Gut microbiota from androgen-altered donors alter pulmonary responses to ozone in female mice

In mice, both androgens and the gut microbiota modify pulmonary responses to ozone. We hypothesized that androgens affect gut microbiota and thereby impact pulmonary responses to ozone. To address this hypothesis, we transferred cecal microbiota from male castrated or sham castrated C57BL/6J mice into female germ-free recipient C57BL/6J mice. Four weeks later mice were exposed to ozone (2 ppm) or room air for 3 hr. The gut microbiomes of castrated versus sham castrated donors differed, as did those of recipients of microbiota from castrated versus sham castrated donors. In recipients, ozone-induced airway hyperresponsiveness was not affected by donor castration status. However, compared to mice receiving microbiota from sham castrated donors, mice receiving microbiota from castrated donors had elevated numbers of bronchoalveolar lavage (BAL) neutrophils despite evidence of reduced lung injury as measured by BAL protein. Serum concentrations of IL-17A and G-CSF were significantly greater in recipients of castrated versus sham castrated microbiota. Furthermore, BAL neutrophils correlated with both serum IL-17A and serum G-CSF. Our data indicate that androgen-mediated effects on the gut microbiota modulate pulmonary inflammatory responses to ozone and suggest a role for circulating IL-17A and G-CSF in these events.