{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:56:07Z","timestamp":1789682167856,"version":"4.0.1"},"reference-count":123,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"publisher","award":["MA120172B88445A7"],"award-info":[{"award-number":["MA120172B88445A7"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"publisher","award":["RD12318AAABE3A08"],"award-info":[{"award-number":["RD12318AAABE3A08"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>The human bladder hosts a resident, low-biomass microbial community (urobiota) that has only become the subject of intense investigation in the last 15 years. The advantages that the urobiota may confer to the bladder, in contrast to the microbiota of other mucosal sites, remain to be elucidated. Alterations in the urobiota have been associated with various pathological urogenital conditions, including urinary tract infections (UTIs) and recurrent UTIs. A potential link between bladder cancer (BC), the ninth most common human cancer by incidence worldwide, and a dysbiotic urobiota is still unclear and represents an emerging field of study. In this review, we focus on recent studies that not only analyzed the urobiota of BC patients using urine specimens to identify biomarkers and microbial signatures of the disease, but also monitored therapeutic responses to therapies. We also discuss novel techniques of culturing, such as culturomics, animal models of BC, and 3D organotypic models. Furthermore, we review studies on the gut\u2013bladder axis which, though still limited, already suggest that diet- and gut-derived bacterial metabolites can influence BC progression and individual responses to therapy.<\/jats:p>","DOI":"10.3390\/ijms262110558","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"10558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Urinary Microbiota and the Gut\u2013Bladder Axis in Bladder Cancer"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6987-3393","authenticated-orcid":false,"given":"Usman Akhtar","family":"Butt","sequence":"first","affiliation":[{"name":"Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8118-9807","authenticated-orcid":false,"given":"Daniela","family":"De Biase","sequence":"additional","affiliation":[{"name":"Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Berg, G., Rybakova, D., Fischer, D., Cernava, T., Verges, M.C., Charles, T., Chen, X., Cocolin, L., Eversole, K., and Corral, G.H. (2020). Microbiome definition re-visited: Old concepts and new challenges. Microbiome, 8.","DOI":"10.1186\/s40168-020-00875-0"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1128\/JCM.02876-13","article-title":"Urine is not sterile: Use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder","volume":"52","author":"Hilt","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e01283-14","DOI":"10.1128\/mBio.01283-14","article-title":"The female urinary microbiome: A comparison of women with and without urgency urinary incontinence","volume":"5","author":"Pearce","year":"2014","journal-title":"mBio"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.cmi.2022.08.010","article-title":"The urobiome in men and women: A clinical review","volume":"29","author":"Roth","year":"2023","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lewis, D.A., Brown, R., Williams, J., White, P., Jacobson, S.K., Marchesi, J.R., and Drake, M.J. (2013). The human urinary microbiome; bacterial DNA in voided urine of asymptomatic adults. Front. Cell. Infect. Microbiol., 3.","DOI":"10.3389\/fcimb.2013.00041"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.ajog.2015.05.032","article-title":"The new world of the urinary microbiota in women","volume":"213","author":"Brubaker","year":"2015","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Siddiqui, H., Nederbragt, A.J., Lagesen, K., Jeansson, S.L., and Jakobsen, K.S. (2011). Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-244"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s11884-019-00543-6","article-title":"The Bladder is Not Sterile: An Update on the Urinary Microbiome","volume":"14","author":"Ackerman","year":"2019","journal-title":"Curr. Bladder Dysfunct. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41385-020-00372-5","article-title":"The microbiome and host mucosal interactions in urinary tract diseases","volume":"14","author":"Chonwerawong","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, J., Lei, Y., Du, H., Li, Z., Wang, X., Yang, D., Gao, F., and Li, J. (2025). Exploring urinary microbiome: Insights into neurogenic bladder and improving management of urinary tract infections. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1512891"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jpurol.2022.02.025","article-title":"A Child\u2019s urine is not sterile: A pilot study evaluating the Pediatric Urinary Microbiome","volume":"18","author":"Storm","year":"2022","journal-title":"J. Pediatr. