Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma

Abstract

Studies on the possible association between bacteria and oral squamous cell carcinoma (OSCC) remain inconclusive, largely due to methodological variations/limitations. The objective of this study was to characterize the species composition as well as functional potential of the bacteriome associated with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep-epithelium swabs (matched control subjects) was sequenced for the V1-V3 region using Illumina’s 2 × 300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a prioritized BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum was the most significantly overrepresented species in the tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44, while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae were the most significantly abundant in the controls. Functional prediction showed that genes involved in bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors while those responsible for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were significantly associated with the controls. This is the first epidemiological evidence for association of F. nucleatum and P. aeruginosa with OSCC. Functionally, an “inflammatory bacteriome” is enriched in OSSC.

World Workshop on Oral Medicine VII: Targeting the oral microbiome Part 2: Current knowledge on malignant and potentially malignant oral disorders

“…Al‐Hebshi et al. () and Schmidt et al. () found that Fusobacterium was significantly enriched in OSCC, whereas Mukherjee et al.…”

“…() found that Streptococcus was significantly enriched in OSCC, whereas Al‐Hebshi et al. () found this genus to be significantly enriched in the controls. Al‐Hebshi et al.…”

“…Twenty‐three non‐specific sequence‐based identification studies of the microbiota were included, 14 of which were published in 2017–2018 (Table ) (Al‐Hebshi, Nasher, Idris, & Chen, ; Al‐Hebshi et al., ; Bebek et al., ; Börnigen et al., ; Guerrero‐Preston et al., , ; Hayes et al., ; Hooper et al., ; Hu, Zhang, Hua, & Chen, ; Lee et al., ; Li et al., ; Mukherjee et al., ; Perera et al., , ; Pushalkar et al., , ; Schmidt et al., ; Shin et al., ; Wang et al., ; Wolf et al., ;Yang, Huang et al., ; Yang, Yeh et al., ; Zhao et al., ). Twenty‐one studies focused on bacterial identification (all by 16S rRNA gene regions), one of which also identified fungi (ITS2 gene fragment), one only fungi, and one was restricted to viral identification (human rRNA detection followed by search for viral sequences).…”

“…() found this genus to be significantly enriched in the controls. Three studies reported that Peptostreptococcus was significantly enriched in OSCC (Al‐Hebshi et al., ; Pushalkar et al., ; Zhao et al., ). Six studies that analysed tissue/swab samples included identification to species level, in which cases the diversity was even more pronounced.…”

Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus

“…The prevalence of oropharyngeal SCC related to high-risk human papillomaviruses (HPV) has increased from 40.5% in 2000 to 72.2% in 2010. [12][13][14] However, the significance of many of the studies associating the oral microbiome with OC-SCC remains unclear due to the lack of statistical correction for false discoveries associated with multiple comparisons, heterogeneous patient population with mixed oropharyngeal and OC-SCC, and no control for important confounding risk factors for OC-SCC. In contrast, the prevalence of HPV in OC-SCC is unclear and greatly varied across multiple studies with an average of 23.3%.…”