The alteration of intestinal mucosal α-synuclein expression and mucosal microbiota in Parkinson’s disease
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Published:2023-02-16
Issue:5-6
Volume:107
Page:1917-1929
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ISSN:0175-7598
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Container-title:Applied Microbiology and Biotechnology
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language:en
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Short-container-title:Appl Microbiol Biotechnol
Author:
Shi Jihua, Wang Yiran, Chen Dan, Xu Xue, Li Wenbin, Li Kai, He Jing, Su Wen, Luo QingfengORCID
Abstract
Abstract
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.
Funder
Fundamental Research Funds for the Central Universities Peking Union Medical College Hospital and National High Level Hospital Clinical Research Funding National High Level Hospital Clinical Research Funding
Publisher
Springer Science and Business Media LLC
Subject
Applied Microbiology and Biotechnology,General Medicine,Biotechnology
Reference43 articles.
1. Aldecoa I, Navarro-Otano J, Stefanova N, Sprenger FS, Seppi K, Poewe W, Cuatrecasas M, Valldeoriola F, Gelpi E, Tolosa E (2015) Alpha-synuclein immunoreactivity patterns in the enteric nervous system. Neurosci Lett 602:145–149. https://doi.org/10.1016/j.neulet.2015.07.005 2. Arvans DL, Vavricka SR, Ren H, Musch MW, Kang L, Rocha FG, Lucioni A, Turner JR, Alverdy J, Chang EB (2005) Luminal bacterial flora determines physiological expression of intestinal epithelial cytoprotective heat shock proteins 25 and 72. Am J Physiol-Gastr L 288(4):G696–G704. https://doi.org/10.1152/ajpgi.00206.2004 3. Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, Alexander H, Alm EJ, Arumugam M, Asnicar F, Bai Y, Bisanz JE, Bittinger K, Brejnrod A, Brislawn CJ, Brown CT, Callahan BJ, Caraballo-Rodríguez AM, Chase J et al (2019) Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol 37(8):852–857. https://doi.org/10.1038/s41587-019-0209-9 4. Bottner M, Zorenkov D, Hellwig I, Barrenschee M, Harde J, Fricke T, Deuschl G, Egberts JH, Becker T, Fritscher-Ravens A, Arlt A, Wedel T (2012) Expression pattern and localization of alpha-synuclein in the human enteric nervous system. Neurobiol Dis 48(3):474–480. https://doi.org/10.1016/j.nbd.2012.07.018 5. Boussarie G, Bakker J, Wangensteen OS, Mariani S, Bonnin L, Juhel JB, Kiszka JJ, Kulbicki M, Manel S, Robbins WD, Vigliola L, Mouillot D (2018) Environmental DNA illuminates the dark diversity of sharks. Sci Adv 4(5):eaap9661. https://doi.org/10.1126/sciadv.aap9661
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