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The Effect of Probiotic Lactobacillus Reuteri Prodentis Consumption on Gingival Crevicular Fluid Inflammatory Response and Metagenomic Profiles of Oral Microbiome in Orthodontic Patients.

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ClinicalTrials.gov Identifier: NCT04847960
Recruitment Status : Active, not recruiting
First Posted : April 19, 2021
Last Update Posted : November 14, 2022
Sponsor:
Collaborators:
Duke-NUS Graduate Medical School
Indonesia University
BioGaia AB
Information provided by (Responsible Party):
Armelia Sari Widyarman, Trisakti University

Brief Summary:

In this study, researchers will test the effectiveness of probiotic consumption against oral pathogenic bacteria and reduce the occurrence of gingival inflammation in subjects using orthodontic fixed appliances (braces).

Lactobacillus reuteri is one of the probiotic bacteria that has been identified for its health benefits. L. reuteri produces antimicrobial substances, reuterin and reutericyclin which are active against wide range of pathogenic organisms. Previously, investigator performed a pilot study on the beneficial health effect of probiotic L. reuteri containing lozenges on a few orthodontic patients and it was proven that taking this probiotic for two weeks could significantly reduce the number of pathogenic bacteria in the patients' saliva. In vitro study showed that L. reuteri has the ability to modulate the inflammatory response such as TNF alpha and interleukins. However, The ability of L. reuteri in modulating the inflammatory response viz. Interleukin 1-beta, Interleukin 6, interleukin 8, interleukin 10, TNF alpha, MMP-9 and RANKL and effect on oral metagenomic microbiome profile in patients undergoing orthodontic treatment has not been previously investigated.

Objective:

  1. To evaluate the effect of consumption of L. reuteri Prodentis probiotic lozenges on the inflammatory response (inflammation) of gingival fluid.
  2. To evaluate the effect of consumption of the probiotic lozenges of L. reuteri Prodentis against oral pathogens in dental plaque and saliva.

Research Benefits:

This study was conducted to observe the effectiveness of L. reuteri (ProDentis) probiotic against oral pathogenic bacteria on patients using orthodontic fixed appliance, to reduce gum inflammation and improve oral health.


Condition or disease Intervention/treatment Phase
Healthy Subjects With Fixed Orthodontics Dietary Supplement: BioGaia Probiotic Lozenges Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: intervention group
Masking: None (Open Label)
Masking Description: Open label trial of BioGaia's Probiotic lozenges
Primary Purpose: Basic Science
Official Title: The Effect of Probiotic Lactobacillus Reuteri Prodentis Consumption on Gingival Crevicular Fluid Inflammatory Response and Metagenomic Profiles of Oral Microbiome in Orthodontic Patients.
Actual Study Start Date : March 22, 2021
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Orthodontia

Arm Intervention/treatment
Experimental: L.reuterii probiotic lozenges from BioGaia
Subjects were willing to provide 2 samples of saliva, dental plaque and gingival fluid (gum fluid), on the first day (before consuming lozenges) and on the 14th day after the subject consumed lozenges containing L. reuteri probiotic. Probiotics are taken once a day for two weeks after breakfast and brushing their teeth.
Dietary Supplement: BioGaia Probiotic Lozenges
BioGaia Prodentis lozenges is a food supplement for oral health that contains patented lactic acid bacteria Limosilactobacillus reuteri (formerly known as Lactobacillus reuteri) Prodentis (a combination of strains of L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289) which helps good microorganisms maintain natural balance in the mouth. This product is safe for daily use and this product can be used during pregnancy and breastfeeding. The ingredients of this product are: bulking agent (isomalt), L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289, fully hydrogenated palm oil, peppermint flavoring, menthol flavoring, peppermint oil and sweetener (sucralose). One candy contains a minimum of 200 million live L. reuteri Prodentis. Net weight per candy is 800 mg. Excessive consumption can have a laxative effect due to the sweetener content in the product. This product has obtained a distribution permit in Indonesia with a BPOM number: SI194510521 with the name Probiotic Prodentis (Pro-D).




