title: Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer.
abstract: 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.
authors.affiliation: 1] Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27713, USA [2].
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Arthur
authors.affiliation: 1] Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA [2] Bioinformatics Services Division, Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Kannapolis, North Carolina 28081, USA [3].
authors.forename: Raad Z
authors.initials: RZ
authors.lastname: Gharaibeh
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27713, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Mühlbauer
authors.affiliation: 1] Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27713, USA [2] Department of Medicine, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Perez-Chanona
authors.affiliation: 1] Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27713, USA [2].
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Uronis
authors.affiliation: Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McCafferty
authors.affiliation: Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fodor
authors.affiliation: 1] Department of Medicine, University of Florida, Gainesville, Florida 32611, USA [2] Department of Infectious Diseases and Pathology, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D004926:Escherichia coli / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D044404:Genomic Islands; D054884:Host-Pathogen Interactions; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota / Q000235:genetics / Q000276:immunology; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: C556062:IL10 protein, mouse; D012336:RNA, Ribosomal, 16S; D016753:Interleukin-10