基于肠道菌群探讨药食两用类中药防治原发性骨质疏松的应用

Application and Mechanisms of Medicine-Food Homology Substances in the Prevention and Treatment of Primary Osteoporosis via Gut Microbiota Regulation

摘要

原发性骨质疏松症（primary osteoporosis，POP）是目前影响中老年人群生存质量的重要慢性骨代谢疾病之一。该病以骨量进行性减少、骨微结构破坏、骨脆性增加及骨折风险升高为主要病理特征。肠道菌群作为调控机体整体稳态的“第二基因组”，可通过代谢产物调控、免疫炎症平衡及肠屏障完整性维持等多条途径参与骨代谢稳态调控，构成“肠-骨轴”核心调控网络。药食两用类中药兼具营养支持与药理干预双重优势，作用温和、安全性高，契合慢病长期调治需求，可通过重塑肠道菌群结构、优化菌群代谢产物谱、修复肠屏障功能、调控骨免疫炎症反应等多靶点、多通路方式发挥抗骨质疏松效应。该文系统梳理肠道菌群与POP的内在关联，归纳常用药食同源单味药及经典复方通过调控肠道菌群干预POP的研究进展与临床应用特点，并对该领域未来研究方向进行展望，以期为POP的中医药精准防治及药食同源资源的开发应用提供理论依据与实践参考。

Abstract

Primary osteoporosis(POP) has emerged as a major chronic metabolic bone disease compromising the quality of life in middle-aged and elderly populations. It is pathologically characterized by progressive bone loss, microstructural deterioration, increased bone fragility, and a consequent elevated risk of fracture. This review examines the gut microbiota, considered the "second genome" in maintaining host homeostasis, which actively participates in the regulation of bone metabolism through multiple pathways—including the production of bioactive metabolites, modulation of immune-inflammatory balance, and preservation of intestinal barrier integrity—collectively forming the core regulatory network of the "gut-bone axis." Substances used in medicine and food homology offer a dual advantage, providing both nutritional support and pharmacological intervention. Their mild action and favorable safety profile make them particularly suitable for the long-term management required by chronic diseases. Emerging evidence suggests that these substances exert anti-osteoporotic effects through multi-target and multi-pathway mechanisms, such as remodeling the gut microbiota structure, optimizing the microbial metabolite profile, restoring intestinal barrier function, and regulating bone immune-inflammatory responses. This review systematically examines the intrinsic relationship between the gut microbiota and primary osteoporosis. It summarizes the current research progress and clinical applications of commonly used single-herb medicine-food homology substances and classical compound prescriptions in modulating the gut microbiota to intervene in POP. Finally, future research directions and emerging trends in this field are discussed, aiming to provide a theoretical basis and practical reference for the precision prevention and treatment of primary osteoporosis with traditional Chinese medicine and for the development and application of medicine-food homology resources.

关键词

肠骨轴 / 肠道菌群 / 肠道微生态 / 药食同源 / 作用机制

Key words

gut-bone axis / gut microbiota / gut microecology / medicine-food homology / mechanism of action

参考文献

[1] Ines Foessl, Hans P Dimai, Barbara Obermayer—Pietsch. Long—term and sequential treatment for osteoporosis[J]. Nature Reviews Endocrinology, 2023, 19(9): 520-533.

[2] Zhang Yuan—wei, Cao Mu—min, Li Ying—juan, et al. A narrative review of the moderating effects and repercussion of exercise intervention on osteoporosis: Ingenious involvement of gut microbiota and its metabolites[J]. J Translational Medicine, 2022, 20(1): 490.

[3] 杨琦, 陈晓雯. 中医传统运动在老年性骨质疏松症防治中的应用[J]. 西安文理学院学报: 自然科学版, 2024, 27(1): 55-59.

[4] 余凡, 吴伟, 董春华. 运动调控肠道菌群防治骨质疏松症机制研究[J]. 中国骨质疏松杂志, 2026, 32(2): 269-275+301.

[5] 杨琦, 朱昱成, 程丽丽, 等. 基于肠道菌群探讨中医药治疗高尿酸血症及痛风机制[J]. 风湿病与关节炎, 2023, 12(11): 40-43+80.

[6] 宋昕, 孙莹, 张琦, 等. 基于RANKL/RANK/OPG通路研究绝经后老年骨质疏松患者骨代谢与肠道菌群失调的关系[J]. 河北医科大学学报, 2022, 43(3): 302-306.

