• A Corrigendum to this article was published on 04 March 2015


Yeasts, which have been a component of the human diet for at least 7,000 years, possess an elaborate cell wall α-mannan. The influence of yeast mannan on the ecology of the human microbiota is unknown. Here we show that yeast α-mannan is a viable food source for the Gram-negative bacterium Bacteroides thetaiotaomicron, a dominant member of the microbiota. Detailed biochemical analysis and targeted gene disruption studies support a model whereby limited cleavage of α-mannan on the surface generates large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes. Co-culturing studies showed that metabolism of yeast mannan by B. thetaiotaomicron presents a ‘selfish’ model for the catabolism of this difficult to breakdown polysaccharide. Genomic comparison with B. thetaiotaomicron in conjunction with cell culture studies show that a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet.

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Data deposits

The protein crystal structures reported in this study have been deposited under the following PDB accession codes: 4C1R (BT3783-Mg binary complex); 4C1S (BT3792); and 4UTF (BxGH99/Man-IFG/mannobiose ternary complex).


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This work was supported by grants from the European Research Council (G.J.D., Glycopoise; H.J.G., No. 322820), The Wellcome Trust (H.J.G., WT097907AIA), BBSRC (M.J.T., G.J.D.; BB/G016127/1), US Department of Energy (DOE) Bioenergy Research Center (BESC) supported by the Office of Biological and Environmental Research in the DOE Office of Science (M.J.P.) and the National Institutes of Health (E.C.M. and T.J.T., GM090080). Gnotobiotic mouse experiments were supported by a subsidy from the University of Michigan Medical School Host Microbiome Initiative, Agriculture and Agri-Food Canada, AgriFlex (D.W.A., #2510), Canadian Institute of Health Research operating grant (A.B.B., MOP-68913), Australian Research Council; Mizutani Foundation (S.J.W.). We thank the staff of the Diamond Light Source for the provision of beamline facilities. We would also like to thank various members of ICaMB for providing the yeast strains used in this work. We were greatly saddened by the passing of C.Z. during the course of this work.

Author information

Author notes

    • Fiona Cuskin
    • , Elisabeth C. Lowe
    •  & Max J. Temple

    These authors contributed equally to this work.

    • Cherie J. Ziemer



  1. Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK

    • Fiona Cuskin
    • , Elisabeth C. Lowe
    • , Max J. Temple
    • , Yanping Zhu
    • , Artur Rogowski
    • , Jose L. Munōz-Munōz
    • , Andrew Day
    •  & Harry J. Gilbert
  2. Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, USA

    • Fiona Cuskin
    • , Yanping Zhu
    • , Maria J. Peña
    • , D. Wade Abbott
    •  & Harry J. Gilbert
  3. Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109 USA

    • Elizabeth A. Cameron
    • , Nicholas A. Pudlo
    • , Nathan T. Porter
    • , Karthik Urs
    •  & Eric C. Martens
  4. Department of Chemistry, University of York, York YO10 5DD, UK

    • Andrew J. Thompson
    •  & Gideon J. Davies
  5. School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia

    • Alan Cartmell
    • , Zalihe Hakki
    • , Gaetano Speciale
    •  & Spencer J. Williams
  6. Interdisciplinary Biochemistry Graduate Program, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, USA

    • Brian S. Hamilton
  7. Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, USA

    • Rui Chen
  8. Department of Pharmaceutical Chemistry, University of Kansas School of Pharmacy, 2095 Constant Avenue, Lawrence, Kansas 66047, USA

    • Thomas J. Tolbert
  9. Oxyrane, 9052 Ghent, Belgium

    • Kathleen Piens
    • , Debby Bracke
    •  & Wouter Vervecken
  10. Agriculture and Agri-Food Canada, Lethbridge Research Centre, Lethbridge, Alberta T1J 4B1, Canada

    • Richard McLean
    •  & D. Wade Abbott
  11. Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8P 5C2, Canada

    • Michael D. Suits
    •  & Alisdair B. Boraston
  12. USDA, Agricultural Research Service, National Laboratory for Agriculture and the Environment, Ames, Iowa 50011, USA

    • Todd Atherly
    •  & Cherie J. Ziemer


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Enzyme characterization: F.C., M.J.T., J.L.M.-M. and D.W.A. Capillary electrophoresis: D.B., K.P. and W.V. E.C.L. created gene deletion strains and determined phenotypes with F.C. E.C.L., F.C. and A.R. performed enzyme localisation. F.C. and E.C.L. carried out the co-culturing experiments. Gene expression analysis: E.A.C., N.A.P. and E.C.M. Growth analysis on purified mannans and HMNG: E.C.L., N.A.P., K.U. and E.C.M. Characterization of HMNG binding proteins: Y.Z. Characterization of the Δbt3774 mutant: A.D. Phylogenetic reconstruction and metagenomic analysis: E.C.M. Gnotobiotic mouse experiments: E.A.C., N.A.P., N.T.P. and E.C.M. Purification of HMNG: T.J.T., B.S.H. and R.C. Isolation and genomic analysis of pig gut strains: T.A., C.J.Z. A.C. and G.S. performed NMR experiments on GH76 and M.J.P. on GT products. Z.H. and G.S. synthesized substrates. Crystallographic studies by A.J.T., G.J.D., M.D.S., A.B.B. and R.M. Experiments designed by F.C., E.C.L., G.J.D., S.J.W., D.W.A., E.C.M. and H.J.G. The manuscript was written primarily by H.J.G. and E.C.M. with contributions from S.J.W., G.J.D. and D.W.A. E.C.L. and E.C.M. prepared the figures.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to D. Wade Abbott or Eric C. Martens or Harry J. Gilbert.

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