Multi-Omics Insights into the Mechanism of Liver Injury in Dextran Sulfate Sodium-Induced Colitis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE181959 | GEO | 2021/08/16
REPOSITORIES: GEO
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Project description:In the DSS-induced colitis model, the epithelial damage and resulting inflammation is restricted to the colon, with a potential influence on the microbial composition in the adjacent cecum. Several studies have reported changes of the gut microbiota in the DSS-induced colitis model and other mouse models of IBD. Furthermore, metaproteomics analysis of the gut microbiome in a mouse model of Crohn’s disease demonstrated that disease severity and location are microbiota-dependent, with clear evidence for the causal role of bacterial dysbiosis in the development of chronic ileal inflammation. We have developed a refined model of chronic DSS-induced colitis that reflects typical symptoms of human IBD without a risky body weight loss usually observed in DSS models [Hoffmann et al., submitted]. In this study, we used metaproteomics to characterize the disease-related changes in bacterial protein abundance and function in the refined model of DSS-induced colitis. To assess the structural and functional changes, we applied 16S rRNA gene sequencing and metaproteomics analysis of the intestinal microbiota in three different entities of the intestinal environment, i.e. colon mucus, colon content and cecum content.
2020-03-17 | PXD007220 | Pride
Project description:Abstract. Background: The cause of ulcerative colitis (UC) is not yet fully understood. Previous research has pointed towards a potential role for mutations in NOD2 in promoting the onset and progression of inflammatory bowel disease (IBD) by altering the microbiota of the gut. However, the relationship between toll-like receptor 4 (TLR4) and gut microbiota in IBD is not well understood. To shed light on this, the interaction between TLR4 and gut microbiota was studied using a mouse model of IBD. Methods: To examine the function of TLR4 signaling in intestinal injury repair, researchers developed Dextran Sulfate Sodium Salt (DSS)-induced colitis and injury models in both wild-type (WT) mice and TLR4 knockout (TLR4-KO) mice. To assess changes in the gut microbiota, 16S rRNA sequencing was conducted on fecal samples from both the TLR4-KO and WT enteritis mouse models. Results: The data obtained depicted a protective function of TLR4 against DSS-induced colitis. The gut microbiota composition was found to vary considerably between the WT and TLR4-KO mice groups as indicated by β-diversity analysis and operational taxonomic units (OTUs) cluster. Statistical analysis of microbial multivariate variables depicted an elevated abundance of Escherichia coli/Shigella, Gammaproteobacteria, Tenerlcutes, Deferribacteres, Enterobacteria, Rikenellaceae, and Proteobacteria in the gut microbiota of TLR4-KO mice, whereas there was a considerable reduction in Bacteroidetes at five different levels of the phylogenetic hierarchy including phylum, class, order, family, and genus in comparison with the WT control. Conclusion: TLR4 may protect intestinal epithelial cells from damage in response to DSS-induced injury by controlling the microbiota in the gut.
2023-11-01 | GSE227565 | GEO
Project description:Purpose: Gut microbiota-derived metabolites play a pivotal role in the maintenance of local gut homeostasis and can even induce systemic effects via accumulation in the bloodstream. Here, we demonstrate that mono-colonization of germ-free (GF) mice with Clostridium sporogenes protects mice from inflamation and death induced by DSS colitis. Method: 8-12-week-old male mice (GF, SPF and GF colonized with C. sporogenes (CS)) were treated with 2.5% DSS in drinking water for 5 days and colon tissue was isolated on day 7. RNA was isolated from the colon tissue and RNA sequenzing was performed. Results: Mono-colonization of GF mice with Clostridium sporogenes protected the mice from DSS colitis induced death, while producing high amounts of indole-3-propionic acid (IPA), branched chain (BCFA) and short-chain (SCFA) fatty acids. In comparison to CS mice, SPF mice showed much higher levels of inflammatory related genes and a worse histological score. Conclusion: Histological stainings and the RNAseq both showed high levels of protection of C. sporogenes colonized mice in colitis, compared to SPF and GF animals. The data provide evidence for a therapeutic potential of C. sporogenes for IBD patients.
