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系统疾病。为了满足它们的高能量需求，这些动物接受高谷物饮食。这可能导致消化系统疾病，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细胞和微生物群的功能。这种情况发生的机制尚不清楚。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，饲喂高谷物日粮增加了发酵酸的浓度，改变了瘤胃和大肠中微生物的底物利用率，降低了瘤胃缓冲。我们进一步假设，这些变化降低了pH值和微生物群的功能，并增加了内毒素的浓度，包括脂多糖（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细胞的屏障功能，导致免疫原性化合物易位出消化道，并且这些易位导致在牛的高谷物喂养期间观察到的急性期反应。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。问题包括：1）为什么静脉注射（i. v.）管理E.大肠杆菌LPS导致的炎症比LPS从消化道移位更严重; 2）奶牛是否随着时间的推移对LPS产生耐受性; 3）为什么牛对过量谷物/淀粉喂养症状的易感性不同。为了回答问题1，将静脉内给予来自普通革兰氏阴性瘤胃细菌的LPS，并将所产生的炎症反应与静脉内给予类似量的E. coli LPS。通过比较不同饲料淀粉含量的奶牛重复静脉注射LPS来回答问题2。问题3将通过比较对高谷物饲喂症状（包括瘤胃pH值和LPS含量降低以及外周血中急性期蛋白和LPS浓度升高）敏感或耐受的奶牛之间的瘤胃微生物群、瘤胃上皮细胞和肝脏的基因组和转录组来回答。回答问题1和2将涉及一名MSC学生，回答问题3将涉及2名博士生。解决这些问题将导致奶牛和肉牛饲养策略的发展，允许在不损害其健康和福利的情况下满足其高生产潜力，从而提高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.