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。当这一平衡被打破时，会引发骨质疏松症、骨关节炎、类风湿关节炎等诸多带来重大公共卫生挑战的疾病。肠道菌群（gut microbiota, GM）是调控骨骼健康的重要因子，这一特性凸显了肠-骨轴在骨骼研究中的关键作用。本综述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动态变化，以及肠道来源代谢物在调控参与骨重塑的免疫、内分泌与炎症应答过程中发挥的作用。本文还评估了以肠道菌群为靶点的各类治疗策略改善骨骼健康的潜力，涵盖饮食干预、益生菌、益生元及粪便菌群移植。本综述同时探讨了两种尚未被充分探索但极具应用前景的策略：传统中药与生物工程材料。这两类策略均展现出通过与肠道菌群相互作用以恢复骨稳态的潜力。此外，基于肠-骨轴的干预手段在骨骼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、相关机制阐释尚不充分，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-骨轴成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。