Contemporary view on the microbiota of kidney stones and urine in patients with urolithiasis: a narrative review
- Authors: Pushkarev A.M.1, Sabirzyanov S.S.2, Artemeva A.V.1, Isekeyev Y.L.3, Popkova V.A.3, Efremova A.I.3, Kharrasova A.I.1, Zaripova Y.A.1, Romanova K.R.4, Lynova A.V.5, Nasypova A.I.3, Kaerov D.D.3, Rasulova A.A.6
-
Affiliations:
- Bashkir State Medical University
- Republican Clinical Hospital named after G.G. Kuvatov
- Izhevsk State Medical Academy
- Pirogov Russian National Research Medical University
- Academician I.P. Pavlov First St. Petersburg State Medical University
- The First Sechenov Moscow State Medical University
- Issue: Vol 15, No 4 (2025)
- Pages: 427-438
- Section: Reviews
- URL: https://journal-vniispk.ru/uroved/article/view/381660
- DOI: https://doi.org/10.17816/uroved696823
- EDN: https://elibrary.ru/KSQNHU
- ID: 381660
Cite item
Abstract
Urolithiasis is a highly prevalent disease with a frequent recurrent course, indicating the limited effectiveness of existing preventive and therapeutic strategies. The revision of the long-standing paradigm of urinary tract sterility, enabled by the advent of high-throughput sequencing technologies, has led to the emergence of the urobiome concept as a complex ecosystem involved in the pathogenesis of urolithiasis. The present review systematizes current data on the role of the microbiota of urine and renal calculi in the pathogenesis of urolithiasis. The analysis demonstrated that urobiome dysbiosis, characterized by reduced alpha diversity and altered proportions of major taxa, represents a pathogenetic factor of lithogenesis rather than its consequence. Metagenomic studies show that the microbiome of kidney stones consists of specific bacterial consortia encapsulated within the mineral matrix. It has been established that different bacterial taxa directly influence stone formation through the production of enzymes initiating the formation of struvite stones (urease) and oxalate-degrading enzymes, with Oxalobacter formigenes being one of the principal producers. An important role in pathogenesis is played by the formation of bacterial biofilms, which serve as a scaffold for microbial colonization and subsequent crystallization. In addition, the role of the gut–kidney axis has been identified, in which intestinal dysbiosis triggers systemic inflammation, disruption of lithogenic metabolite homeostasis, and increased intestinal barrier permeability, collectively creating conditions favorable for lithogenesis. Thus, the available data provide a contemporary and in-depth understanding of the pathogenesis of urolithiasis, in which the microbiota is considered an active pathogenetic factor. Integration of data on the taxonomic and functional status of the urobiome opens new prospects for the development of innovative diagnostic, prognostic, and therapeutic strategies aimed at correcting dysbiosis for the treatment and prevention of urolithiasis recurrence.
About the authors
Aleksei M. Pushkarev
Bashkir State Medical University
Author for correspondence.
