阴茎鳞状细胞癌（PSCC）是一种罕见疾病，在巴西等发展中国家更为普遍，与生殖器卫生状况不佳有关，从而促进微生物的增殖。生态失调会影响局部免疫反应，增加病毒感染的风险，并可能产生炎症过程。目前对阴茎组织中微生物群的了解有限，PSCC 的细菌多样性仍然未知。在这项研究中，鉴定了与阴茎癌相关的微生物群及其在肿瘤发生和进展中的潜在作用。通过二代测序分析了19个肿瘤及其各自的非肿瘤邻近组织中的16S rRNA基因，以进行分类学分类、分析核心微生物组、扩增子序列变体 (ASV) 的丰度和多样性 (QIIME2 v.2020.2)，以及计算机功能预测 (PICRUST2，p < 0.05)。在这两种组织中，变形菌门和厚壁菌门，以及产碱菌属和梭杆菌属，最为普遍。肿瘤中梭杆菌门、弯曲杆菌门和梭杆菌门的相对丰度较高（分别为 p = 0.04、p = 0.04 和 p = 0.039）。此外，β多样性分析揭示了当仅考虑晚期肿瘤（pT2和pT3）时形成两个不同组的趋势。此外，功能分析确定了前 35 条途径，79.5% 的 PSCC 样本含有促炎微生物。我们描述了阴茎癌的第一个微生物组，揭示了丰富多样的微生物群以及与炎症相关的分类单元（变形菌门）厚壁菌门、梭杆菌属和普氏菌属，以及 Finegoldia magma 和 Pseudomonas geniculata 种）和分子途径（几丁质衍生物降解、原儿茶酸途径、肌醇代谢和蔗糖途径），这些途径也与炎症和癌变有关。此外，我们在肿瘤和非肿瘤组织中发现了特异性且丰富的 ASV。我们的数据鼓励进一步研究，以更好地了解这些微生物在阴茎癌发生中的作用，为诊断、预后和早期治疗的进展提供机会。© 2023 美国男科学会和欧洲男科学会。

Penile squamous cell carcinoma (PSCC) is a rare disease that is more prevalent in developing countries, such as Brazil, and is linked to poor genital hygiene, which promotes the proliferation of microorganisms. Dysbiosis has an effect on the local immune response, increases the risk of viral infection, and can generate inflammatory processes. Current knowledge of the microbiota found in penile tissues is limited, and the bacterial diversity of the PSCC remains unknown. In this investigation, the microbiota associated with penile cancer and its potential role in tumor development and progression were identified.The 16S rRNA gene was analyzed by next-generation sequencing in 19 tumors and their respective non-tumor adjacent tissues to perform taxonomic classification, analysis of core microbiome, abundance, and diversity of amplicon sequence variants (ASVs) (QIIME2 v.2020.2), and in silico functional prediction (PICRUST2, p < 0.05).In both tissues, the phyla Proteobacteria and Firmicutes, and genera Alcaligenes and Fusobaterium, were the most prevalent. Tumors presented a greater relative abundance of Fusobacteriota, Campilobacteria, and Fusobacterium (p = 0.04, p = 0.04, and p = 0.039, respectively). In addition, the beta diversity analysis revealed a tendency for the formation of two distinct groups when only advanced tumors (pT2 and pT3) were considered. Further, the functional analysis identified the top 35 pathways, and 79.5% of PSCC samples contained pro-inflammatory microorganisms.We describe the first microbiome of penile carcinoma, which revealed an abundant and diverse microbiota as well as inflammatory-related taxa (the phyla Proteobacteria and Firmicutes, the genera Fusobacterium and Prevotella, and the species Finegoldia magma and Pseudomonas geniculata) and molecular pathways (chitin derivates degradation, the protocatechuic acid pathway, inositol metabolism, and the sucrose pathway), which have also been linked to inflammation and carcinogenesis. Moreover, we found specific and abundant ASVs in both tumor and non-tumor tissues. Our data encourage further study to better understand the role of these microorganisms in penile carcinogenesis, offering an opportunity for advances in diagnosis, prognosis, and early therapy.© 2023 American Society of Andrology and European Academy of Andrology.