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

ABSTRACT

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 Pseudomonas 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 Pseudomonas 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 Pseudomonas, as the dominant microflora, may promote the progression of BPH through LPS activation of NF-κB signalling.

KEYWORDS:

• Benign prostatic hyperplasia
• microbiome
• Pseudomonas
• lipopolysaccharide
• NF-κB

Acknowledgements

We deeply appreciate all the subjects in the study.

We are also grateful to Wei Tang and Genming Xu from Hunan Yearth Biotechnology Co., Ltd., Changsha, China, for their experimental advice and technical guidance.

Data availability statement

The sequencing data are available and have been uploaded to the National Center for Biotechnology Information (NCBI) under the BioProject ID PRJNA1061468.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval

The experiments involving patient samples were conducted with prior approval from the Institutional Review Board of Third Xiangya Hospital, Central South University (No.22239). All patients were duly informed, willingly agreed, and provided the consent to participate.

Author contributions

J.L., H.X. and L.W.: conceptualization and writing; Y.L., L.Z. and H.L.: resources, investigation and revision; T.W., J.T. and L.Z.: methodology, data curation, and statistical analysis. All authors read and approved the final manuscript.

Supplemental material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2024.2313410.

Additional information

Funding

The study was supported by the National Natural Science Foundation of China (No.82370779) and the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hospital of Central South University (No.20210312).