Procyanidin C1 Modulates the Microbiome to Increase FOXO1 Signaling and Valeric Acid Levels to Protect the Mucosal Barrier in Inflammatory Bowel Disease

• DOI: 10.1016/j.eng.2023.10.016
• Publication Date: 2024-02-08T04:14:58Z
• Authors: Xifan Wang; Pengjie Wang; Yixuan Li; Huiyuan Guo; Ran Wang; Siyuan Liu; Ju Qiu; Xiaoyu Wang; Yanling Hao; Yunyi Zhao; Haiping Liao; Zhongju Zou; Josephine Thinwa; Rong Liu
• Keywords: Valeric acid; FOXO1

Inflammatory bowel disease (IBD) refers to a pair of prevalent conditions (Crohn's and ulcerative colitis) distinguished by persistent inflammation the large intestine. Procyanidin C1 (PCC1) is naturally occurring substance derived from grape seeds that has demonstrated notable anti-inflammatory properties. This study examines potential utility PCC1 as treatment for IBD subsequently host-cell- microbiome-related mechanisms underlying detected therapeutic benefits. Working with classic dextran sodium sulfate (DSS)-induced mouse model, we show protects mucosal barrier thereby confers strong protective effects against IBD. pretreatment resulted in protection multiple pathological phenotypes model mice, including reduced weight loss, lower Disease Activity Index (DAI) totals, enhanced colon size, well obviously beneficial on (e.g., thickness activity mucus-degrading enzymes). We also analyzed autophagy marker LC3 found level was significantly elevated intestinal epithelial cell samples PCC1-pretreatment group compared non-model mice samples. altered fecal microbiome composition, which included elevating abundance Akkermansia muciniphila Christensenella minuta. Fecal transplant (FMT) experiments showed delivering PCC1-treated animals into PCC1-naïve conferred protection. Metabolic profiling revealed both FMT groups had levels microbiota-derived metabolite valeric acid, supplementation this short-chain fatty acid (SCFA) Finally, inhibitor confirmed mucus layer are mediated FOXO1 signaling goblet cells epithelium. Beyond showing altering microbiome, our demonstrates proof principle straightforward interventions (PCC1, FMT, supplementation) ameliorating damage treat