Heat Stress, Consequences of Gut Barrier Dysfunction

Farm animals are frequently immune challenged, and obvious infections include pneumonia, metritis and mastitis. An often-unrecognized source is a hyper-permeable gastrointestinal tract (GIT) barrier; a consequence of stressors including weaning, hind-gut acidosis, systemic inflammation, heat stress (HS), psychological stress, and feed restriction. HS initiates a cardiac event characterized by vasodilatation at the periphery coupled with a coordinated vasoconstriction within the entire splanchnic bed. Reduced blood and nutrient flow compromises the GITs physical barrier and allows unwanted molecules to paracellularly infiltrate into the submucosa, porta blood and potentially systemic circulation. GIT-derived invading pathogens/antigens are recognized and immunoactivation elicits an inflammatory cytokine response(s), culminating in an acute phase response characterized by fever, leukocytosis, and hepatic acute phase protein synthesis. Paradoxically, endotoxemia (a catabolic condition) either causes insulin (a potent anabolic hormone) secretion or markedly enhances glucose stimulated insulin secretion. Hyperinsulinemia is likely needed as insulin has a key role in activating WBC and to ensure adequate leukocyte glucose uptake. We have recently demonstrated an in vivo lipopolysaccharide (LPS)-activated immune system consumes ~1 g glucose/kg BW^0.75/h in growing pigs and cattle and lactating dairy cows; a finding consistent with activated immune cells requiring glucose primarily for fuel and as a biosynthetic precursor. Despite increased glucose requirements, anorexia accompanies immunoactivation, which decreases diet-derived glucose precursors. Additionally, inflammation decreases milk and skeletal muscle synthesis and this presumably represents a strategy to spare glucose for the immune system. To further ensure an adequate fuel supply for the immune system, hepatic glucose output increases via both glycogenolysis and gluconeogenesis. Simultaneously, peripheral insulin resistance develops leading to decreased glucose uptake by skeletal muscle and adipose tissue. Interestingly, ionized circulating calcium is severely decreased following LPS administration, but reasons for (and rationale why) immunoactivation-induced hypocalcemia occurs is not clear. Additionally, despite decreased milk and skeletal muscle protein synthesis, the content of many circulating amino acids decreases (characterized particularly by the branch chains and arginine) post-LPS challenge, likely because of increased AA requirement for acute phase protein synthesis. These metabolic adaptations are indicative of altered homeorhetic nutrient reprioritization towards a new dominant physiological state of immunoactivation. It is becoming increasingly clear that GIT barrier dysfunction negatively affects many economically important phenotypes in animal agriculture. Thus, identifying nutritional strategies that can prevent GIT hyperpermeability will likely improve farm-animal productivity during stress.