Alterations in the oral microbiome associated with risk factors for oral cancer and their contributions to pathogenesis

Oral squamous cell carcinomas are a major cause of morbidity and mortality, and tobacco usage, alcohol consumption, and poor oral hygiene are established risk factors. To date, case-control studies have not considered the effects of these risk factors on the composition of the oral microbiome, nor microbial community associations with oral cancer. We compared the composition, diversity, and function of the oral microbiomes of 121 oral cancer patients to 242 age- and gender-matched controls using a novel metagenomic multivariate analysis pipeline. Significant shifts in composition and function of the oral microbiome were observed with poor oral hygiene (e.g. tooth loss, history of periodontitis), tobacco smoking, and oral cancer. Specifically, we observed dramatically altered community composition after tooth loss, with smaller alterations in current tobacco smokers, increased production of antioxidants in individuals with a history of periodontitis, and significantly decreased glutamate metabolism and polyamine synthesis in oral cancer patients. These alterations in the oral microbiome, in association with established risk factors for oral cancer, may contribute to its pathogenesis.