PhD defence Jari Verbunt

Keywords: Bacterial vesicles, Microbiota, Metabolic health

"From Microbiota to Host: Bacterial membrane vesicles in human metabolic health"

This thesis explored the composition, properties, and inflammatory potential of gut-derived bacterial membrane vesicles (bMVs) in human metabolic and gastrointestinal health. Across cohorts spanning overweight/obesity, prediabetes, and irritable bowel syndrome (IBS), bMV characteristics were investigated alongside their bacterial producer strains and immune-activating potential. bMV compositions were i) found to be distinct from the bacterial communities from which they derived and ii) composition was predictive for inflammatory potential. While prediabetes, overweight/obesity and supplementation with prebiotics including inulin, resistant starch and 2’-fucosyllactose did not relate to differences in bMV profiles, antibiotic-induced microbiota disruption profoundly altered vesicle characteristics. Vancomycin yielded Enterobacteriaceae-enriched bMVs with increased Toll-like receptor (TLR) 4 activating potential, which largely recovered following antibiotic cessation. Conversely, IBS was associated with attenuated bMV-mediated TLR2 activation and inflammatory signaling. Together, these findings establish bMVs as a distinct and dynamic component of microbiota-host interactions and highlight the value of investigating microbial output and functionality alongside conventional compositional microbiota profiling.

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