## 4 Discussion
### Probiotics in Periodontology
#### 4.2.2 Probiotics in Periodontitis  
The uncontrolled expansion of periodontitis bacteria (_Porlymomonas gingivalis_, _Trepenema deticola_, _Tannerella forsythia_, _Fififactor alocis_, _Parximonas micra_, _Aggregatibacter actinomycetemcomitans_ and species of _Fusobacterium and Prevotella_) along with dysregulation of the immune barriers and tissue damage leads to periodontitis [1]. Remodeling of the periodontal extracellular matrix depends on the balance between proteolytic enzymes responsible for the degradation and remodeling of extracellular matrix proteins (MMPs), present in saliva, dental plaque and GCF and tissue inhibitors of MMPs, TIMP-1 and TIMP-2 [42; 43]. In case of periodontal diseases, an imbalance in the ratio of MMPs/TIMPs (e.g., TIMP-1 reduction and MMP 8-9 increase) leads to periodontal destruction. The conventional treatment of periodontitis involves the mechanical removal of the subgingival plaque. Scaling and root planing (SRP) is the standard control method and can be complemented by the addition of antibiotics which can lead to development of resistance, modifications of the commensal flora and risk of dysbiosis [28]. On the other hand, bacterial plaque is difficult to remove in low access sites, and remaining bacteria can cause periodontitis relapse and can invade adjacent tissues (i.e., mucosa, tongue, tonsils) and cause new infections [1]. Probiotics were proposed as adjuncts to the mechanical therapy of periodontitis aiming at restoring the commensal microbiota and reduce inflammation and tissue damage [44; 45]. For this review, 21 randomized clinical trials related to the implementation of probiotics in periodontal conditions were selected (Table S5). Most trials have used species of _Lactobacillus_ because it is a commensal bacterium that antagonizes _P. gingivalis_[10; 46]. In [PERSON] et al. [10], tablets containing _L. reuteri_ ATCC 55,730 and _L. reuteri_ ATCCPTA 5289 were administered to patients with chronic periodontitis for 30 days. All clinical parameters improved significantly in the test group, suggesting a possible synergy between the strains used. In a study by [PERSON] et al. [47], ingestion of milk with _Lactobacillus casei_ for one month provided no clinical benefit to patients with chronic periodontitis in spite of a significant decrease in _P. gingivalis_ counts in the first months after the intervention. _Aggregatibacter actynomycetesatemcomitans_ and _P. intermedia_ counts showed no significant reduction. [PERSON] et al. [48] evaluated the use for 12 weeks of heat-killed _Lactobacillus plantarum_ in patients undergoing supportive periodontal therapy. Mechanical control of plaque was performed and improved clinical parameters in both the test and placebo groups. A significant decrease in favor of the probiotic group was observed at 12 weeks in bleeding on probing (BOP), number of teeth with periodontal pocket depth (PD) >4 mm and number of sites with PD >4 mm, suggesting that this probiotic can prevent a possible recurrence and/or disease progression. [PERSON] et al. [8] evaluated for 12 months the effects of a _Lactobacillus reuteri_ DSM 17938 and PTA 5389 probiotic combination in patients treated for a stage III-IV periodontitis, grade C. In the probiotic group, there was a higher reduction of mean PD throughout the study, higher clinical attachment level (CAL) gain at 6 months, and higher reduction of BOP at 6 and 9 months. In a study by [PERSON] et al. [46], probiotics _L. salivarius_ and _L. reuteri_ were evaluated as an adjunct to SRP in the treatment of patients with chronic periodontitis. The test group received subgingival delivery of probiotics and probiotic mouthwash for 14 days. A significant difference in favor of the test group was observed after 3 months in the number of moderate periodontal pockets. Moreover, there was a significant reduction in the benzoyl-DL arginine-naphthylamide (BANA) test for detecting digesting peptidase in the test group after 1 month, compared to the placebo group, but the difference was no longer observed at 3 months.