"Animal-associated commensal microbiota play a crucial role in protecting their hosts against invading pathogens through a process called colonisation resistance. A number of hypotheses have been proposed to explain this protective effect. These include direct competition between commensal and pathogens (barrier effect), alteration of the host immune defence (immuno-stimulation), or protection by certain species but not the whole community (membership effect). Investigations of bacterial community interactions were carried out extensively based on genomic approaches, but functional studies are still rare. Indeed, investigating bacterial interactions in vivo is often hindered by the complexity of host-associated bacterial communities and a lack of appropriate direct and reproducible experimental approaches for the analysis of community-based colonisation resistance. We propose an innovative approach using the zebrafish (Danio rerio) as a relevant vertebrate model to systematically dissect the mechanisms behind community-protection against exogenous pathogens. Our preliminary data showed that axenic and mono-colonised, but not conventional zebrafish larvae harbouring natural microbiota, rapidly die upon infection by the fish pathogen Flavobacterium columnare. We will use conventional zebrafish survival as a read-out for community-protection and will investigate its molecular and ecological bases. Culturable bacteria isolated from natural zebrafish microbiota will be transplanted into axenic fish to determine key species involved in protection and construct a minimum protective community. We will then characterise the community interactions with ecological tools and identify the molecular determinants for the protection against F. columnare. This approach will generate fundamental knowledge about microbial ecological interactions in host-associated systems and could contribute to a better understanding of strategies for pathogen control."