NCT07508839

Evaluation of the Safety and Efficacy of SALI-10 Probiotic Lozenges

Evaluation of the Safety and Efficacy of SALI-10 Probiotic Lozenges: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Ostia Sciences · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Gingivitis is among the most common oral conditions, affecting 50-90% of adults globally. It is a reversible inflammatory disease triggered primarily by the accumulation of microbial plaque on teeth and gingival tissues. Standard treatment involves plaque reduction and maintenance of oral hygiene, often supplemented with antimicrobial therapeutics to prevent disease progression. While plaque control remains the cornerstone of prevention, emerging research points to certain beneficial microbes that may protect gingival health. Notably, Streptococcus species have been associated with both antimicrobial and anti-inflammatory activities, suggesting their potential as oral probiotics. Recent investigations have focused on a novel strain, Streptococcus salivarius SALI-10, which produces a lantibiotic called Salivaricin 10. This peptide exhibits unique immunomodulatory properties. In murine models, Salivaricin 10 was shown to enhance neutrophil recruitment and activity while directing monocytes toward the M2 pro-resolution macrophage phenotype, a cell population integral to tissue repair and late-stage wound healing. Such effects highlight the potential of SALI-10 to reduce gingival inflammation while fostering microbial balance. The concept of employing S. salivarius strains in oral health is not entirely new. Other variants isolated from the oral cavities of healthy individuals produce lantibiotics with lanthionine or β-methyllanthionine residues that demonstrate antimicrobial effects against pathogens. Clinical investigations have explored these probiotic strains for halitosis, plaque control, and gingivitis, reporting safety and efficacy. Moreover, salivaricin-producing strains are considered valuable in the ongoing search for alternatives to conventional antibiotics in light of increasing resistance. Understanding the microbial ecology of gingivitis helps contextualize this therapeutic potential. In health, gram-positive bacteria, particularly Streptococcus species, dominate the oral microbiome. Gingivitis involves a shift toward gram-negative periopathogens such as Porphyromonas, Tannerella, Treponema, and Prevotella. This dysbiosis provokes an inflammatory cascade characterized by neutrophil infiltration, tissue damage, and, if unresolved, progression to periodontitis. A recent human experimental gingivitis study revealed distinct host response phenotypes. Participants retaining beneficial Streptococcus species, such as S. sanguinis and S. oralis, experienced reduced periopathogen emergence and milder inflammation. By contrast, participants who lost these protective bacteria demonstrated greater inflammatory severity, underscoring the critical role of Streptococcus persistence in oral homeostasis. Neutrophils, the most abundant immune cells in periodontal tissues, are central to this dynamic. Their numbers increase proportionally with gingivitis severity. Importantly, Health Canada has recently recognized salivary neutrophil activity as a valid biomarker for assessing inflammatory burden and risk of gingivitis or periodontal disease. This regulatory approval highlights the growing emphasis on immune function as both a diagnostic measure and therapeutic target in oral health. Against this backdrop, S. salivarius SALI-10 presents a compelling intervention strategy. Its hypothesized benefits include reducing inflammation via promotion of the M2 macrophage phenotype, suppressing periopathogen growth through competitive exclusion and Salivaricin 10 production, and mitigating halitosis by blocking volatile sulfur compound-producing bacteria. To evaluate these benefits, a proposed study design involves administering a twice-daily lozenge , one in the morning and one in the evening, after brushing a tongue scraping each containing 3 billion CFU of SALI-10 over a four-week period. In summary, gingivitis remains highly prevalent but reversible. Beyond traditional hygiene approaches, microbial therapeutics such as S. salivarius SALI-10 may offer a dual antimicrobial and anti-inflammatory benefit. By promoting immune resolution and reshaping the microbial community, SALI-10 could emerge as a novel probiotic strategy in maintaining oral health and addressing the limitations of conventional antimicrobial therapies.

