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

J Nutr Biochem. 2023 Jan;111:109188. doi: 10.1016/j.jnutbio.2022.109188. Epub 2022 Oct 20.

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 fecal oncogenic signatures reflecting colonic health. We hypothesize that an HFD accelerates the inflammatory process and modulates IL-1R/TLR pathways, gut microbiome, and disease-related miRNA in the colon. In this study, 4-week-old C57BL/6 mice were fed a modified AIN93G diet (AIN, 16% energy fat) or an 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, β-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 an HFD compared to the AIN. Furthermore, the content of Alistipes bacteria, the Firmicutes/Bacteroidetes ratio, microRNA-29a, and deoxycholic and lithocholic acids (secondary bile acids with oncogenic potential) were 55% greater in the feces of the HFD group compared to the AIN group. Collectively, this composite, a multimodal profile may represent a unique HFD-induced fecal signature for colonic inflammation and cancer in C57BL/6 mice.

Keywords: Bile acid; cancer; colonic inflammation; high fat diet; microRNA; microbiome.

MeSH terms

  • Animals
  • Bacteria
  • Colon / metabolism
  • Diet, High-Fat* / adverse effects
  • Dysbiosis* / microbiology
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred C57BL