Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic
Autor: | Ye Yang, Raad Z. Gharaibeh, Payam Fathi, Shaoguang Wu, Liam Chung, Anthony A. Fodor, Sarah Tomkovich, Sepideh Besharati, Marcus Mühlbauer, James R. White, Jillian L. Pope, Cynthia L. Sears, Ernesto Perez-Chanona, Drew M. Pardoll, Julia L. Drewes, Kathryn Winglee, Xinqun Wu, Robert A. Anders, Christian Jobin, Franck Housseau, Christine M. Dejea, Hao Wang, Xiaolun Sun, Josee Gauthier, Xiuli Liu, Hua Ding |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Carcinogenesis Colon Colorectal cancer Colonoscopy Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Carcinogen Mice Knockout medicine.diagnostic_test business.industry Biofilm Neoplasms Experimental General Medicine biochemical phenomena metabolism and nutrition medicine.disease Mucus digestive system diseases Gastrointestinal Microbiome Human tumor 030104 developmental biology Mouse Colon Biofilms 030220 oncology & carcinogenesis Colonic Neoplasms business Human colon |
Zdroj: | Journal of Clinical Investigation. 129:1699-1712 |
ISSN: | 1558-8238 0021-9738 |
Popis: | 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. |
Databáze: | OpenAIRE |
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