Tytgat Institute for Liver and Intestinal Research, Department of Gastroenterology and Hepatology, Academic Medical Center , Amsterdam , Netherlands.
Front Immunol. 2013 Aug 1;4:226. doi: 10.3389/fimmu.2013.00226. eCollection 2013.
Intestinal epithelial cells (IECs) are integral players in homeostasis of immunity and host defense in the gut and are under influence of the intestinal microbiome. Microbial metabolites and dietary components, including short chain fatty acids (acetate, propionate, and butyrate, SCFAs), have an impact on the physiology of IECs at multiple levels, including the inhibition of deacetylases affecting chromatin remodeling and global changes in transcriptional activity. The number and diversity of butyrate-producing bacteria is subject to factors related to age, disease, and to diet. At physiological levels, SCFAs are inhibitors of histone deacetylases (HDACs) which may explain the transcriptional effects of SCFAs on epithelial cells, although many effects of SCFAs on colonic mucosa can be ascribed to mechanisms beyond HDAC inhibition. Interference with this type of post-translational modification has great potential in cancer and different inflammatory diseases, because HDAC inhibition has anti-proliferative and anti-inflammatory effects in vitro, and in in vivo models of intestinal inflammation. Hence, the influence of dietary modulators on HDAC activity in epithelia is likely to be an important determinant of its responses to inflammatory and microbial challenges.
肠道上皮细胞（IECs）是肠道中免疫和宿主防御稳态的重要参与者，并且受到肠道微生物组的影响。微生物代谢产物和膳食成分，包括短链脂肪酸（乙酸盐、丙酸盐和丁酸盐，SCFAs），在多个层面上影响 IECs 的生理学，包括抑制影响染色质重塑和转录活性全局变化的去乙酰化酶。产生丁酸盐的细菌的数量和多样性受到与年龄、疾病和饮食相关的因素的影响。在生理水平上，SCFAs 是组蛋白去乙酰化酶（HDACs）的抑制剂，这可以解释 SCFAs 对上皮细胞的转录影响，尽管 SCFAs 对结肠黏膜的许多影响可以归因于 HDAC 抑制以外的机制。这种翻译后修饰的干扰在癌症和不同炎症性疾病中有很大的潜力，因为 HDAC 抑制在体外和肠道炎症的体内模型中具有抗增殖和抗炎作用。因此，饮食调节剂对上皮细胞中 HDAC 活性的影响可能是其对炎症和微生物挑战反应的重要决定因素。
