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

## TL;DR

Researchers found that FABP2 and TNF could be useful markers for detecting intestinal inflammation and hyperpermeability in dairy heifers.

## Contribution

The study identifies FABP2 and TNF as novel serum markers for intestinal barrier dysfunction in dairy heifers.

## Key findings

- FABP2 and TNF were increased by aspirin administration, indicating intestinal inflammation.
- Serum TNF was highly correlated with intestinal hyperpermeability.
- Urinary Co excretion was higher in Jersey than Holstein heifers.

## Abstract

Summary: Intestinal barrier dysfunction (e.g., inflammation, hyperpermeability) may arise due to various stressors and results in reduced cow productivity. Determining the best markers of this phenomenon would be useful for the purpose of diagnosis and intervention. To study this, we used oral aspirin administration for 21 days to induce intestinal barrier dysfunction in 10-month-old Holstein and Jersey heifers. Concentrations of serum proteins (as inflammatory markers) and urinary excretion of an indigestible nonmetabolizable marker (as a marker of hyperpermeability) were measured to assess intestinal barrier dysfunction. For serum proteins measured, neither haptoglobin nor serum amyloid A increased due to aspirin treatment. However, both FABP2 and TNF were increased by aspirin, and TNF was also highly correlated to intestinal hyperpermeability. In summary, FABP2 and TNF appear to be promising markers of intestinal barrier dysfunction.

Summary: Intestinal barrier dysfunction (e.g., inflammation, hyperpermeability) may arise due to various stressors and results in reduced cow productivity. Determining the best markers of this phenomenon would be useful for the purpose of diagnosis and intervention. To study this, we used oral aspirin administration for 21 days to induce intestinal barrier dysfunction in 10-month-old Holstein and Jersey heifers. Concentrations of serum proteins (as inflammatory markers) and urinary excretion of an indigestible nonmetabolizable marker (as a marker of hyperpermeability) were measured to assess intestinal barrier dysfunction. For serum proteins measured, neither haptoglobin nor serum amyloid A increased due to aspirin treatment. However, both FABP2 and TNF were increased by aspirin, and TNF was also highly correlated to intestinal hyperpermeability. In summary, FABP2 and TNF appear to be promising markers of intestinal barrier dysfunction.

•Oral aspirin administration did not induce intestinal hyperpermeability.•Oral aspirin administration did appear to induce intestinal inflammation.•FABP2 appears to be a useful marker of intestinal inflammation.•Serum TNF appears to be a useful marker of intestinal hyperpermeability.

Oral aspirin administration did not induce intestinal hyperpermeability.

Oral aspirin administration did appear to induce intestinal inflammation.

FABP2 appears to be a useful marker of intestinal inflammation.

Serum TNF appears to be a useful marker of intestinal hyperpermeability.

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.