Nitrate, bacteria and human health

Abstract

Nitrate is generally considered a water pollutant and an undesirable fertilizer residue in the food chain. Research in the 1970s indicated that, by reducing nitrate to nitrite, commensal bacteria might be involved in the pathogenesis of gastric cancers and other malignancies, as nitrite can enhance the generation of carcinogenic N-nitrosamines. More recent studies indicate that the bacterial metabolism of nitrate to nitrite and the subsequent formation of biologically active nitrogen oxides could be beneficial. Here, we will consider the evidence that nitrate-reducing commensals have a true symbiotic role in mammals and facilitate a previously unrecognized but potentially important aspect of the nitrogen cycle.

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Figure 1: The entero-salivary circulation of nitrate in humans.
Figure 2: The biological nitrogen cycle.
Figure 3: Multiple pathways for nitrate and nitrite transport and reduction in Escherichia coli.
Figure 4: The putative effects of nitrite in the stomach.
Figure 5: The antibacterial effects of salivary nitrite in gastric juice.

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Acknowledgements

The authors wish to thank the Ekhaga Foundation, the Swedish Research Council, the EU 6th Framework Programme and the Swedish Heart and Lung Foundation for generous support.

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Correspondence to Jon O. Lundberg.

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Competing interests

Jon O. Lundberg and Eddie Weitzberg own shares in Aerocrine AB, a company that manufactures equipment to measure nitric oxide in exhaled air.

Nigel Benjamin is the named inventor on several patents concerning the use of nitrate and nitrite as a therapeutic agent.

Jeff A. Cole declares he has no competing interests.

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DATABASES

Entrez

Bacillus subtilis

Clostridium difficile

Escherichia coli

Helicobacter pylori

Mycobacterium tuberculosis

Pseudomonas aeruginosa

Salmonella enterica serovar Enteritidis

Salmonella enterica serovar Typhi

Salmonella enterica serovar Typhimurium

SwissProt

Nap

NarG

NirK

NirS

Nrf

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Lundberg, J., Weitzberg, E., Cole, J. et al. Nitrate, bacteria and human health. Nat Rev Microbiol 2, 593–602 (2004). https://doi.org/10.1038/nrmicro929

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