The preventive effects of inulin, cellulose, and their mixture on colorectal cancer liver metastasis in mice by regulating gut microbiota.

Abstract

Many studies have found that dietary fiber can protect against colorectal cancer (CRC). Survival in CRC patients is significantly reduced due to metastasis. However, little is known regarding the impact of dietary fiber on the CRC metastasis. In this study, we analyzed the effects of inulin, cellulose, and their mixture on CRC metastasis in a murine orthotopic transplantation model. BALB/C male mice were divided into the normal control (NC) (AIN-93M diet), MOD (AIN-93M diet), INU (10% w/w inulin), CEL (10% w/w cellulose), and MIX (5% w/w inulin+5% w/w cellulose) groups. Dietary fiber intake inhibited the weights of the orthotopic tumors, liver weights, and liver metastasis area (p<0.05) and improved the survival rate of tumor-bearing mice. Compared to the NC, the expression of β-catenin and the epithelial marker E-cadherin were lower, and that of mesenchymal markers, such as N-cadherin, MMP-9, and VEGF, were higher in the MOD group. All inulin, cellulose, and their mixture restored the gut microbiota diversity, and they, respectively, increased the relative abundance of Bifidobacteriales, Lactobacillus, and Lachnospiraceae. Inulin restored the levels of acetic acid, propionic acid, isobutyric acid, and butyric acid. Spearman correlation analysis results showed that there was a positive correlation between five genera and six short-chain fatty acids (SCFAs) (adjusted p<0.05). In conclusion, all inulin, cellulose, and their mixture have inhibitory effects on CRC metastasis, which may be achieved by the regulation of gut microbiota, the production of SCFAs, and the inhibition of the epithelial-to-mesenchymal transition process. Among the three dietary fiber intervention groups, the inhibitory effect of inulin is more significant.