Aged gut microbiome extracellular vesicles impair intestinal barrier and metabolic function

The gut microbiome ages alongside us, accumulating harmful bacterial species that secrete extracellular vesicles capable of breaching the intestinal barrier and systemic metabolism. In a comparative study of 3-month and 24-month-old mice, luminal fecal exosomes (LFEs) from aged intestines displayed distinct proteomic and microRNA profiles enriched in molecules associated with insulin resistance and barrier dysfunction. When these aged vesicles were administered to young mice via gavage, they impaired intestinal integrity and metabolic function in recipients, with reciprocal effects when older mice received LFEs from young donors. Multi-omic analysis identified age- and sex-dependent changes in vesicle cargo, involving both host and microbiome-derived proteins and microRNAs. For longevity-focused biohackers and clinicians, these findings position microbial vesicle composition as an accessible biomarker of intestinal aging and a potential therapeutic target through fecal microbiota transplantation or dietary intervention.