title: 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.
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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02139839.
authors.affiliation: Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada; Microbiology and Immunology, The University of Western Ontario, London, Canada.
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Bisanz
authors.affiliation: Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: Seney
authors.affiliation: Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada; Microbiology and Immunology, The University of Western Ontario, London, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: McMillan
authors.affiliation: Kimberly Clark Corporation, Corporate Research and Engineering-Microbial Control, Neenah, Wisconsin, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Vongsa
authors.affiliation: Kimberly Clark Corporation, Corporate Research and Engineering-Microbial Control, Neenah, Wisconsin, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Koenig
authors.affiliation: Kimberly Clark Corporation, Corporate Research and Engineering-Microbial Control, Neenah, Wisconsin, United States of America.
authors.forename: LungFai
authors.initials: L
authors.lastname: Wong
authors.affiliation: Kimberly Clark Corporation, Corporate Research and Engineering-Microbial Control, Neenah, Wisconsin, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Dvoracek
authors.affiliation: Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Canada; Biochemistry, The University of Western Ontario, London, Canada.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Gloor
authors.affiliation: Agriculture and Agri-Food Canada, London, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Sumarah
authors.affiliation: Springbank Medical Clinic, London, Canada.
authors.forename: Brenda
authors.initials: B
authors.lastname: Ford
authors.affiliation: Springbank Medical Clinic, London, Canada.
authors.forename: Dorli
authors.initials: D
authors.lastname: Herman
authors.affiliation: 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.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Burton
authors.affiliation: 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.
authors.forename: Gregor
authors.initials: G
authors.lastname: Reid
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D052200:Limosilactobacillus reuteri / Q000254:growth & development / Q000378:metabolism*; D052201:Lacticaseibacillus rhamnosus / Q000254:growth & development / Q000378:metabolism*; D064307:Microbiota / Q000502:physiology; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D019936:Probiotics / Q000627:therapeutic use*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D049490:Systems Biology / Q000379:methods; D019108:Tight Junctions / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D016896:Treatment Outcome; D014621:Vagina / Q000382:microbiology*; D016585:Vaginosis, Bacterial / Q000382:microbiology / Q000628:therapy*
chemical_list: D010919:Placebos; D012336:RNA, Ribosomal, 16S; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2