Separation of Cohorts on the Basis of Bacterial Type IV Conjugation Systems Identified From Metagenomic Assemblies

Abstract

\n BackgroundConjugation enables the exchange of genetic elements throughout environments, including the human gut microbiome. Conjugative elements can carry and transfer clinically relevant metabolic pathways which makes precise identification of these systems in metagenomic samples clinically important. ResultsHere, we outline two distinct methods to identify conjugative elements in the human gut microbiome. We first show that conjugative elements exhibit strong population and age-level stratification. Furthermore, the taxonomic compositions of the conjugative elements differ from the composition of the metagenome assembled genomes, both in terms of the number of assembled elements and the relative abundances of the assembled systems. Finally, we demonstrate that the majority of assembled conjugative elements are not included within metagenomic bins, and that only a small proportion of the binned conjugative systems are included in high-quality metagenomic bins. Our findings highlight that conjugative systems differ between a North American inflammatory bowel disease cohort and a cohort of North American pre-term infants, but in a manner different than metagenome assembled genomes, revealing a potential use as an age-related biomarker. Additionally, conjugative systems can distinguish between other geographical-based cohorts. ConclusionsAnalysis of the human gut microbiome by shotgun metagenomic sequencing has revealed numerous connections to human health outcomes. Our findings emphasize the need to identify and analyze conjugative systems outside of standard metagenomic binning pipelines. We suggest that analysis of type IV conjugative systems should be added to the current metagenomic analysis approaches as they contain much information that could explain differences between cohorts beyond those we investigated.