risk in undernourished populations.
2026-07-24 | GSE316654 | GEO
Project description:Background; MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. MUC2 homo-oligomerizes intracellularly into large secreted polymers which give mucus its viscous properties. The inflammatory bowel disease (IBD) ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, whereas goblet cells and the mucus layer are increased in the other major inflammatory bowel disease, Crohnâs disease. Methods and Findings; By murine N-ethyl-N-nitrosourea-mutagenesis we identified two distinct non-complementing missense mutations in Muc2 exons encoding N- and C-terminal homo-oligomerization domains causing an ulcerative colitis-like phenotype. Both strains developed mild spontaneous distal intestinal inflammation, chronic diarrhea, rectal bleeding and prolapse, increased susceptibility to acute and chronic colitis induced by a luminal toxin, aberrant Muc2 biosynthesis, smaller goblet cell thecae (less stored mucin) and a diminished mucus barrier. Enhanced local production of IL-1beta, TNF-alpha and IFN-gamma was seen in the distal colon. The number of leukocytes within mesenteric lymph nodes was increased five-fold and leukocytes cultured in vitro produced both Th1 and Th2 cytokines (IFN-gamma, TNF-alpha and IL-13). Intestinal permeability was increased and the luminal bacterial flora were more heavily coated with immunoglobulin as occurs in IBD. This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis and wound repair. Expression of mutated Muc2 oligomerization domains in vitro demonstrated that aberrant Muc2 oligomerization underlies the ER stress. These models show that mutations in Muc2 oligomerization domains can lead to aberrant assembly of the Muc2 complex leading to ER stress, a depleted mucus barrier and intestinal inflammation. In ulcerative colitis we demonstrate similar accumulation of non-glycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in non-inflamed intestinal tissue. Conclusions; The observations that mucin misfolding and ER stress lead directly to intestinal inflammation and that ER stress and goblet cell pathology occur in ulcerative colitis suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of colitis. Experiment Overall Design: 3 individual mice from the Eeyore, Winnie or Wild-type strains were compared as groups. An Affymetrix ID was compared between groups if the ID was Present within two of the three mice within each grouping. IDs were compared by calculating the log2 of Group One average signal divided by Group 2 average signal.
2008-04-06 | E-GEOD-9913 | biostudies-arrayexpress
Project description:Ulcerative colitis (UC), belonging to inflammatory bowel disease (IBD), is a chronic and relapsing inflammatory disorders of the gastrointestinal tract, which is not completely cured so far. Valeriana jatamansi is a Chinese medicine used clinically to treat "diarrhea", which is closely related to UC. This study was to elucidate the therapeutic effects of V. jatamansi extract (VJE) on dextran sodium sulfate (DSS)-induced UC in mice and its underlying mechanism. In this work, VJE effectively ameliorate the symptoms, histopathological scores and reduce the production of inflammatory factors of UC mice. The colon untargeted metabolomics analysis and 16S rDNA sequencing showed remarkable differences in colon metabolite profiles and intestinal microbiome composition between the control and DSS groups, and VJE intervention can reduce these differences. Thirty-two biomarkers were found and modulated the primary pathways including pyrimidine metabolism, arginine biosynthesis and glutathione metabolism. Meanwhile, twelve significant taxa of gut microbiota were found. Moreover, there is a close relationship between endogenous metabolites and intestinal flora. These findings suggested that VJE ameliorates UC by inhibiting inflammatory factors, recovering intestinal maladjustment, and regulating the interaction between intestinal microbiota and host metabolites. Therefore, the intervention of V. jatamansi is a potential therapeutic treatment for UC.
2023-07-24 | PXD043047 | Pride
Project description:Aims: Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear. Materials and methods: The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics. Key findings: Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro_x0002_inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice. Significance: These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.
2024-11-04 | GSE280960 | GEO