Identification of fecal oncogenic signatures in the inflammatory colon of C57BL/6 mice fed a high fat diet

Authors: Zeng, Huawei; Safratowich, Bryan; CHENG, WEN-HSING - Mississippi State University; Bukowski, Michael

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/15/2022
Publication Date: 10/20/2022
Citation: Zeng, H., Safratowich, B.D., Cheng, W., Bukowski, M.R. 2022. Identification of fecal oncogenic signatures in the inflammatory colon of C57BL/6 mice fed a high fat diet. Journal of Nutritional Biochemistry. 111. https://doi.org/10.1016/j.jnutbio.2022.109188.
DOI: https://doi.org/10.1016/j.jnutbio.2022.109188

Interpretive Summary: Colon cancer is one of the most common cancers in the United States and other Western countries, and the incidence among young adults has increased over the last several decades. Adoption of obesogenic diets such as a high fat diet results in obesity, gut microbial imbalance, chronic inflammation and cancer. However, the mechanisms underlying this relationship remains to be elucidated. Recent studies have shown that accumulation of excess body fat is associated with chronic inflammation and changes in the gut bacteria. In this study, we identified several biochemical markers and bacterial species (in the feces) which were related to colonic inflammation and cancer in a mouse model in the context of obesity-related inflammation. These data provide novel approaches to the quest for a noninvasive biomarker of colonic inflammation / cancer and will be useful for scientists who are interested in diet and colon cancer prevention.

Technical Abstract: Adoption of an obesogenic diet such as a high fat diet (HFD) results in obesity, bacterial dysbiosis, chronic inflammation and cancer. Gut bacteria and their metabolites are recognized by interleukin-1 (IL-1R)/toll-like receptors (TLRs) which are essential to maintain intestinal homeostasis. Moreover, host extracellular microRNAs (miRNAs) can alter bacterial growth in the colon. Characterization of the underlying mechanisms may lead to identifying oncogenic signatures in the feces reflecting colonic health. We hypothesize that a HFD accelerates the inflammatory process and modulates IL-1R/TLR pathways, gut microbiome composition, and disease-related miRNA in the colon. In this study, four-week-old C57BL/6 mice were fed a modified AIN93G diet (AIN, 16% energy fat) or a HFD (45% energy fat) for 15 weeks. In addition to increased body weight and body fat composition, the concentrations of plasma interleukin 6 (IL-6), inflammatory cell infiltration, '-catenin and cell proliferation marker (Ki67) in the colon were elevated > 68% in the HFD group compared to the AIN group. Using a PCR array analysis, we identified 14 out of 84 genes with a = 24% decrease in mRNA content related to IL-1R and TLR pathways in colonic epithelial cells in mice fed a HFD compared to an AIN93 diet. Furthermore, the content of Alistipes bacteria, the Firmicutes/Bacteroidetes ratio, microRNA-29a, and deoxycholic and lithocholic acids (secondary bile acids with oncogenic potential) were at least 55% greater in the feces of the HFD group compared to the AIN group. Collectively, this composite, multimodal profile may represent a unique HFD-induced fecal signature for colonic inflammation and cancer in C57BL/6 mice.