Genetic Causal Association Between Skin Microbiota and Biological Aging: Evidence From a Mendelian Randomization Analysis

IF 2.3 4区医学 Q2 DERMATOLOGY Journal of Cosmetic Dermatology Pub Date : 2025-01-03 DOI:10.1111/jocd.16762

Yuan Li, Liwen Ma, Lipan Fan, Chuyan Wu, Dan Luo, Feng Jiang

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Abstract

Background

The skin microbiota, a complex community of microorganisms residing on the skin, plays a crucial role in maintaining skin health and overall homeostasis. Recent research has suggested that alterations in the composition and function of the skin microbiota may influence the aging process. However, the causal relationships between specific skin microbiota and biological aging remain unclear. Mendelian randomization (MR) analysis provides a powerful tool to explore these causal links by utilizing genetic variants as instrumental variables, thereby minimizing confounding factors and reverse causality that often complicate observational studies.

Methods

We utilized a two-sample MR approach with population-based cross-sectional data from two German cohorts, KORA FF4 (n = 324) and PopGen (n = 273). In total, GWAS summary data from 1656 skin samples and datasets on accelerated biological age were analyzed to investigate the causal relationship between skin microbiota and accelerated biological aging. The primary analysis was performed using the inverse variance weighted (IVW) method with random effects and was further supported by MR-Egger regression, Cochran's Q test, and a range of sensitivity analyses.

Results

The MR analysis revealed that for biological age acceleration (BioageAccel), the IVW analysis identified protective effects from certain skin microbiota, including Alphaproteobacteria_Dry (p = 0.046), Asv033_sebaceous (p = 0.043), Burkholderiales_Moist (p = 0.008), and Proteobacteria_Moist (p = 0.042). Similar protective effects were observed for Burkholderiales_Moist (p = 0.045) and Proteobacteria_Moist (p = 0.012) in the weighted median analysis. In contrast, Paracoccus_Moist (p = 0.013) and Proteobacteria_Sebaceous (p = 0.005) were associated with accelerated aging. When using PhenoAge acceleration as the outcome, the IVW analysis linked skin microbiota like Asv005_Dry (p = 0.026), ASV039_Dry (p = 0.003), Betaproteobacteria_Sebaceous (p = 0.038), and Chryseobacterium_Moist (p = 0.013) with accelerated aging. The weighted median analysis supported these findings and also identified protective effects from ASV011_Dry (p = 0.021), ASV023_Dry (p = 0.040), Bacteroidales_Dry (p = 0.022), Enhydrobacter_Moist (p = 0.038), Proteobacteria_Moist (p = 0.002), and Rothia_Moist (p = 0.038).

Conclusions

This two-sample MR study reveals potential causal relationships between skin microbiota and aging. However, to confirm these findings, further randomized controlled trials (RCTs) are necessary.

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皮肤微生物群与生物衰老之间的遗传因果关系：来自孟德尔随机化分析的证据。

背景：皮肤微生物群是居住在皮肤上的一个复杂的微生物群落，在维持皮肤健康和整体稳态中起着至关重要的作用。最近的研究表明，皮肤微生物群的组成和功能的改变可能会影响衰老过程。然而，特定皮肤微生物群与生物衰老之间的因果关系尚不清楚。孟德尔随机化（MR）分析提供了一个强大的工具，通过利用遗传变异作为工具变量来探索这些因果关系，从而最大限度地减少混淆因素和反向因果关系，这些因素往往使观察性研究复杂化。方法：我们采用两样本MR方法，采用基于人群的横断面数据，来自两个德国队列，KORA FF4 （n = 324）和PopGen （n = 273）。总共分析了来自1656个皮肤样本和加速生物老化数据集的GWAS汇总数据，以探讨皮肤微生物群与加速生物老化之间的因果关系。采用随机效应的逆方差加权（IVW）方法进行初步分析，并进一步采用MR-Egger回归、Cochran’s Q检验和一系列敏感性分析。结果：MR分析显示，对于生物年龄加速（BioageAccel）， IVW分析确定了某些皮肤微生物群的保护作用，包括Alphaproteobacteria_Dry (p = 0.046), Asv033_sebaceous (p = 0.043), Burkholderiales_Moist （p = 0.008）和Proteobacteria_Moist （p = 0.042）。在加权中位数分析中，Burkholderiales_Moist （p = 0.045）和Proteobacteria_Moist （p = 0.012）也观察到类似的保护作用。相反，Paracoccus_Moist （p = 0.013）和Proteobacteria_Sebaceous （p = 0.005）与加速衰老有关。当使用表型加速作为结果时，IVW分析将皮肤微生物群如Asv005_Dry (p = 0.026), ASV039_Dry (p = 0.003), Betaproteobacteria_Sebaceous （p = 0.038）和Chryseobacterium_Moist （p = 0.013）与加速衰老联系起来。加权中位数分析支持这些发现，并且还确定了ASV011_Dry （p = 0.021）、ASV023_Dry （p = 0.040）、Bacteroidales_Dry （p = 0.022）、Enhydrobacter_Moist （p = 0.038）、Proteobacteria_Moist （p = 0.002）和Rothia_Moist （p = 0.038）的保护作用。结论：这项双样本MR研究揭示了皮肤微生物群与衰老之间潜在的因果关系。然而，为了证实这些发现，进一步的随机对照试验（rct）是必要的。

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来源期刊

Journal of Cosmetic Dermatology DERMATOLOGY-

CiteScore

4.30

自引率

13.00%

发文量

818

审稿时长

>12 weeks

期刊介绍： The Journal of Cosmetic Dermatology publishes high quality, peer-reviewed articles on all aspects of cosmetic dermatology with the aim to foster the highest standards of patient care in cosmetic dermatology. Published quarterly, the Journal of Cosmetic Dermatology facilitates continuing professional development and provides a forum for the exchange of scientific research and innovative techniques. The scope of coverage includes, but will not be limited to: healthy skin; skin maintenance; ageing skin; photodamage and photoprotection; rejuvenation; biochemistry, endocrinology and neuroimmunology of healthy skin; imaging; skin measurement; quality of life; skin types; sensitive skin; rosacea and acne; sebum; sweat; fat; phlebology; hair conservation, restoration and removal; nails and nail surgery; pigment; psychological and medicolegal issues; retinoids; cosmetic chemistry; dermopharmacy; cosmeceuticals; toiletries; striae; cellulite; cosmetic dermatological surgery; blepharoplasty; liposuction; surgical complications; botulinum; fillers, peels and dermabrasion; local and tumescent anaesthesia; electrosurgery; lasers, including laser physics, laser research and safety, vascular lasers, pigment lasers, hair removal lasers, tattoo removal lasers, resurfacing lasers, dermal remodelling lasers and laser complications.