Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice.

IF 13.8 1区 生物学 Q1 MICROBIOLOGY
Felix Sommer, Joana P Bernardes, Lena Best, Nina Sommer, Jacob Hamm, Berith Messner, Víctor A López-Agudelo, Antonella Fazio, Georgios Marinos, A Samer Kadibalban, Go Ito, Maren Falk-Paulsen, Christoph Kaleta, Philip Rosenstiel
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引用次数: 0

Abstract

Background: Alterations in the composition and function of the intestinal microbiota have been observed in organismal aging across a broad spectrum of animal phyla. Recent findings, which have been derived mostly in simple animal models, have even established a causal relationship between age-related microbial shifts and lifespan, suggesting microbiota-directed interventions as a potential tool to decelerate aging processes. To test whether a life-long microbiome rejuvenation strategy could delay or even prevent aging in non-ruminant mammals, we performed recurrent fecal microbial transfer (FMT) in mice throughout life. Transfer material was either derived from 8-week-old mice (young microbiome, yMB) or from animals of the same age as the recipients (isochronic microbiome, iMB) as control. Motor coordination and strength were analyzed by rotarod and grip strength tests, intestinal barrier function by serum LAL assay, transcriptional responses by single-cell RNA sequencing, and fecal microbial community properties by 16S rRNA gene profiling and metagenomics.

Results: Colonization with yMB improved coordination and intestinal permeability compared to iMB. yMB encoded fewer pro-inflammatory factors and altered metabolic pathways favoring oxidative phosphorylation. Ecological interactions among bacteria in yMB were more antagonistic than in iMB implying more stable microbiome communities. Single-cell RNA sequencing analysis of intestinal mucosa revealed a salient shift of cellular phenotypes in the yMB group with markedly increased ATP synthesis and mitochondrial pathways as well as a decrease of age-dependent mesenchymal hallmark transcripts in enterocytes and TA cells, but reduced inflammatory signaling in macrophages.

Conclusions: Taken together, we demonstrate that life-long and repeated transfer of microbiota material from young mice improved age-related processes including coordinative ability (rotarod), intestinal permeability, and both metabolic and inflammatory profiles mainly of macrophages but also of other immune cells. Video Abstract.

终身微生物组再生改善小鼠肠道屏障功能和炎症。
背景:肠道微生物群的组成和功能的改变已经在广泛的动物门的有机体衰老中被观察到。最近的研究结果主要来自简单的动物模型,甚至建立了与年龄相关的微生物变化与寿命之间的因果关系,表明微生物群指导干预是减缓衰老过程的潜在工具。为了测试终身微生物组恢复策略是否可以延缓甚至防止非反刍哺乳动物的衰老,我们在小鼠的一生中进行了反复的粪便微生物转移(FMT)。转移材料要么来自8周龄小鼠(年轻微生物组,yMB),要么来自与受体相同年龄的动物(等慢性微生物组,iMB)作为对照。通过旋转杆和握力测试分析运动协调性和力量,通过血清LAL测试分析肠道屏障功能,通过单细胞RNA测序分析转录反应,通过16S rRNA基因分析和宏基因组学分析粪便微生物群落特性。结果:与iMB相比,myb定殖改善了肠道的协调性和通透性。yMB编码较少的促炎因子和改变有利于氧化磷酸化的代谢途径。与iMB相比,yMB中细菌之间的生态相互作用更具拮抗性,这意味着微生物群落更稳定。肠粘膜单细胞RNA测序分析显示,yMB组细胞表型发生显著变化,ATP合成和线粒体通路显著增加,肠细胞和TA细胞中年龄依赖性间充质标志转录物减少,但巨噬细胞中的炎症信号传导减少。综上所述,我们证明了年轻小鼠的微生物群物质的终身和反复转移改善了与年龄相关的过程,包括协调能力(rotarod),肠道通透性,以及巨噬细胞(主要是巨噬细胞)和其他免疫细胞的代谢和炎症谱。视频摘要。
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来源期刊
Microbiome
Microbiome MICROBIOLOGY-
CiteScore
21.90
自引率
2.60%
发文量
198
审稿时长
4 weeks
期刊介绍: Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.
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