Impact of subacute ruminal acidosis on health of dairy cows

亚急性瘤胃酸中毒(SARA)是奶牛常见的代谢性疾病，在此期间，奶牛的瘤胃pH值每天都会降低几个小时。造成这种疾病症状的机制还不完全清楚。这阻碍了SARA的诊断、预防和治疗。在我之前的NSERC Discovery Grant期间进行的研究为SARA的病因学提供了新的见解，但也提出了关于这种病因学的新问题。我的研究表明，通过饲喂高谷物饲料进行的SARA挑战与瘤胃液、大肠和外周血中细菌脂多糖内毒素(LPS)的增加以及炎症有关。通过饲喂含有磨碎的紫花苜蓿颗粒的饲料进行的SARA挑战也与瘤胃内毒素的增加有关，但与大肠和外周血中的内毒素增加以及炎症无关。我认为，这些SARA挑战之间的差异是由于在以谷物为基础的SARA挑战中，膳食淀粉含量相对较高。我假设，与紫花苜蓿颗粒SARA挑战相比，基于谷物的SARA挑战增加了大肠中消化液的酸度和内毒素含量，这导致了内毒素的移位，并随后导致了全身炎症。使用我的新NSERC发现赠款，我将回答以下问题，通过在牛身上进行体内实验来验证我的假设：1.SARA挑战是否影响消化道上皮细胞的形态，从而使内毒素移位并导致全身炎症？2.SARA挑战期间移位发生在哪里？3.大肠消化中的淀粉含量是否影响大肠内毒素和大肠屏障功能？4.SARA挑战期间观察到的炎症是否与内毒素移位有关？这笔助学金还将用于培训至少1名博士、1名硕士和5名本科生。这项研究将为SARA的病因学提供关键的见解，也将对营养挑战对牛的消化道屏障功能和大肠发酵的影响提供重要的见解。

Subacute ruminal acidosis (SARA) is a common metabolic disease of dairy cows during which the rumen pH is depressed for several hours daily. The mechanisms responsible for the symptoms of this disease are not fully understood. This hinders the diagnosis, prevention, and treatment of SARA. Research conducted during my previous NSERC Discovery Grant provided new insights into the etiology of SARA, but also brought up new questions about this etiology. My research showed that SARA challenges conducted by feeding high-grain diets were associated with increased bacterial lipopolysaccharide endotoxins (LPS) in rumen fluid, in digesta in the large intestine, and in peripheral blood, and with inflammation. SARA challenges conducted by feeding diets containing pellets of ground alfalfa were also associated with increased LPS in the rumen, but were not associated with increased LPS in the large intestine and in peripheral blood, and with inflammation. I believe that the differences between these SARA challenges were due to the comparatively higher dietary starch content during grain-based SARA challenges. I hypothesize that, in contrast to alfalfa-pellet SARA challenges, grain-based SARA challenges increase the acidity and LPS content of digesta in the large intestine, and that this causes translocation of LPS and, subsequently, systemic inflammation. Using my new NSERC Discovery Grant, I will answer to following questions to test my hypotheses by conducting in vivo experiments with cattle: 1. Do SARA challenges affect the morphology of the epithelia of the digestive tract in a manner that enables translocation of LPS and causes systemic inflammation?; 2. Where do translocations during SARA challenges occur?; 3. Does the starch content of digesta in the large intestine affect LPS and barrier function in the large intestine?; 4. Is the inflammation observed during SARA challenges related to translocation of LPS? The grant will also be used to train at least 1 Ph.D, 1 M.Sc., and 5 undergraduate students. This research will provide critical insights in the etiology of SARA, but also on the effects of nutritional challenges on the barrier function of the digestive tract and on fermentation in the large intestine in cattle.