Glucocorticoid Receptor Agonists to Improve the Productivity and Health of Early-Weaned Pigs: What is the Best Method of Delivery?

The purpose of the current study was to determine the best method of delivery for glucocorticoid receptor agonist (GRA) treatment. A total of 167 Pig Improvement Company (PIC) piglets (body weight (BW) 7.35 ± 1.24 kg) 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 (gilts vs. barrows), in-feed antibiotic (ANT; 110 mg/kg in-feed tylosin), repeated intramuscular (I.M.) injection of GRA (two injections, 0.2 mg/kg BW dexamethasone (DEX)), low dose in-feed GRA (LF, 2.5 mg/kg diet DEX ), high dose in-feed GRA (HF, 5 mg/kg diet DEX), low dose in-water GRA (LW, 0.8 mg/L DEX ), high dose in-water GRA (HW, 1.6 mg/L DEX ), and no treatment control (CON) as the main factors. Body weight and feed intake were measured daily from days 0 to 7 and weekly from days 7 to 28 post-weaning. The interaction effect for average daily gain (ADG) was significant with gilts performing better in the I.M., ANT, and LF groups (p = 0.05). All treatment groups, with the exception of the HW group, had a higher ADG than the CON group. Gilts in the I.M., LF, and HF groups had the highest ADG compared to other treatment groups (p ≤ 0.05). Sex and the interaction between sex and treatments had no effect on the gain-to-feed ratio (G:F; p ≥ 0.21). All treatment groups had a higher G:F than the CON group (p ≥ 0.04). These results suggest that the low-dose, in-feed GRA treatment is the best GRA delivery method and is a suitable alternative to in-feed sub-therapeutic antibiotics.

The Effects of a Glucocorticoid Receptor Agonist (GRA) on the Immune Function, Nutrient Digestibility, and Wean-to-Finish Growth Performance of Early-Weaned Pigs.

This study assessed the viability of glucocorticoid receptor agonist (GRA) treatment as an alternative to in-feed antibiotics (ANT) in wean-to-finish pigs. A total of 209 piglets were assigned to eight treatments based on a factorial arrangement, with GRA (+ vs. -; dexamethasone, 0.2 mg/kg body weight, BW), ANT (+ vs. -; 110 mg/kg in-feed Tylosin) and sex (gilt vs. barrow) as the main factors. The serial slaughter technique and serial blood collection were performed on 115 pigs during the first week post-weaning to collect blood, tissue and ileal digesta samples. Fecal samples were collected to determine energy digestibility. In comparison to ANT, GRA more effectively improved the measures of systemic inflammation, protein utilization and recovery-associated biomarkers (p ≤ 0.05). Relative to the control group, GRA treatment improved (p ≤ 0.03) dietary nutrient digestibility relative to control pigs, which was comparable to ANT effects. Relative to the control group, all groups had a higher ADG and BW during the starter phase (p < 0.01). Similar to the ANT group, GRA improved the gain-to-feed ratio relative to the control group during the starter phase. Relative to control pigs, overall BW was higher in GRA and ANT pigs during the grow-to-finish phase (p < 0.01). Collectively, these results suggest that GRA injection improves the growth performance of newly weaned pigs by reducing weaning-induced inflammation and improving nutrient digestibility. GRA can be used as an alternative to in-feed ANT to mitigate the effects of weaning stress on pigs.

Effects of divergent selection for residual feed intake on nitrogen metabolism and lysine utilization in growing pigs.

