Prospects for using D-mannose in the prevention and treatment of urinary tract infection in women

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Abstract

Today it is known that approximately half of all women during their lifetime will have at least one episode during their lifetime, and 27% to 48% among them will experience recurrent infection episodes in the future. The recent guidelines of international urology associations, as well as the summarized results of researches in the past years emphasize the advisability of the limited use of antibiotics in urinary tract infections, which is due to the constant increase in antibiotic resistance of uropathogens. Under these conditions, the promising area in the prevention and treatment is to use D-mannose, a monosaccharide that is excreted unchanged from the body with urine, where it competitively inhibits bacterial cell adhesion to the urothelium, by creating a biomechanical barrier.

This review gives new scientific data concerning the mechanisms of adhesion of E. coli to the umbrella cells of the urothelium; describes the key features of the pharmacokinetics of D-mannose in the human body, its role in countering E. coli adhesion to the mucous membrane of the urinary tract. The paper presents the results of experimental studies establishing that it is advisable to use D-mannose in urinary tract infection. It analyzes the clinical trials, the results of which demonstrate that the prevention of urinary tract infections in women with D-mannose is highly competitive with the prophylactic use of antibiotics. The today’s concept of the pathogenesis of urinary tract infection in women presumes that urobioma damage precedes symptomatic infection. In this connection, the paper analyzes the intermediate results of combined prophylactic use of D-mannose in women and some Lactobacillus species.

Conclusion: The use of D-mannose may become a promising area in the prevention and treatment of urinary tract infection in women who have no contraindications or apparently side effects.

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About the authors

Lev E. Belyi

Ulyanovsk State University

Author for correspondence.
Email: lbely@yandex.ru
ORCID iD: 0000-0003-0908-1321

Professor at the Department of Hospital Surgery, Anesthesiology, Reanimatology, Urology, Traumatology, Orthopedics