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hadjifrangiskou, M., Reasoner, S., Flores, V., Van Horn, G., Morales, G., Peard, L., Abelson, B., Manuel, C., Lee, J., and Baker, B. (2023). Defining the Infant Male Urobiome and Moving Towards Mechanisms in Urobiome Research. Res. Sq.","DOI":"10.21203\/rs.3.rs-2618137\/v1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.jpurol.2024.05.016","article-title":"Characterization of pediatric urinary microbiome at species-level resolution indicates variation due to sex, age, and urologic history","volume":"20","author":"Kelly","year":"2024","journal-title":"J. Pediatr. Urol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/INF.0000000000002622","article-title":"Assessment of the Urinary Microbiome in Children Younger Than 48 Months","volume":"39","author":"Kinneman","year":"2020","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.tim.2018.09.008","article-title":"The Human Microbiome and Child Growth\u2014First 1000 Days and Beyond","volume":"27","author":"Robertson","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"154.E1","DOI":"10.1016\/j.ajog.2019.08.011","article-title":"Defining the relationship between vaginal and urinary microbiomes","volume":"222","author":"Komesu","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Thomas-White, K., Forster, S.C., Kumar, N., Van Kuiken, M., Putonti, C., Stares, M.D., Hilt, E.E., Price, T.K., Wolfe, A.J., and Lawley, T.D. (2018). Culturing of female bladder bacteria reveals an interconnected urogenital microbiota. Nat. Commun., 9.","DOI":"10.1038\/s41467-018-03968-5"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Jeries, L.M., Sysoeva, T.A., Karstens, L., and Kelly, M.S. (2024). Synthesis of current pediatric urinary microbiome research. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1396408"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Colella, M., Topi, S., Palmirotta, R., D\u2019Agostino, D., Charitos, I.A., Lovero, R., and Santacroce, L. (2023). An Overview of the Microbiota of the Human Urinary Tract in Health and Disease: Current Issues and Perspectives. Life, 13.","DOI":"10.3390\/life13071486"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Perez-Carrasco, V., Soriano-Lerma, A., Soriano, M., Gutierrez-Fernandez, J., and Garcia-Salcedo, J.A. (2021). Urinary Microbiome: Yin and Yang of the Urinary Tract. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.617002"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e14626","DOI":"10.1111\/iwj.14626","article-title":"Evolution of the urinary microbiota in spinal cord injury patients with decubitus ulcer: A snapshot study","volume":"21","author":"Morsli","year":"2024","journal-title":"Int. Wound J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.euf.2018.08.001","article-title":"Male Bladder Microbiome Relates to Lower Urinary Tract Symptoms","volume":"6","author":"Bajic","year":"2020","journal-title":"Eur. Urol. Focus"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1002\/nau.24707","article-title":"Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women","volume":"40","author":"Burnett","year":"2021","journal-title":"Neurourol. Urodyn."},{"key":"ref_24","first-page":"7","article-title":"Urine microbiota differ in bladder cancer","volume":"20","author":"Stone","year":"2023","journal-title":"Nat. Rev. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wu, P., Zhang, G., Zhao, J., Chen, J., Chen, Y., Huang, W., Zhong, J., and Zeng, J. (2018). Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China. Front. Cell. Infect. Microbiol., 8.","DOI":"10.3389\/fcimb.2018.00429"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"190","DOI":"10.5213\/inj.2244016.008","article-title":"The Urobiome and Its Role in Overactive Bladder","volume":"26","author":"Bae","year":"2022","journal-title":"Int. Neurourol. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ejogrb.2018.06.011","article-title":"Age, menopausal status and the bladder microbiome","volume":"228","author":"Curtiss","year":"2018","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11908-016-0522-0","article-title":"Urine Culture in Uncomplicated UTI: Interpretation and Significance","volume":"18","author":"Stapleton","year":"2016","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Saginala, K., Barsouk, A., Aluru, J.S., Rawla, P., Padala, S.A., and Barsouk, A. (2020). Epidemiology of Bladder Cancer. Med. Sci., 8.","DOI":"10.3390\/medsci8010015"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/s41585-022-00611-3","article-title":"Bladder cancer, inflammageing and microbiomes","volume":"19","author":"Martin","year":"2022","journal-title":"Nat. Rev. Urol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.juro.2016.06.049","article-title":"Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA\/SUO Guideline","volume":"196","author":"Chang","year":"2016","journal-title":"J. Urol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1001\/jama.2020.17598","article-title":"Bladder Cancer: A Review","volume":"324","author":"Lenis","year":"2020","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Grabe-Heyne, K., Henne, C., Mariappan, P., Geiges, G., Pohlmann, J., and Pollock, R.F. (2023). Intermediate and high-risk non-muscle-invasive bladder cancer: An overview of epidemiology, burden, and unmet needs. