Article | Published:

A microbial symbiosis factor prevents intestinal inflammatory disease

Nature volume 453, pages 620625 (29 May 2008) | Download Citation

Abstract

Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.

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Acknowledgements

We thank R. T. Bronson for discussions about histopathology; members of the Mazmanian laboratory for critical comments throughout the course of the work; and J. McCoy for editorial expertise. S.K.M. acknowledges a fellowship from the Helen Hay Whitney Foundation; J.L.R. acknowledges support from the Jane Coffin Childs Memorial Fund. This work was supported by funding from the NIH/NIAID (R01 AI039576) to D.L.K., and by grants from the Searle Scholars Program, the Damon Runyon Cancer Research Foundation, and the Crohn’s and Colitis Foundation of America to S.K.M.

Author Contributions S.K.M., J.L.R. and D.L.K. designed the research; S.K.M. and J.L.R. performed the research; S.K.M., J.L.R. and D.L.K. analysed the data and wrote the paper.

Author information

Author notes

    • Sarkis K. Mazmanian
    •  & June L. Round

    These authors contributed equally to this work.

Affiliations

  1. Division of Biology, California Institute of Technology, Pasadena, California 91125, USA

    • Sarkis K. Mazmanian
    •  & June L. Round
  2. Channing Laboratory, Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Dennis L. Kasper
  3. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Dennis L. Kasper

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Correspondence to Sarkis K. Mazmanian or Dennis L. Kasper.

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    The file contains Supplementary Figures 1 – 8 with Legends and Supplementary Methods with additional references.

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DOI

https://doi.org/10.1038/nature07008

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