Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson’s Disease

BackgroundThe intestine is one of the first affected organs in Parkinson’s disease (PD). PD subjects show abnormal staining for Escherichia coli and α-synuclein in the colon.MethodsWe recruited 52 PD patients and 36 healthy cohabitants. We measured serum markers and quantified the numbers of 19 fecal bacterial groups/genera/species by quantitative RT-PCR of 16S or 23S rRNA. Although the six most predominant bacterial groups/genera/species covered on average 71.3% of total intestinal bacteria, our analysis was not comprehensive compared to metagenome analysis or 16S rRNA amplicon sequencing.ResultsIn PD, the number of Lactobacillus was higher, while the sum of analyzed bacteria, Clostridium coccoides group, and Bacteroides fragilis group were lower than controls. Additionally, the sum of putative hydrogen-producing bacteria was lower in PD. A linear regression model to predict disease durations demonstrated that C. coccoides group and Lactobacillus gasseri subgroup had the largest negative and positive coefficients, respectively. As a linear regression model to predict stool frequencies showed that these bacteria were not associated with constipation, changes in these bacteria were unlikely to represent worsening of constipation in the course of progression of PD. In PD, the serum lipopolysaccharide (LPS)-binding protein levels were lower than controls, while the levels of serum diamine oxidase, a marker for intestinal mucosal integrity, remained unchanged in PD.ConclusionsThe permeability to LPS is likely to be increased without compromising the integrity of intestinal mucosa in PD. The increased intestinal permeability in PD may make the patients susceptible to intestinal dysbiosis. Conversely, intestinal dysbiosis may lead to the increased intestinal permeability. One or both of the two mechanisms may be operational in development and progression of PD.

背景
肠道是帕金森病（Parkinson’s disease, PD）最早受累的器官之一。帕金森病患者的结肠黏膜中可见大肠杆菌（Escherichia coli）与α-突触核蛋白（α-synuclein）染色异常。

方法
本研究招募52例帕金森病患者及36名健康同居对照。我们检测了血清标志物，并通过16S或23S核糖体RNA（rRNA）的定量RT-PCR（quantitative RT-PCR）对19种粪便细菌类群、属或种的数量进行定量。尽管6种丰度最高的细菌类群、属或种平均占肠道总细菌的71.3%，但与宏基因组分析或16S rRNA扩增子测序相比，本研究的分析并不全面。

结果
帕金森病患者的乳酸杆菌（Lactobacillus）数量高于对照组，而所分析的细菌总数、梭菌群（Clostridium coccoides group）及脆弱拟杆菌群（Bacteroides fragilis group）的总和低于对照组。此外，帕金森病患者的潜在产氢细菌总和低于对照组。用于预测病程的线性回归模型显示，梭菌群与加氏乳酸杆菌亚种（Lactobacillus gasseri subgroup）分别具有最大的负系数与正系数。而用于预测排便频率的线性回归模型表明，上述细菌与便秘无关联，因此这些细菌的变化不太可能反映帕金森病进展过程中便秘的加重。帕金森病患者的血清脂多糖（lipopolysaccharide, LPS）结合蛋白水平低于对照组，而作为肠黏膜完整性标志物的血清二胺氧化酶水平在帕金森病患者中未发生改变。

结论
帕金森病患者的脂多糖通透性可能升高，但并未破坏肠黏膜完整性。帕金森病患者的肠道通透性升高可能使其易患肠道菌群失调。反之，肠道菌群失调也可能导致肠道通透性升高。这两种机制中的一种或两种共同参与了帕金森病的发生与进展。