Jiayi Huatu Decoction mitigates intestinal fibrosis via a gut microbiota–metabolite axis

Ulcerative colitis (UC)-associated intestinal fibrosis represents a serious and currently untreatable complication, highlighting an urgent need for novel therapeutic strategies. This study investigates the therapeutic potential of Jiayi Huatu Decoction (JHD), a traditional Chinese herbal formula and provides substantial innovation by identifying a previously unexplored “gut microbiota–metabolite” axis through which JHD alleviates colonic fibrosis. We believe our study makes a significant contribution to the literature. We provide the first demonstration that JHD can selectively enrich two distinct beneficial bacteria, Faecalibaculum rodentium and Akkermansia muciniphila. Furthermore, we elucidate a novel mechanistic cascade in which F. rodentium-derived butyrate reduces the pro-fibrotic metabolite 2-piperidone by inhibiting copper amine oxidase 3 (AOC3), while A. muciniphila-produced 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine (LysoPE16:0) decreases taurocholic acid levels through the activation of farnesoid X receptor (FXR), ultimately suppressing extracellular matrix deposition and inflammatory signaling.