The gut microbes of young killifish can extend the lifespans of older fish – hinting at the microbiome’s role in ageing.
It may not be the most appetizing way to extend life but researchers have shown for the first time that older fish live longer after they consumed microbes from the poo of younger fish. The findings were posted to the bioRxiv preprint server on 27 Marchby Dario Valenzano, a geneticist at the Max Planck Institute for Biology of Ageing in Cologne, Germany, and colleagues.
So-called ‘young blood’ experiments that join the circulatory systems of two rats — one young and the other old — have found that factors coursing through the veins of young rodents can improve the health and longevity of older animals. But the new first-of-its-kind study examined the effects of 'transplanting' gut microbiomes on longevity.
“The paper is quite stunning. It’s very well done,” says Heinrich Jasper, a developmental biologist and geneticist at the Buck Institute for Research on Aging in Novato, California, who anticipates that scientists will test whether such microbiome transplants can extend lifespan in other animals.
To test whether the changes in the microbiome had a role in ageing, Valenzano’s team ‘transplanted’ the gut microbes from 6-week-old killifish into middle-aged 9.5-week-old fish. They first treated the middle-aged fish with antibiotics to clear out their gut flora, then placed them in a sterile aquarium containing the gut contents of young fish for 12 hours. Killifish don’t usually eat faeces, Valenzano notes, but they would probe and bite at the gut contents to see whether it was food, ingesting microbes in the process.
The transplanted microbes successfully recolonized the guts of the fish that received them, the team found. At 16 weeks of age, the gut microbiomes of middle-aged fish that received 'young microbes' still resembled those of 6-week-old fish.
The young microbiome ‘transplant’ also had dramatic effects on the longevity of fish that got them: their median lifespans were 41% longer than fish exposed to microbes from middle-aged animals, and 37% longer than fish that received no treatment (antibiotics alone also lengthened lifespan, but to a lesser extent).
And at 16 weeks — old age, by killifish standards — the individuals that received young gut microbes darted around their tanks more frequently than other elderly fish, with activity levels more like 6-week-old fish. By contrast, gut microbes from older fish had no effect on the lifespans of younger fish, Valenzano and his team report
Gut bacteria occupy the interface between the organism and the external environment, contributing to homeostasis and disease. Yet, the causal role of the gut microbiota during host aging is largely unexplored. Here, using the African turquoise killifish (Nothobranchius furzeri), a naturally short-lived vertebrate, we show that the gut microbiota plays a key role in modulating vertebrate life span. Recolonizing the gut of middle-age individuals with bacteria from young donors resulted in life span extension and delayed behavioral decline. This intervention prevented the decrease in microbial diversity associated with host aging and maintained a young-like gut bacterial community, characterized by overrepresentation of the key genera Exiguobacterium, Planococcus, Propionigenium and Psychrobacter. Our findings demonstrate that the natural microbial gut community of young individuals can causally induce long-lasting beneficial systemic effects that lead to life span extension in a vertebrate model.