Dietary Stimuli, Intestinal Bacteria and Peptide Hormones Regulate Female Defecation Rate.

Peptide hormones control gut motility, but the intestinal stimuli and the gene networks coordinating this trait remain poorly defined. Here, we customized an assay to quantify female defecation rate as a proxy of intestinal motility. We found that bacterial infection with the human opportunistic bacterial pathogen (strain PA14) increases defecation rate in wild-type female flies, and we identified specific bacteria of the fly microbiota able to increase defecation rate. In contrast, dietary stress, imposed by either water-only feeding or high ethanol consumption, decreased defecation rate and the expression of enteroendocrine-produced hormones in the fly midgut, such as Diuretic hormone 31 (Dh31). The decrease in defecation due to dietary stress was proportional to the impact of each stressor on fly survival. Furthermore, we exploited the Drosophila Genetic Reference Panel wild type strain collection and identified strains displaying high and low defecation rates. We calculated the narrow-sense heritability of defecation rate to be 91%, indicating that the genetic variance observed using our assay is mostly additive and polygenic in nature. Accordingly, we performed a genome-wide association (GWA) analysis revealing 17 candidate genes linked to defecation rate. Downregulation of four of them (, , and ) in either the midgut enteroendocrine cells or in neurons reduced defecation rate and altered the midgut expression of , that in turn regulates defecation rate via signaling to the visceral muscle. Hence, microbial and dietary stimuli, and -controlling genes, regulate defecation rate involving signaling within and among neuronal, enteroendocrine, and visceral muscle cells.