Induction of intestinal barrier dysfunction in dairy heifers: Evaluation of new serum inflammatory markers and method for quantifying intestinal hyperpermeability

Abstract

Experimental induction of intestinal barrier dysfunction (e.g., inflammation and hyperpermeability) has been shown to induce a systemic inflammatory response and reduce productivity in lactating dairy cows. Because numerous natural situations on-farm (e.g., ruminal acidosis, heat stress, weaning) can impair intestinal barrier function, this is an important phenomenon to study. Therefore, our objective was to induce intestinal barrier dysfunction and evaluate new serum inflammatory markers as well as a new approach to measuring intestinal hyperpermeability. This was accomplished via oral aspirin administration for 21 d in 10-mo-old Holstein and Jersey heifers. Twelve heifers (6 each, Holsteins and Jerseys) were blocked by breed and then randomly assigned (3 heifers per breed) to receive either 0 or 200 mg aspirin/kg BW per day orally. At 0600 h on d 21 of the experiment, urine and blood samples were collected from each animal. Heifers then were dosed orally with gelatin capsules containing 50 g of Co-EDTA using a balling gun. Urine samples were subsequently collected at 1, 3, 6, 8, 12, 18, 24, 30, and 36 h after dosing. Urine samples were analyzed for Co and creatinine, and serum samples were analyzed for the inflammatory markers haptoglobin (Hp), LBP, FABP2, and TNF. Modeling urinary Co:creatinine ratios using a nonlinear function yielded an excellent fit and indicated that urinary Co excretion, a measure of intestinal permeability, was not increased due to aspirin but was higher for Jersey than for Holstein heifers. Also, serum concentrations of Hp and LBP were unaffected, but serum concentrations of FABP2 and TNF were increased due to aspirin administration. Finally, analysis of covariance indicated that serum TNF concentrations were highly correlated with urinary Co excretion. These data suggest that FABP2 and TNF may be valuable additional markers for the study of intestinal barrier dysfunction.