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Evaluating nursery pig responses to in-feed sub-therapeutic antibiotics.

ABSTRACT: Antibiotics have been used for over 60 years by the swine industry to improve growth performance and feed efficiency. With rising concerns over antimicrobial resistance and government restrictions such as the Veterinary Feed Directive on usage of in-feed antibiotics, alternatives to feeding antibiotic growth promoters (AGPs) to nursery pigs are needed. However, the mechanism of action by which AGPs work is poorly understood. Thus, the objective of this study was to investigate the mechanisms of action by which AGPs increase nursery pig performance. Over two replicates, 24 weaned pigs (6.75 ± 0.75 kg body weight) were randomly allotted to either control (CON, n = 12) or sub-therapeutic antibiotic (sCTC, n = 12) treatments and housed individually. A 2-phase corn-soybean-based nursery diet was fed, with the sCTC diets containing 40 ppm feed-grade chlortetracycline. Individual pig average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F) were calculated weekly for 5 weeks. Thereafter, all pigs were euthanized and necropsied for tissue collection. The overall performance data indicated that sCTC pigs had increased ADG (0.43 vs. 0.32 kg/d, P = 0.001) and ADFI (0.51 vs. 0.37 kg/d, P = 0.002) compared with CON pigs; however, G:F was not different as a result of dietary treatment (0.85 vs. 0.88, P = 0.617). Intestinal barrier permeability, ileal active nutrient transport, and cecal short chain fatty acid concentrations did not differ (P > 0.10) due to dietary treatment, however changes in several ileum mRNA transcripts suggest that inflammation may be reduced in sCTC pigs. Further, the changes observed in the proteomes of the ileum, colon, skeletal muscle, and liver suggest that the sub-therapeutic mode of action of AGPs may include post-absorptive changes and warrants further investigation.

SUBMITTER: Helm ET

PROVIDER: S-EPMC6485771 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Evaluating nursery pig responses to in-feed sub-therapeutic antibiotics.

Helm Emma T ET Curry Shelby S Trachsel Julian M JM Schroyen Martine M Gabler Nicholas K NK

PloS one 20190426 4

Antibiotics have been used for over 60 years by the swine industry to improve growth performance and feed efficiency. With rising concerns over antimicrobial resistance and government restrictions such as the Veterinary Feed Directive on usage of in-feed antibiotics, alternatives to feeding antibiotic growth promoters (AGPs) to nursery pigs are needed. However, the mechanism of action by which AGPs work is poorly understood. Thus, the objective of this study was to investigate the mechanisms of ...[more]

PMID: 31026263

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Project description:Weaning is a stress every piglet has to face. It is a main cause of antibiotic uses due to digestive disorders. In this study, response to weaning was analyzed in pigs from two lines divergently selected for residual feed intake (RFI) during growth. A total of 132 pigs from each line, housed per line and diet in conventional postweaning units of 12 castrated males and 12 females, were fed either a conventional control (two successive diets) or a complex (three successive diets) dietary sequence during the postweaning period (4 to 10 wk of age). BWs were recorded at weaning (days 0 and 28 of age), days 1, 2, 6, 12, 19, 26, and 42 (10 wk of age), and at 23 wk of age. Feces texture was examined before weaning (day -1), at day 1, 2, 6, 12, and 19. Feed intake was recorded at pen level from days 0 to 42 after weaning, and individually thereafter. Plasma was collected after blood samplings at days -1, 6, 19, and 42 on half of the piglets: all piglets of a given sex in each pen were sampled, to achieve a balanced number across factors. Pigs of the low RFI (LRFI) line were heavier at weaning, had greater glucose concentration, and lower levels of diarrhea at days 1 and 2 than pigs from the high RFI (HRFI) line (P < 0.01). At day 42, there was no BW difference between lines, and G:F ratio did not differ between lines (P = 0.40). The LRFI pigs had lower feed intake and growth rate from day 0 to day 19 (P < 0.005), and greater plasma concentration of non-esterified fatty acid (P < 0.001), indicating an increased mobilization of body lipids and proteins immediately after weaning compared with HRFI pigs. They also had greater levels of diarrhea at day 6 (22% for LRFI vs. 14% for HRFI, P = 0.002), but the concentration of plasma haptoglobin did not indicate acute inflammation. The complex diet sequence improved feed intake and growth, and reduced diarrhea, mainly in the LRFI line (P < 0.001). To conclude, pigs from the LRFI line were more negatively affected by weaning stress, but managed to recover afterwards. The complex diet sequence ameliorated some of the negative effects that weaning had on the LRFI pigs, but limited effects of nursery period feeding sequence on growth performance were observed during the growing-finishing period.

Project description:UNLABELLED:Antibiotics are a cost-effective tool for improving feed efficiency and preventing disease in agricultural animals, but the full scope of their collateral effects is not understood. Antibiotics have been shown to mediate gene transfer by inducing prophages in certain bacterial strains; therefore, one collateral effect could be prophage induction in the gut microbiome at large. Here we used metagenomics to evaluate the effect of two antibiotics in feed (carbadox and ASP250 [chlortetracycline, sulfamethazine, and penicillin]) on swine intestinal phage metagenomes (viromes). We also monitored the bacterial communities using 16S rRNA gene sequencing. ASP250, but not carbadox, caused significant population shifts in both the phage and bacterial communities. Antibiotic resistance genes, such as multidrug resistance efflux pumps, were identified in the viromes, but in-feed antibiotics caused no significant changes in their abundance. The abundance of phage integrase-encoding genes was significantly increased in the viromes of medicated swine over that in the viromes of nonmedicated swine, demonstrating the induction of prophages with antibiotic treatment. Phage-bacterium population dynamics were also examined. We observed a decrease in the relative abundance of Streptococcus bacteria (prey) when Streptococcus phages (predators) were abundant, supporting the "kill-the-winner" ecological model of population dynamics in the swine fecal microbiome. The data show that gut ecosystem dynamics are influenced by phages and that prophage induction is a collateral effect of in-feed antibiotics. IMPORTANCE:This study advances our knowledge of the collateral effects of in-feed antibiotics at a time in which the widespread use of "growth-promoting" antibiotics in agriculture is under scrutiny. Using comparative metagenomics, we show that prophages are induced by in-feed antibiotics in swine fecal microbiomes and that antibiotic resistance genes were detected in most viromes. This suggests that in-feed antibiotics are contributing to phage-mediated gene transfer, potentially of antibiotic resistance genes, in the swine gut. Additionally, the so-called "kill-the-winner" model of phage-bacterium population dynamics has been shown in aquatic ecosystems but met with conflicting evidence in gut ecosystems. The data support the idea that swine fecal Streptococcus bacteria and their phages follow the kill-the-winner model. Understanding the role of phages in gut microbial ecology is an essential component of the antibiotic resistance problem and of developing potential mitigation strategies.

Project description:This review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant (P<0.001) line differences for RFI (-165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (-270 g/day). Low responses were observed on growth rate (-12.8 g/day, P<0.05) and body composition (+0.9 mm backfat thickness, P=0.57; -2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (-0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat (P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (-10% after five generations of selection) and activity (-21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors, via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory.

Dataset Information

Evaluating nursery pig responses to in-feed sub-therapeutic antibiotics.

Publications

Evaluating nursery pig responses to in-feed sub-therapeutic antibiotics.

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