Effect of milk protein hydrolysate supplementation on protein energy malnutrition-induced gut dysbiosis.

Dairy proteins in the diet are beneficial for the growth of probiotics; however, what is unknown is the gut-mediated immune responses under protein energy malnutrition (PEM) and if dairy protein hydrolysates can be effective as dietary interventions. This study compares the composition of the gut microbiota of rats with moderate protein deficiency (M.PEM) and severe protein deficiency (S.PEM) induced by feeding 5% and 1% hypoprotein diets, followed by replenishment with buffalo and whey protein hydrolysates. Fecal samples were collected, and the composition of the gut bacteria was analyzed by whole genome sequencing using long-read sequencing. Gene expression studies of the immunomodulatory cytokines involved and quantification of sIgA were carried out. IL-6 and IFN-γ were downregulated by about 0.17 ± 0.06 and 0.12 ± 0.10 fold when supplemented with whey protein hydrolysate in SP-RWC rats and by about 0.02 ± 0.06 and 0.35 ± 0.12 fold when using buffalo milk hydrolysate. The percentage of Firmicutes decreased in M.PEM and S.PEM rats (33.57%, 28.83 versus 47.73% of control at 3 weeks) but increased upon protein replenishment for all three protein sources at the end of nine weeks. The percentage of Bacteroidetes increased to 31.03% in S.PEM-induced rats as against 28.17% in control rats. The relative abundance of Lactobacillus sp. decreased in M.PEM and S.PEM rats while it showed the opposite effect upon protein replenishment. Gut microbiota modulated the pathogenesis of PEM differentially based on protein intervention along with a significant increase in the relative abundance of the keystone Lactobacillus genus.