Grant: Discovery Grants Program - Individual

The gastrointestinal (GI) tract secretes a variety of hormones that control many aspects of normal metabolism. These hormone secreting cells are regulated by several factors including nutrients, the nervous system and even other hormones. My laboratory's long term research focus is understanding the mechanisms controlling this hormone regulation. However, one factor that has been largely overlooked is how the microorganisms that live in the GI tract (the GI microbiome) influence GI hormone secretion. This is surprising since the GI tract is replete with microorganisms, and these microorganisms have already been shown to regulate various aspects of physiology. My proposal seeks to provide the missing link in how the GI microbiome can directly regulate GI hormone secretion. This will be achieved through 2 research aims that examine the effects of microbial metabolites (products that microorganisms produce) on intestinal hormone secretion. This will be investigated using hormone secreting endocrine cell models in aim 1, followed by validation in live animals in aim 2. As the GI hormones being studied play pivotal roles in metabolic regulation, we will examine how these bacterial metabolites cause changes in metabolism (aim 2). Through these studies, we predict that microbial metabolites including short chain fatty acids and the microbial gases H2S and methane will directly regulate the secretion of metabolic GI hormones (including Ghrelin, glucagon-like peptide-1, glucose-dependent insulinotropic peptide, and cholecystokinin). We also predict that hormone changes brought on by microbial metabolites will cause physiological changes including appetite and glucose regulation.*My lab's work on the mechanisms of hormone release from unique primary cell models and animal models will enable a clear understanding of how the gut microbiome is able to influence GI hormone secretion and host metabolism. This approach to understanding the potential roles of the microbiome is innovative since it will provide a direct functional link between the GI microbiome and physiological (something that at present is largely lacking). This will impact several fields of research including microbiology and endocrinology, but may also influence individuals in nutrition and clinical science who aim to determine how changes in the microbiome can influence physiology.*