When it comes to the gut, it’s not which microbes you have but how they interact that appears to affect health.
This insight comes from a recent study of fruit fly gut microbes that explored the puzzling results of a UC Berkeley study from 91 years ago. Conducted in 1927 by Helen Steinfeld for her Ph.D. dissertation in zoology, her experiment demonstrated that by simply removing the gut bacteria from fruit flies, she could extend their lifespans by 14 percent.
Will Ludington, a former UC Berkeley Bowes Fellow now at the Carnegie Institution for Science in Baltimore, MD, confirmed Steinfeld’s results but carried the experiment much further, adding back different combinations of five bacterial species to see how interactions among them affected the flies’ health, in particular lifespan and fertility.
He and his team found that the interactions that take place among the microbial populations are as important to the fly’s physiology as which individual species are present. While removing all microbes increased a fly’s lifespan by 23 percent, adding back any one of the species could account for only one-quarter of this effect. Interactions among the five separate species accounted for the rest.
"The classic way we think about bacterial species is in a black-and-white context as agents of disease - either you have it or you don’t," Ludington said. "Our work shows that isn’t the case for the microbiome. The effects of a particular species depend on the context of which other species are also present."
Moreover, flies with a more diverse gut community had more offspring, even though they lived shorter lives. The longer-lived flies with sterile guts had fewer offspring.
"As we examined the total of what we call a fly’s fitness - its chances of surviving and creating offspring - we found that there was a tradeoff between having a short lifespan with lots of offspring, versus having a long lifespan with few offspring," Ludington explained. "This tradeoff was mediated by microbiome interactions."
The experiment required development of a novel system for mapping all the possible interactions between the five species of bacteria found in the fly gut in order to see how they affected an insect’s development, production of offspring and lifespan, which are a measure of its fitness. The analysis of the interactions also required developing new mathematical approaches.
Though the fruit fly gut is much simpler than that of humans, the results mean "that if we want to understand how the microbiome impacts our health, we need to develop a predictive understanding of how combinations of bacteria affect the host, not just the individual species," he added.
Ludington and his team, including molecular biologists Alison Gould, Vivian Zhang and Benjamin Obadia of UC Berkeley, physicists Eric Jones and Jean Carlson of UC Santa Barbara, mathematicians Lisa Lamberti, Nikolaos Korasidis and Niko Beerenwinkel of ETH Zurich and Alex Gavryushkin of the University of Otago, published their findings online last month in the Proceedings of the National Academy of Sciences .