Department of Physical and Rehabilitation Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2908-2919. doi: 10.1002/jcsm.13096. Epub 2022 Oct 11.
A gut-muscle axis through which the microbiome influences skeletal muscle has been hypothesized. However, sex-specific association between the characteristics of gut microbiota and skeletal muscle mass has not yet been reported. Herein, we performed sex-specific analyses of faecal microbiota composition for the skeletal muscle mass in a population-based cohort.
We collected faecal samples of 1052 middle-aged participants (621 men and 431 women) who attended health screenings, and we analysed the intestinal microbiota using 16S rRNA gene sequencing. Relative muscle mass was calculated using a bioelectrical impedance analysis and presented as the skeletal muscle mass index [SMI (%) = total appendicular muscle mass (kg)/weight (kg) × 100]. We categorized the subjects into four groups by the quartile of the SMI. Association tests between gut microbiota and SMI were conducted according to the microbial diversity, taxonomic profiling and functional inference in a sex-stratified manner.
The mean age and SMI of the total participants were 44.8 years (standard deviation [SD], 8.2) and 41.4% (SD, 3.9), respectively. After adjustments for possible covariates such as age, body mass index and regular physical activity, the highest quartile (Q4) group of SMI had higher alpha diversity than the lowest quartile (Q1) group in male participants (coefficient = 10.79, P < 0.05, linear regression model), whereas there was no difference in diversity among SMI groups in females. At the species level, Haemophilus parainfluenzae (coefficient = 1.910) and Roseburia faecis (coefficient = 1.536) were more abundant in the highest SMI (Q4) group than in the lowest SMI (Q1) group in males. However, no significant taxon was observed along the SMI groups in females. The gut microbiota of the lowest SMI group (Q1) was enriched with genes involved in biosynthesis of amino acids and energy generation compared with that of the highest SMI group (Q4) in both sexes, although the significance of the inferred pathways was weak (P < 0.05 but the false discovery rate q > 0.05).
In this large sample of middle-aged individuals, this study highlights fundamental sex-specific differences in the microbial diversity, composition and metabolic pathways inferred from gut microbiota according to SMI. The gut microbiota may provide novel insights into the potential mechanisms underlying the sex dependence of skeletal muscle mass.
人们假设存在一个肠道-肌肉轴，其中微生物组影响骨骼肌。然而，肠道微生物群的特征与骨骼肌质量之间的性别特异性关联尚未被报道。在此，我们在一个基于人群的队列中对粪便微生物群组成与骨骼肌质量进行了性别特异性分析。
我们收集了参加健康筛查的 1052 名中年参与者（621 名男性和 431 名女性）的粪便样本，并使用 16S rRNA 基因测序分析肠道微生物群。使用生物电阻抗分析计算相对肌肉质量，并以骨骼肌质量指数[SMI（%）=四肢总附着肌肉质量（kg）/体重（kg）×100]表示。我们根据 SMI 的四分位数将受试者分为四组。根据微生物多样性、分类分析和功能推断，以性别分层的方式进行了肠道微生物群与 SMI 之间的关联检验。
总参与者的平均年龄和 SMI 分别为 44.8 岁（标准差[SD]，8.2）和 41.4%（SD，3.9）。在调整了年龄、体重指数和有规律的体育活动等可能的混杂因素后，男性参与者中 SMI 的最高四分位数（Q4）组的 alpha 多样性高于最低四分位数（Q1）组（系数=10.79，P<0.05，线性回归模型），而女性参与者中 SMI 组之间的多样性没有差异。在物种水平上，副流感嗜血杆菌（系数=1.910）和粪玫瑰菌（系数=1.536）在男性的最高 SMI（Q4）组中比在最低 SMI（Q1）组中更为丰富。然而，在女性中，没有观察到沿着 SMI 组的显著分类群。在两性中，最低 SMI 组（Q1）的肠道微生物群富含与氨基酸生物合成和能量生成相关的基因，而最高 SMI 组（Q4）则较少，尽管推断途径的显著性较弱（P<0.05，但错误发现率 q>0.05）。
在这项针对中年个体的大型样本研究中，本研究强调了根据 SMI 从肠道微生物群中推断出的微生物多样性、组成和代谢途径的基本性别特异性差异。肠道微生物群可能为骨骼肌质量的潜在性别依赖性提供新的见解。
