Citrus flavonoid-enriched milk protects against intestinal oxidative stress and barrier dysfunction in mice

This study investigated the impact of dietary citrus flavonoid extract (CFE) supplementation in dairy cows on milk composition and its protective effects against intestinal oxidative stress. Supplementation with 150 g/d CFE significantly enriched bovine milk with bioactive flavonoids, including hesperidin, narirutin, naringin, a their conjugated metabolites, as well as polymethoxyflavones such as nobiletin and tangeretin. These changes were accompanied by elevated total phenolic and flavonoid concentrations and enhanced milk antioxidant capacity. In a lipopolysaccharide (LPS)-challenged mouse model, CFE-enriched milk improved systemic and intestinal antioxidant enzyme activities, reduced inflammatory cytokine production, and upregulated tight junctions and Nrf2/HO-1/NQO1 pathway gene expression. Histological analyses confirmed restoration of intestinal morphology and goblet cell abundance. Moreover, supplementation modulated gut microbiota, increasing beneficial taxa (e.g., Lactobacillus, Bacteroides) and reducing harmful genera (e.g., Desulfovibrio). Collectively, these findings demonstrate that citrus flavonoid-fortified milk confers antioxidant, anti-inflammatory, and gut-protective effects, supporting its potential as a functional dairy product.