Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies

Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies
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DOI:
10.1038/s41586-022-05546-8
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发表时间:
2023-01-26
期刊:
影响因子:
64.8
通讯作者:
Walter, Jens
Walter, Jens
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kennedy, Katherine M.;de Goffau, Marcus C.;Walter, Jens

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人类胎儿和产前宫内环境(羊水和胎盘)在健康妊娠期间是否稳定地被微生物群落定植仍然是一个争论的主题。在这里,我们从生殖生物学、微生物生态学、生物信息学、免疫学、临床微生物学和灵芝生物学的角度对最近关于人类胎儿微生物种群特征的研究进行评估,并评估胎儿可能与微生物相互作用的可能机制。我们的分析表明,检测到的微生物信号可能是在获取胎儿样本的临床过程中或在DNA提取和DNA测序过程中受到污染的结果。此外,在健康的胎儿组织中存在活的和复制的微生物种群与免疫学、临床微生物学和无菌哺乳动物的起源的基本概念不相容。这些结论对我们理解人类免疫发展很重要,并说明了在许多其他低生物量环境的微生物分析中的常见陷阱。对胎儿微生物组的追求是一个警示例子,说明在生物量较低或没有生物量时,基于序列的微生物组研究面临的挑战,并强调需要一种跨学科的方法,通过纳入生物学、生态学和机械学的概念,超越污染控制。
Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.