Causal relationship between gut microbiota and ageing: A multi-omics Mendelian randomization study

IF 3.5 3区医学 Q2 GERIATRICS & GERONTOLOGY

Archives of gerontology and geriatrics Pub Date : 2025-01-20 DOI:10.1016/j.archger.2025.105765

Guolin Zhang , Yuqing Lu , Zhen Wang , Ruicong Ma , Hongjin Jin , Jingsi Zhang , Fengyi Liu , Yanchun Ding

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引用次数: 0

Abstract

Introduction

Observational studies and clinical trials have suggested a connection between gut microbiota and aging. However, the causal relationship between them remains undetermined.

Objectives

This study aimed to use bidirectional two-sample Mendelian randomization (TSMR) analysis to explore the causal relationship between gut microbiota and aging.

Methods

Summary statistics from genome-wide association studies (GWAS) on gut microbiota and seven aging-related phenotypes were employed for TSMR analysis. Reverse Mendelian randomization (MR) analysis was performed to assess the potential for reverse causality. Additionally, the relationship between Akkermansia muciniphila and inflammation-related proteins and metabolites was further investigated. The effects of Akkermansia muciniphila on aging were also examined in Caenorhabditis elegans by measuring both lifespan and healthspan.

Results

MR analysis of 207 microbial taxa and seven aging phenotypes revealed 44 causal relationships between the gut microbiota and aging. Akkermansia muciniphila was found to be causally linked to several aging-related traits, including mvAge, appendicular lean mass, and grip strength (P < 0.05). Reverse MR analysis identified 23 causal relationships, but no bidirectional causality was observed. Moreover, Akkermansia muciniphila is causally related to ST1A1, taurine bile acid, and mannose (P < 0.05). In Caenorhabditis elegans, treatment with Akkermansia muciniphila significantly extended lifespan (P < 0.05) and improved mobility in aging nematodes.

Conclusion

TSMR analysis uncovers multiple potential causal links between gut microbiota and aging, particularly Akkermansia muciniphila. Experimental results support its role in alleviating aging. This study provides a strong foundation for future research on gut microbiota's role in aging.

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肠道微生物群与衰老之间的因果关系：一项多组学孟德尔随机研究

观察性研究和临床试验表明，肠道微生物群与衰老之间存在联系。然而，它们之间的因果关系仍不确定。目的采用双向双样本孟德尔随机化（TSMR）方法探讨肠道菌群与衰老的因果关系。方法采用全基因组关联研究（GWAS）对肠道微生物群和7种衰老相关表型进行TSMR分析。进行反向孟德尔随机化（MR）分析以评估反向因果关系的可能性。此外，我们还进一步研究了嗜粘液阿克曼氏菌与炎症相关蛋白和代谢物的关系。通过测量秀丽隐杆线虫的寿命和健康寿命，还研究了嗜黏液阿克曼氏菌对衰老的影响。结果通过对207个微生物类群和7种衰老表型的smr分析，揭示了肠道微生物群与衰老之间的44种因果关系。研究发现嗜粘液阿克曼氏菌与几个与衰老相关的特征有因果关系，包括mvAge、阑尾瘦质量和握力(P <；0.05)。反向MR分析确定了23种因果关系，但未观察到双向因果关系。此外，嗜粘阿克曼氏菌与ST1A1、牛磺酸、胆汁酸和甘露糖有因果关系(P <；0.05)。在秀丽隐杆线虫中，嗜黏液阿克曼氏菌治疗可显著延长寿命(P <；0.05)，提高了衰老线虫的活动性。结论tsmr分析揭示了肠道微生物群与衰老之间的多种潜在因果关系，特别是嗜粘阿克曼氏菌。实验结果支持其延缓衰老的作用。该研究为进一步研究肠道菌群在衰老中的作用提供了坚实的基础。

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来源期刊

Archives of gerontology and geriatrics 医学-老年医学

CiteScore

7.30

自引率

5.00%

发文量

198

审稿时长

16 days

期刊介绍： Archives of Gerontology and Geriatrics provides a medium for the publication of papers from the fields of experimental gerontology and clinical and social geriatrics. The principal aim of the journal is to facilitate the exchange of information between specialists in these three fields of gerontological research. Experimental papers dealing with the basic mechanisms of aging at molecular, cellular, tissue or organ levels will be published. Clinical papers will be accepted if they provide sufficiently new information or are of fundamental importance for the knowledge of human aging. Purely descriptive clinical papers will be accepted only if the results permit further interpretation. Papers dealing with anti-aging pharmacological preparations in humans are welcome. Papers on the social aspects of geriatrics will be accepted if they are of general interest regarding the epidemiology of aging and the efficiency and working methods of the social organizations for the health care of the elderly.