Abstract
BACKGROUND: The oral microbiome has been shown to be associated with the development of oral squamous cell carcinoma (OSCC). Research has primarily focused on elucidating the oncogenic mechanisms of specific pathogens by comparing the microbiomes of OSCC and normal tissues. However, the characteristics of the microbiome in the precancerous state remain less understood, as does the influence of metabolic and environmental factors on OSCC-associated microbiomes. METHODS: In this study, we analyzed mucosa-associated microbiomes in normal, precancerous, and OSCC lesions from a cohort of 51 patients using 16S rRNA amplicon sequencing. We investigated compositional changes in the microbiome, including the specific abundances and co-occurrences of OSCC-associated bacteria. RESULTS: Our findings indicate that the microbiome associated with precancerous lesions is indistinguishable from that of the normal mucosa, whereas the OSCC microbiome significantly differs from both normal and precancerous conditions. Specifically, the OSCC microbiome harbors less Streptococcus, coupled with an increase in amino-acid-degrading anaerobes such as Fusobacterium and Prevotella. The metabolic properties of individual microbes reported suggest that the overrepresentation of OSCC-specific bacteria is a result of metabolic adaptation to tumor microenvironments, although this possibility needs to be experimentally confirmed. CONCLUSIONS: Our results demonstrate oral microbiome patterns across OSCC progression, offering insights into microbial ecological perspectives.