2024-10-15 | GSE264024 | GEO
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:How pathogenesis of inflammatory bowel disease (IBD) depends on the complex interplay of host genetics, microbiome and the immune system is not fully understood. Here, we showed that Downstream of Kinase 3 (DOK3), an adaptor protein involved in immune signaling, confers protection of mice from dextran sodium sulfate (DSS)-induced colitis. DOK3-deficiency promotes gut microbial dysbiosis and enhanced colitis susceptibility, which can be reversed by the transfer of normal microbiota from wild-type mice. Mechanistically, DOK3 exerts its protective effect by suppressing JAK2/STAT3 signaling in colonic neutrophils to limit their S100a8/9 production, thereby maintaining gut microbial ecology and colon homeostasis. Hence, our findings reveal that the immune system and microbiome function in a feed-forward manner, whereby DOK3 maintains colonic neutrophils in a quiescent state to establish a gut microbiome essential for intestinal homeostasis and protection from IBD.
2021-11-10 | GSE186597 | GEO
Project description:Inflammatory bowel disease (IBD) is a multiple-genes-involved chronic disease and current available targeted drugs for IBD only deliver moderate efficacy. Whether there is a single gene that systematically regulates IBD is not yet known. Here we showed that the expression of miR-146a in colon was elevated in Dextran Sulfate Sodium Salt (DSS)-induced IBD mice and patients with IBD. DSS induced dramatic body weight loss and much more rectal bleeding, shorter colon length and colitis in miR-146a knock-out mice than wild type (WT) mice. The miR-146a mimics alleviated DSS-induced symptoms in both DSS-induced miR-146a-/- and WT mice. Further RNA sequencing illustrated that deficiency of miR-146a de-repressed majority of DSS-induced IBD-related genes which cover multiple genetic regulatory networks in IBD, and supplement of miR-146a mimics inhibited expression of many IBD-related genes. DOI 10.3389/fimmu.2024.1366319
2024-04-24 | GSE247433 | GEO
Project description:Temporal genome profiling of DSS colitis The DSS induced mouse colitis model is often used to emulate Ulcerative Colitis (UC) in order understand pathophysiological mechanism of inflammatory bowel disease (IBD). Given the progressive nature of IBD, colon tissue gene expression changes during the evolution of disease, and knowing the changes in gene expression profiles could indentify potential diagnostic markers or additional therapeutic targets for colitis. Therefore, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis. Keywords: Expression time course of mouse colon tissue induced by 3% DSS. C57BL/6J mice were given 3% DSS in the drinking water and tissues from individual cohorts were collected at days 0, 2, 4 and 6. Total RNA were extracted from the colon tissue and detected by Affymerix GeneChip Mouse Genome 430 2.0 Array.
2010-10-13 | E-GEOD-22307 | biostudies-arrayexpress
Project description:Background & Aims: The complex interactions between diet and the microbiota that influence mucosal inflammation and inflammatory bowel disease are poorly understood. Experimental colitis models provide the opportunity to control and systematically perturb diet and the microbiota in parallel to quantify the contributions between multiple dietary ingredients and the microbiota on host physiology and colitis. Methods: To examine the interplay of diet and the gut microbiota on host health and colitis, we fed over 40 different diets with varied macronutrient sources and concentrations to specific pathogen free or germ free mice either in the context of healthy, unchallenged animals or dextran sodium sulfate colitis model. Results: Diet influenced physiology in both health and colitis across all models, with the concentration of protein and psyllium fiber having the most profound effects. Increasing dietary protein elevated gut microbial density and worsened DSS colitis severity. Depleting gut microbial density by using germ-free animals or antibiotics negated the effect of a high protein diet. Psyllium fiber influenced host physiology and attenuated colitis severity through microbiota-dependent and microbiota-independent mechanisms. Combinatorial perturbations to dietary protein and psyllium fiber in parallel explain most variation in gut microbial density, intestinal permeability, and DSS colitis severity, and changes in one ingredient can be offset by changes in the other. Conclusions: Our results demonstrate the importance of examining complex mixtures of nutrients to understand the role of diet in intestinal inflammation. Keywords: IBD; Diet; Microbiota; Mouse Models; Systems Biology
