Streptococcus rattus

Streptococcus rattus (Strain JH145): An Oral Probiotic Bacterium

1. Identity, Nomenclature, and Taxonomy

Streptococcus rattus is the historically used orthographic variant of the species now formally designated Streptococcus ratti, a species of gram-positive, facultatively anaerobic oral bacterium belonging to the family Streptococcaceae, within the order Lactobacillales. The species carries NCBI Taxonomy ID 1341 and was formally proposed by Coykendall in 1977 as part of a reclassification of Streptococcus mutans subspecies into distinct species; type strain designations include ATCC 19645, DSM 20564, and CIP 102509, among others. The name Streptococcus rattus is currently considered an inaccurate spelling (a misspelling) of the correct name Streptococcus ratti, which was established through a nomenclatural correction; the organism is classified as biosafety Risk Group 1.

The parent taxon is Streptococcus Rosenbach 1884; the formal proposal to separate this species was based on molecular composition, specifically from a proposal to elevate subspecies of Streptococcus mutans to species status, published in the International Journal of Systematic Bacteriology in 1977. Phylogenetic studies using oligonucleotide cataloguing of 16S ribosomal RNA placed S. rattus alongside S. mutans, S. salivarius, and other oral streptococci within the streptococcal–enterococcal cluster of gram-positive eubacteria. The taxonomic literature also notes a heterotypic synonym: Streptococcus ursoris Shinozaki-Kuwahara et al. 2011, with type strain DSM 22768 and JCM 16316.

Streptococcus ratti is a cariogenic species of mutans streptococcus that has been isolated from both rat and human teeth. The strain JH145, derived from strain BHT-2, is notable for oral health research because it does not produce cariogenic lactic acid but retains robust biofilm production.

In the dietary supplement and oral probiotic context, the strain that has attracted all scientific and commercial attention is designated Streptococcus rattus JH145 (deposited at ATCC as accession number 31377). Streptococcus oralis (strain KJ3), Streptococcus uberis (strain KJ2), and Streptococcus rattus (strain JH145) are characterized as naturally-occurring oral bacteria that can act as antagonists and may be welcome adjuncts in efforts to reduce or replace harmful oral bacteria.

1.1 Common Names and Commercial Forms

The oral care probiotic formulation known as ProBiora3® contains a cocktail of three strains of naturally occurring oral bacteria: Streptococcus oralis KJ3®, Streptococcus uberis KJ2®, and Streptococcus rattus JH145®. ProBiora3 contains freeze-dried strains of bacteria delivered in the form of a quick-dissolving mint. The product has also been formulated as a mouthwash and as chewing tablets intended for oral local delivery.

2. Natural Source and Ecological Origin

Streptococcus ratti is a species of mutans streptococcus that has been isolated from both rat and human teeth; it is closely related to Streptococcus mutans and, like S. mutans, has been isolated from carious lesions in humans and can cause experimental caries in rodent models.

Streptococcus rattus strain JH145 is a probiotic strain within the Streptococcus genus; this bacterium is a spontaneous mutant of a Streptococcus mutans strain isolated from a carious lesion in an adult subject. Strain JH145 was isolated from the parent strain BHT-2 following mutagenesis; BHT-2 is a spontaneous streptomycin-resistant derivative of BHT. Although S. ratti BHT was isolated from human dental caries and was shown to be cariogenic, the mutant strain JH145 did not produce lactic acid or cause caries in a rodent model.

Streptococcus ratti can be viewed as a type of oral bacterium; it is found in healthy individuals and is also a component of dental biofilms. As a member of the broader mutans streptococci group, it naturally inhabits dental plaque on the tooth surface alongside many other oral streptococcal species.

3. Traditional and Historical Use

Streptococcus rattus JH145 has no documented traditional or ethnobotanical use in the historical sense applicable to botanical medicines or natural remedies. It is not a plant-derived or mineral ingredient with centuries of traditional medicinal application. Its history is entirely scientific and modern, rooted in mid-20th-century oral microbiology research.

At the same time Dr. Hillman's group conducted studies on the cavity-causing bacterium Streptococcus mutans, which is very effective at causing cavities because it attaches strongly to the teeth and produces lactic acid that eats away at tooth enamel. While working with this bacterium, Dr. Hillman's group found that sometimes during cell division S. mutans would produce variant strains with different characteristics; one of those variant strains, JH145, was unique because it was unable to produce lactic acid. Dr. Hillman's group hypothesized that this variant strain would be able to compete with S. mutans on the teeth for nutrients and attachment sites while also reducing cavities because of its inability to produce lactic acid.

