微生物群作为治疗靶点
Microbiota as Therapeutic Targets.
作者信息
Xavier Ramnik J
机构信息
Gastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, and Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass., USA.
出版信息
Dig Dis. 2016;34(5):558-65. doi: 10.1159/000445263. Epub 2016 Jun 22.
BACKGROUND
Inflammatory bowel disease (IBD) represents a family of diseases including Crohn's disease and ulcerative colitis. IBD has garnered significant attention in recent years due to successes in 2 areas of basic science: complex human genetics and host-microbe interactions. Advances in understanding the genetics of IBD, mainly driven by genome-wide association studies, have identified more than 160 genetic loci that modulate the risk of disease. Notably, several of these genes have pointed to alterations in host-microbe interactions as being critical factors in pathogenesis. Investigations into the microbial communities of the gastrointestinal tract (or the 'gut microbiome') in IBD have yielded important insights into several aspects of interactions between microbiota and the host immune system, including how alterations to microbial community composition and function have important consequences for immune homeostasis.
KEY MESSAGES
The anatomy of the gastrointestinal tract plays a role in defining not only intestinal function, but also the microbial ecosystem that lives within the gut. Careful investigations into the composition and function of these microbial communities have suggested that patients with IBD have an imbalance in their gut microbiota, termed dysbiosis. These studies, as well as studies using samples from healthy individuals, have begun to uncover mechanisms of crosstalk between particular microbes (and microbial products) and immunomodulatory pathways, alterations which may drive immune diseases such as IBD.
CONCLUSIONS
Investigations into the role of the microbiome in IBD have provided important clues to potential pathogenic mechanisms. Harnessing this knowledge to develop therapeutics and identify biomarkers is currently a major translational goal, holding great promise for clinically meaningful progress.
背景
炎症性肠病(IBD)是一类疾病,包括克罗恩病和溃疡性结肠炎。近年来,由于在基础科学的两个领域取得了成功,即复杂的人类遗传学和宿主-微生物相互作用,IBD受到了广泛关注。在理解IBD遗传学方面的进展,主要由全基因组关联研究推动,已经确定了160多个调节疾病风险的基因位点。值得注意的是,其中一些基因指向宿主-微生物相互作用的改变是发病机制中的关键因素。对IBD患者胃肠道微生物群落(即“肠道微生物组”)的研究,已经在微生物群与宿主免疫系统相互作用的几个方面取得了重要见解,包括微生物群落组成和功能的改变如何对免疫稳态产生重要影响。
关键信息
胃肠道的解剖结构不仅在定义肠道功能方面发挥作用,而且在定义肠道内的微生物生态系统方面也发挥作用。对这些微生物群落的组成和功能进行的仔细研究表明,IBD患者的肠道微生物群存在失衡,称为生态失调。这些研究以及使用健康个体样本的研究,已经开始揭示特定微生物(和微生物产物)与免疫调节途径之间的相互作用机制,这些改变可能会引发IBD等免疫疾病。
结论
对微生物组在IBD中作用的研究为潜在的致病机制提供了重要线索。利用这些知识开发治疗方法和识别生物标志物,目前是一个主要的转化目标,有望在临床上取得有意义的进展。