The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities.
The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities.
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DOI：
10.1007/s00125-017-4278-3
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发表时间：
2017-06
期刊：
影响因子：
8.2
通讯作者：
Orho-Melander M
中科院分区：
文献类型：
--
作者：
Brunkwall L;Orho-Melander M
肠道中微生物基因组的总量超过了人类基因组的大小，拥有大约500倍的基因，这些基因对我们的编码潜力起到了重要的补充作用。微生物基因对于关键的代谢过程是必不可少的，例如将不可消化的膳食纤维分解为短链脂肪酸、氨基酸和维生素的生物合成以及神经递质和激素的产生。在过去的十年中，已经积累了证据来支持肠道微生物群（从粪便样本中分析）在血糖控制和2型糖尿病中的作用。小鼠的机制研究支持肠道微生物群在代谢性疾病中的因果作用，尽管支持因果关系的人类数据不足。由于从该领域的大量动物研究中分类人类证据可能具有挑战性，因此需要提供对人类研究的综述。因此，本综述的目的是涵盖当前和未来使用肠道微生物群的可能性和挑战，其能力被修改，在预防和治疗人类高血糖症和2型糖尿病的策略的发展。我们讨论了2型糖尿病中人类肠道微生物群的组成和功能，并总结了目前治疗策略的最新证据，这些策略涉及或基于肠道微生物群的改变（饮食，益生菌，二甲双胍和减肥手术）。我们继续审查一些潜在的未来基于肠道的降糖方法，涉及微生物群，包括个性化营养和益生菌方法的开发，益生菌治疗成分的鉴定，丙酸盐在近端结肠的靶向递送，二甲双胍在下肠道的靶向递送，粪便微生物群移植，以及将表达治疗因子的转基因细菌纳入微生物群。最后，未来的途径和挑战，了解人类营养，遗传学和微生物遗传学之间的相互作用，以及需要整合人类多组学数据（如遗传学，转录组学，表观遗传学，蛋白质组学和代谢组学）与微生物组学数据（如应变水平的变化，转录组学，蛋白质组学和代谢组学），使个性化治疗成功的未来现实进行了讨论。本文的在线版本（doi：10.1007/s 00125 -017-4278-3）包含同行评审但未经编辑的补充材料，包括可供下载的数字幻灯片，可供授权用户使用。
The totality of microbial genomes in the gut exceeds the size of the human genome, having around 500-fold more genes that importantly complement our coding potential. Microbial genes are essential for key metabolic processes, such as the breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis of amino acids and vitamins, and production of neurotransmitters and hormones. During the last decade, evidence has accumulated to support a role for gut microbiota (analysed from faecal samples) in glycaemic control and type 2 diabetes. Mechanistic studies in mice support a causal role for gut microbiota in metabolic diseases, although human data favouring causality is insufficient. As it may be challenging to sort the human evidence from the large number of animal studies in the field, there is a need to provide a review of human studies. Thus, the aim of this review is to cover the current and future possibilities and challenges of using the gut microbiota, with its capacity to be modified, in the development of preventive and treatment strategies for hyperglycaemia and type 2 diabetes in humans. We discuss what is known about the composition and functionality of human gut microbiota in type 2 diabetes and summarise recent evidence of current treatment strategies that involve, or are based on, modification of gut microbiota (diet, probiotics, metformin and bariatric surgery). We go on to review some potential future gut-based glucose-lowering approaches involving microbiota, including the development of personalised nutrition and probiotic approaches, identification of therapeutic components of probiotics, targeted delivery of propionate in the proximal colon, targeted delivery of metformin in the lower gut, faecal microbiota transplantation, and the incorporation of genetically modified bacteria that express therapeutic factors into microbiota. Finally, future avenues and challenges for understanding the interplay between human nutrition, genetics and microbial genetics, and the need for integration of human multi-omic data (such as genetics, transcriptomics, epigenetics, proteomics and metabolomics) with microbiome data (such as strain-level variation, transcriptomics, proteomics and metabolomics) to make personalised treatments a successful future reality are discussed. The online version of this article (doi:10.1007/s00125-017-4278-3) contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, which is available to authorised users.