dr. S (Sylvia) Brugman

Host-Microbe interactions in health and disease: using the zebrafish model to study dysbiosis

All organisms on earth need to find a way to interact with the world they live in. In particular, the interaction with the numerous microbes that live in and on our bodies pose a complex challenge. On the one hand, beneficial species that protect pathogens from colonizing and help us digest food should be tolerated, while on the other hand, those that can cause disease must be eliminated or suppressed. One of the surfaces that is faced with this dichotomy is the intestinal surface. In our group we make use of the zebrafish as a model to interrogate pathways involved in controlling bacterial colonization at the intestinal surface. The zebrafish is a unique model in that it is exposed to the outside world from fertilization onwards. Development of the animal and its immune system goes hand in hand with bacterial colonization. Disturbances of this development might lead to dysbiosis and increased susceptibility to disease later in life. What cells and mediators are involved in establishing homeostasis in the intestine? What are the influences of feed, antibiotics or pollutants on the microbiota and disease susceptibility? In what way does dysbiosis contribute to disease susceptibility? In previous research, we have shown that adaptive immunity (in particular T lymphocytes) play a role in suppressing Vibrio species in the intestines of zebrafish. This suppression was accompanied by an increased expression of chemokine cxcl8a (interleukin 8) in the epithelial cells (1,2). Current research is focusing on the molecular mechanism by which Vibrio and possible other pathobionts are suppressed. By making use of the early life transparency of the zebrafish combined with the availability of transgenic (immune cell) reporter fish we are currently investigating the role of cxcl8a and regulatory cytokines (IL22 and IL10) during development from eggs to larvae to juveniles in which the fish transition from animals that solely rely on innate immunity to fish that have both innate and adaptive immune function. We investigate the effect of feed, antibiotics and other water pollutants during this development on the host as well as its microbiota and aim to understand what processes might underly increased intestinal disease susceptibility.

Current projects:

NWO-TTW: Fishing for functional feeds: using the zebrafish as a screening model to assess novel fish feeds

NWO-ENW: Keeping the peace at the microbial surface: how does the host control pathobionts

WIAS: It takes IL-22 to tango

EWUU-CUCo grant: Defeating chronic pain

Protein transition Biochemistry project: Establishing a multidisciplinary pipeline to assess protein functionality

Protein transition project: Using the zebrafish to assess the effect of fermented feed on gut health and microbiota