P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Periodontitis relates to benign prostatic hyperplasia via the gut microbiota and fecal metabolome.

Objectives: Periodontitis is associated with benign prostatic hyperplasia (BPH), whether it related to gut floramicrobiota and metabonomics is unclear. Methods: We established ligature-induced periodontitis (EP), testosterone-induced BPH, and composite rat models. Fecal samples were collected to detect gut microbiota by 16S rDNA sequencing and metabonomics were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: Sequencing results revealed differential gut floramicrobiota composition between EP+BPH group and other three groups. The abundances of Ruminococcus flavefaciens were significantly increased in EP+BPH group compared with other groups. Tenericutes, Mollicutes, RF39 and Ruminococcus gnavus were significantly decreased in EP+BPH group compared with BPH group, while Ruminococcus callidus and Escherichia were significantly decreased compared with EP group. For gut metabonomics, LC-MS/MS showed that fecal metabolites and seven metabolic pathways were changed in EP+BPH group, such as biosynthesis of unsaturated fatty acids, steroid hormone biosynthesis. Correlation analysis showed that the alterations of gut metabolism were significantly correlated with differential gut floramicrobiota, such as Ruminococcus callidus and Ruminococcus flavefaciens. Conclusion: Our study highlights the relationship of periodontitis and BPH, the alterations of gut floramicrobiota and metabolites may be involved in two diseases, which provides new idea for prevention and treatment of patients with periodontitis concurrent BPH.