A study was conducted to evaluate the effects of divergent genetic selection for residual feed intake (RFI) on nitrogen (N) metabolism and lysine utilization in growing pigs. Twenty-four gilts (body weight [BW] 66 ± 5 kg) were selected from generation nine of the low RFI (LRFI; n = 12) and high RFI (HRFI; n = 12) Iowa State University Yorkshire RFI selection lines. Six pigs from each genetic line were assigned to each of two levels of lysine intake: 70% and 100% of estimated requirements based on the potential of each genetic line for protein deposition (PD) and feed intake. For all diets, lysine was first limiting among amino acids. Using isotope tracer, N-balance, and nutrient digestibility evaluation approaches, whole-body N metabolism and the efficiency of lysine utilization were determined for each treatment group. No significant interaction effects of line and diet on dietary N or gross energy digestibility, PD, and the efficiency of lysine utilization for PD were observed. The line did not have a significant effect on PD and digestibility of dietary N and GE. An increase in lysine intake improved N retention in both lines (from 15.0 to 19.6 g/d, SE 1.44, in LRFI pigs; and from 16.9 to 19.8 g/d, SE 1.67, in HRFI pigs; P < 0.01). At the low lysine intakes and when lysine clearly limited PD, the efficiency of using available lysine intake (above maintenance requirements) for PD was 80% and 91% (SE 4.6) for the LRFI and HRFI pigs, respectively (P = 0.006). There were no significant effects of line or of the line by diet interaction on N flux, protein synthesis, and protein degradation. Lysine intake significantly increased (P < 0.05) N flux (from 119 to 150, SE 8.7 g/d), protein synthesis (from 99 to 117, SE 10.6 g of N/d), and protein degradation (from 85 to 100, SE 6.6 g of N/d). The protein synthesis-to-retention ratio tended to be higher in the LRFI line compared with the HRFI line (6.5 vs. 5.8 SE 0.62; P = 0.06), indicating a tendency for the lower efficiency of PD in this group. Collectively, these results indicate that genetic selection for low RFI is not associated with improvements in lysine utilization efficiency, protein turnover, and nutrient digestibility.

Immune system stimulation increases the irreversible loss of cysteine to taurine, but not sulfate, in starter pigs.

An isotope tracer study was conducted to evaluate the effects of immune system stimulation (ISS) on the irreversible loss of cysteine (Cys) to taurine (Tau) and sulfate (SO4), as well as glutathione (GSH) synthesis, during the fed state in pigs. We previously have reported that ISS increases plasma Cys flux and the GSH synthesis rate at the tissue and whole-body levels in growing pigs. Thus, the current article presents the data on the irreversible loss of Cys during ISS in pigs. Ten gilts (BW: 7.0 ±â€…0.12 kg) were feed restricted a sulfur amino acids (SAA) limiting diet and injected twice with either saline (n = 4) or increasing amounts of E. coli lipopolysaccharide (n = 6). The day after the second injection, a 5-h primed continuous intravenous infusion of 35S-Cys was conducted. ISS reduced plasma Cys and total SAA concentrations (16% and 21%, respectively; P < 0.05). However, ISS had no effect on the plasma concentrations of Tau and SO4, nor did it affect the appearance of 35S in plasma Tau, plasma SO4, urinary Tau, or urinary SO4 (P > 0.19). On a whole-body basis and including urinary excretion, ISS increased the appearance of 35S in Tau by 67% (P < 0.05), but tended to decrease the appearance of 35S in SO4 by 22% (P < 0.09). Overall, the current findings indicate that during ISS, decreased plasma SAA concentrations and increased plasma Cys flux are attributed in part to increased rates of Cys conversion to Tau, but not Cys catabolism to SO4. Thus, increased utilization of Cys for the synthesis of immune system metabolites, such as GSH and Tau, is likely the main contributor to increased Cys flux during ISS in pigs. In addition, the irreversible loss of Cys during ISS is small and has a minimal impact on the daily SAA requirements of starter pigs.

Acute systemic inflammatory response to lipopolysaccharide stimulation in pigs divergently selected for residual feed intake.

