Gut microbiota and metabolomic: The potential mechanism underlying the female-specific protective effects of Craterellus cornucopioides polysaccharide against chemotherapy-induced intestinal injury.

Chemotherapy agents, including cyclophosphamide (CTX), frequently induce severe intestinal injury characterized by oxidative stress, inflammatory responses, and microbiota dysbiosis, particularly in females who exhibit heightened immune and metabolic sensitivity. This investigation assessed the protective properties of Craterellus cornucopioides polysaccharide (CCP) against CTX-induced intestinal injury, with a focus on their impact on women's health through modulation of the gut microbiota and metabolic pathways. CCP significantly improved antioxidant and immune biomarkers (sIgA, SOD, CAT, T-AOC) while reducing pro-inflammatory markers (TNF-α, MDA) in mice treated with CTX. Histological analysis showed CCP restored intestinal barrier integrity by boosting the levels of tight junction proteins (ZO-1, Claudin-1) and promoting intestinal stem cell repair. Additionally, CCP modulated gut microbiota, increasing beneficial taxa (Lactobacillus, Dubosiella), while decreasing pathogenic genus (Bacteroides), thereby re-establishing microbial balance. Metabolomic analysis indicates that the differential involvement of steroid hormone biosynthesis, bile acid metabolism, and tryptophan metabolism in the observed regulatory effects. This underscored its role in restoring intestinal integrity and overall physiological balance. These findings establish a foundation for the development of female-specific adjunctive therapies to enhance gut health during chemotherapy.