Detailed description

Gingivitis is an oral disease condition affecting 50% to 90% of adults globally. The gingivitis pathology can be reversed by reduction or removal of microbial plaque that accumulates on hard and soft tissues and is considered standard of care in the industry. Regular oral hygiene in combination with therapeutics that deliver an anti-microbial benefit is thought to mitigate the onset of gingivitis. However, some oral microbes, specifically Streptococcal species, have been identified with both antimicrobial and anti-inflammatory attributes that are speculated to play a role in protecting and potentiating healthy gingival tissues and are currently being investigated as probiotic opportunities in oral health support. Recently, a new strain of Streptococcus salivarius SALI-10 has been identified with unique lantibiotic (Salivaracin 10) production that highlights a possible anti-inflammatory benefit. Using a mouse model, S. salivarius SALI-10 isolated Salivaracin 10 was shown to increase neutrophil recruitment and activation while also driving monocyte differentiation toward an M2 pro-resolution macrophage phenotype, widely found to participate in the oral cavity and late stages of the wound healing response. Other studies have shown certain Streptococcus salivarius strains, found in the oral cavity of healthy patients, produce similar lantibiotic salivaricins containing lanthionine and/or β-methyllanthionine residues. These molecules have been found to promote antimicrobial activity towards relevant oral pathogens and have been applied through the development of salivaricin-producing probiotic strains. Indeed, several groups have investigated the efficacy of different Streptococcus salivarius probiotic strains with success in halitosis, safety, plaque and gingivitis clinical trials. These salivaricins may also prove to be of great value in the development of new and novel antibacterial therapies in this era of emerging antibiotic resistance. Gingivitis is a reversible inflammatory condition caused by the accumulation of dental plaque and the associated disruption of the host-microbial homeostasis. During gingivitis, the microbial community transitions from being dominated by gram-positive health-associated bacteria, such as Streptococcus species, to gram-negative periopathogens, including species of the genera Porphyromonas, Tannerella, Treponema and Prevotella. This dysbiotic shift triggers inflammatory responses, subsequent increase in neutrophils, leading to tissue damage and, in some cases, progression to periodontitis. A recent study on human experimental gingivitis identified three distinct host response phenotypes.The microbial analysis revealed that the persistence of beneficial Streptococcus species, such as S. sanguinis and S. oralis, in slow and low responders correlated with a protective effect against the emergence of periopathogens and the associated inflammatory cascade. Conversely, the loss of these beneficial bacteria in high responders was linked to more severe inflammation, highlighting the critical role of the oral microbiome in modulating gingivitis severity. Alterations in the oral microbiome alter host immune functions and stimulate immune cells to dominate the gingival tissues. Neutrophils, a type of white blood cell (leukocyte), represent a key component of the innate defence system that protects periodontal tissue from both gingivitis and periodontitis. Not only are they the first line of cellular defence, but they are among the most abundant leukocytes within the periodontal tissues. During gingivitis a significant increase in the number of neutrophils is seen to correspond to disease severity. In accordance, there was a recent approval by Health Canada for the use of salivary neutrophil activity as a measure of inflammatory load that corresponds with risk for gingivitis and/or periodontal disease. Investigators propose using a novel strain, Streptococcus salivarius SALI-10, as a targeted microbial intervention to reduce oral inflammation. S. salivarius SALI-10 is hypothesized to: * Reduce inflammation by driving M2 Resolution Phenotype. * Inhibit the growth of periopathogens such as Porphyromonas, Tannerella and Prevotella through competition and production of Salivaricin 10. * Reduce halitosis by inhibiting periopathogens that produce volatile sulfur compounds. A twice-daily lozenge, one in the morning and one in the evening, after brushing and tongue scraping, will be issued containing S. salivarius SALI-10 (3 billion CFU/lozenge) for 4 weeks.

Conditions

• Gingivitis
• Halitosis

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	3B SALI-10 Lozenge	A lozenge containing 3B CFUs of the probiotic . S. salivarius SALI-10
OTHER	Placebo	It is a placebo lozenge with no active ingredient.

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-01-01
• Completion: 2027-04-01
• First posted: 2026-04-02
• Last updated: 2026-04-02

Locations

1 site across 1 country: Canada