Regional and kinetic changes in gut permeability and the mechanisms of transport across the piglet gut wall

猪(母猪)的子宫不与胎儿共享循环。因此，小猪天生免疫幼稚。他们必须摄入初乳才能获得被动免疫，否则他们将死于传染病。据报道，仔猪的肠道在出生后的头两天是半透的，以促进初乳来源的细胞和大分子(即抗体、细胞因子、抗菌肽等)的吸收。在这段短暂的时间之后，肠道经历了一个成熟的过程，因此它不再是半透的。我们打算了解仔猪肠道在从半透入状态到闭合状态的转变过程中发生的基本生理和生物变化。*我们实验室的研究表明，在出生的最初几天，维持肠壁上皮细胞之间紧密连接(TJ)的蛋白质的定位发生了变化。这些变化可能有助于从半渗透性肠道向成熟肠道的过渡。我的研究计划专注于确定出生后肠道通透性变化背后的基本生物学，并确定母体细胞/大分子跨越肠壁吸收的机制。为了实现这一目标，我们有以下目标：1)确定肠壁对母体细胞和大分子的通透性停止的动力学；2)确定空肠和回肠上皮细胞基因表达模式随时间的整体变化；3)使用活的完整肠道切片，确定母体细胞、抗体或其他初乳成分是否促进仔猪肠道通透性随时间的变化；以及4)确定母体细胞和大分子随时间穿过肠壁的机制(S)。*这些结果可能会对仔猪生产猪舍的饲养实践产生重大影响。在加拿大，在猪舍里交叉寄养小猪是一种非常普遍的做法*从出生的母猪到另一头母猪。众所周知，无论初乳是否来自初产母猪，初乳中的抗体都很容易穿过肠壁。然而，一份报告表明，只有初乳中的细胞才能穿过哺乳后代的肠壁。因此，在出生母猪哺乳之前被交叉寄养的小猪将不会收到母体细胞，因此也就不会获得被动的细胞免疫。我们打算确定来自杂交母猪的细胞是否真的不能穿过仔猪的肠壁，以及肠壁通透性的动力学。这些数据很重要，因为如果只有刚出生的母猪的细胞可以穿过肠壁，那么小猪在哺乳之前不应该被交叉养育。此外，确定肠壁何时不再对大分子具有渗透性可能会影响口服疫苗或预防性治疗的投放时间。因此，了解肠道通透性是如何调节的，可能会影响被动免疫和可能的疫苗开发。

The uterus of a pig (sow) does not share circulation with the fetus. Therefore piglets are born immunologically naïve. They must ingest colostrum to receive passive immunity or they will die from infectious diseases. The piglet gut is reported to be semi-permeable for the first two days after birth to facilitate uptake of colostrum-derived cells and macromolecules (i.e. antibodies, cytokines, antimicrobial peptides, etc.). After this brief period of time, the gut undergoes a maturation process so that it is no longer semi-permeable. We intend to understand the basic physiological and biological changes that take place in the piglet gut during the transition from a semi-permeable to a 'closed' state.***Research in our lab shows that there are changes in the localization of proteins that maintain the Tight Junctions (TJs) between the gut wall epithelial cells within the first days of life. These changes may contribute to the transition from a semi-permeable gut to a mature gut. My research program is focused on determining the basic biology behind changes in gut permeability after birth and to determine the mechanism of maternal cells/macromolecules uptake across the gut wall. To achieve this, we have the following objectives: 1) Determine the kinetics of cessation of gut-wall permeability to maternal cells and macromolecules, 2) Determine global changes in gene expression patterns in jejunal and ileal gut epithelial cells over time, 3) Using viable whole gut slices, determine whether maternal cells, antibodies or other colostral components promote changes in piglet gut permeability over time, and 4) Determine the mechanism(s) by which maternal cells and macromolecules traverse the gut wall over time. ***These results may significantly impact the husbandry practices in piglet production barns. It is an extremely common practice to cross-foster piglets*from the birth-sow to another sow in pig barns in Canada. It is known that antibodies in colostrum readily cross the gut*wall regardless of whether the colostrum is from the birth-sow or not.*However, one report shows that only colostral cells produced by a*birth-sow cross the gut wall of suckling offspring. Thus, piglets that*are cross-fostered prior to suckling from their birth-sow will not*received maternal cells and are therefore will receive no passive*cell-mediate immunity. We intend to establish whether cells from the cross-fostered sow indeed cannot cross the piglet gut wall and the kinetics of gut wall permeability. These data are important because if only cells from the birth sow can cross the gut wall, then piglets should not be cross-fostered until they have suckled. Furthermore, defining when the gut wall is no longer permeable to macromolecules may impact timing of delivery of oral vaccines or prophylactic treatments. Thus, understanding how gut permeability is regulated may impact passive immunity and possible vaccine development.**