越来越多的证据表明,人类肠道微生物组在骨骼肌质量(SMM)的变化中起着重要作用。然而,人类肠道微生物组与SMM之间的特定因果机制关系仍未解决。了解因果关系可能为SMM丢失的新干预措施提供基础。这项研究调查了在中国社区居住的健康更年期妇女中,人类肠道微生物组是否对SMM有因果关系。
估计的SMM来自全身双能X射线吸收法。我们对全基因组测序进行了整合分析,鸟枪宏基因组测序,和血清短链脂肪酸(SCFA),以及社区居住的健康更年期妇女中可用的宿主SMM测量值(N=482)。我们将结果与人类肠道微生物组(N=952)和SMM性状(N=28.330)的全基因组关联分析的汇总统计数据相结合。作为因果关系的先决条件,我们使用了一种计算协议,该协议被提出来测量肠道宏基因组之间的相关性,代谢组,和宿主性状,以探讨人类肠道菌群与SMM之间的关系。因果推断方法用于评估肠道微生物特征对SMM的潜在因果影响,通过单样本和双样本孟德尔随机化(MR)分析,分别。
在宏基因组关联分析中,肠道微生物合成SCFA丁酸酯的能力增加与血清丁酸酯水平[Spearman相关系数(SCC)=0.13,P=0.02]和骨骼肌指数(SCC=0.084,P=0.002)显著相关.令人感兴趣的是发现两种主要产生丁酸盐的细菌种类都与肠道微生物合成丁酸盐的能力增加呈正相关[PrausnitziiFaeciacteriumprausnitzii(SCC=0.25,P=6.6×10-7)和病毒虫(SCC=0.15,P=0.001)]和骨骼肌指数[F.prausnitzii(SCC=0.16,P=6.2×10-4)和B.virosa(SCC=0.17,P=2.4×10-4)]。单样本MR结果表明,肠道微生物合成的SCFA丁酸酯与阑尾瘦体重之间存在因果关系(β=0.04,95%置信区间0.029至0.051,P=0.003)。两个样本的MR结果进一步证实了SCFA丁酸酯的肠道微生物合成与四肢瘦肉质量之间的因果关系(β=0.06,95%置信区间0至0.13,P=0.06)。
我们的结果可能有助于预防或减轻SMM损失的新型干预方法的未来发展。
Increasing evidence suggests that human gut microbiome plays an important role in variation of skeletal muscle mass (SMM). However, specific causal mechanistic relationship of human gut microbiome with SMM remains largely unresolved. Understanding the causal mechanistic relationship may provide a basis for novel interventions for loss of SMM. This study investigated whether human gut microbiome has a causal effect on SMM among Chinese community-dwelling healthy menopausal women.
Estimated SMM was derived from whole-body dual-energy X-ray absorptiometry. We performed integrated analyses on whole-genome sequencing, shotgun metagenomic sequencing, and serum short-chain fatty acids (SCFAs), as well as available host SMM measurements among community-dwelling healthy menopausal women (N = 482). We combined the results with summary statistics from genome-wide association analyses for human gut microbiome (N = 952) and SMM traits (N = 28 330). As a prerequisite for causality, we used a computational protocol that was proposed to measure correlations among gut metagenome, metabolome, and the host trait to investigate the relationship between human gut microbiome and SMM. Causal inference methods were applied to assess the potential causal effects of gut microbial features on SMM, through one-sample and two-sample Mendelian randomization (MR) analyses, respectively.
In metagenomic association analyses, the increased capacity for gut microbial synthesis of the SCFA butyrate was significantly associated with serum butyrate levels [Spearman correlation coefficient (SCC) = 0.13, P = 0.02] and skeletal muscle index (SCC = 0.084, P = 0.002). Of interest was the finding that two main butyrate-producing bacterial species were both positively associated with the increased capacity for gut microbial synthesis of butyrate [Faecalibacterium prausnitzii (SCC = 0.25, P = 6.6 × 10-7 ) and Butyricimonas virosa (SCC = 0.15, P = 0.001)] and for skeletal muscle index [F. prausnitzii (SCC = 0.16, P = 6.2 × 10-4 ) and B. virosa (SCC = 0.17, P = 2.4 × 10-4 )]. One-sample MR results showed a causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.04, 95% confidence interval 0.029 to 0.051, P = 0.003). Two-sample MR results further confirmed the causal effect between gut microbial synthesis of the SCFA butyrate and appendicular lean mass (β = 0.06, 95% confidence interval 0 to 0.13, P = 0.06).
Our results may help the future development of novel intervention approaches for preventing or alleviating loss of SMM.