Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes

Edited by Peter K. Vogt, The Scripps Research Institute, La Jolla, CA, and approved September 8, 2010 (received for review August 5, 2010)
October 4, 2010
107 (42) 18132-18137

Abstract

Intestinal health requires the coexistence of eukaryotic self with the gut microbiota and dysregulated host-microbial interactions can result in intestinal inflammation. Here, we show that colitis improved in T-bet−/−Rag2−/− mice that consumed a fermented milk product containing Bifidobacterium animalis subsp. lactis DN-173 010 strain. A decrease in cecal pH and alterations in short chain fatty acid profiles occurred with consumption, and there were concomitant increases in the abundance of select lactate-consuming and butyrate-producing bacteria. These metabolic shifts created a nonpermissive environment for the Enterobacteriaceae recently identified as colitogenic in a T-bet−/−Rag2−/− ulcerative colitis mouse model. In addition, 16S rRNA-based analysis of the T-bet−/−Rag2−/−fecal microbiota suggest that the structure of the endogenous gut microbiota played a key role in shaping the host response to the bacterial strains studied herein. We have identified features of the gut microbiota, at the membership and functional level, associated with response to this B. lactis-containing fermented milk product, and therefore this model provides a framework for evaluating and optimizing probiotic-based functional foods.

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Data Availability

Data deposition: The 454 pyrosequencing reads reported in this paper have been deposited in the NCBI Short Read Archive (accession no. SRX025834.5).

Acknowledgments

We thank D. Zhang for histology expertise and M. Montesalvo and staff of the University of Massachusetts Lowell Radiation Laboratory for use of their Gamma Cave Irradiator Facility. This work was supported by National Institutes of Health Grants CA112663 (to L.H.G.) and K08AIO78942 (to W.S.G.) and by a grant from Danone Research.

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 107 | No. 42
October 19, 2010
PubMed: 20921388

Classifications

Data Availability

Data deposition: The 454 pyrosequencing reads reported in this paper have been deposited in the NCBI Short Read Archive (accession no. SRX025834.5).

Submission history

Published online: October 4, 2010
Published in issue: October 19, 2010

Keywords

  1. Enterobacteriaceae
  2. intestinal inflammation
  3. microbiota
  4. probiotics
  5. colitis

Acknowledgments

We thank D. Zhang for histology expertise and M. Montesalvo and staff of the University of Massachusetts Lowell Radiation Laboratory for use of their Gamma Cave Irradiator Facility. This work was supported by National Institutes of Health Grants CA112663 (to L.H.G.) and K08AIO78942 (to W.S.G.) and by a grant from Danone Research.

Notes

This article is a PNAS Direct Submission.

Authors

Affiliations

Patrick Veiga
Harvard School of Public Health, Boston, MA 02115;
Danone Research, 91767 Palaiseau, France
Carey Ann Gallini
Harvard School of Public Health, Boston, MA 02115;
Chloé Beal
Danone Research, 91767 Palaiseau, France
Monia Michaud
Harvard School of Public Health, Boston, MA 02115;
Mary L. Delaney
Brigham and Women's Hospital, Boston, MA 02115;
Andrea DuBois
Brigham and Women's Hospital, Boston, MA 02115;
Artem Khlebnikov
Danone Research, 91767 Palaiseau, France
Dannon Company Inc., White Plains, NY 10603;
Johan E.T. van Hylckama Vlieg
Danone Research, 91767 Palaiseau, France
Shivesh Punit
Harvard School of Public Health, Boston, MA 02115;
Present address: Department of Cell and Developmental Biology, University of Southern California, Health Sciences Campus, Los Angeles, CA 90089.
Jonathan N. Glickman
Brigham and Women's Hospital, Boston, MA 02115;
Harvard Medical School, Boston, MA 02115;
Present address: GI Pathology, Boston Caris Diagnostics, Newton, MA 02464.
Andrew Onderdonk
Brigham and Women's Hospital, Boston, MA 02115;
Harvard Medical School, Boston, MA 02115;
Laurie H. Glimcher
Harvard School of Public Health, Boston, MA 02115;
Dannon Company Inc., White Plains, NY 10603;
Harvard Medical School, Boston, MA 02115;
Ragon Institute of MGH, MIT and Harvard, Charlestown, MA 02129; and
Wendy S. Garrett3 [email protected]
Harvard School of Public Health, Boston, MA 02115;
Harvard Medical School, Boston, MA 02115;
Dana Farber Cancer Institute, Boston, MA 02115

Notes

3
To whom correspondence should be addressed. E-mail: [email protected].
Author contributions: P.V., A.K., J.E.T.v.H.V., A.O., L.H.G., and W.S.G. designed research; P.V., C.A.G., C.B., M.M., M.L.D., A.D., S.P., and W.S.G. performed research; P.V., C.A.G., C.B., M.M., M.L.D., A.D., J.E.T.v.H.V., J.N.G., A.O., and W.S.G. analyzed data; and P.V. and W.S.G. wrote the paper.

Competing Interests

Conflict of interest statement: L.H.G. is a member of the Board of Directors of and holds equity in the Bristol Myers Squibb Corporation. P.V., C.B., A.K., and J.E.T.v.H.V. are employees of and hold equity in Groupe Danone.

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    Bifidobacterium animalis subsp. lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes
    Proceedings of the National Academy of Sciences
    • Vol. 107
    • No. 42
    • pp. 17853-18231

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