Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer

IntroductionIntravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently...

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Main Authors: Christopher James, Kayeromi Gomez, Shalin Desai, Hiten D. Patel, Goran Rac, Chirag P. Doshi, Ryan Dornbier, Petar Bajic, Thomas Halverson, Gopal N. Gupta, Marcus L. Quek, Alex Gorbonos, Robert Flanigan, Alan J. Wolfe
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-04-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125809/full
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author Christopher James
Kayeromi Gomez
Shalin Desai
Hiten D. Patel
Hiten D. Patel
Goran Rac
Chirag P. Doshi
Ryan Dornbier
Petar Bajic
Petar Bajic
Petar Bajic
Thomas Halverson
Gopal N. Gupta
Marcus L. Quek
Alex Gorbonos
Robert Flanigan
Alan J. Wolfe
Alan J. Wolfe
author_facet Christopher James
Kayeromi Gomez
Shalin Desai
Hiten D. Patel
Hiten D. Patel
Goran Rac
Chirag P. Doshi
Ryan Dornbier
Petar Bajic
Petar Bajic
Petar Bajic
Thomas Halverson
Gopal N. Gupta
Marcus L. Quek
Alex Gorbonos
Robert Flanigan
Alan J. Wolfe
Alan J. Wolfe
author_sort Christopher James
collection DOAJ
description IntroductionIntravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC.MethodsPatients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated.ResultsAcross the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort.ConclusionIVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.
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spelling doaj.art-51dde925de874143b962cf99bf0678392023-04-05T13:24:02ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882023-04-011310.3389/fcimb.2023.11258091125809Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancerChristopher James0Kayeromi Gomez1Shalin Desai2Hiten D. Patel3Hiten D. Patel4Goran Rac5Chirag P. Doshi6Ryan Dornbier7Petar Bajic8Petar Bajic9Petar Bajic10Thomas Halverson11Gopal N. Gupta12Marcus L. Quek13Alex Gorbonos14Robert Flanigan15Alan J. Wolfe16Alan J. Wolfe17Loyola University Medical Center, Department of Urology, Maywood, IL, United StatesDepartment of Hematology/Oncology, Loyola University Chicago, Stritch School of Medicine Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesDepartment of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesDepartment of Urology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, United StatesLoyola University Chicago, Department of Microbiology and Immunology, Maywood, IL, United StatesLoyola University Chicago, Department of Microbiology and Immunology, Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesLoyola University Medical Center, Department of Urology, Maywood, IL, United StatesDepartment of Urology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, United StatesLoyola University Chicago, Department of Microbiology and Immunology, Maywood, IL, United StatesIntroductionIntravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC.MethodsPatients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated.ResultsAcross the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort.ConclusionIVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125809/fullBacillus Calmette-Guérin (BCG)intravesical therapymicrobiomebladder cancerintravesical gemcitabine
spellingShingle Christopher James
Kayeromi Gomez
Shalin Desai
Hiten D. Patel
Hiten D. Patel
Goran Rac
Chirag P. Doshi
Ryan Dornbier
Petar Bajic
Petar Bajic
Petar Bajic
Thomas Halverson
Gopal N. Gupta
Marcus L. Quek
Alex Gorbonos
Robert Flanigan
Alan J. Wolfe
Alan J. Wolfe
Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer
Frontiers in Cellular and Infection Microbiology
Bacillus Calmette-Guérin (BCG)
intravesical therapy
microbiome
bladder cancer
intravesical gemcitabine
title Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer
title_full Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer
title_fullStr Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer
title_full_unstemmed Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer
title_short Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer
title_sort impact of intravesical bacillus calmette guerin and chemotherapy on the bladder microbiome in patients with non muscle invasive bladder cancer
topic Bacillus Calmette-Guérin (BCG)
intravesical therapy
microbiome
bladder cancer
intravesical gemcitabine
url https://www.frontiersin.org/articles/10.3389/fcimb.2023.1125809/full
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