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

[en] 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. © This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Disciplines :

Veterinary medicine & animal health

Author, co-author :

Helm, E. T.; Department of Animal Science, Iowa State University, Ames, IA, United States

Curry, S.; Oak Ridge Institute for Science and Education, Oak Ridge, TN, United States

Trachsel, J. M.; Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agriculture Research Service, United States Department of Agriculture, Ames, IA, United States

Schroyen, Martine ; Université de Liège - ULiège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Agronomie, Bio-ingénierie et Chimie (AgroBioChem)

Gabler, N. K.; Department of Animal Science, Iowa State University, Ames, IA, United States

Language :

English

Title :

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

Publication date :

2019

Journal title :

PLoS ONE

eISSN :

1932-6203

Publisher :

Public Library of Science

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 25 September 2019

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Bibliography

Moore PR, Evenson A, Luckey TD, Mccoy E, Elvehjem CA, Hart EB. Use of Sulfasuxidine, Streptothri-cin, and Streptomycin in Nutritional Studies with the Chick. J Biol Chem. 1946; 165(2):437–41. PMID: 20276107
Gaskins HR, Collier CT, Anderson DB. Antibiotics as growth promotants: mode of action. Anim Biotechnol. 2002; 13(1):29–42. https://doi.org/10.1081/ABIO-120005768 PMID: 12212942
FDA. The judicious use of medically important antimicrobial drugs in food-producing animals. Rockville, MD: Food and Drug Administration; 2012.
Wallace HD. Biological responses to antibacterial feed additives in diets of meat producing animals. J Anim Sci. 1970; 31(6):1118–26. PMID: 4926472
Rushton J. Anti-microbial Use in Animals: How to Assess the Trade-offs—Rushton—2015—Zoonoses and Public Health—Wiley Online Library. Zoonoses and Public Health. 2015(2015 suppl 1):10–21. https://doi.org/10.1111/zph.12198 PMID: 25917650
Griffin MO, Ceballos G, Villarreal FJ. Tetracycline compounds with non-antimicrobial organ protective properties: possible mechanisms of action. Pharmacol Res. 2011; 63(2):102–7. https://doi.org/10.1016/j.phrs.2010.10.004 PMID: 20951211
Petkovic H, Lukezic T, Suskovic J. Biosynthesis of Oxytetracycline by Streptomyces rimosus:Past, Present and Future Directions in the Developmentof Tetracycline Antibiotics. Food Technol Biotechnol. 2017; 55(1):3–13. https://doi.org/10.17113/ftb.55.01.17.4617 PMID: 28559729
FDA. Chlortetracycline Breeding Swine Feed FDA2018 [Available from: https://www.fda.gov/downloads/AnimalVeterinary/Products/AnimalFoodFeeds/MedicatedFeed/BlueBirdLabels/ UCM368164.pdf.
Brown K, Uwiera RRE, Kalmokoff ML, Brooks SPJ, Inglis GD. Antimicrobial growth promoter use in livestock: a requirement to understand their modes of action to develop effective alternatives. Int J Antimicrob Agents. 2017; 49(1):12–24. https://doi.org/10.1016/j.ijantimicag.2016.08.006 PMID: 27717740
Flynn WT. Guidance for Industry #209: The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals. In: Services USDoHaH, editor. Food and Drug Administration, Center for Veterinary Medicine2012.
Dibner JJ, Richards JD. Antibiotic growth promoters in agriculture: history and mode of action. Poult Sci. 2005; 84(4):634–43. https://doi.org/10.1093/ps/84.4.634 PMID: 15844822
Coates ME, Fuller R, Harrison G, Lev M, Suffolk S. A comparision of the growth of chicks in the Gustafs-son germ-free apparatus and in a conventional environment, with and without dietary supplements of penicillin. Br J Nutr. 1963; 17(1):141–50.
Costa E, Uwiera RR, Kastelic JP, Selinger LB, Inglis GD. Non-therapeutic administration of a model antimicrobial growth promoter modulates intestinal immune responses. Gut Pathog. 2011; 3(1):14. https://doi.org/10.1186/1757-4749-3-14 PMID: 21943280
National Research Council. Nutrient requirements of swine: Eleventh revised edition. Washington, DC: The National Academies Press; 2012.
Gabler NK, Spencer JD, Webel DM, Spurlock ME. In utero and postnatal exposure to long chain (n-3) PUFA enhances intestinal glucose absorption and energy stores in weanling pigs. J Nutr. 2007; 137 (11):2351–8. https://doi.org/10.1093/jn/137.11.2351 PMID: 17951469
Salanitro JP, Muirhead PA. Quantitative Method for the Gas Chromatographic Analysis of Short-Chain Monocarboxylic and Dicarboxylic Acids in Fermentation Media. Applied Microbiology. 1975; 29(3):374–81. PMID: 1167776
Liu P, Piao XS, Kim SW, Wang L, Shen YB, Lee HS, et al. Effects of chito-oligosaccharide supplementation on the growth performance, nutrient digestibility, intestinal morphology, and fecal shedding of Escherichia coli and Lactobacillus in weaning pigs1. J Anim Sci. 2008; 86(10):2609–18. https://doi.org/10.2527/jas.2007-0668 PMID: 18502883
