Gut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation

作者：Liping Chen, Zhenghao Ye, Junhua Li, Lijia Wang, Yu Chen, Meiping Yu, Jian Han, Jiangeng Huang, Dongyan Li, Yongling Lv, Kai Xiong, Dean Tian, Jiazhi Liao, Ursula Seidler, Fang Xiao · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-024-05873-6 · 被引用次数：35 · 研究领域：Gut microbiota and health、Drug Transport and Resistance Mechanisms、Inflammatory Bowel Disease

BACKGROUND: The conversion of primary bile acids to secondary bile acids by the gut microbiota has been implicated in colonic inflammation. This study investigated the role of gut microbiota related bile acid metabolism in colonic inflammation in both patients with inflammatory bowel disease (IBD) and a murine model of dextran sulfate sodium (DSS)-induced colitis. METHODS: Bile acids in fecal samples from patients with IBD and DSS-induced colitis mice, with and without antibiotic treatment, were analyzed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). The composition of the microbiota in fecal samples from IBD patients and DSS-colitis mice was characterized via Illumina MiSeq sequencing of the bacterial 16S rRNA gene V3-V4 region. Metagenomic profiling further identified metabolism-related gene signatures in stool samples from DSS-colitis mice. Histological analysis, quantitative PCR (qPCR) and Western Blotting were conducted on colonic samples from DSS-induced colitis mice to assess colonic inflammation, mucosal barrier integrity, and associated signaling pathways. The multivariate analysis of bile acids was conducted using Soft Independent Modelling of Class Analogy (SIMCA, Umetrics, Sweden). The relation between the relative abundance of specific phyla/genera and bile acid concentration was assess through Spearman's correlation analyses. Finally, lithocholic acid (LCA), the key bile acid, was administered via gavage to evaluate its effect on colon...