Periodontal pathogen–driven endotoxemia and bacteremia as a mechanistic link to liver disease. A scoping review

OBJECTIVE: This scoping review aimed to map and synthesize the available evidence linking periodontal pathogen-derived endotoxemia and bacteremia to liver abnormalities and to identify the biological mechanisms potentially involved in hepatic injury. DESIGN: Following PRISMA-ScR guidelines, comprehensive electronic searches were conducted across major databases, including MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL, complemented by grey literature sources. Experimental and clinical studies reporting endotoxemia and/or bacteremia attributable to periodontal pathogens in association with liver-related outcomes were included without restrictions on study design or language. Data extraction and study selection were performed in duplicate. Methodological appraisal was conducted using the SYRCLE risk of bias tool for animal studies and the Joanna Briggs Institute checklist for case reports. RESULTS: Twenty studies met the inclusion criteria, comprising experimental animal studies and clinical case reports. Porphyromonas gingivalis was the most frequently investigated pathogen, followed by Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum. Experimental evidence consistently demonstrated that periodontal pathogen-derived endotoxemia and bacteremia promote hepatic inflammation, oxidative stress, lipid dysregulation, steatosis, hepatocyte injury, and fibrogenic remodeling. Reported mechanisms included activation of Toll-like receptor signaling, Galectin-3 accumulation, TGF-β1/Smad-mediated fibrogenesis, hepatic stellate cell activation, and endoplasmic reticulum stress. Clinical reports further linked odontogenic infections to severe hepatic complications, including pyogenic liver abscesses and cirrhosis. CONCLUSION: The available evidence supports a biologically plausible role for periodontal pathogen-derived endotoxemia and bacteremia in the initiation and progression of liver disease. However, the current evidence base is predominantly preclinical, highlighting the need for well-designed human studies to establish causality and clinical relevance.