title: Differential susceptibility to colorectal cancer due to naturally occurring gut microbiota.
abstract: Recent studies investigating the human microbiome have identified particular bacterial species that correlate with the presence of colorectal cancer. To evaluate the role of qualitatively different but naturally occurring gut microbiota and the relationship with colorectal cancer development, genetically identical embryos from the Polyposis in Rat Colon (Pirc) rat model of colorectal cancer were transferred into recipients of three different genetic backgrounds (F344/NHsd, LEW/SsNHsd, and Crl:SD). Tumor development in the pups was tracked longitudinally via colonoscopy, and end-stage tumor burden was determined. To confirm vertical transmission and identify associations between the gut microbiota and disease phenotype, the fecal microbiota was characterized in recipient dams 24 hours pre-partum, and in Pirc rat offspring prior to and during disease progression. Our data show that the gut microbiota varies between rat strains, with LEW/SsNHsd having a greater relative abundance of the bacteria Prevotella copri. The mature gut microbiota of pups resembled the profile of their dams, indicating that the dam is the primary determinant of the developing microbiota. Both male and female F344-Pirc rats harboring the Lewis microbiota had decreased tumor burden relative to genetically identical rats harboring F344 or SD microbiota. Significant negative correlations were detected between tumor burden and the relative abundance of specific taxa from samples taken at weaning and shortly thereafter, prior to observable adenoma development. Notably, this naturally occurring variation in the gut microbiota is associated with a significant difference in severity of colorectal cancer, and the abundance of certain taxa is associated with decreased tumor burden.
authors.affiliation: Rat Resource and Research Center, University of Missouri, Columbia, MO, USA.|MU Metagenomics Center, University of Missouri, Columbia, MO, USA.|Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Ericsson
authors.affiliation: MU Informatics Institute, University of Missouri, Columbia, MO, USA.
authors.forename: Sadia
authors.initials: S
authors.lastname: Akter
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Marina M
authors.initials: MM
authors.lastname: Hanson
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Susheel B
authors.initials: SB
authors.lastname: Busi
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Taybor W
authors.initials: TW
authors.lastname: Parker
authors.affiliation: College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Schehr
authors.affiliation: Rat Resource and Research Center, University of Missouri, Columbia, MO, USA.|Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Hankins
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Carin E
authors.initials: CE
authors.lastname: Ahner
authors.affiliation: MU Informatics Institute, University of Missouri, Columbia, MO, USA.|Department of Health Management and Informatics, University of Missouri, Columbia, MO, USA.
authors.forename: Justin W
authors.initials: JW
authors.lastname: Davis
authors.affiliation: MU Metagenomics Center, University of Missouri, Columbia, MO, USA.|Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Franklin
authors.affiliation: Rat Resource and Research Center, University of Missouri, Columbia, MO, USA.|Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Amos-Landgraf
authors.affiliation: Rat Resource and Research Center, University of Missouri, Columbia, MO, USA.|Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA.|College of Veterinary Medicine, University of Missouri, Columbia, MO, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Bryda
mesh_terms: D000818:Animals; D015179:Colorectal Neoplasms / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley
keywords: Pirc; colorectal cancer; gut; microbiota; rat