The Gut Microbiota and Ageing
The Gut Microbiota and Ageing
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DOI：
10.1007/978-981-13-2835-0_12
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Weinkove, David
中科院分区：
文献类型：
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作者：
Maynard, Claire;Weinkove, David
了解人类肠道微生物群如何影响衰老是一项挑战。肠道微生物群是一个非常复杂的生物生态系统，随着个体和时间的变化而变化很大，使得与年龄相关的变化难以测量。然而，老年人和年轻人的肠道微生物组成确实存在差异。关键问题是，这些差异是否仅反映了宿主生理和饮食的年龄相关变化，或者微生物是否可以驱动宿主衰老？模式生物允许这个问题得到解决。对果蝇（Drosophila melanogaster）的纵向分析表明，微生物组成的变化先于肠道和宿主衰老，抗生素治疗延长了寿命，表明微生物加速了衰老。抗生素也延长了中年鳉鱼的寿命，但从年轻的鳉鱼的肠道微生物的额外移植进一步延长寿命，这表明与年轻动物相关的微生物的积极影响。来自老年小鼠的微生物，而不是年轻小鼠，当添加到无菌小鼠中时会引起炎症，这表明微生物随着年龄的增长对宿主的危害更大。这些研究涉及广泛的细菌类别，特别是变形菌门的成员，作为与肠道降解和炎症的前馈循环中的衰老驱动因素。线虫秀丽隐杆线虫可以与遗传上易处理的细菌的单一菌株相关联，并且这种简化的系统揭示了细菌代谢中的特定干预，例如抑制细菌叶酸合成，从而延长动物寿命。将这种理解转移到人类微生物群是具有挑战性的，但有望揭示如何操纵肠道微生物群可能是维持老年健康的一种途径。
Understanding how the human gut microbiota might influence ageing is challenging. The gut microbiota is a hugely complex ecology of organisms that varies greatly with individuals and time, making age-related changes difficult to measure. However, elderly and younger populations do show differences in gut microbe composition. The key question is whether these differences only reflect age-related changes in host physiology and diet, or if microbes can drive host ageing? Model organisms allow this question to be addressed. Longitudinal analyses in the fruit fly Drosophila melanogaster show that changes in microbial composition precedes intestinal and host ageing, and antibiotic treatment increases lifespan, implicating microbes in accelerating ageing. Antibiotics also extend the lifespan of middle-aged killifish but additional transplantation of gut microbes from young killifish extends lifespan further, suggesting a positive effect of microbes associated with young animals. Microbes from old, but not young, mice induce inflammation when added to germ-free mice suggesting that microbes become more harmful to the host with age. These studies implicate broad classes of bacteria, particularly members of the phylum Proteobacteria, as drivers of ageing in a feed-forward loop with intestinal degradation and inflammation. The nematode Caenorhabditis elegans can be associated with single strains of genetically-tractable bacteria, and this simplified system has revealed specific interventions in bacterial metabolism, such as inhibition of bacterial folate synthesis, that extend animal lifespan. Transferring this understanding to the human microbiota is challenging but promises to reveal how manipulation of the gut microbiota might be a route to maintain health in old age.