(P10-022-23) Sex Differences in Colonic Gene Expression and Fecal Microbiota Composition in a Mouse Model of Obesity-Associated Colorectal Cancer

Objectives: The correlation between obesity and colorectal cancer is more pronounced in males than in females. In this study, we evaluated the effects of genetic and hormonal factors on sex differences in obesity-associated colorectal carcinogenesis. We also investigated the role of gut microbiota in tumor formation and their compositional differences between sexes.

Methods: C57BL/6J male(M), female(F), and ovariectomized (OVX) female mice were subdivided into two groups fed either a low-fat diet (LFD) or high-fat diet (HFD). Colorectal tumors were induced by azoxymethane + DSS administration. Tumor counts, colonic mucin quantification, tissue microarray analysis and fecal gut microbiota analysis using 16s rRNA sequencing were performed.

Results: Final body weights were in the order of M+HFD >M+LFD=OVX+HFD > F+HFD=OVX+LFD >F+LFD. Adipose tissue weight was highest both in M+HFD and OVX+HFD. Colon tumor number was significantly higher in the M+HFD group than that of all female groups. Colonic MUC2 expression was opposite from tumor numbers. Genes modulated by HFD in each group were narrowly overlapped. Also, sex-specific changes in gut microbial composition were observed in response to HFD.

Conclusions: The HFD-induced increase in colon tumor formation was male-specific. Several hub genes and colonic bacteria in association with HFD may contribute to sex-specific colon carcinogenesis.

Funding Sources: The National Research Foundation of Korea (NRF) funded by the Ministry of Education and the National Research Foundation of Korea, and the Sookmyung Women’s University Research Cluster Program.