A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women

Jordan E Bisanz; Shannon Seney; Amy McMillan; Rebecca Vongsa; David Koenig; LungFai Wong; Barbara Dvoracek; Gregory B Gloor; Mark Sumarah; Brenda Ford; Dorli Herman; Jeremy P Burton; Gregor Reid

doi:10.1371/journal.pone.0104511

A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women

PLoS One. 2014 Aug 15;9(8):e104511. doi: 10.1371/journal.pone.0104511. eCollection 2014.

Authors

Affiliations

¹ Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada; Microbiology and Immunology, The University of Western Ontario, London, Canada.
² Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada.
³ Kimberly Clark Corporation, Corporate Research and Engineering-Microbial Control, Neenah, Wisconsin, United States of America.
⁴ Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada; Biochemistry, The University of Western Ontario, London, Canada.
⁵ Agriculture and Agri-Food Canada, London, Canada.
⁶ Springbank Medical Clinic, London, Canada.
⁷ Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada; Microbiology and Immunology, The University of Western Ontario, London, Canada; Surgery, The University of Western Ontario, London, Canada; Division of Urology, The University of Western Ontario, London, Canada.
⁸ Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada; Microbiology and Immunology, The University of Western Ontario, London, Canada; Surgery, The University of Western Ontario, London, Canada.

Abstract

A lactobacilli dominated microbiota in most pre and post-menopausal women is an indicator of vaginal health. The objective of this double blinded, placebo-controlled crossover study was to evaluate in 14 post-menopausal women with an intermediate Nugent score, the effect of 3 days of vaginal administration of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 (2.5×109 CFU each) on the microbiota and host response. The probiotic treatment did not result in an improved Nugent score when compared to when placebo. Analysis using 16S rRNA sequencing and metabolomics profiling revealed that the relative abundance of Lactobacillus was increased following probiotic administration as compared to placebo, which was weakly associated with an increase in lactate levels. A decrease in Atopobium was also observed. Analysis of host responses by microarray showed the probiotics had an immune-modulatory response including effects on pattern recognition receptors such as TLR2 while also affecting epithelial barrier function. This is the first study to use an interactomic approach for the study of vaginal probiotic administration in post-menopausal women. It shows that in some cases multifaceted approaches are required to detect the subtle molecular changes induced by the host to instillation of probiotic strains.

Trial registration: ClinicalTrials.gov NCT02139839.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intravaginal
Adult
Aged
Aged, 80 and over
Double-Blind Method
Female
Humans
Lacticaseibacillus rhamnosus / growth & development
Lacticaseibacillus rhamnosus / metabolism*
Limosilactobacillus reuteri / growth & development
Limosilactobacillus reuteri / metabolism*
Microbiota / physiology
Middle Aged
Placebos
Postmenopause
Probiotics / therapeutic use*
RNA, Ribosomal, 16S / genetics
Systems Biology / methods
Tight Junctions / physiology
Toll-Like Receptor 2 / metabolism
Treatment Outcome
Vagina / microbiology*
Vaginosis, Bacterial / microbiology
Vaginosis, Bacterial / therapy*

Substances

Placebos
RNA, Ribosomal, 16S
TLR2 protein, human
Toll-Like Receptor 2

Associated data

ClinicalTrials.gov/NCT02139839

Grants and funding

This project was funded by Kimberly Clark Corperation who were involved in the study design, analysis and preparation of the manuscript. This work was funded by Kimberly Clark and RV, DK, LW and BD are employees of Kimberly Clark. In order to avoid conflict of interest, all authors, including employees of Kimberly Clark, were blinded to which treatment was received by which subject, until all the sample analysis had been completed.