Protective effect of 1,3-dioleoyl-2-palmitoylglycerol against DSS-induced colitis modulating gut microbiota and maintaining intestinal epithelial barrier integrity.

Inflammatory bowel disease (IBD) is a challenging condition to cure that can occur at any age. The gut microbiome and intestinal epithelial barrier play a crucial role in the development of IBD. 1,3-Dioleoyl-2-palmitoylglycerol (OPO), the predominant triglyceride in breast milk, is a structural lipid with multiple physiological functions. However, the protective effect of OPO on IBD and its underlying mechanism remains unclear. This study showed that oral administration of OPO markedly ameliorated dextran sulfate sodium (DSS)-induced colitis phenotypes. OPO treatment reduced inflammation levels by suppressing the TLR4-MyD88-NF-κB signaling pathway in colitis mice. Furthermore, OPO treatment improved intestinal epithelial barrier function promoting epithelial cell proliferation and differentiation, inhibiting cell apoptosis, and upregulating tight junction protein expression. The 16S rRNA gene sequencing revealed that OPO treatment restored microbial alpha diversity and reshaped the microbiota of colitis mice. Therefore, our study revealed that OPO exhibited a protective role in DSS-induced colitis maintaining intestinal epithelial barrier integrity and modulating gut microbiota. Our results highlight that OPO could be used as effective supplements for individuals with IBD or intestinal dysfunctions.