Evaluating traditional Chinese medicine modulation of the gut microbiota–bile acid axis in metabolic and inflammatory diseases: mechanistic evidence and translational priorities

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, type 2 diabetes mellitus (T2D), and inflammatory bowel disease (IBD) are clinically distinct disorders that share perturbations in intestinal ecology, bile-acid composition, epithelial barrier function, and immune-metabolic regulation. Traditional Chinese medicine (TCM) may modify these interconnected processes, but the translational significance of reported effects remains uncertain. Changes in microbial composition are often interpreted as mechanisms without evidence of altered microbial function, bile-acid profiles or concentrations, receptor engagement, or clinical benefit. Here, we present a structured narrative review that uses the gut microbiota-bile acid axis to evaluate TCM in metabolic and inflammatory disease. We describe how microbial bile salt hydrolases, the bile acid-inducible ( bai ) operon, hydroxysteroid dehydrogenases, and amino-acid conjugation diversify the bile-acid pool and influence farnesoid X receptor (FXR), Takeda G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5), and immune pathways. We then assess evidence for defined TCM constituents and formulae in MASLD, obesity/T2D, and IBD. Across these settings, the most informative studies combine a standardized intervention with longitudinal metagenomic and targeted bile-acid profiling, host-signaling measurements, and an outcome that is attenuated by microbiota depletion, fecal microbiota transplantation, or functional microbial manipulation. Only one eligible human trial, of Qushi Huayu in adults enrolled under the historical NAFLD designation, reported both clinical and microbiota-related outcomes. Evidence for obesity/T2D and IBD was predominantly preclinical or observational, and the framework is therefore a translational assessment tool rather than a clinically validated model. We therefore propose an evidence hierarchy and a minimum translational package that integrates chemical quality control, dietary and co-medication assessment, strain- and gene-resolved microbiome analysis, targeted bile-acid metabolomics, and pathway-directed validation. TCM should be considered a potential precision adjunct to standard care only when reproducible microbial-metabolic phenotypes are linked to clinically meaningful benefit.