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The Not-so-Sterile Womb: Evidence That the Human Fetus Is Exposed to Bacteria Prior to Birth

机译：不那么理想的子宫：人类胎儿出生前暴露于细菌的证据

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The human microbiome includes trillions of bacteria, many of which play a vital role in host physiology. Numerous studies have now detected bacterial DNA in first-pass meconium and amniotic fluid samples, suggesting that the human microbiome may commence in utero. However, these data have remained contentious due to underlying contamination issues. Here, we have used a previously described method for reducing contamination in microbiome workflows to determine if there is a fetal bacterial microbiome beyond the level of background contamination. We recruited 50 women undergoing non-emergency cesarean section deliveries with no evidence of intra-uterine infection and collected first-pass meconium and amniotic fluid samples. Full-length 16S rRNA gene sequencing was performed using PacBio SMRT cell technology, to allow high resolution profiling of the fetal gut and amniotic fluid bacterial microbiomes. Levels of inflammatory cytokines were measured in amniotic fluid, and levels of immunomodulatory short chain fatty acids (SCFAs) were quantified in meconium. All meconium samples and most amniotic fluid samples (36/43) contained bacterial DNA. The meconium microbiome was dominated by reads that mapped to Pelomonas puraquae. Aside from this species, the meconium microbiome was remarkably heterogeneous between patients. The amniotic fluid microbiome was more diverse and contained mainly reads that mapped to typical skin commensals, including Propionibacterium acnes and Staphylococcus spp. All meconium samples contained acetate and propionate, at ratios similar to those previously reported in infants. P. puraquae reads were inversely correlated with meconium propionate levels. Amniotic fluid cytokine levels were associated with the amniotic fluid microbiome. Our results demonstrate that bacterial DNA and SCFAs are present in utero, and have the potential to influence the developing fetal immune system.
机译：人类微生物组包括数万亿细菌，其中许多细菌在宿主生理中起着至关重要的作用。现在，许多研究已经在首过的胎粪和羊水样本中检测到细菌DNA，这表明人类微生物组可能始于子宫。但是，由于潜在的污染问题，这些数据仍然引起争议。在这里，我们使用了先前描述的减少微生物组工作流程中污染的方法来确定是否存在超出背景污染水平的胎儿细菌微生物组。我们招募了50名接受非紧急剖宫产的妇女，没有子宫内感染的证据，并收集了首过的胎粪和羊水样本。使用PacBio SMRT细胞技术进行了全长16S rRNA基因测序，可对胎儿肠道和羊水细菌微生物组进行高分辨率分析。测量羊水中的炎性细胞因子水平，并在胎粪中定量免疫调节性短链脂肪酸（SCFA）的水平。所有胎粪样品和大多数羊水样品（36/43）都含有细菌DNA。胎粪微生物组主要由定位于Pelomonas puraquae的读段主导。除了该物种之外，患者之间的胎粪微生物组明显异质。羊水微生物组更多样化，主要包含与典型皮肤皮肤有关的读物，包括痤疮丙酸杆菌和葡萄球菌属。所有胎粪样品均含有乙酸盐和丙酸盐，其比例与先前报道的婴儿相似。 P. puraquae读数与丙酸二甲酯水平成反比。羊水细胞因子水平与羊水微生物组有关。我们的研究结果表明，子宫内存在细菌DNA和SCFA，并可能影响胎儿发育中的免疫系统。

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