1. Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
2. Channing Laboratory, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
3. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
4. These authors contributed equally to this work.

Correspondence to: Sarkis K. Mazmanian^1,4Dennis L. Kasper^2,3 Correspondence and requests for materials should be addressed to S.K.M. (Email: sarkis@caltech.edu) or D.L.K. (Email: dennis_kasper@hms.harvard.edu).

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.

1. Division of Biology, California Institute of Technology, Pasadena, California 91125, USA
2. Channing Laboratory, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
3. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
4. These authors contributed equally to this work.

Correspondence to: Sarkis K. Mazmanian^1,4Dennis L. Kasper^2,3 Correspondence and requests for materials should be addressed to S.K.M. (Email: sarkis@caltech.edu) or D.L.K. (Email: dennis_kasper@hms.harvard.edu).

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