Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer.

TitleMicrobial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer.
Publication TypeJournal Article
Year of Publication2014
AuthorsArthur JC, Gharaibeh RZ, Mühlbauer M, Perez-Chanona E, Uronis JM, McCafferty J, Fodor AA, Jobin C
JournalNat Commun
Volume5
Pagination4724
Date Published2014 Sep 03
ISSN2041-1723
KeywordsAnimals, Colorectal Neoplasms, Escherichia coli, Escherichia coli Infections, Female, Gene Expression, Genes, Bacterial, Genome, Bacterial, Genomic Islands, Host-Pathogen Interactions, Inflammation, Interleukin-10, Male, Mice, Mice, Knockout, Microbiota, RNA, Ribosomal, 16S
Abstract

<p>Enterobacteria, especially Escherichia coli, are abundant in patients with inflammatory bowel disease or colorectal cancer (CRC). However, it is unclear whether cancer is promoted by inflammation-induced expansion of E. coli and/or changes in expression of specific microbial genes. Here we use longitudinal (2, 12 and 20 weeks) 16S rRNA sequencing of luminal microbiota from ex-germ-free mice to show that inflamed Il10(-/-) mice maintain a higher abundance of Enterobacteriaceae than healthy wild-type mice. Experiments with mono-colonized Il10(-/-) mice reveal that host inflammation is necessary for E. coli cancer-promoting activity. RNA-sequence analysis indicates significant changes in E. coli gene catalogue in Il10(-/-) mice, with changes mostly driven by adaptation to the intestinal environment. Expression of specific genes present in the tumour-promoting E. coli pks island are modulated by inflammation/CRC development. Thus, progression of inflammation in Il10(-/-) mice supports Enterobacteriaceae and alters a small subset of microbial genes important for tumour development.</p>

DOI10.1038/ncomms5724
Alternate JournalNat Commun
PubMed ID25182170
PubMed Central IDPMC4155410
Grant ListR01 DK073338 / DK / NIDDK NIH HHS / United States
P40 OD010995 / OD / NIH HHS / United States
R01 DK047700 / DK / NIDDK NIH HHS / United States
P30 DK034987 / DK / NIDDK NIH HHS / United States
R01 DK053347 / DK / NIDDK NIH HHS / United States
R01 DK47700 / DK / NIDDK NIH HHS / United States
R01DK053347 / DK / NIDDK NIH HHS / United States
5P40OD010995 / OD / NIH HHS / United States
R01 DK73338 / DK / NIDDK NIH HHS / United States