Vaginal Microbiota Diversity of Patients with Embryonic Miscarriage by Using 16S rDNA High-Throughput Sequencing

Abstract

Embryonic miscarriage severely affects the life quality and physical and mental state of pregnant women. However, the detailed mechanism underlying embryonic miscarriage is not fully understood. This study is aimed at analyzing embryonic miscarriage. We collected samples from 25 normal pregnant women and 25 embryonic miscarriage patients of similar age to analyze microbiota isolated from the vagina. Crude examination of the vagina isolates showed that compared with the control group, 80% of the embryonic miscarriage group contained a significantly lower number of Lactobacillus, the major healthy microbe in the vagina. Furthermore, the levels of Th1 and Th2 secreted cytokine interleukin 2 (IL-2) and interleukin10 (IL-10), respectively, were examined. Results showed that the IL2 level was higher, and IL10 level was lower in the embryonic miscarriage group than in the control group, whereas the IL2/IL10 level was higher in the embryonic miscarriage group than in the control group. This finding suggested that the immune response was suppressed in the embryonic miscarriage group. To further dissect the microbiota of the vagina in the two groups, 16S rDNA sequencing was performed. Bioinformatics analysis showed that 1096 and 998 overlapped operational taxonomic units were identified from the embryonic miscarriage and control groups, respectively. At the genus level, the relative abundance of Fam_Finegoldia, Lac_Coprococcus_3, and Lac_Roseburia significantly differed in the embryonic miscarriage group. Overall, our analyses provided potential biomarkers for embryonic miscarriage and elucidated the causative relationship between microbiota and immune responses and may enable the possible diagnosis and therapeutics of early pregnancy loss.

New Insights into Vaginal Environment During Pregnancy

“…As previously observed, first trimester miscarriage can be associated with reduced prevalence of Lactobacillus spp. and with changes in the relative abundance of several bacterial genera, including Fam_Finegoldia, Lac_Coprococcus_3, and Lac_Roseburia (Al-Memar et al, 2020;Xu et al, 2020).…”

“…Moreover, several studies have investigated the association between vaginal bacterial composition and miscarriage (Zhang et al, 2019;Al-Memar et al, 2020;Fan et al, 2020;Xu et al, 2020). First trimester miscarriage seems to be associated with reduced prevalence of Lactobacillus spp.…”

“…First trimester miscarriage seems to be associated with reduced prevalence of Lactobacillus spp. and higher alpha diversity compared to viable pregnancies (Al-Memar et al, 2020;Xu et al, 2020). Furthermore, it has been shown that the vaginal levels of interleukin 2 (IL-2) is higher and interleukin 10 (IL-10) lower in women with embryonic miscarriages than in control subject (Xu et al, 2020).…”

The reproductive tract microbiota in pregnancy

“…Recent work has shown reduced abundance in Lactobacillus spp. and increased α diversity with first trimester miscarriage [ 26 , 27 ]. Lactobacillus -depleted vaginal microbiota also appears to be a risk factor for ectopic pregnancy [ 28 ].…”

Gut Microbiota Composition and Functional Prediction in Recurrent Spontaneous Abortion

“…First trimester miscarriage associated with reduced prevalence of Lactobacillus spp.-dominated vaginal microbiota classi ed using hierarchical clustering analysis [29]. A study of vaginal microbiota showed that at the genus level, the relative abundance of Fam_Finegoldia and Lac_Roseburia signi cantly differed in the embryonic miscarriage group [30]. In the present study, although there was no signi cant difference in the abundance of dominant bacteria (Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria) between the two groups, but Actinobacteria and Proteobacteria tended to a higher in RSA patients at the phylum level.…”