Traditional Chinese medicine modulates immune homeostasis through the gut microbiota–microbial metabolite axis

The gut microbiota is considered a central regulator of immune homeostasis, and microbial metabolites serve as key mediators that translate microbial activity into host immune responses. Traditional Chinese medicine (TCM) can modulate the composition of the gut microbiota; however, changes in microbial communities alone cannot fully explain its immunomodulatory effects. Therefore, this review summarizes the mechanisms by which TCM reshapes the gut microbial metabolome and, in turn, modulates host immune responses. TCM interventions effectively promote the production of beneficial microbial metabolites, suppress potentially harmful metabolites, and enhance microbial-mediated biotransformation of phytochemicals, thereby reshaping the gut immune microenvironment. Immune signaling pathways activated by microbial metabolites include G protein-coupled receptors, aryl hydrocarbon receptors, farnesoid X receptor, Takeda G protein-coupled receptor 5, and epigenetic regulatory mechanisms; these pathways synergistically regulate mucosal immunity, immune cell differentiation, inflammatory responses, and immune homeostasis. Furthermore, this study explored the therapeutic role of the “traditional Chinese medicine–gut microbiota–microbial metabolites” axis in inflammatory bowel disease, cancer, metabolic inflammation, autoimmune diseases, and other immune-mediated conditions. This research provides a new theoretical foundation for how TCM modulates host immunity by reshaping microbial metabolites, and offers new insights for the development of interventions targeting the gut microbiota.