Diet, microorganisms and their metabolites, and colon cancer

Key Points

  • Colorectal cancer is a so-called westernized disease and the second leading cause of cancer death worldwide; approximately half of those with the disease will die from it

  • Geographical variation, migration studies and experimental studies provide compelling evidence that environmental factors, rather than genetic dysfunction, are responsible for the development of colorectal cancer

  • Convincing evidence suggests that risk of colon cancer is increased by processed and unprocessed meat consumption but suppressed by fibre-rich foods

  • Dietary risk is mediated by the colonic microbiota; carbohydrate residues stimulate production of metabolites that maintain mucosal health, proteinaceous residues and fat-stimulated bile acids might result in pro-inflammatory and carcinogenic metabolites

  • A moderate intake of meat and fat is part of our omnivorous diet and the carcinogenic potential can be suppressed by the induction of butyrogenesis from fibre-rich foods

  • Current dietary fibre recommendations need to be reviewed as they are based on the maintenance of cardiovascular health and are below the levels associated with low colon cancer risk

Abstract

Colorectal cancer is one of the so-called westernized diseases and the second leading cause of cancer death worldwide. On the basis of global epidemiological and scientific studies, evidence suggests that the risk of colorectal cancer is increased by processed and unprocessed meat consumption but suppressed by fibre, and that food composition affects colonic health and cancer risk via its effects on colonic microbial metabolism. The gut microbiota can ferment complex dietary residues that are resistant to digestion by enteric enzymes. This process provides energy for the microbiota but culminates in the release of short-chain fatty acids including butyrate, which are utilized for the metabolic needs of the colon and the body. Butyrate has a remarkable array of colonic health-promoting and antineoplastic properties: it is the preferred energy source for colonocytes, it maintains mucosal integrity and it suppresses inflammation and carcinogenesis through effects on immunity, gene expression and epigenetic modulation. Protein residues and fat-stimulated bile acids are also metabolized by the microbiota to inflammatory and/or carcinogenic metabolites, which increase the risk of neoplastic progression. This Review will discuss the mechanisms behind these microbial metabolite effects, which could be modified by diet to achieve the objective of preventing colorectal cancer in Western societies.

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Figure 1: Geographical variation in colorectal cancer rates.
Figure 2: Importance of dietary residues and the colonic microbiota in determining colon cancer risk.
Figure 3: Key metabolic pathways of the colonic microbiota.

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O'Keefe, S. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol 13, 691–706 (2016). https://doi.org/10.1038/nrgastro.2016.165

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