Oral microbial dysbiosis and its performance in predicting oral cancer

Abstract

<jats:title>Abstract</jats:title> <jats:p>Dysbiosis of oral microbiome may dictate the progression of oral squamous cell carcinoma (OSCC). Yet, the composition of oral microbiome fluctuates by saliva and distinct sites of oral cavity and is affected by risky behaviors (smoking, drinking, and betel quid chewing) and individuals’ oral health condition. To characterize the disturbances in the oral microbial population mainly due to oral tumorigenicity, we profiled the bacteria within the surface of OSCC lesion and its contralateral normal tissue from discovery (n=74) and validation (n=42) cohorts of male patients with cancers of the buccal mucosa. Significant alterations in the bacterial diversity and relative abundance of specific oral microbiota (most profoundly, an enrichment for genus Fusobacterium and the loss of genus Streptococcus in the tumor sites) were identified. Functional prediction of oral microbiome shown that microbial genes related to the metabolism of terpenoids and polyketides were differentially enriched between the control and tumor group, indicating a functional role of oral microbiome in formulating a tumor microenvironment via attenuated biosynthesis of secondary metabolites with anti-cancer effects. Furthermore, the vast majority of microbial signatures detected in the discovery cohort was generalized well to the independent validation cohort, and the clinical validity of these OSCC-associated microbes was observed and successfully replicated. Overall, our analyses reveal signatures (a profusion of Fusobacterium nucleatum CTI-2 and a decrease in Streptococcus pneumoniae) and functions (decreased production of tumor-suppressive metabolites) of oral microbiota related to oral cancer.</jats:p>

Dysbiosis of Oral Microbiota During Oral Squamous Cell Carcinoma Development

“…In addition, in line with the previous studies ( 29 , 52 , 53 ) Firmicutes was also found as the most abundant phylum in overall oral microbiome in our study. Of the significantly elevated genera in cancerous lesions, Prevotella and Pseudomonus were previously shown to be highly abundant in both periodontitis and OSCC samples when compared to healthy controls ( 32 , 53 , 59 ). Importantly, periodontitis has been suggested as a self-governing risk factor for OSCC development ( 27 ).…”

“…In agreement with Guerrero-Preston et al study ( 51 ), we also observed a significant loss in richness and diversity of oral bacterial communities in OSCC lesions compared to matched controls. However, several reports revealed enhanced diversity of bacterial communities in OSCC samples ( 31 , 52 , 53 ). Nevertheless, dysbiosis of oral microbiome appears to be strongly associated with OSCC development.…”

Crosstalk between the oral microbiota, mucosal immunity, and the epithelial barrier regulates oral mucosal disease pathogenesis

“…119,120 Recently, a study suggests that compared with the controls, microbial pathway modules associated with the metabolism of terpenoids and polyketides, including the biosynthesis of siderophore group nonribosomal peptides, monoterpenoid biosynthesis, and biosynthesis of 12-, 14-and 16-membered macrolides, are less abundant in oral tumor lesions. 28 In conclusion, these findings reveal that the oral microbiota community dynamically changes and potentially induces oral lesion progression. These findings highlight a novel aspect of OLK and OSCC etiology and the functional role of the oral microbiome in formulating a tumor microenvironment via the attenuated biosynthesis of secondary metabolites with cancer-promoting or anti-cancer effects.…”

“…[20][21][22][23][24] An increasing body of evidence suggests that perturbations of the mucosal microbiota can modulate innate and adaptive immune responses, with inflammation arising due to a reduction in the number of symbiont microorganisms and/or an increase in the number of pathobiont microorganisms (commensal bacteria with pathogenic potential). [25][26][27][28] For example, one mechanism by which these microbes regulate immunity is by controlling regulatory T cells (Tregs) and T helper 17 (Th17) cells. [29][30][31] In addition, the epithelium recognizes and responds to the microbiota, and in turn, microbial dysbiosis and associated metabolite alterations destroy the integrity of the mucosal epithelium and its barrier functions.…”

The Oral Microbiome and Cancer

“…cancer, the search for possible biomarkers of oral cancer and, most specifically, OSCC has not produced conclusive results(52). Different organisms have been shown to increase in OSCC samples, as a few examples: Capnocytophaga gingivalis, Prevotella melaninogenica, and S. mitis (131); F. nucleatum(149); Pseudomonas aeruginosa (150); Campylobacter concisus, Prevotella salivae, Prevotella loeschii, and Fusobacterium oral taxon 204(151); genera Fusobacterium, Dialister, Peptostreptococcus, Filifactor, Peptococcus, Catonella, and Parvimonas (136); and Prevotella oris, Neisseria flava, Neisseria flavescens/subflava, F. nucleatum ss polymorphum, Aggregatibacter segnis, and Fusobacterium periodonticum(152).…”