Diet as a modifiable factor in tumorigenesis: Focus on microbiome-derived bile acid metabolites and short-chain fatty acids

Abstract

Several lines of evidences have implicated the resident microbiome as a key factor in the modulation of host physiology and pathophysiology; including the resistance to cancers. Gut microbiome heavily influences host lipid homeostasis by their modulatory effects on the metabolism of bile acids (BAs). Microbiota-derived BA metabolites such as deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are implicated in the pathogeneses of various cancer types. The pathogenic mechanisms are multimodal in nature, with widespread influences on the host immunes system, cell survival and growth signalling and DNA damage. On the other hand, short-chain fatty acids (SCFAs) produced by the resident microbial activity on indigestible dietary fibres as well as during intermittent fasting regimens (such as the Ramazan fasting) elicit upregulation of the beneficial anti-inflammatory and anticancer pathways in the host. The present review first provides a brief overview of the molecular mechanisms of microbiota-derived lipid metabolites in promotion of tumour development. The authors then discuss the potential of diet as a therapeutic route for beneficial alteration of microbiota and the consequent changes in the production of SCFAs, particularly butyrate, in relation to the cancer prevention and treatment.

Keywords: Bile acid metabolism; Gut microbiota; Host pathophysiology; Ramazan fasting; Short-chain fatty acids (SCFAs); Tumorigenesis.