Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS
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 determ...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-05-01
|
| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.121.023038 |
| _version_ | 1811155554604679168 |
|---|---|
| author | Charlene E. Goh Bruno Bohn Clarisse Marotz Rebecca Molinsky Sumith Roy Bruce J. Paster Ching‐Yuan Chen Michael Rosenbaum Melana Yuzefpolskaya Paolo C. Colombo Moïse Desvarieux Panos N. Papapanou David R. Jacobs Rob Knight Ryan T. Demmer |
| author_facet | Charlene E. Goh Bruno Bohn Clarisse Marotz Rebecca Molinsky Sumith Roy Bruce J. Paster Ching‐Yuan Chen Michael Rosenbaum Melana Yuzefpolskaya Paolo C. Colombo Moïse Desvarieux Panos N. Papapanou David R. Jacobs Rob Knight Ryan T. Demmer |
| author_sort | Charlene E. Goh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T04:35:13Z |
| format | Article |
| id | doaj.art-71adc2e9d9574c09b90412604ec7b59a |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-10T04:35:13Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-71adc2e9d9574c09b90412604ec7b59a2023-03-10T04:02:36ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-05-01111010.1161/JAHA.121.023038Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINSCharlene E. Goh0Bruno Bohn1Clarisse Marotz2Rebecca Molinsky3Sumith Roy4Bruce J. Paster5Ching‐Yuan Chen6Michael Rosenbaum7Melana Yuzefpolskaya8Paolo C. Colombo9Moïse Desvarieux10Panos N. Papapanou11David R. Jacobs12Rob Knight13Ryan T. Demmer14Faculty of Dentistry National University of Singapore SingaporeDivision of Epidemiology and Community Health School of Public Health University of Minnesota Minneapolis MNDepartment of Pediatrics University of California San Diego La Jolla CADivision of Epidemiology and Community Health School of Public Health University of Minnesota Minneapolis MNDepartment of Epidemiology Mailman School of Public Health Columbia University New York NYThe Forsyth Institute Cambridge MADivision of Periodontics Section of Oral, Diagnostic and Rehabilitation Sciences College of Dental Medicine Columbia University New York NYDivision of Molecular Genetics Departments of Pediatrics and Medicine Columbia University New York NYDivision of Cardiology Department of Medicine New York Presbyterian HospitalColumbia University New York NYDivision of Cardiology Department of Medicine New York Presbyterian HospitalColumbia University New York NYDepartment of Epidemiology Mailman School of Public Health Columbia University New York NYDivision of Periodontics Section of Oral, Diagnostic and Rehabilitation Sciences College of Dental Medicine Columbia University New York NYDivision of Epidemiology and Community Health School of Public Health University of Minnesota Minneapolis MNDepartment of Computer Science & Engineering Jacobs School of Engineering University of California San Diego La Jolla CADivision of Epidemiology and Community Health School of Public Health University of Minnesota Minneapolis MNBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.121.02303816S rNA sequencingblood pressureepidemiologyinsulin resistancemetagenomicsnitric oxide |
| spellingShingle | Charlene E. Goh Bruno Bohn Clarisse Marotz Rebecca Molinsky Sumith Roy Bruce J. Paster Ching‐Yuan Chen Michael Rosenbaum Melana Yuzefpolskaya Paolo C. Colombo Moïse Desvarieux Panos N. Papapanou David R. Jacobs Rob Knight Ryan T. Demmer Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 16S rNA sequencing blood pressure epidemiology insulin resistance metagenomics nitric oxide |
| title | Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS |
| title_full | Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS |
| title_fullStr | Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS |
| title_full_unstemmed | Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS |
| title_short | Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS |
| title_sort | nitrite generating and depleting capacity of the oral microbiome and cardiometabolic risk results from origins |
| topic | 16S rNA sequencing blood pressure epidemiology insulin resistance metagenomics nitric oxide |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.121.023038 |
| work_keys_str_mv | AT charleneegoh nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT brunobohn nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT clarissemarotz nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT rebeccamolinsky nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT sumithroy nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT brucejpaster nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT chingyuanchen nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT michaelrosenbaum nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT melanayuzefpolskaya nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT paoloccolombo nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT moisedesvarieux nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT panosnpapapanou nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT davidrjacobs nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT robknight nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins AT ryantdemmer nitritegeneratinganddepletingcapacityoftheoralmicrobiomeandcardiometabolicriskresultsfromorigins |