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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
13 12 2019
Historique:
received: 05 03 2019
accepted: 13 11 2019
entrez: 15 12 2019
pubmed: 15 12 2019
medline: 3 4 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 31836714
doi: 10.1038/s41467-019-13751-9
pii: 10.1038/s41467-019-13751-9
pmc: PMC6911092
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5711

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Auteurs

David Michalovich (D)

Adaptive Immunity Research Unit, GSK R&D, Stevenage, UK.

Noelia Rodriguez-Perez (N)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Sylwia Smolinska (S)

Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland.
ALL-MED' Medical Research Institute, Wroclaw, Poland.

Michal Pirozynski (M)

Department of Allergology and Pulmonology, Centre of Postgraduate Medical Education, Warsaw, Poland.

David Mayhew (D)

Computational Biology, Human Genetics, GSK R&D, Collegeville, PA, USA.

Sorif Uddin (S)

Adaptive Immunity Research Unit, GSK R&D, Stevenage, UK.
Boehringer Ingelheim, 88397, Biberach an der Riß, Germany.

Stephanie Van Horn (S)

Target and Pathway Validation, Target Sciences, GSK R&D, Collegeville, PA, USA.

Milena Sokolowska (M)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.

Can Altunbulakli (C)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Andrzej Eljaszewicz (A)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.

Benoit Pugin (B)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Weronika Barcik (W)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Magdalena Kurnik-Lucka (M)

Department of Pathophysiology, Jagiellonian University Medical College, Krakow, Poland.

Ken A Saunders (KA)

Adaptive Immunity Research Unit, GSK R&D, Stevenage, UK.

Karen D Simpson (KD)

Adaptive Immunity Research Unit, GSK R&D, Stevenage, UK.

Peter Schmid-Grendelmeier (P)

Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
Allergy Unit, Department of Dermatology, University Hospital Zürich, Zürich, Switzerland.

Ruth Ferstl (R)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.

Remo Frei (R)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.

Noriane Sievi (N)

Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.

Malcolm Kohler (M)

Pulmonary Division, University Hospital of Zurich, Zurich, Switzerland.

Pawel Gajdanowicz (P)

Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland.
ALL-MED' Medical Research Institute, Wroclaw, Poland.

Katrine B Graversen (KB)

National Food Institute, Technical University of Denmark, Copenhagen, Denmark.

Katrine Lindholm Bøgh (K)

National Food Institute, Technical University of Denmark, Copenhagen, Denmark.

Marek Jutel (M)

Department of Clinical Immunology, Wroclaw Medical University, Wroclaw, Poland.
ALL-MED' Medical Research Institute, Wroclaw, Poland.

James R Brown (JR)

Computational Biology, Human Genetics, GSK R&D, Collegeville, PA, USA.

Cezmi A Akdis (CA)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.

Edith M Hessel (EM)

Adaptive Immunity Research Unit, GSK R&D, Stevenage, UK.

Liam O'Mahony (L)

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland. liam.omahony@ucc.ie.
Depts of Medicine and Microbiology, APC Microbiome Ireland, National University of Ireland, Cork, Ireland. liam.omahony@ucc.ie.

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