The gut-facial aging axis: A two-sample Mendelian randomization and mediation analysis of gut microbiota, gut microbiota metabolic pathways, and blood metabolites.

IF 2 4区 医学 Q3 DERMATOLOGY Skin Research and Technology Pub Date : 2024-08-01 DOI:10.1111/srt.70006
Sha Yang, Ying Zhao, Jian Liu, Jianning Song, Qingyan Long, Si Cheng
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Abstract

Background: Facial aging (FA) is a complex process influenced by both genetic and environmental factors. Gut microbiota (GM), gut microbiota metabolic pathways (GMMPs), and blood metabolites (BMs) have been implicated in the regulation of FA, but the causal and mediating effects of these factors remain unclear.

Methods: We used summary-level data from genome-wide association studies (GWAS) of 16S rRNA gene sequencing data for GM (n = 18 340), GWAS of GMMPs (n = 7738), BMs (n = 24 925), and GWAS of FA (n = 423 999). We applied Mendelian randomization (MR) methods to estimate the causal effects of GM, GMMPs, and BMs on FA. We performed mediation analysis to quantify the proportion of the effects mediated by blood metabolites.

Results: We identified nine genus, two phylum, two families of GM, nine GM metabolic pathways, and 73 BMs that showed potential causal effects on FA. After Bonferroni correction, three BMs remained causally associated with FA, including average number of methylene groups per double bond (β, -0.023; 95% CI, -0.032∼-0.014; p = 3.120×10-7) and average number of methylene groups in a fatty acid chain (β, -0.031; 95% CI, -0.045∼-0.016; p = 2.062×10-5), which had strong negative causal effects on FA, and ratio of bisallylic groups to total fatty acids (β, 0.023; 95% CI, 0.017∼-0.029; p = 8.441×10-15), which had a strong positive causal effect on FA. Mediation analysis revealed that histidine, average number of methylene groups in a fatty acid chain, and triglycerides in chylomicrons and largest VLDL particles mediated the effects of anaerofilum and/ or superpathway of Laspartate and Lasparagine biosynthesis on FA.

Conclusion: Our study provides novel insights into the causal and mediating effects of GM, GMMPs, and BMs on FA. These findings may have implications for the development of new strategies for preventing or delaying FA.

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肠道-面部衰老轴:肠道微生物群、肠道微生物群代谢途径和血液代谢物的双样本孟德尔随机化和中介分析。
背景:面部衰老(FA)是一个受遗传和环境因素影响的复杂过程。肠道微生物群(GM)、肠道微生物群代谢途径(GMMPs)和血液代谢物(BMs)被认为与 FA 的调控有关,但这些因素的因果关系和中介效应仍不清楚:我们使用了全基因组关联研究(GWAS)的汇总级数据,这些数据来自基因组学 16S rRNA 基因测序数据(n = 18 340)、GMMPs 基因组关联研究(n = 7738)、BMs 基因组关联研究(n = 24 925)和 FA 基因组关联研究(n = 423 999)。我们采用孟德尔随机化(MR)方法估算了GM、GMMPs和BMs对FA的因果效应。我们进行了中介分析,以量化血液代谢物中介效应的比例:结果:我们确定了 9 个属,2 个门,2 个 GM 科,9 条 GM 代谢途径和 73 种 BMs 对 FA 有潜在的因果效应。经 Bonferroni 校正后,3 个 BMs 仍与 FA 存在因果关系,包括每个双键的亚甲基平均数量(β,-0.023;95% CI,-0.032∼-0.014;p = 3.120×10-7)和脂肪酸链中亚甲基的平均数量(β,-0.031;95% CI,-0.045∼-0.016;p = 2.062×10-5),对 FA 有强烈的负向因果效应;双烯丙基与总脂肪酸之比(β,0.023;95% CI,0.017∼-0.029;p = 8.441×10-15),对 FA 有强烈的正向因果效应。中介分析显示,组氨酸、脂肪酸链中亚甲基的平均数量以及乳糜微粒和最大 VLDL 颗粒中的甘油三酯介导了厌氧膜和/或 Laspartate 和 Lasparagine 生物合成超级途径对 FA 的影响:我们的研究为了解转基因、转基因促蛋白和生物膜对 FA 的因果和中介作用提供了新的视角。这些发现可能对开发预防或延缓 FA 的新策略具有重要意义。
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来源期刊
Skin Research and Technology
Skin Research and Technology 医学-皮肤病学
CiteScore
3.30
自引率
9.10%
发文量
95
审稿时长
6-12 weeks
期刊介绍: Skin Research and Technology is a clinically-oriented journal on biophysical methods and imaging techniques and how they are used in dermatology, cosmetology and plastic surgery for noninvasive quantification of skin structure and functions. Papers are invited on the development and validation of methods and their application in the characterization of diseased, abnormal and normal skin. Topics include blood flow, colorimetry, thermography, evaporimetry, epidermal humidity, desquamation, profilometry, skin mechanics, epiluminiscence microscopy, high-frequency ultrasonography, confocal microscopy, digital imaging, image analysis and computerized evaluation and magnetic resonance. Noninvasive biochemical methods (such as lipids, keratin and tissue water) and the instrumental evaluation of cytological and histological samples are also covered. The journal has a wide scope and aims to link scientists, clinical researchers and technicians through original articles, communications, editorials and commentaries, letters, reviews, announcements and news. Contributions should be clear, experimentally sound and novel.
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