Microbial Colonization of Oral Probiotics

Assessment of Colonisation of Probiotic Bacterium Streptococcus Salivarius in the Oral Cavity

The aim of this study is to evaluate the colonization efficacy of probiotic lozenges and powders containing specific prebiotics in healthy adults

Study Overview

• Status: Recruiting
• Conditions: Microbial Colonization
• Intervention / Treatment: Dietary supplement: Streptococcus salivarius K12 lozenge; Dietary supplement: Probiotic S. salivarius K12 lozenges containing prebiotic A; Dietary supplement: Probiotic S. salivarius K12 lozenges containing prebiotic B; Dietary supplement: Probiotic S. salivarius K12 lozenges containing prebiotics A and B; Dietary supplement: Probiotic S. salivarius K12 powder; Dietary supplement: Probiotic S. salivarius K12 powder containing prebiotic A; Dietary supplement: Probiotic S. salivarius K12 powder containing prebiotic B; Dietary supplement: Probiotic S. salivarius K12 powder containing prebiotics A and B; Dietary supplement: Probiotic S. salivarius M18 lozenges; Dietary supplement: Probiotic S. salivarius M18 lozenges containing prebiotic A; Dietary supplement: Probiotic S. salivarius M18 lozenges containing prebiotic B; Dietary supplement: Probiotic S. salivarius M18 + lozenges containing prebiotic A and B

Detailed Description

This is a double-blind, randomized controlled colonization pilot study with no cross over to evaluate the colonization efficacy of lozenges and powders containing two different commercially available probiotic bacteria (S. salivarius K12 ) or S. salivarius M18 with or without 2 different prebiotic sugars or their combinations.

Participants will be randomly assigned to one of the 12 groups consuming probiotic lozenge or powder containing Streptococcus salivarius K12 or S. salivarius M18 with or without prebiotics (e.g. sugars that may promote probiotic activity) over a seven day period. Saliva samples will be collected at predetermined time points pre and post intervention. Colonisation efficacy will be determined by enumerating the probiotic in the saliva samples using standard microbiological techniques.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• New Zealand
  • Otago
    • Dunedin, Otago, New Zealand, 9012
      • Recruiting
      • Blis Technologies Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Male or Female 18y - 80y age
2. In general good health 18 - 80 years of age.
3. Practice good oral hygiene.

Exclusion criteria:

