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Abstract Background The oral microbiota has been implicated in the pathogenesis of rheumatoid arthritis through activation of mucosal immunity. This study tested for associations between oral health, microbial communities and juvenile idiopathic arthritis (JIA). Methods A cross-sectional exploratory study of subjects aged 10–18 years with oligoarticular, extended oligoarticular and polyarticular JIA was conducted. Control groups included pediatric dental clinic patients and healthy volunteers. The primary aim was to test for an association between dental health indices and JIA; the secondary aim was to characterize the microbial profile of supragingival plaque using 16S rRNA gene sequencing. Results The study included 85 patients with JIA, 62 dental patients and 11 healthy child controls. JIA patients overall had significantly more gingival inflammation compared to dental patients, as evidenced by bleeding on probing of the gingiva, the most specific sign of active inflammation (p = 0.02). Overall, however, there was a trend towards better dental hygiene in the JIA patients compared to dental patients, based on indices for plaque, decay, and periodontitis. In the JIA patients, plaque microbiota analysis revealed bacteria belonging to genera Haemophilus or Kingella elevated, and Corynebacterium underrepresented. In poly JIA, bacteria belonging to the genus Porphyromonas was overrepresented and Prevotella was underrepresented. Conclusion Increased gingival inflammation in JIA was independent of general oral health, and thus cannot be attributed to poor dental hygiene secondary to disability. The variation of microbial profile in JIA patients could indicate a possible link between gingivitis and synovial inflammation.

Epidemiological studies reveal significant associations between periodontitis and oral cancer. However, knowledge about the contribution of periodontal pathogens to oral cancer and potential regulatory mechanisms involved is limited. Previously, we showed that nisin, a bacteriocin and commonly used food preservative, reduced oral cancer tumorigenesis and extended the life expectancy in tumor-bearing mice. In addition, nisin has antimicrobial effects on key periodontal pathogens. Thus, the purpose of this study was to test the hypothesis that key periodontal pathogens (Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum) promote oral cancer via specific host-bacterial interactions, and that bacteriocin/nisin therapy may modulate these responses. All three periodontal pathogens enhanced oral squamous cell carcinoma (OSCC) cell migration, invasion, tumorsphere formation, and tumorigenesis in vivo, without significantly affecting cell proliferation or apoptosis. In contrast, oral commensal bacteria did not affect OSCC cell migration. Pathogen-enhanced OSCC cell migration was mediated via integrin alpha V and FAK activation, since stably blocking alpha V or FAK expression abrogated these effects. Nisin inhibited these pathogen-mediated processes. Further, Treponema denticola induced TLR2 and 4 and MyD88 expression. Stable suppression of MyD88 significantly inhibited Treponema denticola-induced FAK activation and abrogated pathogen-induced migration. Together, these data demonstrate that periodontal pathogens contribute to a highly aggressive cancer phenotype via crosstalk between TLR/MyD88 and integrin/FAK signaling. Nisin can modulate these pathogen-mediated effects, and thus has therapeutic potential as an antimicrobial and anti-tumorigenic agent. Author summary Oral squamous cell carcinoma (OSCC), a subset of HNSCC, is the most common malignant oral neoplasm. Risk factors, including smoking, alcohol consumption and human papilloma virus (HPV) infection alone have not been sufficient in explaining the incidence and aggressive behaviors of OSCC. Thus, other factors, such as oral periodontal pathogens may play an important role in OSCC tumor development, progression and metastasis, yet this has not been well explored. Here, we test whether periodontal pathogens promote oral cancer tumorigenesis, and whether bacteriocin/nisin treatment may modulate these responses. We found that periodontal pathogens promote cancer aggressivity via crosstalk between integrin/FAK and TLR/MyD88 signaling pathways that is reversible by bacteriocin/nisin treatment. Our study offers direct evidence that a bacteriocin, nisin has a broad therapeutic potential as an anti-cancer agent, and as an inhibitor of pathogen-mediated carcinogenesis.

Epidemiological studies reveal significant associations between periodontitis and oral cancer. However, knowledge about the contribution of periodontal pathogens to oral cancer and potential regulatory mechanisms involved is limited. Previously, we showed that nisin, a bacteriocin and commonly used food preservative, reduced oral cancer tumorigenesis and extended the life expectancy in tumor-bearing mice. In addition, nisin has antimicrobial effects on key periodontal pathogens. Thus, the purpose of this study was to test the hypothesis that key periodontal pathogens (Porphyromonas gingivalis, Treponema denticola, and Fusobacterium nucleatum) promote oral cancer via specific host-bacterial interactions, and that bacteriocin/nisin therapy may modulate these responses. All three periodontal pathogens enhanced oral squamous cell carcinoma (OSCC) cell migration, invasion, tumorsphere formation, and tumorigenesis in vivo, without significantly affecting cell proliferation or apoptosis. In contrast, oral commensal bacteria did not affect OSCC cell migration. Pathogen-enhanced OSCC cell migration was mediated via integrin alpha V and FAK activation, since stably blocking alpha V or FAK expression abrogated these effects. Nisin inhibited these pathogen-mediated processes. Further, Treponema denticola induced TLR2 and 4 and MyD88 expression. Stable suppression of MyD88 significantly inhibited Treponema denticola-induced FAK activation and abrogated pathogen-induced migration. Together, these data demonstrate that periodontal pathogens contribute to a highly aggressive cancer phenotype via crosstalk between TLR/MyD88 and integrin/FAK signaling. Nisin can modulate these pathogen-mediated effects, and thus has therapeutic potential as an antimicrobial and anti-tumorigenic agent.