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Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

ABSTRACT: Background The enterosalivary nitrate-nitrite-nitric oxide (NO₃-NO₂-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO₂, NO, or ammonia [NH₃]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH₃ summary ratio was inversely associated with a -0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH₃ summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

SUBMITTER: Goh CE

PROVIDER: S-EPMC9238569 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background The enterosalivary nitrate-nitrite-nitric oxide pathway is an alternative pathway of nitric oxide generation, potentially linking the oral microbiome to insulin resistance and blood pressure (BP). We hypothesized that increased abundance of nitrate-reducing oral bacteria would be associated with lower levels of cardiometabolic risk cross-sectionally. Methods and Results ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study) enrolled 300 diabetes mellitus-free adults aged 20 to 55 years (mean=34±10 years) (78% women). Microbial DNA was extracted from subgingival dental plaque (n=281) and V3-V4 regions of the 16S rRNA gene were sequenced to measure the relative abundances of 20 a priori-selected taxa with nitrate-reducing capacity. Standardized scores of each taxon's relative abundance were summed, producing a nitrate-reducing taxa summary score (NO3TSS) for each participant. Natural log-transformed homeostatic model assessment of insulin resistance, plasma glucose, systolic BP, and diastolic BP were regressed on NO3TSS in multivariable linear regressions; prediabetes mellitus and hypertension prevalence were regressed on NO3TSS using modified Poisson regression models. Nitrate-reducing bacterial species represented 20±16% of all measured taxa. After multivariable adjustment, a 1-SD increase in NO3TSS, was associated with a -0.09 (95% CI, -0.15 to -0.03) and -1.03 mg/dL (95% CI, -1.903 to -0.16) lower natural log-transformed homeostatic model assessment of insulin resistance and plasma glucose, respectively. NO3TSS was associated with systolic BP only among patients without hypertension; 1-SD increase in NO3TSS was associated with -1.53 (95% CI, -2.82 to -0.24) mm Hg lower mean systolic BP. No associations were observed with prediabetes mellitus and hypertension. Conclusions A higher relative abundance of oral nitrate-reducing bacteria was associated with lower insulin resistance and plasma glucose in the full cohort and with mean systolic BP in participants with normotension.

Project description:Simple Summary Oral mucosal melanoma (OMM) is one of the most common oral cancers in dogs; however, the risk factors for its development remain obscure and the etiology is unknown. This study aimed to investigate the risk factors and etiology of OMM in dogs. An epidemiological questionnaire was applied to the owners of 15 dogs with OMM and their paired controls, and the oral microbiome was comparatively determined in the two groups. Additionally, the presence of papillomavirus was investigated in the same OMM samples. Most OMM and control dogs had grade 3 periodontal disease. No risk factors were identified through the epidemiological questionnaire, and papillomaviruses were not identified in the samples. The bacteria Tannerella forsythia and Porphyromonas gingivalis were significantly overrepresented in dogs with OMM, and their presence could be considered a risk factor for the development of canine OMM. Abstract Oral mucosal melanoma (OMM) is the most common oral cancer in dogs and is very aggressive in this species; its risk factors and etiology are yet to be determined. This study aimed to unravel the risk factors for the development of OMM in dogs and to investigate the possible presence of papillomaviruses as an etiological factor. A case-control study was conducted in 15 dogs with OMM and 15 paired controls whose owners answered an epidemiological questionnaire. Oral swabs from the same dogs were subjected to 16S rRNA sequencing for microbiome analyses. In addition, DNA fragments of OMM had their DNA extracted and amplified by polymerase chain reaction in an attempt to detect canine papillomaviruses. The gingiva was the most frequent anatomical site (47%) of OMM, and most tumors were stage III when diagnosed. Most dogs bearing OMM and the controls had grade 3 periodontal disease, and this factor, along with tartar treatment and tooth brushing, did not differ between cases and controls. Most dogs with OMM and most controls had contact with smokers; there was no statistically significant difference. Canine papillomaviruses were not detected among OMM cases. Tannerella forsythia and Porphyromonas gingivalis were significantly increased in case dogs compared to the controls. As these bacteria are reportedly involved in the pathogenesis of periodontal disease and esophageal cancer in humans, we suggest that they might be risk factors for the development of canine OMM. The limitations of this study include the low number of dogs, and therefore, further studies on canine OMM with larger numbers of animals are encouraged.

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Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

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