Urinary microbiota changes among NMIBC patients during BCG therapy: comparing BCG responders and non-responders

The gold standard for treating high-risk non-muscle-invasive bladder cancer involves the transurethral removal of cancerous tissue followed by BCG immunotherapy. So far, there is no reliable biomarker for predicting BCG efficacy and identifying patients who will or will not respond to BCG treatment....

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Main Authors: Toni Boban, Blanka Milić Roje, Dora Knezović, Ana Jerončić, Hrvoje Šošić, Marijan Šitum, Janoš Terzić
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1479795/full
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author Toni Boban
Blanka Milić Roje
Dora Knezović
Ana Jerončić
Hrvoje Šošić
Marijan Šitum
Janoš Terzić
author_facet Toni Boban
Blanka Milić Roje
Dora Knezović
Ana Jerončić
Hrvoje Šošić
Marijan Šitum
Janoš Terzić
author_sort Toni Boban
collection DOAJ
description The gold standard for treating high-risk non-muscle-invasive bladder cancer involves the transurethral removal of cancerous tissue followed by BCG immunotherapy. So far, there is no reliable biomarker for predicting BCG efficacy and identifying patients who will or will not respond to BCG treatment. Emerging evidence suggests that urinary microbiota may play a crucial role in BCG efficacy. This study aimed to explore (i) changes in urinary microbiota during the six induction cycles of BCG and (ii) its potential predictive role in determining the outcome of BCG treatment. To this end, catheterized urine samples were collected before each of the six BCG doses and bacterial composition was analyzed using 16S rRNA gene sequencing. Patient inclusion criteria were male gender, no previous history of urothelial cancer, no other malignancies, no active infection, and no antibiotic usage for at least 20 days before the first BCG dose. We observed a significant decrease in biodiversity, measured by the Shannon Index, during the first week of therapy in 10 out of 12 patients (p=0.021). Additionally, differences in microbiota composition before the start of BCG therapy were noted between responders and non-responders to BCG therapy. Non-responders exhibited a 12 times higher abundance of genus Aureispira (p<0.001), and, at the species level, a 27-fold lower abundance of Negativicoccus succinivorans (p<0.001). Throughout the treatment, the abundance of the genus Aureispira decreased, showing an eightfold reduction by the end of therapy among non-responders (p<0.001). Our findings suggest that urinary microbiota plays an active role before and during the course of BCG therapy. However, this is a preliminary study, and further research involving larger patient cohorts is needed.
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spelling doaj-art-d9cc04ad5e48499aa6a31b66621b4ea32025-08-20T02:58:44ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-03-011510.3389/fcimb.2025.14797951479795Urinary microbiota changes among NMIBC patients during BCG therapy: comparing BCG responders and non-respondersToni Boban0Blanka Milić Roje1Dora Knezović2Ana Jerončić3Hrvoje Šošić4Marijan Šitum5Janoš Terzić6Department of Urology, University Hospital of Split, Split, CroatiaLaboratory for Cancer Research, University of Split School of Medicine, Split, CroatiaLaboratory for Cancer Research, University of Split School of Medicine, Split, CroatiaDepartment of Research in Biomedicine and Health, University of Split School of Medicine, Split, CroatiaDepartment of Urology, University Hospital of Split, Split, CroatiaDepartment of Urology, University Hospital of Split, Split, CroatiaLaboratory for Cancer Research, University of Split School of Medicine, Split, CroatiaThe gold standard for treating high-risk non-muscle-invasive bladder cancer involves the transurethral removal of cancerous tissue followed by BCG immunotherapy. So far, there is no reliable biomarker for predicting BCG efficacy and identifying patients who will or will not respond to BCG treatment. Emerging evidence suggests that urinary microbiota may play a crucial role in BCG efficacy. This study aimed to explore (i) changes in urinary microbiota during the six induction cycles of BCG and (ii) its potential predictive role in determining the outcome of BCG treatment. To this end, catheterized urine samples were collected before each of the six BCG doses and bacterial composition was analyzed using 16S rRNA gene sequencing. Patient inclusion criteria were male gender, no previous history of urothelial cancer, no other malignancies, no active infection, and no antibiotic usage for at least 20 days before the first BCG dose. We observed a significant decrease in biodiversity, measured by the Shannon Index, during the first week of therapy in 10 out of 12 patients (p=0.021). Additionally, differences in microbiota composition before the start of BCG therapy were noted between responders and non-responders to BCG therapy. Non-responders exhibited a 12 times higher abundance of genus Aureispira (p<0.001), and, at the species level, a 27-fold lower abundance of Negativicoccus succinivorans (p<0.001). Throughout the treatment, the abundance of the genus Aureispira decreased, showing an eightfold reduction by the end of therapy among non-responders (p<0.001). Our findings suggest that urinary microbiota plays an active role before and during the course of BCG therapy. However, this is a preliminary study, and further research involving larger patient cohorts is needed.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1479795/fullurinary microbiomenon-muscle invasive bladder cancerBCGresponse to therapyimmunotherapy
spellingShingle Toni Boban
Blanka Milić Roje
Dora Knezović
Ana Jerončić
Hrvoje Šošić
Marijan Šitum
Janoš Terzić
Urinary microbiota changes among NMIBC patients during BCG therapy: comparing BCG responders and non-responders
Frontiers in Cellular and Infection Microbiology
urinary microbiome
non-muscle invasive bladder cancer
BCG
response to therapy
immunotherapy
title Urinary microbiota changes among NMIBC patients during BCG therapy: comparing BCG responders and non-responders
title_full Urinary microbiota changes among NMIBC patients during BCG therapy: comparing BCG responders and non-responders
title_fullStr Urinary microbiota changes among NMIBC patients during BCG therapy: comparing BCG responders and non-responders
title_full_unstemmed Urinary microbiota changes among NMIBC patients during BCG therapy: comparing BCG responders and non-responders
title_short Urinary microbiota changes among NMIBC patients during BCG therapy: comparing BCG responders and non-responders
title_sort urinary microbiota changes among nmibc patients during bcg therapy comparing bcg responders and non responders
topic urinary microbiome
non-muscle invasive bladder cancer
BCG
response to therapy
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1479795/full
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