Sex Differences in Pulmonary Responses to Ozone in Mice Role of the Microbiome
Sex Differences in Pulmonary Responses to Ozone in Mice Role of the Microbiome
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DOI：
10.1165/rcmb.2018-0099oc
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发表时间：
2019-02-01
影响因子：
6.4
通讯作者：
Shore, Stephanie A.
中科院分区：
文献类型：
--
作者：
Cho, Youngji;Abu-Ali, Galeb;Shore, Stephanie A.
我们之前已经报道过，小鼠肠道微生物群有助于肺部对臭氧的反应，臭氧是一种常见的哮喘触发因素，而细菌发酵的最终产物短链脂肪酸可能有助于微生物群的这一作用。越来越多的证据表明，肠道微生物区系存在性别差异，这些差异可能会产生重要的功能后果。这项研究的目的是确定肠道微生物区系对肺部对臭氧的反应是否存在性别差异。在急性暴露于臭氧后，雄性小鼠比雌性小鼠表现出更强的呼吸道高反应性。在抗生素消融肠道微生物群后，这种差异被消除。此外，饲养在由成年雄性小鼠调节的笼子中的断奶雌性幼崽比饲养在由成年雌性条件调节的笼子中饲养的断奶雌性幼崽发展出更强的臭氧诱导的呼吸道高反应性。最后，通过饮用水随意口服短链脂肪酸丙酸酯导致雄性小鼠臭氧诱导的呼吸道高反应性增强，但雌性小鼠没有。总体而言，这些数据与微生物组在臭氧诱导的呼吸道高反应性方面存在性别差异的假设是一致的，这可能是由于对短链脂肪酸的反应存在性别差异。
We have previously reported that the mouse gut microbiome contributes to pulmonary responses to ozone, a common asthma trigger, and that short-chain fatty acids, end products of bacterial fermentation, likely contribute to this role of the microbiome. A growing body of evidence indicates that there are sex-related differences in gut microbiota and these differences can have important functional consequences. The purpose of this study was to determine whether there are sex-related differences in the impact of the gut microbiota on pulmonary responses to ozone. After acute exposure to ozone, male mice developed greater airway hyperresponsiveness than female mice. This difference was abolished after antibiotic ablation of the gut microbiome. Moreover, weanling female pups housed in cages conditioned by adult male mice developed greater ozone-induced airway hyperresponsiveness than weanling female pups raised in cages conditioned by adult females. Finally, ad libitum oral administration via drinking water of the short-chain fatty acid propionate resulted in augmented ozone-induced airway hyperresponsiveness in male, but not female, mice. Overall, these data are consistent with the hypothesis that the microbiome contributes to sex differences in ozone-induced airway hyperresponsiveness, likely as a result of sex differences in the response to short-chain fatty acids.