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PROVIDER: PRJNA1214154 | ENA |
REPOSITORIES: ENA
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Project description:Microbiota alteration and IFN-γ-producing CD4+ T cell overactivation are implicated in Crohn's disease (CD) pathogenesis. However, it remains unclear how dysbiosis enhances Th1 responses, leading to intestinal inflammation. Here, we identified key metabolites that are derived from dysbiotic microbiota and induce enhanced Th1 responses and severe colitis in mouse models. Patients with CD showed elevated lysophosphatidylserine (LysoPS) concentration in their feces, accompanied with a higher relative abundance of microbiota possessing a gene encoding the phospholipid-hydrolyzing enzyme phospholipase A. LysoPS induced metabolic reprograming, thereby eliciting aberrant effector responses in both human and mouse IFN-?-producing CD4+ T cells. Administration of LysoPS into T cell-dependent mouse colitis models induced severe inflammation. LysoPS-induced aggravation of colitis was impaired in mice lacking P2ry10 and P2ry10b, and their CD4+ T cells were hypo-responsive to LysoPS. Thus, our findings elaborate on the mechanism by which metabolites elevated in patients with CD harboring dysbiotic microbiota induce intestinal pathology.
2022-05-03 | GSE169006 | GEO
Project description:Microbiota composition regulates colitis severity, yet mechanisms employed by the innate immune system to regulate this remain unclear. We show that severity of colitis in Clec12a deficient animals is dependent on microbiota composition. Microbiota from a Clec12a-/- animal has expanded Faecalibaculum rodentium and transplantation of the Clec12a-/- microbiota or treatment with F. rodentium is sufficient to worsen colitis in wild-type mice. However, Clec12a-/- animals are resistant to colitis developmemt when rederived into an 11-member community, while addition of F. rodentium worsens disease. Colitis in Clec12a-/- mice is dependent on monocytes and cytokine and sequencing analysis in Clec12a-/- macrophages and serum shows enhanced inflammation with a reduction in phagocytic genes. We demonstrate that F. rodentium specifically binds to Clec12a and Clec12a-/- deficient macrophages are specifically impaired in their ability to phagocytose F. rodentium. Thus, Clec12a is an innate-immune surveillance mechanism to control the expansion of potentially harmful commensals while limiting inflammation
2025-02-19 | GSE283366 | GEO
Project description:Abstract. Ulcerative colitis (UC) is an intestinal disease characterized by chronic recurrent inflammation, but the underlying mechanism remains undefined and requires in-depth exploration. The aim of the present study was to investigate the biological effects of a small molecular compound M1002 of oxygen-sensing signaling pathway on dextran sulfate sodium (DSS)-induced intestinal inflammation colitis mouse models. It was found that the protective effects of M1002 on DSS-induced colitis. To determine how M1002 exerted its protective effect in DSS-induced colitis, we compared the global gene expression profiles in the gut between DSS control and M1002 treatment colitis mouse groups by RNA-Seq. The results demonstrated that HIF-1 signaling pathway-related genes were significantly upregulated in the gut of M1002 treatment colitis mice, whereas the Inflammatory bowel disease signaling pathway, the TNF signaling pathway, and Cytokines and inflammatory response signaling pathway related genes were significantly downregulated in the M1002 treatment group. 16S rRNA gene sequencing demonstrated remarkable variations in the composition of gut microbiota between DSS control and M1002 treatment colitis mice. Compared with DSS control colitis mice, the relative abundance of Eubacterium_nodatum and Halomonas in the gut microbiota was significantly increased at genus level in the gut of M1002 treatment colitis mice. Based on these findings, we tend to conclude that M1002 might alleviate DSS-induced gut injury in mice by regulation of HIF-1 signaling and up-regulating Eubacterium_nodatum and Halomonas.
2025-07-01 | GSE271173 | GEO
Project description:Background: Advanced-stage cholangiocarcinoma (CCA) leads to poor treatment outcomes and reduced patient survival, highlighting the need for alternative therapies. This study aimed to evaluate the alteration in gut microbiota, host proteomics, and immune response after CCA treatment with a combination of melatonin and gemcitabine in animal.
2025-10-02 | PXD056449 | JPOST Repository
Project description:Microbial dysbiosis has been identified in adult inflammatory bowel disease (IBD) patients. However, microbial composition and functional interplay between host genetics and microorganisms in early IBD onset remain poorly defined. Here, we identified and demonstrated the causal effect of Atopobium parvulum and the gut microbiota in pediatric IBD. Microbiota and proteomic profiling revealed that the abundance of A. parvulum, a potent H2S producer, was associated with increased disease severity and a concurrent reduction in the expression of the host H2S detoxification pathway. In the Il10-/- mouse model of inflammation, A. parvulum induced severe pancolitis that was dependent on the presence of the gut microbiota. In addition, we demonstrated that administration of bismuth, an H2S scavenger, prevented A. parvulum-induced colitis. Our findings identified Atopobium parvulum as a major mediator of inflammation severity, and revealed an alteration of the balance between the production and detoxification of H2S in the gastrointestinal tract.
2022-02-22 | PXD000690 | Pride
Project description:Excessive ultra-processed foods (UPFs) consumption has been reported to increase the risk of inflammatory bowel disease (IBD). However, the specific mechanisms remain unclarified. As an important ingredient of UPFs, 7-ketositosterol (KS) is mainly synthesized from high-temperature heating oils. We find that KS intake is higher in IBD patients and related to disease activity. KS exacerbats colitis in a gut microbiota-dependent manner in mice, altering the gut microbiota composition, increasing the abundance of potential pathogenic bacteria, especially Staphylococcus_lentus (SL). Morevoer, SL aggravates DSS-induced colitis. Mechanically, KS up-regulates the expression of PDZ and LIM Domain 3 (PDLIM3). SL-derived lysin motif peptidoglycan-binding domain-containing protein (LPDP) interacts with PDLIM3, and activates p38MAPK/NF-κB signaling pathway. Furthermore, tubuloside B, selected by high-throughput screening, blocks the interaction of PDLIM3 and LPDP, and ameliorates SL-aggravated colitis. Our study reveals that KS exposure promotes colitis via gut microbiota and PDLIM3 interaction, providing evidence of IBD pathogenesis and potential therapeutic strategy for IBD treatment.
2026-01-01 | GSE299083 | GEO
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:Microbiota dysbiosis has been reported to contribute to the pathogenesis of colitis, to demonstrate whether IL-17D protects against DSS-induced colitis through regulation of microflora, we performed 16S rRNA sequencing in feces from WT and Il17d-deficient mice. Our data indicate that Il17d deficiency results in microbiota dysibiosis in both steady state and DSS-induced colitis.
2021-05-20 | GSE165789 | GEO