类风湿性关节炎中微生物群-肠道关节轴潜在的组胺中枢：机制和转化意义
A Potential Central Hub of Histamine in the Microbiota-Gut-Joint Axis in Rheumatoid Arthritis: Mechanisms and Translational Implications.
摘要(中文译文)
类风湿关节炎（RA）是一种慢性自身免疫性疾病，以疼痛、持续性滑膜炎、进行性关节破坏和全身免疫失调为特征。越来越多的证据表明，微生物群-肠道-关节轴是连接肠道菌群失调与RA异常免疫应答的关键通讯网络。在该轴涉及的多种肠道来源代谢物中，我们提出组胺可能作为连接微生物改变与关节炎症的核心信号节点。宿主和微生物群来源的组胺均通过组氨酸脱羧酶（HDC）合成，并通过组胺受体H1R、H2R和H4R调控关节微环境中的免疫细胞和基质细胞活性。此外，组胺与其他微生物代谢物——如短链脂肪酸（SCFAs）和色氨酸衍生物——相互作用，形成复杂的代谢-炎症网络，从而放大成纤维细胞样滑膜细胞活化、破骨细胞生成和慢性炎症。尽管越来越多的证据支持组胺的免疫调节作用，但介导其与微生物及宿主免疫通路交互对话的精确分子机制仍未被完全阐明。本综述全面概述了微生物群-肠道-关节轴中组胺介导的调控作用，重点强调其与其他微生物代谢物的相互作用及其对RA发病机制的贡献。深入理解这一以组胺为中心的微生物群-肠道-关节轴，将有助于阐明其在免疫失调中的机制作用，并最终为恢复RA免疫平衡和预防关节损伤的未来策略提供依据。
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by pain, persistent synovial inflammation, progressive joint destruction, and systemic immune dysregulation. Increasing evidence has revealed that the microbiota-gut-joint axis represents a crucial communication network linking intestinal dysbiosis to aberrant immune responses in RA. Among the diverse gut-derived metabolites implicated in this axis, we propose that histamine may act as a central signaling node linking microbial alterations to joint inflammation. Both host- and microbiota-derived histamine, synthesized via histidine decarboxylase (HDC), regulate immune and stromal cell activity within the joint microenvironment through histamine receptors H1R, H2R, and H4R. In addition, histamine interacts with other microbial metabolites-such as short-chain fatty acids (SCFAs) and tryptophan derivatives-forming an intricate metabolic-inflammatory network that amplifies fibroblast-like synoviocyte activation, osteoclastogenesis, and chronic inflammation. Despite accumulating evidence supporting the immunomodulatory role of histamine, the precise molecular mechanisms mediating its crosstalk with microbial and host immune pathways remain incompletely defined. This review provides a comprehensive overview of histamine-mediated regulation within the microbiota-gut-joint axis, emphasizing its interplay with other microbial metabolites and its contribution to RA pathogenesis. A deeper understanding of this histamine-centered microbiota-gut-joint axis will help elucidate its mechanistic role in immune dysregulation and may ultimately inform future strategies for restoring immune balance and preventing joint damage in RA.
如何引用
AMA
Yiqing Kong, Yu Deng, Yuan Liu, Yuge Han, Yuandan Zhang, Zihan Qi, et al. A Potential Central Hub of Histamine in the Microbiota-Gut-Joint Axis in Rheumatoid Arthritis: Mechanisms and Translational Implications.. International journal of molecular sciences. 2026; doi:10.3390/ijms27052315.
APA
Yiqing Kong, Yu Deng, Yuan Liu, Yuge Han, Yuandan Zhang, Zihan Qi, et al (2026). A Potential Central Hub of Histamine in the Microbiota-Gut-Joint Axis in Rheumatoid Arthritis: Mechanisms and Translational Implications.. International journal of molecular sciences. https://doi.org/10.3390/ijms27052315
GB/T 7714
Yiqing Kong, Yu Deng, Yuan Liu, Yuge Han, Yuandan Zhang, Zihan Qi, et al. A Potential Central Hub of Histamine in the Microbiota-Gut-Joint Axis in Rheumatoid Arthritis: Mechanisms and Translational Implications.[J]. International journal of molecular sciences, 2026 doi:10.3390/ijms27052315.
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