Young Scholar Presentation: Intestinal Barrier Function Involvement in Inefficient Nutrient Partitioning

The gastrointestinal tract (GIT) serves a dual purpose of both nutrient absorption while preventing pathogen infiltration into portal and systemic circulation. Importance of both roles cannot be underestimated, as a variety of situations in animal agriculture reduce GIT barrier function, leading to immunoactivation and inflammation. Intentionally inducing GIT permeability in mid-lactation dairy cows leads to decreased feed intake and milk yield, increased markers of inflammation, and increased insulin relative to pair-fed controls. Furthermore, feed restriction detrimentally impacts GIT barrier function in cows, and this is accompanied by a linear increase in circulating acute phase proteins with increasing severity of feed restriction. Mild feed restriction decreases the insulin-to-dry matter intake ratio; however, cows under severe feed restriction have a similar ratio to cows fed ad libitum, indicating insulin action is prioritized during severe feed restriction despite marked reductions in dry matter intake. These insulin changes are interesting as feed intake is reduced in both situations, yet endotoxin infusion increases circulating insulin. Production, inflammatory, and metabolic patterns observed during intentionally-induced GIT permeability and feed restriction mimic other inflammatory situations such as heat stress and ketosis, suggesting a common etiological origin of enhanced GIT permeability. Inflammation resulting from these GIT afflicted situations likely contributes to changes in whole-animal energetics, as an activated immune system demands a large amount of energy and nutrients. Interestingly, immune cells become more insulin sensitive and consume copious amounts of glucose upon activation in order to support proliferation and function. In the acutely activated immune system of a mid-lactation dairy cow, glucose utilization by the immune system exceeds 1 kg in a 12 hour period. Such a large demand for glucose certainly has detrimental effects on production, as the mammary gland requires glucose to synthesize and secrete lactose, the primary osmoregulator of milk yield. Immunoactivation increases immune system glucose utilization while simultaneously decreasing feed intake, therefore reprioritizing the hierarchy of glucose partitioning away from economically important phenotypes. In summary, GIT permeability appears to be the etiological origin of a variety of on-farm disorders (heat stress, ketosis, etc.) characterized by inadequate feed intake. Having a better understanding of the energetic and nutrient requirements of the immune response to GIT permeability is critical in order to develop strategies to minimize productivity losses when physiological states or environmental conditions activate the immune system.