Discovery and validation of metabolite biomarkers associated with increased susceptibility to intestinal inflammation

Several studies have shown that disturbed species distribution of the gut microbiota –a condition

termed dysbiosis –correlates with a variety of human diseases including Inflammatory Bowel

Disease (IBD). This triggered the idea that modulating the composition or the actions of the gut

microbiota might offer new therapeutic possibilities for IBD. Indeed, studies in mice confirmed a

causal role for the gut microbiota in the development of intestinal diseases. For instance, dysbiosis

in mice lacking Nlrp6 causes increased susceptibility to intestinal inflammation. Since evidence is

emerging that not the mere absence or presence of particular gut bacteria but rather ‘hat they do’crucially affects host health, we will perform faecal metabolomic fingerprinting of Nlrp6 deficient

mice. This approach will facilitate discovering metabolites that are associated with a colitogenic gut

microbial composition and that may thus predispose to intestinal inflammation. Validating the

effects of these metabolites in a mouse model of colitis will lead to a better understanding of the

mechanisms by which host-microbiota interplay affects susceptibility to these diseases, and may

identify some of these metabolites as biomarkers with potential prognostic or diagnostic value. This

type of knowledge will be essential for improving therapeutic strategies for microbial manipulation

in human IBD, for instance in designing safe and successful faecal transplantation protocols.