Abstract:

Previous investigations into gut microbiota dysbiosis in patients with Parkinson’s disease have relied on 16S rRNA amplicon sequencing and assembly-free metagenomic approaches. However, there is an urgent need to study the function of the gut microbiome at the genome level using metagenome-assembled genomes. Here, we conducted single-sample metagenomic binning analysis using shotgun metagenomic sequencing data and retrieved 2837 metagenome-assembled genomes to explore the gut microbiota profile at the genome level. Reconstructing microbial genomes from metagenomic sequences greatly enriched the diversity and number of microbial genomes, especially those of uncultivable strains. By integrating the analysis of metagenome-assembled genomes with clinical parameters, we observed higher α-diversity indexes and a very different composition of microbial communities in patients with Parkinson’s disease. We also identified microbial species and metagenome-assembled genomes that were significantly associated with clinical characteristics, including disease severity, medication, motor complications, and non-motor symptoms. The genes of Parkinson’s disease severity-associated metagenome-assembled genomes were distributed across multiple pathways, such as carbon metabolism, phosphonate metabolism, carbohydrate metabolism, amino acid metabolism, fatty acid metabolism, bile acid metabolism, metabolism of cofactors and vitamins, neuroprotective molecules, immunogenic components, toxic metabolites, translation, and bacterial secretion. Our work provides a comprehensive resource for investigating the gut microbiota–Parkinson’s disease relationship at the genome level, which may enhance our comprehension of the underlying mechanisms of this disease.

Key words: constipation, dysbiosis, gut microbiota, metagenome-assembled genomes, metagenomic binning, nerve regeneration, Parkinson’s disease, shotgun metagenomic sequencing, α-synuclein