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

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. Ho...

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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
Online Access:Get full text
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Summary: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.
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Authorship note: ST, CMD, CJ, and CLS contributed equally to this work.
ISSN:0021-9738
1558-8238
1558-8238
DOI:10.1172/JCI124196