摘要：SummaryGut microbiota impacts the host metabolome and affects its health span. How bacterial species in the gut influence age-dependent metabolic alteration has not been elucidated. Here we show inDrosophila melanogasterthat allantoin, an end product of purine metabolism, is increased during aging in a microbiota-dependent manner. Allantoin levels are low in young flies but are commonly elevated upon lifespan-shortening dietary manipulations such as high-purine, high-sugar, or high-yeast feeding. RemovingAcetobacter persiciin theDrosophilamicrobiome attenuated age-dependent allantoin increase. Mono-association withA. persici, but not withLactobacillus plantarum, increased allantoin in aged flies.A. persiciincreased allantoin via activation of innate immune signaling IMD pathway in the renal tubules. On the other hand, analysis of bacteria-conditioned diets revealed thatL. plantarumcan decrease allantoin by reducing purines in the diet. These data together demonstrate species-specific regulations of host purine levels by the gut microbiome.Graphical AbstractDisplay OmittedHighlights•Gut bacterial species regulate the age-dependent metabolic shift inDrosophila•Acetobacter persiciincreases purine levels via IMD activation in the renal tubules•Lactobacillus plantarumdecreases the purine levels in theDrosophiladiet•Diet- and bacteria-dependent elevation of purine levels may shorten the lifespanBiological Sciences; Molecular Biology; Immunology; Microbiome
