Department of Physiology, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland.
Exp Physiol. 2023 Sep;108(9):1132-1143. doi: 10.1113/EP091063. Epub 2023 Jun 3.
What is the topic of this review? The contribution of gut microbial signalling to skeletal muscle maintenance and development and identification of potential therapeutic targets in progressive muscle degenerative diseases such as Duchenne muscular dystrophy. What advances does it highlight? Gut microbe-derived metabolites are multifaceted signalling molecules key to muscle function, modifying pathways contributing to skeletal muscle wasting, making them a plausible target for adjunctive therapy in muscular dystrophy.
Skeletal muscle is the largest metabolic organ making up ∼50% of body mass. Because skeletal muscle has both metabolic and endocrine properties, it can manipulate the microbial populations within the gut. In return, microbes exert considerable influence on skeletal muscle via numerous signalling pathways. Gut bacteria produce metabolites (i.e., short chain fatty acids, secondary bile acids and neurotransmitter substrates) that act as fuel sources and modulators of inflammation, influencing host muscle development, growth and maintenance. The reciprocal interactions between microbes, metabolites and muscle establish a bidirectional gut-muscle axis. The muscular dystrophies constitute a broad range of disorders with varying disabilities. In the profoundly debilitating monogenic disorder Duchenne muscular dystrophy (DMD), skeletal muscle undergoes a reduction in muscle regenerative capacity leading to progressive muscle wasting, resulting in fibrotic remodelling and adipose infiltration. The loss of respiratory muscle in DMD culminates in respiratory insufficiency and eventually premature death. The pathways contributing to aberrant muscle remodelling are potentially modulated by gut microbial metabolites, thus making them plausible targets for pre- and probiotic supplementation. Prednisone, the gold standard therapy for DMD, drives gut dysbiosis, inducing a pro-inflammatory phenotype and leaky gut barrier contributing to several of the well-known side effects associated with chronic glucocorticoid treatment. Several studies have observed that gut microbial supplementation or transplantation exerts positive effects on muscle, including mitigating the side effects of prednisone. There is growing evidence in support of the potential for an adjunctive microbiota-directed regimen designed to optimise gut-muscle axis signalling, which could alleviate muscle wasting in DMD.
这篇综述的主题是什么？肠道微生物信号在维持和发育骨骼肌肉中的作用，以及在进行性肌肉退行性疾病（如杜氏肌营养不良症）中识别潜在治疗靶点。它强调了哪些进展？肠道微生物衍生的代谢物是多方面的信号分子，是肌肉功能的关键，可修饰导致骨骼肌消耗的途径，使它们成为肌肉营养不良辅助治疗的合理靶点。
骨骼肌是最大的代谢器官，占体重的 50%左右。由于骨骼肌具有代谢和内分泌特性，它可以控制肠道内的微生物种群。反过来，微生物通过多种信号通路对骨骼肌产生巨大影响。肠道细菌产生代谢物（即短链脂肪酸、次级胆酸和神经递质底物），作为燃料来源和炎症调节剂，影响宿主肌肉发育、生长和维持。微生物、代谢物和肌肉之间的相互作用建立了一个双向的肠-肌肉轴。肌肉营养不良症是一组具有不同残疾程度的广泛疾病。在严重的遗传性疾病杜氏肌营养不良症（DMD）中，骨骼肌的肌肉再生能力下降，导致进行性肌肉消耗，导致纤维化重塑和脂肪浸润。DMD 中呼吸肌的丧失最终导致呼吸功能不全，并最终导致过早死亡。导致异常肌肉重塑的途径可能受到肠道微生物代谢物的调节，因此它们成为益生菌和预生物补充的合理靶点。地塞米松是 DMD 的金标准治疗药物，它会导致肠道菌群失调，诱导炎症表型和肠道通透性增加，导致与慢性糖皮质激素治疗相关的许多已知副作用。有几项研究观察到，肠道微生物补充或移植对肌肉有积极影响，包括减轻地塞米松的副作用。越来越多的证据支持设计一种辅助的微生物定向治疗方案的潜力，以优化肠-肌肉轴信号，从而缓解 DMD 中的肌肉消耗。