The scientific conceptual basis for using S. rattus JH145 in the mouth is grounded in the ecological theory of "bacterial interference" — the idea that commensal or benign organisms can be deliberately introduced to occupy a niche and displace a pathogen. This concept was developed by Dr. Jeffrey D. Hillman and colleagues at institutions including the University of Florida over several decades beginning in the late 1970s. The three strains — S. uberis KJ2, S. oralis KJ3, and S. rattus JH145 — displayed observable oral health benefits, and it was not until the mid-2000s that they were combined into the patented blend now known as ProBiora3.

4. Key Constituents and Active Compounds: Mechanisms of Action

Unlike plant-derived ingredients, S. rattus JH145 is a living bacterial organism, and its "active constituents" are biological properties intrinsic to the bacterium itself rather than discrete extractable phytochemicals.

4.1 Lactate Dehydrogenase Deficiency (LDH⁻ Phenotype)

In contrast to S. mutans, S. rattus JH145 is lactate dehydrogenase deficient (LDH⁻), and thus does not produce lactic acid as part of its metabolism. S. rattus JH145 is a subspecies of S. mutans that, compared with S. mutans, produces only 3% as much lactic acid, as the consequence of a deletion in the structural gene of the lactate dehydrogenase. This single mutation is the cornerstone of the strain's utility as a probiotic.

The genetic basis of this LDH deficiency has been characterized: a spontaneous L(+)-lactate dehydrogenase (LDH)-deficient mutant of Streptococcus rattus, JH146, was also isolated for comparison with JH145; both strains were shown to have single base pair deletion mutations in the structural gene (ldh) for LDH, with approximately the same reversion frequencies.

4.2 Competitive Exclusion

As an oral care probiotic, S. rattus JH145 provides a health benefit through competitive exclusion by consuming the same resources and inhabiting the same ecological niche as S. mutans strains. Because it shares the same adhesion sites and dietary sugar substrates as its pathogenic cousin but does not generate tooth-damaging lactic acid, it effectively displaces cariogenic bacteria from the dental biofilm without itself contributing to acid-mediated enamel demineralization.

4.3 Biofilm Formation and Colonization

The strain JH145 is interesting for oral health because it does not produce cariogenic lactic acid but shows robust biofilm production. This robust biofilm-forming capacity allows it to colonize dental surfaces effectively. ProBiora3 (which includes S. rattus JH145) has been shown to activate when in contact with saliva, adhering to the surfaces of the teeth and gums; the bacterial colonies that constitute the probiotic proliferate and compete for nutrients, promoting the restoration of microbial equilibrium.

4.4 Contribution Within the ProBiora3 Blend

The ProBiora3® probiotic strains consist of Streptococcus oralis KJ3®, Streptococcus uberis KJ2®, and Streptococcus rattus JH145®; the S. oralis strain and, to a lesser degree, the S. uberis strain produce hydrogen peroxide, and the mechanism of antagonistic activity against periodontal pathogens has been demonstrated to depend on this metabolic activity. The role of S. rattus JH145 within the blend is therefore distinct: it targets S. mutans specifically through competitive exclusion and acid suppression, while the other two companion strains handle periodontal pathogen suppression via hydrogen peroxide production.

Mutans streptococci in the oral cavity convert sugar into lactic acid, which is the bacterial byproduct believed to be responsible for dental caries and the erosion of tooth enamel; the probiotic bacterium S. rattus JH145 specifically targets the reduction of acidogenic S. mutans in the oral cavity.

5. Scientific Evidence by Area of Use

5.1 Dental Caries Prevention

Animal Evidence (Preclinical): The foundational animal study on JH145 was published in the Journal of Applied Microbiology (2009). The aim of this study was to assess the ability of daily applications of Streptococcus rattus strain JH145 to affect the numbers of an implanted Streptococcus mutans strain in a rat model. Animals treated once daily with ≥10⁶ CFU of JH145 showed a statistically significant decrease in the proportion of implanted S. mutans to total cultivable bacteria in oral swab samples, and the rate of decrease in S. mutans levels was dose-dependent. The study concluded that daily application of JH145, a naturally occurring LDH-deficient variant of S. rattus, can compete with S. mutans for its habitat on the tooth surface, and that S. rattus JH145 has potential as a probiotic for use in the prevention of dental caries. No adverse effects were observed.

