Large-scale profiling of blood microbial signatures in patients with Parkinson's disease and its association with disease progression: a cross-sectional study.

Abstract

Emerging evidence supports the presence of microbial signatures in the blood, yet their clinical relevance remains poorly understood. In this study, we profiled blood microbial signatures in patients with Parkinson's disease (PD) and investigated their associations with disease progression. We analysed 4018 whole-genome sequencing (WGS) data of blood samples from two independent cohorts. The high-quality non-human reads were extracted for microbial annotation using Kraken 2 and Bracken software with the PlusPF database. To identify PD-associated signatures, we implemented a population-based, cross-cohort filtration process with resequencing validation to minimise noise and putative contaminants. Microbial DNA signals, predominantly bacterial, were extensively detected in the sequencing data and were more abundant in individuals with PD than in controls. Across the two cohorts, 126 bacterial species were identified as key signatures, nearly two-thirds of which are known to colonise human body sites. Among these, 19 species exhibited increased abundance and higher prevalence in PD, and could serve as features to discriminate effectively patients from controls. Furthermore, several microbial signatures were correlated with more severe clinical manifestations, such as motor dysfunction and cognitive impairment. Our findings supported blood microbial signatures as promising biomarkers in PD, although their origin and functional relevance remain to be validated. The analytical framework may facilitate future investigations into the potential clinical implications of blood microbial signatures in disease contexts. This work was supported by Hunan Innovative Province Construction Project, National Natural Science Foundation of China, and Natural Science Foundation of Hunan Province.