{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:01:24Z","timestamp":1787029284857,"version":"build-2736575974"},"reference-count":153,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The oral cavity contains a diverse group of bacteria in the saliva, as well as structured aggregates of bacterial cells on the mucosal surfaces. Oral microbiota (OM) dysbiosis not only induces local inflammation, it can also trigger systemic inflammation leading to metabolic diseases and neuropsychiatric diseases (NPDs). While primary evidence indicates that oral microbiota dysbiosis induces gut microbiota aberrations, which exacerbate inflammation associated with metabolic diseases (obesity, dyslipidemia, diabetes, nonalcoholic fatty liver disease (NAFLD), and insulin resistance), other studies revealed the contribution of the oral microbiota\u2013brain axis in the pathogenesis of NPDs. GM dysbiosis and inflammation also induce epigenetic alterations in cytokine genes, such as IL-1\u03b2, IL-6, TNF-\u03b1, NF-kB, BTLA, IL-18R1, TGF-\u03b2, P13k\/Akt1, Ctnnb1, and Hsp90aa1, as well as DNMTs, HDACs, and DAT1 associated with the development and progression of metabolic disorders and\/or NPDs. Therefore, the epigenome could serve as a target for preventive or therapeutic interventions. Here, we (i) review emerging evidence of the potential impact of OM dysbiosis in the pathogenesis of metabolic diseases and NPDs, (ii) highlight the relationship between OM-induced inflammation and epigenetic alterations driving NPDs pathogenesis and interlinked metabolic aberrations, (iii) discuss therapeutic approaches capable of treating metabolic diseases and NPDs through reshaping the microbiota and its epigenetic metabolites, and hence mitigating epigenetic aberrations linked to metabolic diseases and NPDs. Finally, we outline challenges and current research gaps related to investigating the relationship between microbiota, epigenetic aberrations, and metabolic abnormalities associated with NPDs.<\/jats:p>","DOI":"10.3390\/nu17213367","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T13:59:36Z","timestamp":1761659976000},"page":"3367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Oral\u2013Gut Microbiota Crosstalk and Epigenetic Targets in Metabolic and Neuropsychiatric Diseases"],"prefix":"10.3390","volume":"17","author":[{"given":"Sahar","family":"Mostafavi","sequence":"first","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, Tufts University School of Dental Medicine, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4944-7033","authenticated-orcid":false,"given":"Shabnam","family":"Nohesara","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics), Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Pirani","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Psychosocial Health Research Institute, Iran University of Medical Sciences, Tehran 14535, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8872-5174","authenticated-orcid":false,"given":"Hamid","family":"Mostafavi Abdolmaleky","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics), Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA"},{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5211-266X","authenticated-orcid":false,"given":"Sam","family":"Thiagalingam","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics), Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA"},{"name":"Department of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bransfield, R.C., Mao, C., and Greenberg, R. 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