Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome
Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome
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DOI：
10.1038/s41380-019-0425-1
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发表时间：
2020-10-01
影响因子：
11
通讯作者：
Cryan, John F.
中科院分区：
文献类型：
--
作者：
Boehme, Marcus;van de Wouw, Marcel;Cryan, John F.
男性中年是一个过渡时期，许多生理和心理变化发生，导致认知和行为改变，大脑功能恶化。然而，支撑这种变化的机制尚不清楚。肠道微生物群被认为是肠道和大脑之间沟通的关键媒介，也是调节大脑稳态（包括大脑免疫细胞功能）的关键媒介。因此，我们测试了通过益生元补充剂靶向肠道微生物组是否会改变衰老过程中小胶质细胞的激活和大脑功能。雄性成年C57BL/6小鼠（8周）和中年C57BL/6小鼠（10个月）分别饲喂富含益生元（富含10%低聚果糖菊糖）或对照饲料14周。益生元的补充不同地改变了年轻和中年小鼠的肠道微生物群，其变化与粪便代谢物相关。从功能上讲，这转化为中年小鼠应激诱导免疫启动的逆转。此外，观察到衰老诱导的Ly-6C（hi）单核细胞进入大脑的浸润减少，同时激活的小胶质细胞亚群（Ly-6C(+)）的衰老相关增加逆转。综上所述，这些数据强调了一种潜在的途径，通过这种途径，益生元靶向肠道微生物群可以调节外周免疫反应并改变中年的神经炎症。我们的数据强调了一种改善与年龄相关的神经炎症病理和脑功能的新策略。
Male middle age is a transitional period where many physiological and psychological changes occur leading to cognitive and behavioural alterations, and a deterioration of brain function. However, the mechanisms underpinning such changes are unclear. The gut microbiome has been implicated as a key mediator in the communication between the gut and the brain, and in the regulation of brain homeostasis, including brain immune cell function. Thus, we tested whether targeting the gut microbiome by prebiotic supplementation may alter microglia activation and brain function in ageing. Male young adult (8 weeks) and middle-aged (10 months) C57BL/6 mice received diet enriched with a prebiotic (10% oligofructose-enriched inulin) or control chow for 14 weeks. Prebiotic supplementation differentially altered the gut microbiota profile in young and middle-aged mice with changes correlating with faecal metabolites. Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice. In addition, a reduction in ageing-induced infiltration of Ly-6C(hi)monocytes into the brain coupled with a reversal in ageing-related increases in a subset of activated microglia (Ly-6C(+)) was observed. Taken together, these data highlight a potential pathway by which targeting the gut microbiome with prebiotics can modulate the peripheral immune response and alter neuroinflammation in middle age. Our data highlight a novel strategy for the amelioration of age-related neuroinflammatory pathologies and brain function.