{ "title": "Fasolati evidence ledger", "version": "2026-09-13", "scope": "Selected evidence and design boundaries; not a systematic review or clinical validation.", "reviewPolicy": "Editorial checked dates are not clinical approvals. New public changes require human release review.", "claims": [ { "id": "endothelial-barrier", "title": "Endothelial barrier", "category": "Mechanism", "setting": "Cells + zebrafish", "statement": "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.", "next": "A candidate barrier-response benchmark, with preparation, cargo, and exposure controls.", "sources": [ { "label": "Farrugia et al., 2020", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7684789/" } ], "reviewed": "2026-09-12", "permalink": "https://fasolati.life/evidence/#claim-endothelial-barrier" }, { "id": "hepatic-insulin-signaling", "title": "Hepatic insulin signaling", "category": "Mechanism", "setting": "Mice + cells", "statement": "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.", "next": "A focused metabolic mechanism to test at exposure levels relevant to the intended human question.", "sources": [ { "label": "Seyama et al., 2020", "url": "https://pubmed.ncbi.nlm.nih.gov/32088316/" } ], "reviewed": "2026-09-12", "permalink": "https://fasolati.life/evidence/#claim-hepatic-insulin-signaling" }, { "id": "neuroinflammatory-responses", "title": "Neuroinflammatory responses", "category": "Mechanism", "setting": "Mouse experiment", "statement": "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.", "next": "Retain the animal finding with its dose and route, rather than collapsing it into a mouth-to-brain prediction.", "sources": [ { "label": "Gong et al., 2022", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9397999/" } ], "reviewed": "2026-09-12", "permalink": "https://fasolati.life/evidence/#claim-neuroinflammatory-responses" }, { "id": "innate-immune-activation", "title": "Innate immune activation", "category": "Mechanism", "setting": "Mechanistic assays", "statement": "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.", "next": "A panel of functional readouts with ligand-attribution and interference controls, not one universal inflammation score.", "sources": [ { "label": "Cecil et al., 2016", "url": "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0151967" } ], "reviewed": "2026-09-12", "permalink": "https://fasolati.life/evidence/#claim-innate-immune-activation" }, { "id": "vesicular-rna", "title": "Vesicular RNA", "category": "Mechanism", "setting": "Cells + mouse delivery", "statement": "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.", "next": "Separate cargo biology from transport biology, and require the relevant route to be tested.", "sources": [ { "label": "Han et al., 2019", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6894046/" } ], "reviewed": "2026-09-12", "permalink": "https://fasolati.life/evidence/#claim-vesicular-rna" }, { "id": "fusobacterium-tissue-interactions", "title": "Fusobacterium and tissue interactions", "category": "Mechanism", "setting": "Human tissue + models", "statement": "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.", "next": "A specific tissue-interaction hypothesis. Do not substitute whole-bacterium FadA studies for vesicle-specific FomA evidence.", "sources": [ { "label": "Zheng et al., 2024", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11414721/" }, { "label": "Marker-specificity context", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12003102/" } ], "reviewed": "2026-09-12", "permalink": "https://fasolati.life/evidence/#claim-fusobacterium-tissue-interactions" }, { "id": "human-glycemic-control", "title": "Periodontal treatment and glycemic control", "category": "Human evidence", "setting": "Clinical systematic review", "statement": "In people with diabetes and periodontitis, the Cochrane review found HbA1c 0.43 percentage points lower at three to four months with periodontal treatment versus no active treatment or usual care (95% CI: 0.28 to 0.59 points lower; moderate-certainty evidence).", "boundary": "This concerns periodontal treatment in a defined population. It does not identify OMVs as the mediator or demonstrate Fasolati or Loria efficacy.", "next": "Keep population, comparator, time point, uncertainty and intervention attached to the result.", "sources": [ { "label": "Simpson et al., Cochrane, 2022", "url": "https://pubmed.ncbi.nlm.nih.gov/35420698/" } ], "reviewed": "2026-09-13", "permalink": "https://fasolati.life/evidence/#claim-human-glycemic-control" }, { "id": "human-crp", "title": "Periodontal treatment and systemic inflammation", "category": "Human evidence", "setting": "Clinical systematic review", "statement": "Luthra and colleagues reported lower C-reactive protein at six months after periodontal treatment, with heterogeneous results. The smaller analysis at twelve months or longer did not detect an effect, with limited longer-term evidence.", "boundary": "A change in CRP is not proof of oral-vesicle mediation, a universal sustained effect, or benefit from a Fasolati product.", "next": "Retain follow-up duration and heterogeneity. Do not replace the original