Periodontal diseases, encompassing periodontitis and gingivitis, are inflammatory conditions affecting the tissues supporting the teeth. These conditions often lead to tooth loss, primarily due to an imbalanced immune response that destroys periodontal ligaments and supporting bone structures [6, 7]. A disruption in the oral microbiota, known as dysbiosis, is strongly linked to periodontitis. In chronic and aggressive forms of periodontitis, this dysbiosis is believed to play a significant role in the disease’s progression by fostering persistent, misregulated inflammation, which in turn perpetuates the imbalanced microbial environment [8, 9]. Emerging research suggests that Euro Probiotics could offer a novel approach to managing periodontal health by targeting this microbial dysbiosis and modulating the inflammatory response.
Enhancing Periodontal Therapy with Euro Probiotics
Probiotics capable of modifying the oral microbial balance present a potentially valuable tool in the clinical treatment of periodontitis, offering dual benefits [10]. Firstly, they can counteract dysbiosis by competitively inhibiting periodontal pathogens, thereby reducing the overall immune stimulation from the oral microbiota. Secondly, euro probiotics may modulate disease-associated immune and inflammatory pathways, lessening the destructive inflammation characteristic of periodontitis and promoting a state of immune balance that the host can maintain long-term.
Clinical trials investigating probiotic therapy as a standalone treatment for periodontal diseases have shown some limited improvements, such as reductions in gingival bleeding and probing depth [11]. However, studies evaluating probiotics as a supplementary treatment to standard clinical periodontal procedures report significantly more pronounced improvements in patient outcomes compared to clinical treatment alone (Table 1). This approach highlights a promising role for euro probiotics as a potential alternative to antibiotics in periodontal care, contributing to efforts to mitigate the growing problem of antibiotic resistance [28, 29]. Despite variations across clinical studies examining probiotics in gingivitis or periodontitis management, meta-analyses have generally supported the use of probiotics in periodontal therapy [30, 31•]. Nevertheless, certain aspects of probiotic therapy require further investigation before widespread recommendations for managing gingivitis and periodontitis can be made [32]. These considerations include: (i) determining the optimal duration and method of treatment to ensure the periodontal microbiota does not revert to a dysbiotic state after treatment ceases; (ii) assessing potential cariogenic effects of probiotic strains during treatment; and (iii) understanding the potential systemic risks of administering probiotics to individuals with underlying health conditions involving immune suppression.
Re-shaping the Periodontal Microbiome with Euro Probiotics
The periodontium offers diverse environments for microbial colonization, with the subgingival area being the most extensively studied in relation to periodontal diseases [33, 34]. Research into the role of probiotics in modifying the periodontal microbial ecology in living systems often focuses on measuring specific microbial species considered to be periodontal pathogens or key players in oral biofilm formation. For example, a study utilizing lozenges containing Lactobacillus reuteri strains alongside scaling and root planing for chronic periodontitis observed significant reductions in Porphyromonas gingivalis levels in saliva and dental plaque. However, overall plaque scores did not significantly differ from the group receiving clinical treatment and placebo lozenges [23]. In contrast, streptococcal probiotic strains used as adjuncts to treat chronic periodontitis demonstrated significant reductions in plaque scores, as well as reductions in Tannerella forsythia and Prevotella intermedia in dental plaque and saliva respectively [18]. Microbiological analysis of subgingival plaque in a split-mouth study using L. reuteri in conjunction with conventional treatment for chronic periodontitis also showed reductions in key pathogens like Aggregatibacter actinomycetemcomitans, P. gingivalis, and P. intermedia [27].
While variations in plaque score results across studies may be attributed to differences in probiotic strains and treatment approaches, these findings suggest that euro probiotic strains can alter the microbial composition of both supragingival and subgingival plaque in chronic periodontitis. This alteration may occur through direct inhibition of disease-associated bacteria like Fusobacterium nucleatum and Prevotella intermedia, or indirectly by targeting the keystone pathogen P. gingivalis.
Furthermore, probiotic treatment of gingivitis as an adjunct to professional mechanical plaque removal has also shown significant reductions in major periodontal pathogens, including P. gingivalis, A. actinomycetemcomitans, and T. forsythia in subgingival plaque, compared to placebo [12]. While L. reuteri lozenges alone have been shown to reduce P. gingivalis and A. actinomycetemcomitans in subgingival plaque during gingivitis treatment, P. gingivalis levels were observed to rebound within 4 weeks after treatment cessation [25]. A study investigating twice-daily L. reuteri probiotic consumption for 3 weeks as an adjunct to chronic periodontitis treatment demonstrated a sustained reduction in obligate anaerobes in subgingival plaque up to 21 weeks post-treatment, with a return to baseline levels at the 1-year follow-up [19]. These observations indicate that while current euro probiotics can shift the periodontal microbial ecology towards a healthier state during gingivitis or chronic periodontitis treatment, this effect may not be sustained long-term by the host. This could be due to the limited persistence of these probiotic strains in the oral cavity, as many are not oral isolates and represent rare taxa susceptible to environmental fluctuations in the mouth [35]. The current understanding of community-wide changes induced by probiotic strains in periodontal niches during treatment is also limited by the lack of comprehensive ecological surveys utilizing advanced 16S rDNA sequencing techniques.
