Increasingly, the gut microbiome is implicated in the etiology of cancer, not only as an infectious agent but also by altering exposure to dietary compounds that influence disease risk. Whereas the composition and metabolism of the gut microbiome is influenced by diet, the gut microbiome can also modify dietary exposures in ways that are beneficial or detrimental to the human host. The colonic bacteria metabolize macronutrients, either as specialists or in consortia of bacteria, in a variety of diverse metabolic pathways. Microbial metabolites of diet can also be epigenetic activators of gene expression that may influence cancer risk in humans. Epigenetics involves heritable changes in gene expression via post-translational and post-transcriptional modifications. Microbial metabolites can influence epigenetics by altering the pool of compounds used for modification or by directly inhibiting enzymes involved in epigenetic pathways. Colonic epithelium is immediately exposed to these metabolites, although some metabolites are also found in systemic circulation. In this review, we discuss the role of the gut microbiome in dietary metabolism and how microbial metabolites may influence gene expression linked to colon cancer risk.