Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson's Disease.
Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson's Disease.
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DOI：
10.1371/journal.pone.0142164
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hirayama M
中科院分区：
文献类型：
--
作者：
Hasegawa S;Goto S;Tsuji H;Okuno T;Asahara T;Nomoto K;Shibata A;Fujisawa Y;Minato T;Okamoto A;Ohno K;Hirayama M
肠道是帕金森病（PD）中最先受影响的器官之一。帕金森病患者的结肠中大肠杆菌和α - 突触核蛋白染色异常。
我们招募了52名帕金森病患者和36名健康的同居者。我们测量了血清标志物，并通过16S或23S rRNA的定量逆转录聚合酶链反应对19个粪便细菌群/属/种的数量进行了定量。尽管6种最主要的细菌群/属/种平均占肠道细菌总数的71.3%，但与宏基因组分析或16S rRNA扩增子测序相比，我们的分析并不全面。
在帕金森病中，乳酸杆菌的数量较高，而所分析的细菌总数、球形梭菌组和脆弱拟杆菌组的数量低于对照组。此外，帕金森病中假定的产氢细菌总数较低。一个用于预测疾病病程的线性回归模型表明，球形梭菌组和格氏乳杆菌亚组分别具有最大的负系数和正系数。由于用于预测排便频率的线性回归模型显示这些细菌与便秘无关，因此这些细菌的变化不太可能代表帕金森病进展过程中便秘的恶化。在帕金森病中，血清脂多糖（LPS）结合蛋白水平低于对照组，而血清二胺氧化酶（一种肠道黏膜完整性的标志物）水平在帕金森病中保持不变。
在帕金森病中，脂多糖的通透性可能增加，但肠道黏膜的完整性未受损害。帕金森病中肠道通透性的增加可能使患者易患肠道菌群失调。反过来，肠道菌群失调可能导致肠道通透性增加。这两种机制中的一种或两种可能在帕金森病的发生和发展中起作用。
The 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. We 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. In 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. The 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.