Presence of Specific Periodontal Pathogens in Prostate Gland Diagnosed With Chronic Inflammation and Adenocarcinoma

Abstract

Background Intraprostatic inflammation is frequently observed in the prostate and linked to prostatic diseases, including prostatitis, benign prostatic hyperplasia (BPH), and cancer. The etiology of prostate diseases is unclear. Periodontal diseases are associated with an increased risk of prostate diseases. In men, chronic prostatitis and moderate/severe periodontitis have significantly elevated serum prostate-specific antigen (PSA) levels. Treatment of periodontal disease reduced PSA levels in men. The presence of periodontal pathogens deoxyribonucleic acid (DNA) was identified in the prostate fluid of prostatitis patients. These pathogenic bacteria might have the potential to trigger prostatitis progressing to prostatic adenocarcinoma. The mechanism(s) explaining the etiology of association between periodontal disease and prostate cancer remains unclear. However, the presence of periodontal pathogens has not been analyzed in the prostate gland. Objective To identify and compare the presence of specific periodontal pathogens in the areas of BPH, inflammation, and cancer of the prostate glands diagnosed with malignancy. Materials and methods Whole-mount radical prostatectomy sections from men (n=30) were identified for BPH, inflammation, and cancer areas and marked for tissue procurement. The tissues were subjected to DNA isolation and analysis of microbial DNA and total bacterial load for the following pathogens, including Porphyromonas gingivalis strain ATCC 33277, Prevotella intermedia strain B422, Treponema denticola strain 35405, Fusobacterium nucleatum subsp. fusiform strain, Tannerella forsythia strain ATCC 43037, and Campylobacter​​​​​​​ rectus strain ATCC 33238performed real-time PCR. The universal bacterial primer pairs were used to detect genomic DNA (gDNA) from the total bacteria present in the samples. All species-specific primers were designed to target the variable regions of the 16S ribosomal RNA (rRNA). Data were analyzed using the 2-ΔΔCT method, statistically validated using unpaired t-test and ANOVA test. Results A total of 90 samples of prostate tissue specimens were analyzed for periodontal pathogens; only one pathogen (F. nucleatum subsp. fusiform strain ATCC 51190) showed a significant difference compared to the expression of S. epidermidis (internal control). In particular, F. nucleatum expression was 9, 11.9, and 10.3-fold higher in BPH, inflammation, and cancer, respectively, at p-value <0.05. Moreover, the bacterial load abundance/expression was almost similar in BPH (46.8-fold), inflammation (40.9 fold), and cancer (41.5 fold) higher. There was no significant difference in bacterial load (folder change) among the three areas of BPH, inflammation, and cancer (p-valve>0.05). Similarly, there was no significant difference between F. nucleatum (folder change) among the three areas (p-valve>0.05). Conclusion Fusobacterium nucleatum is identified in the prostates that harbor cancer, chronic inflammation, and BPH.

Keywords: benign prostate hyperplasia; periodontal disease; periodontal pathogens; prostate cancer; prostatitis.

Figure 1. Hematoxylin and eosin-stained and unstained formalin-fixed, paraffin-embedded prostate tissue slides

Figure 2. CT values of control S. epidermidis and F. nucleatum of all three areas, i.e., BPH, inflammation, and cancer

BPH: benign prostatic hyperplasia

Figure 3. Relative expression fold changes 2^ (- ΔΔCT) of bacterial load and F. nucleatum of all three areas, i.e., BPH, inflammation, and cancer

BPH: benign prostatic hyperplasia