[1]何昌禄,周艳,王焕珍.胆汁酸介导“肠-关节轴”调控骨关节炎发生发展的作用机制及相关药物治疗的研究进展[J].中医正骨,2026,38(07):76-80.
 HE Changlu,ZHOU Yan,WANG Huanzhen.Advances in research on the mechanisms of bile acids mediating the gut-joint axis to regulate the onset and progression of osteoarthritis and the related pharmacotherapy[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2026,38(07):76-80.
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胆汁酸介导“肠-关节轴”调控骨关节炎发生发展的作用机制及相关药物治疗的研究进展()

《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第38卷
期数:
2026年07期
页码:
76-80
栏目:
综述
出版日期:
2026-07-20

文章信息/Info

Title:
Advances in research on the mechanisms of bile acids mediating the gut-joint axis to regulate the onset and progression of osteoarthritis and the related pharmacotherapy
作者:
何昌禄; 周艳; 王焕珍
德江县民族中医院,贵州 德江 565200
Author(s):
HE Changlu; ZHOU Yan; WANG Huanzhen
关键词:
骨关节炎;  胆汁酸类;  胃肠道微生物群;  肠-关节轴;  综述
摘要:
骨关节炎(osteoarthritis, OA)是以关节软骨退变为核心特征的退行性疾病。“肠-关节轴”是OA的发病机制之一,肠道菌群失调导致的免疫反应和代谢失衡均可加剧OA的病理进程。胆汁酸作为肠道与关节之间的关键信号介质,可介导“肠-关节轴”,参与调控软骨细胞衰老、炎症反应与基质代谢,维持关节微环境稳态。基于胆汁酸介导“肠-关节轴”调控OA发生发展的作用机制,外源性胆汁酸补充剂、特异性益生菌制剂和肠道菌群调节剂、胰高血糖素样肽-1受体激动剂、法尼酯X受体拮抗剂,以及中药复方、单味中药和中药提取物,在OA的药物治疗中均展现出良好的应用前景。本文概述了胆汁酸的基本特性,从胆汁酸介导“肠-关节轴”调控OA发生发展的作用机制和靶向该调控轴的OA药物治疗两方面进行了综述,为OA的药物治疗和新药开发提供了参考。

参考文献/References:

