# Concentration in Saliva and Antibacterial Effect of Xylitol Chewing Gum: In Vivo and In Vitro Study
## 4 Discussion  
The xylitol salivary level increased after the use of both types of chewing gum; however, the 100% xylitol gum achieved the highest decrease, as expected. The results of the in vivo study run similarly to those available in literature [7; 8; 9]. Salivary xylitol concentrations were elevated for a short period of time (less than 15 min) and then decreased, reaching almost the baseline level at the 25-min evaluation. Xylitol concentration levels in saliva using the 100% xylitol chewing gum did not decrease as linearly as using the 22% gum, but bimodally. This difference could be related to the different distribution of the polyol in the gum: in the 100% the highest amount of xylitol was included in the gum pellet, while in the 22% it was only contained in the hard coating, as described in materials and method. It is, therefore, reasonable to have a second peak concentration after some time from the start of chewing. The sampling technique, stimulated and unstimulated saliva, was postulated as the reason of the bimodal fashion release concentration [7]. In this study, the second peak was observed at the end of the chewing period; chewing saliva stimulation is reduced after 5 min and this may have influenced the presence of the bimodal release concentration; as reported in literature, the highest salivary concentration of drugs (fluoride, nicotine, etc) released from gums was detected between 5 and 10 min from the beginning of use [26; 27; 28; 29]. On the other hand, the skewed distribution of the salivary Xylitol concentration must be taken into account since high inter-subject variability has been observed. This outcome can be explained by several parameters, such as chewing distance, chewing frequency, and the twisting motion of the gum affecting the xylitol release [29]. These parameters were not included in the analysis as subjects were free to chew as they usually do. A relatively high daily dose of xylitol is necessary to obtain positive effects [30; 31; 32; 33; 34; 35; 36; 3; 36; 3]. The frequency of administration is also considered an important factor, since, as reported in this study, its concentration in saliva tends to decrease in a short time. The hypothesis that Xylitol may have an effect on dental plaque is related to the transport and phosphorylation of the polyol through the cell wall by a constitutive fructose-PTS (phosphotransferase) system with accumulation of xylitol-5-phosphate in intracellular substrate [37; 35]. Whilst the current study was conducted in vitro using a pooled sub-gingival plaque sample, significant differences in antibacterial composition were detected using both chewing gums, although most impressive antibacterial actions were observed with the 100% gum. The bacterial viability is reduced over the time of the experiment (24 h), and it was similar in both groups, and the difference observed has to be mainly ascribed to the different concentration of xylitol in the gums. Few studies have focused on the effect of polyols on oral bacteria apart from carigenic ones [11; 38; 11], Xylitol proved to clinically reduce the amount of dental plaque and gingivitis in children and young adults [34; 36; 39]. _In vivo_, xylitol chewing gum was able to decrease _mutans streptococci_ levels [39], while _in vitro_, Xylitol has shown to inhibit the growth of several bacterial strains like _Streptococcus mutans_, _Streptococcus sobrinus_, _Lactobacillus rhamnus_, _Actinomyces viscosus_, _Porhyromonas gingivalis_, and _Fusobacterium nucleatum_[37; 38; 37; 40] with different effect on different strains. Xylitol is able to inhibit the production of inflammatory and proinflammatory cytokines derived from periodontal bacteria as _Porhyromonas gingivalis_ and _Aggregatibacter actinomycetemomitans_[13; 41; 40; 42]. This study has potential limitations. First of all, it is necessary to consider the single administration in the in vivo phase of the study. It is likely that the use of the gums several times a day may also modify the amount of Xylitol in the mouth over a longer period.