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营养基因组学与肠道健康。

Nutrigenomics and gut health.

作者信息

Ferguson Lynnette R, Shelling Andrew N, Lauren Denis, Heyes Julian A, McNabb Warren C

出版信息

Mutat Res. 2007 Sep 1;622(1-2):1-6. doi: 10.1016/j.mrfmmm.2007.05.001. Epub 2007 May 5.

Abstract

Recognition of the interplay between genes and diet in development of disease and for maintenance of optimal metabolism has led to nutrigenomic or nutrigenetic approaches to personalising or individualising nutrition, with the potential of preventing, delaying, or reducing the symptoms of chronic diseases. Some of the development work has focussed on cardiovascular disease or type II diabetes mellitus, where various groups have identified potential diet-gene interactions. However, the available studies also emphasise the exponential increase in numbers of subjects necessary to recruit for clinical evaluation if we are to successfully provide informative high-dimensional datasets of genetic, nutrient, metabolomic (clinical), and other variables. There is also a significant bioinformatics challenge to analyze these. To add to the complexity, many of the pioneering studies had assumed that single nucleotide polymorphisms (SNPs) were the main source of human variability, but an increasing evidence base suggests the importance of more subtle gene regulatory mechanisms, including copy number variants. As an example, the risk of Inflammatory Bowel Disease (IBD) is associated with the inheritance of a number of contributory SNPs as well as with copy number variants of certain other genes. The variant forms of genes often result in disruptions to bacterial homeostasis mechanisms or to signal transduction of the intestinal epithelial cell of the host, and thereby to altered intestinal barrier function, and/or adaptive immune responses. The human gut microbiota is altered in individuals suffering from disorders such as IBD, and probiotic or prebiotic therapies or elemental diets may be beneficial to a high proportion of individuals through modifying the gut microbiota, and also modulating immune responses. New putative foods or dietary therapies may be identified through novel tissue culture screens, followed by further testing with in vivo animal models of human disease. A scientifically based rationale for developing novel foods related to genotype might use a combination of food fractionation, testing in tissue culture models and validation through animal models, before moving into human populations. However, the field of nutrigenomics raises ethical, legal and social issues, and will be of genuine benefit to human health only if developed in linkage with adequately trained health professionals. Such training will widen public understanding, and permit dialogue with regulatory officials to responsibly develop, apply and progress this new field.

摘要

认识到基因与饮食在疾病发展和维持最佳新陈代谢中的相互作用,催生了营养基因组学或营养遗传学方法来实现营养的个性化,这有可能预防、延缓或减轻慢性病症状。一些研发工作聚焦于心血管疾病或II型糖尿病,多个研究团队已确定了潜在的饮食-基因相互作用。然而,现有研究也强调,如果要成功提供包含基因、营养、代谢组学(临床)及其他变量的高维度信息数据集,用于临床评估所需招募的受试者数量将呈指数级增长。分析这些数据还面临重大的生物信息学挑战。更复杂的是,许多开创性研究曾假定单核苷酸多态性(SNP)是人类变异性的主要来源,但越来越多的证据表明更微妙的基因调控机制(包括拷贝数变异)也很重要。例如,炎症性肠病(IBD)的风险与多个致病SNP的遗传以及某些其他基因的拷贝数变异有关。基因的变异形式常常导致细菌稳态机制或宿主肠道上皮细胞信号转导的破坏,进而改变肠道屏障功能和/或适应性免疫反应。患有IBD等疾病的个体的肠道微生物群会发生改变,益生菌或益生元疗法或要素饮食可能通过改变肠道微生物群并调节免疫反应,使很大一部分个体受益。新的潜在食物或饮食疗法可通过新型组织培养筛选来确定,随后在人类疾病的体内动物模型中进行进一步测试。在将与基因型相关的新型食物推向人群之前,基于科学的开发新型食物的基本原理可能包括食物分级、在组织培养模型中进行测试以及通过动物模型进行验证。然而,营养基因组学领域引发了伦理、法律和社会问题,只有与训练有素的健康专业人员合作开展,才会真正有益于人类健康。这样的培训将增进公众理解,并允许与监管官员进行对话,以负责任地发展、应用和推进这一新领域。

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