{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:10:09Z","timestamp":1785859809677,"version":"3.56.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The etiology and pathogenesis of trigeminal neuralgia remain unclear. This study examines the connection between gut microbiota and trigeminal neuralgia using Mendelian randomization analysis to provide insights into the disorder\u2019s origin and propose potential therapies based on our findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used data from the MiBioGen consortium (13,266 participants) for gut microbiota and the IEU OpenGWAS project (800 cases, 195,047 controls) for trigeminal neuralgia. We checked for heterogeneity and horizontal pleiotropy and used the inverse variance weighting method as our main approach to study the causal link between gut bacteria and trigeminal neuralgia, MR-Egger, simple mode, weighted median, and weighted mode as supplementary methods, with a sensitivity test using leave-one-out analysis. If a bacteria-trigeminal neuralgia link was found, we conducted a reverse analysis for confirmation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>According to the final results, these groups include <jats:italic>Butyricimonas<\/jats:italic> (Genus, id = 945, <jats:italic>p<\/jats:italic>-value = 0.007, OR = 1.742, 95% CI: 1.165\u20132.604), <jats:italic>unknowngenus<\/jats:italic> (Genus, id = 1000005479, <jats:italic>p<\/jats:italic>-value = 0.005, OR = 1.774, 95% CI: 1.187\u20132.651) and <jats:italic>Bacteroidales<\/jats:italic> (Family, <jats:italic>p<\/jats:italic>-value = 0.005, OR = 1.774, 95% CI: 1.187\u20132.651) were causally associated with trigeminal neuralgia. No significant results according to reverse Mendelian randomization analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In our study, we identified specific gut bacteria linked to trigeminal neuralgia. To comprehensively understand their impact and mechanisms, additional randomized trials are necessary.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1420978","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T12:47:30Z","timestamp":1740660450000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigating the causal impact of gut microbiota on trigeminal neuralgia: a bidirectional Mendelian randomization study"],"prefix":"10.3389","volume":"16","author":[{"given":"Chuan","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaolong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunming","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haimin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1016\/S1474-4422(20)30233-7","article-title":"Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia.","volume":"19","author":"Bendtsen","year":"2020","journal-title":"Lancet Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"a041302","DOI":"10.1101\/cshperspect.a041302","article-title":"Mendelian randomization.","volume":"12","author":"Birney","year":"2022","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1002\/sim.6835","article-title":"Combining information on multiple instrumental variables in Mendelian randomization: Comparison of allele score and summarized data methods.","volume":"35","author":"Burgess","year":"2016","journal-title":"Stat. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1056\/NEJMra1914484","article-title":"Trigeminal neuralgia.","volume":"383","author":"Cruccu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1212\/WNL.0000000000002840","article-title":"Trigeminal neuralgia: New classification and diagnostic grading for practice and research.","volume":"87","author":"Cruccu","year":"2016","journal-title":"Neurology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"562812","DOI":"10.3389\/fcell.2020.562812","article-title":"The gut microbiota, kynurenine pathway, and immune system interaction in the development of brain cancer.","volume":"8","author":"Dehhaghi","year":"2020","journal-title":"Front. Cell. Dev. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1126\/science.1110591","article-title":"Diversity of the human intestinal microbial flora.","volume":"308","author":"Eckburg","year":"2005","journal-title":"Science (New York, N.Y.)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"E3","DOI":"10.3171\/foc.2005.18.5.4","article-title":"Trigeminal neuralgia: Definition and classification.","volume":"18","author":"Eller","year":"2005","journal-title":"Neurosurg. Focus"},{"key":"B9","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.tins.2013.01.005","article-title":"Gut-brain axis: How the microbiome influences anxiety and depression.","volume":"36","author":"Foster","year":"2013","journal-title":"Trends Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e1007081","DOI":"10.1371\/journal.pgen.1007081","article-title":"Orienting the causal relationship between imprecisely measured traits using GWAS summary data.","volume":"13","author":"Hemani","year":"2017","journal-title":"PLoS Genet."