Metagenomic assembled plasmids of the human microbiome vary across disease cohorts

We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample beta-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome alpha-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.

Automated summary

This study compiled a human metagenome assembled plasmid (MAP) database and investigated differences across multiple studies that were originally designed to explore the composition of the human microbiome under various conditions. The results showed that inter-sample beta-diversity differences of plasmid content could distinguish different cohorts. The study also found that patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections had reduced intra-sample plasmidome alpha-diversity, which could be restored by fecal microbiota transplants. Plasmidome diversity, specific plasmids, and plasmid-encoded functions could potentially serve as biomarkers for IBD or its severity. The human plasmidome is an overlooked aspect of the microbiome and should be included in investigations of the microbiome's role in health and disease. Including MAP databases in analyses will improve our understanding of plasmid-encoded functions within the gut microbiome and inform future human metagenome analyses.