Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice
Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice
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DOI：
10.1038/s41591-019-0504-5
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发表时间：
2019-08-01
期刊：
影响因子：
82.9
通讯作者：
Lopez-Otin, Carlos
中科院分区：
文献类型：
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作者：
Barcena, Clea;Valdes-Mas, Rafael;Lopez-Otin, Carlos
肠道微生物组正在成为多种代谢、免疫和神经内分泌途径的关键调节因子(1,2)。肠道微生物组失调与肥胖、2 型糖尿病、心血管疾病、非酒精性脂肪酸肝病和癌症等主要疾病有关(3-6)，但其在衰老中的确切作用仍有待阐明。在这里，我们发现两种不同的早衰小鼠模型的特征是肠道菌群失调，并发生改变，包括变形菌和蓝藻丰度增加，以及疣微菌丰度减少。与这些发现一致的是，我们发现人类早衰症患者也表现出肠道菌群失调，而长寿的人类（即百岁老人）表现出疣微菌的大幅增加和变形菌的减少。来自野生型小鼠的粪便微生物群移植增强了两种早衰小鼠模型的健康寿命和寿命，并且移植疣微菌 Akkermansia muciniphila 足以发挥有益作用。此外，回肠内容物的代谢组学分析表明，次级胆汁酸的恢复是重建健康微生物组的有益作用的可能机制。我们的结果表明，纠正与加速衰老相关的肠道菌群失调是有益的，这表明衰老与肠道微生物群之间存在联系，这为基于微生物组的针对年龄相关疾病的干预措施提供了理论基础。
The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways(1,2). Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer(3-6), but its precise role in aging remains to be elucidated. Here, we find that two different mouse models of progeria are characterized by intestinal dysbiosis with alterations that include an increase in the abundance of Proteobacteria and Cyanobacteria, and a decrease in the abundance of Verrucomicrobia. Consistent with these findings, we found that human progeria patients also display intestinal dysbiosis and that long-lived humans (that is, centenarians) exhibit a substantial increase in Verrucomicrobia and a reduction in Proteobacteria. Fecal microbiota transplantation from wild-type mice enhanced healthspan and lifespan in both progeroid mouse models, and transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial effects of reestablishing a healthy microbiome. Our results demonstrate that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases.