Dataset Information

Early life microbiome perturbation alters pulmonary responses to ozone in male mice.

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.

SUBMITTER: Brown TA

PROVIDER: S-EPMC6981302 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Early life microbiome perturbation alters pulmonary responses to ozone in male mice.

Brown Traci A TA Tashiro Hiroki H Kasahara David I DI Cho Youngji Y Shore Stephanie A SA

Physiological reports 20200101 2

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 Labor ...[more]

PMID: 31981310

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Project description:BACKGROUND:Interleukin-33 is released in the airways following acute ozone exposure and has the ability to cause airway hyperresponsiveness, a defining feature of asthma. Ozone causes greater airway hyperresponsiveness in male than female mice. Moreover, sex differences in the gut microbiome account for sex differences in this response to ozone. The purpose of this study was to determine whether there were sex differences in the role of interleukin-33 in ozone-induced airway hyperresponsiveness and to examine the role of the microbiome in these events. METHODS:Wildtype mice and mice genetically deficient in ST2, the interleukin-33 receptor, were housed from weaning with either other mice of the same genotype and sex, or with mice of the same sex but opposite genotype. At 15?weeks of age, fecal pellets were harvested for 16S rRNA sequencing and the mice were then exposed to air or ozone. Airway responsiveness was measured and a bronchoalveolar lavage was performed 24?h after exposure. RESULTS:In same-housed mice, ozone-induced airway hyperresponsiveness was greater in male than female wildtype mice. ST2 deficiency reduced ozone-induced airway hyperresponsiveness in male but not female mice and abolished sex differences in the response to ozone. However, sex differences in the role of interleukin-33 were unrelated to type 2 cytokine release: ozone-induced increases in bronchoalveolar lavage interleukin-5 were greater in females than males and ST2 deficiency virtually abolished interleukin-5 in both sexes. Since gut microbiota contribute to sex differences in ozone-induced airway hyperresponsiveness, we examined the role of the microbiome in these ST2-dependent sex differences. To do so, we cohoused wildtype and ST2 deficient mice, a situation that allows for transfer of microbiota among cage-mates. Cohousing altered the gut microbial community structure, as indicated by 16S rRNA gene sequencing of fecal DNA and reversed the effect of ST2 deficiency on pulmonary responses to ozone in male mice. CONCLUSIONS:The data indicate that the interleukin-33 /ST2 pathway contributes to ozone-induced airway hyperresponsiveness in male mice and suggest that the role of interleukin-33 is mediated at the level of the gut microbiome.

Dataset Information

Early life microbiome perturbation alters pulmonary responses to ozone in male mice.

Publications

Early life microbiome perturbation alters pulmonary responses to ozone in male mice.

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