Directed evolution of the microbiome extended lifespan in fruit flies
Gut bacteria selected outside the body extended lifespan in female fruit flies by approximately 20%
On August 9, bioRxiv published a preprint describing an experiment in Drosophila, or fruit flies. For several weeks, the researchers cultured the flies' gut bacteria in medium containing progressively higher doses of paraquat, a pesticide that induces oxidative reactions that damage cells. They then tested the selected cultures in flies.
The researchers passaged bacteria from the flies' intestines 25 times in medium containing progressively higher doses of paraquat. Hundreds of bacterial generations passed during this period. A control culture underwent the same number of passages without paraquat, allowing the researchers to distinguish selection for stress resistance from the effects of laboratory culture itself.
Flies raised without their own microbiota were colonized with one of the two cultures and kept under standard conditions. Females colonized with the selected community lived approximately 20% longer than the control group, while males lived approximately 12% longer. After antibiotics removed the gut bacteria, lifespan no longer differed between the groups. The number of bacteria in the gut and the feeding rate ten days after colonization were also the same in both groups. Together, these controls attribute the difference in lifespan to the transplanted live bacteria.
The authors then tested individual members of the community. Five selected variants of Lactiplantibacillus plantarum, a species of gut bacterium, extended lifespan compared with five control variants. The same result was obtained in flies with a conventional microbiome. These flies received either a selected or a control bacterial variant for three days every ten days.
Each of the five selected variants carried a different mutation within the same set of genes. These cultures produced approximately five times more acetate, a substance generated by bacterial metabolism. Adding acetate to the food extended the lifespan of flies carrying the control bacterium. This experiment linked the changes in the bacterium to the outcome in the fly.
In a 2024 study, researchers adapted E. coli to paraquat and fed it to the nematode C. elegans, a roundworm. In that study, the longer lifespan was linked to iron in the bacteria and the p38-MAPK signaling pathway, a cellular stress-response system. The current preprint applies the same approach to a community of fruit-fly gut bacteria but identifies a different biochemical pathway: increased acetate production.