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Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis

Nature Medicine volume 20, pages 159–166 (2014)Cite this article

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Abstract

Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein–coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.

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Figure 1: A low-fiber diet increased the severity of allergic airway inflammation.
Figure 2: A high-fiber diet decreased susceptibility to allergic airway inflammation.
Figure 3: Dietary fiber content alters the intestinal microbiota and both local and systemic levels of SCFAs.
Figure 4: Mice treated with propionate are protected against the development of allergic airway inflammation.
Figure 5: DCs from the lung-draining lymph nodes of mice treated with propionate are impaired in their ability to induce TH2 cell differentiation.
Figure 6: Propionate treatment increases the production of DC precursors in the bone marrow and results in lung-resident DCs that are less effective at reactivating effector TH2 cells.

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Acknowledgements

This work has been supported by the Swiss National Science Foundation grant 310030.130029 awarded to B.J.M. We thank R. Driscoll and the Fondation Placide Nicod for support and A. Genevaz, B. Berger and E. Rezzonico for scientific assistance related to microbiota analysis. B.J.M. is a Cloetta Medical Research Fellow.

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Authors and Affiliations

  1. Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, BH19.206 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

    Aurélien Trompette, Eva S Gollwitzer, Koshika Yadava, Anke K Sichelstiel, Laurent P Nicod & Benjamin J Marsland

  2. Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland

    Norbert Sprenger, Catherine Ngom-Bru & Carine Blanchard

  3. Novartis Pharma AG, Basel, Switzerland

    Tobias Junt

  4. Global Health Institute, École Polytechnique Fédérale de Lausanne (EPFL)-SV–Global Health Institute (GHI) Station 19, EPFL, Lausanne, Switzerland

    Nicola L Harris

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Contributions

B.J.M. conceived the study. B.J.M. and A.T. designed the study. A.T., E.S.G., K.Y. and A.K.S. performed experiments. A.T. and E.S.G. analyzed data. N.S. performed SCFA analysis. C.N.-B., A.T. and B.J.M. performed microbiota analysis. T.J. provided Ffar3−/− and Ffar2−/− mice. T.J., C.B., N.L.H., L.P.N., E.S.G., A.T. and B.J.M. provided critical analysis and discussions. B.J.M. and A.T. wrote the paper.

Corresponding author

Correspondence to Benjamin J Marsland.

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Competing interests

C.N.-B., C.B. and N.S. are employed by Nestec Ltd, Switzerland. T.J. is employed by Novartis Institutes for Biomedical Research.

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Trompette, A., Gollwitzer, E., Yadava, K. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 20, 159–166 (2014). https://doi.org/10.1038/nm.3444

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