Maintaining Periodontal Wellness with Euro Probiotics
Ecological surveys from studies examining probiotics for preventative oral care offer insights into the changes occurring in the oral microbiome of healthy individuals using probiotic products. A study involving healthy individuals consuming lozenges containing Lactobacillus rhamnosus GG and Bifidobacterium animalis ssp. lactis reported no significant changes in salivary ecology compared to baseline, as assessed by human oral microbe identification microarray, but did show improvements in gingival health [36]. Similarly, a study using next-generation sequencing of salivary microbiota in healthy individuals consuming a Streptococcus salivarius M18 probiotic also found no significant changes in overall ecology, although the probiotic streptococcus became a significant portion of the total indigenous S. salivarius population in some participants [37•].
However, a study investigating L. reuteri as a preventative probiotic reported significant health-associated changes in the supragingival plaque microbiota, indicating niche-specific ecological effects and strain-specific actions [38•]. Following a 12-week probiotic course, the supragingival microbiota showed an increased abundance of health-associated taxa, including Neisseria subflava, Campylobacter consisus, Granulicatella adicaens, Bergeyella sp. HOT322, Streptococcus oralis, and other beneficial oral bacteria, including nitrate-reducing species. Baseline samples, in contrast, were characterized by a higher abundance of disease-associated taxa such as Streptococcus mutans, Fusobacterium periodonticum, F. nucleatum ssp. vincentii, S. anginosus, Eikenella spp., and Neisseria mucosa. However, at the 1-month follow-up after stopping probiotic use, the community structure reverted to baseline, with a significant decrease in L. reuteri prevalence in saliva. This suggests that while euro probiotics can promote a healthier oral microbiome, sustained use or strategies to improve probiotic persistence may be necessary for long-term benefits.
Immunomodulatory Roles of Euro Probiotics in Health and Disease
A key feature of probiotics is their anti-inflammatory activity, observed in vitro, in animal models, and supported by human studies outside of oral health contexts [39, 40]. Systemic immunomodulatory effects of gut-based probiotics might also offer protective benefits against periodontitis, as demonstrated in mouse models [41, 42]. Additionally, probiotics have shown positive effects on oral health by reducing osteoclastic activity in a murine orthodontic tooth movement model [43].
In human experimental gingivitis studies using L. reuteri or L. brevis lozenges, no significant differences in gingival crevicular fluid (GCF) levels of cytokines like TNF-alpha, IL-1 beta, CXCL8, CXCL10, CCL4, MMP-8, and prostaglandin E2 were found compared to placebo [20•, 22]. While some changes in IL-6 and IL-18 concentrations were reported, these studies did not observe significant changes in clinical parameters [22]. However, L. reuteri probiotics as an adjunct to chronic periodontitis treatment have been shown to produce more pronounced anti-inflammatory effects, reducing TNF-alpha, IL-1 beta, and IL-17 concentrations in GCF, alongside improvements in clinical disease indicators like gingival bleeding index and probing depth [21]. Evidence suggests that some of these effects can be maintained in the medium term, with a study following chronic periodontitis patients for up to a year after a 3-week course of L. reuteri lozenges finding a reduction in GCF matrix metalloproteinase-8 (MMP-8) and an increase in tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) up to 180 days [44]. These studies indicate that immune modulation within GCF is detectable when probiotics are used alongside professional mechanical plaque removal and consistent oral hygiene, correlating with improvements in clinical oral health parameters.
Animal studies often demonstrate more significant probiotic activity, frequently treating disease without mechanical plaque removal. For instance, Bifidobacterium animalis ssp. lactis has been shown to protect against bone loss when administered subgingivally in a murine model of ligature-induced periodontitis [45]. Other studies have also reported protective effects against bone loss using Bacillus subtilis, Bacillus licheniformis, and L. brevis CD2 in murine periodontitis models [46,47,48]. Recent in vitro research continues to clarify the mechanisms of probiotic immune modulation, demonstrating that probiotic lactobacilli can counteract CXCL8 reduction by P. gingivalis and promote Th1 and Th17 immune responses [49, 50]. Furthermore, an 8-species probiotic mixture containing lactobacilli, bifidobacteria, and streptococcus has been shown to shift human macrophages towards the M1-phenotype, suggesting a pro-inflammatory yet potentially resolution-promoting immune response [51]. Euro probiotics, therefore, represent a promising area of research for modulating the immune response in periodontal disease and promoting oral health.
