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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Vydáno v:	The Journal of clinical investigation Ročník 129; číslo 4; s. 1699 - 1712
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States American Society for Clinical Investigation 01.04.2019
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Authorship note: ST, CMD, CJ, and CLS contributed equally to this work.
ISSN:	0021-9738 1558-8238 1558-8238
DOI:	10.1172/JCI124196