Is TFF-3 a Biomarker for Functional Gastrointestinal Symptoms?

描述（由申请人提供）：此修订的R21申请响应PA-11 - 261探索/发展研究资助计划，并专注于开发潜在的蛋白质生物标志物，以识别肠易激综合征（IBS）患者的子集。肠易激综合征是一种常见的功能性肠道疾病，以慢性间歇性腹痛和肠道模式改变为特征。IBS症状的严重程度从轻度到重度和衰弱。在美国，每年超过60亿美元的成本可归因于诊断程序、临床医生就诊、药物以及与工作或学校有关的缺勤的数量。IBS影响着美国数百万人，其中女性占更大比例。具体而言，本申请将检查尿液和粪便三叶因子3（TFF3）与症状（腹痛，排便模式）的关系，以及该蛋白质与免疫措施和粪便微生物组特征的相关性。TFF-3是由肠和结肠粘膜的杯状细胞产生的蛋白质。有证据支持其在微生物粘附于胃肠道粘液上皮细胞中的作用。因此，高水平的尿液和粪便TTF 3可能反映了响应于生态失调（不平衡的肠道植物群）和/或GI屏障功能改变（增加的渗透性）的增加的产生。使用先前从先前NINR资助的研究中收集的粪便和尿液样本，对患有IBS的女性进行仔细的表型分析（n = 80），我们将探索TFF3与粪便微生物组组成的关系，如通过细菌DNA分析使用454 pyro测序管道与贝勒医学院的同事合作确定的。将对16sRNA基因测序数据进行多重分析，包括确定每份样本中鉴定的细菌多样性、均匀度、丰富度和相对丰度。此外，我们将探索粪便和尿液TFF3水平与渗透性的相关性，如先前在这些受试者中测量的。这项研究在检查与肠道微生物组和症状相关的肠道炎症/保护/修复蛋白质方面具有创新性和高风险性。

DESCRIPTION (provided by applicant): This revised R21 application is responsive to PA-11-261 Exploratory/Developmental Research Grant Program and is focused on developing a potential protein biomarker to identify a subset of patients with irritable bowel syndrome (IBS). IBS is common functional bowel disorder characterized by chronic, intermittent abdominal pain and alterations in bowel pattern. Severity of symptoms in IBS range from mild to severe and debilitating. Costs, exceeding $6 billion/year in the US are attributable to the number of diagnostic procedures, clinician visits, medications, and work or school-related absences. IBS affects millions of people in the US with a greater proportion being women. Specifically this application will examine the relationship of urine and stool trefoil factor 3 (TFF3) and symptoms (abdominal pain, stooling pattern) as well as the association of this protein with immune measures and characteristics of stool micro biome. TFF-3 is a protein produced by the goblet cells of the intestinal and colonic mucosa. There is evidence to support its role in the adherence of microbes to the mucus epithelia of the GI. Thus, high levels of urine and stool TTF3 may reflect increased production in response to dysbiosis (imbalanced intestinal flora) and/or alterations in GI barrier function (increased permeability). Using previously collected stool and urine specimens from a prior NINR funded study with carefully phenotyped women with IBS (n=80) we will explore the relationship of TFF3 to stool micro biome composition as determined by bacterial DNA analysis using 454 pyro sequencing pipeline in collaboration with colleagues at Baylor College of Medicine. Multiple analyses will be performed on the 16sRNA gene sequencing data including determination of bacterial diversity, evenness, richness and relative abundance of bacteria identified in each sample. In addition, we will explore the correlation of stool and urine TFF3 levels with permeability as previously measured in these subjects. This study is innovative and high risk in the examination of a protein involved in gut inflammation/protection/repair in concert with the gut micro biome and symptoms.