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

肠道通透性的区域和动力学变化以及穿过仔猪肠壁的转运机制

• 批准号: RGPIN-2015-06437
• 负责人: Wilson, Heather
• 金额: $ 2.77万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=668682
• 关键词: Regional; kinetic; changes; gut; permeability

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.**

猪（母猪）的子宫不与胎儿共享循环。因此，仔猪出生时免疫幼稚。他们必须摄入初乳以获得被动免疫力，否则他们将死于传染病。据报道，仔猪肠道在出生后的前两天是半渗透性的，以促进初乳来源的细胞和大分子（即抗体、细胞因子、抗微生物肽等）的摄取。在这短暂的一段时间后，肠道经历了一个成熟过程，使其不再是半渗透性的。我们打算了解在仔猪肠道从半渗透到“封闭”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，在生命的最初几天内，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转变。我的研究项目主要集中在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/大分子通过肠道壁摄取的机制。为此，我们有以下目标：1）确定肠壁对母体细胞和大分子的渗透性停止的动力学，2）确定空肠和回肠肠上皮细胞中基因表达模式随时间的总体变化，3）使用活的全肠切片，确定母体细胞、抗体或其它初乳组分是否促进仔猪肠渗透性随时间的变化，和4）确定母体细胞和大分子随时间穿过肠壁的机制。* 这些结果可能会显著影响仔猪生产畜棚中的饲养实践。在加拿大的猪舍中，将仔猪从一头母猪交叉寄养到另一头母猪是一种非常常见的做法。众所周知，无论初乳是否来自母猪，初乳中的抗体都很容易穿过肠壁。然而，一份报告显示，只有产母猪产生的初乳细胞才能穿过哺乳后代的肠壁。因此，在哺乳前从其出生母猪交叉培养的仔猪不会接受母体细胞，因此不会接受被动细胞介导的免疫。我们打算确定来自交叉饲养的母猪的细胞是否确实无法穿过小猪肠壁以及肠壁渗透性的动力学。这些数据很重要，因为如果只有来自母猪的细胞可以穿过肠壁，那么仔猪在哺乳之前不应该交叉培养。此外，确定肠壁何时不再渗透大分子可能会影响口服疫苗或预防性治疗的递送时间。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。