Impact of Gut Microbiota on Host Physiology
Enterochromaffin (EC) in the colonic mucosa
This image illustrates presence of EC cells (red) co-localized with serotonin receptor (highlighted by arrows) in the colonic mucosa. DAPI was used to localize epithelial nuclear staining.
Calcein-AM labeled murine colonoids
The Gut Microbiome Laboratory at Mayo Clinic is studying the impact of microbial colonization on host physiology. As a part of this project, Dr. Kashyap's research team is exploring the mechanisms via which the gut microbiota and its metabolites influence intestinal secretion and motility.
The human gastrointestinal tract is home to trillions of microbes that make up the gut microbiota. These microbes interact with the host to affect the host's physiological responses, including gastrointestinal motility, secretion and sensation.
Dr. Kashyap's lab has shown that gut bacteria and its metabolites modulate gastrointestinal physiology by increasing serotonin production from the enterochromaffin (EC) cells in the gastrointestinal tract. Serotonin is an important neurotransmitter and paracrine messenger in the gastrointestinal tract that plays a critical role in regulating gastrointestinal physiology in health and disease.
Serotonin released from the EC cells regulates gastrointestinal motility and secretion by acting on multiple serotonin receptor subtypes. The Gut Microbiome Lab is now examining how serotonin receptor subtypes are affected by gut microbiota and the resultant impact on gastrointestinal physiology, including both host mucus release and whole-gut motility.
The lab is investigating the role of gut microbiota metabolites such as short-chain fatty acids, bile acids and bacterially derived tryptophan metabolites on gastrointestinal function. Dr. Kashyap's research team uses a combination of technologies, such as next-generation sequencing including metagenomics and metabolomics, germ-free mouse models, and in vitro models such as organoids.
Research on the impact of the gut microbiome on host physiology in Dr. Kashyap's lab is aimed at improving the understanding of microbiota-mediated modulation of serotonin and other host signaling pathways, which will help scientists develop new targeted therapies for people with functional gastrointestinal disorders such as irritable bowel syndrome.