The major oral diseases, including dental caries and periodontitis, are associated with an imbalance in the oral microbiota (1). Alterations in its composition have been linked not only to oral diseases but also to systemic conditions such as diabetes, obesity, and cardiovascular disease (2, 3). Maintaining oral microbial homeostasis is increasingly recognized as a useful approach for promoting both oral and systemic health.

Probiotics have recently been proposed as an alternative approach to promote health. According to EFSA, probiotics must meet several criteria to be considered safe and effective: they must be non-pathogenic, lack transferable antibiotic resistance genes, be viable at the target site, adhere to and transiently colonize the mucosa, and demonstrate beneficial effects in well-designed clinical studies (4, 5). Probiotics exert their beneficial effects through multiple mechanisms, including competitive exclusion of pathogens, production of antimicrobial metabolites (organic acids, bacteriocins, hydrogen peroxide), modulation of the host immune system, and enhancement of epithelial barrier function (6). They can also help restore microbial balance after dysbiosis caused by antibiotics or infections.

Probiotics have shown potential benefits for oral health, including caries, halitosis, and periodontitis, in healthy individuals and those with systemic diseases (7–9). Some of the most studied and promising strains include Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus acidophilus, Lactobacillus salivarius, Lactobacillus casei and paracasei, Bifidobacterium lactis, among others (10). Collectively, these strains have demonstrated beneficial effects on the oral cavity. Lacticaseibacillus rhamnosus GG is one of the most extensively investigated strains and has shown the ability to counteract the most common oral diseases, including dental caries and periodontal disease (11–14).

Spore-forming probiotics are gaining popularity due to their enhanced survival and stability (15, 16). In functional food research, Bacillus spp. have attracted increasing attention due to their remarkable tolerance in the harsh conditions of the gastrointestinal tract. Furthermore, their superior stability during food and pharmaceutical processing and storage renders them ideal candidates for health-promoting formulations (17). In contrast, vegetative probiotic species are more sensitive to these processes and often require refrigeration to maintain potency (18).

Heyndrickxia coagulans (formerly Bacillus coagulans) is a Gram-positive, facultatively anaerobic bacterium belonging to the Bacillus genus, known for its ability to produce lactic acid (19). This strain exhibits antimicrobial, antioxidant, and immunomodulatory properties (20), and it has recently received considerable attention in dentistry (18, 21, 22). Recent studies highlight its effectiveness in controlling dental caries by reducing Streptococcus mutans and Lactobacillus spp. counts in plaque and saliva (18, 21). Additionally, they have been shown to lower gingival index scores, reduce bleeding on probing, and combat gingival inflammation (23). H. coagulans may exert these effects through several mechanisms: it produces antimicrobial metabolites, including organic acids and bacteriocin-like compounds that can inhibit cariogenic bacteria such as S. mutans (24, 25), and it can modulate host immune responses by enhancing anti-inflammatory cytokine activity and supporting mucosal immunity (26, 27). H. coagulans is listed by the EFSA under the Qualified Presumption of Safety status for recommended biological agents due to the absence of transferable antimicrobial resistance genes and the lack of toxigenic activity (28), unlike other Bacillus spp (29). This microorganism forms heat- and acid-resistant spores, enabling it to survive harsh environmental conditions (30). These features make H. coagulans particularly suitable for use as a probiotic in products subjected to industrial processing, including confectionery and functional foods (16).

Given the increasing scientific interest in Heyndrickxia coagulans as a probiotic strain, recent studies have begun to explore its potential applications in the prevention and treatment of oral diseases. The aim of this systematic review is to summarize and critically assess the current evidence regarding the effects of H. coagulans on oral health.

The results of the database search are illustrated in the flowchart in Figure 1. A total of 81 records were initially identified, and 55 remained after duplicate removal. Of these, 45 records were excluded by title and abstract screening (Supplementary File 4S). As a result, 10 articles were deemed eligible for full-text assessment (Supplementary File 5S). Two of these records (37, 38) were clinical trial registrations; therefore, a search was conducted to verify whether any articles reporting the results of these trials had been published, but none were found. Ultimately, eight studies (18, 21, 22, 39–43) were included in the qualitative synthesis, and three were included in the meta-analysis.

This systematic review analyzed the available literature on the effects of Heyndrickxia coagulans (previously referred to as Bacillus coagulans) on oral health outcomes. Across seven included studies, H. coagulans demonstrated promising benefits, most notably in reducing salivary Streptococcus mutans levels and improving selected periodontal parameters. These findings suggest that H. coagulans may have a potential role as an adjunctive strategy for caries prevention and the management of gingival inflammation. However, these conclusions should be interpreted with caution due to the limited number of studies available, as well as their heterogeneity and methodological limitations.

Overall, the quality of the evidence is low to moderate. This assessment reflects several recurring methodological limitations across the included studies. In particular, the small number of studies and their limited sample sizes lead to substantial imprecision and reduce the robustness of the estimates. Considerable heterogeneity in populations, interventions, and outcome measures further compromises the consistency of the evidence. Moreover, the short intervention and follow-up periods do not allow for an adequate evaluation of long-term effects. Consequently, although the findings are promising, they should be interpreted with caution and confirmed by future, more rigorous research.

