İdrar yolu hastalıklarında ve sitokin üretiminde mesane mikrobiyotasının rolü: sistematik bir derleme ve meta-analiz

Abstract

Amaç Bu sistematik inceleme ve meta-analiz yöntemiyle mesane mikrobiyotası ile idrar yolu hastalıkları arasındaki ilişkiyi ve bunların sitokin üretimi üzerindeki etkisini inceleyen literatür değerlendirilmiştir. Yöntemler Çalışma, PRISMA kriterlerine göre tasarlanmıştır. Google Scholar ve PubMed elektronik veritabanlarında arama yapılmış ve potansiyel çalışmalar dahil etme/hariç tutma kriterlerine göre seçilmiştir. Çalışmalar, random effects modeli kullanılarak meta-analize dahil edilmiştir. Önyargı değerlendirmesi için Newcastle-Ottawa Ölçeği (NOS) kullanılmıştır. Sonuçlar Dahil edilen 46 çalışmadan, 2019-2025 yıllarını kapsayan 12 vaka-kontrol çalışması analiz için uygun bulunmuştur. Çalışmaların çoğu Çin ve ABD'de yapılmıştır. Mikrobiyota ve hastalık arasındaki ilişkiyi değerlendiren meta-analizde, birleşik etki büyüklüğü MD = 1,30 (95% CI: -2,18 – 4,78) olarak bulunmuş ve istatistiksel olarak anlamlı bulunmamıştır (Z = 0,73; p = 0,46). Heterojenlik çok yüksek düzeydedir. Sitokin üretimiyle ilgili meta-analizde, birleşik analiz sonucu MD= 21,05 (95% CI: -9,67–51,77) olarak bulunmuştur ve bu fark istatistiksel olarak anlamlı değildir (Z = 1,34, p = 0,18). Çalışmalar arasında çok yüksek düzeyde heterojenlik tespit edilmiştir. Sonuç Dahil edilen çalışmalar orta ila yüksek metodolojik kaliteye sahiptir ve bulguların güvenilirliği kabul edilebilir düzeydedir. Mevcut veriler, değerlendirilen yaklaşımın etkinliği hakkında kesin bir sonuca varmak için yetersizdir. Daha güçlü kanıt elde etmek için, daha büyük örneklem boyutlarına sahip, standartlaştırılmış yöntemler kullanan ve meta-analiz için uygun veriler bildiren ileri çalışmalara ihtiyaç vardır.

Keywords

• Mesane
• Mikrobiyota
• Sitokinler
• Meta-analiz

Supporting Institution

Aydın Adnan Menderes Üniversitesi Bilimsel Araştırma Projeleri Birimi

Project Number

ADU-TPF-23016

Ethical Statement

Çalışmada etik kurul onayı gerekmemektedir.

The role of bladder microbiota in urinary diseases and cytokine production: a systematic review and meta-analysis

Abstract

Purpose: The literature examining the relationship between bladder microbiota and urinary diseases and their effect on cytokine production was evaluated through a systematic review and meta-analysis.

Methods :The study was designed according to PRISMA criteria. Google Scholar and PubMed electronic databases were searched, and potential studies were selected according to inclusion/exclusion criteria. Studies were included in the meta-analysis using a random effects model. The Newcastle–Ottawa Scale (NOS) was used for bias assessment. 

Result: Results Of the 46 studies included, 12 case-control studies covering the years 2019-2025 were deemed suitable for analysis. Most studies were conducted in China and the USA. In the meta-analysis evaluating the relationship between microbiota and disease, the combined effect size was found to be MD = 1.30 (95% CI: -2.18 – 4.78) and was not statistically significant (Z = 0.73; p = 0.46). Heterogeneity is at a very high level. In the meta-analysis regarding cytokine production, the combined analysis result was found to be MD= 21.05 (95% CI: -9.67–51.77), and this difference was not statistically significant (Z = 1.34, p = 0.18). A very high level of heterogeneity was detected among the studies. 

Conclusion: The included studies have moderate to high methodological quality, and the reliability of the findings is at an acceptable level. The current data are insufficient to draw a definitive conclusion about the effectiveness of the approach evaluated. To obtain stronger evidence, advanced studies with larger sample sizes, using standardized methods, and reporting data suitable for meta-analysis are needed.

Keywords

• Urinary bladder
• Microbiota
• Cytokines
• Meta-analysis

Supporting Institution

Aydin Adnan Menderes University Research Grant

Project Number

ADU-TPF-23016

Ethical Statement

Ethical committee approval is not required for this study.

