Targeting gut microbial metabolism with Chinese herbal medicine in ulcerative colitis: A narrative review

Altered in gut microbial metabolism constitutes a major mechanistic bridge connecting dysbiosis to mucosal inflammation and barrier injury in ulcerative colitis (UC). Although previous reviews have addressed microbial composition or global metabolite changes; alterations, they frequently group diverse molecules as “microbial metabolites,” obscuring the metabolic steps targeted by Chinese herbal medicine (CHM). To address this gap, we established a three-category framework comprising microbiota-derived metabolites, host–microbiota co-metabolites, and microbiota-modulated host metabolites. Using this framework, we integrated evidence across four metabolic axes: short-chain fatty acids (SCFAs); bile acids; tryptophan; and amino acids, polyamines, and nitrogen metabolism. Current evidence suggests that CHM remodels intestinal metabolism through three complementary modes: provision of microbiota-accessible substrates, microbial biotransformation of CHM constituents, and restoration of the host mucosal metabolic environment. Evidence maturity varies across these axes. SCFA studies increasingly validate microbiota dependence and specific microbial strains. Research on bile acids and tryptophan links metabolites with host receptors. In contrast, amino acid, polyamine, and nitrogen metabolism studies remain dominated by correlative omics analyses and pathway inferences. Microbiota-associated metabolites may be the mechanism linking CHM exposure, microbial function, and host responses. They may also inform metabolite supplementation, reconstruction of endogenous metabolic networks, and combination therapies. However, current evidence is derived mainly from animal models. Few studies report causal associations among CHM composition, functional microbes or enzymes, specific metabolites, and host effects. To transition from compositional associations toward clinically translatable and mechanistically verifiable insights, future studies should integrate standardized CHM preparations, longitudinal multicompartment sampling, targeted absolute quantification, stable-isotope tracing, and staged causal interventions.