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Published October 12, 2016 | Supplemental Material + Accepted Version
Journal Article Open

Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

Abstract

Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPSs to interact with the host as well as those with potential probiotic properties.

Additional Information

© 2016 Elsevier. Received 18 November 2015; revised 19 July 2016; accepted 8 September 2016; available online 29 September 2016. We would like to thank Ashleigh Jones for her technical assistance with the mouse experiments. We would also like to express deep gratitude to Eric Martens for sharing with us the pKNOCK-bla-ermGb vector and for his guidance in conducting insertional transposon mutagenesis. This work was funded from R01 DK104047. C.A.L. was also supported by K01 DK090285. C.P.N. was supported by NIH T32 AI007405. C.B.C. was supported by K01 DK099403. S.K.M. is a co-founder of Symbiotix Biotherapies, which did not sponsor this work, nor is the company developing any potential technologies described here.

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Accepted Version - nihms816601.pdf

Supplemental Material - mmc1.pdf

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