The microbiome and colorectal neoplasia: environmental modifiers of dysbiosis

Abstract

The etiology of colon cancer is complex, yet it is undoubtedly impacted by intestinal microbiota. Whether the contribution to colon carcinogenesis is generated through the presence of an overall dysbiosis or by specific pathogens is still a matter for debate. However, it is apparent that interactions between microbiota and the host are mediated by a variety of processes, including signaling cascades, the immune system, host metabolism, and regulation of gene transcription. To fully appreciate the role of microbiota in colon carcinogenesis, it will be necessary to expand efforts to define populations in niche environments, such as colonic crypts, explore cross talk between the host and the microbiota, and more completely define the metabolomic profile of the microbiota. These efforts must be pursued with appreciation that dietary substrates and other environmental modifiers mediate changes in the microbiota, as well as their metabolism and functional characteristics.

Figure 1

The contribution of microbiota to maintenance of gut health and prevention of colon cancer is multidimensional in nature. Complex microbial heterogeneity within the luminal environment, as well as the micro-environment(s) within colonic crypts, modulates colonocyte and immune cell processes. Many modifiers to the human superorganism exist, including diet, antibiotics, radiation and early life exposures. The net effects of these perturbations include changes in the luminal and/or crypt specific microbiota and their functional characteristics, including metabolite generation. Host responses include changes in metabolism, inflammation, and regulation of gene expression.