29-LB: Investigating the Molecular Basis of the Microbiota-Mediated Regulation of Postprandial Chylomicron Production

Obesity and insulin resistance have been identified as major global health concerns. They are associated with increased intestinal chylomicron production and subsequent remnant lipoprotein accumulation which lead to postprandial dyslipidemia. Dietary composition influences metabolic output of the gut microbiota by digesting dietary nutrients and producing various metabolites, which affects host metabolism. Understanding the mechanistic roles of the microbiota in regulating host lipid metabolism is therefore critical in addressing the pathogenesis of dyslipidemia. In this study, we aimed to investigate the effects of microbiota on lipid and lipoprotein metabolism in Syrian golden hamsters which is a more relevant animal model to human. Microbiota depletion was induced in male and female hamsters given either standard chow or a low fat/high fructose (HF) diet via antibiotic oral gavage administration. The results showed that feeding a HF diet increased plasma triglyceride (TG) and cholesterol (CH) levels while substantially reduced microbiota in antibiotic-administered groups led to significant reduction in circulating TG and CH in both diets. Then, we intended to look at the role of dysbiosis on postprandial lipid accumulation. Interestingly, in both sexes postprandial and TRL-TG levels were dramatically reduced after antibiotic administration; the effect was associated with significantly decreased ApoB48 protein levels. These changes appear to be due to a modulation of genes involved in farnesoid X receptor (FXR) receptor signaling in the ileum. Additionally, some critical genes implicated in lipid synthesis and absorption were also altered in the jejunum, with the most remarkable discovery being the extremely substantial down regulation of Scavenger Receptor Class B type 1“SR-B1” at both the mRNA and protein levels in all antibiotic-treated groups independent of sex and diet.

In summary, our results suggest a novel role for the gut microbiota in regulating lipid and lipoprotein metabolism in the gut, urging further studies to determine the underlying mechanisms.