Abstract
Early life changes in the microbiome contribute to the development of allergic asthma, but little is known about the importance of the microbiome for other forms of asthma. Ozone is a nonatopic asthma trigger that causes airway hyperresponsiveness and neutrophil recruitment to the lungs. The purpose of this study was to test the hypothesis that early life perturbations in the gut microbiome influence subsequent responses to ozone. To that end, we placed weanling mouse pups from The Jackson Laboratories or from Taconic Farms in sex‐specific cages either with other mice from the same vendor (same‐housed) or with mice from the opposite vendor (cohoused). Mice were maintained with these cagemates until use. The gut microbial community differs in mice from Jackson Labs and Taconic Farms, and cohousing mice transfers fecal microbiota from one mouse to another. Indeed, 16S rRNA sequencing of fecal DNA indicated that differences in the gut microbiomes of Jackson and Taconic same‐housed mice were largely abolished when the mice were cohoused. At 10–12 weeks of age, mice were exposed to room air or ozone (2 ppm for 3 hr). Compared to same‐housed mice, cohoused male but not female mice had reduced ozone‐induced airway hyperresponsiveness and reduced ozone‐induced increases in bronchoalveolar lavage neutrophils. Ozone‐induced airway hyperresponsiveness was greater in male than in female mice and the sex difference was largely abolished in cohoused mice. The data indicate a role for early life microbial perturbations in pulmonary responses to a nonallergic asthma trigger.
Highlights
Early exposure to antibiotics increases the risk of obesity, consistent with a role for the microbiome in metabolism (Arrieta et al, 2015)
The data indicate a role for early life microbial perturbations in pulmonary responses to a nonallergic asthma trigger
bronchoalveolar lavage (BAL) protein was significantly greater in same-housed Jackson than Taconic mice exposed to ozone, but there was no significant difference in BAL protein in cohoused versus same housed mice from either vendor after ozone exposure
Summary
Ozone recruits neutrophils to the airways and increases the production of acute phase cytokines and chemokines (Balmes et al, 1997). Mice exhibit AHR and increases in bronchoalveolar lavage (BAL) neutrophils after acute ozone exposure (Cho, Zhang, & Kleeberger, 2001; Zhang, Levitt, & Kleeberger, 1995). Life is a critical period for gut colonization with bacteria, and perturbations in the gut microbiome during this time can impact physiological systems which are maturing simultaneously (Zeissig & Blumberg, 2014). In mice, early exposure to antibiotics shifts the Th1/Th2 immune system balance toward a more Th2 dominant profile, including increase in production of interleukin-4 and IgE (Oyama, Sudo, Sogawa, & Kubo, 2001). Early exposure to antibiotics increases the risk of obesity, consistent with a role for the microbiome in metabolism (Arrieta et al, 2015)
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