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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03038-y

摘要内容如下：

深入了解肠道微生物组与新陈代谢和衰老之间的关系，对于制定促进健康长寿的干预措施至关重要。在10，207名年龄为40-93岁的个体的发现队列中，我们使用21个代谢参数将个体分为5个簇，称为代谢多发病簇（MCS），代表不同的代谢亚表型。与归类为代谢健康（MC1）的群组相比，归类为“肥胖相关混合型”（MC4）和“高血糖”（MC5）的群组的11.1年心血管疾病（CVD）风险分别增加了75%（多变量调整风险比（HR）:1.75，95%置信区间（CI）:1.43-2.14）和117%（2.17，1.72-2.74）。这些关联在第二个队列9061名个体中重复，并进行了10.0年的随访。基于对来自发现队列的4，491个鸟枪法粪便元基因组的分析，我们发现肠道微生物组成与MCS和年龄相关。接下来，使用55种特定年龄的微生物物种来捕获生物年龄，我们开发了一种肠道微生物年龄（MA）指标，该指标在包含4，425个宏基因组样本的四个外部队列中得到了验证。在60岁或以上的个体中，与MC1、MC2或MC3相比，与MC4或MC5相关的CVD风险增加在高MA个体中加重，而在低MA个体中减少，这与年龄、性别和其他生活方式和饮食因素无关。在这种模式中，年轻的MA似乎抵消了可归因于代谢功能障碍的CVD风险，这意味着MA在代谢不健康的老年人的心血管健康中的调节作用。

英文原文如下：

Abstracts

Insight into associations between the gut microbiome with metabolism and aging is crucial for tailoring interventions to promote healthy longevity. In a discovery cohort of 10,207 individuals aged 40-93 years, we used 21 metabolic parameters to classify individuals into five clusters, termed metabolic multimorbidity clusters (MCs), that represent different metabolic subphenotypes. Compared to the cluster classified as metabolically healthy (MC1), clusters classified as 'obesity-related mixed' (MC4) and 'hyperglycemia' (MC5) exhibited an increased 11.1-year cardiovascular disease (CVD) risk by 75% (multivariable-adjusted hazard ratio (HR): 1.75, 95% confidence interval (CI): 1.43-2.14) and by 117% (2.17, 1.72-2.74), respectively. These associations were replicated in a second cohort of 9,061 individuals with a 10.0-year follow-up. Based on analysis of 4,491 shotgun fecal metagenomes from the discovery cohort, we found that gut microbial composition was associated with both MCs and age. Next, using 55 age-specific microbial species to capture biological age, we developed a gut microbial age (MA) metric, which was validated in four external cohorts comprising 4,425 metagenomic samples. Among individuals aged 60 years or older, the increased CVD risk associated with MC4 or MC5, as compared to MC1, MC2 or MC3, was exacerbated in individuals with high MA but diminished in individuals with low MA, independent of age, sex and other lifestyle and dietary factors. This pattern, in which younger MA appears to counteract the CVD risk attributable to metabolic dysfunction, implies a modulating role of MA in cardiovascular health for metabolically unhealthy older people.

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