Diet affects the amount and types of microbes present in the gut, and gut microbial metabolism of dietary compounds affects production of both protective and harmful metabolites. Thus, interaction between dietary intake and commensal gut microbes may ultimately influence cancer risk. Functional contributions of the gut microbiota that may shape cancer susceptibility in the broad sense include: 1) harvesting otherwise inaccessible nutrients and/or sources of energy from the diet; 2) metabolizing xenobiotics, both potentially beneficial or detrimental (e.g., dietary constituents, drugs, carcinogens); 3) renewing gut epithelial cells and maintaining mucosal integrity; and 4) affecting immune system development and activity.
The indigenous bacteria in the human gut carry out multiple unique metabolic functions that can influence the health of the host. Metagenomic studies of the gut microbiome have revealed the varied anaerobic metabolisms involved in fermentation and the production of metabolites that may be either beneficial or harmful. Enzymes specific to bacteria, and in some cases specific classes of bacteria, can carry out a range of metabolic reactions, including hydrolysis of glycosides, amides and esters, and reduction, ring-cleavage, demethylation and dehydroxylation. Several microbial metabolites of dietary constituents are associated with increased risk of tumorigenesis. Ingested nitrate can be reduced to nitrite by bacterial nitrate reductase and produce N-nitroso compounds, which can form DNA adducts. Hydrogen sulfide, produced from sulfur-containing amino acids and inorganic sulfur sources (sulfate in water) by sulfate-reducing bacteria, has been shown to have both cytotoxic and genotoxic effects.
Gut bacterial metabolism of dietary fiber and resistant starch is hypothesized to benefit the host in several ways. Favorable effects include: 1) facilitating the metabolic conversion and uptake of dietary components; 2) producing fermentation end-products that affect intestinal pH and interact with gut mucosa epithelial cells; 3) interacting with the intestinal immune system and contributing to the regulation of immune function; and 4) generating fecal bulk that decreases transit time and dilutes toxic substances. Hydrolysis of plant glycosides (i.e., subset of phytochemicals) typically results in metabolites that are more biologically active than the parent compounds. Further bacterial degradation and transformation of aglycones can lead to production of lower molecular weight compounds that systemically may be more or less active. High interindividual variation in excretion and circulating concentrations of phytochemicals and their metabolites is, in part, a reflection of variation in gut microbial activity. Examples of this variation are evident in the metabolism of lignans (high-fiber foods), isoflavones (soy), and glucosinolates (cruciferous vegetables).
As we move forward with research in this area, studies need to consider the gut microbiome as a contributing functional unit in relation to diet and cancer risk. Inter-individual variation in cancer risk may be associated with microbial biomass, composition, and function, and the interaction with host exposures, such as diet. Understanding the complex and dynamic interplay between the gut microbiome and host dietary exposures may help elucidate mechanisms for carcinogenesis and guide future cancer prevention strategies.
Citation Format: Johanna W. Lampe. Diet and the gut microbiome: Who's feeding who? [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED04-02.