Institute of Microoecology, Herborn, Germany.
Department of Neurology, Saarland University, Homburg, Saar, Germany.
Parkinsonism Relat Disord. 2018 May;50:104-107. doi: 10.1016/j.parkreldis.2018.02.022. Epub 2018 Feb 12.
BACKGROUND/OBJECTIVE: Intestinal inflammation and increased intestinal permeability (both possibly fueled by dysbiosis) have been suggested to be implicated in the multifactorial pathogenesis of Parkinson's disease (PD). The objective of the current study was to investigate whether fecal markers of inflammation and impaired intestinal barrier function corroborate this pathogenic aspect of PD.
In a case-control study, we quantitatively analyzed established fecal markers of intestinal inflammation (calprotectin and lactoferrin) and fecal markers of intestinal permeability (alpha-1-antitrypsin and zonulin) in PD patients (n = 34) and controls (n = 28, group-matched for age) by enzyme-linked immunosorbent assay. The study design controlled for potential confounding factors.
Calprotectin, a fecal marker of intestinal inflammation, and two fecal markers of increased intestinal permeability (alpha-1-antitrypsin and zonulin) were significantly elevated in PD patients compared to age-matched controls. Lactoferrin, as a second fecal marker of intestinal inflammation, showed a non-significant trend towards elevated concentrations in PD patients. None of the four fecal markers correlated with disease severity, PD subtype, dopaminergic therapy, or presence of constipation.
Fecal markers reflecting intestinal inflammation and increased intestinal permeability have been primarily investigated in inflammatory bowel disease so far. Our data indicate that calprotectin, alpha-1-antitrypsin and zonulin could be useful non-invasive markers in PD as well. Even though these markers are not disease-specific, they corroborate the hypothesis of an intestinal inflammation as contributing factor in the pathogenesis of PD. Further investigations are needed to determine whether calprotectin, alpha-1-antitrypsin and zonulin can be used to define PD subgroups and to monitor the effect of interventions in PD.
背景/目的：肠道炎症和肠道通透性增加（两者都可能由菌群失调引起）被认为与帕金森病（PD）的多因素发病机制有关。本研究的目的是研究粪便炎症标志物和肠道屏障功能受损是否与 PD 的发病机制相一致。
在一项病例对照研究中，我们通过酶联免疫吸附试验定量分析了 PD 患者（n=34）和对照组（n=28，年龄匹配）粪便中炎症标志物（钙卫蛋白和乳铁蛋白）和肠道通透性标志物（α-1-抗胰蛋白酶和紧密连接蛋白）。该研究设计控制了潜在的混杂因素。
与年龄匹配的对照组相比，PD 患者粪便中炎症标志物（钙卫蛋白）和两种肠道通透性标志物（α-1-抗胰蛋白酶和紧密连接蛋白）显著升高。作为第二种粪便炎症标志物的乳铁蛋白在 PD 患者中也表现出浓度升高的趋势，但无统计学意义。这四种粪便标志物均与疾病严重程度、PD 亚型、多巴胺能治疗或便秘的存在无关。
反映肠道炎症和肠道通透性增加的粪便标志物迄今为止主要在炎症性肠病中进行了研究。我们的数据表明，钙卫蛋白、α-1-抗胰蛋白酶和紧密连接蛋白也可能是 PD 的有用非侵入性标志物。尽管这些标志物不是疾病特异性的，但它们支持肠道炎症作为 PD 发病机制的一个促成因素的假说。需要进一步研究以确定钙卫蛋白、α-1-抗胰蛋白酶和紧密连接蛋白是否可用于定义 PD 亚组并监测 PD 干预的效果。
