Микробиом и мочекаменная болезнь: новые возможности профилактики

Изучение мочекаменной болезни имеет многовековую историю. Лечение уролитиаза эволюционировало от проведения тяжелых калечащих операций до современных малоинвазивных лечебных процедур. Эпидемиологические данные свидетельствуют о неуклонном росте заболеваемости уролитиазом во всем мире. Мочекаменная болезнь имеет эндемичный характер, что определяется влиянием разнообразных модифицируемых факторов, в т. ч. социально-экономических и климатических. Согласно статистическим данным, прирост заболеваемости уролитиазом с 2005 по 2019 г. в Российской Федерации составил 35,45%, что диктует необходимость разработки эффективных профилактических мероприятий. Превентивные меры при мочекаменной болезни основаны главным образом на модификации факторов образа жизни и использования фармакотерапии. Современные данные подтверждают парадигму о том, что микробиом человека является полноценным органом, поскольку изменения его качественного и количественного состава в различных локусах могут оказывать существенное влияние на метаболизм и иммунитет. В исследованиях были установлены механизмы, посредством которых определенные компоненты микробиома мочи способны как ингибировать, так и стимулировать литогенез. Исследования показали, что в микробиоме мочевыводящих путей здоровых людей преобладают комменсальные бактерии, такие как Lactobacillus и Streptococcus, которые поддерживают гомеостаз микросреды. У пациентов с мочекаменной болезнью наблюдается значительное снижение разнообразия кишечного и мочевого микробиома, а также изменение численности отдельных таксонов. Изучение микробиома мочи и кишечника является плацдармом для разработки новых подходов к профилактике мочекаменной болезни. В данной статье представлены данные о взаимосвязи микробиома мочи и мочекаменной болезни и рассмотрены перспективы в развитии нового подхода к ее лечению и профилактике.

1. Shah J, Whitfield HN. Urolithiasis through the ages. BJU Int. 2002;89(8):801–810. https://doi.org/10.1046/j.1464-410x.2002.02769.x.

2. Dardioti V, Angelopoulos N, Hadjiconstantinou V. Renal diseases in the Hippocratic era. Am J Nephrol. 1997;17(3-4):214–216. https://doi.org/10.1159/000169104.

3. Eknoyan G. History of urolithiasis. Clin Rev Bone Miner Metab. 2004;2(3):177–185. https://doi.org/10.1385/BMM:2:3:177.

4. Lоpez M, Hoppe B. History, epidemiology and regional diversities of urolithiasis. Pediatr Nephrol. 2010;25(1):49–59. https://doi.org/10.1007/s00467-008-0960-5.

5. Sachs M. The prohibition of lithotomy within the Hippocratic Oath: historical and ethical considerations on the history of surgery. Zentralbl Chir. 2003;128(4):341–347. https://doi.org/10.1055/s-2003-38802.

6. Tefekli A, Cezayirli F. The history of urinary stones: in parallel with civilization. ScientificWorldJournal.2013;2013:423964. https://doi.org/10.1155/2013/423964.

7. Ellis H. A history of bladder stone. J R Soc Med. 1979;72(4):248–251. https://doi.org/10.1177/014107687907200403.

8. Richet G. Nephrolithiasis at the turn of the 18th to 19th centuries: biochemical disturbances. A genuine cascade giving rise to clinical chemistry. Am J Nephrol.2002;22(2-3):254–259. https://doi.org/10.1159/000063770.

9. Bigelow HJ. Lithotrity by a single operation. Am J Med Sci. 1879;75(149):117–134.https://doi.org/10.1056/NEJM187802280980901.

10. Lingeman JE, Lifshitz DA, Evan AP. Surgical management of urinary lithiasis. In: Walsh PC, Retik AB, Vaughan ED, Wein AJ (eds.). Campbell’s Urology. 8th ed. 2002, pp. 3361–3451.

11. Зимин ИВ, Смирнов АВ, Аль-шукри СХ, Лукичев БҐ. Последняя болезнь и смерть Петра Великого. Нефрология. 2003;7(2):88–92. https://doi.org/10.24884/1561-6274-2003-7-2-88-92.

