Impact of dietary gut microbial metabolites on the epigenome

Within the past decade, epigenetic mechanisms and their modulation by natural products have gained increasing interest. Dietary bioactive compounds from various sources, including green tea, soya, fruit and berries, cruciferous vegetables, whole grain foods, fish and others, have been shown to target enzymes involved in epigenetic gene regulation, including DNA methyltransferases, histone acetyltransferases, deacetylases and demethylases in vitro and in cell culture. Also, many dietary agents were shown to alter miRNA expression. In vivo studies in animal models and humans are still limited. Recent research has indicated that the gut microbiota and gut microbial metabolites might be important mediators of diet–epigenome interactions. Inter-individual differences in the gut microbiome might affect release, metabolism and bioavailability of dietary agents and explain variability in response to intervention in human studies. Only a few microbial metabolites, including folate, phenolic acids, S-(−)equol, urolithins, isothiocyanates, and short- and long-chain fatty acids have been tested with respect to their potential to influence epigenetic mechanisms. Considering that a complex mixture of intermediary and microbial metabolites is present in human circulation, a more systematic interdisciplinary investigation of nutri-epigenetic activities and their impact on human health is called for. This article is part of a discussion meeting issue ‘Frontiers in epigenetic chemical biology’.