Casein-phosphatidylcholine emulsifier remodels LPS-induced intestinal barrier disfunction via regulating ferroptosis and lipid metabolism

Recently, the biosafety of synthetic emulsifier in intestinal barrier has raised significant concerns. Casein- phosphatidylcholine (CP), which is a natural emulsifier, has better emulsification and stability. However, the effect of CP on intestinal barrier remains unknow. Intestinal permeability and lipomics analysis showed that carboxymethyl cellulose (CMC) and CP have no significant effect on intestinal barrier in normal intestinal barrier model, whereas CP increased transmembrane resistance value and remodeled lipid homeostasis in LPS induced intestinal barrier dysfunction model, indicating its superior biosafety. To explore the underlying molecular mechanism of emulsifier on intestinal barrier dysfunction, the bioinformatics analysis of six original microarray datasets including 168 cases in NCBI-Gene Expression Omnibus database showed ferroptosis-related genes showed a significant differential expression. The quantitative polymerase chain reaction analysis demonstrated that CP can repair the imbalance of lipid homeostasis induced by LPS and restore normal intestinal permeability by regulating the expression of ferroptosis-related genes, while CMC could can enhance intestinal permeability by inducing ferroptosis of intestinal epithelial cells through lipid peroxidation. In conclusion, this study highlighted CP could remodel LPS-induced intestinal barrier disfunction via regulating ferroptosis and lipid metabolism. These findings can be used as a new insight for the design of new healthy emulsifier.