BACKGROUND: It is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs' immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells. RESULTS: LPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p = 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count or levels of several plasma cytokines were detected between the two lines. Profiling blood transcriptomes at 0, 2, 6, and 24 hpi by RNA-sequencing revealed that LPS induced dramatic transcriptional changes, with 6296 genes differentially expressed at at least one time point post injection relative to baseline in at least one line (n = 4 per line) (|log2(fold change)| ≥ log2(1.2); q < 0.05). Furthermore, applying the same cutoffs, we detected 334 genes differentially expressed between the two lines at at least one time point, including 33 genes differentially expressed between the two lines at baseline. But no significant line-by-time interaction effects were detected. Genes involved in protein translation, defense response, immune response, and signaling were enriched in different co-expression clusters of genes responsive to LPS stimulation. The two lines were largely similar in their peripheral blood transcriptomic responses to LPS stimulation at the pathway level, although the low-RFI line had a slightly lower level of inflammatory response than the high-RFI line from 2 to 6 hpi and a slightly higher level of inflammatory response than the high-RFI line at 24 hpi. CONCLUSIONS: The pig lines divergently selected for RFI had a largely similar response to LPS stimulation. However, the low-RFI line had a relatively lower-level, but longer-lasting, inflammatory response compared to the high-RFI line. Our results suggest selection for feed efficient pigs does not significantly compromise a pig's acute systemic inflammatory response to LPS, although slight differences in intensity and duration may occur.

Immune System Stimulation Reduces the Efficiency of Whole-Body Protein Deposition and Alters Muscle Fiber Characteristics in Growing Pigs.

The effects of immune system stimulation (ISS), induced by repeated injection of Escherichia coli lipopolysaccharide, on the whole-body protein synthesis versus degradation rates, the efficiency of protein deposition (PD), and muscle fiber characteristics in pigs were evaluated. Twelve growing gilts were assigned to two levels of amino acid intake that was predicted based on the potential of each group's health status for PD and feed intake. Isotope tracer, nitrogen balance, and immunohistochemical staining techniques were used to determine protein turnover, PD, and muscle fiber characteristics, respectively. Protein synthesis, degradation, and PD were lower in immune-challenged pigs than in control pigs (p < 0.05). Strong tendencies for a higher protein synthesis-to-PD ratio (p = 0.055) and a lower protein synthesis-to-degradation ratio (p = 0.065) were observed in immune-challenged pigs. A decrease in muscle cross-sectional area of fibers and a shift from myosin heavy chain (MHC)-II towards MHC-I fibers (p < 0.05) were observed in immune-challenged pigs. These results indicated that ISS reduces PD not only by suppressing the whole-body protein synthesis and degradation rates, but also by decreasing the efficiency of PD in growing pigs. In addition, ISS induces atrophy in skeletal muscles and favors a slow-twitch oxidative fiber type composition.

Immune system stimulation increases the plasma cysteine flux and whole-body glutathione synthesis rate in starter pigs1.

Glutathione (GSH) is the major intracellular thiol that plays a role in numerous detoxification, bio-reduction, and conjugation reactions. The availability of Cys is thought to be the rate-limiting factor for the synthesis of GSH. The effects of immune system stimulation (ISS) on GSH levels and the GSH synthesis rate in various tissues, as well as the plasma flux of Cys, were measured in starter pigs fed a sulfur AA (SAA; Met + Cys) limiting diet. Ten feed-restricted gilts with initial body weight (BW) of 7.0 ± 0.12 kg were injected i.m. twice at 48-h intervals with either sterile saline (n = 4; ISS-) or increasing amounts of Escherichia coli lipopolysaccharide (n = 6; ISS+). The day after the second injection, pigs received a primed constant infusion of 35S-Cys (9,300 kBq/pig/h) for 5 h via a jugular catheter. Blood and tissue free Cys and reduced GSH were isolated and quantified as the monobromobimane derivatives by HPLC. The rate of GSH synthesis was determined by measurement of the specific radioactivity of GSH and tissue free Cys at the end of the infusion period. Plasma Cys and total SAA levels were reduced (16% and 21%, respectively), but plasma Cys flux was increased (26%) by ISS (P < 0.05). Immune system stimulation increased GSH levels in the plasma (48%; P < 0.05), but had no effect on GSH levels in the liver, small and large intestines, heart, muscle, spleen, kidney, lung, and erythrocytes. The fractional synthesis rate (FSR) of GSH was higher (P < 0.05) in the liver (34%), small intestine (78%), large intestine (72%), heart (129%), muscle (37%), and erythrocytes (47%) of ISS+ pigs compared to ISS- pigs. The FSR of GSH tended (P = 0.08) to be higher in the lungs (45%) of ISS+ pigs than in ISS- pigs. The absolute rate of GSH synthesis was increased by ISS (mmol/kg wet tissue/d ± SE, ISS- vs. ISS+; P < 0.05) in the liver (5.22 ± 0.22 vs. 7.20 ± 0.59), small intestine (2.54 ± 0.25 vs. 4.52 ± 0.56), large intestine (0.61 ± 0.06 vs. 1.06 ± 0.16), heart (0.21 ± 0.03 vs. 0.48 ± 0.08), lungs (1.50 ± 0.10 vs. 2.90 ± 0.21), and muscle (0.21 ± 0.03 vs. 0.34 ± 0.04), but it remained unchanged in erythrocytes, the kidney, and the spleen (P > 0.80). The current findings suggest that GSH synthesis is increased during ISS, contributing to enhanced maintenance sulfur amino acid requirements in starter pigs during ISS.

