Gut Microbiota-Mediated Mechanisms of Traditional Chinese Medicine in Obesity Management

Abstract

Abstract Obesity is a major metabolic disorder with increasing global prevalence and limited long-term therapeutic success. Growing evidence indicates that the gut microbiota (GM) plays an important role in energy metabolism, immune homeostasis, and neuroendocrine regulation, making it a potential target for obesity management. Traditional Chinese Medicine (TCM), characterized by holistic and multi-target regulation, has increasingly attracted attention for its potential to modulate host metabolism through interactions with the GM. This review summarizes current evidence on the relationship between GM and obesity and examines how TCM interventions may regulate obesity through microbiota-related mechanisms. Particular attention is given to microbial metabolites, intestinal barrier function, and gut-brain communication. We further reinterpret classical TCM concepts, especially spleen function and the theory of “the spleen stores intent”, from the perspective of microbial activity and gut-brain interactions to establish a conceptual bridge between traditional theory and contemporary microbiome science. According to different therapeutic strategies in TCM, supplementing qi and strengthening the spleen may help restore microbial diversity and short-chain fatty acid production, thereby contributing to improved metabolic homeostasis through the G-protein-coupled receptors 41/43 (GPR41/43)–glucagon-like peptide-1 (GLP-1) pathway. Resolving turbidity to activate the spleen may alleviate metabolic inflammation by reducing lipopolysaccharide translocation, regulating Toll-like receptor 4 (TLR4)-mediated signaling, and modulating bile acid metabolism via the farnesoid X receptor (FXR)/Toll-like receptor 5 (TLR5) axis. Regulating qi and awakening the spleen may help stabilize gut–brain communication through modulation of gut-derived hormones and central appetite-related neuropeptides. Meanwhile, emerging evidence suggests that microbial biotransformation of herbal compounds may influence their bioavailability and therapeutic responsiveness, highlighting the bidirectional nature of TCM–microbiota interactions. Additionally, we introduce the “neuro-immune-microbiome axis” to explain how non-pharmacological therapies may indirectly remodel the GM. Overall, this review proposes an integrative framework linking TCM theory with microbiome research to better understand the therapeutic potential of TCM in obesity. While current evidence remains largely associative and relies heavily on preclinical studies, this perspective may provide new directions for microbiota-targeted and system-level strategies in obesity management.