Immunometabolism, energetics, and intestinal barrier health during immune activation

Abstract

Livestock encounter a multitude of physiological, psychological, nutritional, and environmental stressors that frequently lead to exacerbated immune activation or inflammation, which compromises animal health, production efficiency, and thus, animal agriculture sustainability. Two of the most critical immune activating events/factors affecting dairy farms’ profitability are the transition period and environmentally-induced hyperthermia or heat stress (HS). Animals utilize physiological, metabolic, inflammatory, and endocrine adjustments to homeorhetically survive these insult(s). While inflammation can originate from various sources (i.e., uterus, mammary gland, lungs), intestinal barrier hyperpermeability appears to play a critical role in the etiology of immune activation during the transition period and HS. Regardless of the origin, immune activation burdens animal welfare, and it undoubtedly plays a crucial part in some undesirable production outcomes (i.e., reduced appetite, low milk yield, impaired reproduction). Gastrointestinal tract (GIT) epithelial barrier dysfunction allows bacteria components and pathogen translocation into circulation, which induces local, compartmentalized, and potentially systemic inflammation. Immune activation and inflammation are energetically and amino acid expensive, and nutrients are repartitioned to fuel the immune system to the detriment of production (i.e., growth, reproduction, and lactation). The increased energetic demands of immune activation coincide with a concomitant reduction in feed intake and, subsequently, reduced nutrient absorption. Therefore, the main objectives of this dissertation were to improve our understanding of 1) the etiology of transition cow chronic inflammation, fatty liver, and ketone metabolism, 2) the effects of HS on intestinal physiology and immunometabolism, and 3) dietary strategies that potentially alleviate the negative consequences of HS on intestinal physiology, immunometabolism, and production in lactating dairy cows. In studies 1 and 2 (Chapters 2 and 3) we created a chronic inflammation and mild liver steatosis model, respectively, resembling immunometabolism alterations occurring during the transition period. Overall, immune activation markedly influenced endocrine and metabolic homeostasis, and these alterations closely resembled changes observed in poorly transitioning dairy cows. In study 3 (Chapter 4), we evaluated the effects of a mycotoxin deactivator (MD) dietary supplement on performance, metabolism, inflammation, and intestinal health during acute and chronic HS. In study 4 (Chapter 5) we evaluated the effects of dietary zinc hydroxychloride (HYD) on performance, metabolism, inflammation and GIT integrity during acute and chronic HS and following HS recovery. As anticipated, HS markedly decreased feed intake and milk production. Moreover, HS altered endocrine, metabolic, and inflammatory biomarkers relative to thermoneutral conditions, and although supplementing MD did not have a large impact during HS, HYD reduced GIT barrier permeability during acute HS and increased feed intake during HS recovery. In summary, immune activation impacts a wide range of phenotypical, endocrine, and metabolic parameters. Moreover, inflammation stems from a multitude of stressors (i.e., feed restriction, HS) causing intestinal barrier integrity disruption and subsequent luminal content translocation. This intestinal hyperpermeability may also contribute to metabolic disorders (i.e., ketosis, fatty liver) during the peripartum period, and lead to compromised health and performance. Further investigation is necessary to better understand how immune activation induces metabolic and endocrine alterations and nutrient partitioning observed during the transition period and HS. This would be the requisite for developing strategies to alleviate the negative impact of different stressors on animal health and production and ultimately improve farm profitability and sustainability.