Metagenome-assembled microbial genomes from Parkinson’s disease fecal samples Original paper

What was studied?

This study investigated the genome-level differences in the gut microbiome between individuals with Parkinson’s disease (PD) and healthy controls, utilizing deep shotgun metagenomic sequencing and advanced metagenome-assembled genome (MAG) analysis. The researchers aimed to go beyond conventional 16S rRNA gene profiling to capture strain-level genomic diversity and functional gene content within the gut microbiota associated with PD. By sequencing fecal DNA from participants, assembling and binning genomes, and annotating their genetic features, the study sought to identify microbial signatures and functional genes that may distinguish PD from control populations. Particular focus was placed on microbial diversity, gene presence-absence, growth dynamics, and the prevalence of biosynthetic gene clusters, antiviral defense systems, and phage integrations within the gut ecosystem. The ultimate goal was to generate a comprehensive reference of high-quality gut MAGs and to uncover microbial and genetic hallmarks relevant to the pathogenesis or protection against PD.

Who was studied?

The study cohort comprised 136 Finnish adults, evenly split between 68 individuals diagnosed with Parkinson’s disease and 68 age- and gender-matched healthy controls. All participants were part of the well-characterized Helsinki cohort, previously used in related microbiome and clinical studies of PD. The mean age was approximately 65 years for both groups, and each group was balanced for sex (50% female). BMI was also similar between the groups. Fecal samples were collected, stored, and processed under standardized conditions. All participants provided written informed consent, and ethical approval was obtained according to the Declaration of Helsinki.

Most important findings

The study yielded 952 non-redundant, high-quality MAGs from 136 fecal samples, with most assigned to the phyla Firmicutes and Bacteroidota, reflecting the typical composition of the human gut microbiome. Key findings include:

Strain-level Diversity: Ruminococcus bromii exhibited significantly higher microdiversity (strain-level nucleotide diversity) in controls than in PD patients (p <0.002). This suggests reduced within-species variability of this important gut bacterium in PD.

Gene Signatures: Several gene clusters, notably including the speF (ornithine decarboxylase) gene from Veillonella and Fe–S oxidoreductase from Eubacterium, were significantly more frequent in controls. Many of these genes are involved in metabolism and were nearly absent from PD samples, pointing toward potential protective roles or metabolic disruptions in PD.

Taxa-specific Abundance: Alistipes onderdonkii was more abundant in PD samples, while MAGs from Agathobacter, Prevotella, Dysosmobacter, Clostridium, Choladocola, and Blautia were more abundant in controls. Notably, the abundance of Prevotella (and its diversity) was higher in controls, aligning with previous PD microbiome studies.

Growth Dynamics: The Oscillospiraceae family exhibited higher growth rates (as estimated by the GRiD index) in controls, but no significant growth differences were seen at genus or species levels.

Archaeal Differences: Methanobrevibacter smithii was more abundant in PD samples, while members of Methanomethylophilaceae were enriched in controls.

Biosynthetic and Defense Elements: The vast majority of MAGs harbored genes for antiviral defense (e.g., CRISPR-Cas, restriction-modification systems). Biosynthetic gene clusters for molecules such as yersiniabactin and colibactin were identified in both groups, with some differences.

Phage Associations: Approximately 28% of identified phage contigs could be assigned to MAGs, most commonly infecting Bilophila.

Key implications

This study provides one of the most detailed genome-level characterizations of the PD-associated gut microbiome to date, establishing a valuable reference set of MAGs for future research. The findings highlight reduced strain-level diversity and loss of certain metabolic genes in key taxa among PD patients, suggesting that both taxonomic and functional aspects of the microbiome may be altered in PD. The identification of candidate protective genes and taxa, as well as the observation of increased archaeal abundance in PD, could inform biomarker discovery and therapeutic strategies. Importantly, the demonstration of extensive antiviral defense systems emphasizes the evolutionary arms race within the gut and may have implications for microbial dynamics in PD. These genome-resolved insights underscore the need for functional studies to clarify causal relationships and support the inclusion of strain- and gene-level data in microbiome signature databases for clinical translation.

Citation

Duru IC, Lecomte A, Shishido TK, et al. Metagenome-assembled microbial genomes from Parkinson’s disease fecal samples. Sci Rep. 2024;14:18906. doi:10.1038/s41598-024-69742-4