Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability
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Abstract
The 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. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity (NRC) and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals ( P < 0.05 in all five datasets with n = 20–82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate (a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15 healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment ( P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria ( P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.
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Antibacterial mouthwashes and antibiotics can disrupt nitrate-reducing microbiota, thereby reducing nitrite availability and attenuating blood pressure responses.
“Antibacterial mouthwashes and antibiotics can disrupt nitrate-reducing microbiota, thereby reducing nitrite availability and attenuating blood pressure responses [270,271].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [271]
The Discussion (Potential implications of hampered NRC for systemic health; page unavailable) reports that chlorhexidine impaired oral nitrate reduction, lowered plasma nitrite and increased blood pressure in fasting individuals. This supports the mouthwash portion, but our copy does not establish the same effects for antibiotics; nor does the cited passage directly test an attenuated blood-pressure response to dietary nitrate. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAntibiotics can disrupt the oral and gut microbiota responsible for reducing nitrate to nitrite, thereby impairing endogenous NO generation.
“antibiotics can disrupt the oral and gut microbiota responsible for reducing nitrate to nitrite, thereby impairing endogenous NO generation [106,252,271].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [271]
The Introduction describes oral bacteria reducing nitrate to nitrite, which can then contribute to nitric oxide generation. The Discussion reports that chlorhexidine disruption of the oral microbiota impaired nitrate reduction and lowered plasma nitrite. Our copy does not establish the claim about antibiotics or nitrate-reducing gut microbiota (searched: antibiotics, antibiotic treatment, gut bacteria). (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe timing of optimal intake may affect the efficiency of oral bacterial nitrate reduction.
“the timing of optimal intake may affect the efficiency of oral bacterial nitrate reduction [106,252,271,292].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [271]
The Discussion (Concluding remarks; Study limitations and future perspectives, pages unavailable) links reduced oral nitrate reduction to periodontitis and discusses nitrate availability after vegetable intake. A separate Discussion passage mentions the timing of sample collection, but not whether the timing of nitrate intake affects bacterial reduction efficiency. Searches for optimal intake timing and time of nitrate administration found no passage addressing that claim. (LLM, conf=0.76)
Experimental — accuracy not yet measuredHighly processed beetroot products may exhibit reduced nitrate stability and diminished physiological impact.
“highly processed beetroot products may exhibit reduced nitrate stability and diminished physiological impact [106,252,271,292].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [271]
The Discussion sections on study limitations and systemic health discuss oral nitrate reduction, vegetable intake, and beetroot juice as a possible future intervention. They do not address whether processing beetroot products reduces nitrate stability or physiological impact; searches for those terms found no supporting passage in our copy. (LLM, conf=0.75)
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- Authors
- Rosier, B. T., Johnston, W., Carda-Diéguez, M., Simpson, A., Cabello-Yeves, E., Piela, K., Reilly, R., Artacho, A., Easton, C., Burleigh, M., Culshaw, S., & Mira, A.
- Affiliations
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (ES)
- Glasgow Caledonian University (GB)
- University of the West of Scotland (GB)
- Consejo Superior de Investigaciones Científicas (ES)
- University of Glasgow (GB)
- ORCID
- Venue
- International Journal of Oral Science
- Published
- 2024-01-05
- Volume
- 16
- Issue
- 1
- Pages
- 1-1
- ISSN
- 1674-2818 (ISSN-L)
- 2049-3169
- PMC
- PMC10767001
- OpenAlex
- W4390611285
- Cited by
- 85
- References
- 63
- Citations by year
- 2026: 40 · 2025: 37 · 2024: 8
- FWCI
- 39.05
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-01-26)
- Open access
- gold
- doi.org
- Locations
- International Journal of Oral Science (publishedVersion, cc-by)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ResearchOnline (Glasgow Caledonian University) (acceptedVersion, cc-by)
- The UWS Academic Portal (University of the West of Scotland) (submittedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- The UWS Academic Portal (University of the West of Scotland) (submittedVersion, cc-by)
- ResearchOnline (submittedVersion, cc-by)
- Funders
- Ministerio de Ciencia, Innovación y Universidades (Bio2015-68711-R, RTI2018-102032-B-I00, RTI2018)
- European Commission (290246)
- University of Glasgow
- Versus Arthritis (20823)
- Dentsply Sirona
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
- Biotechnology and Biological Sciences Research Council (BB/P504567/1)
- European Regional Development Fund (RTI2018-102032-B-I00, RTI2018)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › General Dentistry › Dental Research and COVID-19
- Keywords
- periodontitis, oral microbiota, nitric oxide, nitrate-reducing bacteria, subgingival plaque, periodontal treatment, dietary nitrate, nitrite, periodontitis-associated bacteria, saliva
- MeSH terms
- Bacteria, Dental Plaque, Humans, Nitrates, Nitric Oxide, Nitrites, Periodontitis, RNA, Ribosomal, 16S, Saliva, Microbiota
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