Bovine α-lactalbumin hydrolysates ameliorate obesity-associated endotoxemia and inflammation in high-fat diet-fed mice through modulation of gut microbiota

Gut microbiota has been identified as an important factor in the link between nutrient excess and obesity. The aim of this study was to confirm whether bovine alpha-lactalbumin hydrolysates (LAH) can ameliorate high-fat diet (HFD)-induced endotoxemia and systematic inflammation by modulating the structure of gut microbiota in mice. The results showed that LAH changed the overall structure of gut microbiota in HFD-induced obese mice. LAH increased the Bacteroidetes/Firmicutes ratios and the relative abundance of S24-7, Lachnospiraceae and Blautia. Spearman's correlation analysis revealed significant correlations between the alteration of gut microbiota and obesity-related indexes. LAH decreased the HFD-induced protein expression of G protein-coupled receptor 43 (GPR43) and 41 (GPR41) in the colon tissue. Besides, LAH inhibited the destruction of the gut barrier through the up-regulation of tight junction protein (zonulin/zonula occludens (ZO)-1 and occludin) expression and the decrease of toll-like receptor 4 (TLR4) protein expression in the colon tissue. LAH also significantly reduced the concentration of tumour cell necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in both serum and colon and decreased the level of lipopolysaccharides (LPS) in serum and feces, leading to reduced systematic inflammation and metabolic endotoxemia. In summary, LAH partly modulated the gut microbial composition and structure, and alleviated the obesity-associated inflammation. These findings shed light on bovine alpha-lactalbumin hydrolysate as a potential functional food ingredient to prevent obesity-related inflammation.