Shaping functional gut microbiota using dietary bioactives to reduce colon cancer risk

Abstract

Colon cancer is a multifactorial disease associated with a variety of lifestyle factors. Alterations in the gut microbiota and the intestinal metabolome are noted during colon carcinogenesis, implicating them as critical contributors or results of the disease process. Diet is a known determinant of health, and as a modifier of the gut microbiota and its metabolism, a critical element in maintenance of intestinal health. This review summarizes recent evidence demonstrating the role and responses of the intestinal microbiota during colon tumorigenesis and the ability of dietary bioactive compounds and probiotics to impact colon health from the intestinal lumen to the epithelium and systemically. We first describe changes to the intestinal microbiome, metabolome, and epithelium associated with colon carcinogenesis. This is followed by a discussion of recent evidence indicating how specific classes of dietary bioactives, prebiotics, or probiotics affect colon carcinogenesis. Lastly, we briefly address the prospects of using multiple 'omics' techniques to integrate the effects of diet, host, and microbiota on colon tumorigenesis with the goal of more fully appreciating the interconnectedness of these systems and thus, how these approaches can be used to advance personalized nutrition strategies and nutrition research.

Keywords: Bioactives; Colon cancer; Metabolome; Microbiome.

Fig 1. Graphical depiction of the diet-host-microbe interaction

This overview figure represents example mechanisms whereby diet-microbe-host interactions are associated with colon carcinogenesis. In addition to direct effects of diet on host health and metabolism, diet can be a modifier of the gut microbiome (e.g., its composition and functional attributes). Gut microbiota are capable of furtherer metabolizing dietary bioactives to generate secondary bioactive compounds, which can affect host physiology. Exchange of metabolites between different microbes in the gut is possible and adds complexity to the diet-microbe-host interaction network. Native dietary bioactives and microbially-derived metabolites can act on epithelial cells in the colon by extrinsic and intrinsic mechanisms. Dietary bioactives and their derivatives can act as ligands for receptors or alter receptor function, serve as metabolic fuel for cells, function as modifiers of the epigenome, etc. These compounds can also influence immune function and host health beyond the epithelium. Our understanding of the capacity of diet to direct a functionally beneficial gut microbiome for both localized (i.e., colon) and systemic health will continue to increase with improved ‘omics’ techniques and advances in ‘omics’ data integration.