Effects of oral probiotic supplements on vaginal microbiota during pregnancy: a randomised, double‐blind, placebo‐controlled trial with microbiome analysis

Abstract

Objective To determine the effects on the vaginal microbiota of an oral probiotic preparation administered from early pregnancy.Design Randomised, double blind, placebo-controlled trial.Setting Four maternity units in the UK.Population Women aged 16 years or older recruited at 9-14 weeks' gestation.Methods Participants were randomly allocated to receive oral capsules of probiotic containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each at 2.5 9 10 9 colony-forming units (CFUs) or placebo once daily from recruitment until the end of pregnancy.Main outcome measure Rates of bacterial vaginosis (BV, defined as Nugent score ≥7) at 18-20 weeks' gestation compared by logistic regression adjusted for possible confounders. ResultsThe primary analysis included 78% (238/304) of participants who initially consented (probiotic group 123, placebo group 115). Of these participants, 95% (227/238) reported an intake of 93% or more of the required number of capsules. The rates of BV did not differ between groups at 18-20 weeks' gestation (15% (19/123) in the probiotic group vs. 9% (10/115) in the placebo group, adjusted odds ratio 1.82, 95% confidence interval 0.64-5.19). There were also no differences between the groups in the proportion of women colonised with the probiotic strains, Escherichia coli, group B streptococci or other vaginal microbiota. There were no differences in the alpha diversity or composition of the bacterial communities between or within the probiotic and placebo groups at 9-14 and 18-20 weeks' gestation.Conclusions Oral probiotics taken from early pregnancy did not modify the vaginal microbiota.

The complexity of an optimal vaginal biome

“…A probiotic containing Lactobacillus crispatus, or other human Lactobacillus isolates would be theoretically better in preventing BV than food strains that have had a chequered effect on preventing BV . The present report also found no changes between treatment groups in Escherichia coli or group B streptococci or in the overall diversity of microbes using sophisticated 16S DNA identification and analyses …”

“…In the most straightforward theoretical model, increasing the concentration of Lactobacillus might help to stabilise the flora and prevent BV. It is apparent from this report, and other reports, that simply flooding the vagina with Lactobacillus inconsistently prevents BV. Hence, other mechanisms of BV development such as the introduction of vaginal microbes that kill Lactobacillus and/or otherwise destabilise the complex environment need exploration before rational prevention programmes can be expected to work …”

“…In this report, following probiotic or placebo administration, Lactobacillus rhamnosus was detected in the vagina of only 5% of both groups and Lactobacillus reuteri was not detected in either group. A probiotic containing Lactobacillus crispatus, or other human Lactobacillus isolates would be theoretically better in preventing BV than food strains that have had a chequered effect on preventing BV .…”

“…However, two other questions remain with the present study and the first is the continued attempt to use L. rhamnosus and L. reuteri to affect the vaginal flora. Although these strains inhibit some vaginal flora species in vitro , it is probably best for a probiotic to be a lactobacillus species that usually populates the vagina.…”

“…I commend the effort required to undertake a modestly large trial to alter the vaginal microbiome . Its aim was to reduce preterm birth, the single most important and unsolved issue in obstetrics.…”