Human Clinical Evidence (Pilot Trial — Adults): A pilot human clinical trial published in 2009 (Zahradnik et al.) aimed to assess safety and effectiveness of ProBiora3 — containing S. oralis KJ3sm, S. uberis KJ2sm, and the spontaneous lactic acid-deficient variant of S. rattus strain JH145 — when administered twice daily over 4 weeks; the mouthwash was tested at two dose levels: 10⁶ and 10⁸ CFU each of the three strains. Substantial decreases in the levels of the marker bacteria were observed, and no safety issues were noted with the twice daily application of this mouthwash. The investigators acknowledged limitations including the small number of subjects and the use of young, orally healthy adults, along with inherent variability in microbiological measurements.

Human Clinical Evidence (Randomized Controlled Trial — Children): In an independently conducted randomized double-blind placebo-controlled clinical trial, the Caries Risk Test (CRT) values obtained with caries-prone children were significantly affected by the use of ProBiora3, by decreasing the number of S. mutans and lactobacilli present in the salivary samples. In another independently conducted clinical trial, 138 caries-prone children were treated with ProBiora3 for one year and the prevalence and increment of initial and manifest caries lesions was examined at baseline and follow-up.

Hedayati-Hajikand et al. (2015) observed significant reductions of early caries indications in 2–3-year-old children consuming Streptococcus rattus, Streptococcus oralis, and Streptococcus uberis enriched chewing tablets. This study evaluated the effect of ProBiora3™ (with strains S. uberis KJ2, S. oralis KJ3, S. rattus JH145) as an adjunct to the everyday oral hygiene of 2–3-year-old children, and the chewing tablets were found to benefit early childhood caries increment when used in children's daily oral care.

Evidence Characterization: The evidence supporting S. rattus JH145's anti-caries activity is multi-layered, including robust rodent data, in vitro mechanistic data, and several human clinical trials of varying size and design. However, all human studies of JH145 have used it in combination as part of the ProBiora3 blend rather than as a monotherapy, making it impossible to attribute observed effects solely to S. rattus JH145 independent of its companion strains. Overall evidence is promising but still limited in terms of large-scale, adequately powered, long-term randomized controlled trials specifically attributing outcomes to this strain alone. The competitive exclusion effect has been shown in multiple animal and human clinical studies (Hillman et al., 2009; Cannon et al., 2013, 2019; Hedayati-Hajikand et al., 2015).

5.2 Periodontal Disease

Human Clinical Evidence (Randomized Controlled Trial): A double-blind, placebo-controlled clinical trial (Laleman et al.) evaluated the adjunctive effects of a probiotic tablet containing S. oralis KJ3, S. uberis KJ2, and S. rattus JH145 after scaling and root planing (SRP) in 48 periodontitis patients; after root planing, patients used either a placebo or a probiotic tablet twice a day for 12 weeks, with pocket probing depth (PPD), bleeding on probing, and relative attachment levels measured at baseline, 12, and 24 weeks, alongside microbiological sampling and plaque and gingival indices at multiple time points.

The primary and secondary outcome measures were significantly (p < 0.05) improved at the 12- and 24-week evaluation in both groups; however, no significant inter-group differences could be detected at any time point, except that the percentage of sites with plaque was significantly lower in the probiotic group. No significant difference in clinical indices including PPD, bleeding on probing, and clinical attachment level could be detected between the probiotic group and the control group at baseline, 12-week, or 24-week time points.

The probiotic mouthwash ProBiora3™, which contains a mixture of S. oralis KJ3sm, S. uberis KJ2sm, and S. rattus JH145, has been reported to be safe and to significantly reduce the levels of dental pathogens in saliva and periodontal pathogens in subgingival plaque in adults.

Evidence Characterization: For periodontal disease, the evidence for S. rattus JH145 (as part of the ProBiora3 blend) is mixed. While reduction in microbiological markers of dysbiosis has been observed in some trials, the one double-blind randomized controlled trial published found no statistically significant clinical inter-group differences in key periodontal parameters such as probing depth and attachment levels. The evidence for clinically meaningful periodontal improvement remains inconclusive.

