Akkermansia muciniphila-derived extracellular vesicles mitigate smoking-induced prostate inflammation and fibrosis.

BACKGROUND

Cigarette smoking (CS) is a well-known risk factor for inducing prostate inflammation and fibrosis, presenting significant threats to male reproductive health. Recent research has highlighted the significant role of gut microbiota (GM) in regulating extra-intestinal organs. This study aimed to investigate the effects of Akk and its extracellular vesicles (EVs) on CS-induced prostate inflammation and fibrosis.

METHODS

This study utilized a mouse model of mainstream smoke exposure to investigate the effects of Akkermansia muciniphila (Akk) and its EVs on prostate tissue affected by CS. Prostate inflammation and fibrosis was assessed through HE staining, qRT-PCR, IHC staining, and immunofluorescence staining. Functional protein P9 enriched in Akk-EVs was used to intervene cigarette smoke extract (CSE)-exposed BPH-1 cells in vitro to validate the anti-inflammatory and anti-fibrotic effects.

RESULTS

The results revealed that CS exposure leads or led to pronounced prostatic inflammation and fibrosis, accompanied by a notable decrease in intestinal levels of Akk. Supplementation with Akk was found to effectively mitigate prostate lesions caused by CS, with the therapeutic effects primarily attributed to the Akk-derived extracellular vesicles (Akk-EVs). The transport kinetics of Akk-EVs to prostate tissue and cells were elucidated, providing insights into their mechanism of action. Both in vitro and in vivo experiments demonstrated that Akk-EVs and their enriched P9 protein effectively ameliorated CS-induced pro-inflammatory cytokine expression and collagen deposition in the prostate.

CONCLUSIONS

These findings highlight the anti-inflammatory and anti-fibrotic properties of Akk-EVs and P9 protein, suggesting their potential as therapeutic agents for CS-induced prostate lesions.