ArticleEBioMedicine2022
Seizure modulation by the gut microbiota and tryptophan-kynurenine metabolism in an animal model of infantile spasms.
Article in EBioMedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Akkermansia muciniphila enhances washed microbiota transplantation in the treatment of epilepsy.Chinese medical journal · 2026Trial
- The Gut Microbiota-Epilepsy Axis: Bibliometric Trends, Mechanistic Insights, and Microbiota-Targeted Next-Generation Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Epilepsy as a Disorder of Neuroimmune Metabolism: The Kynurenine Pathway as a Link Between Cognitive and Psychiatric Dysfunction.Biomolecules · 2026Review
- Review
- Metabolomic Profiling of Plasma in Children with Drug-Resistant Epilepsy: The Effect of the Ketogenic Diet on Energy and Amino Acid Pathways.Nutrients · 2026Article
- Integrated Multiomics Reveals Gut-Brain Axis Dysregulation and Phenotype-Specific Metabolic Signatures in Children with Febrile Seizures.Biomedicines · 2026Article
- From clinical practice to mechanistic insights in ketogenic diets for epilepsy.The Lancet. Neurology · 2026Review
- Microglial GPR35 Ameliorates Epileptogenesis and Neuroinflammation via PDGFA Domain 2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The ketogenic diet alters microbiome-metabolome profiles to improve West syndrome therapy.Pediatric investigation · 2026Article
- SeizureBiomeDB: a unified database of gut microbiome alterations in pediatric and adult epilepsy.Bioinformatics advances · 2026Article
- Modulation of Gut Microbiome and Metabolome as One of the Potential Mechanisms of Ketogenic Diet Effect in the Treatment of Epilepsy.Nutrients · 2025Review
- Tryptophan Metabolism in Neurodevelopment and Its Implications For Neurodevelopmental Disorders.Molecular neurobiology · 2025Review
- The interplay between metabolism and neuroinflammation in epilepsy: mechanisms and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Ketogenic diet for infantile epileptic spasms.Epilepsia open · 2025Article
- The Interplay between the Gut and Ketogenic Diets in Health and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Gut Microbiota Composition and Modulation in Developmental and Epileptic Encephalopathies.The European journal of neuroscience · 2025Review
- The crucial function of IDO1 in pulmonary fibrosis: From the perspective of mitochondrial fusion in lung fibroblasts and targeted molecular inhibition.Acta pharmaceutica Sinica. B · 2025Article
- Untargeted metabolomics reveals key metabolic alterations in pediatric epilepsy with insights into Tryptophan metabolism and the gut-brain axis.Scientific reports · 2025Article
- Intestinal microbiome alterations in pediatric epilepsy: Implications for seizures and therapeutic approaches.Epilepsia open · 2025Article
- Comparative analysis of machine learning techniques in metabolomic-based preterm birth prediction.Computational and structural biotechnology journal · 2025Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe infantile spasms syndrome is an early-onset epileptic encephalopathy presenting in the first 2 years of life, often with severe developmental consequences. The role of the gut microbiota and metabolism in infantile spasms remains unexplored.
methodsEmploying a brain injury neonatal rat model of infantile spasms intractable to anticonvulsant medication treatments, we determined how the ketogenic diet and antibiotics affected specific microbial communities and the resultant circulating factors that confer spasms protection in the infantile spasms model. To confirm a role of kynurenine metabolism pathway in spasms protection, indoleamine 2,3-dioxygenase 1 was pharmacologically inhibited and comprehensive metabolomics was applied.
findingsWe show that antibiotics reduced spasms and improved the effectiveness of the ketogenic diet when given in combination. Examination of the gut microbiota and metabolomics showed the downregulation of indoleamine 2,3-dioxygenase 1 and upregulation of hippocampal kynurenic acid, a metabolite with antiepileptic effects. To further test the involvement of indoleamine 2,3-dioxygenase 1, a specific antagonist 1-methyltryptophan and minocycline, an antibiotic and inhibitor of kynurenine formation from tryptophan, were administered, respectively. Both treatments were effective in reducing spasms and elevating hippocampal kynurenic acid. A fecal microbiota transplant experiment was then performed to examine the contribution of the gut microbiota on spasm mitigation. Transplant of feces of ketogenic diet animals into normal diet animals was effective in reducing spasms.
interpretationThese results highlight the importance of tryptophan-kynurenine metabolism in infantile spasms and provide evidence for new-targeted therapies such as indoleamine 2,3-dioxygenase 1 inhibition or microbiota manipulation to promote kynurenic acid production as a strategy to reduce spasms in infantile spasms.
fundingThis study was funded by the Alberta Children's Hospital Research Institute and the Owerko Centre.
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