DRP004755
The microbiome contributes to obesity-related increases in the pulmonary response to ozone
Obesity is a risk factor for asthma, especially non-atopic asthma, and attenuates the efficacy of standard asthma therapeutics.  Obesity augments pulmonary responses to ozone, a non-atopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in the gut microbiome contribute to these augmented responses to ozone.  Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese, db/db mice than in lean, wildtype controls and treatment with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for the microbiome.  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 a dietary supplementation with a non-fermentable fiber, cellulose, dietary supplementation with the fermentable fiber, pectin, attenuated obesity-related increases in the pulmonary response to ozone.  Serum short chain fatty acids were greater in obese than lean mice and in pectin- versus cellulose-fed mice, but experiments using treatment with propionate or fiber free diets indicated that microbial modulation of the immune system rather than changes in short chain fatty acids likely accounted for the beneficial effects of pectin.  Our data indicate a role for the microbiome in obesity-related increases in the response to an asthma trigger, and suggest that microbiome-based therapies such as probiotics and prebiotics may provide an alternative therapeutic strategy for obese asthmatic patients.