Dissecting the intestinal mucosal niche with the pathobiont Allobaculum mucolyticum

Muijlwijk, Guus van

Promoter:
Prof.dr J.P.M. (Jos) van Putten
Co-promoter:
Dr M.R. (Marcel) de Zoete
Research group:
Putten , Zoete
Date:
May 19, 2022
Time:
16:15 h

Summary

Our gut microbiota has a large influence on our health and well-being. The gut microbiota composition of inflammatory bowel disease (IBD) patients is often different from healthy people and  this is thought to contribute to disease development and progression. However, the exact molecular mechanisms that underlie disease are unclear. With this research we aimed to identify novel molecular mechanisms that help elucidate the pathways that drive pathological inflammatory conditions such as IBD. We investigated the novel inflammatory bacterium Allobaculum mucolyticum and focused on its interactions with critical components of the protective mucus layer and the mucosal barrier. We provided the first microscopic, genetic and chemical characterization of this novel species. Moreover, we functionally characterized the broad repertoire of mucolytic enzymes that this bacterium secretes and showed that it uses these enzymes to degrade mucins. Next, we showed that one of these enzymes, a sialidase, can alter the metabolic niche and thereby also inhibit the growth of other bacteria, such as the probiotic bacterium Akkermansia muciniphila. This type of inhibition has never been described before and provides important new insights into microbial metabolic pathways and microbial ecological networks in the gut. Finally, we revealed that bacterial sialidases can remove sialic acids from IgA antibodies and the surface of neutrophil, thereby increasing the inflammatory response. Overall, we identified many novel molecular mechanisms that elucidate how certain pathobionts disrupt the intestinal mucosal niche and may drive pathological inflammatory conditions such as IBD. This knowledge may help the development of novel therapies for IBD.