Ovalbumin Peptides Restore Intestinal Barrier Integrity via Gut–Liver Axis Modulation of Bile Salt Hydrolase and Bile Acids Crosstalk

Inflammatory bowel disease (IBD) is characterized by intestinal barrier dysfunction and bile acid (BA) dysmetabolism. BA metabolism was a pivotal regulator in the "gut-liver axis" to maintain intestinal homeostasis. Ovalbumin-derived peptides (OVA-Ps) exhibit potential in barrier repair; however, their systemic mechanisms within the microbiota-BA-host network remain underexplored. This study investigates the therapeutic potential of the oligomer OVA-P in a DSS-induced colitis mouse model. OVA-P administration significantly alleviated colitis symptoms, restored colon length, reduced pro-inflammatory cytokines (tumor necrosis factor-α), and enhanced antioxidant markers (SOD). Mechanistically, the OVA-P reshaped gut microbiota composition, suppressed bile salt hydrolase (BSH), and elevated conjugated BAs (e.g., taurocholic acid) levels. These changes activated the farnesoid X receptor (FXR) pathway, upregulating tight junction protein (ZO-1), and mucin (MUC-2) expression, thereby restoring intestinal barrier integrity. Metabolomic and metagenomic analyses confirmed the OVA-P-mediated modulation of the gut-liver axis through FXR-SHP/FGF15 signaling, highlighting its role in maintaining BA homeostasis. These findings provide insights into the use of OVA-P as a dietary intervention for IBD by targeting microbiota-BA-FXR interactions, offering a foundation for high-value egg protein applications in functional foods.