Objective 1: Define the gut-liver axis in lactating dairy cows experiencing leaky gut. Rationale: The gut-liver axis involves the complex interplay between the gut microbiota, intestinal permeability, systemic endotoxemia, and liver health. In non-ruminants, microbial dysbiosis promotes leaky gut and compromises health, and heat stress modulates the gut microbiome in broilers. Therefore, heat stress likely changes the bovine gut microbiome in dairy cows experiencing heat stress and leaky gut.
Objective 2: Determine whether rumen-protected OA/PB supplementation prevents endotoxemia and liver injury in lactating dairy cows experiencing leaky gut. Rationale: Leaky gut increases circulating endotoxin to promote hepatic steatosis, inflammation, and activation of the acute phase response. Feeding rumen-protected OA/PB may reduce intestinal permeability to minimize these outcomes. Therefore, dietary OA/PB supplementation may be a practical approach to improve gut and liver health in dairy cattle.
Enhanced intestinal permeability disrupts the intestinal barrier to culminate in microbial translocation into the host (Bischoff et al., 2014). Consequently, an increase in circulating gut-derived endotoxin promotes liver injury. Specifically, enhanced uptake of endotoxin by the liver promotes triglyceride accumulation, inflammation, and activates the acute phase response, which is a component of the innate immune system. We hypothesize that heat stress promotes dysbiosis of the dairy cow gut microbiota while enhancing intestinal permeability, endotoxemia, and liver injury. Moreover, we consider the possibility that rumen-protected OA/PB supplementation may restore the intestinal barrier, lower circulating endotoxin, and improve hepatic health in cows challenged by hyperthermia. To test our hypotheses, we will study lactating Holstein dairy cows housed in thermal neutral or heat stress environmental conditions. Our experimental design will include a pair-fed control housed in thermal neutral conditions with intake matched to cows experiencing heat stress. Such an approach will account for effects associated with changes in intake. Regarding our measurements, we will utilize a contemporary omics approach to characterize the fecal microbiome. Although leaky gut predominantly develops in the small intestine, we emphasize that the fecal microbiota is an adequate reflection of the intestinal microbiome (Barko et al., 2018). To measure intestinal permeability, we will quantify circulating levels of intestinal-fatty acid binding protein which is a biomarker of intestinal barrier dysfunction. Plasma endotoxin levels will be quantified to evaluate endotoxemia status. Circulating alanine aminotransferase, haptoglobin, and serum amyloid A will be measured to assess hepatic lipid accumulation, inflammatory status, and the acute phase response. Collectively, our approach will allow us the ability to characterize the gut-liver axis during heat stress and OA/B supplementation.
The current project has not started and an IACUC protocol was submitted in December 2018 (determination due February 2019).