Email: pushkarev.urobsmu@gmail.com
ORCID iD: 0009-0002-6826-3133
SPIN-code: 8521-6208
MD, Dr. Sci. (Medicine), Professor
Russian Federation, UfaSabir S. Sabirzyanov
Republican Clinical Hospital named after G.G. Kuvatov
Email: sobir08-97@mail.ru
ORCID iD: 0000-0003-4044-0396
MD
Russian Federation, UfaAnna V. Artemeva
Bashkir State Medical University
Email: fruitoanya123@yandex.ru
ORCID iD: 0009-0004-6658-8529
MD
Russian Federation, UfaYurii L. Isekeyev
Izhevsk State Medical Academy
Email: tarelkailimon@mail.ru
ORCID iD: 0009-0001-0084-8795
MD
Russian Federation, IzhevskValeria A. Popkova
Izhevsk State Medical Academy
Email: lera.lily@gmail.com
ORCID iD: 0009-0007-1257-123X
MD
Russian Federation, IzhevskAleksandra I. Efremova
Izhevsk State Medical Academy
Email: efremovaaleks@yandex.ru
ORCID iD: 0009-0008-1278-9172
MD
Russian Federation, IzhevskAdelina I. Kharrasova
Bashkir State Medical University
Email: Harrasovaadel150503@gmail.com
ORCID iD: 0009-0001-1820-3653
Russian Federation, Ufa
Yasmina A. Zaripova
Bashkir State Medical University
Email: zaripova_ya2002@mail.ru
ORCID iD: 0009-0001-3849-0047
Russian Federation, Ufa
Karina R. Romanova
Pirogov Russian National Research Medical University
Email: Rudolflukashin555@gmail.com
ORCID iD: 0009-0007-0943-2327
MD
Russian Federation, MoscowAnita V. Lynova
Academician I.P. Pavlov First St. Petersburg State Medical University
Email: afugl@bk.ru
ORCID iD: 0009-0004-5840-9981
MD
Russian Federation, Saint PetersburgAliya I. Nasypova
Izhevsk State Medical Academy
Email: nasypovaaliyaxi@gmail.com
ORCID iD: 0009-0008-7279-2015
MD
Russian Federation, IzhevskDenis D. Kaerov
Izhevsk State Medical Academy
Email: kaerovd@list.ru
ORCID iD: 0009-0009-2613-2240
MD
Russian Federation, IzhevskAlina A. Rasulova
The First Sechenov Moscow State Medical University
Email: alina.ras1223@gmail.com
ORCID iD: 0009-0006-4207-7315
MD
Russian Federation, MoscowReferences
- Protoshchak VV, Paronnikov MV, Orlov DN, et al. Medical and economic rationale for the use of modern methods of treating urolithiasis. Experimental and Clinical Urology. 2019;(3):12–18. doi: 10.29188/2222-08543-2019-11-3-12-18 EDN: OKICOS
- Yao W, Wei X, Jing Q, et al. Epidemiological trends of urolithiasis in working-age populations: Findings from the global burden of disease study 1990–2021. PLoS One. 2025;20(7):e0327343. doi: 10.1371/journal.pone.0327343 EDN: FALBEA
- Lang J, Narendrula A, El-Zawahry A, et al. Global trends in incidence and burden of urolithiasis from 1990 to 2019: an analysis of global burden of disease study data. Eur Urol Open Sci. 2022;35:37–46. doi: 10.1016/j.euros.2021.10.008 EDN: NTJEGZ
- Li S, Huang X, Liu J, et al. Trends in the incidence and DALYs of urolithiasis from 1990 to 2019: results from the global burden of disease study 2019. Front Public Health. 2022;10:825541. doi: 10.3389/fpubh.2022.825541 EDN: XHDOBS
- Zubkov IV, Biteev VKh, Korotaev PN, et al. Epidemiology of urolithiasis and results of a pilot study on the use of fibrocalicolithotripsy. RMJ. 2021;(8):7–10.
- Slesarevskaya MN, Kuzmin IV, Zhumadillaev KG, et al. Microbiome and urine microbiota: modern concepts and gender features. Urology Reports (St.-Petrsburg). 2022;12(2):157–165. doi: 10.17816/uroved109278 EDN: VOVNVA
- Pastuszka A, Tobor S, Łoniewski I, et al. Rewriting the urinary tract paradigm: the urobiome as a gatekeeper of host defense. Mol Biol Rep. 2025;52(1):497. doi: 10.1007/s11033-025-10609-w EDN: DTRHPR
- Cumpanas AA, Bratu OG, Bardan RT, et al. Urinary microbiota–are we ready for prime time? a literature review of study methods’ critical steps in avoiding contamination and minimizing biased results. Diagnostics (Basel). 2020;10(6):343. doi: 10.3390/diagnostics10060343 EDN: RUPSJQ
- Evdokimova NV, Chernen’kaya TV. Modern view on the microbiome of the urinary tract. Pathol Physiol Exp Ther. 2024;68(1):138–144. doi: 10.25557/0031-2991.2024.01.138-144
- Collins L, Sathiananthamoorthy S, Rohn J, et al. A revalidation and critique of assumptions about urinary sample collection methods, specimen quality and contamination. Int Urogynecol J. 2020;31(6):1255–1262. doi: 10.1007/s00192-020-04272-x EDN: BADSXI
- Xie J, Huang JS, Huang XJ, et al. Profiling the urinary microbiome in men with calcium-based kidney stones. BMC Microbiol. 2020;20(1):41. doi: 10.1186/s12866-020-01734-6 EDN: MBGWMG
- Liu H, Hu Q, Yan Q, et al. Alterations in urinary microbiota composition in urolithiasis patients: insights from 16S rRNA gene sequencing. Front Cell Infect Microbiol. 2023;13:1266446. doi: 10.3389/fcimb.2023.1266446 EDN: AFVBDN
- Xie J, Zhang XQ, Guo JN, et al. The urinary microbiota composition and functionality of calcium oxalate stone formers. Front Cell Infect Microbiol. 2024;14:1394955. doi: 10.3389/fcimb.2024.1394955 EDN: SLWAKT
- Hong SY, Yang YY, Xu JZ, et al. The renal pelvis urobiome in the unilateral kidney stone patients revealed by 2bRAD-M. J Transl Med. 2022;20(1):431. doi: 10.1186/s12967-022-03639-6 EDN: KOFCLN
- Kramer H, Kuffel G, Thomas-White K, et al. Diversity of the midstream urine microbiome in adults with chronic kidney disease. Int Urol Nephrol. 2018;50(6):1123–1130. doi: 10.1007/s11255-018-1860-7 EDN: GYZMHM
- Lewis ZJ, Scott A, Madden C, et al. Evaluating urine volume and host depletion methods to enable genome-resolved metagenomics of the urobiome. Microbiome. 2025;13(1):199. doi: 10.1186/s40168-025-02191-x EDN: CYSUHE
- Pohl HG, Groah SL, Pérez-Losada M, et al. The urine microbiome of healthy men and women differs by urine collection method. Int Neurourol J. 2020;24(1):41–51. doi: 10.5213/inj.1938244.122 EDN: TXWPKH
- Nardelli C, Aveta A, Pandolfo SD, et al. Microbiome profiling in bladder cancer patients using the first-morning urine sample. Eur Urol Open Sci. 2024;59:18–26. doi: 10.1016/j.euros.2023.11.003 EDN: XLWGRE
- Liu F, Zhang N, Jiang P, et al. Characteristics of the urinary microbiome in kidney stone patients with hypertension. J Transl Med. 2020;18(1):130. doi: 10.1186/s12967-020-02282-3 EDN: HGXCGH
- Hong SY, Miao LT, Yang YY, et al. A comparison of male and female renal pelvis urobiome of unilateral stone formers using 2bRAD-M. BMC Microbiol. 2024;24(1):456. doi: 10.1186/s12866-024-03618-5 EDN: EWRRKX
- Graells T, Lin YT, Ahmad S, et al. The urinary microbiome in association with diabetes and diabetic kidney disease: A systematic review. PLoS One. 2025;20(1): e0317960. doi: 10.1371/journal.pone.0317960 EDN: OUQUTY
