Is TFF-3 a Biomarker for Functional Gastrointestinal Symptoms?

描述（由申请人提供）：本修订后的R21申请响应PA-11-261探索性/发展性研究资助计划，专注于开发一种潜在的蛋白质生物标志物，以识别肠易激综合征（IBS）患者的亚群。肠易激综合征是一种常见的功能性肠病，其特征是慢性、间歇性腹痛和肠型改变。肠易激综合征症状的严重程度从轻微到严重并使人虚弱。在美国，每年超过60亿美元的费用可归因于诊断程序、临床医生就诊、药物治疗以及工作或学校相关的缺勤。在美国，肠易激综合症影响着数百万人，其中女性的比例更高。具体而言，本应用将检查尿和大便三叶因子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联。TFF-3是一种由肠和结肠粘膜杯状细胞产生的蛋白质。有证据支持其在胃肠道黏液上皮粘附微生物中的作用。因此，尿液和粪便中TTF3的高水平可能反映了对生态失调（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。我们将与贝勒医学院（Baylor College of Medicine）的同事合作，使用454 pyro测序管道，通过细菌DNA分析确定TFF3与粪便微生物组组成的关系，使用先前由NINR资助的一项研究收集的粪便和尿液标本（n=80）进行仔细表型的IBS女性。将对16sRNA基因测序数据进行多项分析，包括测定每个样品中鉴定的细菌的多样性、均匀性、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，正如之前在这些受试者中测量的那样。这项研究是一项创新和高风险的研究，涉及肠道炎症/保护/修复与肠道微生物群和症状相一致的蛋白质。

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.