Resistant starch inhibits high-fat diet-induced oncogenic responses in the colon of C57BL/6 mice

Abstract

The beneficial effects of dietary fiber for colon health may be due to short chain fatty acids (SCFAs), such as butyrate, produced by colonic bacterial fermentation. In contrast, obesogenic diet induced obesity is linked to increased colon cancer incidence. We hypothesize that increasing fiber intake promotes healthy microbiome and reduces bacterial dysbiosis and oncogenic signaling in the colon of mice fed an obesogenic diet. About 5-week-old male C57BL/6 mice were assigned to 5 dietary groups (n=22/group) for 24 weeks:(1) AIN93G as a control diet (AIN); (2) a high fat diet (HFD, 45% energy fat); (3) HFD+5% resistant starch enriched dietary fiber (RSF) from maize; (4) HFD+10%RSF; or (5) HFD+20%RSF. Compared to the AIN group, mice receiving the HFD exhibited more than 15% increase in body mass and body fat composition irrespective of RSF dosage. However, the HFD+RSF groups exhibited an increase (>300%) of fecal butyrate but a decrease (>45%) of secondary bile acids in a RSF dose-dependent manner over the HFD group. Similarly, there were concomitant decreases (>25%) in pro-inflammatory plasma cytokines (TNFα, IL-6 and MCP-1), β-catenin and Ki67 protein staining in the colon of the HFD+20%RSF group relative to the HFD group. Furthermore, the abundance of colonic Proteobacteria, signatures of dysbiosis, was decreased (>63%) in a RSF dose-dependent manner compared to the HFD. Collectively, these data indicate that RSF not only increases butyrate but also reduces secondary bile acids, bacterial dysbiosis and β-catenin in the colon of mice fed a HFD.