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Transcriptional interactions suggest niche segregation among microorganisms in the human gut


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.

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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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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 (

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Authors and Affiliations




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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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).

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