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Supplementary Materials and Methods, Supplementary Figures 1 through 5, and Supplementary Tables 1 through 3 from Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis

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posted on 2023-03-31, 00:23 authored by Sarah Tomkovich, Ye Yang, Kathryn Winglee, Josee Gauthier, Marcus Mühlbauer, Xiaolun Sun, Mansour Mohamadzadeh, Xiuli Liu, Patricia Martin, Gary P. Wang, Eric Oswald, Anthony A. Fodor, Christian Jobin

Supplementary Materials and Methods describing 16S rRNA sequencing analysis. Figure S1. PCR detection of F. nucleatum adhesins. Figure S2. ApcMin/+;Il10-/- mice have increased colon proliferation. Figure S3. Bacteria do not promote colon inflammation and tumorigenesis in ApcMin/+ mice. Figure S4. Microbiota promote proximal colon proliferation in ApcMin/+;Il10-/- mice. Figure S5. Colibactin promotes CRC development in AOM/Il10-/- mice. Table S1. Spearman correlations and corresponding p values from linear models used to generate Figure 3. Table S2. V1-V3 MiSeq Primers. Table S3. Accession numbers for 16S rRNA sequenced ApcMin/+;Il10-/- stool samples from Figure 3.

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ARTICLE ABSTRACT

Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF) ApcMin/+and ApcMin/+;Il10−/− mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found that colon tumorigenesis significantly correlated with inflammation in SPF-housed ApcMin/+;Il10−/−, but not in ApcMin/+mice. In contrast, small intestinal neoplasia development significantly correlated with age in both ApcMin/+;Il10−/− and ApcMin/+ mice. GF ApcMin/+;Il10−/− mice conventionalized by an SPF microbiota had significantly more colon tumors compared with GF mice. Gnotobiotic studies revealed that while Fusobacterium nucleatum clinical isolates with FadA and Fap2 adhesins failed to induce inflammation and tumorigenesis, pks+Escherichia coli promoted tumorigenesis in the ApcMin/+;Il10−/− model in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest a distinct etiology of cancers in different locations of the gut, where colon cancer is primarily driven by inflammation and the microbiome, while age is a driving force for small intestine cancer. Cancer Res; 77(10); 2620–32. ©2017 AACR.

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    Cancer Research

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    Gastrointestinal CancersColorectal cancerPreclinical ModelsAnimal models of cancer

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