Objective: To carry out deep analysis on gut microbiome in patients with Parkinson’s disease (PD) and to evaluate the potential application for diagnosing PD patients from gut metagenomes.

Background: Identification the roles of gut microbiome associated with diseases using metagenome-wide association studies has become a hot area worldwide. Accumulating evidences demonstrated that gut microbiota dysbiosis may play a key role in the progress of PD.

Methods: A case-control study based on deep next-generation shotgun sequencing of gut microbial DNA from 40 Chinese PD patients and their healthy spouses was devised and carried out using Illumina Hiseq Ten platform. Particularly, a fast and sensitive real-time PCR method was developed for specific detection of PD-associated gut microbial gene markers in the original 80 subjects and validated the results in an independent cohort of 70 patients and 64 controls.

Results: Significant differences were detected in the richness and communities of gut microbial gene between PD and healthy groups. A total of different 174,964 genes were identified and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. 153 metagenomic species (MGS) were clustered to be differentially abundant between PD and healthy groups. Strain Alistipes indistinctus YIT 12060 and Alistipes finegoldii DSM 17242 were enriched in the PD group, and Bacteroides vulgatus ATCC 8482 was enriched in the healthy group. The most enriched functional of the gut metagenome associated with PD were involving metabolisms. 25 microbial gene markers were identified to distinguish PD from healthy group with areas under the receiver-operating curve (AUC) of 0.895 and a highly accurate index of PD patient discrimination was created. Detecting the 25 gene markers by method of real-time PCR could classify PD and healthy groups using shotgun sequencing with AUC of 0.922, and validated on an independent larger cohort with AUC of 0.869.

Conclusions: We present firstly the metagenome-wide association study in Chinese PD patients. Alterations of specific species and functional components of the gut metagenome were associated with PD. Particularly, gut microbial gene markers may be a powerful tool for diagnosis of PD, providing new leads for the development of new diagnostic tools and potential treatments.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-gut-microbial-genes-in-parkinsons-disease-by-shotgun-metagenomic-analysis/