[1] 中国骨关节炎诊疗指南专家组,中国老年保健协会疼痛病学分会.中国骨关节炎诊疗指南(2024版)[J].中华疼痛学杂志,2024,20(3):323-338.
[2] 王若瑜,尚赫,杨天翔,等.肠-关节轴在膝关节骨关节炎中的发病机制及靶向干预[J].国际骨科学杂志,2026,47(1):24-27.
[3] 白露,房洋,韩冷,等.基于胆汁酸代谢介导免疫调控的研究进展[J].生命科学,2026,38(3):454-462.
[4] 王思玉,乔喆,王帅,等.胆汁酸代谢与肠道菌群失调相关疾病中医辨证论治的相关研究进展[J].世界中西医结合杂志,2026,21(1):187-191.
[5] 高晖.胆汁酸含量减少介导孕期咖啡因暴露所致成年雄性子代骨关节炎易感[D].武汉:武汉大学,2021.
[6] TRAUNER M,KARPEN S J,DAWSON P A.Benefits and challenges to therapeutic targeting of bile acid circulation in cholestatic liver disease[J].Hepatology,2025,82(4):855-876.
[7] LI X J,FANG C,ZHAO R H,et al.Bile acid metabolism in health and ageing-related diseases[J].Biochem Pharmacol,2024,225:116313.
[8] ALREHAILI B D,LEE M,TAKAHASHI S,et al.Bile acid conjugation deficiency causes hypercholanemia,hyperphagia,islet dysfunction,and gut dysbiosis in mice[J].Hepatol Commun,2022,6(10):2765-2780.
[9] MOHANTY I,ALLABAND C,MANNOCHIO-RUSSO H,et al.The changing metabolic landscape of bile acids-keys to metabolism and immune regulation[J].Nat Rev Gastroenterol Hepatol,2024,21(7):493-516.
[10] XIANG T,DENG Z,YANG C,et al.Bile acid metabolism regulatory network orchestrates bone homeostasis[J].Pharmacol Res,2023,196:106943.
[11] WEI J,ZHANG Y,HUNTER D,et al.The gut microbiome-joint axis in osteoarthritis[J].Sci Bull,2023,68(8):759-762.
[12] RESTA S,BARDI E,D'ARRIGO D,et al.Gut microbiota-targeted interventions for gut-joint axis modulation in experimental osteoarthritis:a systematic review of animal studies[J].J Funct Foods,2025,135:107078.
[13] JEYARAMAN M,RAM P R,JEYARAMAN N,et al.The gut-joint axis in osteoarthritis[J].Cureus,2023,15(11):e48951.
[14] WANG T,XU Y,ZHA H,et al.The “gut microbiota-ferroptosis axis”:a hypothesis for osteoarthritis pathogenesis and therapeutic implications[J].Front Microbiol,2025,16:1685962.
[15] WANG W,LIU H,ZHANG M,et al.Integrative multi-omics analysis reveals gut microbiota-derived metabolites and immune regulatory pathways in osteoarthritis pathogenesis[J].J Orthop Surg Res,2026,21(1):87.
[16] QIN R,YU P,WANG H,et al.Gut-bone axis crosstalk:microbiota-driven immune-metabolic-neural networks in bone disorders and precision interventions[J].J Orthop Translat,2026,58:101126.
[17] ZHAO M,ZHANG L,LIU Z.Gut microbiota-mediated pain sensitization:mechanisms and therapeutic implications[J].Front Pain Res,2025,6:1626515.
[18] HLADKYKH F V,LIADOVA T I,MATVIEIENKO M S,et al.Central sensitization and nociplastic pain:shared mechanisms in fibromyalgia,osteoarthritis,and inflammatory arthritis[J].J Pain Res,2026,19:571311.
[19] HONG S W,PIAO L,CHO E H,et al.Effect of microglial activity on gut microbiota in rats with neuropathic pain[J].Int J Mol Sci,2025,26(11):5181.
[20] BRITTAIN R S A,BRIBIESCAS R G,JASIENSKA G.Industrialization increases the estrogen-recycling capacity of the gut microbiome[J].Proc Natl Acad Sci U S A,2026,123(16):e2523589123.
[21] ATASOY-ZEYBEK A,SHOWEL K K,NAGELLI C V,et al.The intersection of aging and estrogen in osteoarthritis[J].NPJ Womens Health,2025,3(1):15.
[22] SUN X,SHUKLA M,WANG W,et al.Unlocking gut-liver-brain axis communication metabolites:energy metabolism,immunity and barriers[J].NPJ Biofilms Microbiomes,2024,10(1):136.
[23] GUAN Z,XUANQI Z,ZHU J,et al.Estrogen deficiency induces bone loss through the gut microbiota[J].Pharmacol Res,2023,196:106930.
[24] HUANG H,LEI H,YANG F,et al.Activation of the bile acid receptor GPBAR1(TGR5)ameliorates interleukin-1β(IL-1β)-induced chondrocytes senescence[J].Biomed Pharmacother,2018,106:1713-1719.
[25] ZHENG X Q,HUANG J,YUAN W Q,et al.Gut microbiota preserves bone mass through modulating the hyodeoxycholic acid-TGR5 axis[J].Gut Microbes,2025,17(1):2593088.
[26] KUHN K A,YOMOGIDA K,KNOOP K,et al.More than a leaky gut:how gut priming shapes arthritis[J].Nat Rev Rheumatol,2025,21(9):513-525.
[27] HASSAN RIZVI S M M,SHAMI A,KAN Y,et al.FXR in bone metabolism:an emerging regulator[J].iScience,2026,29(3):114842.
[28] YANG Y,HAO C,JIAO T,et al.Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling[J].Science,2025,388(6742):eadt0548.
