Glutamine boosts intestinal stem cell-mediated small intestinal epithelial development during early weaning: Involvement of WNT signaling

Early weaning usually causes small intestine epithelial development abnormality, increasing the risk of gastrointestinal diseases. Glutamine (Gln), enriching in plasma and milk, is widely reported to benefit intestinal health. However, whether Gln affects intestinal stem cell (ISC) activity in response to early weaning is unclear. Here, both the early weaning mice and intestinal organoids were used to study the role of Gln in regulating ISC activities. Results showed that Gln ameliorated early weaning-induced epithelial atrophy and augmented the ISC-mediated epithelial regeneration. Gln deprivation disabled ISC-mediated epithelial regeneration and crypt fission in vitro. Mechanistically, Gln augmented WNT signaling in a dose-dependent manner to regulate ISC activity, while WNT signaling blockage abolished the effects of Gln on ISCs. Together, Gln accelerates stem cell-mediated intestinal epithelial development associated with the augmentation of WNT signaling, which provides novel insights into the mechanism by which Gln promotes intestinal health. [Display omitted] •A novel early weaning mice model that undergoes growth retardation was established•Gln ameliorates early weaning-induced gut atrophy and growth retardation•Gln is essential for ISC self-renewal and epithelial differentiation in vitro•Gln augments Wnt to facilitate ISC-mediated intestinal epithelial development Early weaning usually disrupts small intestinal epithelial development in humans and livestock. In this article, using early weaning mice and organoid models, Yao, Jiang et al. demonstrate that glutamine is essential for stem cell-mediated intestinal epithelial regeneration and boosts intestinal stem cell activity associated with the augmentation of WNT signaling, thereby improving small intestinal epithelial development during early weaning.