The Western Dietary Pattern Combined with Vancomycin-Mediated Changes to the Gut Microbiome Exacerbates Colitis Severity and Colon Tumorigenesis.

Niklas D Aardema,Daphne M Rodriguez,Abby D Benninghoff,Arnaud J Van Wettere,Korry J Hintze

doi:10.3390/nu13030881

Abstract

Previous work by our group using a mouse model of inflammation-associated colorectal cancer (CAC) showed that the total Western diet (TWD) promoted colon tumor development. Others have also shown that vancomycin-mediated changes to the gut microbiome increased colorectal cancer (CRC). Therefore, the objective of this study was to determine the impact of vancomycin on colon tumorigenesis in the context of a standard mouse diet or the TWD. A 2 × 2 factorial design was used, in which C57Bl/6J mice were fed either the standard AIN93G diet or TWD and with vancomycin in the drinking water or not. While both the TWD and vancomycin treatments independently increased parameters associated with gut inflammation and tumorigenesis compared to AIN93G and plain water controls, mice fed the TWD and treated with vancomycin had significantly increased tumor multiplicity and burden relative to all other treatments. Vancomycin treatment significantly decreased alpha diversity and changed the abundance of several taxa at the phylum, family, and genus levels. Conversely, basal diet had relatively minor effects on the gut microbiome composition. These results support our previous research that the TWD promotes colon tumorigenesis and suggest that vancomycin-induced changes to the gut microbiome are associated with higher tumor rates.

Highlights

The risk for colorectal cancer (CRC) is multifaceted and factors can include genetics, age, diet, inflammation, and the composition of the gut microbiome [1]
We have further demonstrated that the total Western diet (TWD), a diet formulated to model the typical American diet, has the significant main effects of increasing colonic inflammation and tumor development
We have demonstrated that vancomycin-induced changes to the gut microbiome increase colitis and CRC

Summary

Introduction

The risk for colorectal cancer (CRC) is multifaceted and factors can include genetics, age, diet, inflammation, and the composition of the gut microbiome [1]. When comparing the relative abundances of taxa present in the intestinal microbiome of healthy individuals to patients with CRC, studies have shown an increased abundance of Fusobacterium [10,11,12], Enterococcaceae [12,13], Peptostreptococcus [11,12], and Erysipelotrichaceae [12,14], and decreased Faecalibacterium [11,12], Roseburia [11,12], Blautia [11], and Bifidobacterium [11,15,16], among others. The results of these studies support the growing idea that changes to the gut microbiome, whether a cause or a consequence of CRC, are related to the disease

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