[7] Huang Da—geng, Wang Ji—jan, Zeng Yu—hong, et al. Identifying microbial signatures for patients with postmenopausal osteoporosis using gut microbiota analyses and feature selection approaches[J]. Front Microbiol, 2023, 14: 1113174.

[8] 陈燕超, 林涛, 郑梓灌, 等. 肝肾阴虚证和脾肾阳虚证老年性骨质疏松症患者肠道菌群分布特征[J]. 中国中医骨伤科杂志, 2025, 33(12): 68-74+80.

[9] 邱学力, 崔浩, 吴晨阳, 等. 肠道菌群色氨酸代谢产物吲哚—3—丙酸改善炎症性肠病模型小鼠的骨质疏松症[J]. 中国组织工程研究, 2026, 30(10): 2413-2421.

[10] Niklas Grüner, Anna Lisa Ortlepp, Jochen Mattner. Pivotal role of intestinal microbiota and intraluminal metabolites for the maintenance of gut—bone physiology[J]. Int J Mol Sci, 2023, 24(6): 5161.

[11] Xu Qin, Li Dan, Chen Jing, et al. Crosstalk between the gut microbiota and postmenopausal osteoporosis: mechanisms and applications[J]. Int Immunopharmacol, 2022, 110: 108998.

[12] Laura McCabe, Robert A Britton, Narayanan Parameswaran. Prebiotic and probiotic regulation of bone health: role of the intestine and its microbiome[J]. Curr Osteoporos Rep, 2015, 13(6): 363-371.

[13] Lin Hao, Liu Tian—feng, Li Xiao, et al. The role of gut microbiota metabolite trimethylamine N—oxide in functional impairment of bone marrow mesenchymal stem cells in osteoporosis disease[J]. Ann Transl Med, 2020, 8: 1009.

[14] Luo C Y, Wang L, Sun C, et al. Estrogen enhances the functions of CD4(+)CD25(+)Foxp3(+)regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro[J]. Cellular & Molecular Immunology, 2011, 8(1): 50-58.

[15] Wang Ning, Ma Si—cong, Fu Ling—jie. Gut microbiota dysbiosis as one cause of osteoporosis by impairing intestinal barrier function[J]. Calcified Tissue International, 2022, 110(2): 225-235.

[16] Rozenberg S, Al—danghriI N, Aubertin—leheudre M, et al. Is there a role for menopausal hormone therapy in the management of postmenopausal osteoporosis?[J] Osteoporos Int, 2020, 31(12): 2271-2286.

[17] 赵福红, 闫起, 杨波, 等. 药食同源中药抗骨质疏松的研究进展[J]. 黑龙江科学, 2021, 12(22): 48-49.

[18] 王昊宇, 姚威, 梁爱迪, 等. 黄芪甲苷对去卵巢大鼠肠道菌群和骨质疏松症的影响[J]. 中国病理生理杂志, 2025, 41(2): 311-321.

[19] 熊金华, 樊志强, 戴钦正, 等. 黄芪多糖对维甲酸诱导骨质疏松大鼠的影响[J]. 中国矫形外科杂志, 2024, 32(19): 1791-1796.

[20] Zhao Xin, Ai Ju—qing, Mao Hao—ping, et al. Effects of Eclipta prostrata on gut microbiota of SAMP6 mice with osteoporosis[J]. J Medical Microbiology, 2019, 68(3): 402-416.

[21] 郎海伟, 俞立新, 温颢玮. 杜仲黄酮激活AMPK/PAK2信号通路改善卵巢切除大鼠骨代谢失衡及骨微结构退变[J]. 中国组织化学与细胞化学杂志, 2025, 34(4): 303-310.

[22] 李兰兰, 赵晨阳, 侯刚, 等. 枸杞多糖治疗骨科疾病的作用机制研究[J]. 医学信息, 2025, 38(1): 180-184.

[23] 卓嘉璐, 李子祥, 杨宁, 等. 枸杞多糖对绝经后骨质疏松患者肠道菌群结构及短链脂肪酸的影响[J]. 微循环学杂志, 2023, 33(4): 27-34.

[24] 陈亮, 张君, 陈晓晴, 等. 肉苁蓉多糖的研究进展[J]. 华西药学杂志, 2025, 40(6): 699-704.

[25] Evangelia N Kerezoudi, Evdokia K Mitsou, Katerina Gioti, et al. Fermentation of Pleurotus ostreatus and Ganoderma lucidum mushrooms and their extracts by the gut microbiota of healthy and osteopenic women: Potential prebiotic effect and impact of mushroom fermentation products on human osteoblasts[J]. Food Funct, 2021, 12(4): 1529-1546.

