Stool Immune Profiles Evince Gastrointestinal Inflammation in Parkinson's Disease.
Stool Immune Profiles Evince Gastrointestinal Inflammation in Parkinson's Disease.
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DOI：
10.1002/mds.27326
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Tansey MG
中科院分区：
文献类型：
--
作者：
Houser MC;Chang J;Factor SA;Molho ES;Zabetian CP;Hill-Burns EM;Payami H;Hertzberg VS;Tansey MG
胃肠道症状在帕金森病中很常见，并且经常先于运动障碍的发展。肠道炎症被认为是疾病病理学的驱动因素，对粪便中炎症介质的评估可能会发现有价值的早期生物标志物。我们测量了人类粪便中的免疫和血管生成相关蛋白，以检查与帕金森病相关的炎症特征。粪便样本和受试者自我报告的元数据来自156名帕金森病患者和110名非帕金森病患者，包括配偶和非家庭对照。元数据探讨疾病相关的差异，并通过多重免疫测定法测量粪便匀浆中37种免疫和血管生成因子的水平，并在实验组之间进行比较。帕金森病患者报告的肠道疾病和消化问题的发生率高于对照组。直接比较患者和对照组的粪便分析物水平，发现患者粪便中Flt 1、IL-1α和CXCL 8升高。患者和配偶的配对比较表明患者的多种因素水平较高，但这因性别差异而变得复杂。性别、体重指数、吸烟史和使用益生菌被发现强烈影响粪便分析物的水平。解释这些和其他潜在混杂因素的多变量分析证实了帕金森病患者的IL-1α和CXCL 8水平升高，并额外显示了粪便中IL-1β和CRP升高。这些差异不依赖于受试者年龄或疾病持续时间。粪便免疫因子水平表明帕金森病患者存在肠道炎症。
Gastrointestinal symptoms are common in Parkinson’s disease and frequently precede the development of motor impairments. Intestinal inflammation has been proposed as a driver of disease pathology, and evaluation of inflammatory mediators in stool could possibly identify valuable early-stage biomarkers. We measured immune- and angiogenesis-related proteins in human stool to examine inflammatory profiles associated with Parkinson’s disease. Stool samples and subjects’ self-reported metadata were obtained from 156 individuals with Parkinson’s disease and 110 without, including spouse and non-household controls. Metadata were probed for disease-associated differences, and levels of 37 immune and angiogenesis factors in stool homogenates were measured by multiplexed immunoassay and compared across experimental groups. Parkinson’s disease patients reported greater incidence of intestinal disease and digestive problems than controls. Direct comparison of levels of stool analytes in patients and controls revealed elevated Flt1, IL-1α, and CXCL8 in patients’ stool. Paired comparison of patients and spouses suggested higher levels of multiple factors in patients, but this was complicated by sex differences. Sex, body mass index, a history of smoking, and use of probiotics were found to strongly influence levels of stool analytes. Multivariate analysis accounting for these and other potential confounders confirmed elevated levels of IL-1α and CXCL8 and additionally revealed increased IL-1β and CRP in stool in Parkinson’s disease. These differences were not dependent on subject age or disease duration. Levels of stool immune factors indicate that intestinal inflammation is present in patients with Parkinson’s disease.
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