{
  "title": "Fasolati science spine: selected mechanism map",
  "version": "2026-09-12",
  "website": "https://fasolati.life/science/",
  "scope": "Selected published evidence with interpretation boundaries. Not a systematic review.",
  "clinicalStatus": "Research architecture. No validated Fasolati assay, personal disease-risk score, or clinical utility is established by this map.",
  "mechanisms": [
    {
      "id": "endothelial-barrier",
      "name": "Endothelial barrier",
      "route": "P. gingivalis OMVs / gingipains → barrier effects",
      "setting": "Cells + zebrafish",
      "finding": "Wild-type and gingipain-deficient OMV comparisons supported a gingipain contribution to endothelial-barrier disruption, with PECAM-1 loss associated with the response. The zebrafish experiments used direct systemic injection, not oral exposure.",
      "boundary": "This does not calibrate an oral-rinse measurement to vascular leak, heart attack, or stroke risk in a person.",
      "use": "A candidate barrier-response benchmark, with preparation, cargo, and exposure controls.",
      "source": "Farrugia et al., 2020",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7684789/",
      "permalink": "https://fasolati.life/science/#endothelial-barrier",
      "attribution": "Published-study finding summarized by Fasolati, not a completed Fasolati experiment."
    },
    {
      "id": "hepatic-insulin-signaling",
      "name": "Hepatic insulin signaling",
      "route": "P. gingivalis OMVs → liver and glycogen signaling",
      "setting": "Mice + cells",
      "finding": "Seyama and colleagues reported liver translocation and reduced insulin-responsive hepatic glycogen synthesis in mice. In HepG2 cells, OMVs attenuated insulin-stimulated Akt/GSK-3β signaling in a gingipain-dependent manner.",
      "boundary": "This is not proof that a person’s glucose excursions are caused by oral vesicles, and it does not establish the same effect in muscle or adipose tissue.",
      "use": "A focused metabolic mechanism to test at exposure levels relevant to the intended human question.",
      "source": "Seyama et al., 2020",
      "url": "https://pubmed.ncbi.nlm.nih.gov/32088316/",
      "permalink": "https://fasolati.life/science/#hepatic-insulin-signaling",
      "attribution": "Published-study finding summarized by Fasolati, not a completed Fasolati experiment."
    },
    {
      "id": "neuroinflammatory-responses",
      "name": "Neuroinflammatory responses",
      "route": "P. gingivalis OMV exposure → brain-related phenotypes",
      "setting": "Mouse experiment",
      "finding": "Aged male mice given OMVs by oral gavage at 4 mg/kg every other day for eight weeks showed neuroinflammatory, tau-phosphorylation, and memory-task effects.",
      "boundary": "The experimental dose is not established as ordinary human exposure. This is not evidence for a personal Alzheimer’s risk meter or proof of human disease causation.",
      "use": "Retain the animal finding with its dose and route, rather than collapsing it into a mouth-to-brain prediction.",
      "source": "Gong et al., 2022",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9397999/",
      "permalink": "https://fasolati.life/science/#neuroinflammatory-responses",
      "attribution": "Published-study finding summarized by Fasolati, not a completed Fasolati experiment."
    },
    {
      "id": "innate-immune-activation",
      "name": "Innate immune activation",
      "route": "Periodontal-bacterial OMVs → receptor responses",
      "setting": "Mechanistic assays",
      "finding": "Vesicles from different periodontal organisms produced different TLR2 and TLR4 response profiles under the tested conditions.",
      "boundary": "A receptor response does not identify every active ligand. Comparing species individually does not establish synergy when their vesicles are combined.",
      "use": "A panel of functional readouts with ligand-attribution and interference controls, not one universal inflammation score.",
      "source": "Cecil et al., 2016",
      "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151967",
      "permalink": "https://fasolati.life/science/#innate-immune-activation",
      "attribution": "Published-study finding summarized by Fasolati, not a completed Fasolati experiment."
    },
    {
      "id": "vesicular-rna",
      "name": "Vesicular RNA",
      "route": "A. actinomycetemcomitans OMV RNA → host-cell responses",
      "setting": "Cells + mouse delivery",
      "finding": "RNA-associated inflammatory effects were studied in U937 macrophage-like cells. The mouse brain-delivery experiment used intracardiac administration, bypassing the oral barrier.",
      "boundary": "Delivery by injection does not establish natural oral escape, human brain transit, or Alzheimer’s causation.",
      "use": "Separate cargo biology from transport biology, and require the relevant route to be tested.",
      "source": "Han et al., 2019",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6894046/",
      "permalink": "https://fasolati.life/science/#vesicular-rna",
      "attribution": "Published-study finding summarized by Fasolati, not a completed Fasolati experiment."
    },
    {
      "id": "fusobacterium-tissue-interactions",
      "name": "Fusobacterium and tissue interactions",
      "route": "F. nucleatum EVs / FomA → adhesion and colonization",
      "setting": "Human tissue + models",
      "finding": "In five paired colorectal-cancer and adjacent-normal tissue samples, Zheng and colleagues found greater FomA signal in tumor-derived EV-enriched fractions, interpreted as F. nucleatum EV enrichment. Separate cell and mouse experiments supported FomA-transfer effects on adhesion, colonization, and tumor progression.",
      "boundary": "FomA is not a vesicle-exclusive marker. Human tissue enrichment and model mechanisms are separate observations; they do not establish oral origin in an individual or validate an oral-rinse cancer predictor.",
      "boundaryUrl": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12003102/",
      "use": "A specific tissue-interaction hypothesis. Do not substitute whole-bacterium FadA studies for vesicle-specific FomA evidence.",
      "source": "Zheng et al., 2024",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11414721/",
      "permalink": "https://fasolati.life/science/#fusobacterium-tissue-interactions",
      "attribution": "Published-study finding summarized by Fasolati, not a completed Fasolati experiment."
    }
  ]
}