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1170124"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.eururo.2007.10.006","article-title":"Prognostic factors in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin: Multivariate analysis of data from four randomized CUETO trials","volume":"53","author":"Solsona","year":"2008","journal-title":"Eur. Urol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3233\/BLC-180175","article-title":"Immunology, Immunotherapy, and Translating Basic Science into the Clinic for Bladder Cancer","volume":"4","author":"Ingersoll","year":"2018","journal-title":"Bladder Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.euo.2020.08.013","article-title":"Sex Differences in Bladder Cancer Immunobiology and Outcomes: A Collaborative Review with Implications for Treatment","volume":"3","author":"Koti","year":"2020","journal-title":"Eur. Urol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.eururo.2012.07.033","article-title":"Epidemiology and risk factors of urothelial bladder cancer","volume":"63","author":"Burger","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.eururo.2022.11.011","article-title":"Re: Oncological Benefit of Re-resection for T1 Bladder Cancer: A Comparative Effectiveness Study","volume":"83","author":"Babjuk","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.eururo.2011.07.010","article-title":"Smoking status is a risk factor for recurrence after transurethral resection of non-muscle-invasive bladder cancer","volume":"60","author":"Lammers","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.urolonc.2011.10.010","article-title":"Bladder cancer risk from occupational and environmental exposures","volume":"30","author":"Kiriluk","year":"2012","journal-title":"Urol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1128\/CMR.12.1.97","article-title":"Relationship between schistosomiasis and bladder cancer","volume":"12","author":"Mostafa","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41392-023-01693-0","article-title":"Intratumoural microbiota: A new frontier in cancer development and therapy","volume":"9","author":"Cao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/bjc.2015.465","article-title":"Epidemiologic studies of the human microbiome and cancer","volume":"114","author":"Vogtmann","year":"2016","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1158\/1940-6207.CAPR-16-0249","article-title":"The Human Microbiome and Cancer","volume":"10","author":"Rajagopala","year":"2017","journal-title":"Cancer Prev. Res."},{"key":"ref_45","first-page":"307","article-title":"Multidisciplinary Management of Muscle-Invasive Bladder Cancer: Current Challenges and Future Directions","volume":"Volume 38","author":"Werntz","year":"2018","journal-title":"American Society of Clinical Oncology Educational Book, Proceedings of the 2018 ASCO Annual Meeting, Chicago, IL, USA, 1\u20135 June 2018"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zeng, J., Zhang, G., Chen, C., Li, K., Wen, Y., Zhao, J., and Wu, P. (2020). Alterations in Urobiome in Patients With Bladder Cancer and Implications for Clinical Outcome: A Single-Institution Study. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.555508"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.semcancer.2021.12.010","article-title":"Urinary microbiota and bladder cancer: A systematic review and a focus on uropathogens","volume":"86","author":"Yacouba","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.urolonc.2020.04.014","article-title":"Characterization of urinary microbiome in patients with bladder cancer: Results from a single-institution, feasibility study","volume":"38","author":"Chipollini","year":"2020","journal-title":"Urol. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1099\/jmm.0.001058","article-title":"Urinary microbiota\u2014A potential biomarker and therapeutic target for bladder cancer","volume":"68","author":"Bi","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bucevic Popovic, V., Situm, M., Chow, C.T., Chan, L.S., Roje, B., and Terzic, J. (2018). The urinary microbiome associated with bladder cancer. