Brief Hydromorphone Exposure During Pregnancy Sufficient to Induce Maternal and Neonatal Microbial Dysbiosis.
Brief Hydromorphone Exposure During Pregnancy Sufficient to Induce Maternal and Neonatal Microbial Dysbiosis.
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DOI：
10.1007/s11481-021-10019-2
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发表时间：
2022-06
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影响因子：
--
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中科院分区：
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--
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产前阿片类药物暴露与后代的严重不良医疗、发育和行为结果相关，尽管导致这些损害的潜在机制仍不清楚。越来越多的证据表明肠道微生物生态失调是这些不良反应的潜在调节剂。然而，妊娠期间阿片类药物暴露如何改变母体和新生儿微生物组仍有待阐明。在这里，我们利用了在妊娠期间短暂暴露于氢吗啡酮的小鼠模型（妊娠第11-13天; i. p.; 10 mg/kg），以检查其对母体和新生儿微生物组的影响。在母鼠（氢吗啡酮暴露后4天、出生和断奶）和后代（2、3和5周）的不同时间点收集粪便样品，以询问微生物组的纵向变化。还收集了2周时的胃内容物作为母乳的替代物，并使用16 S rRNA测序进行微生物分析。除了母体肠道微生物组成的改变，后代肠道微生物群在2周和3周时表现出不同的群落。此外，微生物群落的功能分析显示，与对照组相比，母体和/或新生儿氢吗啡酮暴露组的微生物群落水平表型（革兰氏阴性、革兰氏阳性和潜在致病性）存在显著差异。我们还观察到阿片类药物暴露与非暴露后代的胃微生物群差异，这表明母乳也可能在塑造新生儿肠道微生物群的发育中发挥作用。我们共同提供了即使在怀孕期间短暂接触氢吗啡酮也会引起孕产妇和新生儿微生物生态失调的证据。
Prenatal opioid exposure is associated with significantly adverse medical, developmental, and behavioral outcomes in offspring, though the underlying mechanisms driving these impairments are still unclear. Accumulating evidence implicates gut microbial dysbiosis as a potential modulator of these adverse effects. However, how opioid exposure during pregnancy alters the maternal and neonatal microbiome remain to be elucidated. Here, we utilize a murine model of brief hydromorphone exposure during pregnancy (gestation day 11-13; i.p.; 10mg/kg) to examine its impact on the maternal and neonatal microbiome. Fecal samples were collected at various timepoints in dams (4 days post hydromorphone exposure, birth, and weaning) and offspring (2, 3, and 5 weeks) to interrogate longitudinal changes in the microbiome. Stomach contents at 2 weeks were also collected as a surrogate for breastmilk and microbial analysis was performed using 16S rRNA sequencing. Alongside alterations in the maternal gut microbial composition, offspring gut microbiota exhibited distinct communities at 2 and 3 weeks. Furthermore, functional profiling of microbial communities revealed significant differences in microbial community-level phenotypes gram-negative, gram-positive, and potentially pathogenic in maternal and/or neonatal hydromorphone exposed groups compared with controls. We also observed differences in stomach microbiota in opioid-exposed vs non-exposed offspring, which suggests breast milk may also play a role in shaping the development of the neonatal gut microbiota. Together, we provide evidence of maternal and neonatal microbial dysbiosis provoked even with brief hydromorphone exposure during pregnancy.
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影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
4.2
作者：
Grecco GG;Gao Y;Gao H;Liu Y;Atwood BK
通讯作者：
Atwood BK
影响因子：
4.4
作者：
Gonzalez-Perez, Gabriela;Hicks, Allison L.;Lamouse-Smith, Esi S. N.
通讯作者：
Lamouse-Smith, Esi S. N.
影响因子：
3.7
作者：
Bruce-Keller AJ;Fernandez-Kim SO;Townsend RL;Kruger C;Carmouche R;Newman S;Salbaum JM;Berthoud HR
通讯作者：
Berthoud HR
DOI：
10.1007/s11481-018-9805-6
发表时间：
2019-06
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Sindberg GM;Callen SE;Banerjee S;Meng J;Hale VL;Hegde R;Cheney PD;Villinger F;Roy S;Buch S
通讯作者：
Buch S