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Tryptophan metabolism

autism

Tryptophan metabolism has meaningful literature visibility in autism, but the current evidence mix suggests a substantial risk of overclaiming.

Tryptophan metabolism shows a moderate evidence base in autism, with multiple central papers and additional supporting literature.

tryptophan_metabolism
Credibility score
82
Human translation
2/5
Reproducibility
5/5
Novelty
1/5
Actionability
3/5
Credibility 82Human translation 2/5Reproducibility 5/5Novelty 1/5Actionability 3/5
Why this scores the way it does
  • moderate central evidence base
  • dense review literature
  • substantial preclinical support
Main caveats
  • preclinical evidence outweighs human evidence

Internal review flags

2 flags
preclinical_heavy

Preclinical evidence exceeds central human evidence. Interpret translational relevance cautiously.

review_heavy

Review literature is very dense relative to primary central evidence.

Primary central evidence

14 papers
Decreased tryptophan metabolism in patients with autism spectrum disorders.
2013
Molecular autism
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Chromosomal microarray analysis of consecutive individuals with autism spectrum disorders or learning disability presenting for genetic services.
2014
Gene
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism.
2016
Molecular autism
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Altered Urinary Amino Acids in Children With Autism Spectrum Disorders.
2019
Frontiers in cellular neuroscience
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Changes in the Gut Microbiota of Children with Autism Spectrum Disorder.
2020
Autism research : official journal of the International Society for Autism Research
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
The Urine Metabolome of Young Autistic Children Correlates with Their Clinical Profile Severity.
2020
Metabolites
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Fecal Microbiome Transplantation from Children with Autism Spectrum Disorder Modulates Tryptophan and Serotonergic Synapse Metabolism and Induces Altered Behaviors in Germ-Free Mice.
2021
mSystems
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Alterations in Gut Vitamin and Amino Acid Metabolism are Associated with Symptoms and Neurodevelopment in Children with Autism Spectrum Disorder.
2022
Journal of autism and developmental disorders
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Cryo-EM Structure and Activator Screening of Human Tryptophan Hydroxylase 2.
2022
Frontiers in pharmacology
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
[Diversity and functional prediction of gut microbiota in children with autism spectrum disorder].
2022
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Vitamin A deficiency from maternal gestation may contribute to autistic-like behaviors and gastrointestinal dysfunction in rats through the disrupted purine and tryptophan metabolism.
2023
Behavioural brain research
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
The fecal microbiota from children with autism impact gut metabolism and learning and memory abilities of honeybees.
2023
Frontiers in microbiology
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Infant microbes and metabolites point to childhood neurodevelopmental disorders.
2024
Cell
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.
Melatonin ameliorates autistic-like behaviors by restoring gut microbiota-derived tryptophan metabolites.
2026
Cellular and molecular life sciences : CMLS
Direct disease-relevant human paper with strong clinical, biomarker, or mechanistic framing.

Supporting primary evidence

1 papers
Relationships between tryptophan-related gut metabolites, brain activity, and autism symptomatology.
2024
Research square
Relevant preprint retained as supporting evidence, not central evidence.

