Microbiome and Pain in IBS

描述（由申请人提供）：大约10-20%的成年人经历慢性腹部症状(腹痛/不适和相关的肠道变化[便秘和/或腹泻]，与肠易激综合征（IBS）的诊断相一致。在美国和其他西方国家，女性寻求医疗服务的比例高于男性。IBS的定义是慢性腹痛/不适伴有肠道形态改变（腹泻、便秘或两者混合）。在美国，肠易激综合症对公共卫生的影响是巨大的，每年的直接和间接成本总计约为60亿美元。研究表明，胃肠道（GI）渗透性增加（“漏肠”）与肠道成分异常之间存在相互作用

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.