d-i.INFLACOW: Characterization and prevention of diet- induced inflammation and related immune and metabolic disorders in dairy cows

State of the art: d-i.inflaCOW will address a key issue of high-producing dairy cattle nutrition and metabolism: how the enhanced plane of nutrition, needed to support high milk yields and cost-efficiency, can induce rumen metabolic disorders including subacute rumen acidosis (SARA). More specifically, the project will evaluate how the release of rumen-derived deleterious compounds during SARA, such as endotoxin, can modulate immunity and systemic health of cows. Three key advances stay in the forefront of the research hypotheses. Firstly, that SARA is associated with the release of large amounts of endotoxin, an abundant pro-inflammatory molecule of Gram-negative bacteria. Secondly, that the translocated rumen-derived endotoxin can induce strong inflammatory reactions in cattle, and thirdly, that a priming and gradual exposure of endotoxin to mucosal sites improves the mucosal tolerance, lowering the negative consequences of endotoxin in cattle.
Research questions: However, the exact mechanisms behind translocation of endotoxin from rumen into the systemic circulation, and the precise role of SARA in the disruption of these epithelial barrier functions are largely unknown. Little is known about the mucosal and systemic tolerance to sustained exposure to endotoxin in cattle in response to an energy-enhanced nutritional plane and the resultant SARA conditions.
Also, consequences of metabolic inflammation and endotoxin tolerance, during prolonged rumen-induced endotoxin insult, on metabolism have yet to be determined.
Methodology: Several models of elevated plane of nutrition will be evaluated in rumen-cannulated cows to induce SARA-like conditions, including a transient and persistent SARA challenge, in order to understand the molecular mechanisms behind SARA and the resultant disruptions of the ecological balance as well as barriers of the rumen epithelia. The same models will be evaluated in intact dairy cows, which will be simultaneously challenged with parenteral endotoxin, to evaluate the effects of SARA and its resulting endotoxin insult on mucosal and endotoxin tolerance as well as immune competence and metabolomic profile.
Benefits: d-i.inflaCOW will provide important information on the adaptive metabolic capacities of rumen epithelia and innate immune system of cows in response to an enhanced plane of nutrition. We presume that findings of mucosal and systemic tolerance to endotoxin will underpin further immunological studies in cattle. Metabolomic profiling will not only help to monitoring the challenges metabolically, but also in developing biomarkers for both the diagnosis and understanding the process of metabolic alterations in cattle due to the SARA and immune challenges. Indeed, metabolic phenotyping applied to diet-induced SARA models as well as those coupled with endotoxin-challenge will increase our aetiopathogenetic knowledge and will help in the discovery of novel biomarkers related to this kind of malnutrition in cattle.