Intestinal microbes shorten host lifespan through increased intestinal permeability in Drosophila melanogaster

Intestinal microbes that live in a symbiotic relationship with their host are well known to affect host fitness such as metabolism, obesity, and inflammation. However, the effects of intestinal microbes on host lifespan are not well characterized. In this study, we investigated the effects and mechanisms of intestinal microbes on host lifespan using the Drosophila melanogaster as a powerful model animal to study host-microbes interaction.We generated axenic flies by dechorionation of eggs with sodiumhy pochlorite, and measured its lifespan. The lifespan of flies was increased under axenic condition, and it was decreased by the oral ingestion of the extracts of guts from female flies, indicating that the microbes existing in the gut of flies affect host lifespan. To investigate which commensal bacteria affect the host lifespan, adult flies was subjected to oral ingestion with the single species of microbes such as Lactobacillus brevis , Acetobacter persici , Lactobacillus plantarum and Acetobater malorum which are dominated in the guts of young or old flies. We hypothesized dysbiosis of the intestinal microbiota leads to systemic influences on aging files with increased intestinal permeability. The incidence of intestinal dysfunction was increased by aging and intestinal dysfunction increased the permeability of microbes in the gut of flies. In addition, we interestingly observed that L. plantarum , Sphingomonas yunnanensis , L. brevis , and Acetobacter indonesiensis were found in the hemolymph of flies with intestinal barrier dysfunction. Taken together, our findings suggest the possibility that intestinal microbes decrease the host lifespan with increased intestinal permeability by aging.