Low-digestible glucans promote rapid recovery from 5-fluorouracil-induced small intestinal villous atrophy while enhancing glucagon-like peptide-2 secretion in rats.

Small intestinal villous atrophy, a frequent complication of cancer chemotherapy, impairs nutrient absorption and worsens participant quality of life. Although the glucagon-like peptide-2 (GLP-2) analog teduglutide can promote villus regeneration, its clinical application is limited. We hypothesized that dietary low-digestible glucans (LDGs) would enhance GLP-2 secretion and accelerate mucosal recovery. This study evaluated whether LDGs stimulate GLP-2 secretion and facilitate recovery from 5-fluorouracil (5-FU)-induced villous atrophy in rats. Male Sprague-Dawley rats were treated with 5-FU to induce villous atrophy, followed by diets containing resistant maltodextrin (RMD) or isomaltodextrin as LDGs. Portal GLP-2 concentrations, small intestinal villus height, maltase activity, and cecal short-chain fatty acid concentrations were assessed at 3 and 6 days after LDG supplementation. LDG supplementation significantly increased portal GLP-2 concentrations and accelerated recovery of villus height in the small intestine, especially in the ileum, compared with controls. Notably, villus height in the RMD group recovered within 3 days, whereas 6 days were required in controls. Both RMD and isomaltodextrin increased cecal tissue weight, and LDGs induced only a transient reduction in cecal acetate concentration. However, when 5-FU was administered concurrently, LDGs did not promote villus recovery, suggesting that their effect requires preserved epithelial proliferative capacity. In summary, LDGs promote rapid recovery of small intestinal villi after chemotherapy-induced injury, possibly through enhanced GLP-2 secretion. Dietary LDGs may offer a novel nutritional intervention to support mucosal recovery in participants undergoing cancer chemotherapy.