Microbial solutions to dietary stress: experimental evolution reveals host-microbiome interplay in .

Can the microbiome serve as a reservoir of adaptive potential for hosts? To address this question, we leveraged approximately 150 generations of experimental evolution in on a stressful, high-sugar diet. We performed a fully reciprocal transplant experiment using the control and high-sugar bacteria. If the microbiome confers benefits to hosts, then transplant recipients should gain fitness benefits compared with controls. Interestingly, we found that such benefits exist, but their magnitude depends on evolutionary history-mismatches between fly evolution and microbiome reduced fecundity and potentially exerted fitness costs, especially in the stressful high-sugar diet. The dominant high-sugar bacteria () uniquely encoded several genes to enable uric acid degradation, mediating the toxic effects of uric acid accumulation due to the high-sugar diet for flies. Our study demonstrates that host genotype × microbiome × environment interactions have substantial effects on host phenotype, highlighting how host evolution and ecological context together shape the adaptive potential of the microbiome.