Mouse gut metagenome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA781983 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17017819_1.fastq.gz | Fastqsanger.gz | |||
| SRR17017819_2.fastq.gz | Fastqsanger.gz | |||
| SRR17017820_1.fastq.gz | Fastqsanger.gz | |||
| SRR17017820_2.fastq.gz | Fastqsanger.gz | |||
| SRR17017821_1.fastq.gz | Fastqsanger.gz |
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2024-09-01 | GSE272179 | GEO
Project description:Hepcidin is demonstrated to be the key iron regulatory hormone, produced by the liver. Here we show an unexpected role of hepcidin as a master initiator of the local and systemic inflammatory response. We found that hepcidin was highly expressed in the colon of two major idiopathic inflammatory bowel diseases : Crohn's disease (CD) and ulcerative colitis (UC). Thanks to the generation of intestinal specific hepcidin KO mice (Hepc{delta}int), we found in a DSS-induced colitis model that hepcidin mediated the induction of key inflammatory cytokines and was protective against intestinal injury. In a model of LPS-induced acute inflammation, intestinal hepcidin expression was increased through a TLR4 dependent pathway andwas required for intestinal neutrophil infiltration and inflammation. Strikingly, intestinal hepcidin was absolutely required for the systemic production of key inflammatory cytokines (IL-6, CXCL1, TNF-alpha ...) as well as for the setting of the hypoferremia of inflammation. In a sepsis model, Hepc{delta}int mice were protected against LPS-induced mortality. Mechanistically, we showed that hepcidin was a direct neutrophil chemoattractant and a proinflammatory molecule in macrophages through a Myd88 dependent pathway. Altogether, we demonstrated that Hepcidin is a key new essential component of the immune system and may be a promising target in many inflammatory diseases. We used microarrays to detail the global program of gene expression of BMDM treat with hepcidin for 1 hour.
2016-07-16 | E-GEOD-71073 | biostudies-arrayexpress
Project description:Background and Objectives: Antibiotic (ABx) therapy is associated with an increased risk for Crohn´s Disease but the underlying mechanisms are unknown. We observed high fecal serine protease activity (PA) to be a frequent side effect of ABx therapy in patients. The aim of the present study was to unravel whether this rise in PA may promote colitis development via detrimental effects on the large intestinal barrier. Design: Transwell experiments were used to assess the impact of high PA in ABx-treated patients or vancomycin/metronidazole (V/M)-treated mice on the epithelial barrier. Serine protease profiling was performed using LC-MS/MS analysis. The impact of high PA on the intestinal barrier in WT/IL10-/- mice and on colitis development in IL10-/- mice was investigated using V/M+/-oral serine protease inhibitor (AEBSF) treatment. Results: The ABx-induced high PA was found to be due to significantly increased levels of pancreatic proteases and to impair the epithelial barrier. In WT mice, the rise in PA caused a transient increase in intestinal permeability but did not affect susceptibility towards DSS-induced acute colitis. In IL10-/- mice, the rise in PA caused a lasting impairment of the intestinal barrier, which was associated with inflammatory activation of the large intestinal tissue. In the long term, the lasting increase in PA upon repeated V/M treatment aggravated colitis development in IL10-/-mice. Conclusion: High PA is a frequent adverse effect of ABx therapy which is detrimental to the large intestinal barrier and may contribute to the development of chronic inflammation in genetically susceptible individuals.
2018-05-11 | PXD007914 | Pride
Project description:In the present study we investigate the role of IL-4 receptor a subunit in intestinal inflammation using DSS-induced colitis model. Our finding suggest that IL-4Ra deficiency enhances intestinal mucosal barrier function through the upregulation of NOX1-dependent ROS production, thereby suppressing the development of intestinal inflammation.
2020-09-10 | GSE157754 | GEO
Project description:Compromise of the intestinal barrier have been associated with a series of inflammatory conditions where the routine controls nutrient absorption and pathogens exclusion is lost to different degrees. The intestinal epithelial cells form a barrier of selective permeability which protects from invasion by the normal bacteria present in the gut. When the barrier is compromised, bacteria and their products can attack the cells and cause inflammation, which can (in severe cases) cause sepsis. Mesenteric lymph nodes play a crucial role in the immune response and are of particular importance in the study of Inflammatory Bowel Disease (IBD) patients due to their involvement in the disease process. To assess the efficiency of gut immune barrier, we collected the pre-nodal lymph from Inflammatory Bowel Disease (IBD) subjects and performed a comprehensive proteomic analysis. The current study is complementary extension of the proteomics signature found in DSS-induced colitis mouse model, providing an insight in the lymph composition, and associated biochemical changes, in the set of samples (n=6) recruited from the Inflammatory Bowel Disease (IBD), subjects undergoing intestinal resection. Following bottom-up analysis, the enrichment analysis – GO and Ingenuity pathway analysis (IPA) analysis identified several pathways pointing towards a damaging phenotype.
