RESEARCH ARTICLE
Altered Interactions between the Gut Microbiome and Colonic Mucosa Precede Polyposis in APCMin/+ Mice Joshua S. Son1, Shanawaj Khair1, Donald W. Pettet, III1, Nengtai Ouyang1, Xinyu Tian2, Yuanhao Zhang2, Wei Zhu2, Gerardo G. Mackenzie3, Charles E. Robertson4, Diana Ir4, Daniel N. Frank4, Basil Rigas1, Ellen Li1* 1 Department of Medicine, Stony Brook University, Stony Brook, NY, United States of America, 2 Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, United States of America, 3 Department of Preventive Medicine, Stony Brook University, Stony Brook, NY, United States of America, 4 Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America *
[email protected]
OPEN ACCESS Citation: Son JS, Khair S, Pettet DW, III, Ouyang N, Tian X, Zhang Y, et al. (2015) Altered Interactions between the Gut Microbiome and Colonic Mucosa Precede Polyposis in APCMin/+ Mice. PLoS ONE 10(6): e0127985. doi:10.1371/journal.pone.0127985 Editor: Markus M. Heimesaat, Charité, Campus Benjamin Franklin, GERMANY Received: December 23, 2014 Accepted: April 21, 2015 Published: June 29, 2015 Copyright: © 2015 Son et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper. Raw 16S rRNA gene sequence data are deposited in NCBI Short Read Archive under BioProject Assession Number: PRJNA270112 (www. ncbi.nlm.nih.gov/bioproject/PRJNA270112). The RNA-Sequence data are deposited in NCBI's Gene Expression Omnibus database with accession number GSE67634. Funding: This work was supported by 269010 Simons Foundation (www.simonsfoundation.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Abstract Mutation of the adenomatous polyposis coli (APC gene), an early event in the adenoma-carcinoma sequence, is present in 70-80% of sporadic human colorectal adenomas and carcinomas. To test the hypothesis that mutation of the APC gene alters microbial interactions with host intestinal mucosa prior to the development of polyposis, culture-independent methods (targeted qPCR assays and Illumina sequencing of the 16S rRNA gene V1V2 hypervariable region) were used to compare the intestinal microbial composition of 30 sixweek old C57BL/6 APCMin/+ and 30 congenic wild type (WT) mice. The results demonstrate that similar to 12-14 week old APCMin/+ mice with intestinal neoplasia, 6 week old APCMin/+ mice with no detectable neoplasia, exhibit an increased relative abundance of Bacteroidetes spp in the colon. Parallel mouse RNA sequence analysis, conducted on a subset of proximal colonic RNA samples (6 APCMin/+, 6 WT) revealed 130 differentially expressed genes (DEGs, fold change 2, FDR
