Lee Ji-Youn, Seo Sumin, Shin Bohyun, Hong Se Hee, Kwon Eunjin, Park Sunwha, Hur Young Min, Lee Dong-Kyu, Kim Young Ju, Han Sang Beom
College of Pharmacy, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Korea.
Department of Obstetrics and Gynecology and Ewha Medical Research Institute, College of Medicine, Ewha Womans University, Seoul 07984, Korea.
Metabolites. 2022 Aug 9;12(8):734. doi: 10.3390/metabo12080734.
Preterm birth (PTB) is a social problem that adversely affects not only the survival rate of the fetus, but also the premature babies and families, so there is an urgent need to find accurate biomarkers. We noted that among causes, eubiosis of the vaginal microbial community to dysbiosis leads to changes in metabolite composition. In this study, short chain fatty acids (SCFAs) representing dysbiosis were derivatized using (-butyldimethylsilyl--methyltrifluoroacetamide, MTBSTFA) and targeted analysis was conducted in extracted organic phases of cervicovaginal fluid (CVF). In residual aqueous CVF, polar metabolites produced biochemistry process were derivatized using methoxyamine and ,-bis(trimethylsilyl)trifluoroacetamide (BSTFA), and non-targeted analysis were conducted. Nine SCFAs were quantified, and 58 polar metabolites were detected in 90 clinical samples using gas chromatography/mass spectrometry (GC/MS). The criteria of statistical analysis and detection rate of clinical sample for development of PTB biomarkers were presented, and 19 biomarkers were selected based on it, consisting of 1 SCFA, 2 organic acids, 4 amine compounds, and 12 amino acids. In addition, the model was evaluated as a suitable indicator for predicting PTB without distinction between sample collection time. We hope that the developed biomarkers based on microbiota-derived metabolites could provide useful diagnostic biomarkers for actual patients and pre-pregnancy.
早产（PTB）是一个社会问题，不仅会对胎儿的存活率产生不利影响，还会影响早产儿及其家庭，因此迫切需要找到准确的生物标志物。我们注意到，在各种原因中，阴道微生物群落从共生状态转变为失调会导致代谢物组成发生变化。在本研究中，代表失调的短链脂肪酸（SCFAs）使用（叔丁基二甲基硅烷基 - 甲基三氟乙酰胺，MTBSTFA）进行衍生化，并在宫颈阴道液（CVF）的萃取有机相中进行靶向分析。在剩余的CVF水相中，对生物化学过程产生的极性代谢物使用甲氧基胺和双（三甲基硅基）三氟乙酰胺（BSTFA）进行衍生化，并进行非靶向分析。使用气相色谱/质谱（GC/MS）对90份临床样本中的9种短链脂肪酸进行了定量，并检测到58种极性代谢物。提出了用于开发早产生物标志物的临床样本统计分析标准和检测率，并据此选择了19种生物标志物，包括1种短链脂肪酸、2种有机酸、4种胺类化合物和12种氨基酸。此外，该模型被评估为一种适用于预测早产的指标，且不区分样本采集时间。我们希望基于微生物群衍生代谢物开发的生物标志物能够为实际患者和孕前人群提供有用的诊断生物标志物。
