CRISPR targeting reveals a reservoir of common phages associated with the human gut microbiome

  1. Rotem Sorek1,5
  1. 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel;
  2. 2School of Computer Science and Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel
    1. 4 These authors contributed equally to this work.

    • 3 Present addresses: Department of Microbiology and Immunology, University of California, San Francisco, CA 94122, USA; Department of Integrative Biology, University of California, Berkeley, CA 94720, USA.

    Abstract

    The bacterial community in the human gut has crucial health roles both in metabolic functions and in protection against pathogens. Phages, which are known to significantly affect microbial community composition in many ecological niches, have the potential to impact the gut microbiota, yet thorough characterization of this relationship remains elusive. We have reconstructed the content of the CRISPR bacterial immune system in the human gut microbiomes of 124 European individuals and used it to identify a catalog of 991 phages targeted by CRISPR across all individuals. Our results show that 78% of these phages are shared among two or more individuals. Moreover, a significant fraction of phages found in our study are shown to exist in fecal samples previously derived from American and Japanese individuals, identifying a common reservoir of phages frequently associated with the human gut microbiome. We further inferred the bacterial hosts for more than 130 such phages, enabling a detailed analysis of phage–bacteria interactions across the 124 individuals by correlating patterns of phage abundance with bacterial abundance and resistance. A subset of phages demonstrated preferred association with host genomes as lysogenized prophages, with highly increased abundance in specific individuals. Overall, our results imply that phage–bacterial attack–resistance interactions occur within the human gut microbiome, possibly affecting microbiota composition and human health. Our finding of global sharing of gut phages is surprising in light of the extreme genetic diversity of phages found in other ecological niches.

    Footnotes

    • 5 Corresponding author

      E-mail rotem.sorek{at}weizmann.ac.il

    • [Supplemental material is available for this article.]

    • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.138297.112.

    • Received February 2, 2012.
    • Accepted April 25, 2012.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.

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