Han Xu, Ouyang Li, Dayoung Kim, Zhijun Bao, Fan Yang
{"title":"Gut microbiota and epigenetic age acceleration: a bi-directional Mendelian randomization study","authors":"Han Xu, Ouyang Li, Dayoung Kim, Zhijun Bao, Fan Yang","doi":"10.1007/s40520-024-02877-6","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The gut microbiota is closely related to aging, but the genetic relationship between gut microbiota and aging has not been well investigated. The aim of the study was to explore the association of microbiota with epigenetic age acceleration (EAA) using the Mendelian randomization.</p><h3>Method</h3><p>The independent genetic instruments of gut microbiota were obtained from MiBioGen consortium and the Dutch Microbiome Project. EAA data were derived from genome-wide association study. To assess the causal relationship between gut microbiota and EAA, we applied four different methods of Mendelian Randomization (MR) analysis: the inverse variance weighted method (IVW), the MR-Egger regression, the weighted median analysis (WMA), and the weighted mode. Furthermore, sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.</p><h3>Results</h3><p>We identified potential causal associations between 12 bacterial taxa and EAA (<i>P</i><sub><i>IVW</i></sub> and <i>P</i><sub><i>WMA</i></sub> < 0.05). Among them, species Holdemania_unclassified (OR: 1.31, 95% CI: 1.13–1.52, <i>P =</i> 0.0004) retained a strong positive association with GrimAge acceleration. Family Acidaminococcaceae (OR: 0.64, 95% CI: 0.44–0.93, <i>P =</i> 0.019) and family Clostridiaceae1 (OR: 0.69, 95% CI: 0.49–0.97 <i>P =</i> 0.031) were negative association with GrimAge acceleration. Reverse MR analyses indicated that EAA was associated with 6 bacterial taxa in IVW and WMA. Among them, a strong inverse association was found between Phenoage acceleration and genus Turicibacter (OR: 0.928, 95%CI: 0.888–0.971, <i>P</i><sub><i>IVW</i></sub> and <i>P</i><sub><i>WMA</i></sub> < 0.001).</p><h3>Conclusion</h3><p>Our study implicates the potential causal effects of specific microbiota on EAA, potentially providing novel insights into the prevention aging through specific gut microbiota.</p></div>","PeriodicalId":7720,"journal":{"name":"Aging Clinical and Experimental Research","volume":"36 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s40520-024-02877-6.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging Clinical and Experimental Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s40520-024-02877-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
The gut microbiota is closely related to aging, but the genetic relationship between gut microbiota and aging has not been well investigated. The aim of the study was to explore the association of microbiota with epigenetic age acceleration (EAA) using the Mendelian randomization.
Method
The independent genetic instruments of gut microbiota were obtained from MiBioGen consortium and the Dutch Microbiome Project. EAA data were derived from genome-wide association study. To assess the causal relationship between gut microbiota and EAA, we applied four different methods of Mendelian Randomization (MR) analysis: the inverse variance weighted method (IVW), the MR-Egger regression, the weighted median analysis (WMA), and the weighted mode. Furthermore, sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.
Results
We identified potential causal associations between 12 bacterial taxa and EAA (PIVW and PWMA < 0.05). Among them, species Holdemania_unclassified (OR: 1.31, 95% CI: 1.13–1.52, P = 0.0004) retained a strong positive association with GrimAge acceleration. Family Acidaminococcaceae (OR: 0.64, 95% CI: 0.44–0.93, P = 0.019) and family Clostridiaceae1 (OR: 0.69, 95% CI: 0.49–0.97 P = 0.031) were negative association with GrimAge acceleration. Reverse MR analyses indicated that EAA was associated with 6 bacterial taxa in IVW and WMA. Among them, a strong inverse association was found between Phenoage acceleration and genus Turicibacter (OR: 0.928, 95%CI: 0.888–0.971, PIVW and PWMA < 0.001).
Conclusion
Our study implicates the potential causal effects of specific microbiota on EAA, potentially providing novel insights into the prevention aging through specific gut microbiota.
期刊介绍:
Aging clinical and experimental research offers a multidisciplinary forum on the progressing field of gerontology and geriatrics. The areas covered by the journal include: biogerontology, neurosciences, epidemiology, clinical gerontology and geriatric assessment, social, economical and behavioral gerontology. “Aging clinical and experimental research” appears bimonthly and publishes review articles, original papers and case reports.