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Original article
Gut microbiota disturbance during antibiotic therapy: a multi-omic approach
  1. Ana Elena Pérez-Cobas1,2,
  2. María José Gosalbes1,2,
  3. Anette Friedrichs3,4,
  4. Henrik Knecht3,
  5. Alejandro Artacho1,
  6. Kathleen Eismann5,
  7. Wolfgang Otto5,
  8. David Rojo6,
  9. Rafael Bargiela7,
  10. Martin von Bergen5,8,9,
  11. Sven C Neulinger10,
  12. Carolin Däumer11,
  13. Femke-Anouska Heinsen3,
  14. Amparo Latorre1,2,
  15. Coral Barbas6,
  16. Jana Seifert5,
  17. Vitor Martins dos Santos12,13,
  18. Stephan J Ott3,4,
  19. Manuel Ferrer7,
  20. Andrés Moya1,2
  1. 1 Unidad Mixta de Investigación en Genómica y Salud del Centro Superior de Investigación en Salud Pública (CSISP) e Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, Valencia, Spain
  2. 2 CIBER en Epidemiología y Salud Pública (CIBEResp), Madrid, Spain
  3. 3 Institute for Clinical Molecular Biology, Christian-Albrechts University, Kiel, Germany
  4. 4 Department of Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
  5. 5Department of Proteomics, Helmholtz Centre for Environmental Research, Leipzig, Germany
  6. 6 Center for Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Madrid, Spain
  7. 7 CSIC-Institute of Catalysis, Madrid, Spain
  8. 8Department of Metabolomics, Helmholtz Centre for Environmental Research, Leipzig, Germany
  9. 9Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg, Denmark
  10. 10Institute for General Microbiology at the Christian-Albrechts University, Kiel, Germany
  11. 11Institute of Medical Informatics and Statistics, Christian-Albrechts University, Kiel, Germany
  12. 12Chair of Systems and Synthetic Biology, Wageningen University, The Netherlands
  13. 13LifeGlimmer GmbH, Berlin, Germany
  1. Correspondence to Professor Andrés Moya, Cavanilles Institut on Biodiversity and Evolutionary Biology, University of València, José Beltrán 2, 46980 Paterna, Valencia, Spain; andres.moya{at}uv.es Dr. Manuel Ferrer, CSIC-Institute of Catalysis, Marie Curie 2, 28049 Madrid, Spain; mferrer@icp.csic.es

Abstract

Objective Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy.

Methods The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS2 instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated.

Results Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by ‘presumptive’ naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while ‘presumptively’ attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host–microbial interactions significantly improved after treatment cessation.

Conclusions This proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and diseases may alter gut microbial ecology and interactions with host metabolism at a much higher level than previously assumed.

  • Colonic Microflora
  • Antibiotic Therapy
  • Meta-Analysis
  • Gastrointestinal Function
  • Gene Expression

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

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