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-29054-w"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Friedrich, V., and Choi, H.W. (2022). The Urinary Microbiome: Role in Bladder Cancer and Treatment. Diagnostics, 12.","DOI":"10.3390\/diagnostics12092068"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1097\/JU.0000000000001336","article-title":"The Microbiome of Catheter Collected Urine in Males with Bladder Cancer According to Disease Stage","volume":"205","author":"Oresta","year":"2021","journal-title":"J. Urol."},{"key":"ref_53","first-page":"57","article-title":"Mini-review: Perspective of the microbiome in the pathogenesis of urothelial carcinoma","volume":"2","author":"Xu","year":"2014","journal-title":"Am. J. Clin. Exp. Urol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mai, G., Chen, L., Li, R., Liu, Q., Zhang, H., and Ma, Y. (2019). Common Core Bacterial Biomarkers of Bladder Cancer Based on Multiple Datasets. BioMed Res. Int., 2019.","DOI":"10.1155\/2019\/4824909"},{"key":"ref_55","first-page":"359","article-title":"Urinary Microbiome Evaluation in Patients Presenting with Hematuria with a Focus on Exposure to Tobacco Smoke","volume":"11","author":"Moynihan","year":"2019","journal-title":"Res. Rep. Urol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mansour, B., Monyok, A., Makra, N., Gajdacs, M., Vadnay, I., Ligeti, B., Juhasz, J., Szabo, D., and Ostorhazi, E. (2020). Bladder cancer-related microbiota: Examining differences in urine and tissue samples. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-67443-2"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.euo.2020.04.002","article-title":"Sex-specific Alterations in the Urinary and Tissue Microbiome in Therapy-naive Urothelial Bladder Cancer Patients","volume":"3","author":"Pederzoli","year":"2020","journal-title":"Eur. Urol. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hourigan, S.K., Zhu, W., W, S.W.W., Clemency, N.C., Provenzano, M., Vilboux, T., Niederhuber, J.E., Deeken, J., Chung, S., and McDaniel-Wiley, K. (2020). Studying the urine microbiome in superficial bladder cancer: Samples obtained by midstream voiding versus cystoscopy. BMC Urol., 20.","DOI":"10.1186\/s12894-020-0576-z"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"370.e9","DOI":"10.1016\/j.urolonc.2020.12.011","article-title":"Investigating the association between the urinary microbiome and bladder cancer: An exploratory study","volume":"39","author":"Hussein","year":"2021","journal-title":"Urol. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ma, W., Zhang, W., Shen, L., Liu, J., Yang, F., Maskey, N., Wang, H., Zhang, J., Yan, Y., and Yao, X. (2021). Can Smoking Cause Differences in Urine Microbiome in Male Patients With Bladder Cancer? A Retrospective Study. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.677605"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Qiu, J., Liu, J., Zhong, Y., Liu, W., Zhou, Z., Li, Y., and Li, S. (2022). Analysis of Urinary Flora Characteristics in Urinary Tumor Based on 16S rRNA Sequence. BioMed Res. Int., 2022.","DOI":"10.1155\/2022\/9368687"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"11795549231206796","DOI":"10.1177\/11795549231206796","article-title":"Is the Urinary and Gut Microbiome Associated With Bladder Cancer?","volume":"17","author":"Chorbinska","year":"2023","journal-title":"Clin. Med. Insights Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.3390\/biom5031762","article-title":"Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology","volume":"5","author":"Grasso","year":"2015","journal-title":"Biomolecules"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s11523-019-00643-7","article-title":"The Urinary Microbiome and Anticancer Immunotherapy: The Potentially Hidden Role of Unculturable Microbes","volume":"14","author":"Bersanelli","year":"2019","journal-title":"Target. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.ccell.2021.04.008","article-title":"Intratumoral bacteria generate a new class of therapeutically relevant tumor antigens in melanoma","volume":"39","author":"Carter","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"101015","DOI":"10.1016\/j.lanmic.2024.101015","article-title":"Geographical variation in the incidence of colorectal cancer and urinary tract cancer is associated with population exposure to colibactin-producing Escherichia coli","volume":"6","author":"Maklin","year":"2025","journal-title":"Lancet Microbe"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e70012","DOI":"10.1002\/cai2.70012","article-title":"Identification and Evaluation of the Urinary Microbiota Associated With Bladder Cancer","volume":"4","author":"Li","year":"2025","journal-title":"Cancer Innov."