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Science China Life Sciences

, Volume 60, Issue 11, pp 1260–1270 | Cite as

Antibiotic growth promoter olaquindox increases pathogen susceptibility in fish by inducing gut microbiota dysbiosis

  • Suxu He
  • Quanmin Wang
  • Shuning Li
  • Chao Ran
  • Xiaoze Guo
  • Zhen Zhang
  • Zhigang ZhouEmail author
Research Paper

Abstract

Low dose antibiotics have been used as growth promoters in livestock and fish. The use of antibiotics has been associated with reduced pathogen infections in livestock. In contrast, antibiotic growth promoter has been suspected of leading to disease outbreaks in aquaculture. However, this phenomenon is circumstantial and has not been confirmed in experimental conditions. In this study, we showed that antibiotic olaquindox increased the susceptibility of zebrafish to A. hydrophila infection. Olaquindox led to profound alterations in the intestinal microbiota of zebrafish, with a drastic bloom of Enterobacter and diminishing of Cetobacterium. Moreover, the innate immune responses of zebrafish were compromised by olaquindox (P<0.05). Transfer of microbiota to GF zebrafish indicated that while the immuo-suppression effect of olaquindox is a combined effect mediated by both OLA-altered microbiota and direct action of the antibiotic (P<0.05), the increased pathogen susceptibility was driven by the OLA-altered microbiota and was not dependent on direct antibiotic effect. Taken together, these data indicate that low level of OLA induced gut microbiota dysbiosis in zebrafish, which led to increased pathogen susceptibility.

Keywords

antibiotic growth promoter pathogen susceptability gut microbiota fish olaquindox 

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Notes

Acknowledgements

This work was supported by the National Basic Research Program of China (2015CB150605), the National Natural Science Foundation of China (31272672, 31572633), the Beijing Earmarked Fund for Modern Agro-industry Technology Research System (SCGWZJ 20161104-4), and the Fundamental Research Funds for the Central Public Welfare Research Institute (1610382016013).

Supplementary material

11427_2016_9072_MOESM1_ESM.docx (402 kb)
Antibiotic growth promoter olaquindox increases pathogen susceptibility in fish by inducing gut microbiota dysbiosis

