Kotronarou Katerina, Charalambous Anna, Evangelou Amalia, Georgiou Olympiada, Demetriou Andri, Apidianakis Yiorgos
Department of Biological Sciences, University of Cyprus, P.O. Box 20537, Nicosia 2109, Cyprus.
Metabolites. 2023 Feb 12;13(2):264. doi: 10.3390/metabo13020264.
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.
肽类激素控制肠道蠕动，但肠道刺激以及协调这一特性的基因网络仍未明确界定。在这里，我们定制了一种测定方法，以量化雌性果蝇的排便率作为肠道蠕动的指标。我们发现，感染人类机会致病菌（PA14菌株）会增加野生型雌性果蝇的排便率，并且我们鉴定出果蝇微生物群中能够增加排便率的特定细菌。相比之下，仅饮水或高乙醇摄入量所施加的饮食压力会降低排便率以及果蝇中肠内分泌产生的激素的表达，例如利尿激素31（Dh31）。饮食压力导致的排便率下降与每种压力源对果蝇生存的影响成正比。此外，我们利用果蝇遗传参考面板野生型菌株集合，鉴定出排便率高和低的菌株。我们计算出排便率的狭义遗传力为91%，这表明使用我们的测定方法观察到的遗传变异在本质上大多是加性的和多基因的。因此，我们进行了全基因组关联（GWA）分析，揭示了17个与排便率相关的候选基因。在中肠内分泌细胞或神经元中下调其中四个基因（、、和）会降低排便率，并改变的中肠表达，而又通过向内脏肌肉发出信号来调节排便率。因此，微生物和饮食刺激以及控制基因通过神经元、肠内分泌和内脏肌肉细胞内以及它们之间的信号传导来调节排便率。
