Yogurt Supplementation Attenuates Insulin Resistance in Obese Mice by Reducing Metabolic Endotoxemia and Inflammation

Background: Inflammation is an underlying mechanism for the development of obesity-related health complications. Yogurt consumption inhibits obesity-associated inflammation, but the tissue-specific mechanisms have not been adequately described. Objectives: We aimed to determine the tissue-specific responses by which yogurt supplementation inhibits inflammation.Methods: C57BL/6 male mice (5 wk old) were fed a Teklad Global 14% Protein Rodent Maintenance diet as a control or a high-fat diet (60% calories from fat) to induce obesity for 11 wk, followed by feeding a Western diet (WD; 43% carbohydrate and 42% fat) or WD supplemented with 5.6% lyophilized yogurt powder for 3 wk to test for the impact of yogurt supplementation. Markers of metabolic endotoxemia and inflammation were assessed in plasma and tissues. Cecal and fecal microbiota were profiled by 16S rRNA sequencing. Results: In obese mice, relative to the WD control group, yogurt supplementation attenuated HOMA-IR by 57% (P = 0.020), plasma TNF-alpha by 31% (P < 0.05) and colonic IFN-gamma by 46% (P = 0.0034), which were accompanied by a 40% reduction in plasma LPS binding protein (LBP) (P = 0.0019) and 45% less colonic Lbp expression (P = 0.037), as well as alteration in the beta diversity of cecal microbiota (P = 0.0090) and relative abundance of certain cecal microbes (e.g., Lachnospiraceae Dorea longicatena with P = 0.049). There were no differences in the LBP, Lbp, and Cd14 levels in the liver and small intestine between obese mice with and without yogurt supplementation (P > 0.05).Conclusions: Yogurt consumption inhibits obesity-induced inflammation in mice by modulating colonic endotoxin detoxification, changing the gut microbiota, and improving glucose metabolism. This work helps to establish the underlying mechanisms by which yogurt con-sumption affects markers of metabolic and immune health.