Effect of probiotic chewing tablets on early childhood caries – a randomized controlled trial

Probiotics are defined as live microorganisms that confer a health benefit on the host when administrated in appropriate amounts [1]. During the last decade, the use of such beneficial bacteria has gained interest within the dental research community with focus on caries development, periodontal health and halitosis [2‐4]. For caries prevention and root caries arrest, some studies have provided encouraging results in children and adults [5‐8], albeit the quality of evidence still is regarded as insufficient [9]. It is generally thought that exposure to probiotic bacteria early in life may have a greater impact on general and oral health compared to adult regimes [10, 11]. For example, it has been shown that administration of probiotic drops containing strains of Lactobacillus reuteri during the first year of life had an impact on caries prevalence and frequency at the age of 9 years [12] Others have however presented contrasting results [13]. As early childhood caries is one of the most serious and costly health conditions among young children [14], it seems important to investigate novel self-administrated preventive strategies that could be added to existing evidence-based recommendations [15]. The aim of the present study was therefore to evaluate the effect of a probiotic chewing tablet, given as a daily supplement after fluoride toothpaste use, on the development of early childhood caries in preschool children living in a multicultural low-socioeconomic area. The null hypothesis was that the caries increment would not differ from that of a control group with similar intake of placebo tablets.

The baseline characteristics of the two study groups and the dropouts are presented in Table 1. The test and placebo groups were balanced in all aspects and the dropouts did not differ from those that completed the study. The caries prevalence and increment is shown in Table 2. The 1-year increment (Δds) was significantly lower (p < 0.05) in the test group compared with the placebo group and the prevented fraction was 75 %. Based on the caries prevalence, the absolute risk reduction was 22 % and the number needed to treat was close to five. The majority of the new lesions were enamel (initial) lesions but no statistically significant differences between the groups concerning the severity, or arrestment of lesions, were displayed (Table 3). An intention-to-treat analysis based on caries increment revealed a relative risk reduction of 0.47 (95 % CI 0.24–0.98). There were no significant differences between the test and the placebo group regarding the prevalence of visible plaque (29 vs. 25 %) or bleeding-on-brushing (13 vs. 10 %) at the 1-year follow-up.

The compliance was graded as acceptable among 72 % of the children in the test group and 69 % in the placebo group. No harmful events were reported during the study period among those that completed the intervention. No permanent restorative treatment or extractions were carried out in any of the participants.

To our knowledge, this is the first clinical study that demonstrated a significant reduction of early childhood caries following daily intake of oral probiotic tablets. Thus, the null hypothesis was rejected. The findings were clearly in agreement with some previous reports on probiotic lactobacilli added to milk and served to preschool children attending in public day care centers [5, 6]. In contrast, Taipale and co-workers [17] failed to affect the caries occurrence in 4-year old children after administration of probiotic bifidobacteria with a pacifier or spoon during the first two years of life. However, the latter study was performed in a low-caries population which was in contrast to the present project. It is well known that there is a strong link between socioeconomic status and oral health [18] and it is a challenge to address and overcome such inequalities, especially among young children. Therefore, any educational, lifestyle or behavior-based initiatives to improve oral health among disadvantaged children are important and likely beneficial for their well-being and quality of life [19]. The most important component of such programs is without doubt daily fluoride exposure [20] but our findings indicate that probiotic therapy can be a valuable adjunct in order to increase the effectiveness of the recommended and established preventive care. It should be noted that over 94 % of the parents reported that they helped their children with tooth brushing with fluoride toothpaste, at least once daily, during the intervention period. The fluoride exposure from diet and water (<0.3 ppm) was however considered as low.

The mechanisms of probiotic action are not fully clear but rely on local events, such as co-aggregation, competitive inhibition and bacteriocin production as well as systemic immune-based avenues [3]. For the caries disease, the local effects seem most relevant and in animal models, a competitive inhibition has previously been shown for S. rattus and peroxide production for S. oralis and S. uberis [21]. Furthermore, systematic reviews have concluded that there is good evidence that probiotic supplements can reduce the levels of mutans streptococci in plaque and saliva [9, 22]. Such reductions have also been demonstrated with the ProBiora3® concept [23, 24]. Our results indicated that the intervention mainly affected the early enamel demineralization rather than the cavitated lesions. With the relatively small sample size and short study period in mind, it would have been interesting to follow the impact of an extended intervention on the caries progression. Notably, no new children in the test group exhibited caries lesions during the study period.

The enrollment of healthy volunteers for this project was far from smooth and only around one fourth of the eligible families gave their consent. Many parents hesitated to give their children “pills” on a daily basis for a period of one year. Furthermore, culture and language barriers did not facilitate the recruitment process. Therefore, a certain selection bias cannot be excluded and the external validity for other high caries populations, or age groups, is unclear. The parents that agreed to participate seemed highly motivated for health-promoting actions and this was illustrated by the acceptable compliance reached among the majority of the participants. The relatively high attrition rate of 20.3 % was not unexpected given the volatile nature of the immigrant population. It can be anticipated that the families that did not show up to collect new tablets failed to follow the study protocol. The number of participants indicated in the initial power calculation was not reached, but the caries activity in this study population was somewhat higher than expected which, in part, saved the study from being underpowered. The fact that no adverse events were reported was encouraging and in accordance with the generally recognized as safe (GRAS) nature of probiotic supplements. Initially, a number of children perceived the tablets as “big” and “hard” and refused to take them. In those cases, the parents were encouraged to “crush” the tablets and give them in smaller pieces and this recommendation was clearly helpful.

Within the limitations of the present study, the results suggested that early childhood caries development could be reduced through daily administration of these probiotic chewing tablets as adjunct to daily use of fluoride toothpaste in preschool children. Therefore, further studies to confirm these findings and clarify a possible dose–response relationship, as well as health economic issues, seem justified.