研究动态
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非肌肉侵袭性膀胱癌患者膀胱微生物组对膀胱卡介苗和化疗的影响。

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

发表日期:2023
作者: 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
来源: Frontiers in Cellular and Infection Microbiology

摘要:

膀胱内治疗(IVT),包括Calmette-Guerin卡介苗(BCG),是高级别(HG)非肌肉侵袭性膀胱癌(NMIBC)的标准治疗方法。尽管使用IVT治疗,许多患者治疗后仍会复发。最近,膀胱微生物群及其在疾病进程中的作用受到了关注。我们的目标是描述在膀胱内治疗过程中膀胱微生物群中发生的变化,并评估这些变化是否与NMIBC患者的治疗结果有关。从2019年1月到2020年3月,有NMIBC的患者进行诱导BCG或膀胱内治疗并进行前瞻性入组登记。在入组时排除临床T2或更高级别的病理学或活动性泌尿道感染的患者。29例患者在引入膀胱内治疗之前和每次IVT注入之前收集了导管(膀胱)尿样。27例接受了BCG治疗,而2例接受了膀胱内吉西他滨治疗。使用16S核糖体RNA基因测序识别细菌。评估膀胱微生物群的变化,并研究IVT后复发和未复发患者之间的差异。在分析的29例患者中,膀胱内治疗后细菌的丰富度显著下降(丰富度,P = 0.01)。即使是均匀性和总体多样性也没有显著变化(Pielou,P = 0.62;Shannon,P = 0.13)。患有复发经历的患者尿液中的Aerococcus相对丰度更高(P <0.01),而未复发的患者中则明显有更多的Ureaplasma(P = 0.01)和Escherichia/Shigella物种(P = 0.05)。alpha多样性水平下降的患者更有可能属于未复发组。NMIBC的IVT似乎通过降低丰度而不改变均匀性或总体多样性来改变尿液微生物群。Aerococcus物种的存在可能预示IVT的癌症反应不佳,而Ureaplasma和Escherichia/Shigella的存在可能预示IVT的良好反应。有必要进行进一步的研究以阐明和确认膀胱微生物群变化的重要性。 版权所有 © 2023 James,Gomez,Desai,Patel,Rac,Doshi,Dornbier,Bajic,Halverson,Gupta,Quek,Gorbonos,Flanigan和Wolfe。
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.Copyright © 2023 James, Gomez, Desai, Patel, Rac, Doshi, Dornbier, Bajic, Halverson, Gupta, Quek, Gorbonos, Flanigan and Wolfe.