中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (23): 6000-6009.doi: 10.12307/2026.318

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

肌肉减少症与非酒精性脂肪肝：肠道微生物群分析

张  政1，张艺博1，许  斌2， 颜士朝1，郭  徽1   

  1. 1广西中医药大学，广西壮族自治区南宁市   530000；2广西中医药大学第一附属医院肝胆外科，广西壮族自治区南宁市   530000
  • 收稿日期:2025-05-06 接受日期:2025-06-11 出版日期:2026-08-18 发布日期:2025-12-31
  • 通讯作者: 许斌，硕士，教授，硕士生导师，广西中医药大学第一附属医院肝胆外科，广西壮族自治区南宁市 530000
  • 作者简介:张政，男，1997年生，河北省邢台市人，汉族，广西中医药大学在读硕士，主要从事外科疾病的中西医结合防治研究。 共同第一作者：张艺博，女，1997年生，黑龙江省哈尔滨市人，汉族，广西中医药大学在读硕士，主要从事心血管疾病防治研究。
  • 基金资助:
    广西中医药大学“岐黄工程”高层次人才团队培育项目(202411)，项目负责人：许斌

Sarcopenia and non-alcoholic fatty liver disease: analysis of the gut microbiota

Zhang Zheng1, Zhang Yibo1, Xu Bin2, Yan Shichao1, Guo Hui1   

  1. 1Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China; 2Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • Received:2025-05-06 Accepted:2025-06-11 Online:2026-08-18 Published:2025-12-31
  • Contact: Xu Bin, MS, Professor, Master’s supervisor, Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China
  • About author:Zhang Zheng, MS candidate, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China Zhang Yibo, MS candidate, Guangxi University of Chinese Medicine, Nanning 530000, Guangxi Zhuang Autonomous Region, China Zhang Zheng and Zhang Yibo contributed equally to this work.
  • Supported by:
    “Qihuang Engineering” High-level Talent Team Cultivation Project of Guangxi University of Chinese Medicine, No. 202411 (to XB)

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摘要：



文题释义：
非酒精性脂肪肝：是与代谢异常密切相关的慢性肝病，特征是肝细胞中脂肪堆积过多，与过量饮酒或其他可识别的肝损伤因素无关。
肌肉减少症：是一种与年龄相关的骨骼肌疾病，特征是肌肉质量下降、肌肉力量和身体功能下降。

背景：既往研究已证明非酒精性脂肪肝与肌肉减少症之间存在相关性，但因果关系仍不清楚。肠道-肌肉-肝脏轴表明，肠道菌群与肌肉减少症和非酒精性脂肪肝之间存在复杂的相互作用，但具体发病机制仍未阐明。
目的：通过孟德尔随机化分析探讨肌肉减少症与非酒精性脂肪肝之间是否存在因果关系，深入研究肠道菌群在非酒精性脂肪肝和肌肉减少症之间的潜在作用。
方法：肌肉减少症数据来自英国生物银行(是英国国家级生物医学数据库，由英国政府支持，联合牛津大学、曼彻斯特大学等机构于2006年开发，包含50万名参与者的基因、影像、健康记录等多维度数据)，肌肉减少症相关特征包括四肢肌肉质量、握力和步行速度；非酒精性脂肪肝数据集源自GHODSIAN等编制的可公开访问GWAS摘要数据集，该数据集包括来自eMERGE和FinnGen的GWAS队列的汇总统计数据，来自英国生物库更新的非酒精性脂肪肝GWAS数据及爱沙尼亚生物库新进行的GWAS数据；211种肠道菌群数据来自MiBioGen联盟进行的大型人类肠道微生物群组成研究。使用逆方差加权法、加权中位数法、MR-Egger法、加权模型法和简单模型法评估非酒精性脂肪肝、肌肉减少症及肠道菌群相关性状之间的相互影响。
结果与结论：①逆方差加权法分析结果表明，步行速度、四肢肌肉质量与非酒精性脂肪肝呈负相关，左、右手握力与非酒精性脂肪肝风险无显著相关性。反向孟德尔随机化分析结果显示，非酒精性脂肪肝和四肢肌肉质量呈负相关，非酒精性脂肪肝与步行速度、左、右手握力并无显著相关性。39种肠道菌群与肌肉减少症发病具有显著相关性，6种肠道菌群与非酒精性脂肪肝之间存在因果关系。②研究提示肠道菌群可能通过短链脂肪酸代谢调控“肠-肝-肌轴”，为中国学者提供了跨器官机制研究的新方向。结合中国人群特有的遗传背景(如ALDH2突变、高盐饮食相关基因)，可进一步解析代谢-肌肉共病的种族特异性通路，为制定符合中国膳食结构(如高谷物摄入)的饮食建议提供科学依据。
https://orcid.org/0009-0009-0595-8852 (张艺博); https://orcid.org/0009-0000-9181-6520(张政)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 肌肉减少症, 非酒精性脂肪肝, 肠道微生物群, 肠道菌群, 孟德尔随机化分析, 因果关联

