Study validates the association between vaginal microbiota and preterm birth

Altered maternal vaginal microbiota composition contributes to the pathophysiology of preterm birth (PTB), according to a study of two racially distinct cohorts of US pregnant women.

The findings, which were reported in PNAS, extend and corroborate previous studies that have shown this link. However, in recent years, conflicting results have questioned the association.

The authors of the current study note that these conflicting outcomes may be due to black women having a different risk profile, resulting in a dissimilar range of normal vaginal community composition.

The new study compared PTB to term birth in predominately Caucasian women at low risk for PTB birth from Stanford University School of Medicine (n = 39) and in mostly African-American women at high risk for PTB from the University of Alabama at Birmingham (n = 96).

The investigators profiled the taxonomic composition of 2,179 vaginal swabs collected prospectively and weekly during gestation with 165 rRNA gene sequencing.

“Previously proposed associations between preterm birth and lower Lactobacillus and higher Gardnerella abundances replicated in the low-risk cohort, but not in the high-risk cohort,” the authors wrote.

The odds ratios for the associations with frequencies of  Lactobacillus and Gardnerella in the low-risk cohort were calculated to be 5.81 and 5.12, respectively.

The study demonstrates the value of high-resolution statistical bioinformatics for clinical microbiome trials. Such methodology allowed taxonomic assignment to the species and subspecies level, for which Lactobacillus crispatus corresponded to low risk of PTB in both cohorts, whereas Lactobacillus iners did not.

However, in the high-risk cohort, a decreased abundance of the less common species Lactobacillus jensenii and Lactobacillus gasseri was linked to PTB.

On the other hand, the refined Lactobacillus and Gardnerella associations in the low-risk cohort suggest that the replicated relationship is evident from early on in the second trimester.

The genus associated with PTB is a subspecies clade of Gardnerella vaginalis.

The study also concluded that patterns of co-occurrence between L. crispatus and Gardneralla were highly exclusive; in contrast, Gardnerella and Lactibacillus iners often coexisted at high frequencies.

Combined, the Lactobacillus and Gardnerella genera comprised more than two-thirds of the vaginal microbiota from the two cohorts. One notable difference, however, was the higher frequency of Gardneralla in the high-risk cohort (8.3%) compared to the low-risk cohort (4.7%).

There was also a lower frequency of L. crispatus in the high-risk cohort (15%) than in the low-risk cohort (45%).

In addition, Prevotella was associated with PTB in both cohorts, but most other genera frequently linked to bacterial vaginosis (BV) and tested were significantly linked to the low-risk group only.

“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,” the authors wrote.

The authors advocate a more precise characterization of PTB -associated alterations in the vaginal microbiota because of the nonspecific diagnosis of BV and the previous failures of antibiotic treatment for BV to reduce PTB.

Furthermore, for clinical applications, the authors believe exact sequence variants should be chosen over operational taxonomic units, given that the impact on health can vary substantially among closely related taxa.

Despite the study’s many strengths, the investigators were unable to distinguish between the effects of race, progesterone treatment and prior history of PTB. In addition, heterogeneity for the type of PTB, like spontaneous or medically indicated, is missing.

Nonetheless, “Our findings elucidate the ecology of the vaginal microbiota and advance our ability to predict and understand the cause of preterm birth,” the authors wrote.