World Journal of Urology

, Volume 24, Issue 1, pp 21–27 | Cite as

Reduction of Escherichia coli adherence to uroepithelial bladder cells after consumption of cranberry juice: a double-blind randomized placebo-controlled cross-over trial

  • P. Di MartinoEmail author
  • R. Agniel
  • K. David
  • C. Templer
  • J. L. Gaillard
  • P. Denys
  • H. Botto
Topic Paper


To determine the efficacy of the consumption of cranberry juice versus placebo with regard to the presence of in vitro bacterial anti-adherence activity in the urine of healthy volunteers. Twenty healthy volunteers, 10 men and 10 women, were included. The study was a double-blind, randomized, placebo-controlled, and cross-over study. In addition to normal diet, each volunteer received at dinner a single dose of 750 ml of a total drink composed of: (1) 250 ml of the placebo and 500 ml of mineral water, or (2) 750 ml of the placebo, or (3) 250 ml of the cranberry juice and 500 ml of mineral water, or (4) 750 ml of the cranberry juice. Each volunteer took the four regimens successively in a randomly order, with a washout period of at least 6 days between every change in regimen. The first urine of the morning following cranberry or placebo consumption was collected and used to support bacterial growth. Six uropathogenic Escherichia coli strains (all expressing type 1 pili; three positive for the gene marker for P-fimbriae papC and three negative for papC), previously isolated from patients with symptomatic urinary tract infections, were grown in urine samples and tested for their ability to adhere to the T24 bladder cell line in vitro. There were no significant differences in the pH or specific gravity between the urine samples collected after cranberry or placebo consumption. We observed a dose dependent significant decrease in bacterial adherence associated with cranberry consumption. Adherence inhibition was observed independently from the presence of genes encoding type P pili and antibiotic resistance phenotypes. Cranberry juice consumption provides significant anti-adherence activity against different E. coli uropathogenic strains in the urine compared with placebo.


Urinary tract infection Cranberry Escherichia coli Adherence Colonization Pili Trial 



This study was funded, in part, by a grant from Ocean Spray Cranberries, Inc., Lakeville-Middleboro, MA, USA. The authors thank Gunter Haessaerts from Gika and Loïc Renard from Pharmatoka for their support related to this research.


