Microbial ColonizationPROROBIOTICSNCT04891523
Probiotic Modulation of Oral Microbiota
A study testing Probiotics-O (Burgerstein) in people with Microbial Colonization, run by Prof. Jacques SCHRENZEL at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Microbial Colonization
- What is being tested?
- Probiotics-O (Burgerstein)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Nov 2021to 24 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Informed Consent as documented by signature
- Good oral and general health
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Dissecting Probiotic Modulation of Oral Microbiota in Healthy Individuals
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.
Read the 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.
- Conditions
- Microbial Colonization
- Being tested
- Probiotics-O (Burgerstein), Placebo [inactivated Probiotics-O (Burgerstein)]
- Medical subject headings
- Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotics-O (Burgerstein)Dietary supplement
Topical oral treatment with the probiotic Streptococcus salivarius K12 (BIOTICS-O, Burgerstein) in form of a lozenge, daily, during 3 weeks.
Placebo [inactivated Probiotics-O (Burgerstein)]Other
Topical oral treatment with the placebo [inactivated probiotic Streptococcus salivarius K12 (BIOTICS-O, Burgerstein)] in form of a lozenge, daily, during 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo-Probiotic | Other | First receive placebo, then active probiotics. Receives: Dietary Supplement: Probiotics-O (Burgerstein); Other: Placebo [inactivated Probiotics-O (Burgerstein)] |
| Probiotic-Placebo | Other | First receive active probiotics, then placebo. Receives: Dietary Supplement: Probiotics-O (Burgerstein); Other: Placebo [inactivated Probiotics-O (Burgerstein)] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in the overall taxonomic profiles of the salivary bacterial communities (microbiota) following probiotics treatment
PERMANOVA test
Measured: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Changes in the relative abundance of individual bacterial taxa following probiotics treatment
ANCOM test
Measured: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Changes in the absolute abundance of individual bacterial taxa following probiotics treatment
Wilcoxon test
Measured: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Changes in the relative abundance of gene functions following probiotics treatment
Wilcoxon test
Measured: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Changes in the bacterial diversity (Shannon index)
Wilcoxon test
Measured: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Changes in the salivary cytokines levels following probiotics treatment
Wilcoxon test
Measured: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Secondary outcomes (2)
Positive and negative correlations between overall bacterial community taxonomic profile and salivary cytokine levels
DISTLM
Measured: Will be assessed at weeks 1, 4, 7, 10, 13, 16, 19
Positive and negative correlations between salivary bacterial taxa and salivary cytokine levels
Spearman Rho
Measured: Will be assessed at weeks 1, 4, 7, 10, 13, 16, 19
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2021
- Study start1 Nov 2021
- Primary completion24 Oct 2022
- Study completion24 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Microbial ColonizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof. Jacques SCHRENZEL
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Prof. Jacques SCHRENZEL, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04891523
- Sponsor's protocol ID
- 320030_197598
- Acronym
- PROROBIOTICS
- Status last verified
- May 2023
- First submitted
- 7 May 2021
- Last updated
- 11 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dissecting Probiotic Modulation of Oral Microbiota in Healthy Individuals
- ClinicalTrials.gov ID
- NCT04891523
- Acronym / sponsor ID
- PROROBIOTICS / 320030_197598
- Conditions
- Microbial Colonization
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Prof. Jacques SCHRENZELUniversity, hospital or other
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 24 Oct 2022 (actual)
- Study completion
- 24 Oct 2022 (actual)
- First posted
- 18 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo-Probiotic | Other | Dietary Supplement: Probiotics-O (Burgerstein), Other: Placebo [inactivated Probiotics-O (Burgerstein)]First receive placebo, then active probiotics. |
| Probiotic-Placebo | Other | Dietary Supplement: Probiotics-O (Burgerstein), Other: Placebo [inactivated Probiotics-O (Burgerstein)]First receive active probiotics, then placebo. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Informed Consent as documented by signature
- Good oral and general health
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotics-O (Burgerstein)Topical oral treatment with the probiotic Streptococcus salivarius K12 (BIOTICS-O, Burgerstein) in form of a lozenge, daily, during 3 weeks. | Dietary supplement | Placebo-Probiotic, Probiotic-Placebo |
| Placebo [inactivated Probiotics-O (Burgerstein)]Topical oral treatment with the placebo [inactivated probiotic Streptococcus salivarius K12 (BIOTICS-O, Burgerstein)] in form of a lozenge, daily, during 3 weeks. | Other | Placebo-Probiotic, Probiotic-Placebo |
Primary outcome
Changes in the overall taxonomic profiles of the salivary bacterial communities (microbiota) following probiotics treatment
Time frame: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
PERMANOVA test
Changes in the relative abundance of individual bacterial taxa following probiotics treatment
Time frame: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
ANCOM test
Changes in the absolute abundance of individual bacterial taxa following probiotics treatment
Time frame: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Wilcoxon test
Changes in the relative abundance of gene functions following probiotics treatment
Time frame: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Wilcoxon test
Changes in the bacterial diversity (Shannon index)
Time frame: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Wilcoxon test
Changes in the salivary cytokines levels following probiotics treatment
Time frame: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo
Wilcoxon test
2 secondary outcomes
Positive and negative correlations between overall bacterial community taxonomic profile and salivary cytokine levels
Time frame: Will be assessed at weeks 1, 4, 7, 10, 13, 16, 19
Positive and negative correlations between salivary bacterial taxa and salivary cytokine levels
Time frame: Will be assessed at weeks 1, 4, 7, 10, 13, 16, 19
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotics-O (Burgerstein) in people with Microbial Colonization, run by Prof. Jacques SCHRENZEL at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the overall taxonomic profiles of the salivary bacterial communities (microbiota) following probiotics treatment (time frame: Will be assessed at the end of a three-week course of no treatment, probiotics or placebo). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2023.