Russian Federation, Ulyanovsk

References

  1. Flores-Mireles A.L., Walker J.N., Caparon M., Hultgren S.J. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat. Rev. Microbiol. 2015; 13(5): 269-84. https://dx.doi.org/10.1038/nrmicro3432.
  2. EAU Guidelines. Edn. presented at the EAU Annual Congress Milan, Italy 2023.
  3. Moreno E., Andreu A., Pérez T., Sabaté M., Johnson J.R., Prats G. Relationship between Escherichia coli strains causing urinary tract infection in women and the dominant faecal flora of the same hosts. Epidemiol. Infect. 2006; 134(5): 1015-23. https://dx.doi.org/10.1017/S0950268806005917.
  4. Аляев Ю.Г., Глыбочко П.В., Пушкарь Д.Ю., ред. Российские клинические рекомендации. Урология. М.: ГЭОТАР-Медиа; 2016. [Alyaev Y.G., Glybochko P.V., Pushkar D.Y., eds. Russian clinical guidelines. Urology. Moscow: GEOTAR-Media; 2016. (in Russian)].
  5. Рафальский В.В., Моисеева Е.М. Эпидемиология неосложнённых внебольничных инфекций мочевыводящих путей в Российской Федерации. Вестник урологии. 2018; 6(2): 30-7. [Rafalsky V.V., Moiseeva E.M. Epidemiology of uncomplicated outpatient urinary tract infections in the Russian Federation. Urology Herald. 2018; 6(2): 30-7. (in Russian)]. https://dx.doi.org/10.21886/2308-6424-2018-6-2-30-37.
  6. Foxman B., Brown P. Epidemiology of urinary tract infections: transmission and risk factors, incidence, and costs. Infect. Dis. Clin. North Am. 2003; 17(2): 227-41. https://dx.doi.org/10.1016/s0891-5520(03)00005-9.
  7. Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect. Dis. Clin. North Am. 2014; 28(1): 1-13. https://dx.doi.org/ 10.1016/j.idc.2013.09.003.
  8. Brumbaugh A.R., Smith S.N., Mobley H.L. Immunization with the yersiniabactin receptor, FyuA, protects against pyelonephritis in a murine model of urinary tract infection. Infect. Immun. 2013; 81(9): 3309-16. https://dx.doi.org/10.1128/IAI.00470-13.
  9. Micali S., Isgro G., Bianchi G., Miceli N., Calapai G., Navarra M. Cranberry and recurrent cystitis: more than marketing? Crit. Rev. Food Sci. Nutr. 2014; 54(8): 1063-75. https://dx.doi.org/ 10.1080/10408398.2011.625574.
  10. Палагин И.С., Сухорукова М.В., Дехнич А.В., Эйдельштейн М.В., Перепанова Т.С., Козлов Р.С. и исследовательская группа «ДАРМИС-2018». Антибиотикорезистентность возбудителей внебольничных инфекций мочевых путей в России: результаты многоцентрового исследования «ДАРМИС-2018». Клиническая микробиология и антимикробная химиотерапия. 2019; 21(2): 134-46. [Palagin I.S., Sukhorukova M.V., Dekhnich A.V., Edelstein M.V., Perepanova T.S., Kozlov R.S. and “DARMIS-2018” Study Group. Antimicrobial resistance of pathogens causing community-acquired urinary tract infections in Russia: results of the multicenter study “DARMIS-2018”. Clinical Microbiology and Antimicrobial Chemotherapy. 2019; 21(2): 134-46. (in Russian)]. https://dx.doi.org/ 10.36488/cmac.2019.2.134-146.
  11. Приоритизация патогенов как ориентир для поиска, научного исследования и разработки новых антибиотиков для лечения инфекций, вызванных лекарственно-резистентными бактериями, включая туберкулез. Женева: ВОЗ; 2021. [Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Geneva: WHO; 2021.].
  12. Ali I., Rafaque Z., Ahmed S., Malik S., Dasti J.I. Prevalence of multidrug resistant uropathogenic Escherichia coli in Potohar region of Pakistan. Asian Pac. J. Trop. Biomed. 2016; 6(1): 60-6. https://dx.doi.org/10.1016/j.apjtb.2015.09.022.
  13. Shakhatreh M.A.K., Swedan S.F., Al-Odat M.A., Khabour O.F. Uropathogenic Escherichia coli (UPEC) in Jordan: prevalence of urovirulence genes and antibiotic resistance. J. King Saud Univ. Sci. 2019; 31(4): 648-52. https://dx.doi.org/10.1016/j.jksus.2018.03.009.
