Use of aspirin to intentionally induce gastrointestinal tract barrier dysfunction in feedlot cattle

<div> <p>The beef cattle industry segmentation causes stress on cattle as they are weaned and transported to a feedlot or stocker operation. Through this stress and others (acidosis, feed restriction, heat), gastrointestinal tract (GIT) barrier dysfunction occurs, which can lead to numerous additional disorders, such as liver abscesses or laminitis. In order to develop therapies that can minimize leaky gut, a better understanding of how compromised GIT integrity affects the health and growth of beef cattle is needed. Currently, the most common way to study leaky gut is to induce GIT barrier dysfunction by imposing a stress, which can include transportation, feed restriction, pathogen challenge, or heat stress, and then using various markers to measure GIT permeability. However, these methods are resource intensive, cause unwanted side effects for the animal (sickness, decreased growth), and there is large variation among animals in their response to stress, thus these models are less than ideal. To fully understand the GIT without ambiguity, a clearer picture of which effects are from the stress and which effects are from a compromised GIT is needed. In this thesis, the use of aspirin to intentionally induce GIT barrier dysfunction in feedlot cattle was evaluated through Cr-EDTA kinetics, tight junction protein mRNA expression, and blood serum inflammatory indicators. The long-term effects of GIT barrier dysfunction was evaluated through cattle performance and carcass physiology. Cattle receiving aspirin can enter into the food chain at the end of research, which makes research less costly, and aspirin more attractive as a model for inducing leaky gut. Appearance of Cr-EDTA in urine is commonly used as an indicator of GIT barrier permeability. </p> <p> Chapter 2 includes two complimentary experiments that evaluate the efficacy of aspirin at inducing leaky gut. Experiment 1 used sixteen crossbred heifers (425.0 ± 8.6 kg) in two experimental periods and allotted by BW to 0, 50, 100, or 200 mg/kg BW aspirin. Each treatment had four heifers that received the same aspirin dose during each period, which were separated by 4 wks. Heifers were fed a 49.4% corn silage, 50.6% concentrate diet. Aspirin boluses were administered orally to animals. The 200 mg/kg BW aspirin treatment was dosed as 100 mg/kg BW aspirin 36 and 24 h prior to Cr-EDTA dosing (1 L; 180 mM). The 50 and 100 mg/kg BW treatment were dosed 24 h prior to Cr-EDTA dosing. Every 3 h for 48 h, urine was collected and analyzed for Cr using atomic absorption spectroscopy. At 0, 24, and 48 h, serum was collected and analyzed for lipopolysaccharide binding protein (LBP), interleukin-6 (IL-6), serum amyloid A (SAA), haptoglobin, and aspartate amino transferase (AST). Experiment 2 used sixteen crossbred steers (576.0 ± 14.2 kg), fed a similar diet for 6 wks. Steers were allotted by BW to the 0 and 200 mg/kg BW aspirin treatments (8 steers/treatment) 36 h before slaughter. Twenty-four h after the last aspirin dose, steers were slaughtered, jejunal tissues were collected and tight junction mRNA expression was determined. Data were analyzed using the MIXED procedure of SAS. Aspirin linearly increased Cr absorption (<i>P</i> = 0.02) and elimination (<i>P</i> = 0.04) rates and linearly decreased mean retention time of Cr (<i>P</i> = 0.02). Aspirin tended to increase serum LBP (<i>P</i> = 0.09), but did not affect any other serum inflammatory marker (<i>P</i> ≥ 0.16). Aspirin tended to increase jejunal claudin-1 mRNA expression (<i>P</i> = 0.10), but did not affect expression of other jejunal tight junction mRNA (<i>P</i> ≥ 0.20). Results from this study indicate that aspirin disrupts GIT barrier function in beef cattle and has potential as a model in GIT permeability research. </p> <p>Chapter 3 evaluated the long-term effect of GIT barrier dysfunction on animal performance and physiology. Ninety-six Simmental x Angus steers (355.0 ± 14.8 kg) were allotted by body weight and breed into two treatments: control (no aspirin); and aspirin fed at 50 mg/kg/d. Steers were housed in 16 pens (8 pens/treatment) with 6 steers in each pen. Weight was recorded monthly and blood was collected on d 159 and serum was analyzed for LBP, IL-6, SAA, haptoglobin, and AST. Data were analyzed using the MIXED procedure of SAS. Aspirin tended to decrease average daily gain (ADG, <i>P</i> = 0.10) and did decrease hot carcass weight (<i>P</i> = 0.05) and rib-eye area (<i>P</i> = 0.01), while increasing fat thickness (<i>P</i> = 0.02), marbling score (<i>P </i>= 0.003), and yield grade (<i>P </i>= 0.01). Aspirin tended to increase percent KPH (<i>P</i> = 0.10). Aspirin had no effect on body weight, dry matter intake, gain:feed, days on feed, dressing percentage, liver abscess score, or percent liver abscesses. Aspirin tended to increase serum LBP (<i>P</i> = 0.07), but had no effect on serum concentrations of IL-6, haptoglobin, SAA, and AST (<i>P</i> ≥ 0.30). This study indicates that aspirin induced leaky gut has negative impacts on feedlot performance and carcass leanness. The negative impact of aspirin induced leaky gut on animal performance suggests that leaky gut caused by other factors (subacute acidosis, stress) may be a significant problem for the feedlot industry.</p> <p>Overall, aspirin can be used as a model for leaky gut research in both short-term and long-term studies in cattle. The versatility of this model to be used in both short-term and long-term, while allowing animals to enter into the food chain, shows the value that this model brings to research. Additional research is needed to fully understand the mechanisms of leaky gut, and how to mitigate the negative effects of leaky gut. The aspirin model is a new method in cattle to further research. </p> </div> <br>