Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery

Elovitz, Michal A.; Gajer, Pawel; Riis, Valerie; Brown, Amy G.; Humphrys, Michael S.; Holm, Johanna B.; Ravel, Jacques

doi:10.1038/s41467-019-09285-9

Cited by 285 publications

(382 citation statements)

References 40 publications

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“…The paucity of effective strategies for predicting and preventing PTB has led to concerted research efforts in recent years to identify and characterize biomarkers associated with preterm delivery. In parallel, the vaginal microbiome field has revealed that changes in the vaginal microbiota can precede the onset of PTB [14,18,44,45].…”

Section: Discussionmentioning

confidence: 99%

Vaginal microbiota and cytokine levels predict preterm delivery in Asian women

Kumar

Murugesan

Singh

et al. 2020

Preprint

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Background: Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality worldwide. Approximately half of PTBs are linked with microbial etiologies, including pathologic changes to the vaginal microbiota, which vary according to ethnicity. Globally more than 50% of PTBs occur in Asia, but studies of the vaginal microbiome and its association with pregnancy outcomes in Asian women are lacking. This study aimed to characterize the vaginal microbiome and cytokine environment of 18 Karen and Burman pregnant women who delivered preterm and 36 matched controls delivering at full term. Results: Using 16S ribosomal RNA gene sequencing we identified a predictive vaginal microbiota signature for PTB that was detectable as early as the first trimester of pregnancy, characterized by higher levels of Prevotella buccalis , and lower levels of Lactobacillus crispatus and Finegoldia , accompanied by decreased levels of cytokines including IFNγ, IL-4 and TNFα. Conclusion: Our findings highlight new opportunities to predict PTB in Asian women in low-resource settings who are at highest risk of adverse outcomes from unexpected PTB, as well as in Burman/Karen ethnic minority groups in high-resource regions.

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Section: Discussionmentioning

confidence: 99%

Vaginal microbiota and cytokine levels predict preterm delivery in Asian women

Kumar

Murugesan

Singh

et al. 2020

Preprint

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“…During pregnancy menses cease and there is a consistently elevated level of estrogen with a concomitant increase in Lactobacillus dominance (47). Several studies have suggested that altered microbiota are associated with preterm birth (48)(49)(50). Preterm premature rupture of membranes (PPROM), chorioamnionitis and early or late miscarriages have also been associated with changes in the vaginal microbiome (51)(52)(53)(54)(55)(56).…”

Section: Vaginal Microbiomementioning

confidence: 99%

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

et al. 2020

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Understanding what happens at the time of embryo implantation has been the subject of significant research. Investigators from many differing fields including maternal fetal medicine, microbiology, genetics, reproductive endocrinology and immunology have all been studying the moment the embryo interacts with the maternal endometrium. A perfect relationship between the uterus and the embryo, mediated by a tightly controlled interaction between the embryo and the endometrium, is required for successful implantation. Any factors affecting this communication, such as altered microbiome may lead to poor reproductive outcomes. Current theories suggest that altered microbiota may trigger an inflammatory response in the endometrium that affects the success of embryo implantation, as inflammatory mediators are tightly regulated during the adhesion of the blastocyst to the epithelial endometrial wall. In this review, we will highlight the various microbiome found during the periconceptual period, the microbiomes interaction with immunological responses surrounding the time of implantation, its effect on implantation, placentation and ultimately maternal and neonatal outcomes.

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“…On the one hand, high abundance of certain Lactobacillus species, but on the other hand, also a generally low abundance of lactobacilli (along with bacterial vaginosis) has been associated with PTB [11] [12]. A very recent study, however, highlighted the role of an immune-system component, namely beta-defensin-2, which was found to be negatively correlated with spontaneous PTB, largely independent of the microbiome profile assessed [13]. A causal link between vaginal microbiome composition and PTB has not been established to date.…”

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confidence: 99%

Human Milk Oligosaccharides modulate the risk for preterm birth in a microbiome dependent and independent manner

Pausan

Kolovetsiou-Kreiner

Richter

et al. 2019

Preprint

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BackgroundPreterm birth is one of the leading causes of neonatal mortality. The causes for spontaneous preterm birth (PTB) are multifactorial and remain often unknown. In this study, we tested the hypothesis that human milk oligosaccharides (HMOs) in blood and urine modulate the maternal urinary and vaginal microbiome and influence the risk for PTB. We analyzed the vaginal and urinary microbiome of a cross-sectional cohort of women with and without preterm labor and correlated our findings with measurements of metabolites and HMOs in urine and blood. ResultsWe identified several microbial signatures associated with short cervix, PTB and/or preterm contractions such as Lactobacillus jensenii, L. gasseri, Ureaplasma sp. and Gardnerella sp..Additionally, we observed associations between sialylated HMOs, in particular 3'-sialyllactose, with PTB, short cervix and increased inflammation and confirmed an influence of HMOs on the microbiome profile. ConclusionsIdentifying serum and urinary HMOs and several key microorganisms associated with PTB, our findings point at two distinct processes modulating the risk for PTB. One process seems to be driven by sterile inflammation, characterized by increased concentrations of sialylated HMOs in serum.Another process might be microbiome-mediated, potentially driven by secretor-active HMOs in urine. Our results support current efforts to improve diagnostics and therapeutic strategies.

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Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery

Cited by 285 publications

References 40 publications

Vaginal microbiota and cytokine levels predict preterm delivery in Asian women

Vaginal microbiota and cytokine levels predict preterm delivery in Asian women

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

Human Milk Oligosaccharides modulate the risk for preterm birth in a microbiome dependent and independent manner

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