Microbiome and Pain in IBS

本申请旨在修订R 01 NR 014479-02 IBS中的微生物组和疼痛（母体）的研究目的 格兰特），包括对粪便代谢组的额外措施的重点。肠易激综合征（IBS） 影响了全世界10-20%的成年人，造成了巨大的经济、社会和情感负担。我们 研究生物标志物（肠道微生物群和通透性、血清免疫标志物和靶向遗传标记物）， 多态性[Parent Grant]，在此修订的目标中，粪便色氨酸（TRY）代谢物和胆汁酸 (BA)这可能是成人肠易激综合征患者的特征。这一修订目标是创新的，因为我们将增加 代谢组学分析与其他临床和微生物群分析相结合， 迄今为止主要是表型定义的病症。基于先前的血清研究，我们将 开展针对TRY代谢物的靶向粪便代谢组学分析。我们目前正在进行 家长研究的三个目标目标1.比较粪便GI微生物群组成、GI渗透性， IBS成人（18-45岁）（n=100）与 (vs)无IBS的健康对照（HC）（n=50）。目标二。在IBS患者中，比较腹痛， 其他肠易激综合征症状和心理困扰症状的那些与正常的胃肠道生物标志物异常。 HC组结果将用于确定渗透性、细胞因子和聚类分析的正常范围 将用于基于微生物群群落的类型来识别IBS亚型。目标3：探索模式 GI生物标志物之间的关联（渗透性、细胞因子、微生物群）;以及GI生物标志物之间的关联 腹痛、其他IBS症状、压力、心理困扰、遗传多态性（SERT，IL-10， IL-10R）。目标是基于生物标志物和临床表型的组合来鉴定IBS亚组， 可能对应不同的病因聚类分析将应用于微生物群数据， 识别具有不同微生物群特征的亚型。修订目标4：探索粪便TRP代谢物和BA， 初步比较IBS和HC，并检查与 目标3微生物组。目标3和4是探索性的，任何提议的亚型都需要在一个 独立样本我们的提案涉及NINR目标，包括开发新的诊断工具， 预测生物标志物，鼓励冒险，创新和创造力，以解决医疗保健成本（成本 57%以上的IBS）。拟议的修订是重要的，因为供应商受到挑战， 肠易激综合征的病理生物学定义不明确，治疗也不是普遍有效的。未来的研究可以针对 与无生物标志物异常的患者相比， 心理困扰

This application is for revision of the study aims of R01 NR 014479-02 Microbiome and Pain in IBS (Parent Grant) to include a focus on the additional measure of fecal metabolome. Irritable bowel syndrome (IBS) affects 10-20% of adults worldwide exerting a tremendous economic, social, and emotional burden. We are studying biomarkers (gut microbiota and permeability, serum immune markers, and targeted genetic polymorphisms [Parent Grant] and in this revised aim fecal tryptophan (TRY) metabolites and bile acids (BA) that likely characterize subsets of adults with IBS. This revised aim is innovative because we will add metabolomics analyses to other clinical and microbiota analyses to characterize pathobiologically what heretofore has been primarily a phenotypically-defined condition. Building on prior serum studies we will conduct targeted fecal metabolomics analyses focused on those TRY metabolites. We are currently conducting the following 3 aims of the Parent Study. Aim 1. Compare stool GI microbiota composition, GI permeability, and pro- and antiinflammatory cytokines (GI biomarkers) in adults (18-45 yr of age) with IBS (n=100) versus (vs) Healthy Controls (HC) (n=50) without IBS. Aim 2. Among individuals with IBS, compare abdominal pain, other IBS symptoms and psychological distress symptoms in those with abnormal vs. normal GI biomarkers. The HC group results will be used to determine normal ranges for permeability, cytokines, and cluster analyses will be used to identify IBS subtypes based on type of microbiota community. Aim 3. Explore patterns of associations among GI biomarkers (permeability, cytokines, microbiota); and associations of GI biomarkers with abdominal pain, other IBS symptoms, stress, psychological distress, genetic polymorphisms (SERT, IL-10, IL-10R). The goal is to identify IBS subgroups based on combinations of biomarkers and clinical phenotypes, which could potentially correspond to different etiologies. Cluster analyses will be applied to microbiota data to identify subtypes with different microbiota profiles. Revised Aim 4: Explore fecal TRP metabolites and BAs, preliminarily compare IBS and HCs and examine patterns of association similar to that described in Aim 3 for microbiome. Aims 3 & 4 are exploratory and any proposed subtypes will need validation in an independent sample. Our proposal addresses NINR goals including developing new diagnostic tools and predictive biomarkers, encouraging risk taking, innovation, and creativity, to address a healthcare cost (costs are 57% greater for IBS). The proposed revision is important because providers are challenged given the pathobiology of IBS is poorly defined and treatments are not universally effective. Future studies could target management with abnormal biomarkers differently from those with no biomarker abnormalities but greater psychological distress.