Probiotic Modulation of Oral Microbiota (PROROBIOTICS)
Primary Purpose
Microbial Colonization
Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Probiotics-O (Burgerstein)
Placebo [inactivated Probiotics-O (Burgerstein)]
Sponsored by
About this trial
This is an interventional other trial for Microbial Colonization
Eligibility Criteria
Inclusion Criteria:
- Informed Consent as documented by signature
- Good oral and general health
Exclusion Criteria:
- Women who are pregnant or breast feeding
- Intention to become pregnant during the course of the study
- Systemic disease
- Previous enrolment into the current study
- Clinically diagnosed severe oral lesions
- Use of antibiotics and topical oral probiotics within the 3 months preceding the study or during the study
- Dental treatments and use of oral disinfectants within 30 days preceding the study or during the study
Sites / Locations
- Geneva University Hospitals (HUG)
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
Placebo-Probiotic
Probiotic-Placebo
Arm Description
First receive placebo, then active probiotics.
First receive active probiotics, then placebo.
Outcomes
Primary Outcome Measures
Changes in the overall taxonomic profiles of the salivary bacterial communities (microbiota) following probiotics treatment
PERMANOVA test
Changes in the relative abundance of individual bacterial taxa following probiotics treatment
ANCOM test
Changes in the absolute abundance of individual bacterial taxa following probiotics treatment
Wilcoxon test
Changes in the relative abundance of gene functions following probiotics treatment
Wilcoxon test
Changes in the bacterial diversity (Shannon index)
Wilcoxon test
Changes in the salivary cytokines levels following probiotics treatment
Wilcoxon test
Secondary Outcome Measures
Positive and negative correlations between overall bacterial community taxonomic profile and salivary cytokine levels
DISTLM
Positive and negative correlations between salivary bacterial taxa and salivary cytokine levels
Spearman Rho
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04891523
Brief Title
Probiotic Modulation of Oral Microbiota
Acronym
PROROBIOTICS
Official Title
Dissecting Probiotic Modulation of Oral Microbiota in Healthy Individuals
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 1, 2021 (Actual)
Primary Completion Date
October 24, 2022 (Actual)
Study Completion Date
October 24, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Prof. Jacques SCHRENZEL
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Targeting human microbiota, in particular those of the gastrointestinal tract, by means of prebiotics, probiotics, symbiotics or antibiotics has gained interest for its potential in the management of human health. Oral bacterial communities have been extensively studied over the last decade both in normal and pathological states; however, little data are available on the possibility to modify microbiota composition in a controlled and 'non-aggressive' manner by using probiotics, in order to improve oral health.
Saliva contains microorganisms attached to exfoliated human cells and released from oral biofilms; its microbiota is most similar (proportionally) to those of the dorsal and lateral tongue. In addition, bacteria belonging to genera Porphyromonas, Tannerella and Treponema, which contain species associated with periodontitis, are consistently identified in saliva. Salivary microbial communities are relatively stable and thus potentially interesting as an indicator of oral and general health. Indeed, it has been suggested that interventions aimed at improving oral health should target mucosal microbiota (to which saliva is most similar) in addition to dental microbial communities. Whole saliva also constitutes an alternative to gingival crevicular fluid when analysing analytes present in periodontal pockets. It has been suggested that saliva reflects a consensus inflammatory status of the whole mouth with potentially significant clinical relevance.
Strain K12 of Streptococcus salivarius is available internationally as a food supplement, notably for oral hygiene. Several studies investigated the effectiveness of S. salivarius as a probiotic in the context of pharyngeal infections, halitosis, plaque formation and caries. Our study will focus on the effects of supplementation with this commercially available oral probiotic on the resident microbiota and inflammatory markers in order to identify signatures associated with resistance/susceptibility to colonization by probiotic strains.
Detailed Description
OBJECTIVES
This is a monocentric, prospective, cross-over, randomized, double-blinded study in which all participants will receive placebo and active probiotic treatment, 15 of which will first be treated with placebo and then will be given probiotics. The other 15 participants will first get probiotics and then, after a 3-week wash out period, the placebo.
The main objective of the study is to assess changes in salivary microbiota profiles and inflammatory markers following S. salivarius probiotic treatment. Our secondary objective is to identify correlations between specific salivary microbial taxa (subspecies to phylum levels) and inflammatory markers. Clinical outcome is not the focus of this study, although basic information about the oral health will be measured.
METHODOLOGY
BIOTICS-O (Burgerstein) probiotic that will be used is a commercial food supplement available over the counter in the pharmacy as blister packs of 30 lozenges containing 10^9 CFU of S. salivarius K12. Participants will let melt the lozenge after tooth brushing in the evening.
Placebo lozenges (inactivated probiotic) will have the same look, taste and smell as the active treatment lozenges, and they will be administered in the same way as the active treatment lozenges.
Metagenomic analysis of the microbiota:
Indexed paired-end metagenomic libraries will be prepared using DNA extracted from saliva and sequenced for 2x150 cycles on an Illumina NovaSeq 6000 instrument to generate 5-10 million read pairs per sample. Our standard metagenomic analysis pipeline (HUGE-MAP) will be used; it includes: (i) read quality filtering; (ii) removal of replicate sequences; (iii) removal of read pairs that match human genome sequence and, (iv) classification of read pairs with CLARK against the collection of NCBI reference and representative bacterial, archaeal and fungal genomes, as well as Latest RefSeq NCBI genomes of prophages and DNA virus families whose members may infect humans. Functional assignments i.e. profiling the presence/absence and abundance of microbial gene families and pathways will be performed using MG-RAST server. Bacterial abundance will be measured by qPCR and/or relative to the number of reads obtained from the spiked calibrator.
