Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer.
Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer.
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DOI：
10.3389/fcimb.2023.1125809
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发表时间：
2023
影响因子：
5.7
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中科院分区：
文献类型：
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膀胱内治疗（IVT），包括卡介苗（BCG），是高级别（HG）非肌层浸润性膀胱癌（NMIBC）的标准治疗。尽管使用IVT，但许多患者在治疗后复发。膀胱微生物组及其在疾病过程中的作用最近变得突出。我们的目的是描述膀胱内治疗过程中膀胱微生物组发生的变化，并评估这些变化是否与NMIBC患者的结局相关。2019年1月至2020年3月前瞻性入组接受诱导BCG或膀胱内治疗的NMIBC患者。排除入组时临床T2或更高病理学或活动性尿路感染的患者。29例患者在诱导膀胱内治疗前和每次IVT滴注前采集了插管（膀胱）尿液样本。27例接受BCG治疗，2例接受吉西他滨膀胱灌注治疗。使用16 S核糖体RNA基因测序鉴定细菌。评估了膀胱微生物组的变化，并研究了IVT后复发患者和未复发患者之间的差异。在分析的29例患者中，膀胱内治疗后细菌丰富度显著降低（丰富度，P=0.01）。均匀度和总体多样性没有显著变化（Pielou，P=0.62; Shannon，P=0.13）。复发患者尿液中气球菌相对丰度较高（P<0.01），而未复发患者尿液中脲原体（P=0.01）和大肠杆菌/志贺菌（P=0.05）明显较多。α多样性水平降低的患者更有可能属于非复发队列。NMIBC的IVT似乎通过降低丰富度而改变了尿液微生物组，同时不改变均匀性或整体多样性。气球菌属的存在可能预示着癌症对IVT的不良反应，而支原体和埃希氏菌/志贺氏菌的存在可能预示着对IVT的良好反应。进一步的研究是必要的，以阐明和确认膀胱微生物组变化的意义。
Intravesical 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. Patients 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. Across 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. IVT 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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