Abstract
BackgroundPeriodontal disease represents a major health concern. The administration of beneficial microbes has been increasing in popularity over efforts to manipulate the microbes using antimicrobial agents. This study determined the ability of Streptococcus salivarius to inhibit IL-6 and IL-8 production by gingival fibroblasts when activated by periodontal pathogens and their effect on the salivary microbiome.MethodsPrimary human gingival fibroblasts were challenged with Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum and a combination of all three. IL-6 and IL-8 cytokine release were measured. Using this same model, S. salivarius K12, M18 and different supernatant and whole-cell lysate fractions of S. salivarius K12 were administered to pathogen-induced fibroblasts. A patient study of healthy participants was also conducted to determine the effect S. salivarius K12 had on the native microbiome using 16S next generation sequence analysis.ResultsAll pathogens tested induced a significant IL-6 and IL-8 response. S. salivarius K12 or M18, did not exhibit an increase in inflammatory cytokines. When either of the probiotic strains were co-administered with a pathogen, there were significant reductions in both IL-6 and IL-8 release. This effect was also observed when gingival fibroblasts were pre-treated with either S. salivarius K12 or M18 and then stimulated with the oral pathogens. Chewing gum containing S. salivarius K12 did not alter the salivary microbiome and did not increase inflammatory markers in the oral cavity.ConclusionS. salivarius K12 and M18 prevented immune activation induced by periodontal disease pathogens. S. salivarius K12 did not alter the salivary microbiome or induce immune activation when administered as a chewing gum. These results warrant further study to determine if it may be an effective treatment in a model of periodontal disease.
Highlights
Periodontal disease represents a major health concern
S. salivarius interaction with oral pathogens Based on previous literature, it was confirmed that both S. salivarius K12 and M18 showed strong direct- and deferred-inhibition to all 9 indicator strains (Table 2), giving it P-Type 7–7-7
A coaggregation assay demonstrated that both K12 and M18 were able to coaggregate moderately with P. gingivalis and F. nucleatum and weakly with A. actinomycetemcomitans (Table 3)
Summary
Periodontal disease represents a major health concern. The administration of beneficial microbes has been increasing in popularity over efforts to manipulate the microbes using antimicrobial agents. MacDonald et al BMC Oral Health (2021) 21:245 actinomycetemcomitans and Fusobacterium nucleatum [3] These are anaerobic bacteria that trigger the release of pro-inflammatory cytokines, leading to immune cell recruitment, tissue destruction, and eventual bone loss. Combined with the increase in antibiotic resistance, many novel therapeutic approaches are being developed to aid in oral health and minimizing the impact on the patient. One of these include the use of beneficial bacteria to defend the oral microbiota from a dysbiotic state and exacerbating disease. Other mechanisms enhancing immune regulation [7], improving the integrity of epithelial barriers and function of tight junctions [8, 9], and production of metabolites [10], enzymes, co-factors, and vitamins [11], all of which benefit the health of the host
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