## 3 Modes of Action of Oral Probiotics  
Several microorganisms serve as oral probiotics. Probiotics that have been used in clinical trials are classified regarding the genus, the species, and the strain (Table 1). Figure 1: Synbiotics are products containing both probiotics and prebiotics. The probiotics' mechanisms of action generally have not been precisely determined [56]. Nevertheless, in general, the three main modes through which probiotics exert their action are (a) modulation of host's defense (b) direct destruction of pathogens, and (c) indirect removal of pathogens. Probiotics and their extracellular products are found to interact with the host's mucous cells, determining in a strain-specific manner the cytokines' and chemokine's production, which leads to the enhanced phagocytic activity of macrophages, neutrophils, and Natural Killer (NK) cells [57]. For example, _B. lactis_ Bb-12, _L. rhamn_s GG, and _L. acidophilus_ La1 increase the phagocytic capacity of leukocytes [58; 59; 60; 61]. Probiotics, however, manipulate not only innate immunity but also stimulate adaptive immunity by increasing IgA levels in the serum and regulating the development of T helper cells and the proportion of Th1/Th2 cells [57; 62; 63; 64]. In the oral environment, much less has been elucidated [56]. Indeed, specific probiotics inhibit the interleukin-8 (IL-8) response of the oral mucous cells caused by some periodontal pathogens as much as other inflammatory biomarkers, such as prostaglandin E2 (PGE2) [65; 66; 67]. Still, no alteration in salivary IgA levels has been observed [68]. Additionally, _L. paracaei_ has been proved to augment the detectable counts of a defensin [69], salivary human neutrophil peptide 1-3 [70]. Probiotic bacteria can produce various antimicrobial substances, such as bacteriocins, bacteriocin-like peptides, lactic acid, and hydrogen peroxide. All of the above have an immediate effect on the host's microbiome, as they preconeive the death of specific pathogens, while the producer strains survive [71; 72; 73]. For example, _L. rhamn_s GG secretues a broad-spectrum antimicrobial substance affecting many Gram-positive (_Streptococci_, _Lactobacillus_, _Clostridium_ spp.) and Gram-negative bacteria (_E. coli_, _Bacillus fragilis_) [74]. _L. reuteri_ produces \begin{table}
\begin{tabular}{c c c} \hline
**Genus** & **Species** & **Strain** \\ \hline _Lactobacillus_ & _rhamnosus_ & GG (ATCC 53103) [20; 21; 22; 23], hct 70 [24], LB21 [25], LC 705 [22] \\ \hline  & _reuteri_ & ATCC 55,730 (SD2112) [26; 27; 28], ATCC PTA 5289 [29; 30; 31; 32], DSM 17,938 [39; 30; 31; 32] \\ \hline  & _casei_ & Shirota [33] \\ \hline  & _paracasei_ & F19 [34], GMNL-33 [35], SD1 [36; 37; 38] \\ \hline  & _achidophilus_ & ATCC 4356 [39], La-5 [40] \\ \hline  & _salivarius_ & TI 2711 [41], WB21 [41] \\ \hline  & _brevis_ & CD2 [42] \\ \hline  & _bifidum_[43] \\ \hline  & _bulgaricus_[43] \\ \hline  & _sporogens_[43] \\ \hline  & _thermophilus_[43] \\ \hline _Bifidobacterium_ & _animals lactis_ & BB-12 (ATCC 27536) [40; 44; 45; 46], DN-173010 [47; 48] \\ \hline  & _bifidum_ & ATCC 29,521 [39] \\ \hline  & _longum_[49] \\ \hline _Streptococci_ & _mutans_ & A2 JM [50] \\ \hline  & _rattus_ & JH145 TM [51; 52] \\ \hline  & _oralis_ & KJ3 TM [52] \\ \hline  & _uberis_ & KJ2 TM [52] \\ \hline  & _dentisani_ & CECT7746 [53] \\ \hline  & _salivarius_ & M18 [54] \\ \hline _Bacillus_ & _coagulans_[55] \\ \hline \end{tabular}
\end{table} 
Table 1: Microorganisms are serving as oral probiotics. reuterin and reutericyclin [75; 76], which exert their antimicrobial properties by inducing oxidative stress and altering the transmembrane \(\Delta\)pH in target cells [77; 78], respectively. The indirect effects of probiotic microorganisms on the host's microbiome have to do with the phenomenon of competing with the pathogenic bacteria either for an adhesion niche or for essential nutrients [79; 80; 81; 82]. Whenever salutary strains preoccupy potential sites of pathogens' adhesion, disease establishment is subverted [56].