2017-10-30 | GSE104461 | GEO
Project description:Background: The etiology of Inflammatory Bowel Disease (IBD) is unclear but involves both genetics and environmental factors, including the gut microbiota. Indeed, exacerbated activation of the gastrointestinal immune system toward the gut microbiota occurs in genetically susceptible hosts and under the influence of the environment. For instance, a majority of IBD susceptibility loci lie within genes involved in immune responses, such as caspase recruitment domain member 9 (Card9). However, the relative impacts of genotype versus microbiota on colitis susceptibility in the context of CARD9 deficiency remain unknown. Results: Card9 gene directly contributes to recovery from dextran sodium sulfate (DSS)-induced colitis by inducing the colonic expression of the cytokine IL-22 and the antimicrobial peptides Reg3 and Reg3 independently of the microbiota. On the other hand, Card9 is required for regulating the microbiota capacity to produce AhR ligands, which leads to the production of IL-22 in the colon, promoting recovery after colitis. In addition, cross-fostering experiments showed that five weeks after weaning, the microbiota transmitted from the nursing mother before weaning had a stronger impact on the tryptophan metabolism of the pups than the pups' own genotype. Conclusions: These results show the role of CARD9 and its effector IL-22 in mediating recovery from DSS-induced colitis in both microbiota-independent and microbiota-dependent manners. Card9 genotype modulates the microbiota metabolic capacity to produce AhR ligands, but this effect can be overridden by the implantation of a WT or healthy microbiota before weaning. It highlights the importance of the weaning reaction occurring between the immune system and microbiota for the host metabolism and immune functions throughout life. A better understanding of the impact of genetics on microbiota metabolism is key to developing efficient therapeutic strategies for patients suffering from complex inflammatory disorders.
2024-05-01 | GSE262585 | GEO
Project description:Background: MicroRNAs (miRNAs) acting as negative regulators of gene expression are differentially expressed in intestinal tissues of patients with inflammatory bowel disease (IBD). Assessing the functional role of miRNAs in murine models of colitis facilitates elucidating the role of specific miRNAs in human IBD. The aim of this study was to determine the miRNA signature of murine models of colitis and to assess the influence of miR-21 on intestinal inflammation. Methods: miRNAs expression was accessed by microarray for acute and chronic murine model of colitis induced by DSS or TNBS. miR-21-deficient mouse and littermates controls were assessed in the standard DSS, TNBS and CD4+ T cell transfer models of colitis. RNAs of mouse colon and CD4+CD45RBHigh cells were analyzed by miRNA and mRNA microarray, and quantitative RT-PCR. Th1 polarization was accessed by flow-cytometry and ELISA. Results: Alterations of in miRNAs expression were identified for acute and chronic DSS colitis and TNBS colitis, receptively. The Expression of miRs-21, -142-3p and -223 was were distinct between DSS and TNBS models while overlap of numerous miRNAs was seen. Importantly, miRs-19b, -192 and -215, that are decreased in IBD, were significantly decreased in all 4 models of colitis. miR-21, which is increased in IBD, was increased in TNBS colitis but not the DSS colitis models. Further assessment of the miR-21-deficient 1-/- mice revealed that the deletion of miR-21 results in the exacerbation of both the TNBS and T cell-transfer models of colitis. Conclusions: miRNAs are differentially expressed in both human IBD and murine colitis, with overlap of several IBD-associated miRNAs. The demonstration that miR-21 deletion exacerbated CD4+ T cell-mediated models of colitis provides further evidence that miRNAs play significant roles in the pathogenesis of IBD. Gene expression profiles were established for normal miR-21-/- mice and wild type c57BL/6 mice (WT). Total of 6 samples with replicates were included in this study.
2014-07-23 | E-GEOD-59648 | biostudies-arrayexpress