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Original article
Antibiotics-induced monodominance of a novel gut bacterial order
  1. Falk Hildebrand1,
  2. Lucas Moitinho-Silva1,
  3. Sonja Blasche1,
  4. Martin T Jahn2,
  5. Toni Ingolf Gossmann3,
  6. Jaime Huerta-Cepas1,4,
  7. Rajna Hercog5,
  8. Mechthild Luetge1,
  9. Mohammad Bahram6,7,
  10. Anna Pryszlak1,
  11. Renato J Alves1,8,
  12. Sebastian M Waszak9,
  13. Ana Zhu1,10,
  14. Lumeng Ye11,
  15. Paul Igor Costea1,
  16. Steven Aalvink12,
  17. Clara Belzer12,
  18. Sofia K Forslund1,13,
  19. Shinichi Sunagawa1,14,
  20. Ute Hentschel2,
  21. Christoph Merten1,
  22. Kiran Raosaheb Patil1,
  23. Vladimir Benes1,
  24. Peer Bork1,15,16
  1. 1 Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
  2. 2 RD3 Marine Microbiology, GEOMAR Helmholtz Centre for Ocean Research Kiel, Kiel, Germany
  3. 3 Department of Animal and Plant Sciences, University of Sheffield, Sheffield, UK
  4. 4 Computational systems biology and genomics, Centro de Biotecnología y Genómica de Plantas, Universidad Politécnica de Madrid (UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain
  5. 5 Genomics Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany
  6. 6 Department of Ecology, Swedish University of Agricultural Sciences, Uppsala, Sweden
  7. 7 Department of Botany, Institute of Ecology and Earth Sciences, Tartu University, Tartu, Estonia
  8. 8 Structural and Computational Biology Unit, Joint PhD degree between EMBL and Heidelberg University, Heidelberg, Germany
  9. 9 Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
  10. 10 Host Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, UK
  11. 11 Biotechnology Dept., GenScript Corporation (NanJing), NanJing, China
  12. 12 Institute of Microbiology, Wagenigen University, Wageningen, Netherlands
  13. 13 Experimental and ClinicalResearch Centre, Max Delbrück Centre for Molecular Medicine, Berlin, Germany
  14. 14 Department of Biology, Institute of Microbiology, ETH Zurich, Zurich, Switzerland
  15. 15 Molecular Medicine Partnership Unit (MMPU), University of Heidelberg and European Molecular Biology Laboratory, Heidelberg, Germany
  16. 16 Department of Bioinformatics, University of Würzburg, Würzburg, Germany
  1. Correspondence to Professor Peer Bork, Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg 69117, Germany; bork{at}


Objective The composition of the healthy human adult gut microbiome is relatively stable over prolonged periods, and representatives of the most highly abundant and prevalent species have been cultured and described. However, microbial abundances can change on perturbations, such as antibiotics intake, enabling the identification and characterisation of otherwise low abundant species.

Design Analysing gut microbial time-series data, we used shotgun metagenomics to create strain level taxonomic and functional profiles. Community dynamics were modelled postintervention with a focus on conditionally rare taxa and previously unknown bacteria.

Results In response to a commonly prescribed cephalosporin (ceftriaxone), we observe a strong compositional shift in one subject, in which a previously unknown species, U Borkfalki ceftriaxensis, was identified, blooming to 92% relative abundance. The genome assembly reveals that this species (1) belongs to a so far undescribed order of Firmicutes, (2) is ubiquitously present at low abundances in at least one third of adults, (3) is opportunistically growing, being ecologically similar to typical probiotic species and (4) is stably associated to healthy hosts as determined by single nucleotide variation analysis. It was the first coloniser after the antibiotic intervention that led to a long-lasting microbial community shift and likely permanent loss of nine commensals.

Conclusion The bloom of U B. ceftriaxensis and a subsequent one of Parabacteroides distasonis demonstrate the existence of monodominance community states in the gut. Our study points to an undiscovered wealth of low abundant but common taxa in the human gut and calls for more highly resolved longitudinal studies, in particular on ecosystem perturbations.

  • antibiotics
  • bacterial overgrowth
  • intestinal microbiology
  • molecular genetics

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  • Contributors FH and PB designed the study. RH and VB were responsible for sequencing and sample handling. MTTJ and UH designed and implemented FISH detection of U B. ceftriaxensis. SB, LY and KRP tested putative beta lactamase genes in vitro. SB, SA and CB attempted to culture U B. ceftriaxensis. FH conceived, designed and implemented the metagenomic pipelines. The SNV calling pipeline was conceived by FH, TIG and SMW. LM-S and FH conducted the functional characterization of U B. ceftriaxensis. mOTU abundances were calculated by SS and RJA. Phylogenetic analysis was done by FH, TIG, ML,and JHC. Statistical analysis was conceived and implemented by FH, ML, JHC, LS and MB. FH and PB wrote the manuscript with contributions from SB, MTTJ, TIG, MB, LS, RJA, SMW, AZ, PIC and SKF.

  • Funding H received funding through the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 660375. FH, JHC and PB were supported by European Union’s Horizon 2020 Research and Innovation Programme #686070; DD-DeDaF as well as EC/H2020/ES/ERC-AdG-669830; MicrobioS. The work was partiallyfunded by EMBL. MTJ was supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Würzburg. MB received funding from the Swedish Research Council (VR grant 2017-05019). SMW was supported by a SNSF Early Postdoc Mobility Fellowship (P2ELP3_155365) and an EMBO Long-Term Fellowship (ALTF 755-2014). TIG was supported by a Leverhulme Early Career Fellowship Grant (ECF-2015-453) and Natural Environment Research Council grant (NE/N013832/1). This study was supported by the PD Fonds Deutschland gGmbH.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data sets generated and analysed during the current study are available on EBI (see Methods).

  • Correction notice This article has been corrected since it published Online First. The author names have been corrected.

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