1. Have a history of autoimmune disease or are immunocompromised.
2. Are on concurrent antibiotic therapy or regular antibiotic use within last 1 week
3. History of allergy (e.g. dairy).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Streptococcus salivarius K12 lozenge	Dietary supplement: Streptococcus salivarius K12 lozenge; In this study, a lozenge will be evaluated for its potential of delivering probiotic Streptococcus salivarius K12 to the oral cavity.
Active Comparator: Probiotic S. salivarius K12 lozenges containing prebiotic A; Streptococcus salivarius K12 lozenge with prebiotic	Dietary supplement: Probiotic S. salivarius K12 lozenges containing prebiotic A; In this study, a lozenge containing a prebiotic will be evaluated for its potential of delivering probiotic Streptococcus salivarius K12 to the oral cavity.
Active Comparator: Probiotic S. salivarius K12 lozenges containing prebiotic B; Streptococcus salivarius K12 lozenge with prebiotic	Dietary supplement: Probiotic S. salivarius K12 lozenges containing prebiotic B; In this study, a lozenge containing a prebiotic will be evaluated for its potential of delivering probiotic Streptococcus salivarius K12 to the oral cavity.
Active Comparator: Probiotic S. salivarius K12 lozenges containing prebiotic A and B; Streptococcus salivarius K12	Dietary supplement: Probiotic S. salivarius K12 lozenges containing prebiotics A and B; In this study, a lozenge containing two prebiotics will be evaluated for its potential of delivering probiotic Streptococcus salivarius K12 to the oral cavity.
Active Comparator: Probiotic S. salivarius K12 powder; Streptococcus salivarius K12 powder	Dietary supplement: Probiotic S. salivarius K12 powder; In this study, a powder will be evaluated for its potential of delivering probiotic Streptococcus salivarius K12 to the oral cavity
Active Comparator: Probiotic S. salivarius K12 powder containing prebiotic A; Streptococcus salivarius K12 powder with prebiotic	Dietary supplement: Probiotic S. salivarius K12 powder containing prebiotic A; In this study, a powder containing a prebiotic will be evaluated for its potential of delivering probiotic Streptococcus salivarius K12 to the oral cavity
Active Comparator: Probiotic S. salivarius K12 powder containing prebiotic B; Streptococcus salivarius K12 powder with prebiotic	Dietary supplement: Probiotic S. salivarius K12 powder containing prebiotic B; In this study, a powder containing a prebiotic will be evaluated for its potential of delivering probiotic Streptococcus salivarius K12 to the oral cavity
Active Comparator: Probiotic S. salivarius K12 powder containing prebiotic A and B; Streptococcus salivarius K12 powder with prebiotic	Dietary supplement: Probiotic S. salivarius K12 powder containing prebiotics A and B; In this study, a powder containing two prebiotics will be evaluated for its potential of delivering probiotic Streptococcus salivarius K12 to the oral cavity
Active Comparator: Probiotic S. salivarius M18 lozenges; Streptococcus salivarius M18 lozenge	Dietary supplement: Probiotic S. salivarius M18 lozenges; In this study, a lozenge containing will be evaluated for its potential of delivering probiotic Streptococcus salivarius M18 to the oral cavity.
Active Comparator: Probiotic S. salivarius M18 lozenges containing prebiotic A; Streptococcus salivarius M18 lozenge with prebiotic	Dietary supplement: Probiotic S. salivarius M18 lozenges containing prebiotic A; In this study, a lozenge containing a prebiotic will be evaluated for its potential of delivering probiotic Streptococcus salivarius M18 to the oral cavity.
Active Comparator: Probiotic S. salivarius M18 lozenges der containing prebiotic B; Streptococcus salivarius M18 lozenge with prebiotic	Dietary supplement: Probiotic S. salivarius M18 lozenges containing prebiotic B; In this study, a lozenge containing a prebiotic will be evaluated for its potential of delivering probiotic Streptococcus salivarius M18 to the oral cavity.
Active Comparator: Probiotic S. salivarius M18 + lozenges containing prebiotic A and B; Streptococcus salivarius M18 lozenge with prebiotic	Dietary supplement: Probiotic S. salivarius M18 + lozenges containing prebiotic A and B; In this study, a lozenge containing two prebiotics will be evaluated for its potential of delivering probiotic Streptococcus salivarius M18 to the oral cavity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in microbial colonization from baseline (Day 0) to 1 hour for S. salivarius K12 lozenges	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius K12 with or without prebiotics from a lozenge format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to one hour after later across different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	1 hour
Change in microbial colonization from baseline (Day 0) to 8 hours or S. salivarius K12 lozenges	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius K12 with or without prebiotics from a lozenge format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to eight hours after later across different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	8 hour
Change in microbial colonization from baseline (Day 0) to 24 hours or S. salivarius K12 lozenges	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius K12 with or without prebiotics from a lozenge format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to 24 hours after later across different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	24 hour
Change in microbial colonization from baseline (Day 0) to 48 hours or S. salivarius K12 lozenges	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius K12 with or without prebiotics from a lozenge format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to 48hours after later across different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	48 hour
in microbial colonization from baseline (Day 0) to 1 hour for S. salivarius K12 powder format	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius K12 with or without prebiotics from a powder format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to one hour after later across two different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	1 hour
in microbial colonization from baseline (Day 0) to 8 hour for S. salivarius K12 powder format	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius K12 with or without prebiotics from a powder format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to 8 hours after later across two different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	8 hours
in microbial colonization from baseline (Day 0) to 24 hours for S. salivarius K12 powder format	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius K12 with or without prebiotics from a powder format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to 24 hours after later across two different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	24 hours
in microbial colonization from baseline (Day 0) to 48 hours for S. salivarius K12 powder format	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius K12 with or without prebiotics from a powder format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to 48 hours after later across two different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	48 hours
Change in microbial colonization from baseline (Day 0) to 1 hour for S. salivarius M18 lozenges	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius M18 with or without prebiotics from a lozenge format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to one hour after later across different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	1 hour
Change in microbial colonization from baseline (Day 0) to 8 hours for S. salivarius M18 lozenges	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius M18 with or without prebiotics from a lozenge format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to 8 hour after later across different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	8 hour
Change in microbial colonization from baseline (Day 0) to 24 hours for S. salivarius M18 lozenges	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius M18 with or without prebiotics from a lozenge format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to 24 hour after later across different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	24 hour
Change in microbial colonization from baseline (Day 0) to 48 hours for S. salivarius M18 lozenges	Study will determine the change in microbial colonization efficacy of Streptococcus salivarius M18 with or without prebiotics from a lozenge format. The statistical analysis (e.g. Students t-test) will be carried out to compare the participants data from baseline to 48 hour after later across different formulations with the level of significance of p≤0.05.Overall colonization based on percentage of population colonized for different interventions will also be analyzed average and standard deviation functions using appropriate statistical analysis software (e.g. Microsoft Excel).	48 hour

