Letter | Published:

Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice

Nature volume 487, pages 104108 (05 July 2012) | Download Citation

Abstract

The composite human microbiome of Western populations has probably changed over the past century, brought on by new environmental triggers that often have a negative impact on human health1. Here we show that consumption of a diet high in saturated (milk-derived) fat, but not polyunsaturated (safflower oil) fat, changes the conditions for microbial assemblage and promotes the expansion of a low-abundance, sulphite-reducing pathobiont, Bilophila wadsworthia2. This was associated with a pro-inflammatory T helper type 1 (TH1) immune response and increased incidence of colitis in genetically susceptible Il10−/−, but not wild-type mice. These effects are mediated by milk-derived-fat-promoted taurine conjugation of hepatic bile acids, which increases the availability of organic sulphur used by sulphite-reducing microorganisms like B. wadsworthia. When mice were fed a low-fat diet supplemented with taurocholic acid, but not with glycocholic acid, for example, a bloom of B. wadsworthia and development of colitis were observed in Il10−/− mice. Together these data show that dietary fats, by promoting changes in host bile acid composition, can markedly alter conditions for gut microbial assemblage, resulting in dysbiosis that can perturb immune homeostasis. The data provide a plausible mechanistic basis by which Western-type diets high in certain saturated fats might increase the prevalence of complex immune-mediated diseases like inflammatory bowel disease in genetically susceptible hosts.

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Primary accessions

GenBank/EMBL/DDBJ

Data deposits

Data have been deposited in GenBank under accession numbers JQ890637–JQ894320.

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Acknowledgements

This work was supported by the National Center for Research Resources and the NIDDK, NIGMS and NCCAM of the National Institutes of Health through grant number DK-42086 (E.B.C.), DK47722 (E.B.C.), UH3DK083993 (E.B.C.), F31AT006073 (S.D.). Also, the Gastrointestinal Research Foundation, Crohns and Colitis Foundation of America (Y.W.), the Peter and Carol Goldman Family Research Fund, and the Harry and Leona Helmsley Trust Foundation (SHARE). We are also indebted to S. Finegold for his suggestions on successful culture of B. wadsworthia and Alistipes, J. Tiedje and M. Vital for dsrA primer sequences, L. Hagey for mass spectrometry, E. Huang, B. Theriault and J. Stencel for assistance with experiments, and R. Bouziat for T-cell purification.

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Affiliations

  1. Department of Medicine, Section of Gastroenterology, The University of Chicago, Knapp Center for Biomedical Discovery, 900 East 57th Street, Chicago, Illinois 60637, USA

    • Suzanne Devkota
    • , Yunwei Wang
    • , Mark W. Musch
    • , Vanessa Leone
    • , Hannah Fehlner-Peach
    • , Anuradha Nadimpalli
    • , Bana Jabri
    •  & Eugene B. Chang
  2. Institute for Genomics and Systems Biology, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA

    • Dionysios A. Antonopoulos

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Contributions

S.D. and E.B.C. were involved in all aspects of this study, especially in the development of the hypothesis, experimental plan and data analysis. Y.W., M.W.M., V.L., H.F.-P. and A.N. helped perform the experiments. D.A.A. and B.J. provided critical feedback and expertise and assisted in the analysis of data.

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Eugene B. Chang.

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https://doi.org/10.1038/nature11225

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