Influences of diet and the gut microbiome on epigenetic modulation in cancer and other diseases

Abstract

Epigenetic modulation of gene activity occurs in response to non-genetic factors such as body weight status, physical activity, dietary factors, and environmental toxins. In addition, each of these factors is thought to affect and be affected by the gut microbiome. A primary mechanism that links these various factors together in mediating control of gene expression is the production of metabolites that serve as critical cofactors and allosteric regulators of epigenetic processes. Here, we review the involvement of the gut microbiota and its interactions with dietary factors, many of which have known cellular bioactivity, focusing on particular epigenetic processes affected and the influence they have on human health and disease, particularly cancer and response to treatment. Advances in DNA sequencing have expanded the capacity for studying the microbiome. Combining this with rapidly improving techniques to measure the metabolome provides opportunities to understand complex relationships that may underlie the development and progression of cancer as well as treatment-related sequelae. Given broad reaching and fundamental biology, both at the cellular and organismal levels, we propose that interactive research programs, which utilize a wide range of mutually informative experimental model systems—each one optimally suited for answering particular questions—provide the best path forward for breaking ground on new knowledge and ultimately understanding the epigenetic significance of the gut microbiome and its response to dietary factors in cancer prevention and therapy.

Depression in cancer: The many biobehavioral pathways driving tumor progression

“…Several studies suggest that microbiota dysbiosis also plays a pivotal role also in cancer, influencing the dynamic control of gene expression and immunosurveillance 138 . The production by the microbiota of several low-molecular weight bioactive substances, including folate, butyrate, biotin and acetate is involved in the regulation of DNA expression, replication and repair, while also enabling immune-tolerance 138 .…”

“…The production by the microbiota of several low-molecular weight bioactive substances, including folate, butyrate, biotin and acetate is involved in the regulation of DNA expression, replication and repair, while also enabling immune-tolerance 138 .…”

Novel perspectives on therapeutic modulation of the gut microbiota

“…Consumption of red meat delivers L-carnitine to certain gut bacteria converting it to trimethylamine-N-oxide which has been shown to cause atherosclerosis in mice [Koeth et al 2013]. In contrast, cruciferous vegetables such as cabbage, broccoli, kale, and cauliflower are rich sources of fiber, lutein, flavonoids, phytosterols, folic acid, sulphur-containing glucosinolates, and vitamin C, each of which have been associated with reduced risk of various kinds of cancer [Paul et al 2015]. Sulphur-containing glucosinolates can be converted to biologically active compounds such as indoles, nitriles, and isothiocyanates by β thioglucosidases produced by the gut microbiome.…”

“…Diets high in red meat and fat, particularly polyunsaturated fatty acids, induce large-scale changes in the microbiota composition and bacterial metabolites that may be involved in the pathogenesis of metabolic disorders, IBD or cancer [Daniel et al 2014;Lee et al 2015]. For instance, bacteria can metabolize meat proteins and produce nitrosamines, which may be linked to carcinogenesis [Hughes et al 2001;Paul et al 2015]. Consumption of red meat delivers L-carnitine to certain gut bacteria converting it to trimethylamine-N-oxide which has been shown to cause atherosclerosis in mice [Koeth et al 2013].…”

“…Bacterial Products: -Nitrosamines [Paul et al 2015] -Trimethylamine-N-oxide [Koeth et al 2013] HDAC Th1/Th17 cells…”