## 4 Discussion
Their positive action is still an object of study, and possible explanations can be found in the exclusion of pathogenetic bacteria and the competition with pathogenetic bacteria for nutrients and epithelial cell adhesion, the production of antimicrobial molecules towards these harmful microorganisms, the enhancement of the mucosal barrier function, and the reestablishment of the physiological immunomodulatory function of the host [24]. According to a recent study, probiotics provide valid support to non-surgical periodontal treatment, with a positive improvement on periodontal indexes and a decrease in specific periodontal bacteria; additionally, it has been suggested that probiotics not only reduce microbic counts but also exert an immunomodulatory action, thus switching from a pro-inflammatory towards an anti-inflammatory response [16]. The improvement of BoP occurred in both groups, but was more evident for the trial one: the more evident influence of Biorepair Parodontgel Plus toothpaste on the BoP could be explained by the effect of its content, which includes soothing extracts like Lactoferrin, hamamelis virginiana leaf extract, Spirulina platensis extract, Calendula officinalis flower extract, andtocopherol acetate. This outcome confirms previous findings demonstrating the high influence of hyaluronic acid and lactoferrin-based toothpaste on periodontal bleeding indexes [14]. In particular, the effect of Biorepair Parodontgel Plus toothpaste on BoP could be ascribed to its content of lactoferrin. The anti-inflammatory action of this element has been studied both by means of in vitro periodontitis models as well as through observational clinical studies: in vitro lactoferrin has shown strong anti-inflammatory properties against gingival fibroblasts infected with the periodonontpathogen _Prerotella intermedia_, whereas in vivo the topical administration to periodontal patients leads to the decrease of cytokines levels in crevicular fluid and other inflammatory periodontal indexes [25]. Furthermore, Biorepair Plus Parodontgel contains tocoperly acetate (vitamin E), an antioxidant agent whose positive role in periodontitis has been suggested [26]. Considering oral hygiene and the periodontal status, previous research has demonstrated the relationship between these two factors. For example, [PERSON] et al. [27] have found among children with T1 DM that caries prevalence and gingival health in permanent dentition are affected by metabolic control: with lower levels of glycemia, the caries prevalence and gingival inflammation increased. Interestingly, the association between oral hygiene and diabetes has been shown to be bidirectional: on one hand, periodontitis could be a potential complication of diabetes, but, on the other hand, the increased levels of periodontal inflammatory markers, such as C-reactive protein and interleukin-6, are found to be significant risk factors for T2 DM [28]. According to a recent systematic review with meta-analysis, scaling and root planing exert a positive effect on metabolic control (i.e., reduction of HbA1c) and reduction in systemic inflammation (decrease of C-reactive protein, CRP) in patients with T2 DM [29]. According to the findings of the study, only the natural extracts-based toothpaste caused a significant decrease of HbA1c, whereas the probiotics-based agents had no influence. This could be due to a more anti-inflammatory power of the natural extracts exerting not only a local effect but also a systemic one. This outcome appears to be particular inter esting from a clinical point of view. According to [PERSON] et al. [30], the literature highlights that worse periodontal parameters are found among children with T1 DM. Accordingly, every effort should be made by clinicians to ensure proper oral hygiene protocols to these patients, considering their systemic condition.