膀胱癌是常见的恶性肿瘤，复发率较高。早期诊断和复发监测对于患者的治疗结果至关重要，这需要新型的微创诊断工具。尿液微生物组与膀胱癌相关，可作为生物标志物，但其潜在机制有待充分阐明，诊断性能有待提高。 共有 23 名初治膀胱癌患者和 9 名非癌症受试者入组之前组和对照组。手术后，术前组中的10名患者进一步被分配到术后组。收集中段尿液样本并送去进行 16S rDNA 测序、靶向代谢组学分析和流式细胞术。接下来，分析微生物群、代谢物和细胞因子之间的相关性。最后，绘制并比较尿液生物标志物的受试者工作特征（ROC）曲线。与对照组相比，IL-6（p<0.01）、IL-8（p<0.05）和IL-10（p）水平< 0.05）在之前组中显着升高。尿液微生物群的α多样性也显着较高，特征微生物群与IL-6水平呈正相关（r = 0.58，p < 0.01）。治疗前和对照组之间的代谢组成也存在显着差异，治疗前组中脂肪酸和脂肪酰肉碱含量较高。肿瘤切除后，治疗后组的细胞因子水平和整体微生物组结构与治疗前组相似，但脂肪酰肉碱显着降低（p<0.05）。通路富集分析显示脂肪酸的β-氧化显着参与（p<<0.001）。 ROC曲线显示，放线菌  花生四烯酸  IL-6生物标志物组合具有优越的诊断性能，敏感性为0.94，特异性为1.00。微生物群失调、促炎环境和脂肪酸代谢改变参与了膀胱癌的发病机制，这可能会导致膀胱癌的发生。关注新型非侵入性诊断工具的开发。© 2024。作者。

Bladder cancer is a common malignancy with high recurrence rate. Early diagnosis and recurrence surveillance are pivotal to patients' outcomes, which require novel minimal-invasive diagnostic tools. The urinary microbiome is associated with bladder cancer and can be used as biomarkers, but the underlying mechanism is to be fully illustrated and diagnostic performance to be improved.A total of 23 treatment-naïve bladder cancer patients and 9 non-cancerous subjects were enrolled into the Before group and Control group. After surgery, 10 patients from the Before group were further assigned into After group. Void mid-stream urine samples were collected and sent for 16S rDNA sequencing, targeted metabolomic profiling, and flow cytometry. Next, correlations were analyzed between microbiota, metabolites, and cytokines. Finally, receiver operating characteristic (ROC) curves of the urinary biomarkers were plotted and compared.Comparing to the Control group, levels of IL-6 (p < 0.01), IL-8 (p < 0.05), and IL-10 (p < 0.05) were remarkably elevated in the Before group. The α diversity of urine microbiome was also significantly higher, with the feature microbiota positively correlated to the level of IL-6 (r = 0.58, p < 0.01). Significant differences in metabolic composition were also observed between the Before and Control groups, with fatty acids and fatty acylcarnitines enriched in the Before group. After tumor resection, cytokine levels and the overall microbiome structure in the After group remained similar to that of the Before group, but fatty acylcarnitines were significantly reduced (p < 0.05). Pathway enrichment analysis revealed beta-oxidation of fatty acids was significantly involved (p < 0.001). ROC curves showed that the biomarker panel of Actinomycetaceae + arachidonic acid + IL-6 had superior diagnostic performance, with sensitivity of 0.94 and specificity of 1.00.Microbiome dysbiosis, proinflammatory environment and altered fatty acids metabolism are involved in the pathogenesis of bladder cancer, which may throw light on novel noninvasive diagnostic tool development.© 2024. The Author(s).