The gastrointestinal tract is emerging as a key regulator of appetite and metabolism, but daunting neuroanatomical complexity has hampered identification of the relevant signals. Invertebrate models could provide a simple and genetically amenable alternative, but their autonomic nervous system and its visceral functions remain largely unexplored. Here we develop a quantitative method based on defecation behavior to uncover a central role for the Drosophila intestine in the regulation of nutrient intake, fluid, and ion balance. We then identify a key homeostatic role for autonomic neurons and hormones, including a brain-gut circuit of insulin-producing neurons modulating appetite, a vasopressin-like system essential for fluid homeostasis, and enteric neurons mediating sex peptide-induced changes in intestinal physiology. These conserved mechanisms of visceral control, analogous to those found in the enteric nervous system and hypothalamic/pituitary axis, enable the study of autonomic control in a model organism that has proved instrumental in understanding sensory and motor systems.
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