ECCO Grant Study Synopsis: Harry Sokol
Harry Sokol, ECCO Grant Awardee
Host–microbiota crosstalk through tryptophan metabolism in Inflammatory Bowel Diseases (IBD)
© Harry Sokol
Aim of Research
The aim of this work is to study the communication between host cells and microbiota through tryptophan (Trp) metabolism and particularly: (i) the effects of microbes on Trp metabolism in host cells, (ii) the effects of Trp metabolites on host cell response to microbes and (iii) the interaction between epithelial and immune cells through Trp metabolism and the consequences for inflammatory responses.
The first step is the evaluation of the effects of microbial extracts and intestinal bacteria on intestinal epithelial and dendritic cells of healthy subjects and Trp metabolism response using a mass spectrometry approach already set up in the laboratory. The same experiments will be conducted on cells from patients with IBD. Conversely, effects of ten Trp metabolites (from host and gut microbiota) on host cells will be evaluated. The production of different cytokines (IL-8, TNF-α and IL-10) and the expression of several genes involved in aryl hydrocarbon receptor response will be evaluated. Moreover, global inflammation responses will be analysed using multiplex analysis of 249 mRNA (NanoString®). Data obtained in vitro will be expanded in vivo using colitis models already set up in the lab.
The first round of application of different microbial extracts on both epithelial and immune cells was already completed in September, at the same time as mass spectrometry analysing of Trp metabolism in intestinal epithelial cells. The effect of some Trp metabolites on inflammation is under investigation and samples were sent for multiplex analysis in August; results are currently being analysed. Taking account of the results, further experiments will have been conducted by the end of the year.