Cited by 58Nitric Oxide and Endothelin EffectsGut microbiota and healthOral microbiology and periodontitis research

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From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease

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Liu, Hongyu, Huang, Yisheng, Huang, Mingshu, Wang, Min, Ming, Yue, Chen, Weixing, Chen, Yuanxin, Tang, Zhengming, Jia, Bo·2023·European Journal of Medical Research

DOI 10.1186/s40001-023-01413-yPMC PMC10566198

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Abstract

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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Fig. 1 Summary of NRB in the human OC, esophagus, and GTCC BY · PubMed Central

Fig. 2 Metabolic process of nitrate in human bodyCC BY · PubMed Central

Fig. 3 Biochemical processes of nitrate metabolismCC BY · PubMed Central

Fig. 4 Bacteria with nitrate reductase ultimately reduce nitrate from dietary sources to NO via the enterosalivary cycle; the body can synthesize NO through the l-NOS pathway, but this pathway is inhibited by inflammatory factors or reactive oxygen species stimulationCC BY · PubMed Central

Fig. 5 Process of Sialin transporting nitrate in salivary gland cellsCC BY · PubMed Central

Fig. 6 Potential role of NRB in human systemic health and disease through the NO3−/NO2−/NO pathwayCC BY · PubMed Central

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“Gilchrist and his colleagues [223] found that while dietary supplementation with nitrate caused a noticeable rise in circulating nitrite in patients with T2D, it did not improve islet function in patients with T2D.”
Background
Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans
Vanhatalo, A., Blackwell, J. R., L’Heureux, J. E., Williams, D. W., Smith, A., van der Giezen, M., Winyard, P. G., Kelly, J., & Jones, A. M. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.05.078 · Cited by 256 · cited 3×
“More recently, Vanhatalo and his colleagues [14] showed in a clinical study that supplementation with nitrate-rich beet juice for 10 days similarly increased the abundance of NRB ( Rhodobacter spp. and Neisseria spp.) in the salivary microbiota in both older (70–79 years) and younger (18–22 years)…”
Background
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Nitrate ameliorates dextran sodium sulfate-induced colitis by regulating the homeostasis of the intestinal microbiota
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Integrated Genomic Analyses in Bronchopulmonary Dysplasia
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AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis
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Nitrate and gastric cancer risks
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Nitrous Oxide Production in Sputum from Cystic Fibrosis Patients with Chronic Pseudomonas aeruginosa Lung Infection
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Dietary Nitrate and the Epidemiology of Cardiovascular Disease: Report From a National Heart, Lung, and Blood Institute Workshop
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Carlstrom M, Montenegro MF. Therapeutic value of stimulating the nitrate-nitrite-nitric oxide pathway to attenuate oxidative stress and restore nitric oxide bioavailability in cardiorenal disease. J Intern Med. 2019;285(1):2–18. · DOI

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See all 58

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: Liu, Hongyu
Huang, Yisheng
Huang, Mingshu
Wang, Min
Ming, Yue
Chen, Weixing
Chen, Yuanxin
Tang, Zhengming
Jia, Bo
Venue: European Journal of Medical Research
Publisher: Springer Science and Business Media LLC
Published: 2023-10-11
Volume: 28
Issue: 1
Pages: 425-425
ISSN: 0949-2321 (ISSN-L)
2047-783X
DOI: 10.1186/s40001-023-01413-y
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
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
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 (medical) › 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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From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease

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