Article | Published:

Allergic inflammation and disease

Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids

Mucosal Immunology volume 11, pages 785795 (2018) | Download Citation

Abstract

The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4 (IL4)-producing CD4+ T cells and decreased levels of circulating immunoglobulin E (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less motile in response to CCL19 in vitro, and exhibit a dampened ability to transport inhaled allergens to lung draining nodes. Our data thus demonstrate that gut dysbiosis can exacerbate allergic lung inflammation through both T cell- and DC-dependent mechanisms that are inhibited by SCFAs.

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Acknowledgements

We thank the BRC Animal Care facility; Taka Murakami of the BRC Genotyping facility; Les Rollins, Rupinder Dhesi, and Michael Williams of the BRC core staff; and Ingrid Barta of the BRC histology facility.

Author contributions

A.C. and M.R.H. conceived and initiated the project, planned and performed the experiments, analyzed the data, and wrote the manuscript. F.A. planned and performed experiments, and analyzed the data. P.A.D. and K.R.M. assisted with data analysis. L.A.R. planned and performed experiments. J.C., L.H., and J.M. performed experiments. C.Z., K.M.M., B.B.F., and W.W.M. co-supervised the study. C.Z., K.M.M., and W.W.M. edited the manuscript.

Author information

Affiliations

  1. Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada

    • A Cait
    • , P A Dimitriu
    • , K R Maas
    • , B B Finlay
    •  & W W Mohn
  2. The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, Canada

    • M R Hughes
    • , F Antignano
    • , J Cait
    • , L Hacker
    • , J Mohr
    •  & K M McNagny
  3. Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada

    • L A Reynolds
    •  & B B Finlay
  4. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada

    • B B Finlay
  5. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    • C Zaph
  6. Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

    • C Zaph
  7. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

    • K M McNagny

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Competing interests

The authors declared no conflict of interest.

Corresponding authors

Correspondence to M R Hughes or W W Mohn.

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DOI

https://doi.org/10.1038/mi.2017.75

SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/mi

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