Alterations in oral bacterial communities are associated with risk factors for oral and oropharyngeal cancer

Daniela Börnigen,Curtis Huttenhower,Mary Ellen Davey,Boyu Ren,Dirk Gevers,Maura L Gillison,Erica M Hartmann,Robert Pickard,Timothy Tickle,Jennifer Rider,Jingfeng Li,Weihong Xiao,Enver Ozer,Eric A Franzosa

doi:10.1038/s41598-017-17795-z

Abstract

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, no large-scale case-control studies have 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 metagenomic multivariate analysis pipeline. Significant shifts in composition and function of the oral microbiome were observed with poor oral hygiene, tobacco smoking, and oral cancer. Specifically, we observed dramatically altered community composition and function after tooth loss, with smaller alterations in current tobacco smokers, increased production of antioxidants in individuals with periodontitis, and significantly decreased glutamate metabolism metal transport in oral cancer patients. Although the alterations in the oral microbiome of oral cancer patients were significant, they were of substantially lower effect size relative to microbiome shifts after tooth loss. Alterations following tooth loss, itself a major risk factor for oral cancer, are likely a result of severe ecological disruption due to habitat loss but may also contribute to the development of the disease.

Highlights

Head and neck squamous cell carcinomas are a major cause of cancer morbidity and mortality, with an estimated incidence of 549,000 cases worldwide in 20081
We compared the oral microbiome in 121 oral cancer cases and 242 matched controls using multivariate analysis targeted at microbial taxonomic and inferred functional profiles
Microbial community effects included a loss of ecological diversity and increased glutamate metabolism in tobacco smoking individuals, disruptions in both structure and function in individuals after tooth loss, and a decrease in glutamate metabolism and metal transport in cancer cases

Summary

Introduction

Head and neck squamous cell carcinomas are a major cause of cancer morbidity and mortality, with an estimated incidence of 549,000 cases worldwide in 20081 The majority of these are oral cancers arising in the oral cavity and oropharynx, for which tobacco usage, betel chewing, alcohol consumption, and human papillomavirus (HPV) infection are established risk factors[2,3,4,5,6,7,8,9]. We evaluated associations between lifestyle factors (alcohol and tobacco use), health characteristics (history of periodontitis, tooth status), case-control status, and the composition and function of oral microbial communities (Table 1). Microbial community effects included a loss of ecological diversity and increased glutamate metabolism in tobacco smoking individuals, disruptions in both structure and function in individuals after tooth loss, and a decrease in glutamate metabolism and metal transport in cancer cases. We conclude that alterations in the structure, diversity, and function of the oral microbiome occur in association with established risk factors for oral cancer, especially after complete tooth loss; these alterations may contribute to disease development but are likely due to severe ecological disruption and habitat loss

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Conclusion