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Experiment Proposal: h-var-08a4d5c07a
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experiment proposal
Created: 2026-04-28T13:02:35
By: forge_experiment_proposal_generator
Quality:
75%
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ID: experiment_proposal-fa36c80e-5e55-4e39-9
🧬 Experiment Proposal
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▸Metadata
| citations | ['29263430', '30679038', '33875891', '33741860', '31748742', '31043694', '27519954', '30610225'] |
| generated_at | 2026-04-28T20:02:35.464403+00:00 |
| intervention | Next-generation probiotic consortium (Akkermansia muciniphila 1×10^9 CFU + Faecalibacterium prausnitzii 1×10^9 CFU + Bifidobacterium longum 1×10^9 CFU, oral gavage, 5 days/week for 12 weeks) plus MCC9 |
| key_controls | ['WT C57BL/6J mice receiving identical probiotic+MCC950 regimen to establish baseline variability', 'NLRP3 knockout mice crossed to APP/PS1 (APP/PS1/Nlrp3−/−) receiving probiotics to confirm inflammas |
| model_system | APP/PS1dE9 transgenic mice on C57BL/6J background; both sexes; 3 months (pre-plaque, n=24/group) and 6 months (post-plaque, n=24/group) cohorts; total N=192 animals across 8 groups |
| timeline_weeks | 14 |
| _schema_version | 1 |
| null_hypothesis | Gut microbiome remodeling via next-generation probiotic consortium does not reduce systemic NLRP3 inflammasome priming or attenuate neurodegeneration-associated neuroinflammation compared to vehicle-t |
| primary_readout | Cortical and hippocampal IL-1β concentration (pg/mg tissue) measured by ELISA in CD11b+ MACS-isolated microglia; NLRP3 activation assessed by ASC speck count per CD68+ microglial cell via confocal mic |
| estimated_cost_usd | 185000.0 |
| secondary_readouts | ['Serum LPS concentration via LAL assay and soluble CD14 (eBioscience) reflecting bacterial translocation', 'Fecal SCFA profile (acetate, propionate, butyrate) by GC-MS at baseline, week 6, and week 1 |
| expected_effect_size | Cohen's d = 0.85 for IL-1β reduction in combination arm vs APP/PS1 vehicle based on MCC950 literature (PMID 29263430); power = 0.80, alpha = 0.05, two-tailed; effect on amyloid burden anticipated d = |
| statistical_approach | Mixed-effects ANOVA with time as repeated measure and treatment as between-subject factor; post-hoc Tukey HSD; two-way ANOVA for interaction effects of timing × intervention; Benjamini-Hochberg FDR co |
| sample_size_rationale | Power analysis (G*Power 3.1): n=24 per group provides 80% power to detect d=0.80 (alpha=0.05, two-tailed); assumes 15% attrition; sample size anchored to IL-1β outcome variability (SD=0.35) from publi |
| falsification_criterion | Hypothesis falsified if combination therapy fails to reduce microglial IL-1β by ≥40% (pre-registered threshold) and fails to improve Barnes maze performance by ≥20% compared to vehicle APP/PS1 control |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
1
0 supporting
0 contradicting
0 neutral
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