References

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians. 2021;71(3):209-49.
2. 2. Society AC. Key Statistics for Bladder, Cancer 2026 [cited 2026 1 March]. Available from: https://www.cancer.org/cancer/types/bladder-cancer/about/key-statistics.html.
3. 3. Heidar NA, Bhat TA, Shabir U, et al. The urinary microbiome and bladder cancer. Life. 2023;13(3):812.
4. 4. Friedrich V, Choi HW. The urinary microbiome: role in bladder cancer and treatment. Microbiome in Urological Diseases. 2022;12(9):2068.
5. 5. Brubaker L, Wolfe A. The urinary microbiota: a paradigm shift for bladder disorders? Current Opinion in Obstetrics and Gynecology. 2016;28(5):407-12.
6. 6. Wolfe AJ, Brubaker L. “Sterile urine” and the presence of bacteria. European urology. 2015;68(2):173.
7. 7. Ackerman AL, Underhill DM. The mycobiome of the human urinary tract: potential roles for fungi in urology. Annals of Translational Medicine. 2017;5(2):31.
8. 8. Pearce MM, Hilt EE, Rosenfeld AB, et al. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. MBio. 2014;5(4):10.1128/mbio. 01283-14.

9. 9. Santiago-Rodriguez TM, Ly M, Bonilla N, et al. The human urine virome in association with urinary tract infections. Frontiers in microbiology. 2015;6:14.
10. 10. Fouts DE, Pieper R, Szpakowski S, et al. Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury. J Transl Med. 2012;10(1):174.
11. 11. Lewis DA, Brown R, Williams J, et al. The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults. Frontiers in cellular and infection microbiology. 2013;3:41.
12. 12. Alfano M, Canducci F, Nebuloni M, et al. The interplay of extracellular matrix and microbiome in urothelial bladder cancer. Nature Reviews Urology. 2016;13(2):77-90.
13. 13. Kiraly O, Gong G, Olipitz W, et al. Inflammation-induced cell proliferation potentiates DNA damage-induced mutations in vivo. PLoS genetics. 2015;11(2):e1004901.
14. 14. El‐Deeb OS, Atef MM, Hafez YM. The interplay between microbiota‐dependent metabolite trimethylamine N‐oxide, transforming growth factor β/SMAD signaling and inflammasome activation in chronic kidney disease patients: A new mechanistic perspective. Journal of cellular biochemistry. 2019;120(9):14476-85.
15. 15. Jones-Freeman B, Chonwerawong M, Marcelino VR, et al. The microbiome and host mucosal interactions in urinary tract diseases. Mucosal immunology. 2021;14(4):779-92.
16. 16. Institute NC. Cancer Stat Facts: Bladder Cancer. 2026 [cited 2026 6 March ]. Available from: https://seer.cancer.gov/statfacts/html/urinb.html.
17. 17. Pederzoli F, Ferrarese R, Amato V, et al. Sex-specific alterations in the urinary and tissue microbiome in therapy-naïve urothelial bladder cancer patients. European urology oncology. 2020;3(6):784-8.
18. 18. Bonnet M, Buc E, Sauvanet P, et al. Colonization of the human gut by E. coli and colorectal cancer risk. Clinical Cancer Research. 2014;20(4):859-67.
19. 19. Peek Jr RM, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nature Reviews Cancer. 2002;2(1):28-37.
20. 20. Oliva M, Mulet-Margalef N, Ochoa-De-Olza M, et al. Tumor-associated microbiome: where do we stand? International Journal of Molecular Sciences. 2021;22(3):1446.
21. 21. Hussein AA, Smith G, Guru KA. The Association Between the Urinary Microbiome and Bladder Cancer. The Urologic Clinics of North America. 2023;50(1):81-9.
22. 22. Wu P, Zhang G, Zhao J, et al. Profiling the urinary microbiota in male patients with bladder cancer in China. Front Cell Infect Microbiol. 2018;8:167.
23. 23. Naito S, Koga H, Yamaguchi A, et al. Prevention of recurrence with epirubicin and lactobacillus casei after transurethral resection of bladder cancer. The journal of urology. 2008;179(2):485-90.
24. 24. Takahashi T, Kushiro A, Nomoto K, et al. Antitumor effects of the intravesical instillation of heat killed cells of the Lactobacillus casei strain Shirota on the murine orthotopic bladder tumor MBT-2. The Journal of urology. 2001;166(6):2506-11.
25. 25. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Bmj. 2009;339.
26. 26. Wells GA SB, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Assessed March 23, 2026 2026 [Available from: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
27. 27. Liu F, Liu A, Lu X, et al. Dysbiosis signatures of the microbial profile in tissue from bladder cancer. Cancer Medicine. 2019;8(16):6904-14.
