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

Development. 2021 Aug 1;148(15):dev195222. doi: 10.1242/dev.195222. Epub 2021 Jul 29.


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 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 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.

Keywords: Acetobacter; Arc1; Growth regulation; Insulin signaling; Metabolism; Microbiota.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetobacter / physiology
  • Animals
  • Brain / metabolism
  • Brain / physiology
  • Cytoskeletal Proteins / metabolism*
  • Drosophila / metabolism*
  • Drosophila / physiology*
  • Homeostasis / physiology
  • Larva / metabolism
  • Larva / physiology
  • Microbiota / physiology*
  • Mutation / physiology
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Neurons / physiology
  • Phenotype


  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • activity regulated cytoskeletal-associated protein