Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila

Animals can detect and consume nutritive sugars without the influence of taste. However, the identity of the taste-independent nutrient sensor and the mechanism by which animals respond to the nutritional value of sugar are unclear. Here, we report that six neurosecretory cells in the Drosophila brain that produce Diuretic hormone 44 (Dh44), a homolog of the mammalian corticotropin-releasing hormone (CRH), were specifically activated by nutritive sugars. Flies in which the activity of these neurons or the expression of Dh44 was disrupted failed to select nutritive sugars. Manipulation of the function of Dh44 receptors had a similar effect. Notably, artificial activation of Dh44 receptor-1 neurons resulted in proboscis extensions and frequent episodes of excretion. Conversely, reduced Dh44 activity led to decreased excretion. Together, these actions facilitate ingestion and digestion of nutritive foods. We propose that the Dh44 system directs the detection and consumption of nutritive sugars through a positive feedback loop. •Six Dh44+ cells in the brain are essential for post-ingestive nutrient selection•Dh44 neurons are specifically activated by nutritive sugars found in the hemolymph•Activation of the Dh44 circuit results in increased proboscis extension and excretion•The brain-gut axis connects the ability to detect nutrients with effector mechanisms Sugar is sweet and nutritive. The taste cells that detect its sweetness were identified, but the sensor that detects its nutritional value is unknown. Dus et al. identify a brain-gut microcircuit expressing Dh44/CRH as the nutrient sensor.