Effect of Diet Quality on Gastrointestinal Integrity, Innate Immunity, and Circulating Lipoproteins

Human nutrition has largely focused on energy intake and recommended macronutrients to prevent obesity and disease development. Increased gut permeability, through diet or obesity, is thought to play a causative role in chronic systemic inflammation leading to disease. Dairy milk and its fractions have been shown by others to reduce body weight gain and adiposity and improve intestinal integrity relative to control diets. Studies using accelerated disease models, i.e. high-fat diet feeding, have allowed for assessing specific mechanisms but may not physiologically relevant for human dietary patterns and disease. To assess the effects of dairy milk or fractions within a moderate fat macronutrient distribution, 60 weanling C57Bl/6 male mice were fed one of four experimental diets for 13 weeks: isolated soy protein (ISP), dried whole milk powder (DWMP), milk protein concentrate (MPC) or milk fat globule membrane (MFGM). Isocaloric and isonitrogenous diets provided 20% energy (EN) as protein, 50 EN% carbohydrate and 30 EN% fat. Mice (n=15/diet treatment) grew and consumed feed similarly. Gut permeability, plasma LPS, and whole blood cytokine concentrations were low for all groups. Overall, dairy proteins had similar effects on lipoprotein classes. Relative to ISP, dairy proteins increased triacylglycerol-rich lipoproteins (2.8% v.1.4%) and high-density lipoproteins (75.6% v. 70.0%) and decreased low density lipoproteins (LDL) (21.6% v. 28.5%, p<0.05). Consumption of dairy proteins appears to improve lipoprotein profiles in C57/Bl6 mice when consumed in a moderate fat diet. A second study sought to if degree of dietary refinement altered gut health and lipoprotein biology. In a 14 week feeding trial, weanling C57Bl/6 mice (n=15/diet) were fed one of four diets differing in dietary protein source (soy or milk protein) and degree of refinement. All diets provided 20%EN PRO, 30% EN fat, and 50% EN CHO. Purified diets contained either isolated soy protein (ISP) or dried whole milk powder (DWMP) as the protein source, while non-purified diets contained either soybean meal (SPC), or dried whole milk powder (DMC) as protein sources. Mice fed purified diets were heavier than those fed non-purified diets, with ISP-fed mice being heaviest and having the most fat. At week 12, in vivo intestinal permeability was highest in ISP-fed mice (12.8 ng/mL), being significantly increased over DMC (8.96 ng/mL; p<0.02) Purified diet feeding resulted in increased apparent GI-p, regardless of protein source (12.1 ng/mL vs. 9.56 ng/mL; p<0.004). Measured cytokines were generally low and nonindicative of either tissue or systemic inflammation. Density distributions of NBDstained lipoproteins showed that diets containing milk protein increased triacylglycerolrich lipoproteins and high-density lipoproteins and decreased low-density lipoproteins (p<0.04) Compared to all other diets, mice fed ISP had a 30% increase in small dense LDL (p