{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:01:47Z","timestamp":1790787707981,"version":"4.1.0"},"reference-count":102,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although periodontal disease (PD) is reported to be associated with changes in various genes and proteins in both invading bacteria and the host, its molecular mechanism of pathogenesis remains unclear. Changes in immune and inflammatory genes play a significant role in PD pathogenesis. Some reports relate alterations in cellular epigenetic patterns to PD characteristics, while several high-throughput analyses indicate thousands of differentially methylated genes in both PD patients and controls. Furthermore, changes in DNA methylation patterns in inflammation-related genes have been linked to the efficacy of periodontal therapy, as demonstrated by findings related to the cytochrome C oxidase II gene. Distinct DNA methylation patterns in mesenchymal stem cells from PD patients and controls persisted despite the reversal of phenotypic PD. Methyl groups for DNA methylation are supplied by S-adenosylmethionine, which is synthesized with the involvement of folate, an essential nutrient known to play a role in maintaining mitochondrial homeostasis, reported to be compromised in PD. Folate may benefit PD through its antioxidant action against reactive oxygen and nitrogen species that are overproduced by dysfunctional mitochondria. As such, DNA methylation, dietary folate, and mitochondrial quality control may interact in PD pathogenesis. In this narrative\/hypothesis review, we demonstrate how PD is associated with changes in mitochondrial homeostasis, which may, in turn, be improved by folate, potentially altering the epigenetic patterns of immune and inflammatory genes in both the nucleus and mitochondria. Therefore, a folate-based dietary intervention is recommended for PD prevention and as an adjunct therapy. At the same time, further research is needed on the involvement of epigenetic mechanisms in the beneficial effects of folate on PD studies.<\/jats:p>","DOI":"10.3390\/ijms26073225","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T03:25:02Z","timestamp":1743391502000},"page":"3225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["DNA Methylation in Periodontal Disease: A Focus on Folate, Folic Acid, Mitochondria, and Dietary Intervention"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-4783","authenticated-orcid":false,"given":"Elzbieta","family":"Pawlowska","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Szczepanska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-271X","authenticated-orcid":false,"given":"Marcin","family":"Derwich","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Sobczuk","sequence":"additional","affiliation":[{"name":"Emergency Medicine and Disaster Medicine Department, Medical University of Lodz, Pomorska 251, 92-209 Lodz, Poland"},{"name":"Department of Orthopaedics and Traumatology, Polish Mothers\u2019 Memorial Hospital\u2014Research Institute, Rzgowska 281, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6159-1391","authenticated-orcid":false,"given":"Nejat","family":"D\u00fczg\u00fcne\u015f","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of the Pacific\u2014San Francisco Campus, San Francisco, CA 94103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9539-9584","authenticated-orcid":false,"given":"Janusz","family":"Blasiak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Collegium Medicum, The Mazovian University in Plock, 04-920 Plock, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bezerra, B., Monajemzadeh, S., Silva, D., and Pirih, F.Q. 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