Microbiome and Pain in IBS

IBS 中的微生物组和疼痛

• 批准号: 8848431
• 负责人: Margaret McLean Heitkemper
• 金额: $ 36.92万
• 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: 2014-05-13 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8848431
• 关键词: Abdomen; Abdominal Pain; Address; Adult; Affect; Age; Anti-Inflammatory Agents; Anti-inflammatory; Anxiety; Autonomic Dysfunction; Bacteria; Behavioral; Biological Markers; Child; Childhood; Chronic; Cluster Analysis; Cognitive; Cognitive Therapy; Communities; Constipation; Control Groups; Country; Creativeness; Data; Diagnosis; Diarrhea; Diet; Direct Costs; Distress; Economics; Emotional; Enterobacteriaceae; Etiology; Facilities and Administrative Costs; Feces; Future; Gammaproteobacteria; Genes; Genetic Polymorphism; Genome; Genotype; Goals; Health; Health Care Costs; Health Personnel; Health Services; High Prevalence; Immune response; Immunologic Markers; Individual; Inflammatory; Interleukin-10; Interleukin-6; Intestines; Irritable Bowel Syndrome; Lead; Normal Range; Pain; Patients; Pattern; Peripheral; Permeability; Physiological; Probiotics; Production; Proteobacteria; Psychosocial Factor; Public Health; Research; Risk-Taking; Sampling; Serotonin; Serum; Serum Markers; Stress; Subgroup; Symptoms; TNF gene; United States National Institutes of Health; Validation; Woman; Work; base; chronic abdominal pain; clinical phenotype; cost; cytokine; experience; gastrointestinal; gut microbiota; innovation; men; microbiome; novel; novel diagnostics; psychological distress; psychosocial; reuptake; social; tool

DESCRIPTION (provided by applicant): Approximately 10-20% of adults experience chronic abdominal symptoms (abdominal pain/discomfort and associated bowel changes [constipation and/or diarrhea] compatible with a diagnosis of irritable bowel syndrome (IBS). In the US as well as other western countries, women seek health care services disproportionately to men. IBS is defined as chronic abdominal pain/discomfort accompanied by altered bowel pattern (diarrhea, constipation or both [mixed]). The public health impact of IBS in the US is enormous with direct and indirect costs totaling approximately $6 billion/year. Studies suggest an interplay between increased gastrointestinal (GI) permeability ('leaky gut'), abnormalities in the composition of the GI microbiome (defined as bacteria, their genomes and interaction with the host), altered immune responses, autonomic dysfunction (high sympathetic tone), and psychosocial distress lead to the symptoms and the subsequent functional impact of IBS. Our long term goal is to delineate the contribution of pathobiology and psychosocial distress to better inform patient management e.g., diet versus cognitive behavioral approaches). We propose to compare GI microbiota, intestinal permeability, cytokines, and GI and psychological distress symptoms in menstruating women with IBS and without IBS. We also will derive important information about women with IBS with no evidence of abnormal GI markers. The current proposal will also allow us to define microbiome composition and pathophysiological features tied to symptoms, and likely etiology. Thus, the first specific aim is to compare GI microbiome, permeability and cytokines in women (18-45 yr. of age) with IBS (n=100) vs. Healthy Controls (HC) (n=50) without IBS. Based on pediatric data, we hypothesize that among women with IBS, those with a GI microbiome enriched with Proteobacteria/Enterobacteriaceae, increased GI permeability or increased cytokine levels will have greater abdominal pain symptoms versus those without this Proteobacteria/Enterobacteriaceae enriched microbiota composition, normal permeability, or lower cytokine levels. The second aim will be to compare abdominal pain, other IBS symptoms and psychosocial distress symptoms in those IBS subjects with abnormal versus normal GI biomarkers. In addition we will explore patterns of associations among GI biomarkers, and of GI biomarkers with abdominal pain and other symptoms. The goal is to identify possible IBS subgroups based on biomarkers. This research is innovative because we will use biomarkers (e.g., GI microbiome analyses, permeability, and serum markers applied novelty to characterize pathobiologically what heretofore has been primarily a phenotypically and arbitrarily defined condition. We will integrate psychosocial factors (e.g., anxiety, somatization, co-morbid functional conditions) that our preliminary data suggest are likely to predominate in some women with IBS.

描述（由申请人提供）：大约10-20％的成年人经历了慢性腹部症状（腹部疼痛/不适和相关的肠变化[便秘和/或腹泻]与诊断肠综合征（IBS）（IBS）兼容。肠模式（腹泻，便秘或两者都有[美国IBS的公共卫生影响。 胃肠道微生物组（定义为细菌，其基因组和与宿主的相互作用），免疫反应改变，自主功能障碍（高交感神经语调）和心理社会困扰会导致IBS的症状和随后的功能影响。我们的长期目标是描述病理生物学和社会心理困扰的贡献，以更好地告知患者管理，例如饮食与认知行为方法）。我们建议在月经中与IBS和无IBS的妇女中的胃肠道菌群，肠通透性，细胞因子以及GI以及心理困扰症状进行比较。我们还将获得有关IBS女性的重要信息，而没有异常的GI标记。当前的建议还将使我们能够定义与症状和可能病因相关的微生物组组成和病理生理特征。因此，第一个具体目的是将女性（18-45岁）女性（n = 100）与健康对照组（HC）（HC）（HC）（n = 50）的女性（18-45岁）中的GI微生物组，渗透率和细胞因子进行比较。根据小儿数据，我们假设在IB的女性中，患有胃肠道微生物组的女性富含蛋白质细菌/肠杆菌科，胃肠道渗透性增加或细胞因子水平增加将具有较大的腹部疼痛与没有这种原生质细菌/肠杆菌含量较低的耐伴侣的腹部疼痛，或者具有较低的Microbobiota Composition，正常情况下。第二个目的是比较那些异常与正常胃肠道生物标志物的IBS受试者中腹痛，其他IBS症状和社会心理困扰症状。此外，我们将探索GI生物标志物之间的关联模式，以及具有腹痛和其他症状的GI生物标志物。目的是根据生物标志物确定可能的IBS子组。这项研究具有创新性，因为我们将使用生物标志物（例如GI微生物组分析，渗透率和血清标记物应用新颖性来表征病理学表征什么迄今为止是一种表型和任意定义的条件。我们将主要是焦虑，焦虑，某些可能是官能化的，可能是某些妇女的情况，可能是某些人脉络性，可能是某些妇女的条件，可能是有效的。与IBS。