Oral leukoplakia patients exhibit a specific oral microbiome dysbiosis

We examined the microbiome in 216 swabs of histologically-proven oral leukoplakia (OLK) from 177 patients. Compared to healthy controls (n=120 swabs from 61 patients) who had better oral health and smoked less, the OLK patients exhibited increased abundance Rothia mucilaginosa, Streptococcus parasanguinis and S. salivarius, resembling a dysbiotic acetaldehyde generating community described previously (J. Oral. Microbiol. 2018,10,1492316). Compared to the patients healthy CLN mucosa (n=202), OLK sites exhibited increased S. infantis clade 431, Leptotrichia spp., Bergeyella spp., Porphyromonas spp. and F. nucleatum. The OLK microbiome was also influenced by the degree of epithelial dysplasia. Low risk OLK (no or mild dysplasia) was characterised by reduced abundance of specific taxa relative to high-risk (moderate or severe dysplasia). Using machine learning techniques, clinical and microbiome data could effectively discriminate high-risk and low-risk dysplasia (sensitivity 87.4 percent; specificity 76.5 percent). Follow-up swabs (n=107) were recovered from 58 patients twelve months after the initial swab. Eight of these OLKs progressed to a higher grade of dysplasia or to OSCC and these patients exhibited significantly higher levels of Fusobacterium species at initial presentation compared to those who did not progress. In summary, the microbiome shifts observed in OLK patients may play a role in the genesis or progression of dysplasia, perhaps involving increased generation of carcinogenic acetaldehyde. Future work will investigate whether the specific microbiome signatures observed here may be useful in predicting the degree of dysplasia or the risk of progression.