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Transcriptional interactions suggest niche segregation among microorganisms in the human gut

Nature Microbiology volume 1, Article number: 16152 (2016) Cite this article

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Abstract

The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species1. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting species2,3. To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species–species transcriptional interactions were enriched for functions important for H2 and CO2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level.

The gut microbiota is generally considered an ecosystem with many biological interactions2–4. Together with host effect5, dietary habits6, antibiotics7 and other external factors8,9, interactions between microbes may also be a defining factor for the gut microbiota. Known cooperative activities of microbial species include the formation of biofilms10, fermentation of complex substrates11 and exchange of metabolites12, and antagonistic interactions that include competition for resources13 or adhesion sites14 and the production of antimicrobial compounds15. At the community level, microbes with shared genetic potential tend to coexist in the human GI tract, which suggests that the microbiome ensemble is driven by habitat filtering4. Classic population ecology theory, however, predicts that competition between two undifferentiated species eventually will lead to the extinction of one of them16, which raises the question of how microbes with overlapping functional potential differentiate in the human GI tract. One possibility is that coexistence with other species invokes differentiation by transcriptional adaptations.

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Figure 1: Microbial co-occurrence in the GI tract results in transcriptional adaptations between coexisting species.
Figure 2: Orthologous gene expression in a companion species coincides with modulation of a gene expression in a responder species.
Figure 3: Activity of the Wood–Ljungdahl pathway in B. hydrogenotrophica is influenced by other microbial species.

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Acknowledgements

The research leading to these results has received funding from the European Community's Seventh Framework Programme FP7-HEALTH-F4-2007-201052, MetaHIT and FP7-HEALTH-2010-261376: International Human Microbiome Standards. Additional funding was from the Metagenopolis grant ANR-11-DPBS-0001. E.R., A.N.D.M., M.C.R.E. and M.O.A.S. acknowledge funding from the Novo Nordisk Foundation and the Lundbeck Foundation. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).

Author information

Author notes

  1. A list of additional MetaHIT Consortium members and their affiliations is given in the Supplementary Information.

Authors and Affiliations

  1. Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark

    Damian Rafal Plichta, Agnieszka Sierakowska Juncker, Marcelo Bertalan, Laurent Gautier, Thomas Sicheritz-Pontén, Søren Brunak & H. Bjørn Nielsen

  2. Clinical-Microbiomics A/S, DK-2200 Copenhagen, Denmark

    Damian Rafal Plichta & H. Bjørn Nielsen

  3. The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark

    Elizabeth Rettedal, Ana Manuel Dantas Machado, Mari Cristina Rodriguez de Evgrafov & Morten O. A. Sommer

  4. Department of Systems Biology, DTU Multi-Assay Core, Technical University of Denmark, DK-2800 Kongens Lyngby, Denmark

    Laurent Gautier

  5. Digestive System Research Unit, University Hospital Vall d'Hebron, Ciberehd, 08035 Barcelona, Spain

    Encarna Varela, Chaysavanh Manichanh & Francisco Guarner

  6. INRA, Institut National de la Recherche Agronomique, Metagenopolis, Cedex 78350 Jouy en Josas, France

    Charlène Fouqueray & Florence Levenez

  7. MGP, MetaGenoPolis, INRA, Université Paris-Saclay, Cedex 78350 Jouy en Josas, France

    Florence Levenez, Joël Doré & S. Dusko Ehrlich

  8. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

    Trine Nielsen, Torben Hansen & Oluf Pedersen

  9. MICALIS, INRA, Université Paris-Saclay, Cedex 78350 Jouy en Josas, France

    Joël Doré & S. Dusko Ehrlich

  10. Faculty of Health Sciences, University of Southern Denmark, DK-5230 Odense, Denmark

    Torben Hansen

  11. Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark

    Torben Jørgensen & Oluf Pedersen

  12. Research Centre for Prevention and Health, Capital region, Glostrup Hospital, DK-2600 Glostrup, Denmark

    Torben Jørgensen

  13. Faculty of Medicine, Aalborg University, DK-9220 Aalborg, Denmark

    Torben Jørgensen

  14. European Molecular Biology Laboratory, 69117 Heidelberg, Germany

    Peer Bork

  15. King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, London SE1 9RT, UK

    S. Dusko Ehrlich

  16. Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Protein Research, Disease Systems Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark

    Søren Brunak

Authors
  1. Damian Rafal Plichta
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Consortia

Metagenomics of the Human Intestinal Tract (MetaHIT) Consortium

Contributions

All the authors are members of the MetaHIT Consortium. S.B. and H.B.N. managed the project. T.N., F.G., T.J., T.H. and O.P. performed clinical sampling. E.V., C.F., C.M. and F.L. performed RNA extraction. L.G. organized the microarray hybridizations. H.B.N., S.B., T.S.-P. and S.D.E designed the analyses. E.R., A.M.D.M., M.C.R.E. and M.O.A.S. did the co-cultivation and qPCR experiments. D.R.P., H.B.N., M.B. and A.S.J. performed the data analyses. D.P. and H.B.N. wrote the manuscript. D.R.P., H.B.N., S.B., E.R., A.S.J., C.M., S.D.E., O.P., J.D., M.O.A.S. and P.B. revised the manuscript. The MetaHIT Consortium members contributed to the design and execution of the study.

Corresponding authors

Correspondence to Søren Brunak or H. Bjørn Nielsen.

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Competing interests

The authors declare no competing interests.

Supplementary information

Supplementary information

Supplementary Data, Supplementary Figures 1-6, Supplementary Table 4, Legends for Supplementary Tables 1-3 and 5-7, additional MetaHIT consortium members list (PDF 1617 kb)

Supplementary Dataset

Supplementary Tables 1-3 and 5-7 (XLSX 125 kb)

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Plichta, D., Juncker, A., Bertalan, M. et al. Transcriptional interactions suggest niche segregation among microorganisms in the human gut. Nat Microbiol 1, 16152 (2016). https://doi.org/10.1038/nmicrobiol.2016.152

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