Immune system stimulation induced by porcine reproductive and respiratory syndrome virus alters plasma free amino acid flux and dietary nitrogen utilization in starter pigs1.

Changes in plasma free amino acid (AA) flux reflect the modification of AA metabolism in different metabolic states. Infectious diseases repartition AA away from protein retention toward processes involved in immune defense, thus impacting AA utilization in pigs. The current study sought to evaluate the effects of disease induced by a live pathogen on plasma free AA flux and whole-body nitrogen (N) utilization. Twenty gilts (BW 9.4 ± 0.9 kg) were surgically catheterized into the jugular vein, individually housed in metabolism crates, and feed-restricted (550 g/d). Intramuscular inoculation of a live field strain of porcine reproductive and respiratory syndrome virus (PRRSV) was used to induce disease. Whole-body N-balance was conducted across 3 d both before PRRSV inoculation (PRRSV-) and also after PRRSV inoculation (PRRSV+). At the end of each N-balance period, a bolus dose of a labeled [U-13C, U-15N]-AA mixture (Ile, Leu, Lys, Met, Phe, Thr, Trp, Val, and Gln) was infused intravenously, followed by serial blood collection for measurement of isotopic enrichment. A double exponential model was fitted with plasma enrichment data for each pig and each AA, and equation parameters were used to estimate plasma free AA flux and pool size. Apparent ileal digestibility (AID) of dietary N was determined using the slaughter technique and an indigestible marker. Blood chemistry, hematology, body temperature, and serum viremia indicated that PRRSV induced effective immune response in pigs (P < 0.05). Challenge with PRRSV reduced the AID of N (P < 0.05), but had no effect on apparent total tract digestibility of dietary energy (P = 0.12). Plasma flux (µmol/kg BW/h) for Met and Thr was increased by PRRSV infection (P < 0.05). A strong tendency of increased Val flux was observed in PRRSV+ pigs (P = 0.06). Infection with PRRSV increased the pool size for Lys, Met, Thr, Trp, Leu, Val, and Gln (P < 0.05). Collectively, these results suggest that PRRSV alters the utilization of dietary N and AA flux, as well as pool size, in growing pigs. The increase in Thr and Met flux in PRRSV+ pigs may be associated with enhanced utilization of these AA for the synthesis of immune system metabolites and increased catabolism of these AA. Thus, dietary Met, Thr, and Val requirements may increase in pigs infected with PRRSV, relative to the requirements for other AA.

Preliminary Study: Depriving Piglets of Maternal Feces for the First Seven Days Post-Partum Changes Piglet Physiology and Performance before and after Weaning.