[29] LI J,YE J,YANG T,et al.Bile acids metabolism in symptomatic hand osteoarthritis[J].Arthritis Rheumatol,2026,78(7):1465-1476.
[30] FU K,SI S,JIN X,et al.Exploring antidiabetic drug targets as potential disease-modifying agents in osteoarthritis[J].EBioMedicine,2024,107:105285.
[31] JAMAL N,HOLLABAUGH W,SCOTT L,et al.Unravelling the ties that bind:the intersection of obesity,osteoarthritis,and inflammatory pathways with emphasis on glucagon-like peptide-1 agonists[J].Clin Obes,2025,15(1):e12700.
[32] LIAN W S,WANG F S.Gut microbiota and articular cartilage interacting axis:links with host genetics,chromatin dynamics and potential mechanisms in aging-related osteoarthritis[J].Osteoarthritis Cartilage,2024,32:S464-S465.
[33] LIU C,CAO Y,YANG X,et al.Tauroursodeoxycholic acid suppresses endoplasmic reticulum stress in the chondrocytes of patients with osteoarthritis[J].Int J Mol Med,2015,36(4):1081-1087.
[34] ARAI Y,CHOI B,KIM B J,et al.Tauroursodeoxycholic acid counters osteoarthritis by regulating intracellular cholesterol levels and membrane fluidity of degenerated chondrocytes[J].Biomater Sci,2019,7(8):3178-3189.
[35] SHINE B K,LI Q,SONG M,et al.Efficacy and safety of Latilactobacillus sakei LB-P12 in patients with knee osteoarthritis:an exploratory randomized,double-blind,placebo-controlled clinical trial[J].Sci Rep,2025,15(1):25980.
[36] GUZIOR D V,QUINN R A.Review:microbial transformations of human bile acids[J].Microbiome,2021,9(1):140.
[37] BLIDDAL H,BAYS H,CZERNICHOW S,et al.Once-weekly semaglutide in persons with obesity and knee osteoarthritis[J].N Engl J Med,2024,391(17):1573-1583.
[38] BILGIN E,VENERITO V,BOGDANOS D P.Glucagon-like peptide-1(GLP-1)receptor agonists in rheumatology:a review of current evidence and future directions[J].Auto-immun Rev,2025,24(9):103864.
[39] ZHANG X,JIANG J,XU J,et al.Liraglutide,a glucagon-like peptide-1 receptor agonist,ameliorates inflammation and apoptosis via inhibition of receptor for advanced glycation end products signaling in AGEs induced chondrocytes[J].BMC Musculoskelet Disord,2024,25(1):601.
[40] RYAN M,MEGYERI S,NUFFER W,et al.The potential role of GLP-1 receptor agonists in osteoarthritis[J].Pharmacotherapy,2025,45(3):177-186.
[41] MEUROT C,MARTIN C,SUDRE L,et al.Liraglutide,a glucagon-like peptide 1 receptor agonist,exerts analgesic,anti-inflammatory and anti-degradative actions in osteoarthritis[J].Sci Rep,2022,12(1):1567.
[42] URSINI F,CIAFFI J,CAPORALI R.If the evidence is there,why are GLP-1 receptor agonists not on-label for hip and knee osteoarthritis in overweight patients?[J].RMD Open,2025,11(3):e006025.
[43] PATHAK P,XIE C,NICHOLS R G,et al.Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism[J].Hepatology,2018,68(4):1574-1588.
[44] 卢一帆,徐无忌,熊辉,等.基于16S rDNA测序分析独活寄生汤对膝骨关节炎大鼠肠道菌群的影响[J].湖南中医药大学学报,2024,44(12):2277-2285.
[45] BIAN M,ZHU C,NIE A,et al.Guizhi Shaoyao Zhimu Decoction ameliorates gouty arthritis in rats via altering gut microbiota and improving metabolic profile[J].Phytomedicine,2024,131:155800.
[46] 顾富城,杨美鑫,吴伟欣,等.龟鹿二仙胶对膝骨关节炎大鼠肠道菌群的影响:机器学习与16S rDNA分析[J].中国组织工程研究,2026,30(4):1058-1072.
[47] LIU J,ZHANG D,ZHOU Y,et al.Fuzi alleviates cold-related rheumatoid arthritis via regulating gut microbiota and microbial bile acid metabolism[J].Chin Med,2025,20(1):64.
[48] ZHAO J A,ZHENG Y Z,WANG F,et al.Mulberry water extract alleviates osteoarthritis via Lactobacillus johnsonii-dependent bile acid restoration[J].Phytomedicine,2026,150:157679.
[49] 李兰清,许海樱,瞿领航,等.何首乌水提物及其活性成分大黄素通过调控胆固醇代谢抑制软骨细胞炎症缓解骨关节炎的研究[J].针灸和草药(英文),2023,3(2):96-106.
[50] TIAN F,CHEN T,XU W,et al.Curcumin compensates GLP-1 deficiency via the microbiota-bile acids axis and modulation in functional crosstalk between TGR5 and FXR in ob/ob mice[J].Mol Nutr Food Res,2023,67(22):e2300195.

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备注/Memo

备注/Memo:
基金项目:贵州省科技计划项目(黔科合基础-ZK[2022]一般001)
通信作者:何昌禄 E-mail:407300084@qq.com
(收稿日期:2026-02-28 本文编辑:杨雅)
更新日期/Last Update: 2026-07-20