28. 28. Moynihan M, Sullivan T, Provenzano K, et al. Urinary microbiome evaluation in patients presenting with hematuria with a focus on exposure to tobacco smoke. Research and Reports in Urology. 2019:359-67.
29. 29. Drage LK, Robson W, Mowbray C, et al. Elevated urine IL-10 concentrations associate with Escherichia coli persistence in older patients susceptible to recurrent urinary tract infections. Immunity & Ageing. 2019;16(1):16.
30. 30. Hussein AA, Elsayed AS, Durrani M, et al., editors. Investigating the association between the urinary microbiome and bladder cancer: An exploratory study. Urologic Oncology: Seminars and Original Investigations; 2021: Elsevier.
31. 31. Pirdel L, Pirdel M. A Case-control Study of Urinary Tract Infection, 25hydroxyvitamin D Status and Associated Inflammatory and Regulatory Responses. Research in Molecular Medicine. 2021;9(1):51-60.
32. 32. Oresta B, Braga D, Lazzeri M, et al. The microbiome of catheter collected urine in males with bladder cancer according to disease stage. The Journal of urology. 2021;205(1):86-93.
33. 33. Sun Y-Y, Ding S-Z. Diversity of urine bacteria in female type 2 diabetes mellitus patients and its correlation with serum IL-6. Chinese Journal of Microecology. 2021.
34. 34. Parra-Grande M, Oré-Arce M, Martínez-Priego L, et al. Profiling the bladder microbiota in patients with bladder cancer. Front Microbiol. 2022;12:718776.
35. 35. Abbas S, Mahdi N, Ahmed K. Blood Groups, IL-6, IL-8 and HS-CRP Levels in Non-Pregnant Women With Urinary Tract Infection Caused by Escherichia coli. 2022;5(2):33-43.
36. 36. Hrbáček J, Tláskal V, Čermák P, et al. Bladder cancer is associated with decreased urinary microbiota diversity and alterations in microbial community composition. Urologic Oncology: Seminars and Original Investigations. 2023;41(2):107. e15-. e22.
37. 37. Guo Y-L, Yu J, Peng W-X, et al. Profiling of urinary tract microbiome and its impact on clinical outcome in patients with urothelial bladder cancer. Chinese Journal of Microecology. 2023.
38. 38. Li N, Wang L, Yang Q, et al. Identification and evaluation of the urinary microbiota associated with bladder cancer. Cancer innovation. 2025;4(4):e70012.
39. 39. Houenstein H, Ramahi Y, Shah AA, et al. MP59-07 Does the urinary microbiome profile change after treatment of bladder cancer? The Journal of Urology. 2022;207(Supplement 5):e1003.
40. 40. Siddiqui H, Nederbragt AJ, Lagesen K, et al. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol. 2011;11(1):244.
41. 41. Klugman Y, Carlson J, Bhat TA, et al. IP14-36 Does the urinary microbiome reflect the bladder-cancer-associated microbiome? characterizing the microbiome in urine and cancer tissue in bladder cancer. The Journal of Urology. 2025;213(5S):e761.
42. 42. Ishaq A, Zahid S, Mukhtar S, et al. Comparative analysis of microbiome of bladder cancer patients. 2020.
43. 43. Mansour B, Monyók Á, Makra N, et al. Bladder cancer-related microbiota: examining differences in urine and tissue samples. Scientific Reports. 2020;10(1):11042.
44. 44. Li J, Zhang Y, He L. The role of urine microbiota in culture-negative patients with pyuria. World J Urol. 2025;43(1):227.
45. 45. Mercier BD, Castro DV, Pal SK. Defining the mycobiome in bladder cancer. European Urology Open Science. 2023;48:70-1.
46. 46. Oudah NA, Ghareeb AKR, Abd Kelkawi AH, et al. Assessment of the binding immunoglobulin protein, il-1β, and some hematological indices in patients with urinary tract infections. Medical Journal of Babylon. 2024;21(3):579-84.
47. 47. Karlsson M, Jass J. Lactobacilli differently regulate expression and secretion of CXCL8 in urothelial cells. Beneficial microbes. 2012;3(3):195-203.
48. 48. Parizadeh M, Arrieta M-C. The global human gut microbiome: genes, lifestyles, and diet. Trends in Molecular Medicine. 2023;29(10):789-801.
49. 49. Colella M, Topi S, Palmirotta R, et al. An overview of the microbiota of the human urinary tract in health and disease: current issues and perspectives. 2023;13(7):1486.
50. 50. Kachroo N, Lange D, Penniston KL, et al. Meta-analysis of clinical microbiome studies in urolithiasis reveal age, stone composition, and study location as the predominant factors in urolithiasis-associated microbiome composition. 2023;12(4):10.1128/mbio. 02007-21.
51. 51. Özkul C, Yalınay M, Karakan TJTTJoG. Islamic fasting leads to an increased abundance of Akkermansia muciniphila and Bacteroides fragilis group: A preliminary study on intermittent fasting. 2019;30(12):1030.