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e04688","DOI":"10.1002\/advs.202504688","article-title":"Gut Parabacteroides distasonis-derived Indole-3-Acetic Acid Promotes Phospholipid Remodeling and Enhances Ferroptosis Sensitivity via the AhR-FASN Axis in Bladder Cancer","volume":"12","author":"Li","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1007\/s12672-025-03219-2","article-title":"Causal relationships between gut microbiota and urothelial carcinoma mediated by inflammatory cytokines and blood cell traits identified through Mendelian randomization analysis","volume":"16","author":"Wu","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/nrurol.2015.292","article-title":"The interplay of extracellular matrix and microbiome in urothelial bladder cancer","volume":"13","author":"Alfano","year":"2016","journal-title":"Nat. Rev. Urol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.1128\/iai.64.9.3646-3651.1996","article-title":"Novel pathogenic mechanism of microbial metalloproteinases: Liberation of membrane-anchored molecules in biologically active form exemplified by studies with the human interleukin-6 receptor","volume":"64","author":"Vollmer","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1128\/iai.56.11.2925-2932.1988","article-title":"Pseudomonas aeruginosa alkaline protease degrades human gamma interferon and inhibits its bioactivity","volume":"56","author":"Horvat","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Min, K., Kim, H.T., Lee, E.H., Park, H., and Ha, Y.S. (2022). Bacteria for Treatment: Microbiome in Bladder Cancer. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081783"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Jiang, S., and Redelman-Sidi, G. (2022). BCG in Bladder Cancer Immunotherapy. Cancers, 14.","DOI":"10.3390\/cancers14133073"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e0051821","DOI":"10.1128\/msystems.00518-21","article-title":"Species-Level Resolution of Female Bladder Microbiota from 16S rRNA Amplicon Sequencing","volume":"6","author":"Hoffman","year":"2021","journal-title":"mSystems"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Jung, C.E., Chopyk, J., Shin, J.H., Lukacz, E.S., Brubaker, L., Schwanemann, L.K., Knight, R., Wolfe, A.J., and Pride, D.T. (2019). Benchmarking urine storage and collection conditions for evaluating the female urinary microbiome. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49823-5"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Bundgaard-Nielsen, C., Ammitzboll, N., Isse, Y.A., Muqtar, A., Jensen, A.M., Leutscher, P.D.C., Arenholt, L.T.S., Hagstrom, S., and Sorensen, S. (2020). Voided Urinary Microbiota Is Stable Over Time but Impacted by Post Void Storage. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00435"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.euf.2016.11.001","article-title":"The Urinary Tract Microbiome in Health and Disease","volume":"4","author":"Aragon","year":"2018","journal-title":"Eur. Urol. Focus"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1128\/JCM.05852-11","article-title":"Evidence of uncultivated bacteria in the adult female bladder","volume":"50","author":"Wolfe","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.forsciint.2018.03.035","article-title":"Simple DNA extraction of urine samples: Effects of storage temperature and storage time","volume":"287","author":"Ng","year":"2018","journal-title":"Forensic Sci. Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.urology.2019.01.031","article-title":"Financial Burden of Recurrent Urinary Tract Infections in Women: A Time-driven Activity-based Cost Analysis","volume":"128","author":"Gaitonde","year":"2019","journal-title":"Urology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1001\/archinte.1957.00260110025004","article-title":"Bacteriuria and the diagnosis of infections of the urinary tract; with observations on the use of methionine as a urinary antiseptic","volume":"100","author":"Kass","year":"1957","journal-title":"AMA Arch. Intern. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1038\/s41467-018-03968-5","article-title":"Culturing of female bladder bacteria reveals an interconnected urogenital microbiota","volume":"9","author":"Forster","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1128\/JCM.00044-16","article-title":"The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms","volume":"54","author":"Price","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.euo.2022.03.006","article-title":"Microbiomes of Urine and the Prostate Are Linked to Human Prostate Cancer Risk Groups","volume":"5","author":"Hurst","year":"2022","journal-title":"Eur. Urol. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1128\/CMR.00014-14","article-title":"The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota","volume":"28","author":"Lagier","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"9768","DOI":"10.1073\/pnas.1404753111","article-title":"Gene-targeted microfluidic cultivation validated by isolation of a gut bacterium listed in Human Microbiome Project\u2019s Most Wanted taxa","volume":"111","author":"Ma","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Ugarcina Perovic, S., Ksiezarek, M., Rocha, J., Cappelli, E.A., Sousa, M., Ribeiro, T.G., Grosso, F., and Peixe, L. (2022). Urinary Microbiome of Reproductive-Age Asymptomatic European Women. