Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Obstetrics, Gynecology and Women's Health, University of Hawaii at Manoa, Honolulu, HI, USA.
Reprod Sci. 2021 Mar;28(3):828-837. doi: 10.1007/s43032-020-00374-5. Epub 2020 Oct 26.
Intrauterine growth restriction (IUGR) is an obstetrical complication with an increased risk of perinatal mortality and morbidity. The uterus, once considered to be a sterile environment, has now been described in recent microbiome studies to harbor diverse commensal placenta microbiota, as well as potentially pathogenic flora known to cause infection. Therefore, in this pilot study, we tested whether IUGR was associated with changes to the reproductive microbiome. The reproductive microbiome was surveyed using 16S sequencing (20 IUGR, 20 controls). Alpha and beta diversity were compared, and differential taxa features associated with IUGR were identified. Microbial screening of the placenta demonstrated a diverse range of flora predominantly including Proteobacteria, Fusobacteria, Firmicutes, and Bacteroidetes. Neither alpha- nor beta-diversity was significantly different by IUGR status. However, at the taxa level, IUGR patients had significantly higher prevalence of Neisseriaceae, mucosal β-hemolytic bacteria known to uptake iron-bound host proteins including hemoglobin. Moreover, the increase in anaerobic bacteria such as Desulfovibrio reflects the emergence of a hypoxic environment in the IUGR placenta. Further analysis of the reproductive microbiome of IUGR samples showed lower levels of H0-producing Bifidobacterium and Lactobacillus that switch from respiration to fermentation, a less energetic metabolic process, when oxygen levels decrease. Source tracking analysis showed that the placental microbial contents were predominantly contributed from an oral source, as compared to a gut or vaginal source. Our results suggest that the reproductive microbiome profiles may, in the future, constitute potential biomarkers for fetal health during pregnancy, while Neisseriaceae may constitute promising therapeutic targets for IUGR treatment.
胎儿宫内生长受限（IUGR）是一种产科并发症，围产期死亡率和发病率增加。子宫，曾经被认为是一个无菌的环境，现在在最近的微生物组研究中被描述为拥有多样化的共生胎盘微生物群，以及已知会引起感染的潜在致病菌群。因此，在这项初步研究中，我们测试了 IUGR 是否与生殖微生物组的变化有关。使用 16S 测序（20 例 IUGR，20 例对照）调查生殖微生物组。比较了 alpha 和 beta 多样性，并确定了与 IUGR 相关的差异分类群特征。对胎盘进行微生物筛查，结果显示菌群多样，主要包括变形菌门、梭杆菌门、厚壁菌门和拟杆菌门。无论 IUGR 状态如何，alpha 和 beta 多样性均无显著差异。然而，在分类群水平上，IUGR 患者中 Neisseriaceae 的患病率显著升高，这种黏膜β-溶血性细菌已知会摄取含铁的宿主蛋白，包括血红蛋白。此外，厌氧菌如脱硫弧菌的增加反映了 IUGR 胎盘缺氧环境的出现。对 IUGR 样本生殖微生物组的进一步分析显示，产生 H0 的双歧杆菌和乳杆菌水平降低，当氧气水平下降时，这些细菌会从呼吸切换到发酵，这是一种能量较低的代谢过程。来源追踪分析表明，与肠道或阴道来源相比，胎盘微生物组的主要来源是口腔。我们的结果表明，生殖微生物组特征可能在未来构成怀孕期间胎儿健康的潜在生物标志物，而奈瑟氏菌可能构成 IUGR 治疗的有前途的治疗靶点。
