The commensal microbes of the gut microbiome generate a range of metabolites that are beneficial or necessary to cell function. Levels of a number of these metabolites have been shown to decline with age as the composition of the gut microbiome changes for the worse. Overall the gut microbiome clearly makes a meaningful contribution to health and longevity, as demonstrated by the sizeable benefits resulting from providing a young microbiome to an old animal, but it isn't clear as to how much of these effects derive from changes in the production of any specific metabolite.
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.
Link: https://doi.org/10.1128/mbio.01484-26
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