A critical assessment of the "sterile womb" and "in utero colonization" hypotheses: implications for research on the pioneer infant microbiome.
A critical assessment of the "sterile womb" and "in utero colonization" hypotheses: implications for research on the pioneer infant microbiome.
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DOI：
10.1186/s40168-017-0268-4
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发表时间：
2017-04-28
期刊：
影响因子：
15.5
通讯作者：
Walter J
中科院分区：
文献类型：
--
作者：
Perez-Muñoz ME;Arrieta MC;Ramer-Tait AE;Walter J
经过世纪的积极研究，人类胎儿环境是无菌的，新生儿的微生物组是在出生期间和出生后获得的，这是一个公认的教条。然而，最近使用分子技术的研究表明，细菌群落存在于健康妊娠的胎盘、羊水和胎粪中。这些发现导致许多科学家挑战“无菌子宫范式”，并提出微生物组的获得从子宫内开始，这一想法将从根本上改变我们对肠道微生物群获得及其在人类发育中的作用的理解。在这篇综述中，我们对支持这两种相反假设的证据进行了严格的评估，特别是因为它涉及到（i）胎盘和胎儿的解剖学，免疫学和生理学特征;（ii）目前用于研究宫内环境中微生物种群的研究方法;（iii）生命最初几天的粪便微生物组;（iii）胎盘和胎儿的解剖学，免疫学和生理学特征。和（iv）产生纯性动物和人。基于这一分析，我们认为支持“子宫内定植假说”的证据非常薄弱，因为它几乎完全建立在以下研究基础上：（i）使用检测限不足的分子方法研究“低生物量”微生物种群，（ii）缺乏适当的污染控制，（iii）未能提供细菌活力的证据。最重要的是，通过剖腹产可靠地获得纯动物的能力强烈支持哺乳动物中胎儿环境的无菌性。我们的结论是，目前的科学证据并不支持健康胎儿环境中存在微生物组，这对预防出生后微生物组扰动的临床实践的发展和未来研究重点的建立具有影响。
After more than a century of active research, the notion that the human fetal environment is sterile and that the neonate’s microbiome is acquired during and after birth was an accepted dogma. However, recent studies using molecular techniques suggest bacterial communities in the placenta, amniotic fluid, and meconium from healthy pregnancies. These findings have led many scientists to challenge the “sterile womb paradigm” and propose that microbiome acquisition instead begins in utero, an idea that would fundamentally change our understanding of gut microbiota acquisition and its role in human development. In this review, we provide a critical assessment of the evidence supporting these two opposing hypotheses, specifically as it relates to (i) anatomical, immunological, and physiological characteristics of the placenta and fetus; (ii) the research methods currently used to study microbial populations in the intrauterine environment; (iii) the fecal microbiome during the first days of life; and (iv) the generation of axenic animals and humans. Based on this analysis, we argue that the evidence in support of the “in utero colonization hypothesis” is extremely weak as it is founded almost entirely on studies that (i) used molecular approaches with an insufficient detection limit to study “low-biomass” microbial populations, (ii) lacked appropriate controls for contamination, and (iii) failed to provide evidence of bacterial viability. Most importantly, the ability to reliably derive axenic animals via cesarean sections strongly supports sterility of the fetal environment in mammals. We conclude that current scientific evidence does not support the existence of microbiomes within the healthy fetal milieu, which has implications for the development of clinical practices that prevent microbiome perturbations after birth and the establishment of future research priorities.