Title of Oral/Poster Presentation

The Total Western Diet and Vancomycin Increase Inflammation Mediated Colorectal Cancer.

Class

Article

College

College of Agriculture and Applied Sciences

Faculty Mentor

Korry Hintze

Presentation Type

Oral Presentation

Abstract

Total Western Diet (TWD) fed mice have increased azoxymethane/dextran sodium sulfate (AOM/DSS) induced colorectal cancer (CRC). Using the AOM/DSS model, another group found that vancomycin (VM) reduced CRC via changes to the microbiome. This study was done to determine interactions between diet and VM induced changes to the microbiome on CRC. C57BL/6J mice were allotted into 4 treatments in a 2X2 factorial design: 1)AIN93G diet+no VM (AN, n=33); 2)AIN93G+VM in drinking water (2g/L, AVM, n=30); 3)TWD+no VM (TN, n=35); 4)TWD+VM (TVM, n=29). Food and water was provided ad libitum with intakes measured weekly. Fecal samples were collected for microbiome analysis. After 14 days, mice were injected with AOM (10 mg/kg) to induce CRC, followed by 1% DSS added to drinking water for 10 days to induce inflammation. Mice were evaluated for colitis disease activity (CAD). After recovery (24 days post AOM), 48 mice (n=12 per group) were sacrificed and colons were examined by histopathology. Remaining mice were kept on treatments for 9 additional weeks, sacrificed, and colons were examined for tumor burden and histopathology. TWD increased CAD compared to AIN93G during active colitis (P<0.001); the same effect was found when assessing mucosal injury (P=0.01). TWD and VM increased tumor burden (P=0.02 for diet, P=0.002 for VM treatment) and multiplicity (P<0.001 for diet and VM treatment); there were significant interactions between these factors for tumor burden (P=0.03) and multiplicity (P=0.04). The greatest difference for tumor burden was between TVM mice (49.7510.06mm3, meanSEM) and AN mice (12.343.67mm3, P<0.01). Tumor multiplicity showed similar results. Beta diversity analysis of the microbiome demonstrated that VM determined whether samples clustered together. The TWD increased CRC; contrary to a prior report, we demonstrate VM increases CRC. There are significant interactions between these factors. These results suggest that diet and the gut microbiome modulate CRC.

Location

Room 421

Start Date

4-12-2018 1:30 PM

End Date

4-12-2018 2:45 PM

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Apr 12th, 1:30 PM Apr 12th, 2:45 PM

The Total Western Diet and Vancomycin Increase Inflammation Mediated Colorectal Cancer.

Room 421

Total Western Diet (TWD) fed mice have increased azoxymethane/dextran sodium sulfate (AOM/DSS) induced colorectal cancer (CRC). Using the AOM/DSS model, another group found that vancomycin (VM) reduced CRC via changes to the microbiome. This study was done to determine interactions between diet and VM induced changes to the microbiome on CRC. C57BL/6J mice were allotted into 4 treatments in a 2X2 factorial design: 1)AIN93G diet+no VM (AN, n=33); 2)AIN93G+VM in drinking water (2g/L, AVM, n=30); 3)TWD+no VM (TN, n=35); 4)TWD+VM (TVM, n=29). Food and water was provided ad libitum with intakes measured weekly. Fecal samples were collected for microbiome analysis. After 14 days, mice were injected with AOM (10 mg/kg) to induce CRC, followed by 1% DSS added to drinking water for 10 days to induce inflammation. Mice were evaluated for colitis disease activity (CAD). After recovery (24 days post AOM), 48 mice (n=12 per group) were sacrificed and colons were examined by histopathology. Remaining mice were kept on treatments for 9 additional weeks, sacrificed, and colons were examined for tumor burden and histopathology. TWD increased CAD compared to AIN93G during active colitis (P<0.001); the same effect was found when assessing mucosal injury (P=0.01). TWD and VM increased tumor burden (P=0.02 for diet, P=0.002 for VM treatment) and multiplicity (P<0.001 for diet and VM treatment); there were significant interactions between these factors for tumor burden (P=0.03) and multiplicity (P=0.04). The greatest difference for tumor burden was between TVM mice (49.7510.06mm3, meanSEM) and AN mice (12.343.67mm3, P<0.01). Tumor multiplicity showed similar results. Beta diversity analysis of the microbiome demonstrated that VM determined whether samples clustered together. The TWD increased CRC; contrary to a prior report, we demonstrate VM increases CRC. There are significant interactions between these factors. These results suggest that diet and the gut microbiome modulate CRC.