From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease
Open accessAbstract
Abstract Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3−) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional l-arginine–NO synthase (l-NOS) pathway, whereas endogenous NO production by l-arginine is inhibited under hypoxia–ischemia or disease conditions. In contrast, exogenous NO3−/NO2−/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3−/NO2−/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3−/NO2−/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.
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The enterosalivary circulation maintains a circulating nitrate reservoir that supports NO production, particularly under hypoxic conditions where endogenous NOS activity is limited.
“This enterosalivary circulation, comprising intestinal absorption, systemic distribution, salivary concentration, and re-swallowing, maintains a circulating nitrate reservoir that supports NO production, particularly under hypoxic conditions where endogenous NO synthase (NOS) activity is limited [27,28].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [27]
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Flagged first, then by citations
Research works printed but not linked: 2
- [25]Carlstrom M Montenegro MF Oxidative stress and compromised nitric oxide signaling in cardiorenal disease therapeutic value of stimulating the nitrate-nitrite-nitric oxide pathway J Intern Med 2019 285 1 2 18 30039620
- [98]Machha A Schechter AN Inorganic nitrate: a major player in the cardiovascular health benefits of vegetables? Nutr Rev 2012 70 6 367 372 22646129 PMC3367800
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- Authors
- Liu, H., Huang, Y., Huang, M., Wang, M., Ming, Y., Chen, W., Chen, Y., Tang, Z., & Jia, B.
- Affiliations
- Southern Medical University (CN)
- Corresponding author
- Jia, Bo
- ORCID
- Venue
- European Journal of Medical Research
- Published
- 2023-10-11
- Volume
- 28
- Issue
- 1
- Pages
- 425-425
- ISSN
- 0949-2321 (ISSN-L)
- 2047-783X
- PMC
- PMC10566198
- OpenAlex
- W4387539320
- Cited by
- 58
- References
- 274
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 11
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- European journal of medical research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Bo Jia (201802020018)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- nitrate-reducing bacteria, nitrate reductase, dietary nitrate, nitric oxide, nitrite, gut microbiota, hypoxia-ischemia, cardiovascular disease, metabolic disorders, geriatric diseases, host-microbe interactions
- MeSH terms
- Aged, Arginine, Bacteria, Humans, Nitrate Reductases, Nitrates, Nitric Oxide, Nitrites, Nitrogen Dioxide
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