- Yang Y, Miao L, Lu Y, et al. The genetics of urinary microbiome, an exploration of the trigger in calcium oxalate stone. Front Genet. 2023;14:1260278. doi: 10.3389/fgene.2023.1260278 EDN: ZXCDVW
- Lemberger U, Pjevac P, Hausmann B, et al. The microbiome of kidney stones and urine of patients with nephrolithiasis. Urolithiasis. 2023;51(1):27. doi: 10.1007/s00240-022-01403-5 EDN: TDANGT
- Chorbińska J, Krajewski W, Karpiński P, et al. Comparison of the microbiome of bladder urine, upper urinary tract urine, and kidney stones in patients with urolithiasis. Cent European J Urol. 2025;78(2):206–220. doi: 10.5173/ceju.2025.0020 EDN: ACCGKO
- Coffey EL, Gomez AM, Burton EN, et al. Characterization of the urogenital microbiome in Miniature Schnauzers with and without calcium oxalate urolithiasis. J Vet Intern Med. 2022;36(4):1341–1352. doi: 10.1111/jvim.16482 EDN: YVVFKU
- Fargue S, Suryavanshi M, Wood KD, et al. Inducing oxalobacter formigenes colonization reduces urinary oxalate in healthy adults. Kidney Int Rep. 2025;10(5):1518–1528. doi: 10.1016/j.ekir.2025.02.004 EDN: TIEFHF
- Gao H, Lin J, Xiong F, et al. Urinary microbial and metabolomic profiles in kidney stone disease. Front Cell Infect Microbiol. 2022;12:953392. doi: 10.3389/fcimb.2022.953392 EDN: RGQLNM
- Grases F, Costa-Bauzá A, Julià F, et al. Evidence of bacterial imprints in different types of non-struvite kidney stones. BMC Urol. 2025;25(1):63. doi: 10.1186/s12894–025–01755–1 EDN: NFQBLU
- Saw JJ, Sivaguru M, Wilson EM, et al. In vivo entombment of bacteria and fungi during calcium oxalate, brushite, and struvite urolithiasis. Kidney360. 2021;2(2):298–311. doi: 10.34067/KID.0006942020 EDN: AANOQF
- Halinski A, Bhatti KH, Boeri L, et al. Spectrum of bacterial pathogens from urinary infections associated with struvite and metabolic stones. Diagnostics (Basel). 2023;13(1):80. doi: 10.3390/diagnostics13010080 EDN: KCIIQD
- Al-Rubaeaee A, Hameed ZC, Al-Tamemi S. Estimation of some plant extract activity against bacterial cystitis isolated from urinary tract infection. In: Update on Bladder Cancer. IntechOpen; 2023. doi: 10.5772/intechopen.107514
- Manzoor MA, Singh B, Agrawal AK, et al. Morphological and micro-tomographic study on evolution of struvite in synthetic urine infected with bacteria and investigation of its pathological biomineralization. PLoS One. 2018;13(8): e0202306. doi: 10.1371/journal.pone.0202306
- Rekha PD, Hameed A, Manzoor MAP, et al. First report of pathogenic bacterium kalamiella piersonii isolated from urine of a kidney stone patient: draft genome and evidence for role in struvite crystallization. Pathogens. 2020;9(9):711. doi: 10.3390/pathogens9090711 EDN: CJBNYM
- Wasfi R, Hamed SM, Amer MA, et al. Proteus mirabilis biofilm: development and therapeutic strategies. Front Cell Infect Microbiol. 2020;10:414. doi: 10.3389/fcimb.2020.00414 EDN: XKXVJF
- Kaman A, Barua SK, Sharma A, et al. Study of differences in urine and stone microbiome and stone composition in patients with staghorn and non-staghorn renal calculi. J Clin Sci Res. 2025;14(3):171–175. doi: 10.4103/jcsr.jcsr_106_24 EDN: CDIRVN
- Saw JJ, Sivaguru M, Wilson EM, et al. In vivo entombment of bacteria and fungi during calcium oxalate, brushite, and struvite urolithiasis. Kidney360. 2021;2(2):298–311. doi: 10.34067/KID.0006942020 EDN: AANOQF
