Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic

• Published in: The Journal of clinical investigation Vol. 129; no. 4; pp. 1699 - 1712
• Main Authors: Tomkovich, Sarah, Dejea, Christine M., Winglee, Kathryn, Drewes, Julia L., Chung, Liam, Housseau, Franck, Pope, Jillian L., Gauthier, Josee, Sun, Xiaolun, Mühlbauer, Marcus, Liu, Xiuli, Fathi, Payam, Anders, Robert A., Besharati, Sepideh, Perez-Chanona, Ernesto, Yang, Ye, Ding, Hua, Wu, Xinqun, Wu, Shaoguang, White, James R., Gharaibeh, Raad Z., Fodor, Anthony A., Wang, Hao, Pardoll, Drew M., Jobin, Christian, Sears, Cynthia L.
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.04.2019
• Subjects: Animal models; Animals; Biofilms; Biomedical research; Biopsy; Cancer patients; Carcinogenesis; Carcinogens; Colon - metabolism; Colon - microbiology; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - microbiology; Colonic Neoplasms - pathology; Colonoscopy; Colorectal cancer; Colorectal carcinoma; Diagnosis; Gastrointestinal diseases; Gastrointestinal Microbiome; Genes; Genetic aspects; Genetic research; Genomes; Germfree; Humans; Hypotheses; Inflammation; Inflammatory bowel disease; Interleukin 1; Interleukin 10; Invasiveness; Laboratory rats; Mice; Mice, Knockout; Microbial mats; Microbiota; Microbiota (Symbiotic organisms); Mucosa; Mucus; Neoplasms, Experimental - genetics; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - microbiology; Neoplasms, Experimental - pathology; RNA; RNA sequencing; rRNA 16S; Tumorigenesis; Tumors; Oncology; Bacterial infections; Microbiology; Mouse models; Colorectal cancer
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI124196

Mucus-invasive bacterial biofilms are identified on the colon mucosa of approximately 50% of colorectal cancer (CRC) patients and approximately 13% of healthy subjects. Here, we test the hypothesis that human colon biofilms comprise microbial communities that are carcinogenic in CRC mouse models. Homogenates of human biofilm-positive colon mucosa were prepared from tumor patients (tumor and paired normal tissues from surgical resections) or biofilm-positive biopsies from healthy individuals undergoing screening colonoscopy; homogenates of biofilm-negative colon biopsies from healthy individuals undergoing screening colonoscopy served as controls. After 12 weeks, biofilm-positive, but not biofilm-negative, human colon mucosal homogenates induced colon tumor formation in 3 mouse colon tumor models (germ-free ApcMinΔ850/+;Il10-/- or ApcMinΔ850/+ and specific pathogen-free ApcMinΔ716/+ mice). Remarkably, biofilm-positive communities from healthy colonoscopy biopsies induced colon inflammation and tumors similarly to biofilm-positive tumor tissues. By 1 week, biofilm-positive human tumor homogenates, but not healthy biopsies, displayed consistent bacterial mucus invasion and biofilm formation in mouse colons. 16S rRNA gene sequencing and RNA-Seq analyses identified compositional and functional microbiota differences between mice colonized with biofilm-positive and biofilm-negative communities. These results suggest human colon mucosal biofilms, whether from tumor hosts or healthy individuals undergoing screening colonoscopy, are carcinogenic in murine models of CRC.