Arc1 and the microbiota together modulate growth and metabolic traits in Drosophila

Perturbations to animal-associated microbial communities (the microbiota) have deleterious effects on various aspects of host fitness, but the molecular processes underlying these impacts are poorly understood. Here we identify a novel connection between the microbiota and the neuronal factor Arc1 that affects growth and metabolism in Drosophila. We find that Arc1 exhibits tissue-specific microbiota-dependent expression changes, and that germ-free flies bearing a null mutation of Arc1 exhibit delayed and stunted larval growth, along with a variety of molecular, cellular, and organismal traits indicative of metabolic dysregulation. Remarkably, we show that the majority of these phenotypes can be fully suppressed by mono-association with a single Acetobacter sp. isolate, through mechanisms involving both bacterial diet modification and live bacteria. Additionally, we provide evidence that Arc1 function in key neuroendocrine cells of the larval brain modulates growth and metabolic homeostasis under germ-free conditions. Our results reveal a novel role for Arc1 in modulating physiological responses to the microbial environment, and highlight how host-microbe interactions can profoundly impact the phenotypic consequences of genetic mutations in an animal host. SUMMARYDrosophila Arc1 exhibits microbiota-dependent, tissue-specific differential expression and functionally interacts with a key Acetobacter sp. isolate to regulate developmental growth and metabolic traits.