Emerging regulatory networks and multimodal intervention targeting the gut-bone axis

Bone metabolism depends on a delicate balance between bone formation and resorption. Disruptions to this balance results in conditions such as osteoporosis, osteoarthritis, and rheumatoid arthritis that have significant public health challenges. The gut microbiota (GM) is an important regulator of skeletal health. This feature highlights the role of the gut-bone axis in bone research. This review explores how GM influences bone metabolism, with emphasis on microbial community shifts and the role of gut-derived metabolites in shaping immune, endocrine, and inflammatory responses involved in bone remodeling. Therapeutic strategies that target GM, including dietary modification, probiotics, prebiotics, and fecal microbiota transplantation, are examined for their potential to improve bone health. The review also discusses two less-explored but promising approaches: traditional Chinese medicine and bioengineered materials. Both approaches demonstrate potential in restoring bone homeostasis by engaging in GM interactions. In addition, gut-bone axis-based interventions have made initial progress in clinical randomized controlled trials of bone diseases. Although preclinical findings are encouraging, translating them into clinical applications is challenging because of individual variability in microbiota composition, limited mechanistic insight, and the need for long-term safety data. By integrating cross-disciplinary findings, the present review sets the stage for advancing the gut-bone axis as a therapeutic target and outlines future directions for research and clinical intervention in bone metabolic diseases.

骨代谢依赖于骨形成与骨吸收之间的精细动态平衡。这种平衡的破坏会引发骨质疏松症、骨关节炎、类风湿关节炎等疾病，给公共卫生带来严峻挑战。肠道菌群（gut microbiota，GM）是骨骼健康的重要调控因子。本综述专题着重阐述肠-骨轴在骨研究中的核心作用，探讨了肠道菌群如何影响骨代谢，重点关注微生物群落结构的改变，以及肠道来源的代谢物在调控骨重塑相关免疫、内分泌与炎症反应中的作用。本综述还探讨了以肠道菌群为靶点的治疗策略，包括饮食干预、益生菌、益生元及粪便菌群移植，评估其改善骨骼健康的潜力。本综述同时讨论了两种尚未被充分探索但颇具前景的干预手段：传统中药与生物工程材料，这两种手段均展现出通过与肠道菌群相互作用恢复骨稳态的潜力。此外，基于肠-骨轴的干预手段在骨疾病的临床随机对照试验中已取得初步进展。尽管临床前研究结果令人鼓舞，但由于菌群组成存在个体差异、机制阐释尚不充分，且缺乏长期安全性数据，将这些发现转化为临床应用仍面临诸多挑战。本综述整合了跨学科研究成果，为推动肠-骨轴作为治疗靶点奠定了基础，并勾勒出骨代谢疾病研究与临床干预的未来发展方向。