The impact of diet patterns and PUFA-related polymorphisms on ulcerative colitis in Hispanics

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Summary This is an extension of my K23 study for a period of 12 months to complete recruitment for the study, perform pilot metabolite and microbiota analyses, and acquire necessary training in ‘omic’ data analysis and interpretation important for my career development and R01 proposal. My K23 research project delves into the study of ulcerative colitis (UC), a devastating immune-mediated disease that is on the rise globally including among Hispanics. The proposal was based on the hypothesis that greater adoption of a Western diet among Hispanics in the US could explain differences in UC severity observed in my prior studies between US and foreign-born Hispanics. 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, heterogeneity of results in dietary intervention studies suggests that underlying genetic variation in PUFA metabolism may modify diet effects. Our preliminary data for the K23 indicated that Hispanics with UC have polymorphisms in PUFA not present in Hispanic controls. I hypothesized that Hispanics with UC whose diet follows a higher Western dietary pattern, defined by a reproducible dietary pattern score, would have more active disease, than those whose diet scores are lower. Further, I proposed that carriage of PUFA variants augments the effect of a Western diet on relapse leading to a disproportionate pro-inflammatory effect of the diet. I am examining the influence of a Western dietary pattern on relapse of UC among Hispanics (Aim 1). We are testing PUFA variants and whether carriage of these enhances the effect of a Western diet on UC relapse (Aim 2). A total of 320 self-identified, Hispanic participants with UC were recruited and we will include these for our diet portion in Aim 1. We have included a total of ~700 Hispanics with UC and ~900 Hispanic controls for our Aim 2 genetics portion. We have recruited a total of 320 patients already for Aim 1 and have identified that Western diet patterns are associated with relapse in a subset of 214 analyzed. We have detailed demographic and clinical information on these patients, as well as whole genome sequencing of PUFA variants pending to be analyzed upon completion of recruitment. Participants complete a validated food-frequency dietary questionnaire, at baseline and at 1-year follow up. Disease activity using the validated simple clinical colitis activity index will be assessed at baseline and at 1 year follow up in combination with fecal calprotectin. We have calculated scores for a Western dietary pattern and are determining the influence of diet on relapse using multivariable regression analysis. In Aim 2, we will examine the effect of PUFA variants on relapse and determine gene-environment interactions influencing disease activity between PUFA variants and Western diet upon completion of recruitment. During the extension period, I will complete data visits for all 320 patients to complete Aims 1 and 2 and work on analyzing the stool microbiome species, function and derived metabolites and their associations to disease relapse in a subset of 24 patients with complete diet and clinical data. Results gathered from this study will be a step towards personalizing IBD treatment by targeting specific dietary patterns in Hispanics with highest metabolic genetic risk.