The DOI matches its Crossref record; 118 of the 118 references it cites were found in a registry or an index.
The oral microbiome and nitric oxide homoeostasis
Open accessAbstract
The tiny radical nitric oxide (NO) participates in a vast number of physiological functions including vasodilation, nerve transmission, host defence and cellular energetics. Classically produced by a family of specific enzymes, NO synthases (NOS s), NO signals via reactions with other radicals or transition metals. An alternative pathway for the generation of NO is the nitrate–nitrite–NO pathway in which the inorganic anions nitrate () and nitrite () are reduced to NO and other reactive nitrogen intermediates. Nitrate and nitrite are oxidation products from NOS‐dependent NO generation but also constituents in our diet, mainly in leafy green vegetables. Irrespective of origin, active uptake of circulating nitrate in the salivary glands, excretion in saliva and subsequent reduction to nitrite by oral commensal bacteria are all necessary steps for further NO generation. This central role of the oral cavity in regulating NO generation from nitrate presents a new and intriguing aspect of the human microbiome in health and disease. In this review, we present recent advances in our understanding of the nitrate–nitrite–NO pathway and specifically highlight the importance of the oral cavity as a hub for its function.
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In the citing paper
“Since humans lack efficient endogenous nitrate reductases, this step is crucial for the nitrate-nitrite-NO pathway [29].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [29]
In the citing paper
“Disruption to the oral microbiome by antibacterial mouthwashes, such as chlorhexidine, significantly impairs nitrate reduction and decreases nitrite bioavailability, thereby attenuating the blood-pressure-lowering effects of dietary nitrate [29,31,33].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [29]
In the citing paper
“Although there is no formal protocol for dietary nitrate intake”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [29]
In the citing paper
“These include avoiding antibacterial mouthwashes around the time of consumption, ensuring adequate salivary flow and consuming nitrate-rich beetroot products 1–2 h prior to the desired physiological effect.”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [29]
In the citing paper
“dietary nitrate can theoretically enhance the vasodilatory effects of pharmacological NO donors by providing additional nitrite-derived NO [29,31,33,108].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [29]
In the citing paper
“there are several practical guidelines that can enhance nitrate reduction and NO bioavailability [29,31,33,108].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [29]
In the citing paper
“the majority of nitrate and nitrite are absorbed in the proximal small intestine[233,270].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [270]
In the citing paper
“it is unlikely they significantly contribute to the enterosalivary circulation given that the majority of nitrate and nitrite are absorbed in the proximal small intestine[233,270].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [270]
Citations
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Flagged first, then by citations
Research works printed but not linked: 2
- Speijers GJA, 2003, Nitrate (and potential endogenous formation of N‐nitroso compounds), WHO FAS, 50
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Cited by
Sorted by citations
Drinking Water Nitrate and Human Health: An Updated Review
Ward, M., Jones, R., Brender, J., De Kok, T., Weyer, P., Nolan, B., Villanueva, C., & Van Breda, S. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15071557 · Cited by 1,576
Resilience of the Oral Microbiota in Health: Mechanisms That Prevent Dysbiosis
Rosier, B. T., Marsh, P. D., & Mira, A. (2018) · Journal of Dental Research · doi:10.1177/0022034517742139 · Cited by 448
A practical guide to the oral microbiome and its relation to health and disease
Krishnan, K., Chen, T., & Paster, B. (2017) · Oral Diseases · doi:10.1111/odi.12509 · Cited by 347
“An intriguing suggestion has been that oral bacteria may play a role in nitric oxide (NO) homeostasis, which is important in renal and cardiovascular health (Hezel & Weitzberg, 2015).”
BackgroundOral Microbiome Geography: Micron-Scale Habitat and Niche
Welch, J. L. M., Ramírez-Puebla, S. T., & Borisy, G. G. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.07.009 · Cited by 267
Functional properties of beetroot (Beta vulgaris) in management of cardio-metabolic diseases
Mirmiran, P., Houshialsadat, Z., Gaeini, Z., Bahadoran, Z., & Azizi, F. (2020) · Nutrition & Metabolism · doi:10.1186/s12986-019-0421-0 · Cited by 215
Metadata
- Authors
- Hezel, M., & Weitzberg, E.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Weitzberg, E
- ORCID
- Weitzberg, E
- Venue
- Oral Diseases
- Publisher
- Wiley
- Published
- 2013-07-10
- Volume
- 21
- Issue
- 1
- Pages
- 7-16
- ISSN
- 1354-523X (ISSN-L)
- 1601-0825
- OpenAlex
- W2113616233
- Semantic Scholar
- 3b5c2b57f5b193c903aecf55ee5f4d077dc8f448
- Cited by
- 201
- References
- 118
- Citations by year
- 2026: 24 · 2025: 18 · 2024: 20 · 2023: 24 · 2022: 24 · 2021: 18 · 2020: 18 · 2019: 16 · 2018: 11 · 2017: 9 · 2016: 13 · 2015: 3 · 2014: 3
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Oral Diseases (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Swedish Research Council
- Torsten and Ragnar Söderbergs Foundation
- David and Astrid Hagelén Foundation
- Stockholm City Council (ALF) and Funds
- Karolinska Institutet
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- nitric oxide, nitrate-nitrite-NO pathway, oral microbiota, nitrate uptake, nitrite reduction, salivary glands, oral commensal bacteria, nitric oxide synthase, reactive nitrogen species, saliva
- MeSH terms
- Homeostasis, Humans, Mouth, Nitrates, Nitric Oxide, Nitrites, Signal Transduction, Microbiota
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