Primary Outcome Measures :
  1. Metagenomic microbiome profile comparison between Pre- and Post-treatment described using Alpha Diversity analysis. [ Time Frame: 8 weeks ]
    Using next-generation sequencing to acquire both bacterial and fungal metagenomic profile from plaque, gingival crevicular fluid, and saliva samples, whilst comparing both profile between pre-treatment and post-treatment. The data will be analysed and presented after observed operational taxonomic units (OTU), Shannon's richness, Chao's richness, and Simpson's evenness analysis has been done.

  2. Bacterial gene expression profile from dental plaque comparison between Pre- and Post-treatment described using relative quantification of fold gene expression (2-∆∆Ct). [ Time Frame: 16 weeks ]
    Using RT-PCR to acquire the gene expression of bacterial dental plaque that are acquired from both pre-treatment and post-treatment samples, therefore comparing bacterial dental plaque's gene expression between pre-treatment and post-treatment.

  3. Proteomic profile assessed from gingival crevicular fluid and comparing its results between Pre- and Post-treatment as assessed using enzyme-linked immunosorbant assay. [ Time Frame: 12 weeks ]
    Using enzyme-linked immunosorbant assay to assess inflammatory responses and comparing it between pre-treatment samples and post-treatment samples. Standard curves for each marker will also be conducted. Final protein concentrations of each marker will be generated after the sample's absorbance value detected is converted using the standard curve of each marker.

  4. OHI status and Plaque index as assessed by the dental general practitioners. [ Time Frame: 2 weeks ]
    Assessment done by dentists to analyze oral health comparisons between pre-treatment and post-treatment



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 28 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18 - 28 years old (M/F)
  • Using orthodontic fixed appliance for at least 1 year
  • Do not consume probiotics and antibiotics (at least 3 months before)
  • No history of systemic disease

Exclusion Criteria:

  • Subjects with systemic diseases
  • Allergic to probiotics

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04847960


Locations
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Indonesia
Trisakti University
Jakarta, DKI Jakarta, Indonesia, 11440
Sponsors and Collaborators
Trisakti University
Duke-NUS Graduate Medical School
Indonesia University
BioGaia AB
Investigators
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Principal Investigator: Armelia Sari Widyarman, Ph.D Trisakti University
Study Director: Chaminda Jayampath Seneviratne, Ph.D Duke-NUS Graduate Medical School
Study Chair: Citra Fragnantia Theodora, Ph.D Indonesia University
Study Chair: Joko Kusnoto, Sp.Ortho Trisakti University
Study Chair: Tri Erri Astoeti, Professor Trisakti University
  Study Documents (Full-Text)

Documents provided by Armelia Sari Widyarman, Trisakti University:
Study Protocol  [PDF] January 10, 2021
Informed Consent Form  [PDF] November 23, 2020

Publications:
Özyildiz F, Uzel A, Hazar A, Güden M, Ölmez S, Aras I et al. Photocatalytic antimicrobial effect of TiO2 anatase thin-film-coated orthodontic arch wires on 3 oral pathogens. Turkish Journal of Biology. 2014;38:289-295.
Marsh P, Martin M V., Lewis MAO. Oral Microbiology. 5th ed. Elsevier Ltd; 2009:78-84.

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Responsible Party: Armelia Sari Widyarman, Lecturer, Head of Microbiology Department, Head of MiCORE Laboratory, Trisakti University
ClinicalTrials.gov Identifier: NCT04847960    
Other Study ID Numbers: 0191
First Posted: April 19, 2021    Key Record Dates
Last Update Posted: November 14, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Armelia Sari Widyarman, Trisakti University:
probiotics
Lactobacillus reuterii
oral microbiome
fixed orthodontics