Yijia Wang1, Xuehua Wan2, Xiaojing Wu1, Chunze Zhang1, Jun Liu3, Shaobin Hou4. 1. Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, No. 190 Jieyuan Rd., Hongqiao district, Tianjin, 300121, China. 2. TEDA Institute of Biological Sciences and Biotechnology, Nankai University, TEDA, Tianjin, 300071, China. 3. Laboratory of Oncologic Molecular Medicine, Tianjin Union Medical Center, Nankai University, No. 190 Jieyuan Rd., Hongqiao district, Tianjin, 300121, China. junliu_sci@163.com. 4. Advanced Studies in Genomics, Proteomics, and Bioinformatics, University of Hawaii At Manoa, 2538 McCarthy Mall, Snyder Hall, Honolulu, HI, 96822, USA. Shaobin@hawaii.edu.
Abstract
BACKGROUND: Inflammatory bowel disease caused by microbial dysbiosis is an important factor contributing to colorectal cancer (CRC) initiation. The 'driver-passenger' model in human gut microbial dysbiosis suggests that 'driver' bacteria may colonize with low relative abundance on tumor site but persistently induce chronic change in normal intestinal epithelium and initiate CRC. They are gradually replaced by 'passenger' bacteria later on, due to their low adaptability to the on-tumor site niche. RESULTS: To reveal site-specific bacterial taxon markers in CRC patients, we analyzed the gut mucosal microbiome of 75 paired samples of on-tumor and tumor-adjacent sites, 75 off-tumor sites, and 26 healthy controls. Linear discriminant analysis of relative abundance profiles revealed unique bacterial taxon distribution correlated with specific tumor sites, with Eubacterium having the distribution characteristic of potential driver bacteria. We further show that Eubacterium rectale endotoxin activates the transcription factor NF-κΒ, which regulates multiple aspects of innate and adaptive immune responses in normal colon epithelial cells. Unlike the 'passenger' bacterium Fusobacterium nucleatum, E. rectale promotes dextran sodium sulfate-induced colitis in Balb/c mice. CONCLUSIONS: Our findings reveal that E. rectale functions as a 'driver' bacterium and contributes to cancer initiation via promoting inflammation.
BACKGROUND:Inflammatory bowel disease caused by microbial dysbiosis is an important factor contributing to colorectal cancer (CRC) initiation. The 'driver-passenger' model in human gut microbial dysbiosis suggests that 'driver' bacteria may colonize with low relative abundance on tumor site but persistently induce chronic change in normal intestinal epithelium and initiate CRC. They are gradually replaced by 'passenger' bacteria later on, due to their low adaptability to the on-tumor site niche. RESULTS: To reveal site-specific bacterial taxon markers in CRC patients, we analyzed the gut mucosal microbiome of 75 paired samples of on-tumor and tumor-adjacent sites, 75 off-tumor sites, and 26 healthy controls. Linear discriminant analysis of relative abundance profiles revealed unique bacterial taxon distribution correlated with specific tumor sites, with Eubacterium having the distribution characteristic of potential driver bacteria. We further show that Eubacterium rectale endotoxin activates the transcription factor NF-κΒ, which regulates multiple aspects of innate and adaptive immune responses in normal colon epithelial cells. Unlike the 'passenger' bacterium Fusobacterium nucleatum, E. rectale promotes dextran sodium sulfate-induced colitis in Balb/c mice. CONCLUSIONS: Our findings reveal that E. rectale functions as a 'driver' bacterium and contributes to cancer initiation via promoting inflammation.
Entities:
Keywords:
Colitis; Colorectal cancer; Eubacterium rectale; Microbiota; ‘driver-passenger’ model
Authors: J Gregory Caporaso; Justin Kuczynski; Jesse Stombaugh; Kyle Bittinger; Frederic D Bushman; Elizabeth K Costello; Noah Fierer; Antonio Gonzalez Peña; Julia K Goodrich; Jeffrey I Gordon; Gavin A Huttley; Scott T Kelley; Dan Knights; Jeremy E Koenig; Ruth E Ley; Catherine A Lozupone; Daniel McDonald; Brian D Muegge; Meg Pirrung; Jens Reeder; Joel R Sevinsky; Peter J Turnbaugh; William A Walters; Jeremy Widmann; Tanya Yatsunenko; Jesse Zaneveld; Rob Knight Journal: Nat Methods Date: 2010-04-11 Impact factor: 28.547
Authors: Amr Mohamed; Sylvia L Asa; Thomas McCormick; Hilmi Al-Shakhshir; Arvind Dasari; Retuerto Mauricio; Iman Salem; Lee M Ocuin; David Bajor; Richard T Lee; J Eva Selfridge; Arash Kardan; Zhenghong Lee; Norbert Avril; Shelby Kopp; Jordan M Winter; Jeffrey M Hardacre; John B Ammori; Mahmoud A Ghannoum Journal: Curr Issues Mol Biol Date: 2022-04-30 Impact factor: 2.976
Authors: Marc-André Gagné; Claude Barbeau; Geneviève Frégeau; Kim Gilbert; Olivier Mathieu; Jérémie Auger; Thomas A Tompkins; Emmanuel Charbonney; Roger Godbout; Guy Rousseau Journal: Sci Rep Date: 2022-10-03 Impact factor: 4.996