Ulcerativecolitis(UC)isadevastatingimmune-mediateddiseasethatisontheriseglobally.Inourpriorstudy, wefoundthatHispanicshavelessseverediseasethannon-Hispanics,butyetwithinoneUS-borngeneration develop a disease course that is similar. Differences in adoption of a Western diet between US- born and foreign-born Hispanics could explain differences in UC severity observed. A Western diet, high in n-6 to n-3 polyunsaturated fatty acids (PUFA), is up to 10-20 times the recommended intake and is considered pro- inflammatory.However,heterogeneityofresultsindietaryinterventionstudiessuggeststhatunderlyinggenetic variation in PUFA metabolism may modify diet effects. Our preliminary data indicates that Hispanics with UC have polymorphisms in PUFA not present in Hispanic controls. In UC, disease activity measured by rectal bleeding, number of bowel movements, and urgency correlates with endoscopic inflammation. I hypothesize that Hispanics with UC whose diet follows a higher Western dietary pattern, defined by a reproducible dietary pattern score, have more active disease, than those whose diet scores are lower. Further, I propose that carriageofPUFAvariantsaugmentstheeffectofaWesterndietonrelapseleadingtoadisproportionatepro- inflammatoryeffectofthediet.Inthisstudy,IexaminetheinfluenceofaWesterndietarypatternonremission and relapse of UC among Hispanics (Aim 1). We will test whether PUFA variants influence relapse and enhancetheeffectofaWesterndietonUCrelapse(Aim2).Atotalof320self-identified,Hispanicparticipants with UC are followed at our GI clinics and we will include these for our diet portion in Aim 1. We will include a total of 691 Hispanics with UC and 900 Hispanic controls for our Aim 2 genetics portion. We have detailed demographic and clinical information on these patients, as well as whole genome sequencing of PUFA variants. Participants will be asked to complete a validated food-frequency dietary questionnaire, at baseline andat1-yearfollowup.Diseaseactivityusingthevalidatedsimpleclinicalcolitisactivityindexwillbeassessed at baseline and at 1 year follow up in combination with fecal calprotectin. We will calculate scores for a Westerndietarypatternanddeterminetheinfluenceofdietonrelapseusingmultivariableregressionanalysis.
In Aim 2, we will examine the effect of PUFA variants on relapse and also determine gene-environment interactions influencing disease activity between PUFA variants and Western diet. Results gathered from this studywillbeasteptowardspersonalizingIBDtreatmentbytargetingspecificdietarypatternsinHispanicswith highestmetabolicgeneticrisk.
This prospective study will examine dietary and genetic underpinnings of Hispanics with ulcerative colitis (UC) and determine risk for remission and relapse over the course of 1 year. At the end of this study, we seek to gain a better understanding of the role of a Western diet on UC relapse when underlying genetic susceptibility for abnormal polyunsaturated fatty acid (PUFA) metabolism exists. The findings from this study may guide food-based recommendations based on individual genetic variation in future studies.
