在健康和患病状态下人的肠道微生物组 - NEJM医学前沿
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在健康和患病状态下人的肠道微生物组
The Human Intestinal Microbiome in Health and Disease


Susan V. Lynch ... 其他 • 2016.12.15
相关阅读
• 减轻抗生素对肠道微生物组的影响 • 年龄、粪菌和艰难梭菌感染性疾病 • 肠道微生物组影响小鼠和人类的盐敏感性高血压

人体微生物在之前主要是通过单一种类及其环境进行观察。免培养技术取得的进展表明,人体微生物组具有高度多样性、功能能力及与年龄相关的动力学(参见词汇表)。大量不同的微生物种类栖息在胃肠道远端,而肠道微生物区系的生态失调,这些肠道微生物在构成和功能方面发生失衡,与多种疾病相关,这些疾病的范围从局限性胃肠紊乱至神经、呼吸、代谢、肝脏和心血管疾病。目前的大量努力专注于探讨潜在因果关系及相关微生物区系介导的疾病机制,目的是希望在更好地理解这些问题之后,可以有助于构思和实现新型治疗和预防策略。

最近,我们的人体微生物学观点基本上都是由对单一微生物(细菌、古菌、真菌和病毒)进行的培养研究所决定,而这些微生物通常是从患急性感染或慢性疾病的患者分离出。然而,几十年前,环境微生物生态学家认识到,通过显微镜观察到的微生物多样性远远超过采用传统的培养方法回收的生物的多样性1。可检测和分类微生物(微生物区系),并且评估编码基因(微生物组)和基因产物的多种免培养的分子检测法(表1)表明,微生物很少孤立存在。相反,它们在一个生境内,以复杂、相互作用、跨界、多种类微生物群落的形式生存。随着这一领域的发展,可以明显看出,事实上地球上的每个生境和每种生物都有其自身的微生物区系。其中包括人体的共生有机体——在空间隔离的生态系统内,哺乳动物和多种类微生物细胞的集合,其基因组含量受到地形学和生物个体的影响2

在人体内,胃肠道相当于一个大的微生物生态系统,里面有数万亿微生物细胞。以美国、中国和欧洲1,200人的数据为基础,对人粪便微生物宏基因组所做的综合编目发现这些粪便微生物组总计有990万个微生物基因3。超过十亿年的哺乳动物-微生物共同进化导致了两者的相互依赖。因此,肠道微生物区系在宿主免疫应答的成熟和继续训练过程中发挥关键作用4;在阻止病原体过度生长方面提供保护5;影响宿主细胞增殖6和血管形成7;调节肠道内分泌功能8、神经信号传导9和骨密度10;提供能量生源的一个来源11(宿主每日能量需求的5%~10%);生物合成维生素12、神经递质9和靶点迄今仍不明确的多种其他化合物;代谢胆盐13;对特定药物产生反应或修饰这些药物;以及消除外源毒素14(图1)。微生物的这些活性与健康之间的相关性在不同人群之间可能有差异。鉴于肠道微生物区系具有多样的功能谱,它们成为包括癌症以及涉及炎症、代谢、心血管、自身免疫、神经和精神等方面多种慢性疾病的研究重点也就不足为奇了。





作者信息

Susan V. Lynch, Ph.D., and Oluf Pedersen, M.D., D.M.Sc.
From the Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco (S.V.L.); and the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen (O.P.). Address reprint requests to Dr. Lynch at the Division of Gastroenterology, Department of Medicine, University of California, San Francisco, 513 Parnassus Ave., S357D, San Francisco, CA 94143, or at susan.lynch@ucsf.edu; or to Dr. Pedersen at the Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 1st floor, DIKU, 2100 Copenhagen, Denmark, or at oluf@sund.ku.dk.

 

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