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Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients

Author

Listed:
  • David Michalovich

    (Adaptive Immunity Research Unit, GSK R&D)

  • Noelia Rodriguez-Perez

    (University of Zurich)

  • Sylwia Smolinska

    (Wroclaw Medical University
    ALL-MED’ Medical Research Institute)

  • Michal Pirozynski

    (Centre of Postgraduate Medical Education)

  • David Mayhew

    (Computational Biology, Human Genetics, GSK R&D)

  • Sorif Uddin

    (Adaptive Immunity Research Unit, GSK R&D
    Boehringer Ingelheim)

  • Stephanie Horn

    (Target and Pathway Validation, Target Sciences, GSK R&D)

  • Milena Sokolowska

    (University of Zurich
    Christine Kühne-Center for Allergy Research and Education (CK-CARE))

  • Can Altunbulakli

    (University of Zurich)

  • Andrzej Eljaszewicz

    (University of Zurich
    Christine Kühne-Center for Allergy Research and Education (CK-CARE)
    Medical University of Bialystok)

  • Benoit Pugin

    (University of Zurich)

  • Weronika Barcik

    (University of Zurich)

  • Magdalena Kurnik-Lucka

    (Jagiellonian University Medical College)

  • Ken A. Saunders

    (Adaptive Immunity Research Unit, GSK R&D)

  • Karen D. Simpson

    (Adaptive Immunity Research Unit, GSK R&D)

  • Peter Schmid-Grendelmeier

    (Christine Kühne-Center for Allergy Research and Education (CK-CARE)
    University Hospital Zürich)

  • Ruth Ferstl

    (University of Zurich
    Christine Kühne-Center for Allergy Research and Education (CK-CARE))

  • Remo Frei

    (University of Zurich
    Christine Kühne-Center for Allergy Research and Education (CK-CARE))

  • Noriane Sievi

    (University Hospital of Zurich)

  • Malcolm Kohler

    (University Hospital of Zurich)

  • Pawel Gajdanowicz

    (Wroclaw Medical University
    ALL-MED’ Medical Research Institute)

  • Katrine B. Graversen

    (Technical University of Denmark)

  • Katrine Lindholm Bøgh

    (Technical University of Denmark)

  • Marek Jutel

    (Wroclaw Medical University
    ALL-MED’ Medical Research Institute)

  • James R. Brown

    (Computational Biology, Human Genetics, GSK R&D)

  • Cezmi A. Akdis

    (University of Zurich
    Christine Kühne-Center for Allergy Research and Education (CK-CARE))

  • Edith M. Hessel

    (Adaptive Immunity Research Unit, GSK R&D)

  • Liam O’Mahony

    (University of Zurich
    National University of Ireland)

Abstract

In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.

Suggested Citation

  • David Michalovich & Noelia Rodriguez-Perez & Sylwia Smolinska & Michal Pirozynski & David Mayhew & Sorif Uddin & Stephanie Horn & Milena Sokolowska & Can Altunbulakli & Andrzej Eljaszewicz & Benoit Pu, 2019. "Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13751-9
    DOI: 10.1038/s41467-019-13751-9
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    Cited by:

    1. Urszula Radzikowska & Andrzej Eljaszewicz & Ge Tan & Nino Stocker & Anja Heider & Patrick Westermann & Silvio Steiner & Anita Dreher & Paulina Wawrzyniak & Beate Rückert & Juan Rodriguez-Coira & Damir, 2023. "Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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