PROJECT DESCRIPTION Campylobacter jejuni is the most common cause of food-born diarrhea in the United States. Although it is most often associated with self-limiting diarrheal disease, a small proportion of infected patients develop a more serious neuro-degenerative complication known as Guillain-Barré Syndrome. Despite many important advances in the field, still remarkably little is known about its mechanisms of pathogenicity. C. jejuni has the ability to efficiently colonize the intestine of a broad range of hosts, which allows this pathogen to gain access to the food chain thus presenting major challenges to the food industry. It has been widely observed that the attack rate of C. jejuni during well-documented point-source outbreaks or controlled human infections is under 50%, and that even under conditions of heavy exposure, only a subset of individuals developed symptomatic infections. It is well established that under physiological conditions, the resident microbiota exerts a restricting effect over bacterial enteropathogens. We therefore hypothesize that some of the documented differences in susceptibility to C. jejuni infection is due to differences in the composition of the intestinal microbiota. We intend to conduct experiments to better understand the mechanisms by which the resident intestinal microbiota restricts C. jejuni colonization. To achieve this objective we plan to leverage a germ-free chicken gut colonization model that we have recently established in our laboratory along with our long-standing expertise in the study of C. jejuni. These studies will provide the foundation for the understanding of the role of the resident microbiota in C. jejuni intestinal colonization, which may serve as the bases for the development of novel strategies to combat C. jejuni infections.