{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:50:51Z","timestamp":1786600251985,"version":"build-2736575974"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3500500, 2022YFC3500503, SQ2023YFC3500018"],"award-info":[{"award-number":["2022YFC3500500, 2022YFC3500503, SQ2023YFC3500018"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study investigates the therapeutic mechanisms of electroacupuncture (EA) in regulating the vagal nerve for functional dyspepsia (FD) using an integrated multi-omics approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      A rat model of FD was established via iodoacetamide gavage combined with tail-clamp stress. Rats were randomly assigned to five groups (n=6 per group): control (CON), model (MOD), electroacupuncture (EA), subdiaphragmatic vagotomy and electroacupuncture (SDV+EA), and subdiaphragmatic vagotomy (SDV). EA was administered at ST36 (Zusanli) and ST37 (Shangjuxu) for 20 minutes per session, once daily for 14 days. EA treatment restored vagal tone, improved sympathovagal balance, and enhanced gastrointestinal motility in FD model rats. 16S rDNA sequencing revealed that EA modulated vagus nerve-dependent changes in the relative abundance of 12 microbial taxa, including\n                      <jats:italic>f_Lactobacillaceae<\/jats:italic>\n                      and\n                      <jats:italic>f_Peptostreptococcaceae<\/jats:italic>\n                      . Crucially, the vagotomy procedure significantly attenuated EA\u2019s restorative effects on these microbial populations. Metabolomics identified 24 differential metabolites regulated by EA through the vagus nerve, including Cholesta-3,5-dien-7-one, Licofelone, Digoxigenin, 7-Hydroxymethotrexate, Hydroxymethylbilane, among others. Similarly, subdiaphragmatic vagotomy largely reversed the normalizing effects of EA on these metabolite levels. Transcriptomics, on the other hand, identified 23 differential genes, including Prss22, Lypd3, and Tnfrsf12a. KEGG analysis of differential metabolites and differential genes suggested that arachidonic acid metabolism may represent a potential therapeutic target for EA in the treatment of FD through vagus nerve modulation. Mechanistic analyses of the key differentially expressed gene\n                      <jats:italic>Tnfrsf12a<\/jats:italic>\n                      and the arachidonic acid metabolic pathway demonstrated that EA attenuated inflammatory responses by suppressing TWEAK\/Fn14\/NF-\u03baB pathway activation and arachidonic acid metabolism, leading to decreased levels of TNF-\u03b1, IL-1\u03b2, IL-6, and PGE\n                      <jats:sub>2<\/jats:sub>\n                      . Importantly, the anti-inflammatory effects of EA were significantly attenuated in the SDV+EA group, confirming that vagal integrity is essential for EA to fully exert its suppressive action on these key inflammatory pathways and mediators.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>EA ameliorates FD by modulating vagal nerve activity, concurrently suppressing TWEAK\/Fn14\/NF-\u03baB pathway activation and arachidonic acid metabolism, thus attenuating duodenal low-grade inflammation in FD model rats. These findings demonstrate the potential of EA as an effective therapeutic intervention for FD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1746351","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T10:53:23Z","timestamp":1773140003000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Electroacupuncture alleviates functional dyspepsia by modulating the vagus nerve to regulate duodenal microbiota and suppress TWEAK\/Fn14\/NF-\u03baB and arachidonic acid metabolic pathways"],"prefix":"10.3389","volume":"17","author":[{"given":"Xueping","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine, Wangjing Hospital, China Academy of Chinese Medical Sciences","place":["Beijing, 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