A New Era of the Vaginal Microbiome: Advances Using Next‐Generation Sequencing

Fettweis, Jennifer M.; Serrano, Myrna G.; Girerd, Philippe H.; Jefferson, Kimberly K.; Buck, Gregory A.

doi:10.1002/cbdv.201100359

Cited by 75 publications

(69 citation statements)

References 105 publications

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“…High-throughput sequencing methods have facilitated new lines of investigation into the microbial etiology of PTB (9,10). Amplification and high-throughput sequencing of the 16S rRNA gene (metabarcoding) simultaneously measures the presence and relative abundance of thousands of bacterial taxa (composition), and resolves differences to the level of genus and sometimes species or subspecies.…”

mentioning

confidence: 99%

Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women

Callahan

DiGiulio

Goltsman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

326

482

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Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. Previous studies have suggested that the maternal vaginal microbiota contributes to the pathophysiology of PTB, but conflicting results in recent years have raised doubts. We conducted a study of PTB compared with term birth in two cohorts of pregnant women: one predominantly Caucasian (n = 39) at low risk for PTB, the second predominantly African American and at high-risk (n = 96). We profiled the taxonomic composition of 2,179 vaginal swabs collected prospectively and weekly during gestation using 16S rRNA gene sequencing. Previously proposed associations between PTB and lower Lactobacillus and higher Gardnerella abundances replicated in the low-risk cohort, but not in the high-risk cohort. High-resolution bioinformatics enabled taxonomic assignment to the species and subspecies levels, revealing that Lactobacillus crispatus was associated with low risk of PTB in both cohorts, while Lactobacillus iners was not, and that a subspecies clade of Gardnerella vaginalis explained the genus association with PTB. Patterns of cooccurrence between L. crispatus and Gardnerella were highly exclusive, while Gardnerella and L. iners often coexisted at high frequencies. We argue that the vaginal microbiota is better represented by the quantitative frequencies of these key taxa than by classifying communities into five community state types. Our findings extend and corroborate the association between the vaginal microbiota and PTB, demonstrate the benefits of high-resolution statistical bioinformatics in clinical microbiome studies, and suggest that previous conflicting results may reflect the different risk profile of women of black race.pregnancy | prematurity | vaginal microbiota | Lactobacillus | Gardnerella P reterm birth (PTB; delivery at <37 gestational wk) affects ≈12% of US births and is the leading cause of neonatal death and morbidity worldwide. Multiple lines of evidence support a role for the indigenous microbial communities of the mother (the maternal microbiota) in the pathophysiology of PTB. Microbial invasion of the amniotic cavity is one of the most frequent causes of spontaneous PTB (1), and the most common invading taxa are consistent with maternal origin (2-4). Bacterial vaginosis (BV), a condition involving an altered vaginal microbiota, has been consistently identified as a risk factor for PTB (5, 6). Multiple studies have also found chronic periodontitis, another condition associated with an altered microbiota, to be a risk factor for PTB (7,8).High-throughput sequencing methods have facilitated new lines of investigation into the microbial etiology of PTB (9, 10). Amplification and high-throughput sequencing of the 16S rRNA gene (metabarcoding) simultaneously measures the presence and relative abundance of thousands of bacterial taxa (composition), and resolves differences to the level of genus and sometimes species or subspecies. To date, metabarcoding studies of the relationship between the vaginal microbiota and PTB have y...

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mentioning

confidence: 99%

Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women

Callahan

DiGiulio

Goltsman

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

326

482

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“…Since the first microbiological study of the human vagina, lactobacilli have been considered the dominant members of the microbiota of this organ (Doderlein, 1982), a finding that has been further confirmed by several recent metagenomic studies (Biagi et al, 2009;Fettweis et al, 2012;Martín et al, 2014;Pavlova et al, 2002;Song et al, 1999;Verhelst et al, 2004;Vitali et al, 2007;Wilks et al, 2004;Zhou et al, 2004). In total, around 20 different species of lactobacilli have been consistently isolated from the vagina, although only one or two species predominate at a time in a given individual.…”

Section: Introductionmentioning

confidence: 92%

Effect of iron on the probiotic properties of the vaginal isolate Lactobacillus jensenii CECT 4306

et al. 2015

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The vaginal microbiota of healthy, fertile women is dominated by lactobacilli. As a defence mechanism, these bacteria produce H 2 O 2 to discourage colonization of the vagina by undesirable micro-organisms. In particular, Lactobacillus jensenii CECT 4306 is a strong producer of H 2 O 2 and has been found to protect itself from the bactericidal effects of this compound through the activity of extracellular peroxidases. However, this peroxidase activity is dependent on the presence of Fe 3+ , which is found in elevated concentrations in the vaginal mucosa as a consequence of the menstrual discharge. The aim of the present work was to evaluate whether Fe 3+ is able to modulate other potential probiotic properties of strain 4306. We found that Fe 3+ enhances the adhesion of L. jensenii CECT 4306 to mucin and to HT-29 and HT-29 MTX cells, and, in addition, improves the anti-inflammatory profile, as judged by an increase in the ratio of IL-10/IL-12p70 that were secreted by macrophages. A comparison of total, secreted and surface proteins produced in the presence and absence of Fe 3+ revealed significant differences in the concentration of the moonlighting protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In conclusion, Fe 3+ seems to improve the probiotic characteristics of L. jensenii CECT 4306, and future research of the interactions of this strain with its vaginal environment may reveal further information about different aspects of its probiotic potential.

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“…Although several recent studies have described the vaginal microbiome [18], only a recent study, sampling DNA isolated from exfoliated cervical cells, has shown the existence of six cervical microbiome community types, characterized by a predominance of either Gardnerella vaginalis or Lactobacillus spp. [29].…”

Section: Cervical and Vaginal Microbiome Characterizationmentioning

confidence: 99%

“…This mixed community of microbial cells and the genes they contain, is collectively known as the microbiome. The total number of microbial cells found in the human body is ten times more than those of human cells [18,19,20], and the total number of genes associated with the human microbiome is considered more than 100 times the number of human genes [20]. The NIH launched the Human Microbiome Project in 2007 in order to understand human microbial communities [20,21].…”

Section: Next-generation Sequencing In the Study Of The Human Microbiomementioning

confidence: 99%

Role of Next-Generation Sequencing in Understanding the Interactions between Human Papillomavirus and the Cervicovaginal Microbiome

Cervantes

Hong

2013

Gynecol Obstet Invest

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The applications of next-generation sequencing in the field of human papillomavirus and associated neoplasias have extended beyond the accurate genotyping of human papillomavirus types. Next-generation sequencing is able to provide important information on the interactions of the cervicovaginal microbiome and environment with the virus, and the role that these factors play on its transmission and persistence. The advances in sequencing technologies have greatly contributed to the current knowledge of human cervicovaginal microbiome in recent years, allowing the assessment of microbiome variability between species, individuals and populations.

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A New Era of the Vaginal Microbiome: Advances Using Next‐Generation Sequencing

Cited by 75 publications

References 105 publications

Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women

Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women

Effect of iron on the probiotic properties of the vaginal isolate Lactobacillus jensenii CECT 4306

Role of Next-Generation Sequencing in Understanding the Interactions between Human Papillomavirus and the Cervicovaginal Microbiome

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