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

点击翻译按钮获取中文摘要

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.**