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"B12","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1186\/s12864-023-09608-7","article-title":"Gut microbiome causal impacts on the prognosis of breast cancer: A Mendelian randomization study.","volume":"24","author":"Hong","year":"2023","journal-title":"BMC Genomics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/j.freeradbiomed.2019.12.002","article-title":"Nitrate ameliorates dextran sodium sulfate-induced colitis by regulating the homeostasis of the intestinal microbiota.","volume":"152","author":"Hu","year":"2020","journal-title":"Free Radical Biol. Med."},{"key":"B14","year":"","journal-title":"Trigeminal Neuralgia Dataset: Finn-b-G6_TRINEU."},{"key":"B15","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s13075-023-03157-w","article-title":"Causal associations of Sj\u00f6gren\u2019s syndrome with cancers: A two-sample Mendelian randomization study.","volume":"25","author":"Jia","year":"2023","journal-title":"Arthritis Res. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1121273","DOI":"10.3389\/fimmu.2023.1121273","article-title":"The causality between intestinal flora and allergic diseases: Insights from a bi-directional two-sample Mendelian randomization analysis.","volume":"14","author":"Jin","year":"2023","journal-title":"Front. Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1186\/s12916-022-02657-x","article-title":"Association between gut microbiota and preeclampsia-eclampsia: A two-sample Mendelian randomization study.","volume":"20","author":"Li","year":"2022","journal-title":"BMC Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"23569","DOI":"10.1038\/s41598-021-02911-x","article-title":"Flow cytometry analysis of immune and glial cells in a trigeminal neuralgia rat model.","volume":"11","author":"Lin","year":"2021","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.neuron.2020.08.012","article-title":"Astrocyte crosstalk in CNS inflammation.","volume":"108","author":"Linnerbauer","year":"2020","journal-title":"Neuron"},{"key":"B20","doi-asserted-by":"publisher","first-page":"930318","DOI":"10.3389\/fimmu.2022.930318","article-title":"Causal effects of gut microbiota on diabetic retinopathy: A Mendelian randomization study.","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12916-023-02761-6","article-title":"Causal relationship between gut microbiota and cancers: A two-sample Mendelian randomisation study.","volume":"21","author":"Long","year":"2023","journal-title":"BMC Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1093\/brain\/124.12.2347","article-title":"Trigeminal neuralgia: Pathology and pathogenesis.","volume":"124","author":"Love","year":"2001","journal-title":"Brain"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1160993","DOI":"10.3389\/fcimb.2023.1160993","article-title":"Causal effects of gut microbiota on the risk of periodontitis: A two-sample Mendelian randomization study.","volume":"13","author":"Luo","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1016\/j.semcancer.2021.05.005","article-title":"Metabolic regulation on the immune environment of glioma through gut microbiota.","volume":"86","author":"Lyu","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1177\/0333102416687280","article-title":"Trigeminal neuralgia - Diagnosis and treatment.","volume":"37","author":"Maarbjerg","year":"2017","journal-title":"Cephalalgia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40168-016-0181-2","article-title":"Genomic characterization of the uncultured Bacteroidales family S24-7 inhabiting the guts of homeothermic animals.","volume":"4","author":"Ormerod","year":"2016","journal-title":"Microbiome"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3300","DOI":"10.1038\/s41467-019-10936-0","article-title":"Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits.","volume":"10","author":"Porcu","year":"2019","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1093\/neuonc\/noab208","article-title":"Relationship between genetically determined telomere length and glioma risk.","volume":"24","author":"Saunders","year":"2022","journal-title":"Neuro Oncol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/gepi.22295","article-title":"A comparison of robust Mendelian randomization methods using summary data.","volume":"44","author":"Slob","year":"2020","journal-title":"Genet. Epidemiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1907272","article-title":"Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease.","volume":"13","author":"Stoeva","year":"2021","journal-title":"Gut Microbes"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1093\/bioinformatics\/bty742","article-title":"MOLGENIS research: Advanced bioinformatics data software for non-bioinformaticians.","volume":"35","author":"van der Velde","year":"2019","journal-title":"Bioinformatics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1115014","DOI":"10.3389\/fmicb.2023.1115014","article-title":"Roles of gut microbiome in epilepsy risk: A Mendelian randomization study.","volume":"14","author":"Zeng","year":"2023","journal-title":"Front. Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1420978\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T12:47:35Z","timestamp":1740660455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1420978\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,27]]},"references-count":32,"alternative-id":["10.3389\/fmicb.2025.1420978"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1420978","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,27]]},"article-number":"1420978"}}