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.Trial RegistrationClinicalTrials.gov NCT02139839

Evaluation of the Effect of Probiotic Administration on Gene Expression in Goat Blood

“…Similar studies conducted by Adjei-Fremah et al, (2017) reported that probiotics modulated the expression of TLR 2, 6, 7 and 8 in cow but in our study probiotics modulated the expression of TLR 4, 6, 7 and 9 and induced the expression of TLR 2 and 8. Previous studies conducted by Bisanz et al, (2014) showed that probiotics had an immunemodulatory response on TLR2 which also corroborates with our study. TLR2 is specifically involved in the detection of gram-positive surface markers and also serves as an indicative of increased anti-bacterial innate immune system activity (Bisanz et al, 2014).…”

“…Previous studies conducted by Bisanz et al, (2014) showed that probiotics had an immunemodulatory response on TLR2 which also corroborates with our study. TLR2 is specifically involved in the detection of gram-positive surface markers and also serves as an indicative of increased anti-bacterial innate immune system activity (Bisanz et al, 2014).…”

Long-term irritable bowel syndrome symptom control with reintroduction of selected FODMAPs

“…DNA was extracted using the MoBio 96-well Soil DNA Extraction kit (MoBio Laboratories Inc., Carlsbad, CA, United States) according to the Earth Microbiome Projects protocols (). Samples were then amplified using primers based on the bacterial/archael primers 515F/806R and amplified, sequenced and analyzed as before[44]. Taxonomy was assigned using the RDP classifier[45] to assign taxonomy to genus level with any taxonomic level with a ≤ 0.80 confidence score assigned “unclassified”.…”

The development of probiotics for women’s health

“…In the first studies to use microarrays and transcriptomics for this purpose, vaginal cells were shown to "sense" the GR-1 strain, resulting in upregulation of pattern recognition receptors, antimicrobial peptide psoriasin, mucin 4, cytokine receptors for IL-1␤, IL-8, IL-18, and especially caspase-8, a proapoptotic protease, which has a key role in lymphocyte activation and protective immunity (Kirjavainen et al 2008). A study in which GR-1 and RC-14 or placebo capsules were introduced vaginally again showed an ability to modulate protective immunity (Bisanz et al 2014b).…”