Modulation of intestinal metabolites by calorie restriction and its association with gut microbiota in a xenograft model of colorectal cancer

Abstract

Abstract Background Colorectal cancer (CRC) is a common malignant tumor, and its occurrence and development are closely related to dysbiosis of gut microbes. Previously, we found calorie restriction altered the composition of the microbial community in a colorectal cancer mouse model and inhibited in vivo growth of CRC cells. Here, we aim to further investigate alteration in the intestinal metabolites and explore the interplay between gut microbiota and intestinal metabolites upon calorie restriction. Methods Human colorectal cancer HCT116 cells were used to establish a colorectal cancer xenograft mouse model. The changes of intestinal metabolites in the ad libitum group and calorie restriction group were investigated through untargeted metabolomics analysis. The integrative analysis of gut microbiota and metabolites to elucidate the associations between gut microbiota and intestinal metabolites. Results Compared with the mice in the ad libitum group, mice upon calorie restriction exhibited downregulation of Isoleucyl-Valine, and upregulation of D-Proline, 1-Palmitoylphosphatidylcholine, and 4-Trimethylammoniobutanoic acid. Additionally, an integrative analysis of gut microbiota and metabolites revealed that Lactobacillus, Parabacteroides and rC4-4 genus were upregulated in the calorie restriction group and positively correlated with D-Proline, 4-Trimethylammoniobutanoic acid or 1-Palmitoylphosphatidylcholine, while negatively correlated with Isoleucyl-Valine. In contrast, the Nitrospirae and Deferribacteres phylum exhibited opposite trends. Conclusion Calorie restriction affects the abundance of gut microbes such as Nitrospirae phylum and Lactobacillus genus in mouse model of colorectal cancer, leading to changes in the metabolites such as D-Proline、Isoleucyl-Valine, which contributes to the suppression of in vivo growth of CRC by calorie restriction.

Keywords

• Caloric restriction
• Colorectal cancer
• Intestinal metabolites
• Gut microbiota