A model for the role of gut bacteria in the development of autoimmunity for type 1 diabetes.
A model for the role of gut bacteria in the development of autoimmunity for type 1 diabetes.
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DOI：
10.1007/s00125-015-3614-8
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发表时间：
2015-07
期刊：
影响因子：
8.2
通讯作者：
Triplett, Eric W.
中科院分区：
文献类型：
--
作者：
Davis-Richardson, Austin G.;Triplett, Eric W.
多项证据表明肠道微生物组在 1 型糖尿病中发挥着重要作用。用益生菌或抗生素治疗易患糖尿病的啮齿动物可以预防这种疾病的发展。与健康啮齿动物相比，易患糖尿病的啮齿动物的肠道微生物组也明显不同。最近对 1 型糖尿病遗传风险较高的儿童进行的研究表明，对这种疾病产生自身免疫的儿童与保持健康的儿童之间的肠道微生物组存在显着差异。然而，由于环境（特别是饮食和地理）对微生物组组成的强烈影响，自身免疫儿童和健康儿童之间微生物组组成的差异在所有研究中并不一致。控制微生物组组成的混杂因素揭示细菌与疾病的关联。例如，在来自地理有限的芬兰一个城市的人类队列中，发现了一种主要细菌种类，Bacteroides dorei 与 1 型糖尿病之间存在很强的关联（Davis-Richardson 等人，《Front Microbiol》；5:678）。除此之外，最近的 DNA 甲基化分析表明，可能需要对肠道微生物组进行彻底的表观遗传学分析。这些研究提出了一个可测试的模型，即高脂肪和麸质、低抗性淀粉的饮食可能是肠道菌群失调的主要驱动因素。这种菌群失调可能会导致肠道细菌无法产生丁酸，进而导致可渗透性肠道的发育，进而导致自身免疫。世界各地导致丁酸盐生产变化的细菌群落可能有所不同，但拟杆菌属细菌被认为发挥着关键作用。
Several lines of evidence suggest a role for the gut microbiome in type 1 diabetes. Treating diabetes-prone rodents with probiotics or antibiotics prevents the development of the disorder. Diabetes-prone rodents also have a distinctly different gut microbiome compared with healthy rodents. Recent studies in children with a high genetic risk for type 1 diabetes demonstrate significant differences in the gut microbiome between children who develop autoimmunity for the disease and those who remain healthy. However, the differences in microbiome composition between autoimmune and healthy children are not consistent across all studies because of the strong environmental influences on microbiome composition, particularly diet and geography. Controlling confounding factors of microbiome composition uncovers bacterial associations with disease. For example, in a human cohort from a single Finnish city where geography is confined, a strong association between one dominant bacterial species, Bacteroides dorei, and type 1 diabetes was discovered (Davis-Richardson et al. Front Microbiol;5:678). Beyond this, recent DNA methylation analyses suggest that a thorough epigenetic analysis of the gut microbiome may be warranted. These studies suggest a testable model whereby a diet high in fat and gluten and low in resistant starch may be the primary driver of gut dysbiosis. This dysbiosis may cause a lack of butyrate production by gut bacteria, which, in turn, leads to the development of a permeable gut followed by autoimmunity. The bacterial community responsible for these changes in butyrate production may vary around the world, but bacteria of the genus Bacteroides are thought to play a key role.
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