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Shift from a Simplified to Complex Gut Microbiota Reduces Adenoma Burden in a Preclinical Rat Model of Colon Cancer

Busi, S. B.; Davis, D.; Moskowitz, J.; Amos-Landgraf, J.

2023-01-25 microbiology
10.1101/2023.01.20.524931 bioRxiv
Show abstract

Specific bacterial taxa in the gastrointestinal tract have been strongly associated with cases of colorectal cancer (CRC) cancer in familial adenomatous polyposis and spontaneous disease cases in humans. This has been recapitulated in animal models of CRC with positive correlations with many commensals and pathogens. However, many of these studies are performed either in germ-free animals or employ an antibiotic regime, overlooking the complex interactions of the commensals within the colon. To simplify the challenges associated with the complexity of the microbiota in the GI tract we established the Pirc rat model of colon cancer on an Altered Schaedler Flora (ASF) gut microbiota (GM), maintained in a barrier room. To elucidate the role of the simplified (ASF) and conventional GMs on disease susceptibility, We conventionalized ASF Pirc littermates. We found that the conventionalized F1 rats had increased microbial diversity and decreased colonic adenoma multiplicity. Our findings show that the complexity and the interactions of the GM community and not a Firmicutes to Bacteroidetes ratio are an important factor affecting disease susceptibility.

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