蕈样肉芽肿 (MF) 是皮肤 T 细胞淋巴瘤 (CTCL) 最常见的实体，其特征是皮肤中存在克隆性恶性 T 细胞。目前，人们对皮肤微生物群在 MF 发生和进展中的作用知之甚少。使用鸟枪法宏基因组分析、实时 qPCR 和 T 细胞受体测序，我们比较了 20 名早期和晚期 MF 患者的病变和非病变皮肤。此外，我们从 MF 皮肤中分离出金黄色葡萄球菌和其他细菌，进行功能分析并研究金黄色葡萄球菌毒力因子 spa。我们确定了一个亚组的 MF 患者，其 MF 皮损处存在严重的生态失调，并伴有斑块期皮损上金黄色葡萄球菌的生长，而其他 MF 患者的皮损皮肤上则具有平衡的微生物组。生态失调和金黄色葡萄球菌生长伴随着皮肤抗菌肽（AMP）的异位水平，包括斑块衍生的金黄色葡萄球菌菌株的适应。此外，源自菌斑的金黄色葡萄球菌菌株对抗生素的敏感性降低，毒力因子 spa 上调，这可能会激活 NF-κB 通路。值得注意的是，MF 病变出现菌群失调的患者 T 细胞受体库受到限制，无事件生存率显着降低。我们的研究强调了针对金黄色葡萄球菌的微生物组调节治疗预防 MF 进展的潜力。© 2024。作者。

Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.© 2024. The Author(s).