{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:03:01Z","timestamp":1772118181006,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["No. 2514050000156"],"award-info":[{"award-number":["No. 2514050000156"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraines impose a substantial economic and societal burden, yet their underlying mechanisms remain poorly understood. While observational studies suggest associations between gut microbiota dysbiosis, immunophenotypic alterations, and migraine risk, causal evidence is lacking. This study leverages Mendelian Randomization to investigate the causal relationship between gut microbiota and migraine while exploring the mediating role of immune traits in this association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed a two\u2010sample, two\u2010step Mendelian Randomization approach to examine the mediating effects of immunocyte phenotypes on the relationship between gut microbiota and migraine outcomes, including migraine with aura and migraine without aura. The primary analysis utilized inverse\u2010variance weighted estimation, supplemented by sensitivity analyses to ensure robustness. Summary statistics for gut microbiota were sourced from the MiBioGen consortium and NHGRI\u2010EBI, immunocyte phenotypes from the GWAS catalog, and migraine data from the FinnGen consortium. Next, we evaluated\n                      <jats:italic>Prevotella histicola<\/jats:italic>\n                      level by qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analysis identified suggestive associations between 34 gut microbiota taxa and migraine subtypes. Notably, Family\n                      <jats:italic>Bifidobacteriaceae<\/jats:italic>\n                      (id.433, PIVW: 1.51\u00d710\u207b\u2075, ORIVW: 0.861, 95% CI: 0.765\u20130.970) and Order\n                      <jats:italic>Bifidobacteriales<\/jats:italic>\n                      (id.432, PIVW: 1.51\u00d710\u207b\u2075, ORIVW: 0.861, 95% CI: 0.765\u20130.970) demonstrated strong causal links to a reduced risk of migraine. Mediation analysis revealed that HLA\u2010DR on monocytes mediated 7.74% of the causal pathway from Genus\n                      <jats:italic>Prevotella9<\/jats:italic>\n                      (id.11183, PIVW: 0.002, ORIVW: 0.834, 95% CI: 0.744\u20130.936) to MA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study provides robust evidence of a causal relationship between\n                      <jats:italic>Bifidobacteriaceae<\/jats:italic>\n                      and a decreased risk of migraine. Furthermore, we identify HLA\u2010DR on monocytes as a key inflammatory mediator in the protective effect of\n                      <jats:italic>Prevotella<\/jats:italic>\n                      against migraine with aura. These findings highlight the potential of gut microbiota modulation and immune\u2010targeted therapies in migraine prevention and treatment, offering novel insights into the gut\u2010brain\u2010immune axis in migraine pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70693","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T07:45:13Z","timestamp":1752219913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dissecting Causal Relationships Between Gut Microbiota, Immunocyte Phenotype, and Migraine: A Mendelian Randomization Study"],"prefix":"10.1002","volume":"15","author":[{"given":"Yupei","family":"Lai","sequence":"first","affiliation":[{"name":"The Third Affiliated Hospital of Southern Medical University Guangzhou 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