Impact of Oral Probiotics on Oral Homeostasis

Study Overview
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Brief Summary
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Aim: To evaluate the effect of three months use of tablets containing probiotics on the composition of the supragingival plaque microbiota and salivary levels of inflammation-related proteins in oral healthy individuals. Hypothesis: Three months use of tablets containing probiotics will induce quantifiable changes to the composition of the supragingival plaque microbiota and salivary levels of inflammation-related proteins in oral healthy individuals. Perspectives: Data from the present study will be able to reveal the impact of regular use of probiotics on oral homeostasis in oral healthy individuals. Specifically, simultaneous registration of clinical, microbial and inflammatory characteristics will provide comprehensive information on the potential beneficial effect of regular use of oral probiotics on maintenance of oral homeostasis. Thus, data from the present study will provide a scientific platform, which dentist and dental hygienist can utilize when deciding if oral healthy individuals may benefit from using oral probiotics as a supplement to regular oral hygiene.

Detailed Description
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Oral health is built upon a symbiotic relationship between the resident oral microbiota and the immune system of the host. Therefore, structural or functional changes to either the microbiota or the immune system may result in dysbiosis, which in turn can lead to oral diseases such as gingivitis, periodontitis and dental caries. The composition of the resident oral microbiota in oral health is shaped by ecological properties found at various sites of the oral cavity, which is why major site-specific variations are observed. Interestingly, the composition of the oral microbiota is individualized and relatively time stable as long as oral homeostasis is maintained. However, structure and function of the oral microbiota can be altered by internal and external perturbations. For example, it has previously demonstrated that oral hygiene discontinuation induces structural changes to the supragingival plaque microbiota, whereas non-surgical periodontal treatment has deep impact on the composition of the subgingival plaque microbiota. Interestingly, a recent study demonstrated that the composition of the resident oral microbiota may also be influenced by external perturbations. Specifically, daily use of ZendiumTM toothpaste for 12 weeks was reported to induce significant changes to the supragingival plaque microbiota in oral healthy individuals with an increase in health-associated bacterial species. Probiotics is the term used when a harmless effector strain is implanted in the host's microbiota to maintain or restore a natural microbiome by interference and/or inhibition of other microorganisms, and especially pathogens. In a recent study, it was demonstrated an effect of using tablets containing a mix of Lactobacillus rhamnosus PB01, DSM 14869 and Lactobacillus curvatus EB10, DSM 32307 on gingival inflammation. Specifically, daily use of this probiotic candidate for four weeks resulted in significant reduction in clinical parameters such as bleeding on probing (BOP) and amount of gingival crevicular fluid (GCF). However, at present it is not known if daily use of a probiotic tablet containing a mix of L. rhamnosus PB01, DSM 14869 and L. curvatus EB10, DSM 32307 is able to induce shifts to the composition of the oral microbiota, or cause a decrease in salivary levels of inflammation-related proteins such as neutrophil gelatinase-associated lipocalin (NGAL) and transferrin, which is the purpose of the present study.

Official Title
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Impact of Oral Probiotics on Oral Homeostasis - a Randomized Double Blind Study

Conditions
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Gingivitis

Intervention / Treatment
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* Dietary Supplement: Probiotic tablet
* Dietary Supplement: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 yrs. Exclusion Criteria: gingivitis periodontitis dental caries systemic disease current medication antibiotic treatment within the latest 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double blind clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Probiotic tablets (containing a mix of Lactobacillus rhamnosus PB01, DSM 14869 and Lactobacillus curvatus EB10, DSM 32307, 1*10(9) CFU) 2 times/day for 12 weeks | Dietary Supplement: Probiotic tablet<br>* Probiotic tablet twice a day for 12 weeks<br>|
| Placebo Comparator: Placebo Comparator<br>Placebo tablets 2 times/day for 12 weeks | Dietary Supplement: Placebo tablet<br>* Placebo tablet twice a day for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in bacterial diversity of supragingival plaque microbiota from baseline to week 12 | Alpha-diversity measured by shannon index | Baseline alpha-diversity vs. alpha-diversity at week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in salivary levels of neutrophil gelatinase-associated lipocalin (NGAL) from baseline to week 12 | Mean levels of NGAL (mg/mL) measured by ELISA | Baseline levels vs. leves at week 12. | 
| Change in Salivary levels of transferrin from baseline to week 12 | Mean levels of transferrin (mg/mL) measured by ELISA | Baseline levels vs. leves at week 12. |