[26] 李柯霏. 山楂酸对LPS诱导的小鼠乳腺炎的影响及其机制[D]. 长春: 吉林大学, 2024.

[27] 刘海涛. 山楂酸对糖皮质激素诱发骨质疏松大鼠的干预作用研究[J]. 中国临床药理学杂志, 2015, 31(14): 1443-1445.

[28] 郑旭霞, 魏立伟, 谢艳, 等. 基于肠道菌群及其代谢物探析骨松益骨方抗绝经后骨质疏松症[J]. 中医学报, 2024, 39(7): 1388-1393.

[29] Li Bo, Liu Ming—yan, Wang Yu, et al. Puerarin improves the bone micro—environment to inhibit OVX—induced osteoporosis via modulating SCFAs released by the gut microbiota and repairing intestinal mucosal integrity[J]. Biomed Pharmacother, 2020, 132: 110923.

[30] 李琨, 夏天爽, 范围晴, 等. 马齿苋水醇提取物对小鼠溃疡性结肠炎及骨丢失的保护作用及其机制[J]. 海军军医大学学报, 2025, 46(6): 710-718.

[31] 王斌, 董洪洋, 高松, 等. 积雪草酸调节Treg/Th17平衡和肠道菌群改善卵巢切除小鼠骨质疏松症[J]. 中国优生与遗传杂志, 2025, 33(2): 253-259.

[32] 冯敏, 孙凡中, 万鸣, 等. 茯苓对小鼠肠道菌群的影响[J]. 食品研究与开发, 2025, 46(11): 30-36.

[33] 黄成硕, 陈驹, 吴晓静, 等. 基于STING/NF—κB信号通路探讨茯苓酸对去卵巢小鼠骨质疏松的作用[J]. 广东药科大学学报, 2024, 40(2): 119-123.

[34] 呙燕, 郑近园, 张佳, 等. 川陈皮素对单纯性肥胖症大鼠肠道菌群和短链脂肪酸的影响[J]. 中国病理生理杂志, 2024, 40(1): 148-156.

[35] 梁周, 张驰, 潘成镇, 等. 基于肠道菌群和广泛靶向代谢组学的山柰酚抗骨质疏松的作用机制[J]. 中国组织工程研究, 2025, 29(20): 4190-4204.

[36] 罗淼, 李宁, 裴环, 等. 生姜主要活性成分防治骨质疏松症的肠—骨轴作用机制研究进展[J]. 中医正骨, 2025, 37(8): 42-45.

[37] Xie Hui, Hua Zheng—ying, Guo Meng—yu, et al. Gut microbiota and metabonomics used to explore the mechanism of Qing'e Pills in alleviating osteoporosis[J]. Pharmaceutical Biology, 2022, 60(1): 785-800.

[38] 谢辉, 林上阳, 华政颖, 等. 基于粪菌移植研究青娥丸的抗骨质疏松作用[J]. 南京中医药大学学报, 2021, 37(4): 521-528.

[39] 方春秋, 潘志. 当归补血汤现代药理作用及作用机制的研究进展[J]. 中药材, 2024, 47(10): 2650-2656.

[40] 李畅, 范荣, 李东波, 周威, 黄玉娥. 当归补血汤促进大鼠骨质疏松性骨折愈合及调节Wnt/β—catenin通路作用研究[J]. 吉林中医药, 2022, 42(9): 1069-1075.

[41] 李宁, 吴月滢, 裴环, 等. 基于“肠—骨”轴探讨药食同源复方强骨宁缓解绝经后骨质疏松症的作用机制[J]. 中华中医药杂志, 2024, 39(5): 2308-2315.

[42] Sun Pan, Zhang Chu—tian, Huang Yun—mei, et al. Jiangu granule ameliorated OVX rats bone loss by modulating gut microbiota—SCFAs—Treg/Th17 axis[J]. Biomed Pharmacother, 2022, 150: 112975.

[43] 陈赛楠, 黄云梅, 周芬, 等. Slit3/Robo1通路探讨健骨颗粒对大鼠骨量丢失模型的影响[J]. 中国骨质疏松杂志, 2025, 31(3): 313-320.

基金资助

国家中医药管理局第七批全国老中医药专家学术经验继承工作项目(国中医药人教函[2022]76号)