Microbial Signature Associated with the Development of Prostate and Oral cancers in Eastern Region of India

Abstract

The relationship between humans and microbes dates back to ancient times. Robert Koch's groundbreaking work on‘Pure Culture’ technique illuminated specific role of microbes in causing various human diseases. This technique, however, later met a challenge known as 'The Great Plate Count Anomaly' where many visible microbes under the microscope couldn't be cultivated in pure culture, leading to the concept of 'Uncultivable Microbes'. Advanced sequencing techniques, such as metagenomics sequencing, shotgun sequencing, whole genome sequencing and 16S rRNA amplicon-based sequencing emerged as powerful tools to explore the uncultivable microbial world. In this study, we aimed to uncover the integral connections of microbial communities with both prostate cancer (PCa) and oral squamous cell carcinoma (OSCC) development through utilizing uncultivated sequencing technology along with various bioinformatics analysis. Prostate and oral cancers pose significant health challenges globally as well as with respect to Indian patients. Meticulous analysis of commensal bacteria compositions in both benign prostatic hyperplasia (BPH) and PCa patients’ revealed Prevotella copri, Cupriavidus campinensis and Propionibacterium acnes dominated in diseased prostate lesions. While PCa samples exhibited elevated levels of Cupriavidus taiwanensis and Methylobacterium organophilum, BPH samples were enriched with Kocuria palustris and Cellvibrio mixtus. Several human tumor viruses like Epstein-Barr virus (EBV), hepatitis B virus (HBV) and high-risk human papillomavirus (HPV) strains HPV-16 and HPV-18 were also strongly associated with PCa development, correlating with its bacterial signature. OSCC represents the most common oral malignancy. In contrast to adjancent normal samples, malignant oral tissues showed decreased bacterial genera of Actinomyces, Sutterella, Stenotrophomonas, Anoxybacillus and Serratia along with increased bacterial genera of Prevotella, Corynebacterium, Pseudomonas, Deinococcus and Noviherbaspirillum. In addition, high-risk HPV-16 strain was significantly linked to OSCC progression. Collectively, these findings reveal the complex interaction of bacterial and viral signatures with PCa and OSCC development.