  14. Blaettler L., Mertz D., Frei R., Elzi L., Widmer A.F., Battegay M., Flückiger U. Secular trend and risk factors for antimicrobial resistance in Escherichia coli isolates in Switzerland 1997-2007. Infection. 37(6): 534-9. https://dx.doi.org/10.1007/s15010-009-8457-0.
  15. Erb S., Frei R., Tschudin Sutter S., Egli A., Dangel M., Bonkat G., Widmer A.F. Basic patient characteristics predict antimicrobial resistance in E. coli from urinary tract specimens: a retrospective cohort analysis of 5246 urine samples. Swiss Med. Wkly. 2018; 148: w14660. https://dx.doi.org/10.4414/smw.2018.14660.
  16. Министерство здравоохранения Российской Федерации. Цистит у женщин. Клинические рекомендации. 2021. [Ministry of Health of the Russian Federation. Cystitis in women. Clinical guidelines. 2021.(in Russian)]. Available at: https://cr.minzdrav.gov.ru/recomend/14_2
  17. Перепанова Т.С. Федеральные клинические рекомендации «Антимикробная терапия и профилактика инфекций почек, мочевыводящих путей и мужских половых органов – 2015г.». Терапевтический архив. 2016; 88(4): 100-4. [Perepanova T.S. The 2015 Federal Clinical Guidelines for Antimicrobial Therapy and Prevention of Infections of the Kidney, Urinary Tract, and Male Genitals. Therapeutic Archive. 2016; 88(4): 100-4. (in Russian)]. https://dx.doi.org/10.17116/ terarkh2016884100-104.
  18. Wiedemann B., Heisig A., Heisig P. Uncomplicated urinary tract infections and antibiotic resistance-epidemiological and mechanistic aspects. Antibiotics (Basel). 2014; 3(3): 341-52. https://dx.doi.org/10.3390/antibiotics3030341.
  19. Anger J., Lee U., Ackerman A.L., Chou R., Chughtai B., Clemens J.Q. et al. Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU Guideline. J. Urol. 2019; 202(2): 282-9. https://dx.doi.org/10.1097/JU.0000000000000296.
  20. Barea B.M., Veeratterapillay R., Harding C. Nonantibiotic treatments for urinary cystitis: an update. Curr. Opin. Urol. 2020; 30(6): 845-52. https://dx.doi.org/10.1097/MOU.0000000000000821.
  21. Zalewska-Piątek B.M., Piątek R.J. Alternative treatment approaches of urinary tract infections caused by uropathogenic Escherichia coli strains. Acta Biochim. Pol. 2019; 66(2): 129-38. https://dx.doi.org/10.18388/abp.2018_2787.
  22. Parazzini F., Ricci E., Fedele F., Chiaffarino F., Esposito G., Cipriani S. Systematic review of the effect of D-mannose with or without other drugs in the treatment of symptoms of urinary tract infections/cystitis (Review). Biomed. Rep. 2022; 17(2): 69. https://dx.doi.org/10.3892/br.2022.1552.
  23. Kątnik-Prastowska I., Lis J., Matejuk A. Glycosylation of uroplakins. Implications for bladder physiopathology. Glycoconj. J. 2014; 31(9): 623-36. https://dx.doi.org/10.1007/s10719-014-9564-4.
  24. Hu C.C., Liang F.X., Zhou G., Tu L., Tang C.H., Zhou J. et al. Assembly of urothelial plaques: tetraspanin function in membrane protein trafficking. Mol. Biol. Cell. 2005; 16(9): 3937-50. https://dx.doi.org/10.1091/ mbc.e05-02-0136.
  25. Klein R.D., Hultgren S.J. Urinary tract infections: microbial pathogenesis, host-pathogen interactions and new treatment strategies. Nat. Rev. Microbiol. 2020; 18(4): 211-26. https://dx.doi.org/10.1038/s41579-020-0324-0.
  26. Matuszewski M.A., Tupikowski K., Dołowy Ł., Szymańska B., Dembowski J., Zdrojowy R. Uroplakins and their potential applications in urology. Cent. European J. Urol. 2016; 69(3): 252-7. https://dx.doi.org/10.5173/ceju.2016.638.
  27. Lis J., Kątnik-Prastowska I., Tupikowski K., Matejuk A. Uroplakins as markers of diseases of the urinary system. Postepy Hig. Med. Dosw. (Online). 2015; 69: 98-113. https://dx.doi.org/10.5604/01.3001.0009.6483.