Shen YB, Piao XS, Kim SW, Wang L, Liu P, Yoon I, et al. Effects of yeast culture supplementation on growth performance, intestinal health, and immune response of nursery pigs. J Anim Sci. 2009; 87 (8):2614–24. https://doi.org/10.2527/jas.2008-1512 PMID: 19395514
Cromwell GL. Why and how antibiotics are used in swine production. Anim Biotechnol. 2002; 13(1):7–27. https://doi.org/10.1081/ABIO-120005767 PMID: 12212945
Casewell M, Friis C, Marco E, McMullin P, Phillips I. The European ban on growth-promoting antibiotics and emerging consequences for human and animal health. J Antimicrob Chemother. 2003; 52(2):159–61. https://doi.org/10.1093/jac/dkg313 PMID: 12837737
Levesque CL, Hooda S, Swanson KS, de Lange K. Alterations in Ileal Mucosa Bacteria Related to Diet Complexity and Growth Performance in Young Pigs. PLoS One. 2014; 9(9):e108472. https://doi.org/10.1371/journal.pone.0108472 PMID: 25247930
Ipharraguerre IR, Pastor JJ, Gavaldà-Navarro A, Villarroya F, Mereu A. Antimicrobial promotion of pig growth is associated with tissue-specific remodeling of bile acid signature and signaling. Sci Rep. 2018; 8(1):13671. https://doi.org/10.1038/s41598-018-32107-9 PMID: 30209339
Williams HE, Woodworth JC, DeRouchey JM, Tokach MD, Goodband RD, Amachawadi RG, et al. Effects of chlortetracycline alone or in combination with direct fed microbials on nursery pig growth performance and antimicrobial resistance of fecal Escherichia coli1. J Anim Sci. 2018; 96(12):5166–78. https://doi.org/10.1093/jas/sky370 PMID: 30358839
Unno T, Kim JM, Guevarra RB, Nguyen SG. Effects of antibiotic growth promoter and characterization of ecological succession in Swine gut microbiota. J Microbiol Biotechnol. 2015; 25(4):431–8. PMID: 25370726
Collier CT, Smiricky-Tjardes MR, Albin DM, Wubben JE, Gabert VM, Deplancke B, et al. Molecular ecological analysis of porcine ileal microbiota responses to antimicrobial growth promoters. J Anim Sci. 2003; 81(12):3035–45. https://doi.org/10.2527/2003.81123035x PMID: 14677859
Rettedal E, Vilain S, Lindblom S, Lehnert K, Scofield C, George S, et al. Alteration of the ileal microbiota of weanling piglets by the growth-promoting antibiotic chlortetracycline. Appl Environ Microbiol. 2009; 75(17):5489–95. https://doi.org/10.1128/AEM.02220-08 PMID: 19617391
Kim HB, Borewicz K, White BA, Singer RS, Sreevatsan S, Tu ZJ, et al. Microbial shifts in the swine distal gut in response to the treatment with antimicrobial growth promoter, tylosin. Proc Natl Acad Sci U S A. 2012; 109(38):15485–90. https://doi.org/10.1073/pnas.1205147109 PMID: 22955886
Kalmokoff M, Waddington LM, Thomas M, Liang KL, Ma C, Topp E, et al. Continuous feeding of antimicrobial growth promoters to commercial swine during the growing/finishing phase does not modify faecal community erythromycin resistance or community structure. J Appl Microbiol. 2011; 110(6):1414–25. https://doi.org/10.1111/j.1365-2672.2011.04992.x PMID: 21395944
Bergman EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev. 1990; 70(2):567–90. https://doi.org/10.1152/physrev.1990.70.2.567 PMID: 2181501
Looft T, Johnson TA, Allen HK, Bayles DO, Alt DP, Stedtfeld RD, et al. In-feed antibiotic effects on the swine intestinal microbiome. Proc Natl Acad Sci U S A. 2012; 109(5):1691–6. https://doi.org/10.1073/pnas.1120238109 PMID: 22307632
Niewold TA. The nonantibiotic anti-inflammatory effect of antimicrobial growth promoters, the real mode of action? A hypothesis. Poult Sci. 2007; 86(4):605–9. https://doi.org/10.1093/ps/86.4.605 PMID: 17369528
Visek WJ. The Mode of Growth Promotion by Antibiotics. J Anim Sci. 1978; 46(5):1447–69. https://doi.org/10.2527/jas1978.4651447x
Moeser AJ, Pohl CS, Rajput M. Weaning stress and gastrointestinal barrier development: Implications for lifelong gut health in pigs. Anim Nutr. 2017; 3(4):313–21. https://doi.org/10.1016/j.aninu.2017.06. 003 PMID: 29767141
Veldhuizen EJ, Rijnders M, Claassen EA, van Dijk A, Haagsman HP. Porcine beta-defensin 2 displays broad antimicrobial activity against pathogenic intestinal bacteria. Mol Immunol. 2008; 45(2):386–94. https://doi.org/10.1016/j.molimm.2007.06.001 PMID: 17658606
Lai Y, Gallo RL. AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol. 2009; 30(3):131–41. https://doi.org/10.1016/j.it.2008.12.003 PMID: 19217824
Soler L, Miller I, Hummel K, Razzazi-Fazeli E, Jessen F, Escribano D, et al. Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27. Electrophoresis. 2016; 37(10):1277–86. https://doi.org/10.1002/elps. 201500529 PMID: 26914286
Johnson RW. Inhibition of growth by pro-inflammatory cytokines: an integrated view. J Anim Sci. 1997; 75(5):1244–55. https://doi.org/10.2527/1997.7551244x PMID: 9159271
Jobgen WS, Fried SK, Fu WJ, Meininger CJ, Wu G. Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates. J Nutr Biochem. 2006; 17(9):571–88. https://doi.org/10.1016/j.jnutbio.2005.12.001 PMID: 16524713
Cho I, Yamanishi S, Cox L, Methe BA, Zavadil J, Li K, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature. 2012; 488(7413):621–6. https://doi.org/10.1038/ nature11400 PMID: 22914093