Ovotransferrin Alleviates Ulcerative Colitis by Modulating Ligilactobacillus murinus-Mediated Bile Acid Metabolism via the Ptgs2/JAK-STAT Signaling Axis.

Ovotransferrin (OVT) is a functionally active protein demonstrated to alleviate ulcerative colitis (UC), although its mechanism remains incompletely understood. Notably, UC is closely associated with dysbiosis of the gut microbiota. This study investigates the potential of OVT to alleviate colitis by reshaped gut microbiota composition in a DSS-induced UC mouse model. Specifically, Ligilactobacillus murinus (L. murinus) was isolated from the gut microbiota of OVT-treated UC mice and stimulated by OVT in vitro. Integrated whole-genome sequencing and targeted metabolomics revealed that L. murinus encodes bile salt hydrolase, thereby driving secondary bile acid biosynthesis. Mechanistically, fermentation products (FP) derived from coculture of L. murinus with bile exerts potent anti-inflammatory in both Caco-2 cells and a colitis model by Ptgs2 (COX-2) downregulation and the JAK-STAT signaling pathway inhibition. These results established the "OVT-L. murinus-bile acids-Ptgs2/JAK-STAT" axis as a novel mechanism for UC treatment, providing a foundation for high-value applications of OVT in functional foods.