浙江大学学报（医学版）2026，Vol.55Issue(4)：338-351,14.DOI:10.3724/zdxbyxb-2025-0569
基于肠-脑-关节轴从微生态扰动到多靶点协同的类风湿关节炎调控策略
Gut-brain-joint axis in rheumatoid arthritis:from microecological disturbance to multi-target synergy
摘要
Abstract
Rheumatoid arthritis(RA)is a chronic autoimmune disease characterized by joint inflammation and bone destruction,accompanied by gut microbiota dysbiosis,neuroimmune dysfunction,and systemic inflammatory amplification.Increasing evidence from the gut-joint axis indicates that microbial dysbiosis disrupts intestinal barrier integrity,enhances permeability,and promotes the translocation of microbial products and antigens,thereby triggering systemic inflammation and autoimmune responses.Meanwhile,alterations in microbial metabolites,including short-chain fatty acids,bile acids,and tryptophan derivatives,drive disease progression by regulating mucosal homeostasis,inflammatory resolution,and the Th17 cells/Tr cells balance.Persistent dysbiosis further activates peripheral immunity and promotes the recruitment of pro-inflammatory cells and mediators to the synovium,resulting in synovial hyperplasia,cartilage degradation,and bone erosion.Concurrently,gut-derived metabolic signals,vagal afferents,and immune mediators modulate central nervous system function and neuroinflammation,whereas brain-derived stress responses regulate intestinal barrier function,microbial composition,and gut immune homeostasis via the hypothalamic-pituitary-adrenal(HPA)axis and the autonomic nervous system,collectively exacerbating systemic inflammation.Thus,a dynamic cross-system network linking the gut,brain,and joints is established,involving neural pathway coupling,immune cell migration and recruitment,endocrine regulation,and metabolic messenger-and inflammatory axis-mediated interactions.Microbiota-directed strategies restore microbial homeostasis and barrier integrity to reduce the initiation of inflammation;metabolic interventions rebalance immune and bone homeostasis through key signaling pathways,e.g.,tryptophan and short-chain fatty acid pathways;neuroimmune regulation attenuates inflammatory amplification via the cholinergic anti-inflammatory pathway and HPA axis modulation;and multi-target approaches integrate the advantages of microbiota,metabolism,neural,and local inflammatory control to improve therapeutic efficacy.This review elucidates RA from the integrated perspective of the gut-brain-joint axis,providing mechanistic insights into systemic inflammation and supporting the development of novel therapeutic strategies.关键词
类风湿关节炎/肠-脑-关节轴/肠道菌群/神经免疫调节/炎症/下丘脑-垂体-肾上腺轴/综述Key words
Rheumatoid arthritis/Gut-brain-joint axis/Intestinal flora/Neuroim-munomodulation/Inflammation/Hypothalamic-pituitary-adrenal axis/Review分类
医药卫生引用本文复制引用
伊伸珑,何启旺,李亚楠,万碧江..基于肠-脑-关节轴从微生态扰动到多靶点协同的类风湿关节炎调控策略[J].浙江大学学报（医学版）,2026,55(4):338-351,14.基金项目
国家自然科学基金(82405575) （82405575）
湖北省中医药管理局中医药科研重大项目(ZY2025Z014) （ZY2025Z014）
湖北省自然科学基金(2024AFD305) （2024AFD305）
国家资助博士后研究人员计划(GZC20240445)This study was supported by National Natural Science Foundation of China(82405575),Major Scientific Research Project of Hubei Provincial Administration of Traditional Chinese Medicine(ZY2025Z014),Natural Science Foundation of Hubei Province(2024AFD305),and National Postdoctoral Fellowship Program(GZC20240445). （GZC20240445）
