ArticleAnnals of clinical and translational neurology2018
Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course.
Article in Annals of clinical and translational neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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
53 citing papers in PubMed, 89 citations in OpenAlex.
- Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.Med (New York, N.Y.) · 2025Trial
- Integrated multi-omics analysis identifies microbial and metabolic signatures and drivers of CNS autoimmunity.mSystems · 2026Article
- Novel insight into the effects of the metabolites from gut microbiota in both unmedicated depressive adolescents and mice: key roles of indole derivatives-aryl hydrocarbon receptor signaling in neurogenesis and microglial homeostasis.Molecular psychiatry · 2026Article
- Tobacco smoking disrupts bile acid and tryptophan metabolism in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026Article
- Azetidine-2-carboxylic acid-induced oligodendrogliopathy in vitro and the pathogenesis of multiple sclerosis.Journal of neuropathology and experimental neurology · 2026Article
- A framework for blood biomarker discovery in MS.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026Review
- Integrated multi-omics analysis identifies microbial and metabolic signatures and drivers of CNS autoimmunity.bioRxiv : the preprint server for biology · 2026Article
- Reduced peripheral serotonin levels in women with multiple sclerosis: associations with underweight status, treatment duration, and use of interferon beta 1a.Frontiers in cellular neuroscience · 2026Article
- Unraveling multiple sclerosis: a hidden interaction between intestinal microbiota and host lipid metabolism.Gut microbes · 2025Review
- Smouldering disease in paediatric-onset multiple sclerosis.EBioMedicine · 2025Review
- Dysregulation of the Kynurenine Pathway in Relapsing Remitting Multiple Sclerosis and Its Correlations With Progressive Neurodegeneration.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Plasma and Visceral Organ Kynurenine Metabolites Correlate in the Multiple Sclerosis Cuprizone Animal Model.International journal of molecular sciences · 2025Article
- Restoring the Multiple Sclerosis Associated Imbalance of Gut Indole Metabolites Promotes Remyelination and Suppresses Neuroinflammation.bioRxiv : the preprint server for biology · 2025Article
- Immunotherapy-mediated modulation of the gut microbiota in multiple sclerosis and associations with diet and clinical response-the effect of dimethyl fumarate therapy.Therapeutic advances in neurological disorders · 2025Article
- The gut microbiota composition is shaped by disease activity and individual treatment responses in patients with multiple sclerosis.Frontiers in immunology · 2025Article
- Recent Advances in Metabolomics and Lipidomics Studies in Human and Animal Models of Multiple Sclerosis.Metabolites · 2024Review
- Modulation of multiple sclerosis risk and pathogenesis by the gut microbiota: Complex interactions between host genetics, bacterial metabolism, and diet.Immunological reviews · 2024Review
- Harnessing and delivering microbial metabolites as therapeutics via advanced pharmaceutical approaches.Pharmacology & therapeutics · 2024Review
- Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.medRxiv : the preprint server for health sciences · 2024Article
- The role of the "gut microbiota-mitochondria" crosstalk in the pathogenesis of multiple sclerosis.Frontiers in microbiology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveTo determine if altered tryptophan (Trp) metabolism is associated with MS risk or disease severity in children.
methodsParticipants with pediatric-onset MS and clinically isolated syndrome (CIS) within 4 years of disease onset and healthy controls underwent collection of serum. Longitudinal disability and processing speed measures and relapse data were collected in cases. Global metabolomics were conducted in 69/67 cases/controls. Targeted Trp measurement was performed in a discovery group (82 cases, 50 controls) and a validation group (92 cases, 50 controls), while functional gut microbiome analysis was done in 17 cases. Adjusted logistic, linear and negative binomial regression and Cox-proportional hazard models were used.
resultsUsing global metabolomics data, higher relative abundances of Trp and indole lactate, a known gut microbiota-derived Trp metabolite, were associated with lower risk of MS. In cases, higher relative abundances of gut microbiota-derived Trp metabolites were associated with lower disability and higher processing speed scores and higher relative abundance of kynurenine was associated with higher relapse rate. Using targeted tryptophan measures, in the discovery and validation groups, each 1 mcg/mL increase in serum Trp level was associated with 20% (95% CI: 4-34%) and 32% (95% CI: 16-44%) decrease in adjusted odds of having MS, respectively. A lower relative abundance of gut microbial genes involved in Trp catabolism was associated with higher relapse risk.
interpretationTrp metabolism by the gut microbiota and the kynurenine pathway may be relevant to the risk of MS in children as well as MS activity and severity.
Identifiers
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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 OpenQuestion graph.