Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Jun;40(6):1422–1425. doi: 10.1128/aac.40.6.1422

Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense.

R S Dykhuizen 1, R Frazer 1, C Duncan 1, C C Smith 1, M Golden 1, N Benjamin 1, C Leifert 1
PMCID: PMC163343  PMID: 8726013

Abstract

Dietary intake of nitrate generates salivary nitrite, which is acidified in the stomach, leading to a number of reactive intermediates of nitrogen, among which are the potentially carcinogenic N-nitrosamines. Acidified nitrite, however, also has antimicrobial activity which coincides with the formation of nitric oxide. The present study examines the antimicrobial effect in vitro of acidified nitrite on Salmonella enteritidis, Salmonella typhimurium, Yersinia enterocolitica, Shigella sonnei, and Escherichia coli O157. First-order regression plots showed a linear inverse relationship of log-transformed proton and nitrite concentrations with MICs and MBCs after 30 min, 2 h, and 24 h of exposure (P < 0.001 for all antibacterial activities). Susceptibility to the acidified nitrate solutions ranked as follows: Y. enterocolitica > S. enteritidis > S. typhimurium = Shigella sonnei > E. coli O157 (P < 0.05). Addition of SCN-, but not that of CI-, increased the antibacterial activity (paired t testing, P < 0.001). Generation of salivary nitrite from dietary nitrate may provide significant protection against gut pathogens in humans.

