Growing evidence indicates that dynamic changes in gut microbiome can affect intelligence; however, whether these relationships are causal remains elusive. We aimed to disentangle the poorly understood causal relationship between gut microbiota and intelligence. We performed a 2-sample Mendelian randomization (MR) analysis using genetic variants from the largest available genome-wide association studies of gut microbiota ( = 18,340) and intelligence ( = 269,867). The inverse-variance weighted method was used to conduct the MR analyses complemented by a range of sensitivity analyses to validate the robustness of the results. Considering the close relationship between brain volume and intelligence, we applied 2-step MR to evaluate whether the identified effect was mediated by regulating brain volume ( = 47,316). We found a risk effect of the genus on intelligence (odds ratio = 0.968 change in intelligence per standard deviation increase in taxa; 95% CI, 0.952–0.985; = 1.88 × 10) and a protective effect of the genus on intelligence (odds ratio = 1.053; 95% CI, 1.024–1.082; = 3.03 × 10). The 2-step MR analysis further showed that the effect of genus on intelligence was partially mediated by regulating brain volume, with a mediated proportion of 33.6% (95% CI, 6.8%–60.4%; = .014). Our results provide causal evidence indicating the role of the microbiome in intelligence. Our findings may help reshape our understanding of the microbiota-gut-brain axis and development of novel intervention approaches for preventing cognitive impairment.

中文翻译：

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肠道微生物群、脑容量和智力之间的因果关系：两步孟德尔随机分析

越来越多的证据表明，肠道微生物群的动态变化会影响智力；然而，这些关系是否具有因果关系仍然难以捉摸。我们的目的是解开人们知之甚少的肠道微生物群与智力之间的因果关系。我们使用来自肠道微生物群 (= 18,340) 和智力 (= 269,867) 的最大可用全基因组关联研究的遗传变异进行了 2 个样本孟德尔随机化 (MR) 分析。使用逆方差加权方法进行 MR 分析，并辅以一系列敏感性分析，以验证结果的稳健性。考虑到脑容量与智力之间的密切关系，我们应用两步 MR 来评估所识别的效果是否是通过调节脑容量来介导的（= 47,316）。我们发现该属对智力的风险影响（比值比 = 类群每增加一个标准差，智力变化 0.968；95% CI，0.952–0.985；= 1.88 × 10）以及该属对智力的保护作用（比值比= 1.053；95% CI，1.024–1.082；= 3.03 × 10)。两步MR分析进一步表明，属对智力的影响部分是通过调节脑容量来介导的，介导比例为33.6%（95% CI，6.8%–60.4%；= .014）。我们的结果提供了因果证据，表明微生物组在智力中的作用。我们的发现可能有助于重塑我们对微生物群-肠-脑轴的理解，并有助于开发预防认知障碍的新型干预方法。