ArticleThe Journal of clinical investigation2025
Gut-specific histamine 3 receptor signaling orchestrates microglia-dependent resolution of peripheral inflammation.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
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.
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Who cites it
6 citing papers in PubMed.
- Osteoarthritis Therapeutics: From Microenvironment Understanding to Regenerative Intervention-Current Advances and Future Perspectives.Orthopaedic surgery · 2026Review
- Use of Antihistamine Drugs in Colitis: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Clinical Significance of Gut Microbiota Community Types for Long-Term Response to Fecal Microbiota Transplantation in Patients With Psoriatic Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- The potential role of aberrant microglial synaptic pruning in the neurodevelopmental pathogenesis of tourette syndrome.Frontiers in neuroscience · 2026Review
- Brucellar spondylitis is associated with disturbance in gut microbiota and histamine metabolism associated inflammation.Frontiers in cellular and infection microbiology · 2026Article
- Systems-level investigation of the anxiolytic gut-brain interactions induced by paraprobioticFrontiers in microbiology · 2026Article
Corrections and comments
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Authors and funding
35 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic inflammatory diseases like rheumatoid arthritis (RA) have been described to cause CNS activation. Less is known about environmental factors that enable the CNS to suppress peripheral inflammation in RA. Here, we identified gut microbiota-derived histamine as such a factor. We showed that low levels of histamine activate the enteric nervous system, increase inhibitory neurotransmitter concentrations in the spinal cord, and restore homeostatic microglia, thereby reducing inflammation in the joints. We found that elective histamine 3 receptor (H3R) signaling in the intestine was critical for this effect, as systemic and intrathecal application did not show effects. Microglia depletion or pharmacological silencing of local nerve fibers impaired oral H3R agonist-induced pro-resolving effects on arthritis. Moreover, therapeutic supplementation of the short-chain fatty acid propionate revealed one way to expand local intestinal histamine concentrations in mice and humans. Thus, we define a gut/CNS/joint axis pathway where microbiota-derived histamine initiates the resolution of arthritis via the CNS.
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Registered trials
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.