Sex Differences in the Impact of Dietary Fiber on Pulmonary Responses to Ozone

Ozone causes airway hyperresponsiveness, a defining feature of asthma. We have reported that the gut microbiome contributes to sex differences in ozone-induced airway hyperresponsiveness. Altering dietary fiber affects the gut microbiome. The purpose of this study was to determine the effects of dietary fiber on pulmonary responses to ozone and whether these effects differ by sex. We fed male and female mice fiber-free diets or diets enriched in one of two types of dietary fiber, cellulose and pectin, for 3 days before ozone exposure. Compared with control diets or pectin-enriched diets, cellulose-enriched diets attenuated ozone-induced airway hyperresponsiveness in male but not female mice. In contrast, fiber-free diets augmented responses to ozone in female but not male mice. Analysis of 16S rRNA sequencing of fecal DNA also indicated sex differences in the impact of dietary fiber on the gut microbiome and identified bacterial taxa that were associated with ozone-induced airway hyperresponsiveness. Our data suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for air pollution-triggered asthma, but they indicate that such therapeutics may need to be tailored differently for males and females.