Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability

Abstract

AbstractBackgroundThe reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions, such as hypertension and diabetes. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with healthy conditions, but the impact of periodontitis on nitrate-reducing capacity and therefore nitric oxide availability has not been evaluated. The aim of the current study is to see assess how periodontitis and periodontal treatment affect the nitrate reduction capacity of the oral microbiota.MethodsFirst, 16S rRNA sequencing data of five studies from different countries were analysed with the Dada2 pipeline to compare nitrate-reducing bacteria in health and periodontitis. Additionally, subgingival plaque, saliva and plasma samples from 42 periodontitis patients were collected before and after non-surgical periodontal therapy (NSPT). The subgingival plaque bacterial composition was determined using Illumina sequencing of the 16S rRNA gene and the quantity of the nitrate-reducing biomarker genusRothiawas determined by qPCR. Measurements of nitrate and nitrite in saliva and plasma were performed and the salivary nitrate reduction capacity (NRC) was determined after three hours of incubationin vitroand compared with the NRC of 15 healthy individuals.ResultsNitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals (p < 0.05 in all five datasets). After NSPT, nitrate-reducing bacteria increased in subgingival plaque (p < 0.05) and correlated negatively with periodontitis-associated bacteria (p < 0.001). A post-treatment increase in the genusRothiawas confirmed by qPCR (p < 0.05), as well as an increase in the salivary NRC (p < 0.05). No significant effect was found of NSPT on the plasma nitrate and nitrite levels in this population.ConclusionThe levels of nitrate-reducing bacteria of the subgingival microbiota decrease in periodontitis and both their levels and the salivary NRC increase after NSPT. We hypothesize that an impaired NRC can affect nitric oxide availability and can therefore be an instrumental link between periodontitis and systemic conditions.