2024-08-09 | PXD044801 | Pride
Project description:A compromised pathology of the intestinal barrier have been associated with a series of inflammatory conditions where the routine controls nutrient absorption and pathogens exclusion is lost to different degrees. When the epithelial barrier is compromised, bacteria and their products can attack the cells and cause inflammation, sometime leading to sepsis. Studying the lymph peptidome in inflammatory bowel disease (IBD) can offer valuable insights into the underlying mechanisms, disease progression, and potential therapeutic targets. To assess the efficiency of gut immune barrier, we collected the pre-nodal lymph from Inflammatory Bowel Disease (IBD) subjects and performed a comprehensive peptidomic analysis. . The current study is complementary extension of the proteomics signature found in DSS-induced colitis mouse model, providing an insight in the lymph composition inclined to an inflammatory phenotype which was also mirrored by a unique set of peptidome/degradome. Furthermore, the identified peptides mapped to a wide range of intracellular and extracellular pathways, encompassing cellular stress, apoptosis, and extracellular matrix degradation related pathways. A significant fraction of peptides was also found to be derived from bacterial origin with a predicted binding affinity to different MHC I and MHC II human haplotypes.
2024-08-10 | PXD051024 | 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.
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Project description:To investigate the detailed molecular mechanisms for the regulatory role of HIF-2α in experimental colitis, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-2αF/F, Hif-2αlΔIE mice treated with 3%DSS for 3 days. Background & Aims: Hypoxic inflammation is characterized by decreased oxygen tension in inflammatory foci, and is a notable feature in inflammatory bowel disease (IBD). Hypoxic response is mediated by transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α, both of which are highly induced in IBD. HIF-1α is a protective factor that limits intestinal barrier dysfunction during inflammation. However, the role of HIF-2α has not been assessed in hypoxic inflammation and IBD. Methods: A hypoxia reporter mouse model was used to test the presence of hypoxia and HIF-2α in dextran sulfate sodium (DSS) and Citrobacter rodentium (C.rod)-induced colitis. The role of HIF-2α in these mouse models of colitis was further assessed in mice with an intestinal epithelium-specific gain- and loss-of-function of HIF-2α. Results: Induction of hypoxia and HIF-2α was confirmed in both murine experimental colitis models and human IBD samples. Disruption of HIF-2α attenuated colonic inflammation whereas stabilization of HIF-2α potentiated inflammation in mouse models of colitis. Interestingly, intestine specific overexpression of HIF-2α but not HIF-1α leads to spontaneous colitis and premature death in mice. Further mechanistic analysis showed that HIF-2α is a driver for pro-inflammatory response and is critical regulator of intestinal epithelial-derived tumor necrosis factor (TNF)-α. Blocking TNF-α completely ameliorated HIF-2α potentiated intestinal inflammation. Conclusions: These data demonstrate that HIF-2α is a critical transcription factor essential in intestinal epithelium elicited inflammatory response. Global gene expression profiling in colon RNAs isolated from 7-week-old Hif-2αF/F (n=6, Shah 007) and Hif-2αΔIE (n=5, Shah 008).
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Project description:Hexokinases (HK) catalyze the first step of glycolysis and thereby limit its pace. HK2 is highly expressed in the gut epithelium, plays a role in immune responses and is upregulated in inflammation and ulcerative colitis 1-3. Here, we examined the microbial regulation of HK2 and its impact on intestinal inflammation by generating mice lacking HK2 specifically in intestinal epithelial cells (Hk2∆IEC). Hk2∆IEC mice were less susceptible to acute intestinal inflammation upon challenge with dextran sodium sulfate (DSS). Analyzing the epithelial transcriptome from Hk2∆IEC mice during acute colitis revealed downregulation of cell death signaling and mitochondrial dysfunction dependent on loss of HK2. Using intestinal organoids derived from Hk2∆IEC mice and Caco-2 cells lacking HK2, we identified peptidyl-prolyl cis-trans isomerase (PPIF) as a key target of HK2-mediated regulation of mitochondrial permeability and repression of cell-death during intestinal inflammation. The microbiota strongly regulated HK2 expression and activity. The microbially-derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression and oral supplementation protected wildtype but not Hk2∆IEC mice from DSS colitis. Our findings define a novel mechanism how butyrate may act as a protective factor for intestinal barrier homeostasis and suggest targeted HK2 inhibition as a promising therapeutic avenue in intestinal inflammation.
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Project description:The intestinal epithelial barrier plays critical role in the intestinal homeostasis and dysfunction of the epithelial barrier causes microbial invasion that would lead to inflammation in the gut. Antimicrobial peptides (AMPs) are essential components of the epithelial barrier to inhibit bacterial invasion. The regulatory mechanisms of the expression of AMPs are not fully characterized. Here, we report a cell-type-specific role of ovarian tumor family deubiquitinase 4 (OTUD4) in experimental colitis and bacterial infection. OTUD4 is upregulated in the inflamed mucosa of IBD patients and in the colon of mice treated with dextran sulfate sodium salt (DSS). Knockout of OTUD4 in intestinal organoids promotes the expression of AMPs after the stimulation with lipopolysaccharide (LPS), peptidoglycan (PGN), or Salmonella typhimurium (S.t.). In addition, the expression of AMPs was upregulated in intestinal epithelial cells (IECs) after DSS treatment or S.t. infection. Consistently, Vil-Cre;Otud4fl/fl mice and Def-Cre;Otud4fl/fl mice exhibit hyper-resistance to DSS-induced colitis and S.t. infection compared to Otud4fl/fl mice. Mechanistically, Knockout of OTUD4 results in hyper K63-linked ubiquitination of MyD88 and increases the activation of the NF-κB signaling pathway and MAPK signaling pathway to promote the expression of AMPs. These finds collectively highlight an indispensable role of OTUD4 in paneth cells to modulate AMPs production, indicating OTUD4 as a promoter and potential druggable target for gastrointestinal inflammation and bacterial infection.
2023-03-01 | GSE222836 | GEO