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

Sarah Tomkovich, Christine M. Dejea, Kathryn Winglee, Julia Drewes, Liam Chung, Franck Housseau, Jillian L. Pope, Josee Gauthier, Xiaolun Sun, Marcus Mühlbauer, Xiuli Liu, Payam Fathi, Robert A Anders, Sepideh Besharati, Ernesto Perez-Chanona, Ye Yang, Hua Ding, Xinqun Wu, Shaoguang Wu, James R. WhiteRaad Z. Gharaibeh, Anthony A. Fodor, Hao Wang, Andrew Mark Pardoll, Christian Jobin, Cynthia Louise Sears

Research output: Contribution to journalArticle

Abstract

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 Apc Min Δ 850/+ ;Il10 –/– or Apc Min Δ 850/+ and specific pathogen–free Apc Min Δ 716/+ 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.

Original languageEnglish (US)
Pages (from-to)1699-1712
Number of pages14
JournalJournal of Clinical Investigation
Volume129
Issue number4
DOIs
StatePublished - Apr 1 2019

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Biofilms
Colonic Neoplasms
Colon
Colonoscopy
Neoplasms
Biopsy
Colorectal Neoplasms
Mucus
Mucous Membrane
RNA Sequence Analysis
Microbiota
rRNA Genes
Interleukin-10
Healthy Volunteers

ASJC Scopus subject areas

  • Medicine(all)

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Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic. / Tomkovich, Sarah; Dejea, Christine M.; Winglee, Kathryn; Drewes, Julia; 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, Andrew Mark; Jobin, Christian; Sears, Cynthia Louise.

In: Journal of Clinical Investigation, Vol. 129, No. 4, 01.04.2019, p. 1699-1712.

Research output: Contribution to journalArticle

Tomkovich, S, Dejea, CM, Winglee, K, Drewes, J, Chung, L, Housseau, F, Pope, JL, Gauthier, J, Sun, X, Mühlbauer, M, Liu, X, Fathi, P, Anders, RA, Besharati, S, Perez-Chanona, E, Yang, Y, Ding, H, Wu, X, Wu, S, White, JR, Gharaibeh, RZ, Fodor, AA, Wang, H, Pardoll, AM, Jobin, C & Sears, CL 2019, 'Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic', Journal of Clinical Investigation, vol. 129, no. 4, pp. 1699-1712. https://doi.org/10.1172/JCI124196
Tomkovich, Sarah ; Dejea, Christine M. ; Winglee, Kathryn ; Drewes, Julia ; 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, Andrew Mark ; Jobin, Christian ; Sears, Cynthia Louise. / Human colon mucosal biofilms from healthy or colon cancer hosts are carcinogenic. In: Journal of Clinical Investigation. 2019 ; Vol. 129, No. 4. pp. 1699-1712.
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abstract = "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 Apc Min Δ 850/+ ;Il10 –/– or Apc Min Δ 850/+ and specific pathogen–free Apc Min Δ 716/+ 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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AU - Tomkovich, Sarah

AU - Dejea, Christine M.

AU - Winglee, Kathryn

AU - Drewes, Julia

AU - Chung, Liam

AU - Housseau, Franck

AU - Pope, Jillian L.

AU - Gauthier, Josee

AU - Sun, Xiaolun

AU - Mühlbauer, Marcus

AU - Liu, Xiuli

AU - Fathi, Payam

AU - Anders, Robert A

AU - Besharati, Sepideh

AU - Perez-Chanona, Ernesto

AU - Yang, Ye

AU - Ding, Hua

AU - Wu, Xinqun

AU - Wu, Shaoguang

AU - White, James R.

AU - Gharaibeh, Raad Z.

AU - Fodor, Anthony A.

AU - Wang, Hao

AU - Pardoll, Andrew Mark

AU - Jobin, Christian

AU - Sears, Cynthia Louise

PY - 2019/4/1

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N2 - 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 Apc Min Δ 850/+ ;Il10 –/– or Apc Min Δ 850/+ and specific pathogen–free Apc Min Δ 716/+ 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.

AB - 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 Apc Min Δ 850/+ ;Il10 –/– or Apc Min Δ 850/+ and specific pathogen–free Apc Min Δ 716/+ 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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