5.3 Reduction of Oral Pathogen Burden (Microbiological Outcomes)

Studies on the association of microorganisms in the probiotic group ProBiora3 — combining Streptococcus uberis KJ2, Streptococcus oralis KJ3, and Streptococcus rattus JH145 — indicated a reduced risk of the development of caries. The primary mechanism studied is reduction of S. mutans counts in saliva and plaque, which serve as biomarkers for caries risk. Multiple trials have demonstrated significant reductions in S. mutans salivary levels, although translating microbiological reduction to clinical caries prevention remains an active area of research.

6. Body Systems and Health Areas Associated with Streptococcus rattus JH145

• Oral Cavity / Dental Enamel: Primary target. Reduction of S. mutans colonization on tooth surfaces with the goal of preventing dental caries (tooth decay) through lactic acid suppression and competitive exclusion.
• Periodontal Tissues (Gums): Investigated as an adjunct to scaling and root planing for periodontitis management, targeting reduction of subgingival periodontal pathogens.
• Dental Biofilm / Oral Microbiome: Oral health care professionals face the challenge of managing more than 700 different bacterial species found in dental biofilm; while dental biofilm formation is impossible to prevent, influencing the content of the biofilm is possible through oral probiotics. S. rattus JH145 is specifically designed to shift biofilm composition away from cariogenic species.

7. Dosage Forms and Dosages Reported in Studies

All dosages below are reported directly from the cited studies and refer to the ProBiora3 blend (which includes S. rattus JH145 along with S. oralis KJ3 and S. uberis KJ2) unless otherwise noted, as S. rattus JH145 has not been studied clinically in isolation.

• Pilot Human Clinical Trial (Zahradnik et al., 2009 — Mouthwash): The mouthwash was administered twice daily over a period of 4 weeks and was tested at two dose levels: 10⁶ and 10⁸ colony forming units each of S. oralis KJ3sm, S. uberis KJ2sm, and S. rattus JH145.
• Subchronic Animal Toxicology Study (Hillman et al., 2009): The blend was administered to rats orally once daily (5 days per week) at doses of 0, 10⁶, or 10⁹ colony-forming units of each strain for 14 weeks.
• Animal Efficacy Study (Hillman et al., 2009 — Rat Oral Implantation Model): Animals treated once daily with ≥10⁶ CFU of JH145 showed a statistically significant decrease in the proportion of implanted S. mutans to total cultivable bacteria in oral swab samples.
• Periodontal RCT (Laleman et al., 2015 — Tablet): After root planing, patients used either a placebo or a probiotic tablet twice a day for 12 weeks. The specific CFU dose per tablet was not extracted in the publicly available abstract.
• Children's Caries RCT (Hedayati-Hajikand et al., 2015 — Chewing Tablet): The effect of ProBiora3™ (with strains S. uberis KJ2, S. oralis KJ3, S. rattus JH145) was evaluated as an adjunct to the everyday oral hygiene of 2–3-year-old children. Dosage was in chewing tablet form; specific CFU values per tablet were not reported in available abstracts of this publication.

8. Safety Considerations

8.1 Animal Toxicology

The objective of a dedicated subchronic toxicity study was to investigate adverse effects of the blend of 3 natural strains — Streptococcus uberis KJ2, Streptococcus oralis KJ3, and Streptococcus rattus JH145 (ProBiora3). The blend was administered to rats orally once daily (5 days per week) at doses of 0, 10⁶, or 10⁹ colony-forming units of each strain for 14 weeks. No treatment-related adverse effects were observed in physiological parameters during the study or in the evaluation of blood and tissue samples taken from animals at the end.

8.2 Human Clinical Safety

In the pilot human clinical trial, substantial decreases in marker bacteria levels were observed, and no safety issues were noted with the twice daily application of the mouthwash. In the rodent efficacy model, no adverse effects were observed by in-life observation of treated animals, and histopathological, haematological and blood chemistry analyses were unremarkable.

In a separate clinical trial using the ProBiora3 formulation, it was noted to be safe and well tolerated, with no user complaints of tooth sensitivity or gingival irritation throughout the 8-week treatment period involving twice daily product use.

