2'-Fucosyllactose promotes intestinal epithelial development via modulating gut microbial metabolism in neonatal 2'-Fucosyllactose promotes intestinal epithelial development via modulating gut microbial metabolism in neonatal mice.

2'-Fucosyllactose (2'-FL), a major human milk oligosaccharide, has been demonstrated to support early-life gut maturation and microbial balance. However, the association between 2'-FL, intestinal epithelial development, and gut microbiota remains unclear. In this study, a 3-d-old murine model was established to investigate intestinal epithelial differentiation, variations in gut microbes and metabolism. The results showed that 2'-FL enhanced intestinal barrier function by upregulating the expression of tight junction proteins and increasing goblet cell density in the duodenum, in addition to promoting mucin-2 secretion. Furthermore, 2'-FL stimulated the Lgr5+ intestinal stem cell-Paneth cell axis, resulting in a 4-fold increase in Lgr5 expression and upregulation of the Paneth cell marker lysozyme as well as the progenitor cell marker Musashi, thereby accelerating epithelial regeneration. Microbiota analysis revealed the enrichment of Lactobacillus and Bifidobacterium, accompanied by a significant enhancement in the accumulation of l-arginine and ornithine accumulation, which have been shown to promote intestinal development. These results suggest that 2'-FL promotes intestinal stem cell proliferation and barrier maturation by modulating gut microbial metabolism. These findings provide important insights into the role of 2'-FL in promoting infant gut homeostasis.