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Recovery of gut microbiota in mice exposed to tetracycline hydrochloride and their correlation with host metabolism

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Abstract

Antibiotics can disturb the gut microbial community and host metabolism. However, their recovery after antibiotics exposure needs to be characterized, and the correlation between gut microbiota and host metabolism remains unclear. In this study, mice were exposed to 0.5, 1.5 and 10 g/L tetracycline hydrochloride (TET) for 2 weeks, then recovered without TET for another 2 weeks. The results showed that 2-week TET exposure changed microbial community and functions in the mouse gut, and increased abundance of antibiotic resistance genes (ARGs), especially in the 10 g/L TET group. After a 2-week recovery, these changes could only be recovered to the control level in the 0.5 g/L TET exposure group, except for ARGs. Besides gut microbiota, TET exposure also changed metabolic profiles in mouse urine. The 2-week recovery significantly reduced changes in metabolic profiles. Some altered metabolites were found to have a very high correlation with gut microbial community and functions, indicating that TET exposure might induce certain changes in urinary metabolic profiles by altering the gut microbiota. The results from this study suggest that the influences of low-level TET exposure are reversible, except for ARGs, which should be paid more attention. During the application of TET, their dosage should be effectively considered and controlled.

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References

  • Barlow M (2009) What antimicrobial resistance has taught us about horizontal gene transfer. In: Horizontal gene transfer. Humana Press, Totowa, NJ, p 397–411

  • Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M (2010) The landscape of somatic copy-number alteration across human cancers. Nature 463(7283):899–905

    Article  CAS  Google Scholar 

  • Boerlin P, Reid-Smith RJ (2008) Antimicrobial resistance: its emergence and transmission. Anim Health Res Rev 9(2):115–126

    Article  Google Scholar 

  • Boucher Y, Labbate M, Koenig JE, Stokes H (2007) Integrons: mobilizable platforms that promote genetic diversity in bacteria. Trends Microbiol 15(7):301–309

    Article  CAS  Google Scholar 

  • Butaye P, Devriese LA, Haesebrouck F (2003) Antimicrobial growth promoters used in animal feed: effects of less well known antibiotics on gram-positive bacteria. Clin Microbiol Rev 16(2):175–188

    Article  CAS  Google Scholar 

  • Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI, Huttley GA, Kelley ST, Knights D, Koenig JE, Ley RE, Lozupone CA, McDonald D, Muegge BD, Pirrung M, Reeder J, Sevinsky JR, Turnbaugh PJ, Walters WA, Widmann J, Yatsunenko T, Zaneveld J, Knight R (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336

    Article  CAS  Google Scholar 

  • Cho I, Yamanishi S, Cox L, Methe BA, Zavadil J, Li K, Gao Z, Mahana D, Raju K, Teitler I, Li HL, Alekseyenko AV, Blaser MJ (2012) Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488(7413):621

    Article  CAS  Google Scholar 

  • Ciric L, Mullany P, Roberts AP (2011) Antibiotic and antiseptic resistance genes are linked on a novel mobile genetic element: Tn6087. J Antimicrob Chemother 66:2235–2239

    Article  CAS  Google Scholar 

  • Claus SP, Ellero SL, Berger B, Krause L, Bruttin A, Molina J, Paris A, Want EJ, de Waziers I, Cloarec O (2011) Colonization-induced host-gut microbial metabolic interaction. MBio 2(2):e00271-10

    Article  CAS  Google Scholar 

  • Cole JR, Wang Q, Cardenas E, Fish J, Chai B, Farris RJ, Kulam-Syed-Mohideen AS, McGarrell DM, Marsh T, Garrity GM, Tiedje JM (2009) The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucleic Acids Res 37(Suppl 1):D141–D145

    Article  CAS  Google Scholar 

  • de Vries LE, Vallès Y, Agersø Y, Vaishampayan PA, García-Montaner A, Kuehl JV, Christensen H, Barlow M, Francino MP (2011) The Gut as reservoir of antibiotic resistance: microbial diversity of tetracycline resistance in mother and infant. PLoS ONE 6(6):1–11

    Article  CAS  Google Scholar 

  • Dethlefsen L, Huse S, Sogin ML, Relman DA (2008) The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 6(11):e280

    Article  CAS  Google Scholar 

  • Dethlefsen L, Relman DA (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci USA 108:4554–4561

    Article  CAS  Google Scholar 

  • Dibner JJ, Richards JD (2005) Antibiotic growth promoters in agriculture: history and mode of action. Poult Sci 84(4):634–643