- Yuan T, Xia Y, Li B, et al. Gut microbiota in patients with kidney stones: a systematic review and meta-analysis. BMC Microbiol. 2023;23(1):143. doi: 10.1186/s12866-023-02891-0 EDN: EDOBTL
- Liu Y, Yang A, Zhang Z, et al. A microbiota-based perspective on urinary stone disease: insights from 16S rRNA sequencing and machine learning models. Front Cell Infect Microbiol. 2025;15:1623429. doi: 10.3389/fcimb.2025.1623429 EDN: IIJTZT
- Prywer J, Kozanecki M, Mielniczek-Brzóska E, et al. Solid phases precipitating in artificial urine in the absence and presence of bacteria proteus mirabilis–a contribution to the understanding of infectious urinary stone formation. Crystals (Basel). 2018;8(4):164. doi: 10.3390/cryst8040164 EDN: YGWNSP
- Zaidan N, Wang C, Chen Z, et al. Multiomics assessment of the gut Microbiome in rare hyperoxaluric conditions. Kidney Int Rep. 2024;9(6):1836–1848. doi: 10.1016/j.ekir.2024.03.040 EDN: OOPXSH
- Suryavanshi M, Franklin A, Fargue S, et al. Baseline abundance of oxalate-degrading bacteria determines response to Oxalobacter formigenes probiotic therapy. Gut Microbes. 2025;17(1): 2562337. doi: 10.1080/19490976.2025.2562337 EDN: NZSNNX
- Junier T, Palmieri F, Ubags ND, et al. Prevalence of oxalotrophy in the human microbiome. BMC Genomics. 2025;26(1):954. doi: 10.1186/s12864-025-12113-8 EDN: MICRSA
- De Bellis R, Piacentini MP, Meli MA, et al. In vitro effects on calcium oxalate crystallization kinetics and crystal morphology of an aqueous extract from Ceterach officinarum: Analysis of a potential antilithiatic mechanism. PLoS One. 2019;14(6): e0218734. doi: 10.1371/journal.pone.0218734 EDN: UZGDLA
- Yang X, Li H, Qumu D, et al. Taurine alleviates hyperuricemia-induced nephropathy in rats: insights from microbiome and metabolomics. Front Nutr. 2025;12:1587198. doi: 10.3389/fnut.2025.1587198 EDN: SWQOIE
- Lv Y, Yang X, Sun X, et al. Immune-microbiota dysregulation in maintenance hemodialysis: a 16S rRNA sequencing-based analysis of gut flora and T cell profiles. Ren Fail. 2025;47(1):2498630. doi: 10.1080/0886022X.2025.2498630 EDN: IOMMKG
- Jing J, Yan X, Wang L, et al. Gut microbiota-derived indole-3-acetic acid ameliorates calcium oxalate renal stone formation via AHR/NFκB axis. Urolithiasis. 2025;53(1):134. doi: 10.1007/s00240-025-01779-0 EDN: MZRVPU
- Zhao T, Zhang H, Yin X, et al. Tangshen formula modulates gut Microbiota and reduces gut-derived toxins in diabetic nephropathy rats. Biomed Pharmacother. 2020;129:110325. doi: 10.1016/j.biopha.2020.110325 EDN: WFSLEW
- Liu S, Gao Y, Luo J, et al. Dietary baking soda (NaHCO3) therapy recovered urolithiasis-induced kidney injury in mice by inhibition of oxidative stress, pyroptosis, and inflammation through gut-kidney axis. Ren Fail. 2025;47(1):2521456. doi: 10.1080/0886022X.2025.2521456
- Zhang B, Li T, Qiang Z, et al. Dysbiotic gut microbiota correlates with altered serum and urinary biomarkers in recurrent calcium oxalate stone patients. Int J Gen Med. 2025;18:6497–6506. doi: 10.2147/IJGM.S549804 EDN: EWUQKH
- Zhang L, Zhang TJ, Li Y, et al. Shenqi Yanshen Formula (SQYSF) protects against chronic kidney disease by modulating gut microbiota. Bioengineered. 2022;13(3):5625–5637. doi: 10.1080/21655979.2021.2023789 EDN: CBHVNH
Supplementary files

