Microbiota contribute to obesity-related increases in the pulmonary response to ozone.Am J Respir Cell Mol Biol 2019AJ
Obesity is a risk factor for asthma, especially non-atopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a non-atopic asthma trigger.
The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone.
Obese db/db mice were treated with a cocktail of antibiotics, or fed diets rich in pectin or cellulose prior to ozone exposure. Airway responsiveness was assessed 24 hours after exposure. In addition, germ free mice were gavaged with colonic contents from obese or lean mice two weeks prior to exposure and evaluation.
MEASUREMENTS AND MAIN RESULTS
Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in db/db mice than in lean controls. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ free mice that had been reconstituted with colonic contents of db/db versus wildtype mice. In addition, compared to dietary supplementation with the non-fermentable fiber, cellulose, dietary supplementation with the fermentable fiber, pectin, attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A.
Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger, and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese asthmatic patients.