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A microbial symbiosis factor prevents intestinal inflammatory disease

Mazmanian, Sarkis K. and Round, June L. and Kasper, Dennis L. (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature, 453 (7195). pp. 620-5. ISSN 0028-0836.

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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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Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2008 Nature Publishing Group. Received 7 February; accepted 18 April 2008. 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. Sarkis K. Mazmanian and June L. Round: These authors contributed equally to this work.
Funding AgencyGrant Number
Helen Hay Whitney FoundationUNSPECIFIED
Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
NIHR01 AI039576
Searle Scholars ProgramUNSPECIFIED
Damon Runyon Cancer Research FoundationUNSPECIFIED
Crohn’s and Colitis Foundation of AmericaUNSPECIFIED
Issue or Number:7195
Record Number:CaltechAUTHORS:20200305-103405064
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:101722
Deposited By: Yvette Garcia-Flores
Deposited On:05 Mar 2020 19:47
Last Modified:05 Mar 2020 19:47

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