Extension of host lifespan by polyamines derived from gut bacteria

Metabolites produced by gut bacteria are taken up by the host and have a direct impact on its health. However, to our knowledge, no studies have investigated the effects of gut bacterial metabolites on the lifespan of the host using gnotobiotic animals colonized with gut bacteria deficient in biosynthetic genes involved in the production of specific metabolites. Polyamines, such as putrescine and spermidine, are among the most important metabolites of gut bacteria. Previous studies have shown that increasing polyamines in the colon of mice extends their lifespan and biological functions. In this study, we produced gnotobiotic flies colonized with Escherichia coli, in which polyamine biosynthetic genes were deleted or complemented. Gnotobiotic flies were fed a polyamine-free diet, and the effects of metabolites derived solely from gut bacteria on the lifespan of the host were analyzed. The results showed that polyamines derived from gut bacteria significantly prolonged the lifespan of the flies. Furthermore, the expression of TotM and Halo was suppressed in flies monocolonized with polyamine-producing E. coli compared with those monocolonized with mutant bacteria incapable of producing polyamines.IMPORTANCEThe intestinal tract of a human contains more than 150 species of gut bacteria, which comprise the gut microbiota. Only a very small number of gut bacteria, compared to the bacteria in feces, can come into contact with human tissues due to the barrier mechanism of the intestinal tract, but metabolites of the gut microbiota can pass through the intestinal epithelium and be taken into the body, directly affecting the health of the host. Thus, the importance of gut bacterial metabolites has received increasing attention in recent years. However, analysis into the effects of gut bacterial metabolites on host animals has been limited to only part of the host animal life cycle. In this study, we used Drosophila melanogaster, which has a short average lifespan, as a host and measured its lifespan to provide a simple analysis of the lifetime effects of gut bacterial metabolites on the host.