International Symposium on Ruminant Physiology: Integrating our understanding of stress physiology

Abiotic stressors reduce farm animal productivity, and one of the most globally studied is heat stress (HS) because it compromises almost every profitability metric. Surprisingly, the biological consequences of seemingly very different stressors are highly conserved. Thus, although this review focuses on the broad impact of stress, describing the biology and etiology of how HS alters farm animal productivity provides the conceptual foundation for how all stressors can become pathological. Suboptimal production during HS was traditionally thought to result from hypophagia. However, independent of feed intake, HS affects a plethora of endocrine, physiological, metabolic, circulatory, and immunological variables. It is becoming increasingly clear that these changes are chronologically causal and that the etiological epicenter is a compromised gastrointestinal tract (GIT) barrier. A hyperpermeable GIT allows luminal contents to infiltrate, and these antigens stimulate an immune response with local and systemic inflammatory implications. Once activated, most leukocytes switch from oxidative phosphorylation to aerobic glycolysis and increase their glucose utilization. The glucose requirement of an intensely triggered immune system can exceed 2 kg/d in a lactating dairy cow. Whole-body metabolic adjustments are coordinated to ensure glucose is prioritized for the immune system and this is primarily characterized by increased basal and stimulated circulating insulin, hypercortisolemia, and hyperprolactinemia. This hormonal profile is accompanied by decreased adipose tissue mobilization and skeletal muscle insulin resistance. Interestingly, the aforementioned physiology is almost identical to distinctly different abiotic and biotic stressors. For example, feed restriction, weaning, cold stress, and noise stress all have a similar metabolic and inflammatory footprint, and this physiology can be closely recapitulated by experimentally-induced immune activation. Ultimately, these stressors are "psychological" and emanate their pathology from a compromised GIT barrier. Stress negatively affects GIT epithelia via at least 2 mechanisms: (1) mast cell degranulation and (2) immune cell creation of an apical pro-oxidant environment that paradoxically favors pathogen colonization. The metabolic, physiological, and immunological consequences of stress are highly conserved, and these analogous responses are symmetrical because the GIT is seemingly ground zero for all of them.