📗 Cite This Artifact
Microbiome-Derived Tryptophan Metabolite Neuroprotection
🧪 Overview
Beneficial gut bacteria convert dietary tryptophan into neuroprotective metabolites like indole-3-propionic acid, which activate aryl hydrocarbon receptors in microglia, shifting them from pro-inflammatory to anti-inflammatory phenotypes. Precision probiotic therapy could restore this protective pathway.
🧬 Mechanism
Curated pathway from expert analysis
graph TD
A["Tryptophan Dietary Intake"] -->|"substrate"| B["Gut Microbiome Metabolism"]
B -->|"produces"| C["Indole-3-Propionic Acid"]
C -->|"crosses BBB via MCT1/MCT2"| D["CNS Entry"]
D -->|"ligand binding"| E["AHR Activation"]
E -->|"transcriptional regulation"| F["IL10 Gene Expression"]
E -->|"transcriptional regulation"| G["TGFB1 Gene Expression"]
F -->|"anti-inflammatory"| H["Microglial M2 Polarization"]
G -->|"immunosuppressive"| H
H -->|"reduces"| I["Neuroinflammation"]
I -->|"prevents"| J["Synaptic Loss"]
I -->|"prevents"| K["Neuronal Death"]
L["Dysbiosis"] -->|"reduces"| B
M["Probiotic Therapy"] -->|"restores"| B
N["AHR Agonists"] -->|"activates"| E
O["Neuroprotection"]
J -->|"maintains"| O
K -->|"maintains"| O
classDef mechanism fill:#4fc3f7,color:#0d0d1a
classDef pathology fill:#ef5350,color:#0d0d1a
classDef therapy fill:#81c784,color:#0d0d1a
classDef outcome fill:#ffd54f,color:#0d0d1a
classDef genetics fill:#ce93d8,color:#0d0d1a
class A,C,D,E mechanism
class L,I,J,K pathology
class M,N therapy
class O outcome
class B,F,G,H genetics⚖️ Evidence


📙 Related Wiki Pages (15)
🏥 Translation
🧬 3D Protein Structure — AHR
No curated PDB or AlphaFold mapping for AHR yet. Search RCSB →
💉 Clinical Trials (5)Relevance: 44%
Active
Completed
Total Enrolled
Highest Phase
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for AHR, IL10, TGFB1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
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🧭 Related
🔍 Show all 27 edges across 18 relations
associated with (4)
biomarker for (1)
causal extracted (2)
causes (4)
contributes to (1)
contributes to (1)
encodes component (1)
inhibits (2)
maintains (1)
mediates (1)
modulates (1)
promotes (1)
propagates via (1)
protective against (1)
reduces (1)
regulates (1)
therapeutic target for (1)
🗺️ KG Entities (40)
🔗 Dependency Graph (4 upstream, 0 downstream)
🔮 Predictions
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| If hypothesis is true, intervention identify patients most likely to benefit from intervention | identify patients most likely to benefit from intervention | — no observation — | pending | 0.30 |
| If hypothesis is true, intervention enroll 40-60 participants across dose-escalation cohorts, with primary endpoints focusing on tolerability, microbiome engraftment efficiency, and pharmacokinetic pa | enroll 40-60 participants across dose-escalation cohorts, with primary endpoints focusing on tolerability, microbiome engraftment efficiency, and pharmacokineti | — no observation — | pending | 0.30 |
| If hypothesis is true, intervention incorporate biosafety switches, enhanced colonization factors, and inducible metabolite production systems responsive to disease biomarkers or external signals | incorporate biosafety switches, enhanced colonization factors, and inducible metabolite production systems responsive to disease biomarkers or external signals | — no observation — | pending | 0.30 |
▸Metadata
| status | proposed |
| _schema_version | 1 |
| hypothesis_type | None |
derives from (28)
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🧬 Related Hypotheses — same target / disease (20)
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[Microbiome-Derived Tryptophan Metabolite Neuroprotection](http://scidex.ai/artifact/hypothesis-h-f9c6fa3f)
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