12. Неделько НФ. Медицинские и судебно-медицинские аспекты заболевания и смерти Петра Великого. Байкальский медицинский журнал. 2005;(5):82–87. Режим доступа: https://www.bmjour.ru/jour/issue/viewIssue/103/95.

13. Sorokin I, Mamoulakis C, Miyazawa K, Rodgers A, Talati J, Lotan Y. Epidemiology of stone disease across the world. World J Urol. 2017;35(9):1301–1320. https://doi.org/10.1007/s00345-017-2008-6.

14. Каприн АД, Аполихин ОИ, Сивков АВ, Анохин НВ, Гаджиев НК, Малхасян ВА и др. Заболеваемость мочекаменной болезнью в Российской Федерации с 2005 по 2020 гг. Экспериментальная и клиническая урология. 2022;15(2):10–17. https://doi.org/10.29188/2222-8543-2022-15-2-10-17.

15. Hesse A, Brändle E, Wilbert D, Köhrmann KU, Alken P. Study on the prevalence and incidence of urolithiasis in Germany comparing the years 1979 vs. 2000. Eur Urol. 2003;44(6):709–713. https://doi.org/10.1016/s0302-2838(03)00415-9.

16. Scales CD Jr, Smith AC, Hanley JM, Saigal CS; Urologic Diseases in America Project. Prevalence of kidney stones in the United States. Eur Urol. 2012;62(1):160–165. https://doi.org/10.1016/j.eururo.2012.03.052.

17. Novak TE, Lakshmanan Y, Trock BJ, Gearhart JP, Matlaga BR. Sex prevalence of pediatric kidney stone disease in the United States: an epidemiologic investigation. Urology. 2009;74(1):104–107. https://doi.org/10.1016/j.urology.2008.12.079.

18. Sas DJ, Hulsey TC, Shatat IF, Orak JK. Increasing incidence of kidney stones in children evaluated in the emergency department. J Pediatr. 2010;157(1):132–137. https://doi.org/10.1016/j.jpeds.2010.02.004.

19. Калабеков АА, Казаченко АВ, Иващенко ВВ. Факторы риска кальциевого и уратного нефролитиаза. Роль канальцевых дисфункций в камнеобразовании. Экспериментальная и клиническая урология. 2016;(1):8–14. Режим доступа: https://ecuro.ru/article/faktory-riska-kaltsievogoi-uratnogo-nefrolitiaza-rol-kanaltsevykh-disfunktsii-v-kamneobrazo.

20. Tostivint IN, Castiglione V, Alkouri R, Bertocchio JP, Inaoui R, Daudon M et al. How useful is an oral calcium load test for diagnosing recurrent calcium stone formers? Urolithiasis. 2022;50(5):577–587. https://doi.org/10.1007/s00240-022-01355-w.

21. Акопян АВ, Апакина АВ, Баранов АА, Борисова СА, Боровик ТЭ, Вардак АБ и др. Мочекаменная болeзнь: клиничeскиe рeкомeндации. 2021. Режим доступа: https://cr.minzdrav.gov.ru/view-cr/374_2.

22. Симаненков ВИ, Маев ИВ, Ткачева ОН, Алексеенко СА, Андреев ДН, Бордин ДС и др. Синдром повышенной эпителиальной проницаемости в клинической практике. Мультидисциплинарный национальный консенсус. Кардиоваскулярная терапия и профилактика. 2021;20(1):2758. https://doi.org/10.15829/1728-8800-2021-2758.

23. Rungrasameviriya P, Santilinon A, Atichartsintop P, Hadpech S, Thongboonkerd V. Tight junction and kidney stone disease. Tissue Barriers. 2024;12(1):2210051. https://doi.org/10.1080/21688370.2023.2210051.

24. Chang J, Yan J, Li X, Liu N, Zheng R, Zhong Y. Update on the Mechanisms of Tubular Cell Injury in Diabetic Kidney Disease. Front Med. 2021;8:661076. https://doi.org/10.3389/fmed.2021.661076.

