This Midcareer Investigator Award in Patient-Oriented Research will provide protected time for the applicant to mentor trainees in patient-oriented research and to conduct novel research on the efficacy of a limited restriction diet for patients with Crohn's disease. The applicant, James D. Lewis, MD, MSCE has a strong track record of mentoring, having served as a mentor for 6 junior faculty members, 11 fellows (3 who are now faculty mentees), 3 residents, and 4 medical students during the last 4 years. His trainees have benefitted from this mentoring, as evidenced by their significant career advancements such as new faculty positions, R01, VA Merit, K08/K23, F32 and foundation grants, and numerous peer reviewed publications. IBD, including Crohn's disease (CD) and ulcerative colitis (UC), are chronic and relapsing diseases believed to be caused by both genetic and environmental factors such as the composition of the gut microbiome and diet. These factors, particularly diet, can also impact the course of CD. Exclusive enteral nutrition with elemental, semi-elemental, or defined formula diets is first line therapy for active CD in Europe and is also efficacious to maintain remission. Extreme exclusion diets also have demonstrated efficacy in several small studies. However, these dietary strategies are not practical for long term use. Therefore, it is fundamentally important to determine what specific dietary factors influence disease course so that dietary recommendations can be both practical and effective. Animal models and human data lead to a hypothesis that red and processed meat consumption may be associated with relapse of CD. As such, we will test the hypothesis that exclusion of red and processed meats reduces the risk of relapse of CD in a prospective randomized trial. The interrelated specific aims are: Aim 1. To determine whether a diet with low levels of red and processed meat consumption is associated with a reduced rate of relapse of CD. Exploratory aim. To identify other dietary patterns associated with a lower risk of relapse of CD 194 patients with CD in remission will be randomized to one of two study diets. The control diet reduces consumption of sweetened beverages. The study diet reduces consumption of sweetened beverages and red and processed meats. Patients will be followed for 48 weeks or until they experience a relapse. Exploratory analyses will use a validated food frequency questionnaire to identify other dietary patterns associated with relapse of CD. The results will help physicians to answer patients' most common question, What should I eat? PUBLIC HEALTH RELEVANCE: The most frequently posed question from patients with Crohn's disease is Doctor, what should I eat? Data from humans and animal models suggest that meats, particularly red and processed meats, may worsen the course of Crohn's disease. This randomized trial will test the efficacy of restricting intake of red and processed meats on the course of Crohn's disease.