Fecal Microbiota Transplantation to Reset Microglial Priming States
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:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for GUT yet. Search RCSB →
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.
| 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 |