Ruminococcus torques ameliorates the inflammation bowel disease and gut barrier dysfunction by modulating gut microbiota and bile acid metabolism
Yue Lou, Yao Lv, Xiaoxi Wang, Youyou Luo, Jingan Lou, Yu Yu, Weizhong Gu, Jindan Yu, Youhong Fang, Hong Zhao, Kerong Peng, Jie Chen, Yan Ni
Abstract
BACKGROUND: Recent advances in microbiome-targeted therapies have uncovered immunomodulatory bacterial taxa with strain-specific therapeutic potential; however, the microbial signatures driving exclusive enteral nutrition (EEN) efficacy, particularly protective microbiota, and their mechanistic links to therapeutic outcomes remain uncharacterized in pediatric inflammatory bowel disease (IBD). Elucidating these microbial determinants and their functional pathways is critical for advancing targeted probiotic strategies in children. METHODS: A cohort of treatment-naïve pediatric Crohn's disease (CD) patients and age-matched healthy controls (HC) were enrolled. Fecal samples were collected from both HC and CD patients during active phase and remission following EEN therapy. Metagenomic sequencing, qPCR validation, and targeted bile acid (BA) analysis were conducted to identify candidate protective strains and potential impacts on BA homeostasis. Mechanistic investigations were conducted using dextran sulfate sodium (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis model in male mice. RESULTS: The relative abundance of Ruminococcus torques (R. torques) demonstrated significant depletion in active CD cases (p = 0.02) compared to HC, which was restored after EEN treatment at remission status (p < 0.001). Its level was negatively correlated with the disease severity index (PCDAI r=-0.64; CDEIS r=-0.70) and positively correlated with the secondary to primary BA ratio (r = 0.27). In murine models, R. torques supplementation attenuated colitis severity through enhancing epithelial integrity (claudin-3, 3.3-fold; occludin, 7.5-fold), suppressing pro-inflammatory mediators (TNF-α, -44%; IL-6, -71%), regulating BA metabolism (secondary/unconjugated BAs, 29%) and autophagy pathway (LC3-II/LC3-I ratio, -1.8-fold). CONCLUSIONS: Our findings demonstrated R. torques as a novel microbial therapeutic candidate for IBD management. The anti-colitis mechanisms involve the modulation of BA metabolic homeostasis, epithelial barrier reinforcement, and inflammation resolution.