Effect of Diet and Genetic Background on the Gut Microbiome and Colorectal Cancer in Mice
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Although interest in the gut microbiome is at the forefront of research in recent years, there is still much to discover about its ever-changing nature and its importance to our health. This study examined the effects of diet and genetic background on the microbial composition in the gut and tumor load in mice. Four inbred mouse strains (A/J, C57BL/6J, FVB/NJ, and NOD/ShiltJ) were selected because of their known susceptibilities to colorectal cancer. The four diets used in this experiment were Western, Japanese, ketogenic, and standard mouse chow. The mice were given four weekly azoxymethane injections to induce tumors. To analyze the gut microbial composition, DNA was extracted from feces, sequenced, and analyzed for variation in bacterial species and functional genes associated with tumor proliferation. Colons dissected from the mice postpartum were used to determine average tumor size, tumor count, and overall tumor load as it varied between strains. In the FVB strain, ketogenic diet significantly increased tumor load by over 300%. This was correlated with a decrease in relative abundance of Clostridiales and Lactobacillales. Both of these genera have been shown to synthesize compounds that inhibit tumor proliferation. A significant increase in relative abundance of the genera Bacteroidales and Sphaerochaetales was also seen in mice on the ketogenic diet. The genera Bacteroidales produce a certain oncogenic toxin that encourages growth of tumors in the colon. Several other genera have been overrepresented in the microbiota of mice on ketogenic diet including Spaerochaetales and Verrucmicrobiales. These genera were absent in most mice but were present in all mice that ate a diet that increased their incidence of colorectal cancer. By identifying and understanding how the gut microbiome composition is related to cancer severity, researchers can better understand the tremendous impact the gut microbiome has on health and disease.
Moore, Lora A (2017). Effect of Diet and Genetic Background on the Gut Microbiome and Colorectal Cancer in Mice. Undergraduate Research Scholars Program. Available electronically from