Microbiome, Probiotics & Gut Nutrition

Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer

Diet and energy balance influence CRC by multiple mechanisms. They modulate the composition and function of gut microbiota, which have a prodigious metabolic capacity and can produce oncometabolites or tumor‐suppressive metabolites depending, in part, on which dietary factors and digestive components are present in the GI tract. Gut microbiota also have a profound effect on immune cells in the lamina propria, which influences inflammation and subsequently CRC. The nutrient availability, which is an outcome of diet and energy balance, determines the abundance of certain energy metabolites that are essential co‐factors for epigenetic enzymes and therefore impinges upon epigenetic regulation of gene expression. Aberrant epigenetic marks accumulate during CRC, and epimutations that are selected for drive tumorigenesis by causing transcriptome profiles to diverge from the cell of origin. In some instances, the above mechanisms are intertwined as exemplified by dietary fiber being metabolized by colonic bacteria into butyrate, which is both a short‐chain fatty acid (SCFA) and a histone deacetylase (HDAC) inhibitor that epigenetically upregulates tumor‐suppressor genes in CRC cells and anti‐inflammatory genes in immune cells.