8.3 Antibiotic Susceptibility

Results of an in vitro antibiotic susceptibility study demonstrate that all three ProBiora3 strains (including S. rattus JH145) are susceptible to commonly used therapeutic antibiotics. Streptococcus uberis KJ2, Streptococcus oralis KJ3, and Streptococcus rattus JH145 strains used in the ProBiora3 formulation are susceptible to commonly used antibiotics, with a no-observed-adverse-effect level established in animal studies. This antibiotic susceptibility is a critical safety feature because it means that, in the unlikely event of systemic translocation, the organism could be treated with standard antibiotics.

8.4 Risk Group Classification

The species is classified as Risk Group 1 in the List of Recommended Names for bacteria of medical importance. Risk Group 1 organisms are those not known to cause disease in healthy adult humans. However, as with other viridans group streptococci, the broader species group carries a theoretical risk of opportunistic infection in immunocompromised individuals. Viridans group streptococci are typically part of the commensal flora but can also cause severe invasive diseases such as infective endocarditis, though this is a well-established characteristic of the broader VGS group and has not been specifically linked to the JH145 probiotic strain in any published safety study. The specific strain JH145 has not been associated with invasive infection in published literature.

8.5 Regulatory and Market Status

In the USA, most probiotic products are marketed as dietary supplements or functional food ingredients, which only require pre-market notification, not approval, by the U.S. Food and Drug Administration. ProBiora3 (containing S. rattus JH145) is marketed in the United States under this regulatory framework.

8.6 Noted Limitations in the Current Evidence Base

The following source-backed limitations are relevant to interpreting safety and efficacy data on S. rattus JH145:

• Despite the small number of subjects and the use of young, orally healthy adults, along with the inherent variability in microbiological measurements, the probiotic mouthwash was able to substantially affect the levels of dental pathogens (per Zahradnik et al. conclusions).
• All human studies of S. rattus JH145 tested it within the three-strain ProBiora3 blend, making strain-specific attribution of outcomes impossible without dedicated monotherapy trials.
• The periodontal RCT (Laleman et al., 2015) found no significant clinical inter-group differences in probing depth, attachment level, or bleeding despite apparent microbiological changes, indicating that microbial reduction does not automatically translate to clinical improvement.
• At the time of one review, there was no randomized controlled clinical trial available that had specifically investigated the influence of Streptococcus-containing probiotics as an adjunct to nonsurgical periodontal therapy (scaling and root planing) with statistically significant clinical outcomes favoring the probiotic group.

References

• Frontiers in Microbiology (PMC11228166): Probiotics for oral health: a critical evaluation of bacterial strains
• PubMed (19426263): A spontaneous lactate dehydrogenase deficient mutant of Streptococcus rattus for use as a probiotic in the prevention of dental caries — Hillman et al., Journal of Applied Microbiology, 2009
• PMC7171213: Complete Genome Sequence of Streptococcus ratti JH145
• International Journal of Toxicology: Safety Assessment of ProBiora3, a Probiotic Mouthwash: Subchronic Toxicity Study in Rats — Hillman et al., 2009
• Journal of Applied Microbiology: Preliminary assessment of safety and effectiveness in humans of ProBiora3, a probiotic mouthwash — Zahradnik et al., 2009
• PubMed (26427036): The effect of a streptococci containing probiotic in periodontal therapy: a randomized controlled trial — Laleman et al., 2015
• LPSZ/DSMZ List of Prokaryotic names with Standing in Nomenclature: Streptococcus rattus
• NCBI Taxonomy Browser: Streptococcus ratti (Taxonomy ID 1341)
• OA Text (Open Access): Dental whitening effect of an oral probiotic — Cannon et al.
• MDPI Applied Sciences: Probiotics, Prebiotics, Synbiotics and Dental Caries — 2021
• Special Care in Dentistry (Wiley): Anti-caries Streptococcus spp.: A potential preventive tool for special needs patients — Mato et al., 2024
• PMC6476965: Isolation and Bacteriocin-Related Typing of Streptococcus dentisani — Frontiers in Cellular and Infection Microbiology, 2019
• Nutrire / Springer: Probiotic supplementation in dental caries — 2018
• Microbiology Society: The Phylogenetic Position of Streptococcus and Enterococcus — 1985
• Wikipedia: Streptococcus ratti