The ability to absorb ingested nutrients is an essential function of all metazoans and utilizes a wide array of nutrient transporters found on the absorptive enterocytes of the small intestine. A unique population of patients has previously been identified with severe congenital malabsorptive diarrhea upon ingestion of any enteral nutrition. The intestines of these patients are macroscopically normal, but lack enteroendocrine cells (EECs), suggesting an essential role for this rare population of nutrient-sensing cells in regulating macronutrient absorption. Here, we use human and mouse models of EEC deficiency to identify an unappreciated role for the EEC hormone peptide YY in regulating ion-coupled absorption of glucose and dipeptides. We find that peptide YY is required in the small intestine to maintain normal electrophysiology in the presence of vasoactive intestinal polypeptide, a potent stimulator of ion secretion classically produced by enteric neurons. Administration of peptide YY to EEC-deficient mice restores normal electrophysiology, improves glucose and peptide absorption, diminishes diarrhea and rescues postnatal survival. These data suggest that peptide YY is a key regulator of macronutrient absorption in the small intestine and may be a viable therapeutic option to treat patients with electrolyte imbalance and nutrient malabsorption.

吸收摄入的营养物质的能力是所有后生动物的基本功能，并利用在小肠的吸收性肠细胞上发现的多种营养物质转运蛋白。之前已经确定了一个独特的患者群体在摄入任何肠内营养后患有严重的先天性吸收不良性腹泻。这些患者的肠道在宏观上是正常的，但缺乏肠内分泌细胞 (EEC)，这表明这种罕见的营养感应细胞群在调节常量营养素吸收方面发挥着重要作用。在这里，我们使用 EEC 缺陷的人类和小鼠模型来确定 EEC 激素肽 YY 在调节葡萄糖和二肽的离子耦合吸收方面未被重视的作用。我们发现小肠中需要 YY 肽以在血管活性肠多肽存在的情况下维持正常的电生理学，血管活性肠多肽是一种典型的由肠神经元产生的离子分泌的有效刺激物。对 EEC 缺陷小鼠施用肽 YY 可恢复正常的电生理学，改善葡萄糖和肽的吸收，减少腹泻并挽救出生后的存活率。这些数据表明，肽 YY 是小肠大量营养素吸收的关键调节剂，可能是治疗电解质失衡和营养素吸收不良患者的可行治疗选择。改善葡萄糖和肽的吸收，减少腹泻并挽救产后生存。这些数据表明，肽 YY 是小肠大量营养素吸收的关键调节剂，可能是治疗电解质失衡和营养素吸收不良患者的可行治疗选择。改善葡萄糖和肽的吸收，减少腹泻并挽救产后生存。这些数据表明，肽 YY 是小肠大量营养素吸收的关键调节剂，可能是治疗电解质失衡和营养素吸收不良患者的可行治疗选择。