Mode of action of butyrate in the human colon

Butyrate has recently gained attention as an important microbial compound in human colon health. Several diseases, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and type-2 diabetes (T2D), have been linked with a loss of butyrate in the colon, resulting in the hypothesis that butyrate may be important for disease resistance. Butyrate is produced in the colon by microbial fermentation of dietary fibres. It is the main energy source for our colon cells and it also functions as a histone deacetylase inhibitor inside the nucleus to epigenetically regulate gene expression and cell fate. Many studies, based on animal models and in vitro data, support butyrate as being anti-carcinogenic, anti-inflammatory and barrier protective in the distal human gut. However, up to now our knowledge is primarily based on human cell models and animal studies, and data from clinical studies are lacking.

This project aims to elucidate butyrate’s mode of action in the human colon and how butyrate potentially functions as a signalling molecule between the bacteria that produces it and our cells. Within this project, we will also characterise and quantitatively determine the transport of butyrate across the human colonic epithelium in different study groups. The latter is of importance since many of butyrate’s effects are dependent on its intracellular concentration.  A better understanding of the complex interactions that are associated with an increase of butyrate in the human colon is necessary to improve and record the therapeutic usability of butyrate.