ID: h-b8cedff2
Hypothesis
Fecal Microbiota Transplantation to Reset Microglial Priming States
Fecal Microbiota Transplantation to Reset Microglial Priming States.
🧬 Gut microbiome → LPS/TMAO → HDAC6 → Microglial NF-κB🩺 immunomics🎯 Composite 43%💱 $0.49▲13.2%proposed
EvidencePending (0%)📖 0 cit🗣 1 debates✓ 3 support✗ 4 oppose
🧪 Overview
Fecal Microbiota Transplantation to Reset Microglial Priming States
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["Gut Dysbiosis<br/>Pathobiont Overgrowth"]
B["LPS Lipopolysaccharide<br/>TMAO Trimethylamine-N-Oxide"]
C["Systemic Inflammation<br/>BBB Compromise"]
D["CNS LPS/TMAO<br/>Microglial Exposure"]
E["HDAC6 Epigenetic<br/>Priming Signal"]
F["NF-kB Microglial<br/>Hyperactivation"]
G["Sustained Neuroinflammation<br/>Synaptic Loss"]
H["FMT Intervention<br/>Microbiome Reset"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
H -.-> A
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style E fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style H fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7⚖️ Evidence
⚖️ Evidence Matrix3 supports4 contradicts
Supports
Germ-free mice show reduced microglial maturation and impaired innate immune responses
Contradicts
Probiotic trials (Lactobacillus/Bifidobacterium) show minimal to no benefit in meta-analyses for cognitive improvement in MCI/AD
Contradicts
CRITICAL MECHANISTIC ERROR: HDAC6 is primarily cytoplasmic deacetylase involved in α-tubulin acetylation; does not regulate transcription or chromatin
Contradicts
Gut microbiome compositions vary dramatically across populations, geographies, and diets; 'healthy donor' profile remains undefined
Contradicts
Elevated serum LPS in AD may result from increased intestinal permeability secondary to aging and neurodegeneration rather than causing it
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — GUT
No curated PDB or AlphaFold mapping for GUT yet. Search RCSB →
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
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 Gut microbiome → LPS.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
↔
Stable
7d Momentum
▲ 0.6%
Volatility
Low
0.0082
Events (7d)
2
Price History
▲13.2%💾 Resource Usage
LLM Tokens
36,998
$0.1110
Total Cost
$0.1110
🔮 Predictions
🔎 Predictions vs Observations2 predictions · 0 with recorded observations
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF fecal microbiota transplantation (FMT) from young healthy donors is performed in aged C57BL/6J mice (18 months old, n≥12/group) THEN microglial NF-κB p65 nuclear translocation in the substantia nig | NF-κB p65+ nuclei in IBA-1+ cells will be 30-50% lower in FMT group (expected ~15% vs ~30% in sham). Secondary: serum LPS will be ≥40% lower, hippocampal HDAC6 | — no observation — | pending | 0.55 |
| IF fecal microbiota transplantation from healthy age-matched donors is performed in Parkinson's disease patients (n≥40, Hoehn-Yahr stage 1-3) THEN serum trimethylamine N-oxide (TMAO) will decrease by | Primary: TMAO serum levels will be ≤8 μM in FMT group vs ≥12 μM in placebo (baseline ~15 μM PD patients). TSPO BPnd in substantia nigra will decrease from basel | — no observation — | pending | 0.40 |
🔮 Falsifiable Predictions (2)
pendingconf 55%
IF fecal microbiota transplantation (FMT) from young healthy donors is performed in aged C57BL/6J mice (18 months old, n≥12/group) THEN microglial NF-κB p65 nuclear translocation in the substantia nigra pars compacta will decrease by ≥30% within 4 weeks post-FMT compared to sham-FMT controls receivi
Predicted outcome: NF-κB p65+ nuclei in IBA-1+ cells will be 30-50% lower in FMT group (expected ~15% vs ~30% in sham). Secondary: serum LPS will be ≥40% lower, hippocam
Falsification: NF-κB p65 nuclear translocation does not decrease (remains >25% of microglia) OR serum LPS does not fall below threshold after FMT; or microglial morphology shifts toward hyper-ramified (surveying) ra
pendingconf 40%
IF fecal microbiota transplantation from healthy age-matched donors is performed in Parkinson's disease patients (n≥40, Hoehn-Yahr stage 1-3) THEN serum trimethylamine N-oxide (TMAO) will decrease by ≥35% and microglial PET signal (TSPO binding, [11C]-PK11195) will be reduced by ≥20% in the substant
Predicted outcome: Primary: TMAO serum levels will be ≤8 μM in FMT group vs ≥12 μM in placebo (baseline ~15 μM PD patients). TSPO BPnd in substantia nigra will decrease
Falsification: TMAO levels remain within 15% of baseline or increase; TSPO PET signal does not decrease; or gastrointestinal side effects (diarrhea, infection) in >20% requiring trial halt.
▸Metadatasource: v1_phase_c_backfill · origin_type: gap_debate
| source | v1_phase_c_backfill |
| origin_type | gap_debate |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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