Ma Ning, Chen Xiyue, Liu Chunchen, Sun Yiwei, Johnston Lee J, Ma Xi
State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China.
West Central Research & Outreach Center, University of Minnesota, Morris, Minnesota, USA.
Crit Rev Food Sci Nutr. 2023;63(32):11263-11274. doi: 10.1080/10408398.2022.2087052. Epub 2022 Jun 13.
Intestinal stem cells (ISCs), which locate at the base of intestinal crypts, are key determinants of governing proliferation and differentiation of the intestinal epithelium. The surrounding cells of ISCs and their related growth factors form ISC niche, supporting ISC function and self-renewal. ISC has an underappreciated but emerging role as a sensor of dietary nutrients, which fate decisions is adjusted in response to nutritional states to regulate gut homeostasis. Here, we review endogenous and exogenous factors, such as caloric restriction, fasting, fat, glucose and trace element. They instruct ISCs via mTORC1, PPAR/CPT1α, PPARγ/β-catenin, Wnt/GSK-3β pathway, respectively, jointly affect intestinal homeostasis. These dietary responses regulate ISC regenerative capacity and may be a potential target for cancer prevention. However, without precise definitions of nutrition intervene, it will be difficult to generate sufficient data to extending our knowledge of the biological response of ISC on nutrients. More accurately modeling organoids or high-throughput automated organoid culture in microcavity arrays have provided unprecedented opportunities for modeling diet-host interactions. These major advances collectively provide new insights into nutritional regulation of ISC proliferation and differentiation and drive us ever closer to breakthroughs for regenerative medicine and disease treatment by nutrition intervention in the clinic.
位于肠隐窝底部的肠道干细胞（ISCs）是控制肠上皮细胞增殖和分化的关键决定因素。ISCs周围的细胞及其相关生长因子形成了ISC微环境，支持ISC的功能和自我更新。ISC作为饮食营养的感受器，其作用虽未得到充分认识，但正逐渐显现，它会根据营养状态调整命运决定，以调节肠道内环境稳定。在此，我们综述了内源性和外源性因素，如热量限制、禁食、脂肪、葡萄糖和微量元素。它们分别通过mTORC1、PPAR/CPT1α、PPARγ/β-连环蛋白、Wnt/GSK-3β信号通路作用于ISCs，共同影响肠道内环境稳定。这些饮食反应调节ISC的再生能力，可能是癌症预防的潜在靶点。然而，由于营养干预缺乏精确的定义，将难以生成足够的数据来扩展我们对ISC对营养物质生物学反应的认识。更精确地模拟类器官或在微腔阵列中进行高通量自动化类器官培养，为模拟饮食与宿主的相互作用提供了前所未有的机会。这些重大进展共同为ISC增殖和分化的营养调节提供了新见解，并推动我们在临床上通过营养干预在再生医学和疾病治疗方面更接近突破。
