Evidence map›Paper›PMID 41828539›Full record

ReviewInternational journal of molecular sciences2026

A Potential Central Hub of Histamine in the Microbiota-Gut-Joint Axis in Rheumatoid Arthritis: Mechanisms and Translational Implications.

Yiqing Kong, Yu Deng, Yuan Liu, Yuge Han, Yuandan Zhang, Zihan Qi, Menglei Cao, Yingying Li, Yu Du, Yan Jin and 1 more

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yiqing KongThe Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.ORCID 0009-0006-5395-1346
Yu DengCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Yuan LiuCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Yuge HanThe Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Yuandan ZhangCollege of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Zihan QiKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Menglei CaoKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Yingying LiThe Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Yu DuKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Yan JinThe Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Jie YuKey Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.ORCID 0000-0002-6768-7236

Funding

Foundation of Zhejiang Chinese Medical University 2023JKZKTS38Foundation of Zhejiang Chinese Medical University 2025JKZKTS04Foundation of Zhejiang Chinese Medical University 2025JKZKTS59National Natural Science Foundation of China NO 82204649
6 · The paper itself

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.

Indexed as

Arthritis, RheumatoidGastrointestinal MicrobiomeHistamineJointsAnimalsHumansReceptors, HistamineSignal TransductionHistamineReceptors, Histaminefibroblast-like synoviocyteshistaminehistamine receptorshistidine decarboxylaseimmunometabolismmicrobiota–gut–joint axisrheumatoid arthritis

Identifiers

PMID41828539
PMCPMC12984847

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.