{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T18:29:19Z","timestamp":1787336959310,"version":"build-2736575974"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["NO.2024NSFSC0560"],"award-info":[{"award-number":["NO.2024NSFSC0560"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NO: 82405564"],"award-info":[{"award-number":["NO: 82405564"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["NO.CSTB2022NSCQ-MSX1559;No. CSTB2023NSCQ-MSX0884"],"award-info":[{"award-number":["NO.CSTB2022NSCQ-MSX1559;No. CSTB2023NSCQ-MSX0884"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific and Technological Research Program of Chongqing Municipal Education Commission","award":["NO.KJQN202315124\uff1bKJQN202515117"],"award-info":[{"award-number":["NO.KJQN202315124\uff1bKJQN202515117"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Functional dyspepsia (FD) is characterized by duodenal mucosal barrier dysfunction and chronic low-grade inflammation. Macrophage polarization imbalance, particularly the predominance of pro-inflammatory M1 over anti-inflammatory M2 phenotypes, contributes significantly to FD pathogenesis. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising non-invasive therapeutic approach for gastrointestinal disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the therapeutic mechanisms of taVNS in FD treatment, specifically focusing on its effects on M2 macrophage polarization and the roles of metabolic regulator UCP2 and transcription factor GATA3 in this process.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6J mice (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200927) and\n                      <jats:italic>Gata3<\/jats:italic>\n                      <jats:sup>\u2206mac<\/jats:sup>\n                      mice (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20099), totaling 36 mice were used to establish an FD model through multi-factorial stress induction and were divided into four experimental groups. taVNS treatment was administered for 2 weeks. Feeding behavior, duodenal mucosal inflammatory cytokines, inflammatory markers, macrophage polarization markers, and intestinal barrier function were assessed.\n                      <jats:italic>Gata3<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2206<\/jats:italic>\n                        mac\n                      <\/jats:sup>\n                      \u2009+\u2009taVNS mice were used to determine the transcription factor\u2019s role in taVNS-mediated effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TaVNS treatment significantly improved feeding behavior in FD mice. At the duodenal mucosal level, taVNS markedly reduced the elevated IL-1\u03b2levels and restored the suppressed TGF-\u03b21 levels. TaVNS also promoted M2 macrophage polarization, as evidenced by decreased\n                      <jats:italic>Nos2<\/jats:italic>\n                      expression and increased Arg1 expression. TaVNS partially restored\n                      <jats:italic>Ucp2<\/jats:italic>\n                      and\n                      <jats:italic>Gata3<\/jats:italic>\n                      expression relative to FD mice, elevated the expression of tight junction ZO-1 to relieve duodenal tight junction impairment linked to barrier dysfunction, and modulated inflammatory responses (decreased TNF-\u03b1, increased IL-10). The therapeutic effects of taVNS were significantly attenuated in\n                      <jats:italic>Gata3<\/jats:italic>\n                      <jats:sup>\u2206mac<\/jats:sup>\n                      \u2009+\u2009taVNS mice, confirming the critical role of GATA3 in mediating taVNS-induced M2 polarization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>taVNS promotes M2 macrophage polarization to treat FD through mechanisms involving both metabolic regulation (UCP2) and transcriptional control (GATA3). These findings provide novel insights into the immunometabolic mechanisms underlying taVNS therapy and support its clinical application for FD management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0328670","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:38:06Z","timestamp":1787333886000},"page":"e0328670","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of transcutaneous bilateral auricular vagus nerve stimulation in treating functional dyspepsia through promoting M2 macrophage 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