Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis

Borges, Luiz Gustavo dos Anjos; Pastuschek, Jana; Heimann, Yvonne; Dawczynski, K; Bergner, M; Haase, Roland; Stubert, Johannes; Olbertz, Dirk; Plumeier, Iris; Kahl, Silke; Heroven, Ann Kathrin; Schleußner, E; Pieper, Dietmar H.; Zöllkau, Janine

doi:10.1186/s12916-023-02805-x

Cited by 21 publications

(20 citation statements)

References 66 publications

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“…Lactobacillus is the most dominant genus within the vaginal microbiome, and low counts of Lactobacillus have previously been stated to be indicative of increased PTB risk [5, 28]. Certain species of Anaerococcus are found to be associated with increased PTB risk [1], however, there are also reports that Anaerococcus may be a protective taxon against PTB [19]. There is strong evidence linking high Gardnerella vaginalis presence with PTB and bacterial vaginosis, which also increases PTB risk [44, 46].…”

Section: Resultsmentioning

confidence: 99%

Neural differential equations enable early-stage prediction of preterm birth using vaginal microbiota

Karambelkar,

Baranwal

2023

Preprint

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Preterm births (PTBs), i.e., births before 37 weeks of gestation are completed, are one of the leading issues concerning infant health, and is a problem that plagues all parts of the world. Millions of infants are born preterm globally each year, resulting in developmental disorders in infants and increase in neonatal mortality. Although there are known risk factors for PTB, the current procedures used to assess PTB risk are effective only at the later stages of pregnancy, which reduces the impact of currently possible interventions administered to prevent PTB or mitigate its ill-effects. Vaginal microbial communities have recently garnered attention in the context of PTB, with the notion that a highly diverse microbiome is detrimental as far as PTB is concerned. Increased abundance or scarcity of certain microbial species belonging to specific genera has also been linked to PTB risk. Consequently, attempts have been made towards establishing a correlation between alpha-diversity indices associated with vaginal microbial communities, and PTB. However, the vaginal microbiome varies greatly from individual to individual, and this variation is more pronounced in racially, ethnically and geographically diverse populations, which diversity indices may not be able to overcome. Machine learning (ML)-based approaches have also previously been explored, however, the success of these approaches reported thus far has been limited. Additionally, microbial communities have been reported to evolve during the duration of the pregnancy, and capturing such a signature may require higher, more complex modeling paradigms. Thus, alternative approaches are necessary to identify signatures in these microbial communities that are capable of distinguishing PTB from a full-term pregnancy. In this study, we have highlighted the limitations of diversity indices for prediction of PTB in racially diverse cohorts. We applied Deep Learning (DL)-based methods to vaginal microbial abundance profiles obtained at various stages of pregnancy, and Neural Controlled Differential Equations (CDEs) are able to identify a signature in the temporally-evolving vaginal microbiome during trimester 2 and can predict incidences of PTB (mean test set ROC-AUC = 0.81, accuracy = 75%, F1-score = 0.71) significantly better than traditional ML classifiers such as Random Forests (mean test set ROC-AUC = 0.65, accuracy = 66%, F1-score = 0.42) and Decision Trees (mean test set ROC-AUC = 0.48, accuracy = 46%, F1-score = 0.40), thus enabling effective early-stage PTB risk assessment.

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Section: Resultsmentioning

confidence: 99%

Neural differential equations enable early-stage prediction of preterm birth using vaginal microbiota

Karambelkar,

Baranwal

2023

Preprint

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“…Premature rupture of membranes (PROM), a process of spontaneous rupture of membranes before the onset of labor [57], is another adverse pregnancy closely associated with the imbalance of vaginal microbiota [58][59][60][61]. PPROM has closely related to maternal and neonatal morbidities, such as significantly lower birth weight and gestational age, earlyonset neonatal sepsis, funicity, endometritis, chorioamnionitis urinary tract infection, and postpartum bacteremia [58,62]. Infection is probably one of the most important mechanisms of PROM.…”

Section: Vaginal Microbiota and Premature Rupture Of Membranesmentioning

confidence: 99%

“…Richard G. B found that erythromycin treatment of vaginal microflora disorders in patients with PROM exacerbated vaginal dysbiosis, including Lactobacillus depletion and increased relative abundance of Sneathia and increased the risk of subsequent mycotic vaginitis and neonatal sepsis [13]. The disturbance of vaginal flora caused by antibiotic therapy may aggravate the occurrence of adverse conditions in the mother and fetus [13,62,108]. Therefore, individualized treatment and probiotics should be recommended instead of antimicrobial regimens alone to treat adverse outcomes caused by vaginal dysbiosis [102].…”

Section: Identify Pregnant Women At High Risk and Search For Effectiv...mentioning

confidence: 99%

Advances in Research on the Relationship between Vaginal Microbiota and Adverse Pregnancy Outcomes and Gynecological Diseases

