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However, the specific mechanisms underlying this association remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This population\u2010based study included 478,000 participants from the UK Biobank (mean age: 56.5 years; 54.4% females). The Oral Health Score (OHS) and Periodontal Disease Risk (PDR) Index were developed from six baseline oral health symptoms to evaluate the combined effects of oral health on MASLD risk. Mediation analysis was conducted to investigate potential nutrition\u2013metabolism pathways involving 142 metabolic factors. A Polygenic Risk Score (PRS) was constructed to assess the joint impact and potential interactions between oral health and genetic susceptibility on MASLD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During a median follow\u2010up of 13.2 years, 6980 MASLD cases were ascertained. Painful gums showed the strongest association with MASLD risk among six oral symptoms (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.28\u20131.58,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a01.51 \u00d7 10\n                      <jats:sup>\u221210<\/jats:sup>\n                      ). Poor oral health was associated with a 60% increased MASLD risk (HR: 1.60, 95% CI: 1.42\u20131.80,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a01.13 \u00d7 10\n                      <jats:sup>\u221214<\/jats:sup>\n                      ), while PDR index indicated an 18% increase (HR: 1.18, 95% CI: 1.11\u20131.25,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a02.31 \u00d7 10\n                      <jats:sup>\u22128<\/jats:sup>\n                      ). Several metabolomic pathways\u2014particularly those involving very low\u2010density lipoproteins, fatty acids, and triglycerides\u2014significantly mediated the association, explaining up to 19.4% of the relationship. Across genetic risk strata, both OHS and PDR remained independently associated with MASLD incidence (HR range: 1.28\u20133.68).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Poor oral health and periodontal disease may contribute to an increased risk of MASLD by regulating the metabolic milieu, independently of genetic predisposition. As a modifiable and nutritionally relevant factor, oral health represents a promising target for early MASLD prevention. Integrating dental and metabolic care through a multidisciplinary approach could improve liver outcomes by modulating the oral\u2013gut\u2013liver axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Investigated the association between oral health and metabolic dysfunction\u2010associated steatotic liver disease (MASLD) in a 13\u2010year prospective cohort of \u223c0.5 million individuals.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Explored the potential mediating roles of 142 circulating metabolic biomarkers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Assessed the modifying role of genetic susceptibility in the oral health\u2010MASLD link.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Provided novel evidence supporting the oral\u2013gut\u2013liver axis in metabolic disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain language summary<\/jats:title>\n                    <jats:p>In this study, nearly half a million UK Biobank participants were followed over 13 years to investigate the association between oral health and liver disease. Poor oral health and periodontal disease were associated with an increased risk of developing metabolic dysfunction\u2010associated steatotic liver disease (MASLD), a common chronic liver condition. Further analyses suggest that genetic susceptibility and metabolic alterations may underlie this association. These findings underscore the interconnections of the oral cavity, gut, and liver, and highlight the potential systemic benefits of maintaining good oral health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.70029","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:46:28Z","timestamp":1761763588000},"page":"1116-1129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Genetic susceptibility and metabolic pathways linking oral health to metabolic dysfunction\u2010associated steatotic liver disease"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2300-6117","authenticated-orcid":false,"given":"Xinjian","family":"Ye","sequence":"first","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province  Hangzhou China"},{"name":"Department of Developmental Biology Harvard School of Dental Medicine  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Public Health Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province  Hangzhou 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