## 4 Discussion
### Probiotics in Cardiology  
Dental caries is a multifactorial disease, related to acidogenic and acid tolerant bacteria such as _S. mutans_ and _Lactobacillus_ spp. [70]. These bacteria produce acids from fermentation of carbohydrates that demineralize dental tissues. The prevention of dental caries involves the administration of fluoride, the use of sealants and modification of dietary habits (lower consumption of sucrose) [71]. The treatment and control of dental cariesrequires mechanical removal of the various lesions which should be combined with an antimicrobial in the case of high-risk children. Probiotics have been proposed as an adjunct method to dental caries management strategies as they adhere to oral tissues, prevent adhesion/colonization/proliferation of caries pathogens and formation of pathogenic biofilm, produce inhibitors of cell adhesion and antibacterial agents, and consume nutrients before caries pathogens can use them (Figure 1) [33; 72; 73; 74; 75]. Seventeen clinical trials evaluated the effect of different probiotics on cariology in children and infants (Table S7). Overall, it was easier to modify the immature dental biofilm of children through colonization with probiotics than the established biofilm of adults. Six trials in adults assessed whether permanent integration of probiotics into the mature biofilm can be achieved in a cariogenic environment. In a study by [PERSON] et al. [76], administration of _L. rhamn_s SPI strain in milk to children for 10 months led to a lower prevalence of dental caries relative to the placebo group (54.5% vs. 65.8%), lower incidence of cavitated lesions (9.7% vs. 24.3%), and lower incidence of new lesions. Administration of tablets containing _Streptococcus utberis_ KJ2 TM, _Streptococcus oralis_ KJ3 TM and _Streptococcus rattus_ JH14 STM to children for 3 months, caused a significant reduction in dental caries at the end of one year with prevention of enamel demineralization [77]. In a study by [PERSON] et al. [78], _Streptococcus salivarius_ M18 probiotic in tablets was evaluated for 90 days in children with high risk of caries. There was a significant reduction in the overall caiogram result. In the probiotic group, PI and _S. mutans_ counts were significantly reduced indicating that the consumption of this probiotic may help to prevent the development of new caries in high-risk children. The daily and triweekly consumption of probiotic milk containing _L. paracasei_ SD1 on _Streptococcus mutans_ and lactobacilli counts in saliva and plaque samples was evaluated in preschool children for 6 months [79]. Probiotic administration reduced _S. mutans_ counts and increased total lactobacilli counts in the saliva and plaque samples that persisted at least 6 months after discontinuation. Similar results were obtained by [PERSON] et al. [72] after 3-months consumption of milk containing _L. paracasei_ SD1, and by [PERSON] et al. [75] after 6-months consumption. In the latter study, there was colonization by the probiotic strain already at month 3 which decreased progressively with time to undetectable levels at month 12. Overall, the results suggest that in children with high risk of caries, daily consumption of probiotic _L. paracasei_ SD1 may be recommended to control the amount of _S. mutans_ responsible for the initial process of tooth decay. [PERSON] et al. [80] administered _L. reuteri_ as drops to pregnant women (from the 9 th month of pregnancy) and their infants (up to 1 year old). At 9 years of age, the infants in the test group showed significant improvements in GI and dental caries prevalence relative to placebo (82% children free of carious lesions vs. 58%). _L. reuteri_ was detected in only two children from each group. Diet, oral hygiene, fluoride supplementation and socioeconomic factors were similar in both groups at baseline but were not documented at the end of the study preventing the identification of potential contributors for the benefit of probiotics in dental caries development in early age. In a study by [PERSON] et al.