Traditional Chinese medicine polysaccharides in intestinal disease: From pathological axes to structure–activity relationships

Intestinal diseases, including inflammatory bowel disease and colorectal cancer, share interconnected pathological features characterized by immune-inflammatory dysregulation, disrupted microbiota–host interactions, and impaired epithelial barrier integrity. Traditional Chinese medicine (TCM) polysaccharides have been reported to exert multifaceted bioactivities relevant to these conditions, including immunomodulatory, anti-inflammatory, microbiota-regulating, and barrier-protective effects. Their structural properties—including molecular weight, monosaccharide composition, glycosidic linkages, degree of branching, and 3-dimensional conformation—are closely associated with their biological activities and intestinal behaviors, although the specific contributions of individual structural features remain incompletely understood. Moreover, TCM polysaccharides have attracted attention as functional components of intestinal delivery systems because of their mucoadhesive properties, microbiota-responsive degradation potential, and adaptability to disease-associated microenvironmental cues. These properties may contribute to sustained local exposure and improved therapeutic performance. In this review, we summarize current evidence on the structure–activity and structure–delivery relationships of TCM polysaccharides, with a focus on how specific structural features relate to axis-targeted bioactivities and therapeutic outcomes. Finally, we discuss current limitations, including heterogeneity in polysaccharide sources, variability in experimental models, and the scarcity of clinical data, and propose future directions for developing multifunctional polysaccharide-based therapeutics for the management of intestinal diseases.