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

总结 这是我的K23研究的一个扩展，为期12个月，以完成研究的招募，执行 试验代谢物和微生物群分析，并获得“组学”数据分析和解释方面的必要培训 对我的职业发展和R 01提案很重要。我的K23研究项目深入研究了 溃疡性结肠炎（UC）是一种毁灭性的免疫介导的疾病，在全球范围内呈上升趋势， 西班牙裔这项提议是基于这样一种假设，即西班牙裔美国人更多地采用西方饮食， 可以解释在我之前的研究中观察到的美国和外国出生的UC严重程度的差异 西班牙裔西方饮食中n-6至n-3多不饱和脂肪酸（PUFA）含量高，是美国饮食中的10-20倍。 推荐摄入量，并被认为是促炎症。然而，饮食中的异质性导致 干预研究表明，PUFA代谢的潜在遗传变异可能会改变饮食效应。我们 K23的初步数据表明，患有UC的西班牙裔人在PUFA中存在多态性，而在 西班牙裔控制。我假设饮食遵循西方饮食模式的西班牙裔UC患者， 由可重复的饮食模式评分定义，将有更多的活动性疾病， 更低。此外，我提出携带PUFA变异体会增强西方饮食对复发的影响 导致饮食的不成比例的促炎作用。我在研究一个西方人 饮食模式对西班牙裔UC复发的影响（目的1）。我们正在测试PUFA变体， 这些增强了西方饮食对UC复发的影响（目的2）。共有320名自称是西班牙裔的 招募UC参与者，我们将这些纳入目标1的饮食部分。我们配备了 我们的Aim 2遗传学部分共纳入了约700名患有UC的西班牙裔患者和约900名西班牙裔对照。我们招募了一名 总共有320名患者已经达到目标1，并确定西方饮食模式与复发有关 在214个分析的子集中。我们也有这些患者的详细人口统计和临床信息， 作为待在完成招募后分析的PUFA变体的全基因组测序。 参与者在基线和1年随访时完成一份经验证的食物频率饮食问卷。 将在基线和1年时使用经验证的简单临床结肠炎活动指数评估疾病活动性 与粪便钙卫蛋白联合随访。我们计算了西方饮食模式的得分， 使用多变量回归分析确定饮食对复发的影响。在目标2中，我们将研究 PUFA变异体对复发的影响和确定影响疾病活动的基因-环境相互作用 PUFA变体和西方饮食之间的差异。在延长期内，我将 完成对所有320名患者的数据访问，以完成目标1和2，并分析粪便微生物组 24例患者亚组中的种属、功能和衍生代谢物及其与疾病复发的相关性 有完整的饮食和临床数据从这项研究中收集的结果将是个性化IBD的一步 通过针对具有最高代谢遗传风险的西班牙裔人的特定饮食模式进行治疗。

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.