Regulation of gastrointestinal tract barrier function in cattle

牛胃肠道屏障功能的调节

• 批准号: RGPIN-2021-03713
• 负责人: Penner, Gregory
• 金额: $ 4.01万
• 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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742686
• 关键词: Regulation; gastrointestinal; tract; barrier; function

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.

胃肠道是促进饲料消化、饲料通道和养分吸收的重要器官。由于胃肠道的内容物对动物来说是外部的，胃肠道(上皮)的衬里也必须防止潜在的有害分子和有机体越过其屏障。交叉进入淋巴或全身循环的化合物可引起局部和全身炎症以及这些分子或有机体的移位，被认为是牛某些代谢紊乱和疾病(如肝脓肿和板层炎)进展的中心。胃肠道在防止有害分子和有机体移位或通过的同时促进营养物质的吸收的能力被称为选择性通透性，是免疫系统的重要组成部分。当考虑到胃肠道是暴露表面积最大的器官，并且广泛地被微生物定植时，强调后者。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。*有许多情况可能会导致屏障功能中断。例如，暴露于饲料摄入量的短暂和显著减少会导致胃肠道总屏障功能的下降，潜在地允许不需要的分子或生物穿过胃肠道屏障。暂时性减少采食量的相关性不应被低估，因为这种情况发生在牛暴露于热应激、受到传染病影响、对消化障碍的反应、与运输事件有关以及分娩前后。由于缺乏反刍动物的数据，关于胃肠道中受影响最严重的区域、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的争论仍在继续。拟议计划的假设是，小肠的远端区域和大肠的近端区域具有最大的选择性通透性降低的风险，雌性受影响的程度更大，而且这些远端区域比胃肠道的前部区域恢复得更快。为了验证这一假设，我们将：1)确定当牛暴露于短暂且显著的采食量减少时，胃肠道屏障功能的地区差异；2)确定暴露于低采食量的严重程度(暴露的时间和减少的幅度)如何影响区域渗透性；3)确定是否存在性别影响导致胃肠道屏障功能的降低。