Collaborators and Investigators

• Sponsor: BLIS Technologies Limited
• Investigators: Study Director: John D Hale, PhD, Blis Technologies Ltd

Publications and helpful links

General Publications

• Burton JP, Chilcott CN, Wescombe PA, Tagg JR. Extended Safety Data for the Oral Cavity Probiotic Streptococcus salivarius K12. Probiotics Antimicrob Proteins. 2010 Oct;2(3):135-44. doi: 10.1007/s12602-010-9045-4.
• Di Pierro F, Adami T, Rapacioli G, Giardini N, Streitberger C. Clinical evaluation of the oral probiotic Streptococcus salivarius K12 in the prevention of recurrent pharyngitis and/or tonsillitis caused by Streptococcus pyogenes in adults. Expert Opin Biol Ther. 2013 Mar;13(3):339-43. doi: 10.1517/14712598.2013.758711. Epub 2013 Jan 4.
• Di Pierro F, Colombo M, Zanvit A, Rottoli AS. Positive clinical outcomes derived from using Streptococcus salivarius K12 to prevent streptococcal pharyngotonsillitis in children: a pilot investigation. Drug Healthc Patient Saf. 2016 Nov 21;8:77-81. doi: 10.2147/DHPS.S117214. eCollection 2016.
• Di Pierro F, Colombo M, Giuliani MG, Danza ML, Basile I, Bollani T, Conti AM, Zanvit A, Rottoli AS. Effect of administration of Streptococcus salivarius K12 on the occurrence of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3 years old children. Eur Rev Med Pharmacol Sci. 2016 Nov;20(21):4601-4606.
• Di Pierro F, Zanvit A, Nobili P, Risso P, Fornaini C. Cariogram outcome after 90 days of oral treatment with Streptococcus salivarius M18 in children at high risk for dental caries: results of a randomized, controlled study. Clin Cosmet Investig Dent. 2015 Oct 3;7:107-13. doi: 10.2147/CCIDE.S93066. eCollection 2015.
• Bardellini E, Amadori F, Gobbi E, Ferri A, Conti G, Majorana A. Does Streptococcus Salivarius Strain M18 Assumption Make Black Stains Disappear in Children? Oral Health Prev Dent. 2020;18(1):161-164. doi: 10.3290/j.ohpd.a43359.
• Hyink O, Wescombe PA, Upton M, Ragland N, Burton JP, Tagg JR. Salivaricin A2 and the novel lantibiotic salivaricin B are encoded at adjacent loci on a 190-kilobase transmissible megaplasmid in the oral probiotic strain Streptococcus salivarius K12. Appl Environ Microbiol. 2007 Feb;73(4):1107-13. doi: 10.1128/AEM.02265-06. Epub 2006 Dec 28.
• Gregori G, Righi O, Risso P, Boiardi G, Demuru G, Ferzetti A, Galli A, Ghisoni M, Lenzini S, Marenghi C, Mura C, Sacchetti R, Suzzani L. Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study. Ther Clin Risk Manag. 2016 Jan 19;12:87-92. doi: 10.2147/TCRM.S96134. eCollection 2016.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 15, 2022
• Primary Completion (Anticipated): August 31, 2022
• Study Completion (Anticipated): September 15, 2022

Study Registration Dates

• First Submitted: May 11, 2022
• First Submitted That Met QC Criteria: May 11, 2022
• First Posted (Actual): May 16, 2022

Study Record Updates

• Last Update Posted (Actual): May 16, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: prebiotic; Probiotic; Streptococcus salivarius M18; Streptococcus salivarius K12; lozenges; microbial colonization; oral probiotic; powder
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: BLTCT2022/3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data and information included in the Protocol and Clinical Study Report will be shared to other researchers and/or in publications in due course.
• IPD Sharing Time Frame: Study report 3 months after the completion of the study.
• IPD Sharing Access Criteria: Summary study report will be shared by Principal investigator upon request if not published in public literature.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No