The most consistent finding across the included trials was a significant reduction in Streptococcus mutans counts following H. coagulans administration, particularly among children and individuals at high risk of caries. The high heterogeneity observed in the meta-analysis may be explained by several factors related to differences among the included studies. First, the meta-analysis is based on only three studies, comprising a total sample of approximately one hundred participants. The age of participants varied considerably: two studies (22, 42) involved adolescents and adults without providing stratified data that would allow age-specific subgroup comparisons, while one study focused on children (18). Additionally, one study included patients at high caries risk (18), whereas the other two (22, 42) involved healthy individuals, which may have amplified the observed effect in the high-risk group. Another important source of variability is the form in which the probiotic was administered. In two studies (22, 42), the probiotic was incorporated into a sweet food (cake), while in the third study (18) it was delivered through sugar-free chewable tablets. The consumption of cake, being a sugary food, led to an increase in S. mutans counts overall; however, this increase was less pronounced in the probiotic group, indicating a relative effect. In contrast, the chewable tablets did not contain sugar, resulting in an absolute reduction in S. mutans counts. Differences in probiotic dosage may also have contributed to heterogeneity, as two studies (22, 42) did not report the administered dose. Finally, although follow-up periods varied across studies, they were all relatively short, which likely had only a moderate influence on heterogeneity. Given these limitations, any subgroup or sensitivity analysis would be underpowered, potentially misleading, and unlikely to yield interpretable or clinically meaningful conclusions.

The effects on Lactobacillus spp. were less conclusive, with only one study reporting significant reductions. Considering that Lactobacilli spp. is primarily involved in the progression of dentinal caries rather than the initiation of the caries process, this partial effect may still hold clinical relevance; however, further confirmation in larger, well-designed trials is warranted. Nevertheless, the present results support the hypothesis that H. coagulans can meaningfully modulate the cariogenic microflora.

The impact of H. coagulans on plaque accumulation and gingival inflammation was variable. Some studies reported stabilization or reduction of plaque indices compared with control/placebo groups, while others found no difference. Notably, in gingivitis and periodontitis, H. coagulans was associated with improvements in the gingival index, bleeding on probing, and clinical attachment level. These results are encouraging and suggest a possible role in modulating host inflammatory response.

The findings of this review are in line with broader probiotic research, which has reported reductions in S. mutans levels in saliva and plaque (44, 45). Nonetheless, the evidence regarding effects on Lactobacilli and on clinical outcomes, such as plaque and gingival indices, remains inconsistent (46, 47). Although several meta-analyses have suggested modest improvements in gingival inflammation with probiotic use, these conclusions are tempered by high heterogeneity and generally low certainty of evidence (48, 49). Within this context, the present review provides preliminary insights into the potential role of H. coagulans, a species that may offer specific advantages, such as spore formation that could support survival and colonization. However, given the variability and limitations in the current evidence base, any species-specific claims should be interpreted cautiously until confirmed by more robust and methodologically comparable studies.

Several mechanisms may explain the observed effects. H. coagulans may inhibit cariogenic bacteria through competitive exclusion, production of antimicrobial peptides, and disruption of biofilm formation (50). In addition, it may exert anti-inflammatory effects by modulating cytokine production and oxidative stress markers, as evidenced by reductions in gingival bleeding and Glutathione Peroxidase activity in some trials (23). Unlike chemical antiseptics such as chlorhexidine, probiotics aim to restore microbial balance rather than indiscriminately suppress the oral microbiota, which could explain their favorable safety profile.

The evidence base is strengthened by the predominance of randomized controlled trials, the inclusion of both pediatric and adult populations, and the use of multiple delivery vehicles (tablets, mouthwash, food matrices). Nonetheless, several limitations must be acknowledged. The studies were highly heterogeneous in strain dosage, intervention duration, outcome measures, and control conditions, which precluded robust meta-analysis for most outcomes. Sample sizes were generally limited, and several studies exhibited an unclear or high risk of bias, primarily due to insufficient reporting of randomization procedures and the absence of blinding, which may have introduced methodological weaknesses. Moreover, follow-up periods were quite short, reducing insights into the durability of probiotic effects.

Despite these limitations, the findings may have relevant clinical implications. H. coagulans could serve as a safe adjunct to conventional caries prevention measures, particularly in children at high risk of caries development. Its use in mouthwash or tablets may offer practical advantages for daily application and better compliance. The observed improvements in gingival inflammation indicate potential benefits for individuals with mild periodontal disease, positioning H. coagulans as a useful adjunct to conventional mechanical plaque control and professional prophylaxis. Notably, no significant adverse effects were reported, further supporting its safety and potential suitability for long-term preventive applications.

Further well-designed randomized controlled trials are necessary to confirm these preliminary results and to address remaining gaps. Future studies should standardize probiotic dosages, use validated outcome measures, and include longer follow-up periods to assess the persistence of effects. Investigations employing next-generation sequencing could provide deeper insight into changes in the oral microbiome and clarify whether H. coagulans promotes a sustainable shift toward health-associated microbial communities. Trials evaluating caries incidence, periodontal disease progression, and patient-reported outcomes would help determine the true clinical significance of the observed microbiological changes.

Overall, this systematic review indicates that current evidence is insufficient to support the clinical efficacy of H. coagulans in improving oral health. Nonetheless, the available findings are encouraging and suggest that this species may have potential as a future adjunct in oral care. High-quality, large-scale clinical trials are needed to determine optimal dosing, delivery methods, and long-term effectiveness, and to clarify the precise role of H. coagulans in preventive and therapeutic oral health strategies.