1. Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients.
- Author
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Michalovich D, Rodriguez-Perez N, Smolinska S, Pirozynski M, Mayhew D, Uddin S, Van Horn S, Sokolowska M, Altunbulakli C, Eljaszewicz A, Pugin B, Barcik W, Kurnik-Lucka M, Saunders KA, Simpson KD, Schmid-Grendelmeier P, Ferstl R, Frei R, Sievi N, Kohler M, Gajdanowicz P, Graversen KB, Lindholm Bøgh K, Jutel M, Brown JR, Akdis CA, Hessel EM, and O'Mahony L
- Subjects
- Adult, Akkermansia, Animals, Asthma complications, Asthma diagnosis, Asthma microbiology, Disease Models, Animal, Feces microbiology, Female, Forced Expiratory Volume, Healthy Volunteers, Humans, Male, Mice, Middle Aged, Obesity complications, Obesity microbiology, Respiratory System immunology, Severity of Illness Index, Verrucomicrobia isolation & purification, Asthma immunology, Gastrointestinal Microbiome immunology, Host Microbial Interactions immunology, Obesity immunology, Verrucomicrobia immunology
- 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.
- Published
- 2019
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