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.01308-22"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Baddoo, G., Ene, A., Merchant, Z., Banerjee, S., Wolfe, A.J., and Putonti, C. (2023). Cataloging variation in 16S rRNA gene sequences of female urobiome bacteria. Front. Urol., 3.","DOI":"10.3389\/fruro.2023.1270509"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41579-018-0041-0","article-title":"Culturing the human microbiota and culturomics","volume":"16","author":"Lagier","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.cmi.2017.04.004","article-title":"Women with symptoms of a urinary tract infection but a negative urine culture: PCR-based quantification of Escherichia coli suggests infection in most cases","volume":"23","author":"Heytens","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.cell.2014.06.037","article-title":"Conducting a microbiome study","volume":"158","author":"Goodrich","year":"2014","journal-title":"Cell"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jbiotec.2016.12.022","article-title":"Application of next generation sequencing in clinical microbiology and infection prevention","volume":"243","author":"Deurenberg","year":"2017","journal-title":"J. Biotechnol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.ijantimicag.2019.09.009","article-title":"Shotgun metagenomics for microbiome and resistome detection in septic patients with urinary tract infection","volume":"54","author":"Barraud","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1128\/JCM.02452-13","article-title":"Rapid whole-genome sequencing for detection and characterization of microorganisms directly from clinical samples","volume":"52","author":"Hasman","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1534\/genetics.119.302336","article-title":"The Impact of Genomic and Traditional Selection on the Contribution of Mutational Variance to Long-Term Selection Response and Genetic Variance","volume":"213","author":"Mulder","year":"2019","journal-title":"Genetics"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Moustafa, A., Li, W., Singh, H., Moncera, K.J., Torralba, M.G., Yu, Y., Manuel, O., Biggs, W., Venter, J.C., and Nelson, K.E. (2018). Microbial metagenome of urinary tract infection. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22660-8"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1242\/dmm.017400","article-title":"How informative is the mouse for human gut microbiota research?","volume":"8","author":"Nguyen","year":"2015","journal-title":"Dis. Models Mech."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/s41388-017-0099-6","article-title":"A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer","volume":"37","author":"Fantini","year":"2018","journal-title":"Oncogene"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1002\/ijc.35295","article-title":"A novel mouse model of upper tract urothelial carcinoma highlights the impact of dietary intervention on gut microbiota and carcinogenesis prevention despite carcinogen exposure","volume":"156","author":"Yamamoto","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s13206-023-00103-5","article-title":"Advanced Organotypic In Vitro Model Systems for Host-Microbial Coculture","volume":"17","author":"Kim","year":"2023","journal-title":"BioChip J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5483\/BMBRep.2022-0210","article-title":"Stem cells, organoids and their applications for human diseases: Special issue of BMB Reports in 2023","volume":"56","author":"Shin","year":"2023","journal-title":"BMB Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1111\/j.1524-4725.2009.01238.x","article-title":"Use of tissue-engineered skin to study in vitro biofilm development","volume":"35","author":"Charles","year":"2009","journal-title":"Dermatol. Surg."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2158034","DOI":"10.1080\/19490976.2022.2158034","article-title":"In vitro and ex vivo modeling of enteric bacterial infections","volume":"15","author":"Taebnia","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1186\/s12957-025-03948-2","article-title":"Harnessing organoid technology in urological cancer: Advances and applications in urinary system tumors","volume":"23","author":"Wang","year":"2025","journal-title":"World J. Surg. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Chae, S., Kim, J., Yi, H.G., and Cho, D.W. (2022). 