ArticleThe Journal of clinical investigation2023
Microbiota-dependent indole production stimulates the development of collagen-induced arthritis in mice.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Suggestive Association Between Tryptophan-indole Metabolic Pathway and Total Joint Arthroplasty Early Revision for Heterogeneous Failure Modes in Patients With Primary Osteoarthritis: A Meta-analysis of Metabolomics.Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026Pooled it
- Gut microbiota in early and established stages of rheumatoid arthritis: from pathogenesis to promising prevention and treatment.Annals of medicine · 2026Review
- Bacterial engineering for cancer therapy.Nature cancer · 2026Review
- Gut Microbial Functional Ecology and Microbiota-Derived Metabolites in Rheumatoid Arthritis Autoimmunity.Cells · 2026Review
- Murine and Humanized Mouse Models in Autoimmune Disease Research and Therapeutics Development.Biology · 2026Review
- Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases.Ageing research reviews · 2026Review
- The gut-joint axis in juvenile idiopathic arthritis.Arthritis research & therapy · 2026Review
- TEAD4-driven GPX8 promotes temozolomide resistance in glioma by facilitating CTHRC1 expression to suppress mitochondrial oxidative stress.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Longitudinal peripheral blood multi-omic profiling in seropositive individuals identifies immune endotypes and predictive models for future rheumatoid arthritis conversion.medRxiv : the preprint server for health sciences · 2026Article
- Depression of tryptophan may contribute to adverse effects of naproxen.Nature communications · 2026Article
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Gut microbiota and intestinal permeability in rheumatoid arthritis: pathogenic mechanisms.Frontiers in immunology · 2026Review
- Natural compounds for the treatment of rheumatoid arthritis based on the 'gut‑joint axis' (Review).Molecular medicine reports · 2026Review
- The Gut Microbiota: Emerging Evidence in Autoimmune and Inflammatory Diseases.Research (Washington, D.C.) · 2026Review
- From intestinal immune niches to systemic inflammation: programming cellular plasticity and immune redistribution across organs.Frontiers in immunology · 2026Review
- Gut dysbiosis in difficult-to-treat rheumatoid arthritis: hypothesized microbial endotypes, persistent inflammation, and pharmacological treatment resistance.Frontiers in pharmacology · 2026Review
- Tryptophan-Restricted Intermittent Diet Alleviates Estrogen Deficiency-Induced Osteoporosis via Regulating Coupling Effects of "Gut-Bone" Axis.International journal of biological sciences · 2026Article
- Bacterial metabolism of tryptophan causes toxicity inbioRxiv : the preprint server for biology · 2025Article
- Observational
- Microbial threads in the tapestry of rheumatoid arthritis.The Journal of clinical investigation · 2025Review
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22 authors at 3 institutions in 1 country.
Funding
Abstract
Altered tryptophan catabolism has been identified in inflammatory diseases like rheumatoid arthritis (RA) and spondyloarthritis (SpA), but the causal mechanisms linking tryptophan metabolites to disease are unknown. Using the collagen-induced arthritis (CIA) model, we identified alterations in tryptophan metabolism, and specifically indole, that correlated with disease. We demonstrated that both bacteria and dietary tryptophan were required for disease and that indole supplementation was sufficient to induce disease in their absence. When mice with CIA on a low-tryptophan diet were supplemented with indole, we observed significant increases in serum IL-6, TNF, and IL-1β; splenic RORγt+CD4+ T cells and ex vivo collagen-stimulated IL-17 production; and a pattern of anti-collagen antibody isotype switching and glycosylation that corresponded with increased complement fixation. IL-23 neutralization reduced disease severity in indole-induced CIA. Finally, exposure of human colonic lymphocytes to indole increased the expression of genes involved in IL-17 signaling and plasma cell activation. Altogether, we propose a mechanism by which intestinal dysbiosis during inflammatory arthritis results in altered tryptophan catabolism, leading to indole stimulation of arthritis development. Blockade of indole generation may present a unique therapeutic pathway for RA and SpA.
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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 OpenQuestion graph.