Should probiotics be used as adjuvants in the treatment of periodontitis?

INTERVENTION: The study is randomized into four groups, using the IBM SPSS Statistics 21.0 software or equivalent program (eg https://www.random.org/lists/), including probiotics/placebo groups in patients with periodontitis and probiotics/placebo groups in patients without periodontitis. After performing scaling and root planing in patients with periodontitis, the probiotics group will take a tablet containing two probiotic strains (L. reuteri DSM 17938 and ATCC PTA 5289) twice daily after brushing for 3 months. The placebo group will take a placebo tablet in the same way as the probiotic group. Clinical, microbiological, and immunological parameter data will be collected and adherence rate and adverse effects will be examined at baseline, 3 and 6 months. Patients with Periodontitis: Experimental group (probiotic group): (n=39) Scaling and root planning (SRP) + probiotic implementation: SRP per arcade followed by probiotic implementation: ‐ Strains used: L. reuteri DSM 17938 and L. reuteri ATCC PTA 5289 ‐ Frequency of administration: twice a day (in the morning and evening after brushing) for 3 months ‐ Vehicle of administration: tablets containing at least 2x108 CFUs (L. reuteriProdentis, BioGaia) ‐ Follow‐up appointment: baseline, 3 and 6 months (we will collect clinical, microbiological, immunological parameters, but also, examine adherence rate and appearance of adverse effects*) Placebo group: (n=39) SRP + placebo intake: SRP per arcade followed by placebo intake: ‐ Frequency of administration: twice a day (in the morning and evening after brushing) for 3 months ‐ Vehicle of administrat CONDITION: Periodontitis ; Oral Health PRIMARY OUTCOME: ; The following outcomes will be measured at baseline, 3 and 6 months:; 1. Clinical outcomes: IP, IG, PPD, BoP/suppuration (%); PPD, REC, CAL (mm) measured using a CP12 Hu‐Friedy periodontal probe (0.06 mm diameter ‐ 0.25N force) and a periodontal chart; 2. Microbiological outcomes: subgingival microbiome, samples of subgingival plaque will be collected with Gracey curettes at an affected site (with PPD=/>6mm with or without BoP), placed in tubes containing DNA/RNA stabilizers and stored at ‐80ºC until shipment to a Canadian company Microbiome Insight. Microbiome Insight will perform DNA extraction and sequencing of the V4 region of the 16S rRNA coding gene to identify and quantify the microbial communities present in the samples and to compare the microbial profile changes between the study groups before and after the probiotic/placebo implementation; 3. Immunological outcomes: cytokines (IL1‐ß, IL‐6 and TNF‐a [pg/ml]) and other markers (MMP‐8 and PGE2 [pg/ml]) in gingival crevicular fluid. Samples of gingival crevicular fluid will be collected with sterile absorbent paper strips, and placed for 30 sec in contact with an affected site (bag with PPD=/>6mm with or without BoP). Then, they will be inserted into the Periotron 8000 (Periotron Ide‐interstate, NY, USA) to quantify the volume collected. Afterwards, they will be placed in an Eppendorf tube with a filter and stored at ‐80ºC until they are sent to the Complutense University of Madrid, Spain, which will analyze the concentration of mediators by enzyme immunoassay ELISA; INCLUSION CRITERIA: 1. Adults aged 18‐65 years old diagnosed with untreated periodontitis 2. Adults aged 18‐65 years old without periodontitis (health periodontal) SECONDARY OUTCOME: ; The following outcomes will be measured at baseline, 3 and 6 months:; 1. Adverse effects measured using a questionnaire (nature/severity/duration); 2. Adherence rate measured using a questionnaire and by calculating the remaining tablet numbers;