25. An L, Wu W, Li S, Lai Y, Chen D, He Z et al. Escherichia coli Aggravates Calcium Oxalate Stone Formation via PPK1/Flagellin-Mediated Renal Oxidative Injury and Inflammation. Oxid Med Cell Longev. 2021;2021:9949697. https://doi.org/10.1155/2021/9949697.

26. Vinaiphat A, Aluksanasuwan S, Manissorn J, Sutthimethakorn S, Thongboonkerd V. Response of renal tubular cells to differential types and doses of calcium oxalate crystals: Integrative proteome network analysis and functional investigations. Proteomics. 2017;17(15-16). https://doi.org/10.1002/pmic.201700192.

27. Peerapen P, Thongboonkerd V. Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells. Lab Invest. 2011;91(1):97–105. https://doi.org/10.1038/labinvest.2010.167.

28. Yu L, Gan X, Liu X, An R. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/ Akt/p38 MAPK signaling pathway. Ren Fail. 2017;39(1):440–451. https://doi.org/10.1080/0886022X.2017.1305968.

29. Peerapen P, Thongboonkerd V. Calcium oxalate monohydrate crystal disrupts tight junction via F-actin reorganization. Chem Biol Interact. 2021;345:109557. https://doi.org/10.1016/j.cbi.2021.109557.

30. Goodson HV, Jonasson EM. Microtubules and Microtubule-Associated Proteins. Cold Spring Harb Perspect Biol. 2018;10(6):a022608. https://doi.org/10.1101/cshperspect.a022608.

31. Hadpech S, Peerapen P, Thongboonkerd V. Alpha-tubulin relocalization is involved in calcium oxalate-induced tight junction disruption in renal epithelial cells. Chem Biol Interact. 2022;368:110236. https://doi.org/10.1016/j.cbi.2022.110236.

32. Plain A, Alexander RT. Claudins and nephrolithiasis. Curr Opin Nephrol Hypertens. 2018;27(4):268–276. https://doi.org/10.1097/MNH.0000000000000426.

33. Palsson R, Indridason OS, Edvardsson VO, Oddsson A. Genetics of common complex kidney stone disease: insights from genome-wide association studies. Urolithiasis. 2019;47(1):11–21. https://doi.org/10.1007/s00240-018-1094-2.

34. Ullah I, Murtaza K, Ammara H, Misbah, Bhinder MA, Riaz A et al. Association study of CLDN14 variations in patients with kidney stones. Open Life Sci. 2022;17(1):81–92. https://doi.org/10.1515/biol-2021-0134.

35. Negri AL, Del Valle EE. Role of claudins in idiopathic hypercalciuria and renal lithiasis. Int Urol Nephrol. 2022;54(9):2197–2204. https://doi.org/10.1007/s11255-022-03119-2.

36. Curry JN, Saurette M, Askari M, Pei L, Filla MB, Beggs MR et al. Claudin-2 deficiency associates with hypercalciuria in mice and human kidney stone disease. J Clin Invest. 2020;130(4):1948–1960. https://doi.org/10.1172/JCI127750.

37. Klar J, Piontek J, Milatz S, Tariq M, Jameel M, Breiderhoff T et al. Altered paracellular cation permeability due to a rare CLDN10B variant causes anhidrosis and kidney damage. PLoS Genet. 2017;13(7):e1006897. https://doi.org/10.1371/journal.pgen.1006897.

38. Попов СВ, Улитина АС, Гусейнов РГ, Сивак КВ, Перепелица ВВ, Надеин КА, Буненков НС. Роль эпигенетических факторов в патогенезе мочекаменной болезни: фокус на систему «клаудины – микроРНК». Медицинский вестник Башкортостана. 2023;18(1):79–82. Режим доступа: https://mvb-bsmu.ru/files/journals/1_2023.pdf.

39. Arumugam M, Raes J, Pelletier E, LePaslier D, Yamada T, Mende DR et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–180. https://doi.org/10.1038/nature09944.

40. Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C et al. Microbiota in health and diseases. Signal Transduct Target Ther. 2022;7(1):135. https://doi.org/10.1038/s41392-022-00974-4.

41. Прокопьева НЭ, Новикова ВП, Хавкин АИ. Ось кишечная микробиота – почки. Особенности при заболеваниях мочевыделительной системы и урогенитального тракта. Медицина: теория и практика. 2022;7(4):68–77. Режим доступа: https://ojs3.gpmu.org/index.php/med-theory-and-practice/article/view/5510.

42. Tsuji K, Uchida N, Nakanoh H, Fukushima K, Haraguchi S, Kitamura S, Wada J. The Gut-Kidney Axisin Chronic Kidney Diseases. Diagnostics. 2024;15(1):21. https://doi.org/10.3390/diagnostics15010021.

43. Stern JM, Moazami S, Qiu Y, Kurland I, Chen Z, Agalliu I et al. Evidence for a distinct gut microbiome in kidney stone formers compared to non-stone formers. Urolithiasis. 2016;44(5):399–407. https://doi.org/10.1007/s00240-016-0882-9.

44. Симанов РН, Барышева ОЮ. Оксалурия при воспалительных заболеваниях кишечника (обзор литературы). Колопроктология. 2024;23(3):126–135. https://doi.org/10.33878/2073-7556-2024-23-3-126-135.

45. Dawson KA, Allison MJ, Hartman PA. Isolation and some characteristics of anaerobic oxalate-degrading bacteria from the rumen. Appl Environ Microbiol. 1980;40(4):833–839. https://doi.org/10.1128/aem.40.4.833-839.1980.

46. Allison MJ, Dawson KA, Mayberry WR, Foss JG. Oxalobacterformigenes gen. nov., sp. nov.: oxalate-degrading anaerobes that inhabit the gastrointestinal tract. Arch Microbiol. 1985;141(1):1–7. https://doi.org/10.1007/BF00446731.

47. Mehta M, Goldfarb DS, Nazzal L. The role of the microbiome in kidney stone formation. Int J Surg. 2016;36:607–612. https://doi.org/10.1016/j.ijsu.2016.11.024.

48. Siva S, Barrack ER, Reddy GP, Thamilselvan V, Thamilselvan S, Menon M, Bhandari M. A critical analysis of the role of gut Oxalobacterformigenes in oxalate stone disease. BJU Int. 2009;103(1):18–21. https://doi.org/10.1111/j.1464-410X.2008.08122.x.

49. Daniel SL, Moradi L, Paiste H, Wood KD, Assimos DG, Holmes RP et al. Forty Years of Oxalobacterformigenes, a Gutsy Oxalate-Degrading Specialist. Appl Environ Microbiol. 2021;87(18):e0054421. https://doi.org/10.1128/AEM.00544-21.

50. Mittal RD, Kumar R, Mittal B, Prasad R, Bhandari M. Stone composition, metabolic profile and the presence of the gut-inhabiting bacterium Oxalobacterformigenes as risk factors for renal stone formation. Med Princ Pract. 2003;12(4):208–213. https://doi.org/10.1159/000072285.

51. Kwak C, Jeong BC, Kim HK, Kim EC, Chox MS, Kim HH. Molecular epidemiology of fecal Oxalobacterformigenes in healthy adults living in Seoul, Korea. J Endourol. 2003;17(4):239–243. https://doi.org/10.1089/089277903765444384.

52. Han JZ, Zhang X, Li JG, Zhang YS. The relationship of Oxalobacterformigenes and calcium oxalate calculi. J Tongji Med Univ. 1995;15(4):249–252. https://doi.org/10.1007/BF02887957.

53. Kelly JP, Curhan GC, Cave DR, Anderson TE, Kaufman DW. Factors related to colonization with Oxalobacterformigenes in U.S. adults. J Endourol. 2011;25(4):673–679. https://doi.org/10.1089/end.2010.0462.

