Xian Wu, Shuwen Shi, Chenxi Zhang, Mengya Lu, Zhenyu Zhang, Zixin Luo, Xingchen Yao, Tao Peng, Hao Nie, Junjie Wu, Z. Y. Yuan, Junxing Ye, Tianhao Liu, Xia Li, Feng-lai Yuan
ABSTRACT Introduction Osteoporosis, characterized by disrupted bone remodeling and increased fracture risk, represents a growing global health burden that conventional single-target therapies fail to fully address. Emerging evidence highlights gut microbiota (GM) dysbiosis as a critical pathogenic factor, wherein microbial metabolites—particularly short-chain fatty acids (SCFAs) orchestrate systemic immune responses and bone homeostasis. Traditional Chinese Medicine (TCM) offers a theoretically grounded approach through its classical "Spleen-Kidney interdependence" framework, which conceptualizes gut function as integral to skeletal health. However, the mechanistic pathways through which TCM formulations modulate the GM-bone axis remain insufficiently characterized. Methods We conducted a systematic search of databases (PubMed, Embase, Scopus, Web of Science) to identify studies investigating TCM interventions targeting the gut-bone axis. Ultimately, 46 studies met the inclusion criteria. Results TCM formulations consistently restore GM diversity, enriching SCFAs-producing taxa ( Akkermansia, Lactobacillus, Bifidobacterium ) while suppressing pathogenic populations. Individual medicinals and bioactive constituents exert taxon-specific effects through neuroendocrine, prebiotic, and metabolic pathways. Nano-engineered delivery systems further overcome bioavailability limitations for targeted colonic release. Conclusion TCM operates through a "microbiota-barrier-immune-metabolism-bone" hierarchical network, transforming traditional "tonifying Kidney and strengthening Spleen" efficacy into quantifiable gut-to-bone regulatory mechanisms. This positions TCM as a systems-level alternative to conventional therapies.