The disturbance in the microbial community composition has been implicated to play a role in the pathogenesis of both intestinal and extra-intestinal disorders, including: inflammatory bowel disease, irritable bowel syndrome (IBS), but also metabolic syndromes, cardiovascular disease and obesity. In all of these heterogeneous and multifactorial diseases anaberrant response to the microbiota is observed. Furthermore, in some cases (for example when patients receive anti-inflammatory drugs or antibiotics) these patients fail to control the outgrowth of so-called pathobionts. Pathobionts are members of the endogenous microbiota that normally do not cause disease. However, when not controlled, these species increase in abundance and do cause disease. To date, it is not clear why the ability to control pathobionts is lost, however, we do have indications that failure of adaptive immune processes plays a role.
By using the unique features of the zebrafish as a model, we will be able to identify which immune cells and mediators specifically suppress pathobionts in the gut, while leaving the commensals alone. Unraveling the mechanism of pathobiont control will provide us with new treatment approaches to combat dysbiosis of the gut microbiota.