{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:23:27Z","timestamp":1792805007283,"version":"4.5.0"},"reference-count":40,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Joint Funds for the Innovation of Science and Technology, Fujian Province"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>\n                    Due to the unclear etiology and pathogenesis of temporomandibular joint disorders (TMDs), current treatments often fail to provide long-term relief or halt disease progression. Therefore, this study aims to explore the underlying etiologic mechanisms by focusing on the causal relationship between the gut microbiome (GM) and TMD through a multi-omics approach. This includes mendelian randomization (MR) analysis of GM, metabolomics, and TMD data, as well as transcriptomic analysis. In accordance with MR guidelines, we utilized summary-level genome-wide association study data to perform bidirectional MR, identifying 28 gut microbial taxa with causal effects on TMD. The following species had the strongest associations with TMD incidence:\n                    <jats:italic>RUG147 sp900315495<\/jats:italic>\n                    (odds ratio [OR], 2.016; 95% CI, 1.219 to 3.333;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.006),\n                    <jats:italic>CAG-194 sp002441865<\/jats:italic>\n                    (OR, 0.713; 95% CI, 0.555 to 0.916;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.008),\n                    <jats:italic>CAG-145 sp000435615<\/jats:italic>\n                    (OR, 1.166; 95% CI, 1.040 to 1.308;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.009), and\n                    <jats:italic>CAG-81 sp000435795<\/jats:italic>\n                    (OR, 1.150; 95% CI, 1.036 to 1.276;\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.009). To explore the mediating role of metabolites, a 2-step mediation MR approach was employed, revealing that lipid-related metabolites serve as key mediators in the GM-TMD interaction. Specifically, total cholesterol in high-density lipoprotein 3 was identified as a mediator of\n                    <jats:italic>CAG-145 sp000435615<\/jats:italic>\n                    on TMD (\u22124.13%). Further analysis based on transcriptomic data identified differentially expressed and shared genes between GM and TMD, with the AGE-RAGE (advanced glycation end products\u2013receptor for advanced glycation end products) and processes related to cell adhesion and inflammation emerging as significant pathways. These findings highlight the role of GM dysbiosis in TMD pathogenesis, potentially through disruptions in lipid metabolism and inflammatory processes, suggesting new therapeutic strategies targeting GM and its associated pathways.\n                  <\/jats:p>","DOI":"10.1177\/00220345251332885","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T03:12:12Z","timestamp":1750821132000},"page":"1257-1266","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["The Role of Gut Microbiome in Temporomandibular Joint Disorder Pathogenesis"],"prefix":"10.1177","volume":"104","author":[{"given":"Y.","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Orthodontics, Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4803-9580","authenticated-orcid":false,"given":"L.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7193-576X","authenticated-orcid":false,"given":"Z.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Stomatological Hospital of Xiamen Medical College, Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00890-0"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jormas.2021.08.003"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21965"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-021-00757-1"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2024.2420863"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102974"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12863-022-01082-6"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29153649"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyac004"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.100989"},{"issue":"9","key":"e_1_3_3_12_1","first-page":"5357","article-title":"Expression profile of circular RNA s in TMJ osteoarthritis synovial tissues and potential functions of hsa_circ_0000448 with specific back-spliced junction","volume":"11","author":"Hu Y","year":"2019","unstructured":"Hu Y, Zhu H, Bu L, He D. 2019. 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Am J Transl Res. 11(9):5357\u20135374.","journal-title":"Am J Transl Res"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq243"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07148-y"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202308313"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102559"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-0985"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.01.016"},{"issue":"1","key":"e_1_3_3_20_1","first-page":"52","article-title":"Temporomandibular disorders: rapid evidence review","volume":"107","author":"Matheson EM","year":"2023","unstructured":"Matheson EM, Fermo JD, Blackwelder RS. 2023. Temporomandibular disorders: rapid evidence review. 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