Nutrients. 2014 Oct 28;6(11):4706-4719. The Influence of Early Life Nutrition on Epigenetic Regulatory Mechanisms of the Immune System. Paparo et al. Abstract The immune system is exquisitely sensitive to environmental changes. Diet constitutes one of the major environmental factors that exerts a profound effect on immune system development and function. Epigenetics is the study of mitotically heritable, yet potentially reversible, molecular modifications to DNA and chromatin without alteration to the underlying DNA sequence. Nutriepigenomics is an emerging discipline examining the role of dietary influences on gene expression. There is increasing evidence that the epigenetic mechanisms that regulate gene expression during immune differentiation are directly affected by dietary factors or indirectly through modifications in gut microbiota induced by different dietary habits. Short-chain fatty acids, in particular butyrate, produced by selected bacteria stains within gut microbiota, are crucial players in this network. 1. Introduction The immune system is exquisitely sensitive to environmental changes. One of the clearest reflections of this is the recent and dramatic rise in immune-mediated diseases, mainly allergies, with progressive modern urbanization. Diet constitutes one of the major environmental factor that exerts a crucial effect on immune system development and function, and thus, it greatly influences many aspects of health and disease risk. The rise in allergic diseases is fast becoming a major global health issue. While this was first evident in more developed countries of Australasia, Western Europe and North America, where more than 40% of the population may be affected at some stage, it is now also emerging in virtually all regions of the world undergoing industrial development and Westernization. International trends provide some indication that environmental changes can affect immune function regardless of the genetic background. There is emerging evidence that the epigenetic mechanisms that regulate gene expression during immune differentiation are susceptible to these environmental influences. Epigenetics is the study of mitotically heritable, yet potentially reversible, molecular modifications to DNA and chromatin without alteration to the underlying DNA sequence. Increasingly, it is recognized that epigenetic marks provide a mechanistic link between environment, nutrition and disease. Though the DNA sequence is fairly permanent, epigenetic modifications are dynamic throughout the life course and can be heavily influenced by external factors. The epigenetic program is encoded by specific histone modifications (methylation and acetylation) and DNA methylation patterns, which determine the degree of DNA compaction and, thus, the accessibility of genes for transcription. In addition to histone modifications and DNA methylation, there are also other gene regulatory networks, including microRNAs, small interfering RNAs and long non-coding RNAs, all of which serve to control gene expression. Given that these modifications are reversible and sensitive to environmental factors, they provide a mechanistic link between environmental exposures, developmental programming and the risk for disease. Early life nutrition may influence immune system development through direct epigenetic mechanisms. Some nutritional factors, like folate and vitamins B1, B2 and B12, can change DNA methylation. Retinoic acid, garlic and dietary protein restriction may cause histone modification, and bioactive food compounds, like curcumin, genistein and retinoic acid, can decrease carcinogenic expression by miRNA. Alternatively, dietary factors could influence epigenetic regulation of gene expression through an indirect mechanism mediated by a modulation of gut microbiota. The major metabolites produced by gut microbiota are short-chain fatty acids (SCFAs), such as butyrate, that have multiple beneficial effects at the intestinal and extra-intestinal level. As more dietary fibers are ingested, SCFAs production increases. The circulating SCFAs have a regulatory effect on macrophage and dendritic cell (DC) biology, supporting a strong connection between dietary fibers intake and immune response controlled by these cells. Interestingly, the placenta has recently been shown to contain commensal microbes. This suggests a potential role for maternal diet through an effect on placental commensal microbes on immune pathways during fetal development. Similarly, metabolites from gut microbiota, such as SCFAs, are present in breast milk, and this might be an important point of interaction between metabolites and the immune system.
Posted on: Wed, 12 Nov 2014 19:30:55 +0000
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