Is TFF-3 a Biomarker for Functional Gastrointestinal Symptoms?

描述(由申请人提供)：此修订的R21申请是对PA-11-261探索/发展研究资助计划的响应，重点是开发一种潜在的蛋白质生物标记物来识别肠易激综合征(IBS)患者的子集。肠易激综合征是一种常见的功能性肠病，以慢性间歇性腹痛和肠道模式改变为特征。IBS的症状从轻微到严重不等，使人虚弱。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、药物治疗以及与工作或学校相关的缺勤数量。在美国，IBS影响了数百万人，其中女性所占比例更大。具体地说，这项应用将检查尿便三叶因子3(TFF3)与症状(腹痛、大便模式)的关系，以及该蛋白与免疫措施和粪便微生物群特征的关系。TFF-3是一种由肠道和结肠粘膜的杯状细胞产生的蛋白质。有证据支持它在微生物粘附胃肠道粘液上皮细胞中的作用。因此，尿液和粪便中高水平的TTF3可能反映了对生物失调(肠道菌群失衡)和/或胃肠道屏障功能改变(通透性增加)的反应增加了产量。使用之前NINR资助的一项针对IBS患者(n=80)的仔细表型女性研究的粪便和尿液样本，我们将与贝勒医学院的同事合作，通过使用454焦油测序管道进行的细菌DNA分析，探索TFF3与粪便微生物组组成的关系。将对16sRNA基因测序数据进行多项分析，包括确定每个样本中确定的细菌的多样性、均匀性、丰富度和相对丰度。此外，我们还将探讨这些受试者的大便和尿液中TFF3水平与通透性之间的关系。这项研究在检查一种与肠道微生物群和症状相一致的肠道炎症/保护/修复蛋白方面具有创新性和高风险。

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.