## 4 Discussion
### Probiotics in Periodontology
#### 4.2.3. Probiotics in Peri-Implant Diseases  
Peri-implant mucositis is a reversible soft tissue inflammation around the implants with no bone loss, caused by bacteria biofilm [60]. Its evolution leads to peri-implantitis, characterized by bone resorption and potential implant loss, increased levels of IL-6, IL-1\(\beta\), and IL-8 and increased GCF volume [61]. The mechanical control of the biofilm and the use of antiseptics and antibiotics may be insufficient for the complete cure. Probiotics may aid in the formation of a new protective biofilm compatible with peri-implant health.  
Eight randomized clinical trials investigating the effects of different species of _Lactobacillus_ in peri-implant inflammation in otherwise healthy adults were analyzed (Table S6). [PERSON] et al. [62], studied the use of _L. reuteri_ ATCC PTA 5289 and DSM 17938 in initial peri-implantitis. After SRP, probiotics were administered in drops directly to the site of peri-implantitis and afterwards in lozenges consumed for 12 weeks twice a day. There were no clinical and microbiological benefits from the administration of the probiotics. Similar negative results were obtained by [PERSON] et al. [63], who evaluated the daily consumption of _L. reuteri_ tablets for 28 days in patients with peri-implant mucositis, by [PERSON] et al. [64] who studied the addition for 1 month of _L. reuteri_ DSM 17938 and ATCC PTA in patients with peri-implant mucositis who received mechanical therapy and 0.12% chlorhexidine 15 days before the start of probiotic intervention, by [PERSON] et al. [65] who also evaluated the effects of administration of _L. reuteri_ DSM 17938 and ATCC PTA 5289 in patients with peri-implant mucositis and peri-implantitis for 30 days, and by [PERSON] et al. [29] who administered _L. reuteri_ DSM 17938 and ATCC PTA 5289 in patients with peri-implant mucositis for 3 months. [PERSON] et al. [66] also found no clinical benefits after 14-days administration of _L. plantarum_ and _L. brevis_ on patients with experimental peri-implant mucositis.  
In contrast, [PERSON] et al. [67] found that administration of _L. reuteri_ DSM 17938 and ATCC PTA 5289 for 30 days was useful to treat and prevent peri-implant mucositis. At the end of the study, a single patient developed mucositis and most (17 of 23) of the patients with mucositis were cured. Accordingly, PI, GI, PD and GCF volume were significantly reduced in the probiotic group when compared with placebo. IL-6 and IL-8 levels were also significantly reduced in the mucositis group taking the probiotics. The severity of peri-implant mucositis was also reduced significantly in a more recent trial using a probiotic combination (_L. reuteri_ DSM 26866, _L. rhamns_ DSM 21690, _L. bulgarcius_ DSM21690, and _Bifidobacterium animals_ ssp. _lactis_ DSM 17741) [68]. Clinical parameters (as determined by PI, GI, BOP, and PD) improved significantly in the test group relative to the control group after 1 month of consumption of probiotics. Salivary flow increased after 1 month in test group, with a significant difference between groups. Immunological parameters (salivary cytokines II-1\(\beta\), II-4, TNF-\(\alpha\)) decreased significantly at 1 and 6 months after the start of the intervention. Finally, the pathogenic species _Prevolella intermedia_, _Treponema deticola_, _Aggregathacter actinovuretemomitans_, _Porphyromomas gingivalis_, and _Fusobacterium nucleatum_, decreased after 1 month of probiotic consumption. The positive results obtained in these two trials may be related with a better removal of the subgingival plaque prior to the application of probiotics. On the other hand, the lack of results in the remaining trials may be related with small sample sizes and short administration times [69]. Clearly, further standardized clinical trials are indispensable to determine the usefulness of probiotics in prevention, management, and treatment of gingival, periodontal and peri-implant conditions, and to develop practical recommendations and adequate clinical protocols.