The origin of plasma-derived bacterial extracellular vesicles in healthy individuals and patients with inflammatory bowel disease: A pilot study

The gastrointestinal tract harbours the gut microbiota, structural alterations of which (dysbiosis) are linked with an increase in gut permeability (“leaky gut”) and chronic debilitating diseases including inflammatory bowel disease (IBD). Disruption of the epithelial barrier enables luminal antigens and bacterial products such as nanosized bacterial extracellular vesicles (BEVs) to access the circulatory system. Blood-derived BEVs contain various cargoes and may be useful biomarkers for diagnosis and monitoring disease status and relapse in conditions such as IBD. To progress this concept, we developed a rapid, cost-effective protocol to isolate BEV-associated DNA and use 16S rRNA sequencing to identify bacterial origins of the blood microbiome of healthy individuals and patients with Crohn's disease and ulcerative colitis. We found that the plasma from IBD patients exhibited an increase in BEVs originating from the Actinobacteriota and Proteobacteria phyla and a decrease in Firmicutes phylum compared to healthy controls, which mirrors that of the IBD gut microbiota. Pathobiont genera such as Pseudomonas or Escherichia were increased in IBD plasma. Our pilot study shows blood microbiota profiling could provide a means of analysing microbial dysbiosis and a basis for investigating further the potential of plasma-derived BEVs as a simple and cost-effective diagnostic blood-test for IBD.