Coprophagy has been described in piglets although its importance has not been fully assessed. The aim of this study was to evaluate how deprivation of maternal feces influenced piglet physiology, behavior, and performance. Eight litters were randomly assigned to one of two treatments. Control (CON) litters had access to maternal feces while deprived (DEP) litters were deprived of maternal feces for the first 7 d post-partum. Piglet behavior was quantified for 24 h at 7 d of age. Blood samples were collected from one male and female from each litter at 0, 7, and 21 d for hematological analyses, and post-weaning performance was assessed until 123 d post-weaning. No treatment effects were observed on piglet behavior. DEP piglets had 25% lower leukocyte counts (p < 0.01). Relative to DEP litters, CON litters had increased post-weaning feed intake (0.998 vs 0.901 kg/d; p = 0.02) and weight gain (0.536 vs 0.483 kg/d; p < 0.01). At 123 d post-weaning, CON pigs were 9.3 ± 2.3 kg heavier than treatment pigs (p < 0.01). These results suggest that access to maternal feces improves immunocompetence and growth performance. Further studies are needed to explore the physiological mechanisms through which maternal feces improve growth performance, including nutritional and microbial factors, or the presence of maternal semiochemicals.

Multi-Farm Analyses Indicate a Novel Boar Pheromone Improves Sow Reproductive Performance.

The objective of this study was to examine the effectiveness of a novel 3-molecule boar pheromone (BOARBETTER®, BB,) to improve sow reproductive performance (breeding, conception, farrowing rates, pigs born alive, stillborn, mummies and total born). Data from 12 commercial farm sites were used to evaluate the effectiveness of BB. Each farm was used as the experimental unit in the meta-analyses. Individual sows records were collected, merged and analyzed in overall analyses. Relative to CON, BB increased the number of total born pigs per litter (13.81 ± 0.11 vs. 14.30 ± 0.11 pigs/litter, respectively; p < 0.01) and the number of pigs born alive (12.76 ± 0.14 vs. 13.13 ± 0.14 pigs/litter, respectively; p < 0.05). In the merged dataset analyses, the parity by treatment interaction was significant for total pigs and pigs born alive per litter (p < 0.01). In parities one through three, treatment with BB increased total pigs born by 0.88 per litter, and pigs born alive per litter by 0.73 pigs per litter (p < 0.05). However, BB had no effect on these parameters in sows from parities four through six. BOARBETTER® increased reproductive success, is cost effective, safe, and can meaningfully improve sow reproductive success and performance.

Immune system stimulation induced by Escherichia coli lipopolysaccharide alters plasma free amino acid flux and dietary nitrogen utilization in growing pigs.

Changes in plasma free AA flux reflect the modification of AA metabolism in different metabolic states. Immune system stimulation (ISS) in growing pigs may redistribute AA from protein retention towards processes involved in the immune response, thus impacting AA utilization. The aim of the current study was to evaluate the effect of ISS on whole-body nitrogen (N) utilization and the kinetics of plasma free AA. Ten gilts (BW 9.4 ± 1.1 kg) were surgically fitted with jugular vein catheters, individually housed in metabolism crates, and feed-restricted (550 g/d). Repeated intramuscular injections of increasing amounts of Escherichia coli lipopolysaccharide (LPS) were used to induce ISS (30 and 36 µg/kg BW, given 48 h apart). Whole-body N-balance was determined for 3-d before ISS (ISS-) and 3-d during ISS (ISS+). At the end of each N-balance period, a bolus dose of labeled [U-13C, U-15N]-AA mixture (Ile, Leu, Lys, Met, Phe, Thr, Trp, Val, and Gln) was infused intravenously, followed by serial blood collection for determination of isotopic enrichment. A double exponential model was fitted with plasma enrichment data for each pig and each AA, and equation parameters were used to estimate plasma-free AA flux and pool size. Apparent ileal digestibility (AID) of N was determined using the slaughter technique and an indigestible marker. Blood samples were collected before and 76-h after the initiation of ISS and assayed for hematology and blood chemistry. Body temperature (BT) was monitored during the course of study. Blood chemistry, hematology, and BT results indicated that LPS induced effective ISS in pigs (P < 0.05). ISS tended to reduce N retention (P = 0.09) and the N retention-to-N intake ratio (P = 0.08). Apparent total tract digestibility of dietary energy and AID of N were reduced by ISS (P < 0.05). Plasma flux (µmol/kg BW/h) for Ile and Phe was reduced by ISS (P < 0.05). Strong tendencies for decreased Lys flux and N retention were observed in ISS pigs (P < 0.10). ISS increased the pool size for Leu but reduced the pool size for Ile (P < 0.05). Collectively, these results suggest that ISS alters the utilization of dietary N and AA flux, as well as pool size in growing pigs. The decrease in Lys, Phe, and Ile flux during ISS may be attributed to a reduction in whole-body protein synthesis or decreased catabolism of these AA. Relative to other AA, dietary Lys, Phe, and Ile requirements may decrease in ISS pigs.

