西班牙奥维耶多大学Carlos Lpez-Otn研究组和Pedro M. Quirós研究组，合作发现将粪便微生物群移植到早衰小鼠体内可延长其健康寿命。相关论文于2019年8月发表在《自然—医学》杂志上。

研究人员发现两种不同的早衰小鼠模型的特征是肠道生态失调，其变化包括变形菌（Proteobacteria）和蓝细菌（Cyanobacteria）的丰度增加，以及疣微菌（Verrucomicrobia）丰度的减少。与这些结果一致，研究人员发现人类早衰患者也表现出肠道生态失调，并且长寿人类（即百岁老人）表现出疣状细菌的大量增加和变形菌的减少。来自野生型小鼠的粪便微生物移植增加了两种早衰小鼠模型中的健康和寿命，并且用一种疣微菌（Akkermansia muciniphila）移植足以发挥有益效果。此外，回肠内容物的代谢组学分析指出，二级胆酸的恢复可能是重建健康微生物组有益效果的潜在机制。这些研究结果表明，纠正老化加速的肠道失态是有益的，这提示衰老与肠道微生物群之间存在联系，并为针对年龄相关疾病进行微生物组干预提供了理论基础。

据介绍，肠道微生物组正在成为代谢、免疫和神经内分泌等几种途径的关键调节因子。肠道微生物组的失调与肥胖、2型糖尿病、心血管疾病、非酒精性脂肪肝和癌症等主要疾病有关，但其在衰老中的确切作用仍有待阐明。

Title: Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice

Author: Clea Brcena, Rafael Valds-Mas, Pablo Mayoral, Cecilia Garabaya, Sylvre Durand, Francisco Rodrguez, Mara Teresa Fernndez-Garca, Nuria Salazar, Alicja M. Nogacka, Nuria Garatachea, Nolie Bossut, Fanny Aprahamian, Alejandro Lucia, Guido Kroemer, Jos M. P. Freije, Pedro M. Quirs, Carlos Lpez-Otn

Issue&Volume: Volume 25 Issue 8, August 2019

Abstract: The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways1,2. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer36, 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.

DOI: 10.1038/s41591-019-0504-5

Source:https://www.nature.com/articles/s41591-019-0504-5