Oral microbiome in oral cancers and oral potentially malignant disorders

Abstract

Abstract of the thesis entitled

Oral Microbiome in Oral Cancers and Oral Potentially Malignant Disorders

Submitted by Divya Gopinath

For the degree of Doctor of Philosophy at The University of Hong Kong February 2020

Oral microbial communities were associated with oral health and disease, though until recent times, studies were limited to organisms that could be cultured. Recent advances in culture-independent techniques have identified the association of the oral microbiome with oral cancers. This dissertation aims to expand our current understanding on the association of oral bacteriome with oral cancers (OC) and oral potentially malignant disorders (OPMDs). In the initial set of three reviews, we have systematically reviewed and discussed the current evidence on the association of oral bacterial communities (bacteriome) and human cancers with special emphasis on OC followed by a meta-analysis on the association of periodontal diseases and head and neck cancers (HNC). Our meta-analysis revealed that periodontal disease, which is a polymicrobial disease, could be an independent risk factor for HNC. Subsequently with our studies, we have comprehensively evaluated the compositional and metabolic attributes of the bacteriome associated with oral cancers and potentially malignant disorders in the Indian population using 16S rRNA gene sequencing. Firstly, we examined the salivary bacteriome in patients with oral leukoplakia (OL) and identified a dysbiotic bacteriome to be associated with OL, which resembled oral cancer bacteriome than healthy controls. Through a novel model, we demonstrated that compositional shifts of salivary bacteriome could be a biomarker for epithelial alterations and subsequently tumorigenesis. Secondly, we explored the oral bacteriome of oral submucous fibrosis (OSMF) and did not find any overall differences at the phylum and genus level in the bacteriome of OSMF patients compared to habit-matched controls; however, genus Fusobacterium, Campylobacter, and unclassified Clostridium were significantly increased in controls. Thirdly, we demonstrated that bacterial communities associated with the tumor surface and paired tumor tissue differed significantly, both at the community level and at taxonomic levels. Tumor surfaces carried elevated abundances of taxa belonging to genus Porphyromonas, Enterobacteriae, Neisseria, Streptococcus and Fusobacteria, whereas Prevotella, Treponema, Sphingomonas, Meiothermus and Mycoplasma genera were significantly more abundant in paired tissue samples. The most abundant microbial metabolic pathways were those related to fatty-acid biosynthesis, carbon metabolism and amino-acid metabolism on the tumor surface; carbohydrate metabolism and organic polymer degradation were elevated in cancer tissues. The bacteriome of saliva from patients with oral cancer differed significantly from paired tumor tissue in terms of community structure, however remained similar at taxonomic and metabolic levels except in the elevated abundances of Streptococcus, Lactobacillus as well as Bacteroides and triglycerol degradation respectively. Finally, we studied the oral bacteriome associated with the use of tobacco (smoking and smokeless) and identified compositional similarities between the oral bacteriome of smokers and smokeless tobacco users with elevated levels of genera Fusobacterium in comparison with controls; the overall bacterial metabolome of smokeless tobacco users favored amino acid metabolism instead of saccharolytic metabolism. Taken together our results demonstrate that polymicrobial community with dysbiotic metabolic potential significantly different from healthy controls is related to OC and OPMDs. Improving our understanding of the role of microbiome in oral cancer biology can help to design novel approaches in prevention and management of OC.