Preclinical supporting evidence

23 papers
Response inhibition and serotonin in autism: a functional MRI study using acute tryptophan depletion.
2014
Brain : a journal of neurology
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Tryptophan status in autism spectrum disorder and the influence of supplementation on its level.
2017
Metabolic brain disease
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism.
2017
EBioMedicine
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders.
2018
CNS & neurological disorders drug targets
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Brain hyperserotonemia causes autism-relevant social deficits in mice.
2018
Molecular autism
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Synthesis and Preclinical Evaluation of 6-[18F]Fluorine-α-methyl-l-tryptophan, a Novel PET Tracer for Measuring Tryptophan Uptake.
2020
ACS chemical neuroscience
Disease-relevant preclinical or model-based paper useful as supporting evidence.
The Generalized Adaptation Account of Autism.
2020
Frontiers in neuroscience
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Daily intake of Lactobacillus alleviates autistic-like behaviors by ameliorating the 5-hydroxytryptamine metabolic disorder in VPA-treated rats during weaning and sexual maturation.
2021
Food & function
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Expression analysis of selected genes involved in tryptophan metabolic pathways in Egyptian children with Autism Spectrum Disorder and learning disabilities.
2021
Scientific reports
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Prenatal stress-induced disruptions in microbial and host tryptophan metabolism and transport.
2021
Behavioural brain research
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Kynurenine pathway and autism spectrum phenotypes: an investigation among adults with autism spectrum disorder and their first-degree relatives.
2023
CNS spectrums
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder.
2022
Translational psychiatry
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Maternal LPS Exposure Enhances the 5-HT Level in the Prefrontal Cortex of Autism-like Young Offspring.
2023
Brain sciences
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Maternal exposure of mice to glyphosate induces depression- and anxiety-like behavior in the offspring via alterations of the gut-brain axis.
2023
The Science of the total environment
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Impact of IDO activation and alterations in the kynurenine pathway on hyperserotonemia, NAD+ production, and AhR activation in autism spectrum disorder.
2023
Translational psychiatry
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Gut microbiome and metabolic profiles of mouse model for MeCP2 duplication syndrome.
2024
Brain research bulletin
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Gut microbiota functional profiling in autism spectrum disorders: bacterial VOCs and related metabolic pathways acting as disease biomarkers and predictors.
2023
Frontiers in microbiology
Disease-relevant preclinical or model-based paper useful as supporting evidence.
The metabolic role of vitamin D in children's neurodevelopment: a network study.
2024
Scientific reports
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Taprenepag restores maternal-fetal interface homeostasis for the treatment of neurodevelopmental disorders.
2024
Journal of neuroinflammation
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Exploring the Association Between Human Blood Metabolites and Autism Spectrum Disorder Risk: A Bidirectional Mendelian Randomization Study.
2025
Health science reports
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Parental kynurenine 3-monooxygenase genotype in mice directs sex-specific behavioral outcomes in offspring.
2025
Biology of sex differences
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Relationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology.
2025
Nature communications
Disease-relevant preclinical or model-based paper useful as supporting evidence.
Rethinking ADHD as a neurointestinal syndrome: a gut-brain-parasite hypothesis.
2025
Frontiers in neuroscience
Disease-relevant preclinical or model-based paper useful as supporting evidence.

