Assessing the role of gut biota in obesity and diabetes

Abstract

Obesity, insulin resistance and associated metabolic disorders are reaching epidemic proportions worldwide with more than a billion individuals overweight and over 300 million clinically obese. Easy access and availability to energy-dense diets and sedentary lifestyle choices have led to increased obesity since 1980 in Australia and several parts of the world, including in some of the developing countries.«br /» Gut microbiota is a major component that can make a significant impact on our health and has been linked to obesity, insulin resistance and progression to type 2 diabetes. The modulation of gut microbiota holds significant therapeutic potential to treat this globally growing epidemic. We assessed the changes in gut microbiota in two different animal models of obesity and diabetes. First, in the Thrifty rat model (Hardikar A et al «em»Cell Metabolism«/em» 2015), we identified that multigenerational undernutrition is associatded with reduced SCFA-producing bacteria and transition to a normal diet (Recuperation group) leads to increased SCFA producing bacteria in the gut. The Recuperation group showed a microbiome closer to the Control group rats. These and related studies from the Hardikar lab that were not a part of my Master’s thesis identified the beneficial effects of short chain fatty acids –producing bacteria in metabolic health. We therefore assessed the potential of SCFAs in treating existing obesity using a high fat diet (HFD) mouse model. These studies confirmed that oral supplementation of SCFAs can be a possible therapy. Although SCFA supplementation did not change body weight post intervention, the composition of the microbiome showed increased SCFA producers in treated vs placebo-HFD-fed mice. Intriguingly, though SCFA intervention did not lead to reduction in body weight, these mice were seen to be insulin sensitive as compared to the HFD placebo-mice. «br /» This work represents a small part of a larger study from the Hardikar lab that is aimed at understanding molecular mechanisms underlying epigenetic regulation of obesity and type 2 diabetes. The present work demonstrates that i) multigenerational undernutrition leads to changes in gut biota, but restoration of a normal diet improves the proportion of SCFA-producing bacteria; and ii) SCFA therapy improves insulin sensitivity following oral administration in high-fat diet fed obese mice. These studies demonstrate the need to further explore the role of SCFAs in treatment of obesity and type 2 diabetes.