Fu Jiongxing, Xu Wanghong, Yu Danxia, Jiang Yu, Wang Lei, Cai Hui, Xia Qinghua, Shu Xiao-Ou, Zheng Wei
Department of Epidemiology, NHC Key Laboratory for Health Technology Assessment, Fudan University School of Public Health, Shanghai, China.
Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Aging Cell. 2025 Oct;24(10):e70192. doi: 10.1111/acel.70192. Epub 2025 Aug 4.
Gut microbial stability typically decreases with physiological aging. This decline may vary between sexes and can potentially be mitigated by adopting a healthy lifestyle. Microbial guilds, defined as functionally coherent groups of bacteria, may serve as meaningful ecological indicators of aging. This study included 2944 participants aged 51-89 years from the Shanghai Men's and Women's Health Studies. Using 16S rRNA gene sequencing and a guild-based approach, we evaluated the associations between gut microbiota and age in 1353 relatively healthy individuals. We found that women demonstrated a decline in the Chao1 index, an increase in Pielou evenness, and a remarkable shift in Bray-Curtis distance, whereas men exhibited an increase in Bray-Curtis uniqueness. Of the 45 age-related guilds identified, 16 (8 in men and 10 in women) were considered potential aging biomarkers (p < 0.05), with Guild_6 (Bifidobacterium sp. dominated) and Guild_118 (Veillonella dispar dominated) being common to both sexes. These guilds were associated with consistent predicted functions, particularly 1,4-dihydroxy-2-naphthoate biosynthesis. We estimated sex-specific microbial age using random forest models and found that women and individuals with major chronic diseases had higher microbial ages. Prospective analysis revealed that an "old" microbial age was associated with a higher risk of type 2 diabetes (HR = 2.0, 95% CI: 1.1, 3.7). Individuals with healthier lifestyles had a 0.43-year lower microbial age (95% CI: -0.85, -0.01). Our findings elucidate the sex-differentiated aging patterns of gut microbiota in Chinese adults and imply the potential benefits of healthy lifestyle behaviors in slowing down microbiome aging.
肠道微生物稳定性通常会随着生理衰老而下降。这种下降可能存在性别差异，并且通过采取健康的生活方式有可能得到缓解。微生物群落被定义为功能相关的细菌群体，可能是有意义的衰老生态指标。本研究纳入了来自上海男性和女性健康研究的2944名年龄在51 - 89岁的参与者。我们使用16S rRNA基因测序和基于群落的方法，在1353名相对健康的个体中评估了肠道微生物群与年龄之间的关联。我们发现，女性的Chao1指数下降、Pielou均匀度增加以及Bray - Curtis距离发生显著变化，而男性的Bray - Curtis独特性增加。在鉴定出的45个与年龄相关的群落中，16个（男性8个，女性10个）被认为是潜在的衰老生物标志物（p < 0.05），其中群落6（以双歧杆菌属为主）和群落118（以殊异韦荣球菌为主）在两性中都存在。这些群落与一致的预测功能相关，特别是1,4 - 二羟基 - 2 - 萘甲酸生物合成。我们使用随机森林模型估计了性别特异性的微生物年龄，发现女性和患有主要慢性病的个体具有更高的微生物年龄。前瞻性分析显示，“老”的微生物年龄与2型糖尿病的较高风险相关（风险比 = 2.0，95%置信区间：1.1, 3.7）。生活方式更健康的个体微生物年龄低0.43岁（95%置信区间：-0.85, -0.01）。我们的研究结果阐明了中国成年人肠道微生物群的性别差异衰老模式，并暗示了健康生活方式行为在减缓微生物群衰老方面的潜在益处。
