Infectious Agents MOC
Scope: Hub notes and mechanism notes for infectious agents linked to neurological and cognitive outcomes in the Vitals vault.
Evidence bar for this MOC: Links between bacterial pathogens and Alzheimer’s disease are correlational + mechanistic, not causal. The COR388 gingipain-inhibitor trial failed. H. pylori eradication has not been shown to prevent or treat AD in any large RCT. Do not overstate the clinical actionable relevance of this MOC.
Hub Notes
| Note | Pathogen | Evidence Strength | Key Status |
|---|---|---|---|
| Periodontal Pathogens | Porphyromonas gingivalis | Moderate (B) | COR388 Phase 2 failed; Mendelian randomization null |
| Helicobacter pylori | Helicobacter pylori | Weak–Moderate (B) | No brain detection; AD-specific meta-analyses mostly null |
| P. gingivalis & Alzheimer’s | P. gingivalis | B | AD-specific companion hub; OR 1.78; COR388 failed; wearable relevance as inflammatory confound |
| H. pylori & Alzheimer’s | H. pylori | B− | AD-specific companion hub; RR 1.4–1.7 (all-cause dementia); B12 as most actionable pathway |
Mechanism Notes
| Note | Reusable Across | Key Point |
|---|---|---|
| Gingipain | P. gingivalis notes only | Primary P. gingivalis virulence protease; tau cleavage; COR388 target |
| Bacterial OMVs | P. gingivalis + H. pylori | Both pathogens use OMVs to cross BBB; human relevance unproven |
Evidence Summary
P. gingivalis
- Gingipain antigens detected in AD brains (industry-funded; not independently replicated)
- Periodontitis → AD risk: pooled OR 1.67–1.78 in meta-analyses
- COR388 (gingipain inhibitor): Phase 2 failed primary endpoints; company bankrupt
- Mendelian randomization: no causal effect (PMID:38648391)
- Bidirectional: AD patients get periodontitis at higher rates
H. pylori
- Never detected in AD brain or CSF (PMID:30746447 — used as negative control)
- Associated with all-cause dementia (OR 1.34–1.56); association with AD specifically is inconsistent
- OMV-C3-C3aR mechanism entirely preclinical (mouse models)
- No large RCT of eradication for AD prevention or treatment
Vitals Wearable Relevance
| Signal | P. gingivalis | H. pylori |
|---|---|---|
| HRV | Preclinical murine data only; no human wearable data | No data |
| Sleep | NHANES self-report: short sleep ↔ more periodontitis | No direct data |
| Inflammatory biomarkers | CRP/IL-6 elevated in periodontitis; confounds recovery tracking | Chronic IL-6/TNF-α from gastritis; B12 deficiency → homocysteine |
| Wearable actionability | Low — no direct detection path | Low — no direct detection path |
Practical takeaway: The main Vitals-relevant action is recognizing that active oral/gastric infection elevates baseline inflammation, which may confound CRP/IL-6-based recovery decisions. Oral hygiene (brushing, flossing, dental visits) is a low-cost, low-risk general health measure regardless of AD relevance.
What Not to Do (Clinical Guidance Flags)
- ❌ Do not recommend P. gingivalis targeting (e.g., mastic gum, antibiotic protocols) as AD treatment or prevention
- ❌ Do not recommend H. pylori eradication solely for cognitive protection
- ❌ Do not use serology alone for active H. pylori infection detection
- ❌ Do not stop standard AD medications based on pathogen research
- ❌ Do not claim COR388 or gingipain inhibition is a viable AD treatment
Cross-Cutting Notes
- Both pathogens proposed to act via Bacterial OMVs crossing the BBB — mechanism is preclinical only
- Both create systemic inflammatory burden relevant to Vitals recovery biomarker interpretation
- Neither pathogen should be presented to Vitals users as a proven cause of AD
Related MOCs
- Vitals Knowledge Map — full topic index