  28. Lewis S.A. Everything you wanted to know about the bladder epithelium but were afraid to ask. Am. J. Physiol. Renal Physiol. 2000; 278(6): F867-74. https://dx.doi.org/ 10.1152/ajprenal.2000.278.6.F867.
  29. Hatton N.E., Baumann C.G., Fascione M.A. Developments in mannose-based treatments for uropathogenic Escherichia coli-induced urinary tract infections. Chembiochem. 2021; 22(4): 613-29. https://dx.doi.org/10.1002/cbic.202000406.
  30. Ala-Jaakkola R., Laitila A., Ouwehand A.C., Lehtoranta L. Role of D-mannose in urinary tract infections - a narrative review. Nutr. J. 2022; 21(1): 18. https://dx.doi.org/10.1186/s12937-022-00769-x.
  31. Hanson M.S., Brinton C.C. Jr. Identification and characterization of E. coli type-1 pilus tip adhesion protein. Nature. 1988; 332(6161): 265-8. https://dx.doi.org/10.1038/332265a0.
  32. Spaulding C.N., Schreiber H.L. 4th, Zheng W., Dodson K.W., Hazen J.E., Conover M.S. et al. Functional role of the type 1 pilus rod structure in mediating host-pathogen interactions. Elife. 2018; 7: e31662. https://dx.doi.org/10.7554/eLife.31662.
  33. Schilling J.D., Mulvey M.A., Hultgren S.J. Structure and function of Escherichia coli type 1 pili: new insight into the pathogenesis of urinary tract infections. J. Infect. Dis. 2001; 183(Suppl. 1): S36-40. https://dx.doi.org/10.1086/ 318855.
  34. De Nunzio C., Bartoletti R., Tubaro A., Simonato A., Ficarra V. Role of D-mannose in the prevention of recurrent uncomplicated cystitis: state of the art and future perspectives. Antibiotics (Basel). 2021; 10(4): 373. https://dx.doi.org/10.3390/antibiotics10040373.
  35. Scribano D., Sarshar M., Prezioso C., Lucarelli M., Angeloni A., Zagaglia C. et al. d-Mannose Treatment neither Affects Uropathogenic Escherichia coli properties nor induces stable FimH modifications. Molecules. 2020; 25(2): 316. https://dx.doi.org/10.3390/molecules25020316.
  36. Liu Z., Li Y., Wu J., Chen S. A novel Pseudomonas geniculata AGE family epimerase/isomerase and its application in d-mannose synthesis. Foods. 2020; 9(12):1809. https://dx.doi.org/10.3390/foods9121809.
  37. Hu X., Shi Y., Zhang P., Miao M., Zhang T., Jiang B. d-Mannose: properties, production, and applications: an overview. Compr. Rev. Food Sci. Food Saf. 2016; 15(4): 773-85. https://dx.doi.org/10.1111/1541-4337.12211.
  38. Aronson M., Medalia O., Schori L., Mirelman D., Sharon N., Ofek I. Prevention of colonization of the urinary tract of mice with Escherichia coli by blocking of bacterial adherence with methyl alpha-D-mannopyranoside. J. Infect. Dis. 1979; 139(3): 329-32. https://dx.doi.org/10.1093/infdis/ 139.3.329.
  39. Michaels E.K., Chmiel J.S., Plotkin B.J., Schaeffer A.J. Effect of D-mannose and D-glucose on Edscherichia coli bacteriuria in rats. Urol. Res. 1983; 11(2): 97-102. https://dx.doi.org/10.1007/BF00256954.
  40. Cusumano C.K., Pinkner J.S., Han Z., Greene S.E., Ford B.A., Crowley J.R. et al. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci. Transl. Med. 2011; 3(109): 109ra115. https://dx.doi.org/10.1126/scitranslmed.300302.
  41. Domenici L., Monti M., Bracchi C., Giorgini M., Colagiovanni V., Muzii L., Benedetti Panici P. D-mannose: a promising support for acute urinary tract infections in women. A pilot study. Eur. Rev. Med. Pharmacol. Sci. 2016; 20(13): 2920-5.
  42. Porru D., Parmigiani A., Tinelli C., Barletta D., Choussos D., Di Franco C. Oral D-mannose in recurrent urinarytract infections in women: a pilot study. J. Clin. Urol. 2014; 7(3): 208-13. https://dx.doi.org/10.1177/2051415813518332.
