Sex-specific Alterations in the Urinary and Tissue Microbiome in Therapy-naive Urothelial Bladder Cancer Patients

Sex-specific Alterations in the Urinary and Tissue Microbiome in Therapy-naive Urothelial Bladder Cancer Patients
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DOI:
10.1016/j.euo.2020.04.002
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发表时间:
2020-12-01
影响因子:
8.2
通讯作者:
Alfano, Massimo
Alfano, Massimo
中科院分区:
医学1区
文献类型:
--
作者:
Pederzoli, Filippo;Ferrarese, Roberto;Alfano, Massimo

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膀胱癌(BCa)和健康状态下尿液和尿路上皮结合微生物组的全面表征对于了解这些局部微生物组如何在BCa肿瘤发生和对治疗的反应中发挥作用以及解释BCa病理生物学中基于性别的差异至关重要。对来自接受根治性膀胱切除术的未经治疗的BCa患者和健康对照的166个样本(尿液和配对膀胱组织)进行16 s rDNA微生物组分析,我们定义了(1)尿液和膀胱组织中的性别特异性微生物组差异,以及(2)排泄尿液微生物组的组织微环境代表性。克雷伯氏菌属在女性BCa患者的尿液中比健康对照组更常见,而在男性中没有发现不同的临床相关细菌。在组织中,伯克霍尔德氏菌在两种性别的肿瘤组织中比在非肿瘤组织中更丰富,这表明在BCa病理生物学中具有潜在作用。最后,我们发现尿液微生物组与配对膀胱组织中存在的细菌家族共有>80%,这使得尿液微生物组成为组织细菌环境的合理代表。患者总结:我们鉴定了男性和女性膀胱癌患者尿液和组织中存在的特定细菌。这些新数据代表了了解膀胱微生物组对膀胱癌发展以及对膀胱内和全身治疗反应的影响的第一步。(C)2020年欧洲泌尿外科协会。Elsevier B. V.出版,保留所有权利。
Comprehensive characterization of the urinary and urothelium-bound microbiomes in bladder cancer (BCa) and healthy state is essential to understand how these local microbiomes may play a role in BCa tumorigenesis and response to therapy, as well as to explain sex-based differences in BCa pathobiology. Performing 16 s rDNA microbiome analysis on 166 samples (urine and paired bladder tissues) from therapy-naive BCa patients undergoing radical cystectomy and healthy controls, we defined (1) sex-specific microbiome differences in the urine and bladder tissue, and (2) representativeness of the tissue microenvironment by the voided urinary microbiome. The genus Klebsiella was more common in the urine of female BCa patients versus healthy controls, while no clinically relevant bacteria were found differently enriched in men. In tissues, the genus Burkholderia was more abundant in the neoplastic versus the non-neoplastic tissue in both sexes, suggesting a potential role in BCa pathobiology. Lastly, we found that the urinary microbiome shares >80% of the bacterial families present in the paired bladder tissue, making the urinary microbiome a fair proxy of the tissue bacterial environment.Patient summary: We identified specific bacteria present in the urine and tissues of male and female bladder cancer patients. These novel data represent a first step toward understanding the influence of the bladder microbiome on the development of bladder cancer and on the response to intravesical and systemic therapies. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.