Milk lactopeptide alleviates marginal zinc deficiency-associated gut-immune disturbances in rats: associations with barrier-related signaling and gut microbiota.

Marginal zinc deficiency (MZD) is a common but often overlooked nutritional condition associated with impaired intestinal barrier integrity and immune dysfunction. Milk lactopeptide (LP) have attracted interest as food-derived bioactive ingredients with potential zinc-binding capacity and immunomodulatory activity. In this study, the physicochemical characteristics and predicted Zn2+-binding potential of LP were evaluated, and their effects on gut-immune disturbances in MZD rats were investigated. LP were characterized by molecular weight distribution, amino acid composition, spectroscopy, and in silico peptide screening. An MZD rat model was then established to assess the effects of graded LP intervention on growth performance, immune-related parameters, intestinal morphology, zinc status, barrier-related proteins and genes, and gut microbiota composition. The results showed that LP were rich in low-molecular-weight fractions and contained peptide features consistent with potential Zn2+ interaction. In vivo, LP improved growth retardation, partially restored immune organ development, increased blood zinc levels and apparent zinc absorption, and ameliorated colonic structural damage in a dose-dependent manner. These effects were associated with the modulation of tight junction-associated proteins and genes, as well as changes in ZIP6 expression and NF-κB-related signaling. and alterations in gut microbiota composition. Collectively, these findings suggest that fermented LP may help alleviate MZD-associated gut-immune disturbances and may serve as a promising food-derived ingredient for nutritional intervention.