Effects of a Probiotic on Oral Microbiota and Glycemic Control in Type 2 Diabetics; A Randomized Clinical Trial

Study Overview
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Brief Summary
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The present study evaluated clinically the effects of a probiotic on oral microbiota and glycemic control in T2 diabetic patients with periodontal disease. The study was designed as a prospective randomized, double-blind, placebo- controlled interventional study. At baseline and at the end of the 30 day- probiotic period, all clinical, microbiological, and biochemical measurements were tested. Colony counts of oral microbiota, blood fructosamine levels and CRP were the outcomes of the study.

Detailed Description
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Objectives: To investigate the effects of an oral probiotic use, containing 4 billion colony forming unit (CFU/g) Streptococcus Salivarius M18 strain (Dentoblis™), on the quantities of oral microbiota in saliva and metabolic markers of T2 diabetics such as fructosamine, C-reactive protein (CRP). Materials and Methods: The trial was designed as a prospective randomized, double-blind, placebo- controlled interventional study. Participants were selected from type 2 diabetics with periodontitis and aged 30-65 years, who presented to the Diabetic Center in Istanbul. Totally 70 patients were randomly assigned to probiotic or placebo groups. At baseline and at the end of the 30 day-probiotic period, colony counts of oral microbiota and biochemical measurements of diabetes were assessed.

Official Title
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Effects of Probiotic Streptococcus Salivarius Strain M18 on Oral Microbiota and Glycemic Control in Patients With Type 2 Diabetes Mellitus; A Randomized Clinical Trial

Conditions
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Diabetes Mellitus,Type 2, Periodontitis

Intervention / Treatment
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* Dietary Supplement: Effects of an oral probiotic or placebo use on oral microbiota and glycemic index in Type 2 diabetic patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: being diagnosed with T2 diabetes with <10% HbA1C for at least 6 months, 30-65 years old patients, high caries activity patients with Periodontal Disease Index (PDI) scores of 2, 3, 4 and 5, provision of written informed consent - Exclusion Criteria: patients regularly using probiotics, patients on corticosteroid, non-steroid anti-inflammatory, antibiotic or antibacterial mouthwash therapy, patients with multi-organ deficiency such as liver or kidney failure, patients with Immunodeficiency syndrome or on immunosuppressive therapy, patients with heart valve prosthesis or central venous catheter, patients undergoing chronic or acute disease therapy such as cancer, arthritis, influenza, flu, legal incapability or mental incapacity to give consent.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The trial was a prospective randomized, double-blind, placebo-controlled intervention study. All patients took an oral hygiene education and were invited to give paraffin-stimulated saliva, and blood samples in the Diabetic Center. All patients were examined clinically and the results of the intraoral examination were recorded. During the intervention period of 30 nights, the participants were asked to let one Dentoblis™ or placebo lozenge slowly melt in their mouth for at least one minute before going to bed and after tooth brushing. Dentoblis™, contains 4x 109 CFU/g S. salivarius M18 strain probiotic isolated from a healthy oral microbiota. Neither the investigators nor the subjects were aware of the contents of the lozenges except for the research nurse, who was also responsible for keeping the codes and information confidential until after the statistical calculations. At baseline and at the end of the 30 day- intervention period, all measurements were retested.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dentoblis™ group<br>In Probiotic group; Dentoblis™, as a test lozenge, contains 4 billion CFU/g S. salivarius M18 strain probiotic isolated from a healthy oral microbiota, has been utilized one lozenge a day for 30 days. | Dietary Supplement: Effects of an oral probiotic or placebo use on oral microbiota and glycemic index in Type 2 diabetic patients<br>* The participants were randomized to the interventional groups, probiotic or placebo, by the diabetes nurse. During the intervention period of 30 nights, the participants were asked to let one Dentoblis™ or placebo lozenge slowly melt in their mouth for one minute before going to bed and after tooth brushing. Dentoblis™, as a test lozenge, contains 4x109 CFU/g S. salivarius M18 strain isolated from a healthy oral microbiota and has been utilized as oral probiotic inhibiting dental caries-causing pathogens. The placebo is indistinguishable in form, size, color, and taste from the probiotic lozenge, but contains no bacteria. Placebo and probiotic lozenges were equivalent to 810 mg each and containing same amount of xylitol. Both were provided by the manufacturer, Bluestone Pharma GmbH, Baar, Switzerland, in equal white containers boxes, separated by production code. Neither the investigators nor the subjects were aware of the contents of the lozenges except for the research nurse.<br>|
| Placebo Comparator: Placebo group<br>The placebo was indistinguishable in form, size, color, smell and taste from the probiotic lozenge, but contained no bacteria and utilized one lozenge a day for 30 days . Placebo and probiotic lozenges were equivalent to 810 mg each and containing same amount of xylitol. Both were provided by the manufacturer, Bluestone Pharma GmbH, Baar, Switzerland, in equal white containers boxes, separated by production code. | Dietary Supplement: Effects of an oral probiotic or placebo use on oral microbiota and glycemic index in Type 2 diabetic patients<br>* The participants were randomized to the interventional groups, probiotic or placebo, by the diabetes nurse. During the intervention period of 30 nights, the participants were asked to let one Dentoblis™ or placebo lozenge slowly melt in their mouth for one minute before going to bed and after tooth brushing. Dentoblis™, as a test lozenge, contains 4x109 CFU/g S. salivarius M18 strain isolated from a healthy oral microbiota and has been utilized as oral probiotic inhibiting dental caries-causing pathogens. The placebo is indistinguishable in form, size, color, and taste from the probiotic lozenge, but contains no bacteria. Placebo and probiotic lozenges were equivalent to 810 mg each and containing same amount of xylitol. Both were provided by the manufacturer, Bluestone Pharma GmbH, Baar, Switzerland, in equal white containers boxes, separated by production code. Neither the investigators nor the subjects were aware of the contents of the lozenges except for the research nurse.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Oral Microbiota colony counts at baseline and after intervention | Colony counts of periodontal pathogens, S.mutans and candidas were determined 30 day after the use of the Probiotic in CFU/g | 30 days | 
| Change in blood fructosamine levels in Type 2 diabetic patients an Oral probiotic use | Clinical marker of Type 2 diabetics such as CRP and fructosamine were determined 30 day after the use of the Probiotic | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotics, Diabetes mellitus, Oral microbiota, Periodontitis, Streptococcus salivarius M18