Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States.
Division of Infectious Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, United States.
Elife. 2017 Nov 7;6:e29132. doi: 10.7554/eLife.29132.
The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem-cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.
人类的胃肠道在出生时尚未发育成熟，但必须适应剧烈的变化，例如口腔营养和微生物定植。这些因素的融合可能导致早产儿发生严重的炎症性疾病；然而，由于难以获得未成熟的人体组织，研究复杂的环境-宿主相互作用具有一定难度。在这里，我们证明了由多能干细胞衍生的人类肠道类器官的上皮细胞在整体上与未成熟的人类上皮细胞相似，并且我们利用 HIO 来研究这种幼稚上皮细胞中的复杂宿主-微生物相互作用。我们的研究结果表明，未成熟的上皮细胞从本质上就能够建立稳定的宿主-微生物共生关系。微生物定植导致复杂的接触和缺氧驱动反应，从而增加抗菌肽的产生、粘液层的成熟和改善屏障功能。这些研究为深入了解定植如何影响未成熟人类肠道的发育奠定了基础。
