Network Analysis of Gut Microbiota Including Fusobacterium and Oral Origin Bacteria and Their Distribution on Tumor Surface, Normal Mucosa, and in Feces in Patients with Colorectal Cancer

Abstract

Introduction: Fusobacterium and several bacteria are reported to be associated with colorectal cancer (CRC). However, their relationship and whether they cause CRC or are just adapted to the cancerous environment is not known. We approached this subject by investigating the correlation and distribution of the bacteria throughout the colon in patients with CRC and elucidated the relationship between microbiota and CRC. Methods: Twenty-five patients with CRC who underwent colonoscopy for endoscopic submucosal dissection or surgery were prospectively enrolled. Fecal samples were taken before bowel preparation, and mucosal samples were collected from three sites (tumor surface, tumor-adjacent mucosa, and cecum) during colonoscopy using a cytology brush. The microbiota was identified and analyzed by sequencing of the 16S rRNA gene of the V3–V4 region. We evaluated the correlation between the bacteria based on network analysis and the distribution of Fusobacterium in the colon. Results: A network consisting of many bacteria was found in all sites; especially, oral origin bacteria including Fusobacterium formed a positively correlated network on tumor surface. Streptococcus showed a significantly higher relative abundance on tumor surface than in feces. The relative abundance of Fusobacterium had significant positive correlations between tumor surface and feces, tumor-adjacent mucosa, and cecum. Conclusion: In patients with CRC, many bacteria were correlated with each other, and Fusobacterium and oral origin bacteria formed a positively correlated network on tumor surface. Fusobacterium was equally distributed on tumor surface and throughout the lumen and mucus in the colon. In the colon where Fusobacterium is widely distributed, Fusobacterium would adhere to the tumor surface and be correlated with oral origin bacteria to make a microenvironment that is favorable for CRC.