Oral Microbiota Analysis of Tissue Pairs and Saliva Samples From Patients With Oral Squamous Cell Carcinoma – A Pilot Study

Abstract

Oral microbiota dysbiosis is associated with the occurrence and progression of oral cancer. To investigate the association between the microbiota and risk of oral squamous cell carcinoma (OSCC), we identified the microbial composition of paired tumor (TT)/normal paracancerous tissues (NPT) and saliva (TS) samples in OSCC patients through 16S rRNA gene sequencing. A total of 22 phyla, 321 genera, and 869 species were identified in the oral samples. Paired comparisons revealed significant differences between TT, NPT, and TS groups, with the genus Filifactor significantly enriched in TT. The phylum Actinobacteria; genus Veillonella; and species Granulicatella adiacens, Streptococcus sanguinis, and Veillonella rogosae were significantly enriched in NPT, while the phylum Bacteroidetes; genera Capnocytophaga, Haemophilus, and Prevotella; and seven species, including Capnocytophaga sp., Haemophilus sp., and Neisseria sp., were significantly enriched in TS. In TTs, the abundance of Prevotella intermedia was profoundly higher in the gingiva, while Capnocytophaga gingivalis and Rothia mucilaginosa were enriched in the lining mucosa and tongue. Increasing in abundance from the early tumor stage to the late stage, Solobacterium moorei in TT and Campylobacter sp. strain HMT 044 in TS were positively correlated with OSCC development, suggesting that bacteria were selected by different microenvironments. The correlation between 11 microbial species and 17 pathway abundances was revealed, indicating the potential function of low-abundance bacteria. Overall, our analysis revealed that multiple oral bacterial taxa are associated with a subsequent risk of OSCC and may be used as biomarkers for risk prediction and intervention in oral cancers.

Microbiota and Oral Cancer as A Complex and Dynamic Microenvironment: A Narrative Review from Etiology to Prognosis

“…There was a different composition of the microbiota of the tissue biopsy samples depending on the location of the tumor, for example Capnocytophaga gingivalis , Rothia mucilaginosa , and P. intermedia were significantly enriched in the lining mucosa, tongue, and gingiva, respectively [ 64 ]. These bacteria can secrete peptidases in tumor sites that are activated through proteinase-activated receptors (PARs) [ 65 , 66 ].…”

“…While Capnocytophaga gingivalis, Prevotella melaninogenica, Sreptococcus mitis, Fusobacterium periodonticum, Prevotella tannerae, and Prevotella intermedia were significantly enriched in unstimulated saliva samples of OSCC patients ( Figure 3 b) [ 46 , 64 , 75 , 76 , 77 , 78 , 79 ]. Capnocytophaga gingivalis, Prevotella melaninogenica, and Streptococcus mitis are significantly elevated in the saliva of patients with OSCC with a diagnostic sensitivity and specificity of 80% and 82%, respectively [ 76 ].…”

Oral microbiota in oropharyngeal cancers: Friend or foe?

“…Actinobacteria are particularly represented, alongside with Firmicutes , Bacteroides , and Fusobacteria , in the tongue coating (TC) microbiota ( 8 ). The TC microbiota is particularly related with the development of upper gastrointestinal cancers ( 8 ) and moreover, in the oral squamous cell carcinoma (OSCC) the Actinobacteria genus Veillonella and the species Granulicatella adiacens Veillonella rogosae and Streptococcus sanguinis are particularly abundant in normal paracancerous tissues of OSCC patients ( 9 ).…”

Differences in the microbiota of oral rinse, lesion, and normal site samples from patients with mucosal abnormalities on the tongue

“…Analysis of the oral microbiota associated with oral mucosal disease has been extensively reported. In these studies, saliva 11 – 13 , oral rinse sample/mouthwash 14 – 16 , oral cancer tissues 17 – 20 , swabs 21 – 24 and various clinical specimens 25 were used as the target specimens. The 16S rRNA gene was used as the target gene in most of these studies, but the primer sets used for PCR differed 11 , 15 , 18 , 20 , 21 , 25 .…”

“…In these studies, saliva 11 – 13 , oral rinse sample/mouthwash 14 – 16 , oral cancer tissues 17 – 20 , swabs 21 – 24 and various clinical specimens 25 were used as the target specimens. The 16S rRNA gene was used as the target gene in most of these studies, but the primer sets used for PCR differed 11 , 15 , 18 , 20 , 21 , 25 . Using NGS, nucleotide sequences after filtering and trimming were generally clustered into operational taxonomic units (OTUs) with 97 or 98% similarity and applied to microbiota analysis at the phylum and genus levels.…”