54. Siener R, Bangen U, Sidhu H, Hönow R, von Unruh G, Hesse A. The role of Oxalobacterformigenes colonization in calcium oxalate stone disease. Kidney Int. 2013;83(6):1144–1149. https://doi.org/10.1038/ki.2013.104.

55. Ticinesi A, Milani C, Guerra A, Allegri F, Lauretani F, Nouvenne A et al. Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers. Gut. 2018;67(12):2097–2106. https://doi.org/10.1136/gutjnl-2017-315734.

56. Hoppe B, Groothoff JW, Hulton SA, Cochat P, Niaudet P, Kemper MJ et al. Efficacy and safety of Oxalobacterformigenes to reduce urinary oxalate in primary hyperoxaluria. Nephrol Dial Transplant. 2011;26(11):3609–3015. https://doi.org/10.1093/ndt/gfr107.

57. Tang R, Jiang Y, Tan A, Ye J, Xian X, Xie Y et al. 16S rRNA gene sequencing reveals altered composition of gut microbiota in individuals with kidney stones. Urolithiasis. 2018;46(6):503–514. https://doi.org/10.1007/s00240-018-1037-y.

58. Stern JM, Moazami S, Qiu Y, Kurland I, Chen Z, Agalliu I et al. Evidence for a distinct gut microbiome in kidney stone formers compared to non-stone formers. Urolithiasis. 2016;44(5):399–407. https://doi.org/10.1007/s00240-016-0882-9.

59. Denburg MR, Koepsell K, Lee JJ, Gerber J, Bittinger K, Tasian GE. Perturbations of the Gut Microbiome and Metabolome in Children with Calcium Oxalate Kidney Stone Disease. J Am Soc Nephrol. 2020;31(6):1358–1369. https://doi.org/10.1681/ASN.2019101131.

60. Kim HN, Kim JH, Chang Y, Yang D, Joo KJ, Cho YS et al. Gut microbiota and the prevalence and incidence of renal stones. Sci Rep. 2022;12(1):3732. https://doi.org/10.1038/s41598-022-07796-y.

61. Miller AW, Choy D, Penniston KL, Lange D. Inhibition of urinary stone disease by a multi-species bacterial network ensures healthy oxalate homeostasis. Kidney Int. 2019;96(1):180–188. https://doi.org/10.1016/j.kint.2019.02.012.

62. Zhang R, Zhao W, Zhao R, Zhao Y, Zhang Y, Liang X. Causal relationship in gut microbiota and upper urinary urolithiasis using Mendelian randomization. Front Microbiol. 2023;14:1170793. https://doi.org/10.3389/fmicb.2023.1170793.

63. Wang Y, Sun J, Xie S, Zhou Y, Wang T, Liu Z et al. Increased abundance of bacteria of the family Muribaculaceae achieved by fecal microbiome transplantation correlates with the inhibition of kidney calcium oxalate stone deposition in experimental rats. Front Cell Infect Microbiol. 2023;13:1145196. https://doi.org/10.3389/fcimb.2023.1145196.

64. Ellison JS, Atkinson SN, Hayward M, Hokanson E, Sheridan KR, Salzman N. The intestinal microbiome of children with initial and recurrent nephrolithiasis: A pilot study and exploratory analysis. J Pediatr Urol. 2024;20(1):18–25. https://doi.org/10.1016/j.jpurol.2023.09.015.

65. Jia Y, Han M, Ge H, Qiao J, Chen R, Li C et al. Dysbiosis of gut and urinary microbiota in urolithiasis patients and post-surgical cases. Front Cell Infect Microbiol. 2025;15:1633783. https://doi.org/10.3389/fcimb.2025.1633783.

66. Zheng H, Wang C, Yu X, Zheng W, An Y, Zhang J et al. The Role of Metabolomics and Microbiology in Urinary Tract Infection. Int J Mol Sci. 2024;25(6):3134. https://doi.org/10.3390/ijms25063134.

67. Xia B, Wang J, Zhang D, Hu X. The human microbiome links to prostate cancer risk and treatment (Review). Oncol Rep. 2023;49(6):123. https://doi.org/10.3892/or.2023.8560.

