Zilbauer Matthias, Zellos Aglaia, Heuschkel Robert, Gasparetto Marco, Kraiczy Judith, Postberg Jan, Greco Luigi, Auricchio Renata, Galatola Martina, Embleton Nicholas, Wirth Stefan, Jenke Andreas
*University Department of Paediatrics, University of Cambridge, Cambridge, UK †Department of Paediatric Gastroenterology, Hepatology and Nutrition, Addenbrookes Hospital, Cambridge, UK ‡First Department of Pediatrics, Aghia Sophia Children's Hospital, University of Athens School of Medicine, Athens, Greece §Department of Medical Translational Science and European Institute for Food Induced Disease, University Federico II, Naples, Italy ||Newcastle Hospitals, NHS Foundation Trust, Newcastle upon Tyne ¶Institute of Health and Society, Newcastle University, Newcastle, UK #Department of Pediatrics, Faculty of Health, HELIOS Children's Hospital Wuppertal, Witten/Herdecke University, Germany.
J Pediatr Gastroenterol Nutr. 2016 Apr;62(4):521-9. doi: 10.1097/MPG.0000000000001053.
Epigenetics can be defined as stable, potentially heritable changes in the cellular phenotype caused by mechanisms other than alterations to the underlying DNA sequence. As such, any observed phenotypic changes including organ development, aging, and the occurrence of disease could be driven by epigenetic mechanisms in the presence of stable cellular DNA sequences. Indeed, with the exception of rare mutations, the human genome-sequence has remained remarkably stable over the past centuries. In contrast, substantial changes to our environment as part of our modern life style have not only led to a significant reduction of certain infectious diseases but also seen the exponential increase in complex traits including obesity and multifactorial diseases such as autoimmune disorders. It is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment, and a large body of existing evidence supports the importance of environmental factors such as diet and nutrition, infections, and exposure to toxins on human health. This seems to be particularly the case during vulnerable periods of human development such as pregnancy and early life. Importantly, as the first point of contact for many of such environmental factors including nutrition, the digestive system is being increasingly linked to a number of "modern" pathologies. In this review article, we aim to give a brief introduction to the basic molecular principals of epigenetics and provide a concise summary of the existing evidence for the role of epigenetic mechanisms in gastrointestinal health and disease, hepatology, and nutrition.
由除潜在DNA序列改变之外的机制所引起的细胞表型的稳定且可能可遗传的变化。因此，在细胞DNA序列稳定的情况下，任何观察到的表型变化，包括器官发育、衰老和疾病的发生，都可能由表观遗传机制驱动。事实上，除了罕见的突变外，人类基因组序列在过去几个世纪中一直保持着显著的稳定性。相比之下，作为现代生活方式一部分的环境的重大变化，不仅导致某些传染病显著减少，也见证了包括肥胖症等复杂性状以及自身免疫性疾病等多因素疾病呈指数增长。越来越清楚的是，表观遗传机制在遗传密码与我们的环境之间的界面发挥作用，大量现有证据支持饮食和营养、感染以及接触毒素等环境因素对人类健康的重要性。在人类发育的脆弱时期，如孕期和生命早期，情况似乎尤其如此。重要的是，作为包括营养在内的许多此类环境因素的第一接触点，消化系统与许多“现代”病理学的联系日益紧密。在这篇综述文章中，我们旨在简要介绍表观遗传学的基本分子原理，并简要总结表观遗传机制在胃肠道健康与疾病、肝脏病学和营养方面作用的现有证据。