  1. 1.
    Russo TA, Johnson JR (2003) Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem. Microbes Infect 5:449–456CrossRefPubMedGoogle Scholar
  2. 2.
    Emody L, Kerenyi M, Nagy G (2003) Virulence factors of uropathogenic Escherichia coli. Int J Antimicrob Agents 22:29–33CrossRefPubMedGoogle Scholar
  3. 3.
    Ruiz J, Simon K, Horcajada JP, Velasco M, Barranco M, Roig G, Moreno-Martinez A, Martinez JA, Jimenez de Anta T, Mensa J, Vila J (2000) Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men. J Clin Microbiol 40:4445–4449CrossRefGoogle Scholar
  4. 4.
    Arthur M, Johnson CE, Rubin RH, Arbeit RD, Campanelli C, Kim C, Steinbach S, Agarwal M, Wilkinson R, Goldstein R (1989) Molecular epidemiology of adhesion and hemolysin virulence factors among uropathogenic Escherichia coli. Infect Immun 57:303–313PubMedGoogle Scholar
  5. 5.
    Wullt B (2003) The role of P fimbriae for Escherichia coli establishment and mucosal inflammation in the human urinary tract. Int J Antimicrob Agents 21:605–621CrossRefPubMedGoogle Scholar
  6. 6.
    Bahrani-Mougeot FK, Buckles EL, Lockatell CV, Hebel JR, Johnson DE, Tang CM, Donnenberg MS (2002) Type 1 fimbriae and extracellular polysaccharides are preeminent uropathogenic Escherichia coli virulence determinants in the murine urinary tract. Mol Microbiol 45:1079–1093CrossRefPubMedGoogle Scholar
  7. 7.
    Kahlmeter G (2003) Prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis in Europe. The ECO.SENS study. Int J Antimicrob Agents 22:49–52CrossRefPubMedGoogle Scholar
  8. 8.
    Howell AB (2002) Cranberry proanthocyanidins and the maintenance of urinary tract health. Crit Rev Food Sci Nutr 42:273–278PubMedCrossRefGoogle Scholar
  9. 9.
    Griffiths P (2003) The role of Cranberry juice in the treatment of urinary tract infections. Br J Commun Nurs 557–561Google Scholar
  10. 10.
    Zafriri D, Ofek I, Adar R, Pocino M, Sharon N (1989) Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eukaryotic cells. Antimicrob Agents Chemother 33:92–98PubMedGoogle Scholar
  11. 11.
    Yeap Foo L, Lu Y, Howell AB, Vorsa N (2000) A-type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli. J Nat Prod 63:1225–1228CrossRefPubMedGoogle Scholar
  12. 12.
    Ahuja S, Kaack B, Roberts J (1998) Loss of fimbrial adhesion with the addition of Vaccinium macrocarpon to the growth medium of P-fimbriated Escherichia coli. J Urol 159:559–562PubMedCrossRefGoogle Scholar
  13. 13.
    Habash MB, Van der Mei HC, Busscher HJ, Reid G (1999) The effect of water, ascorbic acid, and cranberry derived supplementation on human urine and uropathogen adhesion to silicone rubber. Can J Microbiol 45:691–694CrossRefPubMedGoogle Scholar
  14. 14.
    Le Bouguenec C, Archambaud M, Labigne A (1992) Rapid and specific detection of the pap, afa, and sfa adhesin-encoding operons in uropathogenic Escherichia coli strains by polymerase chain reaction. J Clin Microbiol 30:1189–1193PubMedGoogle Scholar
  15. 15.
    National committee for clinical laboratory standards. Performance standards for antimicrobial disk susceptibility tests. Approved standard. 7th edn. National committee for clinical laboratory standards, Wayne, Pa. 2000Google Scholar
  16. 16.
    Darfeuille-Michaud A, Neut C, Barnich N, Lederman E, Di Martino P, desreumaux P, Gambiez L, Joly B, Cortot A, Colombel JF (1998) Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn’s disease. Gastroenterology 115:1405–1413CrossRefPubMedGoogle Scholar
  17. 17.
    Miyazaki J, Ba-Thein W., Kumao T, Yasuoka MO, Akaza H, Ayshi H (2002) Type 1, P and S fimbriae, and afimbrial adhesion I are not essential for uropathogenic Escherichia coli to adhere to and invade bladder epithelial cells. FEMS Immunol Med Microbiol 33:23–26CrossRefPubMedGoogle Scholar
  18. 18.
    Scmidt DR, Sobota AE (1988) An examination of the anti-adherence activity of cranberry juice on urinary and nonurinary bacterial isolates. Microbios 55:173–181PubMedGoogle Scholar
  19. 19.
    Soboda AE (1984) Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. J Urol 131:1013–1016PubMedGoogle Scholar
  20. 20.
    Howell AB, Vorsa N, Der Marderosian A, Foo LY (1998) Inhibition of the adherence of P-fimbriated Escherichia coli to uroepithelial cell surfaces by proanthocyanidin extracts from cranberries. N Engl J Med 339:1085–1086CrossRefPubMedGoogle Scholar
  21. 21.
    Howell AB, Foxman B (2002) Cranberry juice and adhesion of antibiotic-resistant uropathogens. JAMA 287:3082–3083CrossRefPubMedGoogle Scholar
  22. 22.
    Reid G, Hsiehl J, Potter P, Mighton J, Lam D, Warren D, Stephenson J (2001) Cranberry juice consumption may reduce biofilms on uroepithelial cells: pilot study in spinal cord injured patients. Spinal Cord 39:26–30CrossRefPubMedGoogle Scholar
  23. 23.
    Koga T, Moro K, Nakamori K, Yamakoshi J, Hosoyama H, Kataota S, Ariga A (1999) Increase of antioxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds. J Agric Food Chem 47:1892–1897CrossRefPubMedGoogle Scholar
  24. 24.
    Harmand MF, Blanquet P (1978) The fate of total flavanoid oligomers (OFT) extracted from ‘VITIS VINIFERAL’ in the rat. Eur J Drug Metab Pharmacokinet 1:15–30CrossRefGoogle Scholar
  25. 25.
    Howell AB, Leahy M, Kurowska E, Guthrie N (2001) In vivo evidence that cranberry proanthocyanidins inhibit adherence of P-fimbriated E. coli bacteria to uroepithelial cells. Fed Amer Soc Exp Biol J 15:A284Google Scholar
  26. 26.
    Bodel PT, Cotran R, Kass EH (1959) Cranberry juice and the antibacterial action of hippuric acid. J Lab Clin Med 54:881–888PubMedGoogle Scholar
  27. 27.
    Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA (1994) Reduction of bacteriura and pyuria using cranberry juice [reply]. JAMA 272:589CrossRefPubMedGoogle Scholar
  28. 28.
    Kunin CM (1994) Chemoprophylaxis and suppressive therapy in the management of urinary tract infections. J Antimicrob Chemother 33:51–62PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • P. Di Martino
    • 1
    Email author
  • R. Agniel
    • 1
  • K. David
    • 1
  • C. Templer
    • 2
  • J. L. Gaillard
    • 3
  • P. Denys
    • 4
  • H. Botto
    • 5
  1. 1.Laboratoire ERRMECe (EA1391)Université de Cergy-PontoisePontoise cedexFrance
  2. 2.Service de médecine des personnelsUniversité de Cergy-PontoisePontoiseFrance
  3. 3.Laboratoire de Microbiologiehôpital Raymond PoincaréGarchesFrance
  4. 4.Service de médecine physique et de réadaptationhôpital Raymond PoincaréGarchesFrance
  5. 5.Service d’urologie hôpital Foch GarchesFrance

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