    Article  CAS  Google Scholar 

  • Frost LS, Leplae R, Summers AO, Toussaint A (2005) Mobile genetic elements: the agents of open source evolution. Nat Rev Micro 3(9):722–732

    Article  CAS  Google Scholar 

  • Ghosh S, LaPara TM (2007) The effects of subtherapeutic antibiotic use in farm animals on the proliferation and persistence of antibiotic resistance among soil bacteria. ISME J 1(3):191–203

    Article  CAS  Google Scholar 

  • Goecks J, Nekrutenko A, Taylor J (2010) Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. Genome Biol 11(8):R86

    Article  Google Scholar 

  • Guarner F, Malagelada J-R (2003) Gut flora in health and disease. The Lancet 361(9356):512–519

    Article  Google Scholar 

  • Gustafson RH, Bowen RE (1997) Antibiotic use in animal agriculture. J Appl Microbiol 83(5):531–541

    Article  CAS  Google Scholar 

  • Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI (2011) Human nutrition, the gut microbiome and the immune system. Nature 474(7351):327–336

    Article  CAS  Google Scholar 

  • Kovatcheva-Datchary P, Tremaroli V, Bäckhed F (2013) The gut microbiota. In: Rosenberg E, DeLong E, Lory S, Stackebrandt E, Thompson F (eds) The prokaryotes. Springer Berlin Heidelberg, p. 3–24

  • López-Gutiérrez JC, Henry S, Hallet S, Martin-Laurent F, Catroux G, Philippot L (2004) Quantification of a novel group of nitrate-reducing bacteria in the environment by real-time PCR. J Microbiol Methods 57(3):399–407

    Article  CAS  Google Scholar 

  • Lindon JC, Nicholson JK, Everett JR (1999) NMR Spectroscopy of Biofluids. In: Webb GA (ed) Annual reports on NMR spectroscopy. vol 38. Academic Press, London UK, 1–88

  • Liu B, Pop M (2009) ARDB—antibiotic resistance genes database. Nucleic Acids Res 37:D443–D447

    Article  CAS  Google Scholar 

  • Looft T, Johnson TA, Allen HK, Bayles DO, Alt DP, Stedtfeld RD, Sul WJ, Stedtfeld TM, Chai BL, Cole JR, Hashsham SA, Tiedje JM, Stanton TB (2012) In-feed antibiotic effects on the swine intestinal microbiome. Proc Natl Acad Sci USA 109(5):1691–1696

    Article  CAS  Google Scholar 

  • Melville CM, Scott KP, Mercer DK, Flint HJ (2001) Novel tetracycline resistance gene, tet (32), in the Clostridium-related human colonic anaerobe K10 and its transmission in vitro to the rumen anaerobe Butyrivibrio fibrisolvens. Antimicrob Agents Chemother 45(11):3246–3249

    Article  CAS  Google Scholar 

  • Moura A, Soares M, Pereira C, Leitão N, Henriques I, Correia A (2009) INTEGRALL: a database and search engine for integrons, integrases and gene cassettes. Bioinformatics 25(8):1096–1098

    Article  CAS  Google Scholar 

  • Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S (2012) Host-gut microbiota metabolic interactions. Science 336(6086):1262–1267

    Article  CAS  Google Scholar 

  • Nicholson JK, Holmes E, Wilson ID (2005) Gut microorganisms, mammalian metabolism and personalized health care. Nat Rev Micro 3(5):431–438

    Article  CAS  Google Scholar 

  • Oakley BB, Buhr RJ, Ritz CW, Kiepper BH, Berrang ME, Seal BS, Cox NA (2014) Successional changes in the chicken cecal microbiome during 42 days of growth are independent of organic acid feed additives. BMC Vet Res 10(1):282

    Article  CAS  Google Scholar 

  • Qian P-Y, Wang Y, Lee OO, Lau SCK, Yang J, Lafi FF, Al-Suwailem A, Wong TYH (2011) Vertical stratification of microbial communities in the Red Sea revealed by 16S rDNA pyrosequencing. ISME J 5(3):507–518

    Article  CAS  Google Scholar 

  • Ridlon JM, Kang D-J, Hylemon PB (2006) Bile salt biotransformations by human intestinal bacteria. J Lipid Res 47(2):241–259

    Article  CAS  Google Scholar 

  • Salyers AA, Gupta A, Wang Y (2004) Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends Microbiol 12(9):412–416

    Article  CAS  Google Scholar 

  • Scanlan PD, Shanahan F, O’Mahony C, Marchesi JR (2006) Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn’s disease. J Clin Microbiol 44(11):3980–3988

    Article  CAS  Google Scholar 

  • Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF (2009) Introducing mothur: open-Source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microb 75(23):7537–7541

    Article  CAS  Google Scholar 

  • Serino M, Luche E, Gres S, Baylac A, Bergé M, Cenac C, Waget A, Klopp P, Iacovoni J, Klopp C (2012) Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 61(4):543–553

    Article  CAS  Google Scholar 

  • Shi P, Jia S, Zhang X-X, Zhang T, Cheng S, Li A (2013) Metagenomic insights into chlorination effects on microbial antibiotic resistance in drinking water. Water Res 47(1):111–120

    Article  CAS  Google Scholar 

  • Sullivan Å, Edlund C, Nord CE (2001) Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis 1(2):101–114

    Article  CAS  Google Scholar 

  • Tatusov RL, Galperin MY, Natale DA, Koonin EV (2000) The COG database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids 28(1):33–36

    Article  CAS  Google Scholar 

  • Tremaroli V, Backhed F (2012) Functional interactions between the gut microbiota and host metabolism. Nature 489(7415):242–249

    Article  CAS  Google Scholar 

  • Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027–1131

    Article  Google Scholar 

  • Vanhoutte T, De Preter V, De Brandt E, Verbeke K, Swings J, Huys G (2006) Molecular monitoring of the fecal microbiota of healthy human subjects during administration of lactulose and Saccharomyces boulardii. Appl Environ Microb 72(9):5990–5997

    Article  CAS  Google Scholar 

  • Visek WJ (1978) The Mode of Growth Promotion by Antibiotics. J Animal Sci 46(5):1447–1469

    Article  Google Scholar 

  • Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, Feldstein AE, Britt EB, Fu X, Chung Y-M (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472(7341):57–63

    Article  CAS  Google Scholar 

  • Wang Z, Zhang X-X, Huang K, Miao Y, Shi P, Liu B, Long C, Li A (2013) Metagenomic profiling of antibiotic resistance genes and mobile genetic elements in a tannery wastewater treatment plant. PLoS ONE 8(10):e76079

    Article  CAS  Google Scholar 

  • Willing BP, Russell SL, Finlay BB (2011) Shifting the balance: antibiotic effects on host–microbiota mutualism. Nat Rev Micro 9(4):233–243

    Article  CAS  Google Scholar 

  • Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ (2006) Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 40(3):235–243

    Article  CAS  Google Scholar 

  • Wu N, Qiao M, Zhang B, Cheng W-D, Zhu Y-G (2010) Abundance and diversity of tetracycline resistance genes in soils adjacent to representative swine feedlots in China. Environ Sci Technol 44(18):6933–6939

    Article  CAS  Google Scholar 

  • Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE (2009a) Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci USA 106(7):2365–2370

    Article  CAS  Google Scholar 

  • Zhang T, Zhang M, Zhang X, Fang HH (2009b) Tetracycline resistance genes and tetracycline resistant lactose-fermenting enterobacteriaceae in activated sludge of sewage treatment plants. Environ Sci Technol 43(10):3455–3460

    Article  CAS  Google Scholar 

  • Zhang T, Zhang XX, Ye L (2011) Plasmid metagenome reveals high levels of antibiotic resistance genes and mobile genetic elements in activated sludge. Plos One 6(10):e26041

  • Zhang Y, Zhang X, Wu B, Cheng S (2012) Evaluating the transcriptomic and metabolic profile of mice exposed to source drinking water. Environ Sci Technol 46(1):78–83

    Article  CAS  Google Scholar 

  • Zhu Y-G, Johnson TA, Su J-Q, Qiao M, Guo G-X, Stedtfeld RD, Hashsham SA, Tiedje JM (2013) Diverse and abundant antibiotic resistance genes in Chinese swine farms. Proc Natl Acad Sci USA 110(9):3435–3440

    Article  CAS  Google Scholar 

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Acknowledgements

This study was financially supported by the National Natural Science Foundation of China (21806079).

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Authors and Affiliations

  1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, PR China

    Wei Zhao, Hanlu Hong, Jinbao Yin, Bing Wu, Fuzheng Zhao & Xu-Xiang Zhang

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  1. Wei Zhao
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Correspondence to Jinbao Yin.

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All experimental processes were in accordance with NIH Guide for the Care and Use of Laboratory Animals. And the protocols were approved by the Animal Care and Use Committee of NGH.

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Zhao, W., Hong, H., Yin, J. et al. Recovery of gut microbiota in mice exposed to tetracycline hydrochloride and their correlation with host metabolism. Ecotoxicology 30, 1620–1631 (2021). https://doi.org/10.1007/s10646-020-02319-9

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