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

Autor: Hiroki Tashiro, Vladimir Yeliseyev, Stephanie A. Shore, David I. Kasahara, Ross S. Osgood, Lynn Bry
Rok vydání: 2020
Předmět:
Zdroj: Physiological Reports
Physiological Reports, Vol 8, Iss 19, Pp n/a-n/a (2020)
ISSN: 2051-817X
DOI: 10.14814/phy2.14584
Popis: 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.
While sex differences in ozone‐induced airway hyperresponsiveness (AHR) are apparent in mouse models, the role of androgens in ozone‐induced AHR have not been examined. Our data confirm previous reports that gut microbiota have the potential to impact host inflammatory responses to ozone and indicate that effects of these microbiota on systemic inflammation may contribute to responses to ozone. A better understanding of the mechanisms by which sex hormones manipulate the gut microbiome may ultimately lead to improved treatment of lung diseases such as asthma.
Databáze: OpenAIRE