References

  1. Araujo, F.G., Slifer, T.L., and Remington, J.S. (2002). Effect of moxifloxacin on secretion of cytokines by human monocytes stimulated with lipopolysaccharide. Clin Microbiol Infect 8, 26–30.CrossRefPubMedGoogle Scholar
  2. Bellmann, C., Tipping, A., and Sumaila, U.R. (2016). Global trade in fish and fishery products: an overview. Mar Policy 69, 181–188.CrossRefGoogle Scholar
  3. Brüssow, H. (2015). Growth promotion and gut microbiota: insights from antibiotic use. Environ Microbiol 17, 2216–2227.CrossRefPubMedGoogle Scholar
  4. Casewell, M., Friis, C., Marco, E., McMullin, P., and Phillips, I. (2003). The European ban on growth-promoting antibiotics and emerging consequences for human and animal health. J Antimicrob Chemother 52, 159–161.CrossRefPubMedGoogle Scholar
  5. Castanon, J.I.R. (2007). History of the use of antibiotic as growth promoters in european poultry feeds. Poult Sci 86, 2466–2471.CrossRefPubMedGoogle Scholar
  6. Cho, I., Yamanishi, S., Cox, L., Methé, B.A., Zavadil, J., Li, K., Gao, Z., Mahana, D., Raju, K., Teitler, I., Li, H., Alekseyenko, A.V., and Blaser, M.J. (2012). Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488, 621–626.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Cox, L.M., Yamanishi, S., Sohn, J., Alekseyenko, A.V., Leung, J.M., Cho, I., Kim, S.G., Li, H., Gao, Z., Mahana, D., Zárate Rodriguez, J.G., Rogers, A.B., Robine, N., Loke, P., and Blaser, M.J. (2014). Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158, 705–721.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Coyne, M.J., Roelofs, K.G., and Comstock, L.E. (2016). Type VIsecretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements. BMC Genomics 17, 58.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Defoirdt, T., Boon, N., Sorgeloos, P., Verstraete, W., and Bossier, P. (2007). Alternatives to antibiotics to control bacterial infections: luminescent vibriosis in aquaculture as an example. Trends Biotech 25, 472–479.CrossRefGoogle Scholar
  10. Faber, F., Tran, L., Byndloss, M.X., Lopez, C.A., Velazquez, E.M., Kerrinnes, T., Nuccio, S.P., Wangdi, T., Fiehn, O., Tsolis, R.M., and Bäumler, A.J. (2016). Host-mediated sugar oxidation promotes post-antibiotic pathogen expansion. Nature 534, 697–699.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Feckaninová, A., Košcová, J., Mudronová, D., Popelka, P., and Toropilová, J. (2017). The use of probiotic bacteria against Aeromonas infections in salmonid aquaculture. Aquaculture 469, 1–8.CrossRefGoogle Scholar
  12. Gao, P., Mao, D., Luo, Y., Wang, L., Xu, B., and Xu, L. (2012). Occurrence of sulfonamide and tetracycline-resistant bacteria and resistance genes in aquaculture environment. Water Res 46, 2355–2364.CrossRefPubMedGoogle Scholar
  13. Hai, N.V. (2015). Research findings from the use of probiotics in tilapia aquaculture: a review. Fish Shellfish Immunol 45, 592–597.CrossRefPubMedGoogle Scholar
  14. Halling-Sørensen, B. (2001). Inhibition of aerobic growth and nitrification of bacteria in sewage sludge by antibacterial agents. Arch Environ Contam Toxicol 40, 451–460.CrossRefPubMedGoogle Scholar
  15. Hermann, A.C., Millard, P.J., Blake, S.L., and Kim, C.H. (2004). Development of a respiratory burst assay using zebrafish kidneys and embryos. J Immunol Methods 292, 119–129.CrossRefPubMedGoogle Scholar
  16. Hornef, M. (2015). Pathogens, commensal symbionts, and pathobionts: discovery and functional effects on the host. ILAR J 56, 159–162.CrossRefPubMedGoogle Scholar
  17. Jeong, S.H., Song, Y.K., and Cho, J.H. (2009). Risk assessment of ciprofloxacin, flavomycin, olaquindox and colistin sulfate based on microbiological impact on human gut biota. Regul Toxicol Pharmacol 53, 209–216.CrossRefPubMedGoogle Scholar
  18. Khadem, A., Soler, L., Everaert, N., and Niewold, T.A. (2014). Growth promotion in broilers by both oxytetracycline and Macleaya cordata extract is based on their anti-inflammatory properties. Br J Nutr 112, 1110–1118.CrossRefPubMedGoogle Scholar
  19. Kim, M., Qie, Y., Park, J., and Kim, C.H. (2016). Gut microbial metabolites fuel host antibody responses. Cell Host Microbe 20, 202–214.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Lange, K., Buerger, M., Stallmach, A., and Bruns, T. (2016). Effects of antibiotics on gut microbiota. Dig Dis 34, 260–268.CrossRefPubMedGoogle Scholar
  21. Li, H., Wang, W., Mai, K., Ai, Q., Zhang, C., and Zhang, L. (2014). Effect of dietary olaquindox on the growth of large yellow croaker (Pseudosciaena crocea R.) and the distribution of its residues in fish tissues. J Ocean Univ China 13, 820–824.CrossRefGoogle Scholar
