Enhancing Gut Health in High Yielding Cattle

我的NSERC资助的研究项目的长期目标是预防高产奶牛和肉牛的消化障碍。为了满足它们的高能量需求，这些动物接受高谷物饲料。这会导致消化障碍，如亚急性瘤胃酸中毒(SARA)，并降低瘤胃和大肠、肝脏和免疫系统的上皮和微生物区系的功能。发生这种情况的机制还不是很清楚。这限制了预防和治疗这些疾病的能力，并危及这些牛的健康、福利和营养利用。我们的团队提出，饲喂高谷物日粮会增加发酵酸的浓度，改变瘤胃和大肠中微生物的底物利用率，并降低瘤胃缓冲。我们进一步假设，这些变化降低了微生物区系的pH和功能，并增加了内毒素的浓度，包括内毒素(LPS)和这些隔室中的其他免疫原性化合物。我们还假设，这降低了这些隔室上皮的屏障功能，导致免疫原性化合物移位到消化道外，这些移位导致了在高谷物饲养牛时观察到的急性时相反应。在最近对我们的假设进行测试的过程中，出现了几个问题。我们的短期目标是回答这些问题。它们包括：1)为什么静脉注射(Iv)注射大肠杆菌和内毒素会导致比从消化道移位的内毒素更严重的炎症；2)随着时间的推移，奶牛是否会对内毒素产生耐受性；以及3)为什么牛对过量谷物/淀粉喂养的症状的敏感度会有所不同。为了回答问题1，来自常见革兰氏阴性瘤胃细菌的内毒素将被静脉注射，所产生的炎症反应将与静脉注射类似剂量的大肠杆菌和内毒素后的炎症反应进行比较。问题2，将通过比较重复的静脉注射回答。日粮淀粉含量不同的奶牛服用脂多糖。问题3将通过比较瘤胃微生物区系、瘤胃上皮细胞和肝脏的基因组和转录本来回答，这些奶牛对高谷物饲喂症状敏感或抵抗，包括瘤胃内pH和内毒素含量的降低，以及外周血中急性期蛋白和内毒素浓度的增加。回答问题1和2将涉及一名理科硕士学生，回答问题3将涉及2名博士生。回答这些问题将导致制定奶牛和肉牛的饲养策略，在不损害它们的健康和福利的情况下满足它们的高生产潜力，从而增强消费者对加拿大养牛业的看法。

The long-term objective of my NSERC-funded research program is to prevent digestive disorders of high yielding dairy cows and beef cattle. In order to meet their high energy requirements, these animals receive high grain diets. This can cause digestive disorders, such as subacute ruminal acidosis (SARA), and reduce the functionalities of the epithelia and microbiota of the rumen and large intestine, the liver, and the immune system. The mechanisms through which this occurs are not yet well understood. This limits the abilities for the prevention and treatment of these disorders, and jeopardizes the health, welfare, and nutrient utilization of these cattle. Our team proposes that feeding high grain diets increases the concentration of fermentation acids and changes the availabilities of substrates for microorganisms in the rumen and large intestine, and lowers rumen buffering. We further hypothesize that these changes decrease the pH and the functionalities of microbiota, and increase the concentrations of endotoxins, including lipopolysaccharide (LPS) and other immunogenic compounds in these compartments. We also hypothesize that this reduces the barrier function of epithelia of these compartments, which leads to translocation of immunogenic compounds out of the digestive tract, and that these translocations cause the acute phase response that is observed during high grain feeding of cattle. During recent testing of our hypotheses, several questions have arisen. Our short-term objectives are to answer these questions. They include: 1) Why does intravenous (i.v.) administration of E. coli LPS result in a more severe inflammation than translocation of LPS from the digestive tract; 2) Do cows develop tolerance to LPS over time; and 3) Why do cattle differ in their susceptibility to the symptoms of excessive grain/starch feeding. In order to answer question 1, LPS from common gram-negative rumen bacteria will be administered intravenously, and the resulting inflammatory response will be compared with that following iv administration of similar amounts of E. coli LPS. Question 2, will be answered by comparing repeated i.v. LPS administrations in cows that differ in their dietary starch content. Question 3 will be answered by comparing the genome, and transcriptomes of rumen microbiota, rumen epithelia, and the liver between cows that are susceptible or resistant to symptoms of high grain feeding, including the reductions in the pH and LPS contents in the rumen, and increases in the concentrations of acute phase proteins and LPS in peripheral blood. Answering questions 1 and 2 will involve one MSC student, and answering Question 3 will involve 2 PhD students. Answering these questions will lead to the development of feeding strategies for dairy cows and beef cattle allow meeting their high production potentials without jeopardizing their health and welfare and, therefore, enhance the consumers' perception of the Canadian cattle industries.