Is TFF-3 a Biomarker for Functional Gastrointestinal Symptoms?

TFF-3 是功能性胃肠道症状的生物标志物吗？

• 批准号: 8816139
• 负责人: Margaret McLean Heitkemper
• 金额: $ 21.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-04 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8816139
• 关键词: Abdominal Pain; Accounting; Adherence; Affect; Area; Autonomic nervous system; Bacteria; Bacterial DNA; Biological Markers; Characteristics; Chronic; Collaborations; Complex; DNA analysis; Data; Development; Diagnostic Procedure; Disease; Elements; Enteral; Epithelium; Etiology; Exploratory/Developmental Grant; Feces; Functional disorder; Funding; Gastrointestinal tract structure; Genes; Genome; Goals; Goblet Cells; Health; Immune; Incubated; Inflammation; Inflammatory disease of the intestine; Ingestion; Interleukin-10; Interleukin-12; Intervention; Intestines; Irritable Bowel Syndrome; Lactulose; Lead; Leukocyte L1 Antigen Complex; Link; Mannitol; Measurement; Measures; Medicine; Microbe; Modeling; Motor; Mucositis; Mucous Membrane; Mucous body substance; Pathology; Patients; Pattern; Peptides; Peripheral Blood Mononuclear Cell; Permeability; Pharmaceutical Preparations; Phenotype; Physiological; Production; Proteins; Quality of life; Randomized Controlled Trials; Recovery; Relative (related person); Reporting; Research; Research Personnel; Research Project Grants; Risk; Role; Sampling; Schools; Sensory; Severities; Small Intestines; Specific qualifier value; Specimen; Staging; Subgroup; Symptoms; Testing; Time; Urine; Visit; Woman; Work; base; biopsychosocial; college; cost; effective intervention; gastrointestinal symptom; health care service utilization; high risk; immune activation; improved; innovation; men; microbial; microbiome; programs; public health relevance; repaired; research study; response; sugar; therapy development; trefoil factor

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.

描述（由申请人提供）：此修订后的R21应用对PA-111-261探索性/发育研究赠款计划有反应，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）的一部分。 IBS是常见的功能性肠道疾病，其特征是慢性，间歇性腹痛和肠模式的改变。 IBS症状的严重程度从轻度到重度和令人衰弱。在美国，费用超过了60亿美元/年，这归因于诊断程序，临床医生就诊，药物以及工作或与学校有关的缺勤量的数量。 IB会影响美国数百万的人，而女性比例更大。具体而言，该应用将检查尿液和粪便三叶因子3（TFF3）和症状（腹痛，僵硬模式）的关系，以及该蛋白质与凳子微生物群的免疫测量和特征的关联。 TFF-3是由肠和结肠粘膜的杯状细胞产生的蛋白质。有证据可以支持其在微生物遵守GI粘液上皮的作用中的作用。因此，高水平的尿液和粪便TTF3可能反映出响应营养不良（肠道菌群不平衡）和/或胃肠道屏障功能的改变（渗透率增加）的产生增加。使用先前收集的粪便和尿液标本来自先前的NINR资助的研究，该研究与精心表现的IBS女性（n = 80），我们将探索TFF3与凳子微生物群体组成的关系，该关系通过细菌DNA分析，使用454 Pyro测序管道与贝勒学院的同事合作，通过细菌DNA分析确定。将对16SRNA基因测序数据进行多次分析，包括确定每个样品中鉴定的细菌的细菌多样性，均匀度，丰富性和相对丰度。此外，我们将探讨粪便和尿液TFF3水平与这些受试者先前测量的渗透性的相关性。这项研究是与肠道炎症/保护/修复涉及的蛋白质的创新性和高风险。