Abstract:The study was conducted to investigate the effects of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) on gut health in weaned mice. Weaned mice were fed for 4 weeks and compared across three groups: the control group (CON group), the low-dose OPO group, and the high-dose OPO group. Various indicators were analyzed, including serum inflammation levels, intestinal tissue morphology, gene expression of tight junction proteins, intestinal permeability markers, gut microbiota diversity, and changes in short-chain fatty acids (SCFAs). The results showed that compared to the CON group, the serum levels of TNF-α and IL-1β in the LOPO group were reduced by 9.05% (P<0.01) and 9.71% (P<0.05), respectively; while in the HOPO group, the reductions were 10.71% (P<0.001) and 7.84%. The relative mRNA expression of claudin-1 in the LOPO group increased by 31.37% (P<0.05) compared to the CON group, whereas in the HOPO group, it increased by 38.24% (P<0.001). Additionally, serum LPS levels in the LOPO and HOPO groups decreased by 8.43% and 8.66% (P<0.05), respectively, compared to the CON group. Furthermore, dietary OPO regulated the gut microbiota composition, increasing the relative abundance of Akkermansia, Dubosiella, and Bifidobacterium, while decreasing the relative abundance of Desulfovibrio. SCFA results indicated that compared to the CON group, the contents of acetic acid, propionic acid, butyric acid, and valeric acid in the LOPO group increased by 162.32%, 72.7%, 216.24%, and 25.2%, respectively; in the HOPO group, they increased by 160.68%, 74.58%, 163.85%, and 23.03% (P<0.001). In conclusion, dietary OPO may enhance intestinal barrier function and inhibit systemic inflammatory responses in weaned mice by modulating gut microbiota and related SCFA metabolism, providing a theoretical basis for targeted regulation of gut microbiota by OPO.