TY - JOUR
T1 - Intermittent Lactobacilli-containing Vaginal Probiotic or Metronidazole Use to Prevent Bacterial Vaginosis Recurrence
T2 - A Pilot Study Incorporating Microscopy and Sequencing
AU - van de Wijgert, Janneke H H M
AU - Verwijs, Marijn C
AU - Agaba, Stephen K
AU - Bronowski, Christina
AU - Mwambarangwe, Lambert
AU - Uwineza, Mireille
AU - Lievens, Elke
AU - Nivoliez, Adrien
AU - Ravel, Jacques
AU - Darby, Alistair C
N1 - Funding Information:
We thank the study participants, the Rinda Ubuzima team, the National Reference Laboratory in Kigali, the Centre for Genomic Research and research support staff at the University of Liverpool, Christina Gill, Robert Meester, Mike Humphreys, Jessica Younes, Vicky Jespers, Tania Crucitti, and Anna Maria Geretti. This work was funded by the DFID/MRC/Wellcome Trust Joint Global Health Trials Scheme as a Development Project (grant reference MR/M017443/1; grant title: “Preparing for a clinical trial of interventions to maintain normal vaginal microbiota for preventing adverse reproductive health outcomes in Africa”) and the University of Liverpool (Technology Directorate Voucher). Vaginal probiotics for use in the trial were donated free of charge by Winclove Probiotics (Amsterdam, The Netherlands) and Biose (formerly Probionov, Arpajon-sur-Cère, France). The findings and conclusions in this paper are those of the authors and do not necessarily represent the views of the authors’ institutions or companies, or the funders.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Bacterial vaginosis (BV) is associated with HIV acquisition and adverse pregnancy outcomes. Recurrence after metronidazole treatment is high. HIV-negative, non-pregnant Rwandan BV patients were randomized to four groups (n = 17/group) after seven-day oral metronidazole treatment: behavioral counseling only (control), or counseling plus intermittent use of oral metronidazole, Ecologic Femi+ vaginal capsule (containing multiple Lactobacillus and one Bifidobacterium species), or Gynophilus LP vaginal tablet (L. rhamnosus 35) for two months. Vaginal microbiota assessments at all visits included Gram stain Nugent scoring and 16S rRNA gene qPCR and HiSeq sequencing. All interventions were safe. BV (Nugent 7-10) incidence was 10.18 per person-year at risk in the control group, and lower in the metronidazole (1.41/person-year; p = 0.004), Ecologic Femi+ (3.58/person-year; p = 0.043), and Gynophilus LP groups (5.36/person-year; p = 0.220). In mixed effects models adjusted for hormonal contraception/pregnancy, sexual risk-taking, and age, metronidazole and Ecologic Femi+ users, each compared to controls, had higher Lactobacillus and lower BV-anaerobes estimated concentrations and/or relative abundances, and were less likely to have a dysbiotic vaginal microbiota type by sequencing. Inter-individual variability was high and effects disappeared soon after intervention cessation. Lactobacilli-based vaginal probiotics warrant further evaluation because, in contrast to antibiotics, they are not expected to negatively affect gut microbiota or cause antimicrobial resistance.
AB - Bacterial vaginosis (BV) is associated with HIV acquisition and adverse pregnancy outcomes. Recurrence after metronidazole treatment is high. HIV-negative, non-pregnant Rwandan BV patients were randomized to four groups (n = 17/group) after seven-day oral metronidazole treatment: behavioral counseling only (control), or counseling plus intermittent use of oral metronidazole, Ecologic Femi+ vaginal capsule (containing multiple Lactobacillus and one Bifidobacterium species), or Gynophilus LP vaginal tablet (L. rhamnosus 35) for two months. Vaginal microbiota assessments at all visits included Gram stain Nugent scoring and 16S rRNA gene qPCR and HiSeq sequencing. All interventions were safe. BV (Nugent 7-10) incidence was 10.18 per person-year at risk in the control group, and lower in the metronidazole (1.41/person-year; p = 0.004), Ecologic Femi+ (3.58/person-year; p = 0.043), and Gynophilus LP groups (5.36/person-year; p = 0.220). In mixed effects models adjusted for hormonal contraception/pregnancy, sexual risk-taking, and age, metronidazole and Ecologic Femi+ users, each compared to controls, had higher Lactobacillus and lower BV-anaerobes estimated concentrations and/or relative abundances, and were less likely to have a dysbiotic vaginal microbiota type by sequencing. Inter-individual variability was high and effects disappeared soon after intervention cessation. Lactobacilli-based vaginal probiotics warrant further evaluation because, in contrast to antibiotics, they are not expected to negatively affect gut microbiota or cause antimicrobial resistance.
UR - http://www.scopus.com/inward/record.url?scp=85080942029&partnerID=8YFLogxK
U2 - 10.1038/s41598-020-60671-6
DO - 10.1038/s41598-020-60671-6
M3 - Article
C2 - 32127550
SN - 2045-2322
VL - 10
SP - 3884
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 3884
ER -