The alteration of intestinal mucosal α-synuclein expression and mucosal microbiota in Parkinson’s disease Original paper

What was studied?

This original research investigated the diagnostic value of intestinal mucosal oligomeric α-synuclein (OSyn) and the relationship between mucosal α-synuclein (αSyn) expression and mucosal microbiota composition in Parkinson’s disease (PD). The study aimed to resolve uncertainties about whether intestinal mucosal αSyn could serve as an early biomarker for PD, given that αSyn aggregation is a hallmark of the disease not only in the brain but also in the enteric nervous system. Using gastrointestinal endoscopy, duodenal and sigmoid mucosal samples were collected from participants. Multiplex immunohistochemistry (mIHC) was employed to detect total, phosphorylated, and oligomeric αSyn simultaneously, while next-generation 16S rRNA amplicon sequencing was used to characterize the mucosal microbiota. The study further explored whether the distribution and ratios of different αSyn species—especially the OSyn/αSyn ratio—correlated with distinct microbial signatures, potentially forming the basis for a microbiome signature database relevant to PD diagnosis and pathogenesis.

Who was studied?

The study involved a total of 41 participants: 19 patients clinically diagnosed with Parkinson’s disease (Hoehn and Yahr stage <5) and 22 age-matched healthy controls with no neurodegenerative diseases. All participants were recruited from Beijing Hospital and provided written informed consent. Gastrointestinal endoscopies were performed to obtain duodenal and sigmoid mucosal biopsies. Notably, duodenal mucosal specimens from 7 healthy controls and 10 PD patients, and sigmoid mucosal specimens from 21 healthy controls and 19 PD patients, were used for mIHC analysis. For microbiota sequencing, post-quality control, duodenal mucosal samples from 7 controls and 7 PD patients, and sigmoid mucosal samples from 18 controls and 17 PD patients, were analyzed. The cohort was balanced in terms of sex and age between groups, and all procedures were conducted under strict ethical guidelines.

Most important findings

The study revealed several key findings with direct relevance to the identification of microbiome signatures in PD:

Key implications

This study provides compelling evidence that the OSyn/αSyn ratio in sigmoid mucosa is a highly promising, minimally invasive biomarker for early PD diagnosis. The findings also demonstrate that PD is associated with proinflammatory shifts in the duodenal mucosal microbiota—particularly increased Proteobacteria—supporting the hypothesis that gut dysbiosis contributes to PD pathogenesis via the microecology-gut-brain axis. The strong correlation between specific microbial taxa and αSyn aggregation highlights the potential for microbiome-based diagnostic and therapeutic strategies. Additionally, the work emphasizes the importance of mucosal (rather than fecal) microbiota profiling for disease-specific signatures, as mucosal communities may better reflect local pathophysiology. These insights could inform the development of microbiome signatures databases and guide future interventions targeting gut microbiota to modify PD progression.

Citation

Shi J, Wang Y, Chen D, Xu X, Li W, Li K, He J, Su W, Luo Q. The alteration of intestinal mucosal α‑synuclein expression and mucosal microbiota in Parkinson’s disease. Applied Microbiology and Biotechnology. 2023;107:1917–1929. doi:10.1007/s00253-023-12410-w