Figure S1: Schematic representation of the AOM-DSS experimental design. Figure S2: Dietary emulsifiers promote metabolic syndrome and low-grade intestinal inflammation in WT mice. Figure S3: Colonic histology analysis of emulsifiers promotion of colitis-associated cancer. Figure S4: Dietary emulsifiers induce alterations of the microbiota. Figure S5: Alpha diversity and summarized taxa of the fecal bacterial community following emulsifier treatment. Figure S6: Identification of bacterial members differentially expressed between experimental groups. Figure S7: Dietary emulsifiers favor a pro-inflammatory microbiota. Figure S8: Metagenome prediction analysis following CMC consumption. Figure S9: Metagenome prediction analysis following P80 consumption. Figure S10: Dietary emulsifiers alter epithelial cell proliferation and apoptosis during colitis-associated cancer development. Figure S11: Dietary emulsifier and AOM injection experiment.
ARTICLE ABSTRACT
The increased risks conferred by inflammatory bowel disease (IBD) to the development of colorectal cancer gave rise to the term “colitis-associated cancer” and the concept that inflammation promotes colon tumorigenesis. A condition more common than IBD is low-grade inflammation, which correlates with altered gut microbiota composition and metabolic syndrome, both present in many cases of colorectal cancer. Recent findings suggest that low-grade inflammation in the intestine is promoted by consumption of dietary emulsifiers, a ubiquitous component of processed foods, which alter the composition of gut microbiota. Here, we demonstrate in a preclinical model of colitis-induced colorectal cancer that regular consumption of dietary emulsifiers, carboxymethylcellulose or polysorbate-80, exacerbated tumor development. Enhanced tumor development was associated with an altered microbiota metagenome characterized by elevated levels of lipopolysaccharide and flagellin. We found that emulsifier-induced alterations in the microbiome were necessary and sufficient to drive alterations in major proliferation and apoptosis signaling pathways thought to govern tumor development. Overall, our findings support the concept that perturbations in host–microbiota interactions that cause low-grade gut inflammation can promote colon carcinogenesis. Cancer Res; 77(1); 27–40. ©2016 AACR.