Zhao

Ying

2023

Microorganisms

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The human microbiota inhabiting different parts of the body has been shown to have a significant impact on human health, with the gut microbiota being the most extensively studied in relation to disease. However, the vaginal microbiota is also an essential commensal microbiota in the female body that plays a crucial role in female health. Despite receiving less attention than gut microbiota, its importance in regulating reproductive immunity and its complex dynamic properties have been increasingly recognized in recent years. Advances in research on the relationship between vaginal microbiota and pregnancy outcomes & gynecological diseases in women have shed light on the importance of maintaining a healthy vaginal microbiota. In this review, we aim to compile recent developments in the study of the vaginal microbial ecosystem and its role in female health and reproductive outcomes. We provide a comprehensive account of the normal vaginal microbiota, the association between the vaginal microbiota and pregnancy outcomes, and the impact of the vaginal microbiota on gynecological diseases in women. By reviewing recent research, we hope to contribute to the advancement of academic medicine’s understanding of the vaginal microbiota’s importance in female health. We also aim to raise awareness among healthcare professionals and the general public of the significance of maintaining a healthy vaginal microbiota for better reproductive health and the prevention of gynecological diseases.

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“…10 BV or vaginal dysbiosis during pregnancy has been linked to several complications such as ascending bacterial infections, preterm birth, preterm premature rupture of membranes, and lower birth weight. 11 Interestingly, African and Hispanic women on average have a higher prevalence of Gardnerella, Atopobium, and Corynebacterium among other obligate and facultative bacterium that normally maintain a higher pH than Lactobacilli without clinical presentation of BV. 12 This suggests that the population of the bacterium may not be the sole factor in identifying or inducing vaginal dysbiosis.…”

Section: Introductionmentioning

confidence: 99%

“…This is likely due to hormonal differences that regulate estrogen production and glycogen metabolism during pregnancy that promote a less‐diverse environment with reduced Lactobacilli abundance 10 . BV or vaginal dysbiosis during pregnancy has been linked to several complications such as ascending bacterial infections, preterm birth, preterm premature rupture of membranes, and lower birth weight 11 . Interestingly, African and Hispanic women on average have a higher prevalence of Gardnerella , Atopobium , and Corynebacterium among other obligate and facultative bacterium that normally maintain a higher pH than Lactobacilli without clinical presentation of BV 12 .…”

Section: Introductionmentioning

confidence: 99%

Validation of vaginal microbiome proxies for in vitro experiments that biomimic Lactobacillus‐dominant vaginal cultures

Zahra,

Menon,

Bento

et al. 2023

American J Rep Immunol

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The vaginal microbiome includes diverse microbiota dominated by Lactobacillus [L.] spp. that protect against infections, modulate inflammation, and regulate vaginal homeostasis. Because it is challenging to incorporate vaginal microbiota into in vitro models, including organ‐on‐a‐chip systems, we assessed microbial metabolites as reliable proxies in addition to traditional vaginal epithelial cultures (VECs). Human immortalized VECs cultured on transwells with an air‐liquid interface generated stratified cell layers colonized by transplanted healthy microbiomes (L. jensenii‐ or L. crispatus‐dominant) or a community representing bacterial vaginosis (BV). After 48‐h, a qPCR array confirmed the expected donor community profiles. Pooled apical and basal supernatants were subjected to metabolomic analysis (untargeted mass spectrometry) followed by ingenuity pathways analysis (IPA). To determine the bacterial metabolites’ ability to recreate the vaginal microenvironment in vitro, pooled bacteria‐free metabolites were added to traditional VEC cultures. Cell morphology, viability, and cytokine production were assessed. IPA analysis of metabolites from colonized samples contained fatty acids, nucleic acids, and sugar acids that were associated with signaling networks that contribute to secondary metabolism, anti‐fungal, and anti‐inflammatory functions indicative of a healthy vaginal microbiome compared to sterile VEC transwell metabolites. Pooled metabolites did not affect cell morphology or induce cell death (∼5.5%) of VEC cultures (n = 3) after 72‐h. However, metabolites created an anti‐inflammatory milieu by increasing IL‐10 production (p = .06, T‐test) and significantly suppressing pro‐inflammatory IL‐6 (p = .0001), IL‐8 (p = .009), and TNFα (p = .0007) compared to naïve VEC cultures. BV VEC conditioned‐medium did not affect cell morphology nor viability; however, it induced a pro‐inflammatory environment by elevating levels of IL‐6 (p = .023), IL‐8 (p = .031), and TNFα (p = .021) when compared to L.‐dominate microbiome‐conditioned medium. VEC transwells provide a suitable ex vivo system to support the production of bacterial metabolites consistent with the vaginal milieu allowing subsequent in vitro studies with enhanced accuracy and utility.

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Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis

Cited by 21 publications

References 66 publications

Neural differential equations enable early-stage prediction of preterm birth using vaginal microbiota

Neural differential equations enable early-stage prediction of preterm birth using vaginal microbiota

Advances in Research on the Relationship between Vaginal Microbiota and Adverse Pregnancy Outcomes and Gynecological Diseases

Validation of vaginal microbiome proxies for in vitro experiments that biomimic Lactobacillus‐dominant vaginal cultures

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