Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• The Journal of clinical investigation, 2019-04, Vol.129 (4), p.1699-1712

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.