Increased adipose tissue Fas alters gut microbiota to aggravate colitis in obesity— Adipose Fas aggravates colitis via gut microbiota in obesity

ABSTRACT: Obesity is increasingly recognized as a factor that may exacerbate inflammatory bowel disease (IBD), yet the underlying mechanisms remain poorly understood. This study investigates whether upregulated Fas (CD95) expression in adipose tissue contributes to obesity-associated aggravation of colitis, with a particular focus on the role of the gut microbiota and its metabolic products. To address this question, we employed a mouse model with adipose tissue-specific Fas overexpression (FasCKI/CKI×Adi-cre) alongside littermate controls (FasCKI/CKI). All animals were maintained on a high-fat diet (HFD) both before and during colitis induction, which was achieved using dextran sulfate sodium (DSS). Disease severity was assessed through clinical scores, histopathological evaluation, and inflammatory markers. Gut microbial composition was analyzed via 16S rRNA sequencing, and fecal short-chain fatty acid (SCFA) levels were quantified using targeted metabolomics. Additionally, fecal microbiota transplantation (FMT) experiments were performed to establish a causal link between microbiota alterations and disease phenotype. Biological samples collected include colonic tissues, adipose tissues, serum, and fecal specimens. Metabolomic data were generated from fecal samples, with a focus on short-chain fatty acids (SCFAs) including acetate, propionate, and butyrate. These metabolomic measurements were integrated with microbial community data and phenotypic parameters to explore correlations between metabolic shifts, microbial dysbiosis, and colitis severity. Our results demonstrate that adipose tissue Fas overexpression exacerbates DSS-induced colitis under obese conditions, accompanied by significant alterations in the gut microbiota—specifically reduced Roseburia abundance and increased Escherichia–Shigella, Erysipelatoclostridium, and UCG_005—alongside decreased fecal SCFA levels. FMT experiments confirmed that the altered microbiota directly contributes to disease aggravation. This study provides novel insights into the crosstalk between adipose tissue Fas signaling, gut microbial metabolism, and intestinal inflammation, highlighting potential metabolic targets for therapeutic intervention.

INSTRUMENT(S): Gas Chromatography MS - positive - medium-polarity

PROVIDER: MTBLS15480 | MetaboLights | 2026-09-03

REPOSITORIES: MetaboLights