Grant: Discovery Grants Program - Individual

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.