  22. Lillicrap, A., Macken, A., and Thomas, K.V. (2015). Recommendations for the inclusion of targeted testing to improve the regulatory environmental risk assessment of veterinary medicines used in aquaculture. Environ Int 85, 1–4.CrossRefPubMedGoogle Scholar
  23. Liu, Z., Liu, W., Ran, C., Hu, J., and Zhou, Z. (2016). Abrupt suspension of probiotics administration may increase host pathogen susceptibility by inducing gut dysbiosis. Sci Rep 6, 23214.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Looft, T., Johnson, T.A., Allen, H.K., Bayles, D.O., Alt, D.P., Stedtfeld, R.D., Sul, W.J., Stedtfeld, T.M., Chai, B., Cole, J.R., Hashsham, S.A., Tiedje, J.M., and Stanton, T.B. (2012). In-feed antibiotic effects on the swine intestinal microbiome. Proc Natl Acad Sci USA 109, 1691–1696.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Morgun, A., Dzutsev, A., Dong, X., Greer, R.L., Sexton, D.J., Ravel, J., Schuster, M., Hsiao, W., Matzinger, P., and Shulzhenko, N. (2015). Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks. Gut 64, 1732–1743.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Oliveri Conti, G., Copat, C., Wang, Z., D’Agati, P., Cristaldi, A., and Ferrante, M. (2015). Determination of illegal antimicrobials in aquaculture feed and fish: an ELISA study. Food Control 50, 937–941.CrossRefGoogle Scholar
  27. Oyarbide, U., Iturria, I., Rainieri, S., and Pardo, M.A. (2015). Use of gnotobiotic zebrafish to study Vibrio anguillarum pathogenicity. Zebrafish 12, 71–80.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Pamer, E.G. (2016). Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science 352, 535–538.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Rivera-Chávez, F., Zhang, L.F., Faber, F., Lopez, C.A., Byndloss, M.X., Olsan, E.E., Xu, G., Velazquez, E.M., Lebrilla, C.B., Winter, S.E., and Bäumler, A.J. (2016). Depletion of butyrate-producing Clostridia from the gut microbiota drives an aerobic luminal expansion of Salmonella. Cell Host Microbe 19, 443–454.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Rolig, A.S., Parthasarathy, R., Burns, A.R., Bohannan, B.J.M., and Guillemin, K. (2015). Individual members of the microbiota disproportionately modulate host innate immune responses. Cell Host Microbe 18, 613–620.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Round, J.L., and Mazmanian, S.K. (2009). The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9, 313–323.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Soler, L., Miller, I., Hummel, K., Razzazi-Fazeli, E., Jessen, F., Escribano, D., and Niewold, T. (2016). Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27. Electrophoresis 37, 1277–1286.CrossRefPubMedGoogle Scholar
  33. Thaiss, C.A., Zmora, N., Levy, M., and Elinav, E. (2016). The microbiome and innate immunity. Nature 535, 65–74.CrossRefPubMedGoogle Scholar
  34. Ubeda, C., and Pamer, E.G. (2012). Antibiotics, microbiota, and immune defense. Trends Immunol 33, 459–466.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Xiong, W., Sun, Y., Zhang, T., Ding, X., Li, Y., Wang, M., and Zeng, Z. (2015). Antibiotics, antibiotic resistance genes, and bacterial community composition in fresh water aquaculture environment in China. Microb Ecol 70, 425–432.CrossRefPubMedGoogle Scholar
  36. Xu, D., Gao, J., Gillilland Iii, M., Wu, X., Song, I., Kao, J.Y., and Owyang, C. (2014). Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology 146, 484–496.e4.CrossRefPubMedGoogle Scholar
  37. Zapata, A., Diez, B., Cejalvo, T., Gutiérrez-de Frías, C., and Cortés, A. (2006). Ontogeny of the immune system of fish. Fish Shellfish Immunol 20, 126–136.CrossRefPubMedGoogle Scholar
  38. Zhang, Q., Cheng, J., and Xin, Q. (2015a. Effects of tetracycline on developmental toxicity and molecular responses in zebrafish (Danio rerio) embryos. Ecotoxicology 24, 707–719.CrossRefPubMedGoogle Scholar
  39. Zhang, Q.Q., Ying, G.G., Pan, C.G., Liu, Y.S., and Zhao, J.L. (2015b. Comprehensive evaluation of antibiotics emission and fate in the river basins of China: source analysis, multimedia modeling, and linkage to bacterial resistance. Environ Sci Technol 49, 6772–6782.CrossRefPubMedGoogle Scholar
  40. Zhu, S.M., Deng, Y.L., Ruan, Y.J., Guo, X.S., Shi, M.M., and Shen, J.Z. (2015). Biological denitrification using poly(butylene succinate) as carbon source and biofilm carrier for recirculating aquaculture system effluent treatment. Bioresour Tech 192, 603–610.CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Suxu He
    • 1
  • Quanmin Wang
    • 1
  • Shuning Li
    • 1
  • Chao Ran
    • 1
  • Xiaoze Guo
    • 1
  • Zhen Zhang
    • 1
  • Zhigang Zhou
    • 1
    Email author
  1. 1.Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research InstituteChinese Academy of Agricultural SciencesBeijingChina

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