  43. Kranjčec B., Papeš D., Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J. Urol. 2014; 32(1): 79-84. https://dx.doi.org//10.1007/s00345-013-1091-6.
  44. Lenger S.M., Bradley M.S., Thomas D.A., Bertolet M.H., Lowder J.L., Sutcliffe S. D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: a systematic review and meta-analysis. Am. J. Obstet. Gynecol. 2020; 223(2): 265.e1-265.e13. https://dx.doi.org/10.1016/j.ajog.2020.05.048.
  45. Захарова И.Н., Османов И.М., Касьянова А.Н., Мумладзе Э.Б., Мачнева Е.Б., Лупан И.Н. Протективные факторы слизистой оболочки мочевого пузыря – ключ к новым подходам к терапии инфекции мочевых путей. Российский вестник перинатологии и педиатрии. 2018; 63(2): 16-21. [Zakharova I.N., Osmanov I.M., Kasyanova A.N., Mumladze E.B., Machneva E.B., Lupan I.N. Protective factors of the urinary bladder mucous memebrane – the key to new approaches of urinary tract infection therapy. Russian Bulletin of Perinatology and Pediatrics. 2018; 63(2): 16-21. (in Russian)]. https://dx.doi.org/10.21508/1027-4065-2018-63-2-16-21.: 28.03.2023).
  46. Brubaker L., Putonti C., Dong Q., Wolfe A.J. The human urobiome. Mamm. Genome. 2021; 32(4): 232-8. https://dx.doi.org/10.1007/s00335-021-09862-8.
  47. Ceprnja M., Oros D., Melvan E., Svetlicic E., Skrlin J., Barisic K. et al. Modeling of urinary microbiota associated with cystitis. Front. Cell. Infect. Microbiol. 2021; 11: 643638. https://dx.doi.org/10.3389/fcimb.2021.643638.
  48. Komesu Y.M., Dinwiddie D.L., Richter H.E., Lukacz E.S., Sung V.W., Siddiqui N.Y. et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Defining the relationship between vaginal and urinary microbiomes. Am. J. Obstet. Gynecol. 2020; 222(2): 154.e1-154.e10. https://dx.doi.org/10.1016/j.ajog.2019.08.011.
  49. Pearce M.M., Hilt E.E., Rosenfeld A.B., Zilliox M.J., Thomas-White K., Fok C. et al. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014; 5(4): e01283-14. https://dx.doi.org/10.1128/mBio.01283-14.
  50. Thomas-White K.J., Gao X., Lin H., Fok C.S., Ghanayem K., Mueller E.R. et al. Urinary microbes and postoperative urinary tract infection risk in urogynecologic surgical patients. Int. Urogynecol. J. 2018; 29(12): 1797-805. https://dx.doi.org/10.1007/s00192-018-3767-3.
  51. Перепанова Т.С. Значение инфекций, обусловленных образованием биопленок, в урологической практике. Эффективная фармакотерапия. 2013; 37: 18-27. [Perepanova T.S. The value of infections with the formation of biofilms in urology. Effective Pharmacotherapy. 2013; (37): 18-27. (in Russian)].
  52. Reid G., Bruce A.W. Probiotics to prevent urinary tract infections: the rationale and evidence. World J. Urol. 2006; 24(1): 28-32. https://dx.doi.org/10.1007/s00345-005-0043-1.
  53. Murina F., Vicariotto F., Lubrano C. Efficacy of an orally administered combination of Lactobacillus paracasei LC11, cranberry and D-mannose for the prevention of uncomplicated, recurrent urinary tract infections in women. Urologia. 2021; 88(1): 64-8. https://dx.doi.org/ 10.1177/0391560320957483.
  54. Vicariotto F. Effectiveness of an association of a cranberry dry extract, D-mannose, and the two microorganisms Lactobacillus plantarum LP01 and Lactobacillus paracasei LPC09 in women affected by cystitis: a pilot study. J. Clin. Gastroenterol. 2014; 48(Suppl. 1): 96-101. https://dx.doi.org/10.1097/MCG.0000000000000224.
  55. Pugliese D., Acampora A., Porreca A., Schips L., Cindolo L. Effectiveness of a novel oral combination of D-Mannose, pomegranate extract, prebiotics and probiotics in the treatment of acute cystitis in women. Arch. Ital. Urol. Androl. 2020; 92(1): 34-8. https://dx.doi.org/10.4081/aiua.2020.1.34.

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