Ovalbumin Peptides Restore Intestinal Barrier Integrity via Gut-Liver Axis Modulation of Bile Salt Hydrolase and Bile...

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.