Regulation of gastrointestinal tract barrier function in cattle

胃肠道是促进饲料消化、饲料通道和营养吸收的重要器官。由于胃肠道的内容物是体外的，胃肠道的内壁（上皮）也必须防止潜在的有害分子和生物体穿过它的屏障。交叉进入淋巴或体循环的化合物可引起局部和全身性炎症以及这些分子或生物体的易位，被认为是某些代谢紊乱和疾病（如牛的肝脓肿和板膜炎）进展的核心。胃肠道促进营养物质吸收，同时防止有害分子和生物体移位或通过的能力被称为选择性渗透性，是免疫系统的重要组成部分。考虑到胃肠道是暴露表面积最大的器官，并且被微生物广泛定植，后者被强调。虽然单胃动物的胃肠道通透性特征已经得到了很好的研究，但直到最近，研究人员才对牛和羊等反刍动物的胃肠道屏障功能进行了评估。有许多情况可能导致屏障功能的破坏。例如，暴露于短暂而明显的采食量减少会导致胃肠道屏障功能的下降，从而可能使不需要的分子或生物体穿过胃肠道屏障。短暂的采食量减少的相关性不应被低估，因为当牛暴露于热应激时，当受到传染病的影响时，当消化系统紊乱时，与运输事件有关时，以及在分娩前后，这种情况都会发生。由于缺乏反刍动物的数据，关于胃肠道受影响最大的区域、基于性别的影响、损害屏障功能所需的侮辱的严重程度、恢复反应以及调节这些反应的潜在机制，一直存在争论。该方案的假设是，小肠远端区域和大肠近端区域选择性通透性降低的风险最大，女性受影响程度更大，并且这些远端区域比胃肠道前肠区域恢复得更快。为了验证这一假设，我们将：1)确定在饲料摄入量短暂显著减少的情况下，牛胃肠道屏障功能的区域差异；2)确定低采食量暴露的严重程度（暴露的持续时间和减少的幅度）如何影响区域渗透率；3)确定胃肠道屏障功能降低是否存在性别效应。

The gastrointestinal tract is a critical organ facilitating feed digestion, feed passage, and nutrient absorption. As contents of the gastrointestinal tract are external to animals, the lining of the gastrointestinal tract (epithelium) must also prevent potentially harmful molecules and organisms from crossing its barrier. Compounds that cross gain access to lymphatic or systemic circulation and can induce local and systemic inflammation and translocation of these molecules or organisms are thought to be central to the progression for some metabolic disorders and diseases such as liver abscesses and laminitis in cattle. The ability for the gastrointestinal tract to promote absorption of nutrients while preventing translocation or passage of harmful molecules and organisms is referred to as selective permeability and is a crucial component of the immune system. The latter is emphasized when considering that the gastrointestinal tract is the organ with the greatest exposed surface area and is extensively colonized by microorganisms. While characteristics of gastrointestinal tract permeability have been well investigated in monogastric species, only recently have researchers evaluated the barrier function of the gastrointestinal tract in ruminants such as cattle and sheep.   There are numerous situations that may cause disruption to barrier function. For example, exposure to a transient and marked reduction in feed intake causes a decrease in total gastrointestinal tract barrier function potentially allowing non-desired molecules or organisms to cross the gastrointestinal barrier. The relevance of a transient reduction in feed intake should not be understated as such circumstances occur when cattle are exposed to heat stress, when affected by infectious disease, in response to digestive disorders, in relation to transportation events, and around parturition. Given the lack of data for ruminants, there is ongoing debate about the regions of the gastrointestinal tract that are most affected, sex-based effects, the severity of the insult required to compromise barrier function, the recovery response, and the underlying mechanisms regulating these responses.  The hypothesis of the proposed program is that the distal regions of the small intestine and proximal regions of the large intestine are at greatest risk for a reduction in selective permeability, with females affected to a greater extent, and that those distal regions recover more rapidly than the foregut regions of the gastrointestinal tract. To test the hypothesis, we will: 1) determine regional differences in barrier function of the gastrointestinal tract in cattle when exposed to a transient and marked reduction in feed intake; 2) determine how the severity of the exposure to low feed intake (duration of exposure and magnitude of reduction) affect regional permeability; 3) determine whether there are sex-based effects  for the reduction in gastrointestinal barrier function.