Microbiome analysis reveals the inducing effect of <i>Pseudomonas</i> on prostatic hyperplasia via activating NF-κB signalling

Benign prostatic hyperplasia (BPH) is a prevalent disease among middle-aged and elderly males, but its pathogenesis remains unclear. Dysbiosis of the microbiome is increasingly recognized as a significant factor in various human diseases. Prostate tissue also contains a unique microbiome, and its dysbiosis has been proposed to contribute to prostate diseases. Here, we obtained prostate tissues and preoperative catheterized urine from 24 BPH individuals, and 8 normal prostate samples as controls, which followed strict aseptic measures. Using metagenomic next-generation sequencing (mNGS), we found the disparities in the microbiome composition between normal and BPH tissues, with <i>Pseudomonas</i> significantly enriched in BPH tissues, as confirmed by fluorescence in situ hybridization (FISH). Additionally, we showed that the prostate microbiome differed from the urine microbiome. In vitro experiments revealed that lipopolysaccharide (LPS) of <i>Pseudomonas</i> activated NF-κB signalling, leading to inflammation, proliferation, and EMT processes, while inhibiting apoptosis in prostatic cells. Overall, our research determines the presence of microbiome dysbiosis in BPH, and suggests that <i>Pseudomonas</i>, as the dominant microflora, may promote the progression of BPH through LPS activation of NF-κB signalling.良性前列腺增生（Benign Prostatic Hyperplasia, BPH）是中老年男性的高发疾病，但其发病机制尚未明确。微生物群失调日益被学界视为多种人类疾病的重要致病因素。前列腺组织亦拥有独特的微生物群，其失调被认为与前列腺疾病的发生发展相关。本研究从24名BPH患者及8名正常前列腺组织对照样本中采集前列腺组织与术前导尿尿液，所有样本均严格遵循无菌操作流程。通过宏基因组下一代测序（metagenomic next-generation sequencing, mNGS）分析，我们发现正常前列腺组织与BPH组织的微生物群组成存在显著差异，其中假单胞菌属（Pseudomonas）在BPH组织中显著富集，该结果经荧光原位杂交（fluorescence in situ hybridization, FISH）验证。此外，本研究证实前列腺微生物群与尿液微生物群存在显著差异。体外实验结果显示，假单胞菌的脂多糖（lipopolysaccharide, LPS）可激活前列腺细胞中的核因子κB（NF-κB）信号通路，进而引发炎症反应、细胞增殖及上皮间质转化（epithelial-mesenchymal transition, EMT）过程，并抑制前列腺细胞凋亡。综上，本研究证实了BPH患者存在微生物群失调现象，并提示以假单胞菌属为优势菌群的微生物群可能通过LPS激活核因子κB信号通路，进而促进BPH的疾病进展。