Prenatal antibiotics exposure does not influence experimental allergic asthma in mice.
Prenatal antibiotics exposure does not influence experimental allergic asthma in mice.
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DOI：
10.3389/fimmu.2022.937577
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发表时间：
2022
影响因子：
7.3
通讯作者：
Schmudde, Inken
中科院分区：
文献类型：
--
作者：
Lingel, Imke;Wilburn, Adrienne N.;Hargis, Julie;McAlees, Jaclyn W.;Laumonnier, Yves;Chougnet, Claire A.;Deshmukh, Hitesh;Koenig, Peter;Lewkowich, Ian P.;Schmudde, Inken
微生物组的变化（生态失调）有助于过敏性哮喘的严重程度。已有的人类流行病学研究将围产期生态失调与长期哮喘严重程度增加相关联。然而，这些研究不能区分产前和产后的生态失调的影响，并遭受从抗生素治疗，剖腹产分娩的早期生活母乳喂养的做法，从一个高变异性的生态失调的原因。考虑到母体接触抗生素会增加后代患新生儿细菌性肺炎的风险，我们假设产前母体抗生素诱导的生态失调会诱导后代的长期免疫效应，这也会增加长期哮喘的严重程度。因此，从胚胎第15天至出生，母体暴露于抗生素（庆大霉素、氨苄青霉素、万古霉素）。六周后，通过反复应用屋尘螨提取物在后代中诱导哮喘。评估气道功能、细胞因子产生、肺细胞组成和分布。我们的研究表明，产前诱导的小鼠生态失调导致肺部Th 17+非常规T细胞的增加，对气道阻力、促哮喘Th 2/Th 17细胞因子产生、肺部定位和细胞-细胞接触的功能作用有限。这些数据表明，对哮喘发展具有长期影响的生态失调相关的免疫调节在产前发生的程度较小，并且将允许将未来的研究集中在更具决定性的产后时间框架上。
Changes in microbiome (dysbiosis) contribute to severity of allergic asthma. Preexisting epidemiological studies in humans correlate perinatal dysbiosis with increased long-term asthma severity. However, these studies cannot discriminate between prenatal and postnatal effects of dysbiosis and suffer from a high variability of dysbiotic causes ranging from antibiotic treatment, delivery by caesarian section to early-life breastfeeding practices. Given that maternal antibiotic exposure in mice increases the risk of newborn bacterial pneumonia in offspring, we hypothesized that prenatal maternal antibiotic-induced dysbiosis induces long-term immunological effects in the offspring that also increase long-term asthma severity. Therefore, dams were exposed to antibiotics (gentamycin, ampicillin, vancomycin) from embryonic day 15 until birth. Six weeks later, asthma was induced in the offspring by repeated applications of house dust mite extract. Airway function, cytokine production, pulmonary cell composition and distribution were assessed. Our study revealed that prenatally induced dysbiosis in mice led to an increase in pulmonary Th17+ non-conventional T cells with limited functional effect on airway resistance, pro-asthmatic Th2/Th17 cytokine production, pulmonary localization and cell-cell contacts. These data indicate that dysbiosis-related immune-modulation with long-term effects on asthma development occurs to a lesser extent prenatally and will allow to focus future studies on more decisive postnatal timeframes.
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