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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=687195
• 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.**

猪的子宫（母猪）不与胎儿共享循环。因此，仔猪天生天真。他们必须摄取初乳才能接受被动免疫学，否则会死于传染病。据报道，在出生后两天，肠道肠道可半渗透，可用于摄取初乳的细胞和大分子（即抗体，细胞因子，抗菌胡椒等）。经过短暂的一段时间，肠道经历了成熟过程，因此不再可半渗透。我们打算了解在从半渗透到“封闭”状态的过渡过程中，小猪肠道中发生的基本生理和生物学变化。***在我们的实验室中的研究表明，蛋白质的定位存在变化，这些蛋白质在生命的第一天内维持紧密连接连接（TJ）的定位会发生变化。这些变化可能导致从半渗透肠道到成熟的肠道的过渡。我的研究计划的重点是确定出生后肠道通透性变化背后的基本生物学，并确定整个肠壁上的成熟细胞/大分子的吸收机理。要实现这一目标，我们有以下目标：1）确定肠壁渗透性对成熟细胞和大分子的渗透性的动力学，2）确定在空肠和回肠肠道上皮细胞中基因表达模式的全球变化，随着时间的流逝，3）使用可行的整个肠道细胞，确定其他肠道，确定仿制物，抗体或抗体，是否会促进抗体或其他肠道细胞的变化随着时间的流逝，渗透性和4）确定基质细胞和大分子随时间越过肠壁的机制。 ***这些结果可能会严重影响小猪生产棒的饲养做法。从生育猪到加拿大的猪棒的另一个母猪，这是一种极为普遍的做法。众所周知，初乳中的抗体都很容易穿越肠道*，无论角色丝是来自出生的生物。这是*在哺乳之前从出生和哺乳之前进行交叉派的仔猪不会*接收到母体细胞，因此不会获得被动*细胞 - 介质免疫。我们打算确定来自交叉播种的细胞是否确实不能越过猪肠壁和肠壁渗透性的动力学。这些数据很重要，因为如果只有从出生母猪发出的细胞才能越过肠壁，那么在吸吮之前，不得将仔猪交叉浇筑。此外，定义肠壁何时不再渗透到大分子可能会影响口服疫苗或预防性处理的时间。这是了解如何调节肠道渗透性可能会影响被动免疫和可能的疫苗开发。**