Gut-derived bacterial membrane vesicles in prediabetes: Vesicle composition dictates inflammatory properties

Systemic inflammation relates to the pathophysiology of metabolic diseases such as obesity or type 2 diabetes. Understanding aberrant microbiota-host interactions is essential for comprehending their pathogenesis. Gut bacteria produce bacterial membrane vesicles (bMVs) reflecting bacterial metabolism and activity. Importantly, in animal models, these vesicles can reach organs and affect metabolism by inducing inflammation. We investigated feces-derived gut bacteria and bMVs in participants diagnosed with prediabetes and in healthy controls. Vesicle and bacterial DNA repertoires were found to be vastly different, with Gram-negative bacterial taxa dominating at the vesicle level (<i>Alistipes</i>, <i>Barnesiella</i>) and Gram-positive taxa (<i>Anaerostipes</i>, <i>Collinsella</i>) dominating at the bacterial level. We observed no compositional differences between participant-phenotype groups. Strikingly, vesicle repertoires characterized by elevated proportional abundance of Lachnospiraceae and Oscillospiraceae DNA were more proinflammatory, whereas the opposite was observed for vesicles rich in Akkermansiaceae DNA. These results may improve our understanding of microbe-host interactions relevant to metabolic and inflammatory diseases.