阴道菌群失调与早孕流产风险的关系

Relationship between vaginal flora dysbiosis and the risk of early pregnancy abortion

摘要

目的 探讨阴道菌群失调与早孕流产风险的关系。方法 选取2021年5月至2022年3月在陕西中医药大学第二附属医院妇科就诊的147名孕妇为研究对象,其中病例组为早孕流产(妊娠12周内确诊)患者(n=64),对照组为健康足月分娩者(n=83).采用基于16S rRNA基因测序,对病例组与对照组研究对象妊娠早期的阴道菌群组成进行比较及分析。结果 病例组与对照组在年龄、体质量指数、吸烟者人数、妊娠情况、既往流产、胎龄、阴道pH值的分布比较差异均无统计学意义(P>0.05).在总样本队列中鉴定出244种细菌.样本分为5个主要类型,其中菌落状态类型(CST)Ⅰ的特征是卷曲乳酸杆菌占优势,CST Ⅱ的特征是加氏乳酸杆菌占优势,CST Ⅲ的特征是内乳酸杆菌占优势,CST Ⅴ的特征是詹氏乳酸杆菌占优势,而CST Ⅳ的特征是乳酸杆菌属的丰度较低.在CST Ⅳ型群落中观察到了最高的α多样性和丰度.与对照组相比,病例组的阴道菌群组成中乳酸杆菌属消耗的比例显著增加[25.0%(16/64)vs.6.0%(5/83),χ²=10.626,P<0.01].病例组中CST Ⅳ型为主阴道菌群组成的比例明显增加[29.7%(19/64)vs.12.0%(10/83),χ²=7.100,P<0.01].病例组的逆辛普森指数(2.81±1.20 vs.1.41±0.48)和丰度(28.06±15.08 vs.17.13±6.83)均明显高于对照组(t值分别为4.641、3.523,P<0.05).当从病例组中排除报告阴道出血评分>1的孕妇时,这种相关性仍然存在.与稽留流产相比,不完全/完全流产的阴道菌群组成中乳酸杆菌属消耗的比例显著增加[19.2%(10/52)vs.75.0%(9/12),χ²=14.527,P<0.01].不完全/完全流产中CST Ⅳ型为主阴道菌群组成的比例显著增加[23.1%(12/52)vs.75.0%(9/12),χ²=11.923,P<0.01]。结论 高度多样性的阴道菌群群落和乳酸杆菌减少是早孕流产的危险因素.

Abstract

Objective To explore the relationship between vaginal flora dysbiosis and the risk of early pregnancy abortion. Methods From May, 2021 to March, 2022, a total of 147 pregnant women in Department of Gynecology, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine participated in this study. Among them, the case group consisted of patients with early pregnancy abortion (diagnosed within 12 gestation weeks) (n=64), and the control group consisted of healthy full-term delivery women (n=83). The composition of vaginal microbiota in early pregnancy was compared and analyzed between the case group and the control group using 16S rRNA gene sequencing. Results There were no statistically significant differences in age, body mass index, number of smokers, pregnancy status, previous abortions, gestational age, and vaginal pH between the case group and the control group (P>0.05). A total of 244 bacterial species were identified in the sample cohort. The samples were divided into 5 major types, among which the characteristic of community state type (CST) Ⅰ was dominance of Lactobacillus crispatus, CST Ⅱ was dominance of Lactobacillus gasseri, CST Ⅲ was dominance of Lactobacillus iners, CST Ⅴ was dominance of Lactobacillus jensenii, and CST Ⅳ had a lower abundance of Lactobacillus species. The highest α-diversity and abundance were observed in CST Ⅳ communities. Compared to the control group, the proportion of Lactobacillus consumption in the vaginal microbiota composition was significantly increased in the case group [25.0% (16/64) vs. 6.0% (5/83), χ²=10.626, P<0.01]. The proportion of CST Ⅳ type as the dominant vaginal microbiota was significantly increased in the case group [29.7% (19/64) vs. 12.0% (10/83), χ²=7.100, P<0.01]. The Simpson's diversity index (2.81±1.20 vs. 1.41±0.48) and abundance (28.06±15.08 vs. 17.13±6.83) were significantly higher in the case group compared to the control group (t=4.641 and 3.523, respectively, P<0.05). This correlation persisted when pregnant women with vaginal bleeding scores >1 were excluded from the case group. Compared to missed abortion, the proportion of Lactobacillus consumption in the vaginal microbiota composition of incomplete/complete abortion was significantly increased [19.2% (10/52) vs. 75.0% (9/12), χ²=14.527, P<0.01]. The proportion of CST Ⅳ type as the dominant vaginal microbiota was significantly increased in incomplete/complete abortion [23.1% (12/52) vs. 75.0% (9/12), χ²=11.923, P<0.01]. Conclusions The high diversity of vaginal bacterial community and the decrease of Lactobacillus are the risk factors for early pregnancy abortion.

关键词

阴道菌群 / 早孕流产 / 稽留流产 / 出血

Key words

vaginal flora / early pregnancy abortion / missed abortion / bleeding

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基金资助

陕西省卫生健康委员会资助项目(20212641)