The Traditional Chinese Medicine–Gut Microbiota–Colorectal Cancer Axis: Mechanistic Insights and Recent Progress

Colorectal cancer (CRC) remains a leading cause of global cancer mortality, with gut microbiota (GM) dysbiosis playing a critical role in its pathogenesis. Traditional Chinese Medicine (TCM) offers a holistic, multi-target approach and has shown increasing promise in CRC prevention and treatment through GM modulation. This review systematically proposes the "TCM-GM-CRC" axis and elucidates seven interconnected mechanisms through which it mediates the anti-CRC effects of TCM: Reshaping microbial balance by inhibiting pathogens and enriching probiotics; repairing intestinal barrier integrity through upregulation of tight junction proteins and mucin production; suppressing oncogenic and pro-inflammatory signaling pathways by pathogenic bacteria; remodeling the tumor immune microenvironment through immunocyte regulation; modulating microbial metabolites such as short-chain fatty acids, bile acids, and tryptophan derivatives; intervening in CRC cell metabolic reprogramming, including aerobic glycolysis and aberrant lipid metabolism; and inhibiting epithelial-mesenchymal transition and metastasis. Key herbal formulas and active compounds discussed include Canmei Formula, Wu Mei Wan, Gegen Qinlian Decoction, Banxia Xiexin Decoction, and Pien Tze Huang, as well as single compounds such as berberine, evodiamine, curcumin, ginsenoside Rh4, and sophocarpine, which exert anti-CRC effects through distinct GM-mediated pathways. We emphasize the synergistic and multi-dimensional role of TCM in targeting GM and its functional metabolites to combat CRC. To deepen the understanding of the "TCM-GM-CRC" interaction mechanisms, future research should integrate multi-omics technologies, germ-free models, fecal microbiota transplantation, and clinical translation. Additionally, the development of "TCM-plus" combinatorial strategies, microbiota-targeted nanodelivery systems, and medically formulated foods is advocated to advance CRC precision prevention and treatment centered on GM.