营养物质和微生物代谢产物对抗菌肽基因表达的调控。
Regulation of antimicrobial peptide gene expression by nutrients and by-products of microbial metabolism.
机构信息
Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, 307 Linus Pauling Science Center, Corvallis, OR 97331, USA.
出版信息
Eur J Nutr. 2012 Dec;51(8):899-907. doi: 10.1007/s00394-012-0415-4. Epub 2012 Jul 15.
BACKGROUND
Antimicrobial peptides (AMPs) are synthesized and secreted by immune and epithelial cells that are constantly exposed to environmental microbes. AMPs are essential for barrier defense, and deficiencies lead to increased susceptibility to infection. In addition to their ability to disrupt the integrity of bacterial, viral and fungal membranes, AMPs bind lipopolysaccharides, act as chemoattractants for immune cells and bind to cellular receptors and modulate the expression of cytokines and chemokines. These additional biological activities may explain the role of AMPs in inflammatory diseases and cancer. Modulating the endogenous expression of AMPs offers potential therapeutic treatments for infection and disease.
METHODS
The present review examines the published data from both in vitro and in vivo studies reporting the effects of nutrients and by-products of microbial metabolism on the expression of antimicrobial peptide genes in order to highlight an emerging appreciation for the role of dietary compounds in modulating the innate immune response.
RESULTS
Vitamins A and D, dietary histone deacetylases and by-products of intestinal microbial metabolism (butyrate and secondary bile acids) have been found to regulate the expression of AMPs in humans. Vitamin D deficiency correlates with increased susceptibility to infection, and supplementation studies indicate an improvement in defense against infection. Animal and human clinical studies with butyrate indicate that increasing expression of AMPs in the colon protects against infection.
CONCLUSION
These findings suggest that diet and/or consumption of nutritional supplements may be used to improve and/or modulate immune function. In addition, by-products of gut microbe metabolism could be important for communicating with intestinal epithelial and immune cells, thus affecting the expression of AMPs. This interaction may help establish a mucosal barrier to prevent invasion of the intestinal epithelium by either mutualistic or pathogenic microorganisms.
背景
抗菌肽（AMPs）由不断暴露于环境微生物的免疫和上皮细胞合成和分泌。AMPs 对屏障防御至关重要，其缺乏会导致感染易感性增加。除了破坏细菌、病毒和真菌膜完整性的能力外，AMPs 还结合脂多糖，作为免疫细胞的趋化剂，并与细胞受体结合，调节细胞因子和趋化因子的表达。这些额外的生物学活性可能解释了 AMP 在炎症性疾病和癌症中的作用。调节 AMP 的内源性表达为感染和疾病提供了潜在的治疗方法。
方法
本综述检查了来自体外和体内研究的已发表数据，这些研究报告了营养物质和微生物代谢的副产物对抗菌肽基因表达的影响，以强调人们对饮食化合物在调节先天免疫反应中的作用的新认识。
结果
发现维生素 A 和 D、膳食组蛋白去乙酰化酶和肠道微生物代谢的副产物（丁酸盐和次级胆汁酸）可调节人类 AMP 的表达。维生素 D 缺乏与感染易感性增加相关，补充研究表明可改善抗感染防御能力。关于丁酸盐的动物和人体临床研究表明，增加结肠中 AMP 的表达可预防感染。
结论
这些发现表明，饮食和/或营养补充剂的摄入可用于改善和/或调节免疫功能。此外，肠道微生物代谢的副产物可能对于与肠道上皮和免疫细胞进行通信很重要，从而影响 AMP 的表达。这种相互作用可能有助于建立粘膜屏障，以防止共生或病原微生物侵袭肠道上皮。
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