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母鼠妊娠和哺乳期使用抗生素会加重实验性自身免疫性脑脊髓炎仔鼠的临床症状和炎症反应。

Antibiotic treatment during pregnancy and lactation in dams exacerbates clinical symptoms and inflammatory responses in offspring with experimental autoimmune encephalomyelitis.

机构信息

Salari Institute of Cognitive and Behavioral Disorders (SICBD), Karaj, Alborz, Iran; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

J Neuroimmunol. 2022 May 15;366:577840. doi: 10.1016/j.jneuroim.2022.577840. Epub 2022 Mar 3.

DOI:10.1016/j.jneuroim.2022.577840
PMID:35259641
Abstract

A growing body of evidence demonstrates that an imbalance in the intensive communication between gut microbiota and the host might be associated with immune-related disorders such as multiple sclerosis. This study set out to determine whether antibiotic treatment during pregnancy and lactation can affect the onset and severity of clinical symptoms and inflammatory responses in offspring with experimental autoimmune encephalomyelitis (EAE; a mouse model of multiples sclerosis). Female C57BL/6 mice received antibiotics or vehicles during pregnancy and lactation, then their offspring were induced with EAE in adulthood. We also measured interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon-gamma (IFN-γ), IL-17A, IL-10, and transforming growth factor (TGF)-β in the serum of offspring. The findings indicate that antibiotic treatment in dams significantly exacerbated the severity of EAE clinical symptoms in both male and female offspring. However, antibiotic treatment only accelerated the onset of EAE disease in male but not female offspring. We did not find any significant changes in cytokines in non-EAE male and female offspring treated with antibiotics. Antibiotic treatment significantly enhanced levels of IL-6, TNF-α, IFN-γ, IL-17A, and TGF-β in EAE-induced male offspring, and IFN-γ, IL-17A, and IL-10 levels in EAE-induced female offspring. There were also sex differences in the onset and severity of EAE disease, and inflammatory cytokines (IL-6, IFN-γ, and IL-17A) between EAE-induced male and female offspring treated with antibiotics. Taken together, this study suggests that antibiotic treatment during pregnancy and lactation in dams might affect the development of the immune system in male and female offspring in adulthood.

摘要

越来越多的证据表明,肠道微生物群与宿主之间的密集交流失衡可能与免疫相关疾病有关,如多发性硬化症。本研究旨在确定妊娠和哺乳期使用抗生素是否会影响实验性自身免疫性脑脊髓炎(EAE;多发性硬化症的小鼠模型)后代的临床症状和炎症反应的发生和严重程度。雌性 C57BL/6 小鼠在妊娠和哺乳期接受抗生素或载体处理,然后在成年期诱导其后代发生 EAE。我们还测量了后代血清中的白细胞介素 (IL)-6、肿瘤坏死因子 (TNF)-α、干扰素-γ (IFN-γ)、IL-17A、IL-10 和转化生长因子 (TGF)-β。研究结果表明,母体抗生素处理显著加重了雄性和雌性后代 EAE 临床症状的严重程度。然而,抗生素处理仅加速了雄性而非雌性后代 EAE 疾病的发生。我们没有发现抗生素处理的非 EAE 雄性和雌性后代中的细胞因子有任何显著变化。抗生素处理显著增强了 EAE 诱导的雄性后代中 IL-6、TNF-α、IFN-γ、IL-17A 和 TGF-β的水平,并增强了 EAE 诱导的雌性后代中 IFN-γ、IL-17A 和 IL-10 的水平。抗生素处理的 EAE 诱导的雄性和雌性后代在 EAE 疾病的发生和严重程度以及炎症细胞因子(IL-6、IFN-γ 和 IL-17A)方面也存在性别差异。综上所述,本研究表明,母体在妊娠和哺乳期使用抗生素可能会影响成年后代雄性和雌性的免疫系统发育。

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