The gut microbiota, bacterial metabolites and colorectal cancer

Key Points Dietary intake has an important effect on the gut environment, much of which is mediated by the metabolic activities of the intestinal microbiota on dietary compounds. Different microbial metabolites have the potential to promote and protect against colorectal cancer (CRC). Accumulating evidence suggests that microbial-derived short chain fatty acids control inflammation and regulatory T cell populations. This involves the inhibition of host histone deacetylases and interactions with cell surface receptors. Multiple species in the gut microbiota have complex roles in releasing and converting diet-derived phytochemicals and host-derived bile acids and glycoconjugates, all of which influence the overall microbial metabolome. Alterations in the composition of the gut microbiota can be detected both in faecal samples and in tumour-associated communities that are associated with CRC. Although many of these changes may be consequential, some specific pathogens seem to contribute to causation and disease progression. It is unlikely that the aetiology of CRC can be ascribed to the presence and activities of single pathogenic species, and it is proposed that the cumulative effects of microbial metabolites should be considered to better predict and prevent cancer progression. Accumulating evidence suggests that the gut microbiota has a role in the aetiology of colorectal cancer (CRC). In this Review, Flint and colleagues discuss the complex interplay between diet, the microbiota and microbial metabolites and argue that the combined metabolome of the microbiota has both protective and detrimental effects on inflammation and the progression of CRC. Accumulating evidence suggests that the human intestinal microbiota contributes to the aetiology of colorectal cancer (CRC), not only via the pro-carcinogenic activities of specific pathogens but also via the influence of the wider microbial community, particularly its metabolome. Recent data have shown that the short-chain fatty acids acetate, propionate and butyrate function in the suppression of inflammation and cancer, whereas other microbial metabolites, such as secondary bile acids, promote carcinogenesis. In this Review, we discuss the relationship between diet, microbial metabolism and CRC and argue that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.