Multiomics Unveils the Anti-inflammatory Mechanisms of Ovotransferrin with Varying Iron Saturation Levels: Insights from the <i>Lactobacillus</i> -Mediated Gut-Liver Axis

The limited understanding of ovotransferrin (OVT) has constrained its potential as a functional protein and a substitute for lactoferrin (LF). Although the anti-inflammatory effects of OVT are well established, the underlying mechanisms, especially those related to its iron-chelating ability, remain unclear. To investigate, we compared the anti-inflammatory effects of OVT at varying iron saturation. The results show that the OVT with different iron saturations reduces intestinal inflammation by reinforcing intestinal barrier function. They also lower liver inflammation by improving the hepatic structure and function. This may be linked to increased intestinal <i>Lactobacillus</i> abundance, which alters short-chain fatty acid profiles and activates hepatic fatty acid oxidation and degradation pathways, thereby lowering toxic lipids. The decrease in the number of toxic lipids helps preserve liver homeostasis by suppressing excessive lipophagy. Notably, Native-OVT and Mono-OVT showed stronger anti-inflammatory activity. These findings elucidate the anti-inflammatory role of the OVT through the gut-liver axis and underscore its functional potential.