Abstract: BACKGROUND: Previous studies have established a correlation between non-alcoholic fatty liver disease and sarcopenia; however, their causal relationship remains uncertain. The gut-muscle-liver axis hypothesis posits intricate interactions between the gut microbiota and both sarcopenia and non-alcoholic fatty liver disease, yet the precise pathogenic mechanisms underlying these interactions remain poorly elucidated.
OBJECTIVE: To investigate the potential causal relationship between sarcopenia and non-alcoholic fatty liver disease using Mendelian randomization analysis and to delve into the potential role of the gut microbiota in mediating or influencing the interplay between non-alcoholic fatty liver disease and sarcopenia.
METHODS: Sarcopenia data were sourced from the UK Biobank (the UK National-Level Biomedical Database, supported by the UK government and developed in 2006 in collaboration with institutions such as the University of Oxford and the University of Manchester, which encompasses multidimensional data including genes, imaging, and health records from 500 000 participants), with relevant traits including appendicular muscle mass, grip strength, and walking speed. The non-alcoholic fatty liver disease dataset was derived from a publicly accessible GWAS summary dataset compiled by Ghodsian et al., comprising aggregated statistics from GWAS cohorts including eMERGE and FinnGen, updated GWAS data of non-alcoholic fatty liver disease from the UK Biobank, and newly conducted GWAS data from the Estonian Biobank. Gut microbiota data for 211 taxa were obtained from the MiBioGen consortium’s large-scale human gut microbiota composition study. Analytical methods included inverse-variance weighted, weighted median, MR-Egger, weighted mode, and simple mode approaches to evaluate the interplay between non-alcoholic fatty liver disease, sarcopenia and gut microbiota-related traits. 
RESULTS AND CONCLUSION: (1) The inverse-variance weighted analysis revealed a negative association between walking speed, appendicular muscle mass, and risk of non-alcoholic fatty liver disease, whereas no significant association was observed between left/right hand grip strength and non-alcoholic fatty liver disease. Reverse Mendelian randomization analysis indicated a negative causal relationship between non-alcoholic fatty liver disease and appendicular muscle mass, but no significant causal links were found between non-alcoholic fatty liver disease and walking speed or grip strength. Additionally, 39 gut microbiota taxa showed significant associations with sarcopenia onset, and causal relationships were identified between 6 gut microbiota taxa and non-alcoholic fatty liver disease. (2) The study suggests that the gut microbiota may regulate the “gut-liver-muscle axis” through the metabolism of short-chain fatty acids, which provides Chinese scholars with a new direction for the study of cross-organ mechanisms. Combined with the unique genetic background of the Chinese population (e.g., ALDH2 mutation and genes related to high salt diet), we can further analyze the race-specific pathways of metabolic-muscle co-morbidities, providing a scientific basis for the development of dietary recommendations that are consistent with the dietary structure of the Chinese population (e.g., high cereal intake). 


Key words: sarcopenia, non-alcoholic fatty liver disease, gut microbiota, intestinal flora, Mendelian randomization analysis, causality

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