Impact of Gut Microbiota on Host Physiology

Ussing chamber studies

Ussing chamber studies help researchers in the Gut Microbiome Lab advance the understanding of epithelial barrier properties and intestinal fluid and ion secretion.

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.

The lab is currently investigating the role of gut microbiota metabolites such as short-chain fatty acids, bile acids and 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.