OGG1-deficient (Ogg1-/-) animals display increased propensity to age-induced and diet-induced metabolic diseases, including insulin resistance and fatty liver. Since the intestinal microbiome is increasingly understood to play a role in modulating host metabolic responses, we examined gut microbial composition in Ogg1-/- mice subjected to different nutritional challenges. Interestingly, Ogg1-/- mice had a markedly altered intestinal microbiome under both control-fed and hypercaloric diet conditions. Several microbial species that were increased in Ogg1-/- animals were associated with increased energy harvest, consistent with their propensity to high-fat diet induced weight gain. In addition, several pro-inflammatory microbes were increased in Ogg1-/- mice. Consistent with this observation, Ogg1-/- mice were significantly more sensitive to intestinal inflammation induced by acute exposure to dextran sulfate sodium. Taken together, these data indicate that in addition to their proclivity to obesity and metabolic disease, Ogg1-/- mice are prone to colonic inflammation. Further, these data point to alterations in the intestinal microbiome as potential mediators of the metabolic and intestinal inflammatory response in Ogg1-/- mice.