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

Nature volume 487, pages 104–108 (2012)Cite this article

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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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Authors and 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

Authors

  1. Suzanne Devkota
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  2. Yunwei Wang
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  3. Mark W. Musch
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  4. Vanessa Leone
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  5. Hannah Fehlner-Peach
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  6. Anuradha Nadimpalli
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  7. Dionysios A. Antonopoulos
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  8. Bana Jabri
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  9. Eugene B. Chang
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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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Correspondence toEugene B. Chang.

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The authors declare no competing financial interests.

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Devkota, S., Wang, Y., Musch, M. et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10 −/− mice.Nature 487, 104–108 (2012). https://doi.org/10.1038/nature11225

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Editorial Summary

Gut flora modified by milk fats

Milk fat is shown here to potentiate experimental colitis in susceptible mice, in association with increased luminal concentrations of sulphite-reducing bacteria. Mice fed a diet with comparable caloric intake containing unsaturated fatty acids are protected. The inflammation is caused by milk-fat-promoted taurine conjugation with bile acids, which increases the availability of organic sulphur used by the bacteria. This finding supports the suggestion that the recent upwards trend in complex immune disorders such as inflammatory bowel diseases could reflect changes in human microbiomes elicited in genetically susceptible individuals by dietary and other environmental changes.

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