You Yanghao, Xiang Tingwen, Yang Chuan, Xiao Shiyu, Tang Yong, Luo Gang, Ling Zhiguo, Luo Fei, Chen Yueqi
Department of Orthopedics, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China.
Department of Biomedical Materials Science, Third Military Medical University (Army Medical University), Chongqing, People's Republic of China.
Gut Microbes. 2025 Dec;17(1):2545417. doi: 10.1080/19490976.2025.2545417. Epub 2025 Aug 28.
Over the past few decades, accumulating evidence has demonstrated that gut microbiota engages in a sustained dialog with the immune system, leading to microbiota-driven immune responses that mediate the regulation of bone-related diseases. Despite the complexity of the dynamic interactions within the gut-immune-bone axis, advancements in high-throughput multi-omics sequencing have significantly facilitated the detailed exploration of this intricate network, thereby providing the potential to develop novel therapeutic strategies for bone-related diseases. In this review, we first summarize the variations in gut microbiota composition observed in patients with bone-related diseases, such as rheumatoid arthritis (RA), osteoarthritis (OA), and osteoporosis (OP), in comparison to healthy controls, along with the factors influencing these changes. The review that follows synthesize evidences highlighting the profound effects of gut microbial dysbiosis on immune homeostasis and bone microenvironment, respectively. We further elaborate that the gut-immune axis and gut-bone axis are not independent but three-dimensional networks, emphasizing gut microbial dysbiosis as a pivotal driver of immune dysregulation and subsequent bone homeostasis imbalance. Therapeutic strategies to manipulate the gut-immune-bone axis based on the use of probiotics as well as prebiotics, fecal microbiota transplantation, dietary modifications, and pharmacological interventions are also discussed. Finally, we discuss the challenges of current research on the gut-immune-bone axis and propose future directions for identifying novel therapeutic targets based on this axis to treat these diseases.
在过去几十年中，越来越多的证据表明，肠道微生物群与免疫系统持续对话，引发由微生物群驱动的免疫反应，从而介导对骨相关疾病的调节。尽管肠道-免疫-骨轴内的动态相互作用十分复杂，但高通量多组学测序技术的进步极大地促进了对这一复杂网络的详细探索，为开发骨相关疾病的新型治疗策略提供了可能。在本综述中，我们首先总结了与健康对照相比，类风湿关节炎（RA）、骨关节炎（OA）和骨质疏松症（OP）等骨相关疾病患者肠道微生物群组成的变化，以及影响这些变化的因素。接下来的综述综合了证据，分别强调了肠道微生物群失调对免疫稳态和骨微环境的深远影响。我们进一步阐述，肠道-免疫轴和肠道-骨轴并非相互独立，而是三维网络，强调肠道微生物群失调是免疫失调及随后骨稳态失衡的关键驱动因素。还讨论了基于使用益生菌、益生元、粪便微生物群移植、饮食调整和药物干预来调控肠道-免疫-骨轴的治疗策略。最后，我们讨论了当前肠道-免疫-骨轴研究面临的挑战，并提出基于该轴识别新型治疗靶点以治疗这些疾病的未来方向。
