Science:肠道细菌也“作恶”——引发自身免疫疾病
2018/03/12
我们常说要“一分为二”的看问题,这不,小编刚刚在《Science重磅成果:高膳食纤维可改善糖尿病,肠道细菌“又立功”了!》一文中介绍了肠道细菌的益处,科学家们又在同日发表的另一篇Science论文中抓住了肠道细菌“作恶”的证据!


图片来源:Science(DOI: 10.1126/science.aar7201)

近年来,越来越多的研究表明,生活在人体内的肠道细菌与一系列疾病有关,包括免疫系统攻击健康组织的自身免疫疾病。为了阐明这一联系,耶鲁大学的一个研究小组聚焦了一种叫做Enterococcus gallinarum的细菌。结果发现,这种细菌能够自发地转移到肠道外,进入淋巴结、肝脏和脾脏。


Fluorescence in situ hybridization (FISH) image of the gut commensal E. gallinarum translocated into the liver tissue of autoimmune mice. Orange dots represent the bacterium. Credit: Manfredo Vieira et al., Science (2018)

借助小鼠模型,科学家们观察到,在肠道外的这些组织中,E. gallinarum启动了自身抗体和炎症(它们都是自身免疫反应的特征)的产生。在健康个体培养的肝细胞中,他们证实了相同的炎症机制。同时,研究发现,自身免疫疾病患者的肝脏中也存在这种细菌。


An oral antibiotic or a vaccine into the muscle that is directed against E. gallinarum prevent autoimmune diseases to occur. Credit: Martin Kriegel

通过进一步的实验,研究小组证实,可以用针对E. gallinarum的抗生素或疫苗来抑制小鼠的自身免疫。利用这两种方法,都能够抑制组织中细菌的生长,并削弱其对免疫系统的影响。

论文的通讯作者Martin Kriegel博士说:“针对E. gallinarum的疫苗是一种特殊的方法。它的给药方式是肌肉注射,这是为了避免靶向肠道中的其他细菌。当阻断导致炎症的途径时,我们成功逆转了E. gallinarum对自身免疫的影响。”

Kriegel及其同事计划进一步调查E. gallinarum及其相关机制。他们认为,使用抗生素和其他方法(如疫苗)进行治疗是改善自身免疫性疾病(如系统性红斑狼疮和自身免疫性肝病)患者生活很有前景的方法。

参考资料:

The enemy within: Gut bacteria drive autoimmune disease

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  • Translocation of a gut pathobiont drives autoimmunity in mice and humans

    Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum–specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.

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