{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:27:15Z","timestamp":1786602435398,"version":"build-2736575974"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Migraine is a debilitating neurological disorder with marked sex differences, as women experience a prevalence two to three times higher than men. Although the gut\u2013brain axis has been implicated in migraine biology, the intersection of sex hormones, microbial signaling, and microbial metabolites remains underexplored. This review evaluates migraine-specific and mechanistically relevant evidence on sex-related microbial and metabolic profiles to examine their potential relevance to sex-related characteristics of migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This narrative review was informed by a structured literature search of PubMed through May 2026, identifying 22 relevant studies, including clinical studies, interventional studies, animal models, and mechanistic investigations. Given heterogeneity in study design, sequencing methods, sampling strategies, clinical populations, and outcome measures, evidence was synthesized narratively to develop a hypothesis-generating framework for interactions among sex hormones, microbiota, microbial metabolites, and migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Current evidence suggests that gut microbial diversity and composition may be altered in migraine, but sex-stratified migraine-specific data remain limited. Female migraine cohorts have shown reduced abundances of taxa such as\n                      <jats:italic>Clostridia<\/jats:italic>\n                      and\n                      <jats:italic>Ruminococcus<\/jats:italic>\n                      , alongside enrichment of pro-inflammatory genera including\n                      <jats:italic>Desulfovibrio<\/jats:italic>\n                      and\n                      <jats:italic>Gemmiger<\/jats:italic>\n                      , with reported associations with inflammatory markers such as interleukin-6 and lipopolysaccharide. Metabolic studies suggest alterations in the tryptophan\u2013kynurenine pathway, including kynurenic acid\/quinolinic acid-related changes, whereas direct evidence for sex-specific short-chain fatty acid or neuroactive metabolite profiles in migraine remains limited. Mechanistically, the estrobolome provides a biologically plausible but incompletely validated link through which sex hormones and microbial enzymes may interact with hormone metabolism, gut barrier function, inflammatory tone, and neuroimmune signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The sex hormone\u2013microbiota\u2013metabolite\u2013brain axis should be considered a hypothesis-generating framework rather than an established causal mechanism for migraine sex differences. Future research should use sex-balanced longitudinal cohorts, menstrual-cycle-aware sampling, migraine-specific models, and integrated multi-omics to validate candidate pathways and determine whether microbiome-related signatures can inform sex-stratified biomarkers or adjunctive microbiome-targeted interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1891150","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:33:18Z","timestamp":1786599198000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The microgenderome in migraine: integrating sex hormones, microbial composition, and metabolic profiles into a sex-related framework"],"prefix":"10.3389","volume":"17","author":[{"given":"Jie","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianzun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huadong","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/s10194-025-02153-6","article-title":"Impact of visceral pain on migraine symptoms in comorbid patients: A retrospective observational study.","volume":"26","author":"Affaitati","year":"2025","journal-title":"J. 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