3D Bioprinting of an In Vitro Model of a Biomimetic Urinary Bladder with a Contract-Release System. Micromachines, 13.","DOI":"10.3390\/mi13020277"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.actbio.2016.12.008","article-title":"3D bioprinting of urethra with PCL\/PLCL blend and dual autologous cells in fibrin hydrogel: An in vitro evaluation of biomimetic mechanical property and cell growth environment","volume":"50","author":"Zhang","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Mingdong, W., Xiang, G., Yongjun, Q., Mingshuai, W., and Hao, P. (2023). Causal associations between gut microbiota and urological tumors: A two-sample mendelian randomization study. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11383-3"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"267.e9","DOI":"10.1016\/j.urolonc.2024.10.014","article-title":"Causal relationship between bladder cancer and gut microbiota contributes to the gut-bladder axis: A two-sample Mendelian randomization study","volume":"43","author":"Yang","year":"2025","journal-title":"Urol. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s12957-025-03822-1","article-title":"Causal effect of gut microbiota on the risk of cancer and potential mediation by inflammatory proteins","volume":"23","author":"Wang","year":"2025","journal-title":"World J. Surg. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1158\/2767-9764.CRC-23-0479","article-title":"Role of Gut Microbiome in Neoadjuvant Chemotherapy Response in Urothelial Carcinoma: A Multi-institutional Prospective Cohort Evaluation","volume":"4","author":"Bukavina","year":"2024","journal-title":"Cancer Res. Commun."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Wang, B., Qiu, Y., Xie, M., Huang, P., Yu, Y., Sun, Q., Shangguan, W., Li, W., Zhu, Z., and Xue, J. (2024). Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses. BMC Microbiol., 24.","DOI":"10.1186\/s12866-024-03372-8"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Zou, J., Xu, B., Luo, P., Chen, T., and Duan, H. (2024). Non-coding RNAs in bladder cancer, a bridge between gut microbiota and host?. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1482765"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-chain fatty acids: Linking diet, the microbiome and immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"101128","DOI":"10.1016\/j.neo.2025.101128","article-title":"Microbial molecules, metabolites, and malignancy","volume":"60","author":"Thomas","year":"2025","journal-title":"Neoplasia"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Tsvetikova, S.A., and Koshel, E.I. (2020). Microbiota and cancer: Host cellular mechanisms activated by gut microbial metabolites. Int. J. Med. Microbiol. IJMM, 310.","DOI":"10.1016\/j.ijmm.2020.151425"},{"key":"ref_117","first-page":"395","article-title":"Gut microbial composition changes in bladder cancer patients: A case-control study in Harbin, China","volume":"29","author":"He","year":"2020","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Then, C.K., Paillas, S., Moomin, A., Misheva, M.D., Moir, R.A., Hay, S.M., Bremner, D., Roberts Nee Nellany, K.S., Smith, E.E., and Heidari, Z. (2024). Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity. Microbiome, 12.","DOI":"10.21203\/rs.3.rs-2686427\/v1"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Then, C.K., Paillas, S., Wang, X., Hampson, A., and Kiltie, A.E. (2020). Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation. BMC Biol., 18.","DOI":"10.1186\/s12915-020-00836-x"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.mrgentox.2011.11.015","article-title":"Tissue-specific mutagenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine as the basis for urothelial carcinogenesis","volume":"742","author":"He","year":"2012","journal-title":"Mutat. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1038\/s41586-024-07754-w","article-title":"Gut microbiota carcinogen metabolism causes distal tissue tumours","volume":"632","author":"Roje","year":"2024","journal-title":"Nature"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2166\/wst.2007.560","article-title":"Reducing micropollutants with source control: Substance flow analysis of 212 pharmaceuticals in faeces and urine","volume":"56","author":"Lienert","year":"2007","journal-title":"Water Sci. Technol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"424","DOI":"10.2533\/chimia.2023.424","article-title":"Microbial Biocatalysis within Us: The Underexplored Xenobiotic Biotransformation Potential of the Urinary Tract Microbiota","volume":"77","author":"Marti","year":"2023","journal-title":"Chimia"}],"updated-by":[{"DOI":"10.3390\/ijms27031521","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000}}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10558\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T09:03:29Z","timestamp":1770195809000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10558"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":123,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110558"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110558","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,30]]}}}