Grant: Operating Grant

Gut contains hundreds of thousands of endocrine cells which react to changes in gut contents by releasing hormones that are, in general, targeted to other parts of the digestive system. Enterochromaffin (EC) cells are best characterized endocrine cells in gut, and are the major source of serotonin which is also known as 5-hydroxytryptamine (5-HT). About 95% of the body's 5-HT is located in gut and 5-HT is implicated in a number of intestinal diseases including inflammatory bowel disease, functional disorders like irritable bowel syndrome, and in a number of intestinal infections. Gut is inhabited by trillions of commensal microorganisms that play crucial roles in gut physiology, aid digestion, provide competitive barriers to pathogen invasion, and contribute to immune system development. Due to the close proximity of endocrine cells to gut microbiota it is very likely that crosstalk between EC cells and microbiota plays a crucial role in gut health. Despite this strategic importance of EC cells and the microbiome, the relationship between the two is poorly defined and deserves further attention. This research proposal is planned to explore the crosstalk between gut microbiota and EC cells by assessing the role of gut flora in regulation of EC cell biology and 5-HT production, the role of 5-HT in regulation of gut microbial composition and the role of EC cells-gut flora axis in intestinal inflammation and host defense. In addition to enhancing our understanding of the EC cell biology this study will provide new information on the role of crosstalk between 5-HT and microbiota in gut pathology and host defense. This research also has significant clinical relevance. Identifying the bacterial species associated with alteration in 5-HT production and the role of 5-HT in modulation of gut flora composition may ultimately lead to improved strategies to treat various GI disorders by utilizing either the bacterial species or targeting 5-HT signaling.