Two′‐Fucosyllactose, a Human Milk Oligosaccharide, Promotes Intestinal Remodeling and Enhances Nutrient and Functional Component Absorption

ABSTRACT 2 ′ ‐Fucosyllactose (2′FL) is an abundant human milk oligosaccharide and is recognized for its diverse biological benefits. The aim of this study was to investigate the effects of 2′FL supplementation on small intestinal remodeling and the associated enhancement of nutrient absorption capabilities. Mice were orally supplemented with 2′FL daily for 20 d. This supplementation significantly increased the length of the small intestine and the density of villi, with no adverse effects on intestinal barrier function. Mice treated with 2′FL exhibited an enhanced absorption of triglycerides containing docosahexaenoic acid in lipid tolerance tests. Additionally, the absorption of CL316,243 and curcumin was significantly increased in the co‐administration groups. This was accompanied by elevated uncoupling protein 1 levels in inguinal adipose tissue. Our study showed that 2′FL enhances nutrient and functional compound absorption by promoting intestinal remodeling. This highlights the novel role of 2′FL—a non‐nutritive compound—in supporting intestinal health. Our findings suggest potential applications of 2′FL in growth promotion, lifestyle‐related disease prevention, and frailty reduction, thereby advancing research on the nutritional functions of food‐derived compounds.