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

Abstract

The human gut microbiome composition has been linked to Parkinson’s disease (PD). However, knowledge of the gut microbiota on the genome level is still limited. Here we performed deep metagenomic sequencing and binning to build metagenome-assembled genomes (MAG) from 136 human fecal microbiomes (68 PD samples and 68 control samples). We constructed 952 non-redundant high-quality MAGs and compared them between PD and control groups. Among these MAGs, there were 22 different versions ofCollinsellaandPrevotellaMAGs, indicating high variability of those genera in the human gut environment. Microdiversity analysis indicated thatRuminococcus bromiiwas statistically significantly (p < 0.002) more diverse on the strain level in the control samples compared to the PD samples. In addition, by clustering all genes and performing presence-absence analysis between groups, we identified several control-specific (p < 0.05) related genes, such asspeFand Fe-S oxidoreductase. We also report detailed annotation of MAGs, including Clusters of Orthologous Genes (COG), Cas operon type, antiviral gene, prophage, and secondary metabolites biosynthetic gene clusters, which can be useful for providing a reference for future studies.

Comparison of phage and plasmid populations present in the gut microbiota of Parkinson’s disease patients

“…In addition, studies have reported the existence of CRISPR-Cas systems in phages, confering a survival advantage to the host organism (ref 27 Seed et al, 2013). Interestingly, 33% of these viral contigs were also found within a metagenome-assembled genome (MAG) constructed from the same dataset in our earlier study (ref 54 Duru et al, 2023), suggesting the possibility that the cas defense systems in these MAGs may have been acquired from the phages. Finally, we have noted the presence of several CRISPR arrays within the viral contigs, lacking any cas genes, with the majority consisting of less than three repeats.…”

“…Previously a gut virome study also reported that “lysogenic” type viruses do not dominate the gut ecosystem (ref 67 Bhardwaj et al, 2022). In our earlier study, we found that about 28% of the predicted viral sequences are actually part of microbial genomes (ref 54 Duru et al, 2023). Possibly, the high number of “lytic” viruses might explain why there were relatively few phages within the microbial genomes.…”

“…Other Cas gene types that were detected in the identified viral contigs included IV-B, V-F1, VI-D, I-C, VI-A, V-A, VI-B1, I-E, II-B, and I-B (Supplementary Table S10). Of the 144 viral contigs in which a cas gene was detected, 47 (33%) were identified within a metagenome-assembled genome that was constructed in our previous study (ref 54 Duru et al, 2023). Notably, our observations revealed that among the cas genes we identified within viral contigs, only 20 had proximate CRISPR arrays, while for the majority (n=124), no nearby CRISPR arrays were detected.…”