Targeting the Microbiota–Metabolism–Immunity Axis: Active Components of Traditional Chinese Medicine in Colitis-Associated Colorectal Cancer

Abstract

Colitis-associated colorectal cancer (CAC) develops in the setting of long-standing intestinal inflammation and remains a major complication of inflammatory bowel disease (IBD). Although effective control of inflammation may reduce cancer risk, approaches that specifically prevent the progression from chronic colitis to neoplasia remain limited. Disruption of the gut microbiota–metabolism–immunity axis is increasingly implicated in this process, as microbial dysbiosis and altered metabolite production can compromise epithelial barrier integrity, sustain inflammatory signaling, and disturb mucosal immune homeostasis. This review examines how active components derived from traditional Chinese medicine (TCM), particularly flavonoids, alkaloids, saponins, and polysaccharides, influence this interconnected network in CAC-related models. Rather than treating these constituents as a single group, we compare the mechanistic patterns and evidence base associated with each class. Flavonoids and alkaloids have been studied mainly in relation to inflammatory signaling and epithelial barrier protection, whereas saponins are more often linked to regulation of the immune microenvironment. Polysaccharides have been studied most frequently in relation to microbiota remodeling, short-chain fatty acid production, and mucosal immune balance. These distinctions are not absolute, and substantial overlap exists across component classes. Moreover, most evidence is derived from animal or cell-based studies, with marked variation in experimental models, compound characterizations, dosing, and outcome assessments. The microbiota–metabolism–immunity axis provides a coherent framework for interpreting the multi-level actions of TCM-derived components, but their causal mechanisms and clinical relevance to human CAC require further validation.