{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:34:31Z","timestamp":1792114471606,"version":"4.4.0"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union NextGeneration EU","award":["PNRR-M4C2-I1.3"],"award-info":[{"award-number":["PNRR-M4C2-I1.3"]}]},{"name":"Andrea Ballini and Lorenzo Lo Muzio","award":["PE_00000019\u2014CUP D73C22001230006"],"award-info":[{"award-number":["PE_00000019\u2014CUP D73C22001230006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dentistry Journal"],"abstract":"<jats:p>Background: Periodontal dysbiosis contributes to liver injury through systemic inflammation, oral\u2013gut microbial translocation, and endotoxemia. Lipopolysaccharides (LPSs) and virulence factors derived from periodontal pathogens, particularly Porphyromonas gingivalis (P. gingivalis) activate Toll-like receptor (TLR) signaling, trigger NF-\u03baB-mediated cytokine release (e.g., TNF-\u03b1, IL-1\u03b2, IL-6), and promote oxidative stress and Kupffer cell activation within the liver. The present systematic review summarized clinical evidence supporting these mechanistic links between periodontal pathogens and hepatic outcomes, highlighting the role of microbial crosstalk in liver pathophysiology. Methods: A PRISMA-compliant systematic review was conducted by searching PubMed, Scopus, and the Cochrane library, as well as gray literature. Eligible study designs were observational studies and trials evaluating P. gingivalis and other periodontal pathogens (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, and Tannerella forsythia) for liver phenotypes (Non-Alcoholic Fatty Liver Disease [NAFLD]\/Metabolic Dysfunction-Associated Steatotic Liver Disease [MASLD], fibrosis\/cirrhosis, acute alcoholic hepatitis [AAH], and Hepatocellular carcinoma [HCC]). Risk of bias was assessed using the Newcastle\u2013Ottawa Scale adapted for cross-sectional studies (NOS-CS) for observational designs and the RoB 2 scale for single randomized controlled trials (RCTs). Due to the heterogeneity of exposures\/outcomes, results were summarized narratively. Results: In total, twenty studies (2012\u20132025; ~34,000 participants) met the inclusion criteria. Population-level evidence was conflicting (no clear association between anti-P. gingivalis serology and NAFLD), while clinical cohorts more frequently linked periodontal exposure, particularly to P. gingivalis, to more advanced liver phenotypes, including fibrosis. Microbiome studies suggested stage-related changes in oral communities rather than the effect of a single pathogen, and direct translocation into ascitic fluid was not observed in decompensated cirrhosis. Signals from interventional and behavioral research (periodontal therapy; toothbrushing frequency) indicate a potential modifiability of liver indices. The overall methodological quality was moderate with substantial heterogeneity, precluding meta-analysis. Conclusions: Current evidence supports a biologically plausible oral\u2013liver axis in which periodontal inflammation, often involving P. gingivalis, is associated with liver damage. Causality has not yet been proven; however, periodontal evaluation and treatment may represent a low-risk option in periodontitis-associated NAFLD. Well-designed, multicenter prospective studies and randomized trials with standardized periodontal and liver measurements are needed.<\/jats:p>","DOI":"10.3390\/dj13110503","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T17:32:01Z","timestamp":1762191121000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Liver Disease and Periodontal Pathogens: A Bidirectional Relationship Between Liver and Oral Microbiota"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-3457","authenticated-orcid":false,"given":"Mario","family":"Dioguardi","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Lo Muzio","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences, University of Bologna, Via San Vitale 59, 40125 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciro","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Sovereto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9864-9347","authenticated-orcid":false,"given":"Enrica","family":"Laneve","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1082-7293","authenticated-orcid":false,"given":"Angelo","family":"Martella","sequence":"additional","affiliation":[{"name":"DataLab, Department of Engineering for Innovation, University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8116-9614","authenticated-orcid":false,"given":"Riccardo","family":"Aiuto","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, Istituto Stomatologico Italiano, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8516-8352","authenticated-orcid":false,"given":"Daniele","family":"Garcovich","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Universidad Europea de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia Apollonia","family":"Caloro","sequence":"additional","affiliation":[{"name":"Unit\u00e0 Operativa Nefrologia e Dialisi, Presidio Ospedaliero Scorrano, ASL (Azienda Sanitaria Locale) Lecce, Via Giuseppina Delli Ponti, 73020 Scorrano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9521-2521","authenticated-orcid":false,"given":"Stefania","family":"Cantore","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania Luigi Vanvitelli, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-4893","authenticated-orcid":false,"given":"Lorenzo","family":"Lo Muzio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8758-1415","authenticated-orcid":false,"given":"Andrea","family":"Ballini","sequence":"additional","affiliation":[{"name":"Department of Life Science, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.23736\/S0026-4806.18.05858-5","article-title":"Liver diseases in the elderly","volume":"110","author":"Durazzo","year":"2019","journal-title":"Minerva Medica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100825","DOI":"10.1016\/j.identj.2025.03.029","article-title":"Emerging Roles of Periodontal Pathogen-Derived Outer Membrane Vesicles in NAFLD","volume":"75","author":"Lv","year":"2025","journal-title":"Int. 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