The Oral Microbiome in Oral Cancer and Potentially Malignant Disorders

Professor Botelho, Michael George   (Principal Investigator (PI))

Emeritus Professor Johnson Newell W   (Co-principal investigator)

Dr Gomez Andrez   (Co-Investigator)

24

2017-06-01

2019-05-31

33240

The Oral Microbiome in Oral Cancer and Potentially Malignant Disorders

Metagenome, Oral Cancer, Oral microbiome,, Potentially malignant disorders

Dentistry,Cancer

201611159283

Seed Fund for PI Research – Basic Research

2016

Completed

Oral cancer is the 6th most common cancer in men throughout the world and the estimated number of new cases per year is 11.1 per 100,000 men with oral squamous cell carcinoma (OSCC) accounting for 90% of all oral cancers. OSCC is often preceded by clinically evident potentially malignant disorders with a malignant transformation rate between 2-13% over several decades. Despite great progress in diagnosis and management strategies the prognosis of OSCC still remains poor. Oral cancer has one of the lowest overall 5-year survival rates globally, close to 50%, with higher rates, as much as 63%, reported in the US and many other low income countries. The commensal microbiome plays a key role in the physiological landscape of the host, and microbial imbalances (dybiosis), have been associated with development and progression of various cancers. Although the studies done on cancer cohorts can deliver insights into association between the oral microbiome and cancer, it is also crucial to determine whether a carcinogenic habitat leads to microbial alterations that functionally contribute to cancer. An understanding of the longitudinal nature of microbial shifts from pre malignant to malignant disorders could thus deliver insights into the role of the oral microbiome in the start and progression of cancer. Few in vitro culture based studies have linked specific microorganisms with the initiation of oral carcinogenesis. However, in the oral cavity, it is unclear whether specific or single bacterial species influence host cells, as demonstrated by the secluded environment of duplicated culture plates. Instead, a continuous cross talk between oral epithelial cells and millions of bacterial strains seems to occurs in health and disease. Therefore, identifying the diversity and functional potential in the complex oral microbiome associated with oral cancer, is critical to unravel the intricate mechanisms involved in initiation and progression of oral cancers. Nevertheless, the microbial diversity and functional capacity of tumor associated bacteria in OSCC have never been comprehensively studied before. Few studies had attempted to investigate the bacterial diversity associated with oral cancer tissue, but the results were inconclusive owing to the limited sample size. There are multiple risk factors which have been correlated with development of oral cancer; tobacco (smoking as well as chewing forms), heavy alcohol use, improper oral hygiene are the most studied examples. Most of these known risk factors can also modify the indigenous microbiome of the oral cavity. In this regard, little is known about the impact of smoking in the oral microbiome, however, some recent studies have shown alter the oral microbial composition. Moreover, the impact of chewing tobacco, or heavy alcohol on the diversity and function of microbial communities residing the oral cavity is virtually unknown. Individual oral bacterial species such as Streptococci and Neisseria have been shown to play a significant role in the degradation of compounds such as alcohol into acetaldehyde which is a carcinogenic compound. Therefore, a change in microbial diversity can lead to alteration of many functional pathways in xenobiotic degradation with serious consequences on oral and systemic health. Nevertheless, the manner in which risk factors of oral cancer such as tobacco and alcohol, and the oral microbiome interact to impact carcinogenesis remains unknown. Along these lines, elucidation of the microbiome associated to OSCC, from a compositional and functional perspective can provide invaluable insights into the role of microbiome in this complex multifactorial disease. Therefore, we propose to conduct a comprehensive characterization of microbial communities in healthy and malignant oral tissues (including potentially malignant and suspected malignant), via 16sr RNA gene sequencing, coupled with shotgun metagenomics to examine the taxonomic and functional attributes of these communities. Moreover, association between the risk factors and microbial diversity and function in malignant and potentially malignant disorders of oral cavity will be investigated. We hypothesize that the microbial communities and their functional attributes at the host-microbe microenvironment in sites with carcinoma significantly differ from those in normal tissue. By profiling the oral microbiome in oral malignant and potentially malignant disorders, this study aims to provide invaluable information for future research addressing the following questions; 1. Is there a significant change in oral microbial diversity in patients with malignant and potentially malignant disorders when compared to healthy controls? 2. Are there any functional pathways enriched or depleted in the oral microbiome of patients with malignant and potentially malignant disorders as compared with healthy controls? 3. Is there any association between the known risk factors for oral cancers such as use of tobacco, alcohol and oral hygiene status and the shift in microbial diversity and potential functions?