intervention with an oral-care product.", "sources": [ { "label": "Luthra et al., 2023", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10087558/" } ], "reviewed": "2026-09-13", "permalink": "https://fasolati.life/evidence/#claim-human-crp" }, { "id": "material-identity", "title": "Identify the material before interpreting activity", "category": "Measurement", "setting": "Methodological guidance", "statement": "The Fasolati research proposal separates bacterial burden, vesicle-associated material, non-vesicular material and functional activity. MISEV2023 is a methodological reference, not validation of a Fasolati assay.", "boundary": "Enrichment is not purity. A detected marker or active fraction alone is not sufficient to establish the identity, origin and activity of intact bacterial vesicles.", "next": "Specify collection, separation, identity, contamination, interference and repeatability controls before interpreting a proposed assay.", "sources": [ { "label": "MISEV2023 guidance", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10850029/" } ], "reviewed": "2026-09-12", "permalink": "https://fasolati.life/evidence/#claim-material-identity" }, { "id": "life-board-boundary", "title": "Life Board is a design demonstration", "category": "Design boundary", "setting": "Fasolati product-design rule", "statement": "The demonstration uses authored fictional observations to show change, missingness and disagreement across separate oral, gut and host-response channels.", "boundary": "It is not a live assay, clinical decision system, validated disease-risk score, patient record or completed clinical study.", "next": "Test whether reviewers understand the separation between observation, interpretation and the next question before considering clinical evaluation.", "sources": [], "reviewed": "2026-09-13", "permalink": "https://fasolati.life/evidence/#claim-life-board-boundary" }, { "id": "product-specific-evidence", "title": "Product claims require product-specific support", "category": "Design boundary", "setting": "Fasolati editorial rule", "statement": "Finished-product identity, current labeling, formulation and intended use must be verified before product-specific efficacy language or purchase instructions are added to the dossier.", "boundary": "An ingredient paper, periodontal-treatment trial or OMV mechanism study cannot be relabeled as a clinical result for Loria. A related brand is not evidence that two products have the same formulation.", "next": "Obtain approved product assets and source documents; have the responsible product and scientific reviewers approve the resulting dossier.", "sources": [], "reviewed": "2026-09-13", "permalink": "https://fasolati.life/evidence/#claim-product-specific-evidence" } ], "revisions": [ { "id": "exposure-route-2026-09-12", "date": "2026-09-12", "claimId": "endothelial-barrier", "title": "Made the exposure route explicit", "before": "The summary described endothelial-barrier disruption without naming the zebrafish exposure route.", "after": "The summary now states that the zebrafish experiments used direct systemic injection, not oral exposure.", "reason": "Prevent a model-delivery experiment from reading as a demonstrated natural oral-to-systemic route." }, { "id": "hepatic-setting-2026-09-12", "date": "2026-09-12", "claimId": "hepatic-insulin-signaling", "title": "Separated animal and cell findings", "before": "The summary grouped liver translocation, signaling and glycogen synthesis as effects in experimental systems.", "after": "Mouse liver translocation and glycogen findings are separated from the HepG2 insulin-signaling experiment.", "reason": "Readers should be able to tell which experimental system supports each statement." }, { "id": "foma-identity-2026-09-12", "date": "2026-09-12", "claimId": "fusobacterium-tissue-interactions", "title": "Narrowed the human-tissue statement", "before": "The summary described EV enrichment in clinical colorectal-cancer tissue.", "after": "The summary specifies five paired samples and greater FomA signal in EV-enriched tumor fractions, with a non-exclusive-marker caveat.", "reason": "Distinguish observed signal, the authors’ interpretation and separate model experiments." }, { "id": "glycemic-context-2026-09-12", "date": "2026-09-12", "claimId": "human-glycemic-control", "title": "Restored the clinical comparison and uncertainty", "before": "The clinical summary gave the average HbA1c reduction, population and time point without the comparator or confidence interval.", "after": "The wording includes no active treatment or usual care as the comparator and the 95% confidence interval.", "reason": "A treatment effect should travel with the comparison and its uncertainty." }, { "id": "crp-duration-2026-09-12", "date": "2026-09-12", "claimId": "human-crp", "title": "Added follow-up limits to the CRP result", "before": "The summary described lower CRP with heterogeneity but did not specify the six-month result.", "after": "The summary separates the six-month result from the smaller, limited longer-term analysis.", "reason": "Avoid implying a demonstrated durable effect across follow-up periods." } ] }