He Yangli, Cui Weipeng, Fang Tuanyu, Zhang Zeng, Zeng Min
Center of Geriatrics, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China.
School of Food Science and Engineering, Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Hainan University, Haikou, Hainan, China.
Front Microbiol. 2023 Dec 21;14:1301805. doi: 10.3389/fmicb.2023.1301805. eCollection 2023.
Sarcopenia, a disease recognized by the World Health Organization, has posed a great challenge to the world in the current aging society. The vital role of the gut microbiome through the gut-muscle axis in sarcopenia is increasingly recognized. However, the working mechanisms by which the gut microbiota functions have not been fully explored in the multi-omics field. Here, we designed a cross-sectional study that recruited patients ( = 32) with sarcopenia and healthy old adults ( = 31). Diagnosis of sarcopenia was based on the Asian Working Group for Sarcopenia (AWGS) in 2019 criteria. Muscle mass was represented by appendicular skeletal muscle mass measured by using direct segmental multi-frequency bioelectrical impedance and muscle strength was evaluated using the handgrip strength. The Short Physical Performance Battery, the 5-time Chair Stand Test, and the 4-metre Walk Test were used to assess physical performance. Shotgun metagenomic sequencing was used to profile the gut microbiome in order to identify its construction and function. Metabolome based on untargeted metabolomics was applied to describe the features and structure of fecal metabolites. In clinical indexes including triglycerides and high-density lipoprotein cholesterol, we noted a significant decrease in triglycerides (TG) and a significant increase in high-density lipoprotein cholesterol (HDL-C) in patients with sarcopenia. Appendicular skeletal muscle mass of patients with sarcopenia was lower than the health group. Based on intestinal metagenomic and fecal metabolomic profiles, we found that the gut microbiome and metabolome were disturbed in patients with sarcopenia, with significant decreases in bacteria such as , , and , as well as metabolites such as shikimic acid. Also, we plotted supervised classification models at the species level of gut bacteria (AUC = 70.83-88.33) and metabolites (AUC = 92.23-98.33) based on machine learning, respectively. Based on the gut-muscle axis network, a potential mechanism is proposed along the gut microbiome - key metabolites - clinical index, that affects appendicular skeletal muscle mass, calf circumference, handgrip strength, and BMI via Shikimic acid metabolites. This study elucidates the potential mechanisms by which the gut microbiome influences the progress of sarcopenia through metabolites and provides a meaningful theoretical foundation for reference in the diagnosis and treatment of sarcopenia.
肌肉减少症是一种被世界卫生组织认可的疾病，在当前老龄化社会中给全球带来了巨大挑战。肠道微生物群通过肠 - 肌肉轴在肌肉减少症中所起的重要作用日益受到认可。然而，在多组学领域，肠道微生物群发挥作用的工作机制尚未得到充分探索。在此，我们设计了一项横断面研究，招募了肌肉减少症患者（n = 32）和健康老年人（n = 31）。肌肉减少症的诊断依据2019年亚洲肌肉减少症工作组（AWGS）标准。肌肉质量通过使用直接节段多频生物电阻抗测量的四肢骨骼肌质量来表示，肌肉力量使用握力进行评估。采用简短体能测试、5次起坐测试和4米步行测试来评估身体机能。使用鸟枪法宏基因组测序来分析肠道微生物群，以确定其组成和功能。基于非靶向代谢组学的代谢组学用于描述粪便代谢物的特征和结构。在包括甘油三酯和高密度脂蛋白胆固醇在内的临床指标方面，我们注意到肌肉减少症患者的甘油三酯（TG）显著降低，高密度脂蛋白胆固醇（HDL - C）显著升高。肌肉减少症患者的四肢骨骼肌质量低于健康组。基于肠道宏基因组和粪便代谢组学图谱，我们发现肌肉减少症患者的肠道微生物群和代谢组受到干扰，诸如[具体细菌名称1]、[具体细菌名称2]和[具体细菌名称3]等细菌以及莽草酸等代谢物显著减少。此外，我们分别基于机器学习在肠道细菌物种水平（AUC = 70.83 - 88.33）和代谢物水平（AUC = 92.23 - 98.33）绘制了监督分类模型。基于肠 - 肌肉轴网络，提出了一种沿着肠道微生物群 - 关键代谢物 - 临床指标的潜在机制，即[具体细菌名称]通过莽草酸代谢物影响四肢骨骼肌质量、小腿围度、握力和BMI。本研究阐明了肠道微生物群通过代谢物影响肌肉减少症进展的潜在机制，并为肌肉减少症的诊断和治疗提供了有意义的理论基础以供参考。
