Editors' ChoiceAsthma

Weighing in on asthma

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Science Translational Medicine  15 Jan 2020:
Vol. 12, Issue 526, eaba2907
DOI: 10.1126/scitranslmed.aba2907

Abstract

Immune activation and microbiota alterations are accentuated in obese asthmatics.

Over the last few decades, the numbers of obese individuals have dramatically increased worldwide, and since 2016, there are more obese than underweight humans populating the earth. Thus, the contribution of obesity to overall health and disease will become increasingly relevant. Besides well-known associations with cardiovascular disease, obesity is linked to various inflammatory conditions, such as asthma. In asthma, increased body mass index is known to be associated with poorer treatment responses, increased hospitalization rates, and increased severity of disease.

In this study, Michalovich et al. characterized the immunological and microbiota changes occurring in asthma patients in the context of obesity. Compared with nonobese controls, the authors found increased inflammatory markers and infiltrating immune cells in bronchoalveolar lavage samples of obese patients even in the absence of overt lung disease, consistent with the fact that obesity can predispose to asthma development. Pathway analyses revealed that genes associated with inflammatory and innate immune responses were accentuated in the blood of obese asthmatics and to a lesser extent in obese nonasthmatics, suggesting additive effects of obesity and asthma, but this connection was less evident in bronchial tissue.

16S ribosomal RNA profiling of bronchoalveolar lavage samples demonstrated that obesity and asthma also had additive effects on microbiome alterations. Interestingly, specific gut microbiome enterotypes correlated with increased serum levels of proinflammatory chemokines such as CCL13 and CCL17. Patients with severe asthma showed significant decreases in the species Akkermansia muciniphila in the gut compared with patients with mild and moderate asthma, regardless of whether they were obese. In a mouse model of ovalbumin-induced respiratory airway disease, the authors demonstrated that oral administration of live, but not heat-killed, A. muciniphila reduced airway inflammation, suggesting that true microbiome alterations are mediating this effect.

Although there seems to be a high level of complexity in the interplay between obesity, the microbiome, and asthma that still needs to be elucidated in more detail, the authors were able to characterize alterations spanning the airways, gut, and peripheral blood. These body compartments all might be relevant for future treatment approaches in asthma patients.

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