Direct on-swab metabolic profiling of vaginal microbiome:host interactions during pregnancy and preterm birth

The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.

Linked cross omic data sets:
Meta-taxonomics data associated with this study are available in the European Nucleotide Archive (ENA): accession number PRJEB11895, PRJEB12577 and PRJEB41427.

妊娠阴道微生物组与早产风险密切相关，而早产是5岁以下儿童死亡的首要诱因。本研究采用解吸电喷雾电离质谱（Desorption Electrospray Ionization Mass Spectrometry, DESI-MS）直接对拭子进行代谢谱分析，无需样本前处理，即可对两个独立妊娠队列的宫颈阴道代谢组进行表征：VMET队列（n=160，共455份拭子）、VMET II队列（n=205，共573份拭子）。通过整合匹配样本的宏分类组学与免疫谱分析数据，本研究证实特定代谢组特征可同时精准预测阴道微生物组组成与宿主炎症状态。在本研究受试者中，经DESI-MS预测得到的阴道菌群不稳定与先天免疫激活特征，与早产发生显著相关，其中也包括因预防早产接受宫颈环扎术的女性。本研究结果表明，采用DESI-MS直接对拭子进行代谢谱分析，可通过快速评估阴道菌群-宿主互作动态，实现早产风险分层，是一种创新性的检测手段。

关联多组学数据集：
本研究关联的宏分类组学数据已上传至欧洲核苷酸档案馆（European Nucleotide Archive, ENA），获取编号为PRJEB11895、PRJEB12577与PRJEB41427。