Department of Biology, Lund University, Lund, Sweden.
Precision Livestock and Nutrition Unit, TERRA Teaching and Research Centre, Gembloux Agro-Biotech, University of Liège, Gembloux, Belgium.
Front Immunol. 2020 Jun 9;11:1153. doi: 10.3389/fimmu.2020.01153. eCollection 2020.
The gut is an efficient barrier which protects against the passage of pathogenic microorganisms and potential harmful macromolecules into the body, in addition to its primary function of nutrient digestion and absorption. Contrary to the restricted macromolecular passage in adulthood, enhanced transfer takes place across the intestines during early life, due to the high endocytic capacity of the immature intestinal epithelial cells during the fetal and/or neonatal periods. The timing and extent of this enhanced endocytic capacity is dependent on animal species, with a prominent non-selective intestinal macromolecular transfer in newborn ungulates, e.g., pigs, during the first few days of life, and a selective transfer of mainly immunoglobulin G (IgG), mediated by the FcRn receptor, in suckling rodents, e.g., rats and mice. In primates, maternal IgG is transferred during fetal life via the placenta, and intestinal macromolecular transfer is largely restricted in human neonates. The period of intestinal macromolecular transmission provides passive immune protection through the transfer of IgG antibodies from an immune competent mother; and may even have extra-immune beneficial effects on organ maturation in the offspring. Moreover, intestinal transfer during the fetal/neonatal periods results in increased exposure to microbial and food antigens which are then presented to the underlying immune system, which is both naïve and immature. This likely stimulates the maturation of the immune system and shifts the response toward tolerance induction instead of activation or inflammation, as usually seen in adulthood. Ingestion of mother's milk and the dietary transition to complex food at weaning, as well as the transient changes in the gut microbiota during the neonatal period, are also involved in the resulting immune response. Any disturbances in timing and/or balance of these parallel processes, i.e., intestinal epithelial maturation, luminal microbial colonization and mucosal immune maturation due to, e.g., preterm birth, infection, antibiotic use or nutrient changes during the neonatal period, might affect the establishment of the immune system in the infant. This review will focus on how differing developmental processes in the intestinal epithelium affect the macromolecular passage in different species and the possible impact of such passage on the establishment of immunity during the critical perinatal period in young mammals.
肠道是一种有效的屏障，可防止病原体微生物和潜在有害大分子进入体内，除了其主要的营养消化和吸收功能。与成年期限制大分子通过相反，在生命早期，由于胎儿和/或新生儿期未成熟肠上皮细胞的高内吞能力，会发生增强的跨肠转移。这种增强的内吞能力的时间和程度取决于动物物种，新生反刍动物（例如猪）在生命的头几天内具有明显的非选择性肠道大分子转移，而吮吸啮齿动物（例如大鼠和小鼠）则通过 FcRn 受体主要转移免疫球蛋白 G（IgG）。在灵长类动物中，母体 IgG 通过胎盘在胎儿期转移，而人类新生儿的肠道大分子转移受到很大限制。肠道大分子传递的时期通过从免疫功能正常的母亲转移 IgG 抗体提供被动免疫保护；甚至可能对后代器官成熟产生额外的免疫有益影响。此外，胎儿/新生儿期的肠道转移导致更多地暴露于微生物和食物抗原，然后将这些抗原呈递给基础免疫系统，该免疫系统是幼稚的。这可能会刺激免疫系统成熟，并促使反应从激活或炎症转向诱导耐受，而这在成年期通常很常见。摄入母乳以及断奶后向复杂食物的饮食过渡，以及新生儿期肠道微生物群的短暂变化，也会影响由此产生的免疫反应。由于早产、感染、抗生素使用或新生儿期营养变化等原因，这些平行过程（即肠上皮细胞成熟、腔微生物定植和粘膜免疫成熟）的时间和/或平衡的任何干扰，都可能影响婴儿免疫系统的建立。本综述将重点讨论肠道上皮细胞的不同发育过程如何影响不同物种的大分子通过，以及这种通过对年轻哺乳动物围产期免疫建立的可能影响。
