Glucocorticoid receptor agoinst (GRA): A potential alternative to in-feed antibiotics for newly weaned pigs

Early weaning is a stressful process that causes systemic inflammation, impaired gut function, and reduced growth in pigs. In a previous study, we found that treatment with a glucocorticoid receptor agonist (GRA) reduced inflammation and improved growth performance immediately following weaning. Therefore, a series of experiments were conducted to further explore the mechanisms of GRA action, effect on wean-to-finish growth performance, and the best method for GRA treatment. For experiments 1 and 2 a total of 209 piglets (BW 7.64 ± 1.33) were weaned at 26.0 ± 1.7 days of age and randomly assigned to 8 treatment groups based on a 2×2×2 factorial arrangement with GRA (+ vs. -), sub-therapeutic antibiotics (ANT) (+ vs. -), and sex (gilt vs. barrow) as the main factors. Pigs in GRA+ groups received 0.2mg/kg body weight (BW) Dexamethasone (DEX) 24 hours prior to and 72 hours post-weaning. Pigs in ANT+ groups received 110 mg/kg in-feed Tylosin for the first 7 days post-weaning. All pigs were fed a typical corn-SBM based diet according to a phase feeding program. Titanium dioxide was included in the first 3 phases of diet. Serial blood collections were performed during the first 7 days following weaning for complete blood cell count (CBC) and blood chemistry analysis. On days 1, 3, and 5 post-weaning a total of 115 pigs were euthanized and segments of the jejunum were collected for morphological, enzyme, and heat-shock protein 70 (HSP-70) analysis. Ileal digesta was also collected from euthanized pigs to determine apparent ileal digestibility (AID) of dietary crude protein (CP). Fecal samples were collected weekly until day 28 post-weaning to determine apparent total tract digestibility (ATTD) of dietary gross energy (GE). Relative to weaning (day 0) body weight (BW) and feed intake were measured daily from day 0 to 7, weekly from day 7 to 28, and then every 1-3 weeks from day 28 to 126 post-weaning. For CBC analysis GRA treatment reduced WBC (17.5 vs. 14.7 ± 0.73 K/μl; P < 0.01) and platelet (857.7 vs. 727.8 ± 47.37 K/μl; P = 0.05). Plasma protein levels were lower in (GRA+, ANT-) pigs relative to control (5.0 vs. 5.9 ± 0.14 g/dL; P < 0.01). Treatment with GRA, not ANT, lowered blood urea nitrogen (BUN) (5.82 vs. 7.63 ± 0.61 mg/dL; P < 0.05) and creatinine (1.11 vs. 1.23 ± 0.04 mg/dL; P < 0.02). Villus height was reduced by GRA treatment (0.24 vs. 0.27 ± 0.01 mm; P < 0.01) but villus density was increased in (GRA+, ANT-) relative to control (9.72 vs. 8.89 ± 0.23 villi/mm; P < 0.01). The abundance of HSP-70 and maltase glucoamylase was increased in (GRA+, ANT-) gilts and barrows relative to control gilts and barrows on day 5 post-weaning (P < 0.01). The overall ATTD of GE was increased by GRA+ relative to GRA- (0.63 vs. 0.57 ± 0.01; P < 0.01) but was not affected by ANT (P = 0.86). Relative to control, the AID of CP was higher in all other treatment groups on day 1, but only in GRA+ pigs remained consistently higher than the control group at days 1, 3, and 5. All groups had higher ADG and BW during the first 28 days post-weaning(i.e., starter phase) relative to control (P < 0.01). Gain-to-feed ratio (G: F) was improved by treatments relative to control during the first 2 weeks post-weaning but not weeks 3 and 4. There was no impact of treatment on ADG and G: F during the grow-to-finish phase (day 49-126 post-weaning). However, overall BW was increased by GRA+ relative to GRA- (63.7 vs. 61.4 ± 2.76 kg; P = 0.01) and ANT+ relative to ANT- (63.4 vs. 61.7 ± 2.75 kg; P = 0.04) during the grow-to-finish phase. For experiment 3 a total of 167 piglets (BW 7.35 ± 1.24) were weaned at 25.0 ± 0.81 days of age and randomly assigned to 14 treatment groups based on a 2×7 factorial arrangement with sex (gilt vs. barrows) and treatment as the factors. The treatments were as follows: 110 ppm in-feed tylosin (ANT), 0.2 mg/kg BW i.m. DEX (IM), 2.5ppm in-feed DEX (LF), 5ppm in-feed DEX (HF), 0.8ppm in-water DEX (LW), 1.6ppm in-water DEX (HW), and no treatment control (CON). Relative to weaning (day 0), BW and feed intake were measured daily from d 0-7 and weekly from day 7-21. All groups, with the exception of HW gilts, had higher ADG than control gilts and barrows. While all treatment groups had higher G: F than CON, the groups with the highest G: F relative to CON were ANT, IM, and LF (0.78, 0.66, 0.63 vs 0.37 ± 0.05 respectively, P < 0.01). These results suggest that GRA improves growth by improving apparent nutrient digestibility and reducing the loss of nutrient availability for growth caused by inflammation. Additionally, it seems the advantage in BW acquired from GRA treatment during the first few weeks of weaning is maintained through 126 days post-weaning and is comparable to sub-therapeutic antibiotics. Finally, in-feed GRA delivery methods are just as effective at improving growth performance during weaning as i.m. GRA and ANT. These results indicate that GRA treatment, administered intramuscularly or in-feed, can be used as an alternative to in-feed sub-therapeutic antibiotics.