Review supporting evidence

44 papers
Tetrahydrobiopterin biosynthesis, regeneration and functions.
2000
The Biochemical journal
Relevant review or meta-analysis for the signal-disease area.
Serotonin in autism and pediatric epilepsies.
2004
Mental retardation and developmental disabilities research reviews
Relevant review or meta-analysis for the signal-disease area.
Role of NAD(+), Oxidative Stress, and Tryptophan Metabolism in Autism Spectrum Disorders.
2013
International journal of tryptophan research : IJTR
Relevant review or meta-analysis for the signal-disease area.
The impact of microbiota on brain and behavior: mechanisms & therapeutic potential.
2014
Advances in experimental medicine and biology
Relevant review or meta-analysis for the signal-disease area.
The impact of gut microbiota on brain and behaviour: implications for psychiatry.
2015
Current opinion in clinical nutrition and metabolic care
Relevant review or meta-analysis for the signal-disease area.
The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease.
2017
Molecular neurobiology
Relevant review or meta-analysis for the signal-disease area.
Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration.
2017
The Journal of physiology
Relevant review or meta-analysis for the signal-disease area.
The Microbiome-Gut-Brain Axis in Health and Disease.
2017
Gastroenterology clinics of North America
Relevant review or meta-analysis for the signal-disease area.
How important is tryptophan in human health?
2019
Critical reviews in food science and nutrition
Relevant review or meta-analysis for the signal-disease area.
Cross Talk: The Microbiota and Neurodevelopmental Disorders.
2017
Frontiers in neuroscience
Relevant review or meta-analysis for the signal-disease area.
Genetic alterations affecting the genes encoding the enzymes of the kynurenine pathway and their association with human diseases.
2018
Mutation research. Reviews in mutation research
Relevant review or meta-analysis for the signal-disease area.
METABOLIC DYSBIOSIS OF THE GUT MICROBIOTA AND ITS BIOMARKERS.
2016
Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease.
2018
Cell host & microbe
Relevant review or meta-analysis for the signal-disease area.
Extreme enhancement or depletion of serotonin transporter function and serotonin availability in autism spectrum disorder.
2019
Pharmacological research
Relevant review or meta-analysis for the signal-disease area.
The Brain-Gut-Microbiome Axis.
2018
Cellular and molecular gastroenterology and hepatology
Relevant review or meta-analysis for the signal-disease area.
Analysis, Nutrition, and Health Benefits of Tryptophan.
2018
International journal of tryptophan research : IJTR
Relevant review or meta-analysis for the signal-disease area.
Man and the Microbiome: A New Theory of Everything?
2019
Annual review of clinical psychology
Relevant review or meta-analysis for the signal-disease area.
The Microbiota-Gut-Brain Axis.
2019
Physiological reviews
Relevant review or meta-analysis for the signal-disease area.
The role of the microbiota-gut-brain axis in neuropsychiatric disorders.
2021
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)
Relevant review or meta-analysis for the signal-disease area.
Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence.
2020
Microorganisms
Relevant review or meta-analysis for the signal-disease area.
Gut microbiota, kynurenine pathway and mental disorders - Review.
2021
Progress in neuro-psychopharmacology & biological psychiatry
Relevant review or meta-analysis for the signal-disease area.
Gut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and disease.
2021
Progress in neuro-psychopharmacology & biological psychiatry
Relevant review or meta-analysis for the signal-disease area.
Melatonin: From Pharmacokinetics to Clinical Use in Autism Spectrum Disorder.
2021
International journal of molecular sciences
Relevant review or meta-analysis for the signal-disease area.
The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine.
2021
International journal of molecular sciences
Relevant review or meta-analysis for the signal-disease area.
Small Molecules Originated from Tryptophan and their Clinical Significance as Potential Biomarkers.
2022
Combinatorial chemistry & high throughput screening
Relevant review or meta-analysis for the signal-disease area.
The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder.
2021
Nutrients
Relevant review or meta-analysis for the signal-disease area.
Varied Composition and Underlying Mechanisms of Gut Microbiome in Neuroinflammation.
2022
Microorganisms
Relevant review or meta-analysis for the signal-disease area.
Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder.
2023
Cells
Relevant review or meta-analysis for the signal-disease area.
The brain serotonin system in autism.
2024
Reviews in the neurosciences
Relevant review or meta-analysis for the signal-disease area.
The tryptophan catabolite or kynurenine pathway in autism spectrum disorder; a systematic review and meta-analysis.
2023
Autism research : official journal of the International Society for Autism Research
Relevant review or meta-analysis for the signal-disease area.
Existing and Future Strategies to Manipulate the Gut Microbiota With Diet as a Potential Adjuvant Treatment for Psychiatric Disorders.
2024
Biological psychiatry
Relevant review or meta-analysis for the signal-disease area.
Once upon a Time Oral Microbiota: A Cinderella or a Protagonist in Autism Spectrum Disorder?
2023
Metabolites
Relevant review or meta-analysis for the signal-disease area.
The correlation between gut microbiota and both neurotransmitters and mental disorders: A narrative review.
2024
Medicine
Relevant review or meta-analysis for the signal-disease area.
Role of Serotonylation and SERT Posttranslational Modifications in Alzheimer's Disease Pathogenesis.
2024
Aging and disease
Relevant review or meta-analysis for the signal-disease area.
Association between small intestine bacterial overgrowth and psychiatric disorders.
2024
Frontiers in endocrinology
Relevant review or meta-analysis for the signal-disease area.
Recent drug delivery systems targeting the gut-brain-microbiome axis for the management of chronic diseases.
2025
International journal of pharmaceutics
Relevant review or meta-analysis for the signal-disease area.
Double-edged sword effect of Sutterella in neurological disorders: implications for the gut-brain axis and neuroimmune interactions.
2025
Neurobiology of disease
Relevant review or meta-analysis for the signal-disease area.
Role of the microbiota in inflammation-related related psychiatric disorders.
2025
Frontiers in immunology
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota in Psychiatric and Neurological Disorders: Current Insights and Therapeutic Implications.
2025
Biomedicines
Relevant review or meta-analysis for the signal-disease area.
Tryptophan Metabolism in Neurodevelopment and Its Implications For Neurodevelopmental Disorders.
2025
Molecular neurobiology
Relevant review or meta-analysis for the signal-disease area.
The Microbiota-Gut-Brain Axis in Autism: Associations, Causal Inference, and Interventions-A Narrative Review.
2025
Pathogens (Basel, Switzerland)
Relevant review or meta-analysis for the signal-disease area.
Gut Microbiota and Autism: Unlocking Connections.
2025
Nutrients
Relevant review or meta-analysis for the signal-disease area.
Interactions of vitamins and gut microbiota in neurodevelopmental disorders.
2026
Behavioural brain research
Relevant review or meta-analysis for the signal-disease area.
The Gut Microbiota-Tryptophan-Brain Axis in Autism Spectrum Disorder: A New Frontier for Probiotic Intervention.
2026
Microorganisms
Relevant review or meta-analysis for the signal-disease area.