68. Brubaker L, Wolfe AJ. The female urinary microbiota, urinary health and common urinary disorders. Ann Transl Med. 2017;5(2):34. https://doi.org/10.21037/atm.2016.11.62.

69. Wang Z, Zhang Y, Zhang J, Deng Q, Liang H. Recent advances on the mechanisms of kidney stone formation (Review). Int J Mol Med. 2021;48(2):149. https://doi.org/10.3892/ijmm.2021.4982.

70. 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):64–68. https://doi.org/10.1177/0391560320957483.

71. Taheri H, Feizabadi MM, Keikha R, Afkari R. Therapeutic effects of probiotics and herbal medications on oxalate nephrolithiasis: a mini systematic review. Iran J Microbiol. 2024;16(1):4-18. https://doi.org/10.18502/ijm.v16i1.14866.

72. Chutipongtanate S, Sutthimethakorn S, Chiangjong W, Thongboonkerd V. Bacteria can promote calcium oxalate crystal growth and aggregation. J Biol Inorg Chem. 2013;18(3):299–308. https://doi.org/10.1007/s00775-012-0974-0.

73. Barr-Beare E, Saxena V, Hilt EE, Thomas-White K, Schober M, Li B et al. The Interaction between Enterobacteriaceae and Calcium Oxalate Deposits. PLoS ONE. 2015;10(10):e0139575. https://doi.org/10.1371/journal.pone.0139575.

74. Jung HD, Cho S, Lee JY. Update on the Effect of the Urinary Microbiome on Urolithiasis. Diagnostics. 2023;13(5):951. https://doi.org/10.3390/diagnostics13050951.

75. Choi HW, Lee KW, Kim YH. Microbiome in urological diseases: Axis crosstalk and bladder disorders. Investig Clin Urol. 2023;64(2):126–139. https://doi.org/10.4111/icu.20220357.

76. Xie J, Huang JS, Huang XJ, Peng JM, Yu Z, Yuan YQ et al. Profiling the urinary microbiome in men with calcium-based kidney stones. BMC Microbiol. 2020;20(1):41. https://doi.org/10.1186/s12866-020-01734-6.

77. Zampini A, Nguyen AH, Rose E, Monga M, Miller AW. Defining Dysbiosis in Patients with Urolithiasis. Sci Rep. 2019;9(1):5425. https://doi.org/10.1038/s41598-019-41977-6.

78. Modi SR, Collins JJ, Relman DA. Antibiotics and the gut microbiota. J Clin Invest. 2014;124(10):4212–4218. https://doi.org/10.1172/JCI72333.

79. Ferraro PM, Curhan GC, Gambaro G, Taylor EN. Antibiotic Use and Risk of Incident Kidney Stones in Female Nurses. Am J Kidney Dis. 2019;74(6):736–741. https://doi.org/10.1053/j.ajkd.2019.06.005.

80. Liu M, Devlin JC, Hu J, Volkova A, Battaglia TW, Ho M et al. Microbial genetic and transcriptional contributions to oxalate degradation by the gut microbiota in health and disease. Elife. 2021;10:e63642. https://doi.org/10.1101/2020.01.27.20018770.

81. Miller AW, Orr T, Dearing D, Monga M. Loss of function dysbiosis associated with antibiotics and high fat, high sugar diet. ISME J. 2019;13(6):1379–1390. https://doi.org/10.1038/s41396-019-0357-4.

82. Tavichakorntrakool R, Prasongwattana V, Sungkeeree S, Saisud P, Sribenjalux P, Pimratana C et al. Extensive characterizations of bacteria isolated from catheterized urine and stone matrices in patients with nephrolithiasis. Nephrol Dial Transplant. 2012;27(11):4125–4130. https://doi.org/10.1093/ndt/gfs057.

83. Pei X, Liu M, Yu S. How is the human microbiome linked to kidney stones? Front Cell Infect Microbiol. 2025;15:1602413. https://doi.org/10.3389/fcimb.2025.1602413.