A-047 Role of the Gut Microbiota in the Efficacy of Dietary Intervention With Flavonoid-Containing Foods in Obesity

Abstract

Abstract Background Flavonoids are an active component of plant-based diets that have been investigated for their beneficial antioxidant properties in high fat diet induced obesity animal models and human intervention trials. Certain bacterial members of the gut microbiota have been reported that transform flavonoids into monophenolic acids. Our goal is to characterize the microbiome link between a flavonoid-rich diet and improved metabolic parameters characteristic of obesity. We hypothesize that flavonoid supplemented diets are most effective in presence of microbiota capable of monophenolic acids formation, and that these bacterial metabolites are a main bioactive compound responsible for the improved metabolic parameters. Methods To test our hypothesis, males and females C57BL/6 mice were fed a high fat control diet, or the same diet supplemented with 1% berry extract, or 1% monophenolic acid for 12 weeks. Separate experimental groups received either regular drinking water or antibiotic water to suppress their gut microbial community. We monitored metabolic parameters, including body weight, lean and fat mass, glucose and insulin tolerance, histological assessment of liver cell, quantification of liver injury biomarkers, and transcriptional changes in metabolically active peripheral tissues. Results For insulin tolerance test, mice on high fat diet with regular water, or antibiotic water control mice had a comparable increase in insulin resistance, demonstrated by the increase in glucose levels after injecting insulin. Similarly, the groups of mice on high fat diet with 1% monophenolic acid and regular water, or antibiotic water, had improved insulin sensitivity, presented as a decrease in glucose levels after insulin injection. Consistent with our hypothesis, mice on high fat diet supplemented with 1% berry extract had an improved insulin sensitivity, and this effect was dependent on an intact microbiome. This suggests that the gut microbiota are required to metabolize the berry extract to produce bioactive metabolites that improve insulin tolerance. We also observed a significant decrease in fasting blood glucose, an improvement in the expression for genes involved in lipid and glucose metabolism, and a noticeable reduction in hepatic steatosis in both 1% monophenolic acid and 1% berry extract with high fat diet group, compared to the high fat diet control group. Conclusion By feeding the mice a flavonoid rich diet, with the presence of an intact gut microbiota, we can improve the metabolic parameters associated with metabolic diseases. Our work will open the door for new benign approaches for treatment, such as dietary flavonoid supplementation with concomitant gut microbial probiotic therapy.