Gut Microbiota-Dependent Tryptophan Metabolism Drives the Therapeutic Effects of Baitouweng Tang in Colitis via the AhR Pathway

With dysregulation of the gut microbiota and its metabolic byproducts playing a pivotal role in inflammatory bowel disease (IBD) pathogenesis. Baitouweng Tang (BTWT), a traditional herbal formulation, has long been employed to treat gastrointestinal disorders and shows promising potential in the management of IBD. However, its precise pharmacological mechanisms remain elusive. In this study, we employed targeted metabolomics, high-throughput sequencing, and molecular biology techniques to elucidate the therapeutic mechanisms of BTWT in the treatment of ulcerative colitis (UC). BTWT significantly enhanced the relative abundance of Bifidobacterium, improved the indole metabolic pathway of tryptophan, and restored the levels of indole metabolites, such as indole-3-lactic acid (ILA). These changes activated the aryl hydrocarbon receptor (AhR) and led to marked improvements in the clinical symptoms of UC in mice. Conversely, the therapeutic effects of BTWT were substantially diminished in an antibiotic-induced gut microbiota depletion model. Notably, fecal microbiota transplantation (FMT) partially restored BTWT efficacy, underscoring the critical role of the gut microbiota in mediating its therapeutic effects. Furthermore, in an in vitro lipoteichoic acid (LTA)-induced HT-29 inflammation model, ILA treatment attenuated inflammation and concurrently increased the expression of AhR, CYP1A1, and CYP1B1. These findings suggest a potential link between BTWT-induced changes in tryptophan metabolites, AhR pathway activation, and the amelioration of colitis, though the causal relationship remains to be established. Our study provides a basis for further mechanistic investigation into the AhR pathway as a possible therapeutic target in UC.