Cytokine measurements:
Salivary cytokines (IL-1β, IL-6, IL-8, TNF-alpha) analysis will be performed using a Salimetrcs Core Cytokine Panel - 4-plex.
OBJECTIVES
This is a monocentric, prospective, cross-over, randomized, double-blinded study in which all participants will receive placebo and active probiotic treatment, 15 of which will first be treated with placebo and then will be given probiotics. The other 15 participants will first get probiotics and then, after a 3-week wash out period, the placebo.
The main objective of the study is to assess changes in salivary microbiota profiles and inflammatory markers following S. salivarius probiotic treatment. Our secondary objective is to identify correlations between specific salivary microbial taxa (subspecies to phylum levels) and inflammatory markers. Clinical outcome is not the focus of this study, although basic information about the oral health will be measured.
METHODOLOGY
BIOTICS-O (Burgerstein) probiotic that will be used is a commercial food supplement available over the counter in the pharmacy as blister packs of 30 lozenges containing 10^9 CFU of S. salivarius K12. Participants will let melt the lozenge after tooth brushing in the evening.
Placebo lozenges (inactivated probiotic) will have the same look, taste and smell as the active treatment lozenges, and they will be administered in the same way as the active treatment lozenges.
Metagenomic analysis of the microbiota:
Indexed paired-end metagenomic libraries will be prepared using DNA extracted from saliva and sequenced for 2x150 cycles on an Illumina NovaSeq 6000 instrument to generate 5-10 million read pairs per sample. Our standard metagenomic analysis pipeline (HUGE-MAP) will be used; it includes: (i) read quality filtering; (ii) removal of replicate sequences; (iii) removal of read pairs that match human genome sequence and, (iv) classification of read pairs with CLARK against the collection of NCBI reference and representative bacterial, archaeal and fungal genomes, as well as Latest RefSeq NCBI genomes of prophages and DNA virus families whose members may infect humans. Functional assignments i.e. profiling the presence/absence and abundance of microbial gene families and pathways will be performed using MG-RAST server. Bacterial abundance will be measured by qPCR and/or relative to the number of reads obtained from the spiked calibrator.
Cytokine measurements:
Salivary cytokines (IL-1β, IL-6, IL-8, TNF-alpha) analysis will be performed using a Salimetrix Core Cytokine Panel - 4-plex..
Samplings will be performed at weeks 1, 4, 7, 10, 13, 16 and 19.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Microbial Colonization
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo-Probiotic
Arm Type
Other
Arm Description
First receive placebo, then active probiotics.
Arm Title
Probiotic-Placebo
Arm Type
Other
Arm Description
First receive active probiotics, then placebo.
Intervention Type
Dietary Supplement
Intervention Name(s)
Probiotics-O (Burgerstein)
Intervention Description
Topical oral treatment with the probiotic Streptococcus salivarius K12 (BIOTICS-O, Burgerstein) in form of a lozenge, daily, during 3 weeks.
Intervention Type
Other
Intervention Name(s)
Placebo [inactivated Probiotics-O (Burgerstein)]
Intervention Description
Topical oral treatment with the placebo [inactivated probiotic Streptococcus salivarius K12 (BIOTICS-O, Burgerstein)] in form of a lozenge, daily, during 3 weeks.
Primary Outcome Measure Information:
Title
Changes in the overall taxonomic profiles of the salivary bacterial communities (microbiota) following probiotics treatment
Description
PERMANOVA test
Time Frame
Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Title
Changes in the relative abundance of individual bacterial taxa following probiotics treatment
Description
ANCOM test
Time Frame
Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Title
Changes in the absolute abundance of individual bacterial taxa following probiotics treatment
Description
Wilcoxon test
Time Frame
Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Title
Changes in the relative abundance of gene functions following probiotics treatment
Description
Wilcoxon test
Time Frame
Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Title
Changes in the bacterial diversity (Shannon index)
Description
Wilcoxon test
Time Frame
Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Title
Changes in the salivary cytokines levels following probiotics treatment
Description
Wilcoxon test
Time Frame
Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Secondary Outcome Measure Information:
Title
Positive and negative correlations between overall bacterial community taxonomic profile and salivary cytokine levels
Description
DISTLM
Time Frame
Will be assessed at weeks 1, 4, 7, 10, 13, 16, 19
Title
Positive and negative correlations between salivary bacterial taxa and salivary cytokine levels
Description
Spearman Rho
Time Frame
Will be assessed at weeks 1, 4, 7, 10, 13, 16, 19
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Informed Consent as documented by signature
Good oral and general health
Exclusion Criteria:
Women who are pregnant or breast feeding
Intention to become pregnant during the course of the study
Systemic disease
Previous enrolment into the current study
Clinically diagnosed severe oral lesions
Use of antibiotics and topical oral probiotics within the 3 months preceding the study or during the study
Dental treatments and use of oral disinfectants within 30 days preceding the study or during the study
Facility Information:
Facility Name
Geneva University Hospitals (HUG)
City
Geneva
ZIP/Postal Code
1211
Country
Switzerland
12. IPD Sharing Statement
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Probiotic Modulation of Oral Microbiota
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