Epithelial chymotrypsin: impact on the host-gut microbial biofilm interface

In the context of a PhD project, we are proposing the theory that intestinal epithelial chymotrypsin may exert both autocrine control on epithelial cells and a paracrine effect on the architecture of the intestinal microbial biofilm. We have already demonstrated the ability of this enzyme to activate intra-epithelial MAPK-type signalling and calcium mobilisation by cleaving the PAR epithelial receptor. Study of the effects of this activation on the biology of epithelial cells, and on the intestinal barrier, will form part of the objectives of this PhD project. During preliminary work, we have shown that host proteases are able to modify the physical and biological characteristics of the intestinal microbial biofilm. Another question will therefore be to establish whether chymotrypsin might affect the structure and functions of the intestinal microbial biofilm. According to data in the literature, anti-inflammatory properties have been attributed to chymotrypsin, but no study has demonstrated these effects in a context of intestinal inflammation. We will determine whether the administration of chymotrypsin can improve the state of the digestive mucosa and its bacterial biofilm in mouse models of intestinal inflammation. This research should throw new light on the role of one of the proteolytic actors in the intestinal mucosa, chymotrypsin, and its involvement in the host-microbiota interface.