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 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 AOC3, while A. muciniphila-produced LysoPE16:0 decreases taurocholic acid levels through the activation of FXR, ultimately suppressing extracellular matrix deposition and inflammatory signaling.