An association between the vaginal microbiota and preterm birth (PTB) has been reported in several research studies. Population shifts from high proportions of lactobacilli to mixed species communities, as seen with bacterial vaginosis, have been linked to a twofold increased risk of PTB. Despite the increasing number of studies using next-generation sequencing technologies, primarily involving 16S rRNA-based approaches, to investigate the vaginal microbiota during pregnancy, no distinct microbial signature has been associated with PTB. Shotgun metagenomic sequencing offers a powerful tool to reveal community structures and their gene functions at a far greater resolution than amplicon sequencing. In this study, we employ shotgun metagenomic sequencing to compare the vaginal microbiota of women at high risk of preterm birth (n = 35) vs. a low-risk control group (n = 14). Although microbial diversity and richness did not differ between groups, there were significant differences in terms of individual species. In particular, Lactobacillus crispatus was associated with samples from a full-term pregnancy, whereas one community state-type was associated with samples from preterm pregnancies. Furthermore, by predicting gene functions, the functional potential of the preterm microbiota was different from that of full-term equivalent. Taken together, we observed a discrete structural and functional difference in the microbial composition of the vagina in women who deliver preterm. Importance: with an estimated 15 million cases annually, spontaneous preterm birth (PTB) is the leading cause of death in infants under the age of five years. The ability to accurately identify pregnancies at risk of spontaneous PTB is therefore of utmost importance. However, no single cause is attributable. Microbial infection is a known risk factor, yet the role of vaginal microbes is poorly understood. Using high-resolution DNA-sequencing techniques, we investigate the microbial communities present in the vaginal tracts of women deemed high risk for PTB. We confirm that Lactobacillus crispatus is strongly linked to full-term pregnancies, whereas other microbial communities associate with PTB. Importantly, we show that the specific functions of the microbes present in PTB samples differs from FTB samples, highlighting the power of our sequencing approach. This information enables us to begin understanding the specific microbial traits that may be influencing PTB, beyond the presence or absence of microbial taxa.

阴道微生物群与早产（PTB）之间的关联已在多项研究中报道。正如细菌性阴道病那样，人口从高比例的乳酸菌转移到混合物种群落，与PTB风险增加两倍有关。尽管使用下一代测序技术（主要涉及基于16S rRNA的方法）来研究怀孕期间的阴道微生物群的研究越来越多，但PTB并没有明显的微生物特征。gun弹枪宏基因组测序提供了一个功能强大的工具，可以以比扩增子测序更高的分辨率揭示群落结构及其基因功能。在这项研究中，我们采用散弹枪宏基因组测序来比较早产高危女性的阴道微生物群（n  = 35）与低风险对照组（n  = 14）。尽管各组之间的微生物多样性和丰富度没有差异，但各个物种之间仍存在显着差异。尤其是薄脆乳杆菌与足月妊娠的样本有关，而一种社区状态类型与早孕的样本有关。此外，通过预测基因功能，早产菌群的功能潜能与足月菌群的潜能不同。两者合计，我们观察到早产妇女阴道微生物组成的离散结构和功能差异。重要性：每年估计有1500万例，自发性早产（PTB）是5岁以下婴儿死亡的主要原因。因此，准确识别具有自发性PTB风险的怀孕的能力至关重要。但是，没有单一原因可归因于。微生物感染是已知的危险因素，但是人们对阴道微生物的作用知之甚少。使用高分辨率的DNA测序技术，我们调查了女性阴道中存在的微生物群落，这些妇女被认为是PTB的高危人群。我们确认松脆乳杆菌与足月妊娠密切相关，而其他微生物群落与PTB相关。重要的是，我们证明了PTB样品中存在的微生物的特定功能与FTB样品不同，这突出了我们测序方法的强大功能。这些信息使我们能够开始了解除存在或不存在微生物类群以外可能影响PTB的特定微生物特征。