Full Text

The Full Text of this article is available as a PDF (324.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benjamin N., O'Driscoll F., Dougall H., Duncan C., Smith L., Golden M., McKenzie H. Stomach NO synthesis. Nature. 1994 Apr 7;368(6471):502–502. doi: 10.1038/368502a0. [DOI] [PubMed] [Google Scholar]
  2. Brunelli L., Crow J. P., Beckman J. S. The comparative toxicity of nitric oxide and peroxynitrite to Escherichia coli. Arch Biochem Biophys. 1995 Jan 10;316(1):327–334. doi: 10.1006/abbi.1995.1044. [DOI] [PubMed] [Google Scholar]
  3. De Groote M. A., Fang F. C. NO inhibitions: antimicrobial properties of nitric oxide. Clin Infect Dis. 1995 Oct;21 (Suppl 2):S162–S165. doi: 10.1093/clinids/21.supplement_2.s162. [DOI] [PubMed] [Google Scholar]
  4. De Groote M. A., Granger D., Xu Y., Campbell G., Prince R., Fang F. C. Genetic and redox determinants of nitric oxide cytotoxicity in a Salmonella typhimurium model. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6399–6403. doi: 10.1073/pnas.92.14.6399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Duncan C., Dougall H., Johnston P., Green S., Brogan R., Leifert C., Smith L., Golden M., Benjamin N. Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat Med. 1995 Jun;1(6):546–551. doi: 10.1038/nm0695-546. [DOI] [PubMed] [Google Scholar]
  6. Dykhuizen R. S., Copland M., Smith C. C., Douglas G., Benjamin N. Plasma nitrate concentration and urinary nitrate excretion in patients with gastroenteritis. J Infect. 1995 Jul;31(1):73–75. doi: 10.1016/s0163-4453(95)91643-1. [DOI] [PubMed] [Google Scholar]
  7. Forman D., Al-Dabbagh S., Doll R. Nitrates, nitrites and gastric cancer in Great Britain. Nature. 1985 Feb 21;313(6004):620–625. doi: 10.1038/313620a0. [DOI] [PubMed] [Google Scholar]
  8. Granger D. L., Lehninger A. L. Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells. J Cell Biol. 1982 Nov;95(2 Pt 1):527–535. doi: 10.1083/jcb.95.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Granli T., Dahl R., Brodin P., Bøckman O. C. Nitrate and nitrite concentrations in human saliva: variations with salivary flow-rate. Food Chem Toxicol. 1989 Oct;27(10):675–680. doi: 10.1016/0278-6915(89)90122-1. [DOI] [PubMed] [Google Scholar]
  10. Klebanoff S. J. Reactive nitrogen intermediates and antimicrobial activity: role of nitrite. Free Radic Biol Med. 1993 Apr;14(4):351–360. doi: 10.1016/0891-5849(93)90084-8. [DOI] [PubMed] [Google Scholar]
  11. Knight T. M., Forman D., Pirastu R., Comba P., Iannarilli R., Cocco P. L., Angotzi G., Ninu E., Schierano S. Nitrate and nitrite exposure in Italian populations with different gastric cancer rates. Int J Epidemiol. 1990 Sep;19(3):510–515. doi: 10.1093/ije/19.3.510. [DOI] [PubMed] [Google Scholar]
  12. Konturek J. W., Thor P., Maczka M., Stoll R., Domschke W., Konturek S. J. Role of cholecystokinin in the control of gastric emptying and secretory response to a fatty meal in normal subjects and duodenal ulcer patients. Scand J Gastroenterol. 1994 Jul;29(7):583–590. doi: 10.3109/00365529409092476. [DOI] [PubMed] [Google Scholar]
  13. Lijinsky W. Nitrosamines and nitrosamides in the etiology of gastrointestinal cancer. Cancer. 1977 Nov;40(5 Suppl):2446–2449. doi: 10.1002/1097-0142(197711)40:5+<2446::aid-cncr2820400909>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  14. Lundberg J. O., Weitzberg E., Lundberg J. M., Alving K. Intragastric nitric oxide production in humans: measurements in expelled air. Gut. 1994 Nov;35(11):1543–1546. doi: 10.1136/gut.35.11.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nakaki T., Nakayama M., Kato R. Inhibition by nitric oxide and nitric oxide-producing vasodilators of DNA synthesis in vascular smooth muscle cells. Eur J Pharmacol. 1990 Dec 15;189(6):347–353. doi: 10.1016/0922-4106(90)90031-r. [DOI] [PubMed] [Google Scholar]
  16. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  17. Neilly I. J., Copland M., Haj M., Adey G., Benjamin N., Bennett B. Plasma nitrate concentrations in neutropenic and non-neutropenic patients with suspected septicaemia. Br J Haematol. 1995 Jan;89(1):199–202. doi: 10.1111/j.1365-2141.1995.tb08931.x. [DOI] [PubMed] [Google Scholar]
  18. Ohshima H., Bartsch H. Quantitative estimation of endogenous nitrosation in humans by monitoring N-nitrosoproline excreted in the urine. Cancer Res. 1981 Sep;41(9 Pt 1):3658–3662. [PubMed] [Google Scholar]
  19. Pryor W. A., Lightsey J. W. Mechanisms of nitrogen dioxide reactions: initiation of lipid peroxidation and the production of nitrous Acid. Science. 1981 Oct 23;214(4519):435–437. doi: 10.1126/science.214.4519.435. [DOI] [PubMed] [Google Scholar]
  20. Snepar R., Poporad G. A., Romano J. M., Kobasa W. D., Kaye D. Effect of cimetidine and antacid on gastric microbial flora. Infect Immun. 1982 May;36(2):518–524. doi: 10.1128/iai.36.2.518-524.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Spiegelhalder B., Eisenbrand G., Preussmann R. Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. Food Cosmet Toxicol. 1976 Dec;14(6):545–548. doi: 10.1016/s0015-6264(76)80005-3. [DOI] [PubMed] [Google Scholar]
  22. Tannenbaum S. R. N-nitroso compounds: a perspective on human exposure. Lancet. 1983 Mar 19;1(8325):629–632. doi: 10.1016/s0140-6736(83)91801-9. [DOI] [PubMed] [Google Scholar]
  23. Tannenbaum S. R., Weisman M., Fett D. The effect of nitrate intake on nitrite formation in human saliva. Food Cosmet Toxicol. 1976 Dec;14(6):549–552. doi: 10.1016/s0015-6264(76)80006-5. [DOI] [PubMed] [Google Scholar]
  24. Tannenbaum S. R., Wishnok J. S., Leaf C. D. Inhibition of nitrosamine formation by ascorbic acid. Am J Clin Nutr. 1991 Jan;53(1 Suppl):247S–250S. doi: 10.1093/ajcn/53.1.247S. [DOI] [PubMed] [Google Scholar]
  25. Verdu E., Viani F., Armstrong D., Fraser R., Siegrist H. H., Pignatelli B., Idström J. P., Cederberg C., Blum A. L., Fried M. Effect of omeprazole on intragastric bacterial counts, nitrates, nitrites, and N-nitroso compounds. Gut. 1994 Apr;35(4):455–460. doi: 10.1136/gut.35.4.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wink D. A., Darbyshire J. F., Nims R. W., Saavedra J. E., Ford P. C. Reactions of the bioregulatory agent nitric oxide in oxygenated aqueous media: determination of the kinetics for oxidation and nitrosation by intermediates generated in the NO/O2 reaction. Chem Res Toxicol. 1993 Jan-Feb;6(1):23–27. doi: 10.1021/tx00031a003. [DOI] [PubMed] [Google Scholar]
  27. Zhu L., Gunn C., Beckman J. S. Bactericidal activity of peroxynitrite. Arch Biochem Biophys. 1992 Nov 1;298(2):452–457. doi: 10.1016/0003-9861(92)90434-x. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES