Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science, No. 1 DaHua Road, DongDan, Beijing, 100730, China.
Peking University Fifth School of Clinical Medicine, Beijing, China.
Appl Microbiol Biotechnol. 2023 Mar;107(5-6):1917-1929. doi: 10.1007/s00253-023-12410-w. Epub 2023 Feb 16.
Parkinson's disease (PD) is the second most common neurodegenerative disease but still lacks a preclinical strategy to identify it. The diagnostic value of intestinal mucosal α-synuclein (αSyn) in PD has not drawn a uniform conclusion. The relationship between the alteration of intestinal mucosal αSyn expression and mucosal microbiota is unclear. Nineteen PD patients and twenty-two healthy controls were enrolled in our study from whom were collected, using gastrointestinal endoscopes, duodenal and sigmoid mucosal samples for biopsy. Multiplex immunohistochemistry was performed to detect total, phosphorylate, and oligomer α-synuclein. Next-generation 16S rRNA amplicon sequencing was applied for taxonomic analysis. The results implied that oligomer α-synuclein (OSyn) in sigmoid mucosa of PD patients was transferred from the intestinal epithelial cell membrane to the cytoplasm, acinar lumen, and stroma. Its distribution feature was significantly different between the two groups, especially the ratio of OSyn/αSyn. The microbiota composition in mucosa also differed. The relative abundances of Kiloniellales, Flavobacteriaceae, and CAG56 were lower, while those of Proteobacteria, Gammaproteobacteria, Burkholderiales, Burkholdriaceae, Oxalobacteraceae, Ralstonia, Massilla, and Lactoccus were higher in duodenal mucosa of PD patients. The relative abundances of Thermoactinomycetales and Thermoactinomycetaceae were lower, while those of Prevotellaceae and Bifidobacterium longum were higher in patients' sigmoid mucosa. Further, the OSyn/αSyn level was positively correlated with the relative abundances of Proteobacteria, Gammaproteobacteria, Burkholderiales, Pseudomonadales, Burkholderiaceae, and Ralstonia in the duodenal mucosa, while it was negatively correlated with the Chao1 index and observed operational taxonomic units of microbiota in sigmoid mucosa. The intestinal mucosal microbiota composition of PD patients altered with the relative abundances of proinflammatory bacteria in the duodenal mucosa increased. The ratio of the OSyn/αSyn level in the sigmoid mucosa indicated a potential diagnostic value for PD, which also correlated with mucosal microbiota diversity and composition. KEY POINTS: • The distribution of OSyn in sigmoid mucosa differed between PD patients and healthy controls. • Significant alterations in the microbiome were found in PD patients' gut mucosa. • OSyn/αSyn level in sigmoid mucosa indicated a potential diagnostic value for PD.
帕金森病（PD）是第二常见的神经退行性疾病，但仍然缺乏用于识别它的临床前策略。肠道黏膜α-突触核蛋白（αSyn）在 PD 中的诊断价值尚未得出统一结论。肠道黏膜αSyn 表达的改变与黏膜微生物群之间的关系尚不清楚。我们从 19 名 PD 患者和 22 名健康对照者中收集了使用胃肠内窥镜检查采集的十二指肠和乙状结肠黏膜活检样本。进行多重免疫组织化学检测以检测总、磷酸化和寡聚α-突触核蛋白。应用下一代 16S rRNA 扩增子测序进行分类分析。结果表明，PD 患者乙状结肠黏膜中的寡聚α-突触核蛋白（OSyn）从肠上皮细胞膜转移到细胞质、腺腔和基质。其分布特征在两组之间有明显差异，尤其是 OSyn/αSyn 比值。黏膜中的微生物群组成也不同。PD 患者十二指肠黏膜中的 Kiloniellales、Flavobacteriaceae 和 CAG56 的相对丰度较低，而 Proteobacteria、Gammaproteobacteria、Burkholderiales、Burkholderiaceae、Oxalobacteraceae、Ralstonia、Massilia 和 Lactococcus 的相对丰度较高。Thermoactinomycetales 和 Thermoactinomycetaceae 的相对丰度较低，而 Prevotellaceae 和 Bifidobacterium longum 的相对丰度较高。此外，OSyn/αSyn 水平与十二指肠黏膜中 Proteobacteria、Gammaproteobacteria、Burkholderiales、Pseudomonadales、Burkholderiaceae 和 Ralstonia 的相对丰度呈正相关，而与乙状结肠黏膜中微生物 Chao1 指数和观察到的操作分类单位呈负相关。PD 患者的肠道黏膜微生物群组成发生改变，随着十二指肠黏膜中促炎细菌的相对丰度增加。乙状结肠黏膜 OSyn/αSyn 水平比值表明其对 PD 具有潜在的诊断价值，且与黏膜微生物多样性和组成相关。关键点：
PD 患者和健康对照组的乙状结肠黏膜 OSyn 分布存在差异。
PD 患者的肠道黏膜微生物组发生显著改变。
乙状结肠黏膜 OSyn/αSyn 水平提示 PD 有潜在的诊断价值。