Immune system stimulation increases dietary threonine requirements for protein deposition in growing pigs.

Previous studies have reported an increase in the utilization of threonine (Thr) during immune system stimulation (ISS). However, increased utilization of an AA during ISS may not reflect an increased dietary requirement, as endogenous sources may supply AA to meet the need for enhanced utilization. The current study evaluated the impact of ISS on components of dietary Thr requirements, i.e., maintenance requirement and the efficiency of Thr utilization. Thirty-nine gilts (initial BW 32 ± 2.1 kg) of commercially relevant genetics were individually housed in metabolism crates and fed one of six experimental diets in which Thr was the first limiting among other AA. Three levels of dietary Thr were tested within each ISS group: 70%, 90%, and 110% of daily Thr requirements, which were estimated based on the potential of each ISS group for protein deposition (PD). Following adaptation to the experimental diets, pigs from each dietary treatment group were injected with either increasing amounts of Escherichia coli lipopolysaccharide (ISS+; 25 and 35 µg/kg BW) or saline (ISS-). Injections were given 48-h apart and whole-body nitrogen balance was measured for 72-h following the first injection. Body temperature (BT) was monitored and blood samples were collected 24 h after initiation of ISS and evaluated for measures of blood chemistry. Blood chemistry and BT results indicated an effective ISS in pigs (P < 0.03). Threonine intake increased PD in a linear fashion in both ISS groups (P < 0.01). The marginal efficiency of standardized ileal digestible (SID) Thr utilization for PD, represented by the slope, was not affected by ISS. However, ISS substantially increased the extrapolated maintenance SID Thr requirements, represented by the intercept at zero PD (ISS- vs. ISS+, -11.2 vs. -56.3 SE 13.2; P < 0.05). Collectively, our results indicated that the physiological changes associated with ISS increased the dietary SID Thr requirements for PD due to an increase in maintenance requirements.

Impact of immune system stimulation on the ileal nutrient digestibility and utilisation of methionine plus cysteine intake for whole-body protein deposition in growing pigs.

The impact of immune system stimulation (ISS) on the ileal nutrient digestibility and utilisation of dietary methionine plus cysteine (SAA) intake for whole-body protein deposition (PD) was evaluated in growing pigs. For this purpose, sixty barrows were used in two experiments: thirty-six pigs in Expt I and twenty-four pigs in Expt II. Pigs were feed restricted and assigned to five levels of dietary SAA allowance (three and two levels in Expt I and II, respectively) from SAA-limiting diets. Following adaptation, pigs at each dietary SAA level were injected with either increasing amounts of Escherichia coli lipopolysaccharide (ISS+; eight and six pigs per dietary SAA level in Expt I and II, respectively) or saline (ISS - ; four and six pigs in Expt I and II, respectively) while measuring the whole-body nitrogen (N) balance. After N-balance observations, pigs were euthanised, organs were removed and ileal digesta were collected for determining nutrient digestibility. Ileal digestibility of gross energy, crude protein and amino acids was not affected by ISS (P>0·20). ISS reduced PD at all levels of dietary SAA intake (P< 0·01). The linear relationship between daily dietary SAA intake and PD observed at the three lowest dietary SAA intake levels indicated that ISS increased extrapolated maintenance SAA requirements (P< 0·05), but had no effect on the partial efficiency of the utilisation of dietary SAA intake for PD (P>0·20). Physiological and metabolic changes associated with systemic ISS had no effect on the ileal digestibility of nutrients per se, but altered SAA requirements for PD in growing pigs.