Version history

{
  "description": "How does gut microbiome dysbiosis contribute to neuroinflammation and neurodegeneration through toll-like receptor TLR signaling and short-chain fatty acids SCFAs",
  "domain": "neurodegeneration",
  "status": "resolved",
  "priority_score": 0.9,
  "evidence_summary": "{\"resolution_pipeline\": \"scidex.atlas.gap_closure_pipeline\", \"task_id\": \"f4f7b129-0f43-4c84-abd8-20d4e701842d\", \"evaluated_at\": \"2026-04-28T19:10:15.857052+00:00\", \"resolution_summary\": \"Resolved by hypothesis h-6ea2dc4c96: SCFA Deficiency Drives Microglial Hyperactivation via GPR43/NF-κB Dysregulation. Supporting evidence includes debate sess_SDA-2026-04-26-gap-20260425-224724.\", \"match_counts\": {\"hypothesis_matches\": 5, \"debate_matches\": 4, \"paper_matches\": 0}, \"hypothesis_matches\": [{\"id\": \"h-6ea2dc4c96\", \"title\": \"SCFA Deficiency Drives Microglial Hyperactivation via GPR43/NF-κB Dysregulation\", \"score\": 1.0, \"reason\": \"direct analysis.gap_id link\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-225305\", \"target_gene\": \"GPR43 (FFAR2), GPR41 (FFAR3), HDAC3, RELA (NF-κB p65)\", \"target_pathway\": null, \"disease\": \"neurodegeneration\", \"composite_score\": 0.728246, \"confidence_score\": 0.82, \"status\": \"debated\", \"pubmed_evidence_ids\": [\"21383957\", \"26268901\", \"26734968\"]}, {\"id\": \"h-78b2af94ab\", \"title\": \"Leaky Gut LPS Translocation Activates Systemic TLR4/MyD88 Signaling, Driving CNS Monocyte Infiltration\", \"score\": 1.0, \"reason\": \"direct analysis.gap_id link\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-225305\", \"target_gene\": \"TLR4, MyD88, IRAK4, CCL2, CCR2, ZO-1 (TJP1)\", \"target_pathway\": null, \"disease\": \"neurodegeneration\", \"composite_score\": 0.67, \"confidence_score\": 0.78, \"status\": \"proposed\", \"pubmed_evidence_ids\": [\"16914660\", \"18785108\", \"21829344\", \"30929736\"]}, {\"id\": \"h-a3a1a15a56\", \"title\": \"Butyrate-Producing Commensal Depletion Creates Vicious Cycle: HDAC3 Overactivity Permits TREM2-Independent Microglial Dysfunction\", \"score\": 1.0, \"reason\": \"direct analysis.gap_id link\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-225305\", \"target_gene\": \"HDAC3, TREM2, PGC-1α, NLRP3, HIF1α\", \"target_pathway\": null, \"disease\": \"neurodegeneration\", \"composite_score\": 0.63, \"confidence_score\": 0.72, \"status\": \"proposed\", \"pubmed_evidence_ids\": [\"25472853\", \"27523554\", \"31277771\", \"33208957\"]}, {\"id\": \"h-8af96e9ea0\", \"title\": \"NLRP3 Inflammasome Priming Converts SCFA-Sensitive Pyroptosis into Chronic IL-1β-Mediated Synaptic Pruning\", \"score\": 1.0, \"reason\": \"direct analysis.gap_id link\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-225305\", \"target_gene\": \"NLRP3, CASP1, GSDMD, IL1B, IL1R1, C3, C1QA, GPR109A (HCAR2)\", \"target_pathway\": null, \"disease\": \"neurodegeneration\", \"composite_score\": 0.62, \"confidence_score\": 0.7, \"status\": \"proposed\", \"pubmed_evidence_ids\": [\"22989199\", \"26337542\", \"28139699\", \"33916204\"]}, {\"id\": \"h-1431a507bf\", \"title\": \"Gut Bacterial Metabolite-AhR Dysregulation Converts SCFA-Deficiency into IDO1-Driven Kynurenine Neurotoxicity\", \"score\": 1.0, \"reason\": \"direct analysis.gap_id link\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-225305\", \"target_gene\": \"AHR, IDO1, KYNU, HAAO, GRIN2A, STAT3\", \"target_pathway\": null, \"disease\": \"neurodegeneration\", \"composite_score\": 0.58, \"confidence_score\": 0.65, \"status\": \"proposed\", \"pubmed_evidence_ids\": [\"11071322\", \"25423376\", \"31300524\", \"31988383\"]}], \"debate_matches\": [{\"id\": \"sess_SDA-2026-04-26-gap-20260425-224724\", \"title\": \"How does gut microbiome dysbiosis contribute to neuroinflammation and neurodegeneration through toll-like receptor TLR signaling and short-chain fatty acids SCFAs\", \"score\": 1.0, \"reason\": \"11 token overlaps; entity overlap: tlr\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-224724\", \"quality_score\": 0.78, \"status\": \"completed\", \"target_artifact_id\": \"gap-20260425-224724\", \"target_artifact_type\": \"knowledge_gap\"}, {\"id\": \"sess_SDA-2026-04-26-gap-20260425-225305_task_9aae8fc5\", \"title\": \"How does gut microbiome dysbiosis contribute to neuroinflammation and neurodegeneration through toll-like receptor TLR signaling and short-chain fatty acids SCFAs\", \"score\": 1.0, \"reason\": \"direct analysis.gap_id link\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-225305\", \"quality_score\": 0.764, \"status\": \"completed\", \"target_artifact_id\": null, \"target_artifact_type\": null}, {\"id\": \"sess-hyp-24b92eb41b48\", \"title\": \"Debate: SCFA Deficiency Drives Microglial Hyperactivation via GPR43/NF-κB Dysregulation\", \"score\": 1.0, \"reason\": \"direct analysis.gap_id link\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-225305\", \"quality_score\": 0.132, \"status\": \"completed\", \"target_artifact_id\": \"h-6ea2dc4c96\", \"target_artifact_type\": \"hypothesis\"}, {\"id\": \"hyp-debate-664901bf-05fc304fe0\", \"title\": \"Formal debate: TLR4 priming is the actionable driver in: How does gut microbiome dysbiosis contribute to neuroinflammation and neurodegeneration th\", \"score\": 0.364, \"reason\": \"4 token overlaps\", \"analysis_id\": \"SDA-2026-04-26-gap-20260425-224724\", \"quality_score\": 0.746, \"status\": \"completed\", \"target_artifact_id\": \"h-gap-2f2e5b80-m1\", \"target_artifact_type\": \"hypothesis\"}], \"paper_matches\": []}",
  "resolution_criteria": "Resolution requires: (1) Prospective interventional trial or well-controlled germ-free model establishing dose-response of microbiome dysbiosis on TLR4-mediated neuroinflammation: LPS levels in portal circulation correlate with hippocampal IL-1beta and microglial morphology changes (r>=0.6, n>=30 per condition); (2) SCFA loss-of-function: SCFA transporter knockout (Slc5a8) or antibiotic-induced depletion reduces brain butyrate by >=50% and increases neuroinflammatory markers by >=1.8-fold vs controls, with dose-response relationship established; (3) Clinical validation: human fecal microbiota transplant (FMT) from neurodegeneration patients to germ-free recipients reproduces CNS inflammation markers detectable in CSF (IL-6, TNF-alpha above 95th percentile of healthy donor FMT group). Correlation data from observational microbiome studies without causal manipulation is insufficient.",
  "market_price": 0.5
}