Calorie restriction remodels gut microbiota and suppresses tumorigenesis of colorectal cancer in mice

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide and the consumption of a high-calorie diet is one of its risk factors. Calorie restriction (CR) slows tumor growth in a variety of cancers, including colorectal cancer; however, the mechanism behind this remains unknown. In the present study, CR effectively reduced the tumor volume and weight in a xenograft BALB/c male nude mouse model. In addition, tumor immunohistochemistry revealed that the CR group had significantly higher expression of Bax (P<0.001) and significantly lower levels of Bcl2 (P<0.0001) and Ki67 (P<0.001) compared with control group. Furthermore, data from 16S ribosomal (r)RNA sequencing implied that CR was able to reprogram the microbiota structure, characterized by increased Lactobacillus constituent ratio (P<0.05), with amelioration of microbial dysbiosis caused by CRC. Further receiver operating characteristic curves demonstrated that the bacteria Bacteroides [area under the curve (AUC)=0.800], Lactobacillus (AUC= 0.760) and Roseburia (AUC= 0.720) served key roles in suppression of CRC in the mouse model. The functional prediction of intestinal flora indicated 'cyanoamino acid metabolism' (P<0.01), 'replication initiation protein REP (rolling circle plasmid replication)' (P<0.01), 'tRNA G10 N-methylase Trm11' (P<0.01) and 'uncharacterized protein with cyclophilin fold, contains DUF369 domain' (P<0.05) were downregulated in CR group. These findings implied that CR suppressed CRC in mice and altered the gut microbiota.

Metabolic Alteration Bridging the Prediabetic State and Colorectal Cancer

“…In mice affected by high-fat diet-induced prediabetes, the calorie-restricting dietary regimen ameliorated glucose metabolism and Cx36 gap junction alterations, Ca2+-mediated mechanisms, and insulin secretion [54]. Similarly, in a CRC mouse model, caloric restriction was able to inhibit tumor growth and survival via upregulation of pro-apoptotic Bax, reduced Bcl2 and Ki67 levels, and restoration of CRC-induced gut dysbiosis [119]. Recent evidence described the role of food-derived bioactive compounds in different diseases, thus, their characterization could represent a critical strategy for a molecular-based nutritional approach for prediabetes and CRC [120,121].…”

The Interplay between Medical Plants and Gut Microbiota in Cancer

“…A diet rich in vegetables has several benefits in terms of health promotion and is linked to a reduction in systemic and local intestinal inflammation. For example, resveratrol is a substance contained in peanuts, grapes, berries, and red wine, in plants after fungal infection, exposure to ultra-violet (UV) radiation, and mechanical injury, and acts by inhibiting NF-KB and consenting Bcl-2 to exert its proapoptotic effect [20,28,55,[100][101][102][103][104][105][106][107][108][109]. During inflammatory processes, immune cells produce interleukin 6 (IL-6) which ties to the soluble IL-6 receptor or the membrane IL-6 receptor and forms a complex that interacts with glycoprotein 130 and determines an upregulation of the transcription factor signal transducer and activator of transcription 3 (STAT-3).…”