Effects of 1,3‐Dioleoyl‐2‐palmitoylglycerol on Intestine Structural and Functional Development in Early Life

1,3-Dioleoyl-2-palmitoyl-glycerol (OPO) is a specific triglyceride in human breast milk, and it has been added to infant formula to mimic human breast milk fat. Existing studies only focused on its effects on fatty acid and calcium absorption, as well as the intestinal microbial composition; however, effects of OPO on the early-life development of intestine were still unclear. Our study explored the effects of OPO on intestinal epithelial structure and barrier construction in neonatal mice and the involvement of intestinal microorganisms. OPO supplementation significantly increased the number of intestinal stem cells, which in turn promoted villus and crypt, and promoted goblet cell and Paneth cell differentiation. OPO also promotes epithelial barrier integrity by increasing the expression of mucin 2, lysozyme 1, and tight junction proteins. Furthermore, the benefits of OPO were associated with the higher abundance of beneficial bacteria (unclassified_f_Muribaculaceae, Akkermansia, Bifidobacterium, and Blautia) and elevated butyrate levels. This study demonstrates the efficacy of OPO on intestinal health in neonatal mice beyond defecation, expands the understanding of the biological functions of OPO, and expands its application in intestinal health products targeting special populations, such as the elderly or individuals with intestinal fragility or injury.