Gut microbes, diet, and cancer

Abstract

An expanding body of evidence supports a role for gut microbes in the etiology of cancer. Previously, the focus was on identifying individual bacterial species that directly initiate or promote gastrointestinal malignancies; however, the capacity of gut microbes to influence systemic inflammation and other downstream pathways suggests that the gut microbial community may also affect risk of cancer in tissues outside of the gastrointestinal tract. Functional contributions of the gut microbiota that may influence cancer susceptibility in the broad sense include (1) harvesting otherwise inaccessible nutrients and/or sources of energy from the diet (i.e., fermentation of dietary fibers and resistant starch); (2) metabolism of xenobiotics, both potentially beneficial or detrimental (i.e., dietary constituents, drugs, carcinogens, etc.); (3) renewal of gut epithelial cells and maintenance of mucosal integrity; and (4) affecting immune system development and activity. Understanding the complex and dynamic interplay between the gut microbiome, host immune system, and dietary exposures may help elucidate mechanisms for carcinogenesis and guide future cancer prevention and treatment strategies.

Fig. 1

Direct and indirect mechanisms by which the gut microbial community may influence cancer risk. Direct colonization of gut epithelium by pathogens, as well as effects of microbial antigens (e.g., lipopolysaccharide—LPS), contribute to inflammation and altered immune function. Indirectly, microbial metabolites of exogenous substrates (i.e., dietary constituents) and endogenous host compounds (i.e., steroid hormones, bile acids, etc.) can affect the carcinogenesis continuum within the colon, as well as in other tissues via systemic effects