The Vaginal Microbial Signatures of Preterm Birth Delivery in Indian Women

Abstract

BackgroundThe incidence of preterm birth (PTB) in India is around 13%. Specific bacterial communities or individual taxon living in the vaginal milieu of pregnant women is a potential risk factor for PTB and may play an important role in its pathophysiology. Besides, bacterial taxa associated with PTB vary across populations.ObjectiveConduct a comparative analysis of vaginal microbiome composition and microbial genomic repertoires of women who enrolled in the Interdisciplinary Group for Advanced Research on Birth Outcomes – A DBT India Initiative (GARBH-Ini) pregnancy cohort to identify bacterial taxa associated with term birth (TB) and PTB in Indian women.MethodsVaginal swabs were collected during all three trimesters from 38 pregnant Indian women who delivered spontaneous term (n=20) and preterm (n=18) neonates. Paired-end sequencing of V3-V4 region of 16S rRNA gene was performed using the metagenomic DNA isolated from vaginal swabs (n=115). Whole genome sequencing of bacterial species associated with birth outcomes was carried out by shotgun method. Lactobacillus species were grown anaerobically in the De Man, Rogosa and Sharpe (MRS) agar culture medium for isolation of genomic DNA and whole genome sequencing.ResultsVaginal microbiome of both term and preterm samples reveals similar alpha diversity indices. However, significantly higher abundance of Lactobacillus iners (p-value All_Trimesters<0.02), Megasphaera sp (p-value1st_Trimester <0.05), Gardnerella vaginalis (p-value2nd_Trimester= 0.01) and Sneathia sanguinegens (p-value2nd_Trimester <0.0001) were identified in preterm samples whereas higher abundance of L. gasseri (p-value3rd_Trimester =0.010) was observed in term samples by Wilcoxon rank-sum test. The relative abundance of L. iners, and Megasphaera sp. were found to be significantly different over time between term and preterm mothers. Analyses of the representative genomes of L. crispatus and L. gasseri indicate presence of secretory transcriptional regulator and several ribosomally synthesized antimicrobial peptides correlated with anti-inflammatory condition in the vagina. These findings indicate protective role of L. crispatus and L. gasseri in reducing the risk of PTB.ConclusionOur findings indicate that the dominance of specific Lactobacillus species and few other facultative anaerobes are associated with birth outcomes.

Contribution of Lactobacillus iners to Vaginal Health and Diseases: A Systematic Review

“…This was also demonstrated by Kindinger et al., who reported that the vaginal microbiome dominated by L. iners at 16 weeks of gestation is a risk factor for both a short cervix and early PTB (<34 weeks), whereas L. crispatus dominance is protective against PTB in a more ethnically diverse cohort ( Kindinger et al., 2017 ). Recent studies from different countries also showed a significant association between L. iners and an increased prevalence of PTB ( Elovitz et al., 2019 ; Aslam et al., 2020 ; Goodfellow et al., 2021 ; Kumar et al., 2021 ; Payne et al., 2021 ; Sarmento et al., 2021 ). However, several studies reported no significant association between L. iners and PTB ( Callahan et al., 2017 ; Blostein et al., 2020 ; Witkin et al., 2021 ).…”

“…Earlier studies confirmed that high estradiol levels and the consequent high glycogen levels in the vagina during pregnancy result in stronger vaginal acidification, thereby promoting the prevalence of Lactobacillu s species as gestation progresses ( Aagaard et al., 2012 ; Basavaprabhu et al., 2020 ). However, many studies have indicated that the L. iners -dominated vaginal microbiome was more likely to shift towards dysbiosis during pregnancy ( Mls et al., 2019 ; Kumar et al., 2021 ; Sarmento et al., 2021 ). In our previous study, we found that the abundance of L. iners decreased significantly in the second and third trimester, whereas that of L. crispatus increased in the second trimester compared with the first trimester in healthy pregnant women ( Zheng et al., 2019 ).…”

Identification of vaginal microbiome associated with IVF pregnancy

“…As for L. gasseri, it is significantly higher in women who delivered term babies compared to those who delivered preterm 30 . The presence of secretory transcriptional regulator and several ribosomally synthesized antimicrobial peptides reported by genomic analysis correlated with L. gasseri anti-inflammatory condition in the vagina.…”

Microbiota of the pregnant mouse: characterization of the bacterial communities in the oral cavity, lung, intestine, and vagina through culture and DNA sequencing

“…These Lactobacillusdominant CSTs (CSTs I-III, and V) are generally perceived as being conducive to reproductive health. Conversely, the relationship between human reproductive health and the non-Lactobacillus-dominant, and thus species rich and diverse, CST IV is more ambiguous (45,(55)(56)(57)(63)(64)(65). This disparity in health outcome potentially related to the structure of the vaginal microbiota is highlighted by the observation that women who do not have a Lactobacillus-dominant vaginal microbiota prior to or during early pregnancy typically transition to a vaginal microbiota of Lactobacillus-dominance as gestation progresses (50,51,66), suggesting that pregnancy entails selective pressures for Lactobacillus-dominance in the vaginal microenvironment.…”