Prenatal low-dose penicillin results in long-term sex-specific changes to murine behaviour, immune regulation, and gut microbiota
Prenatal low-dose penicillin results in long-term sex-specific changes to murine behaviour, immune regulation, and gut microbiota
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DOI：
10.1016/j.bbi.2019.11.020
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发表时间：
2020-02-01
影响因子：
15.1
通讯作者：
Bienenstock, John
中科院分区：
文献类型：
--
作者：
Champagne-Jorgensen, Kevin;Mian, M. Firoz;Bienenstock, John
越来越多的证据表明，母体微生物的环境干扰物可能会对发育中的胎儿产生严重的有害后果。在生命早期接触抗生素可能会对小鼠和人类的神经发育产生长期影响。在这里，我们探索小鼠在怀孕最后一周暴露于低剂量青霉素是否会对后代的行为、大脑、免疫功能和肠道微生物区系产生长期影响。我们发现，这种治疗在成年小鼠后代中具有性别特异性的影响。雌性(而不是雄性)小鼠表现出焦虑样行为的减少，而雄性(而不是雌性)小鼠表现出异常的社会行为，这与AVPR1A、AVPR1B和OXTR脑表达的变化以及脾FOXP3(+)调节T细胞的平衡下降有关。产前接触青霉素也会导致不同性别的微生物区系组成不同。这些数据表明，即使怀孕的小鼠在出生前最后一周接触到即使是低剂量的青霉素，也足以在雄性和雌性后代中诱导长期的性别特异性发育变化。
Growing evidence suggests that environmental disruptors of maternal microbes may have significant detrimental consequences for the developing fetus. Antibiotic exposure during early life can have long-term effects on neurodevelopment in mice and humans. Here we explore whether exposure to low-dose penicillin during only the last week of gestation in mice has long-term effects on offspring behaviour, brain, immune function, and gut microbiota. We found that this treatment had sex-specific effects in the adult mouse offspring. Female, but not male, mice demonstrated decreased anxiety-like behaviours, while male, but not female, mice had abnormal social behaviours which correlated with altered brain expression of AVPR1A, AVPR1B, and OXTR, and decreases in the balance of splenic FOXP3(+) regulatory T cells. Prenatal penicillin exposure also led to distinct microbiota compositions that clustered differently by sex. These data suggest that exposure of pregnant mice to even a low dose of penicillin through only the last week before birth is nonetheless sufficient to induce long-term sex-specific developmental changes in both male and female offspring.