{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T18:20:01Z","timestamp":1782325201255,"version":"3.54.5"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aortic dissection (AD) is a life-threatening cardiovascular emergency characterized by rapid onset and high mortality. While surgery intervention, the primary treatment, improves short-term survival, it frequently leads to postoperative complications including systemic inflammatory response syndrome, gastrointestinal dysfunction, and anxiety\/depression. These complications may be exacerbated by dysregulation of the gut-brain axis (GBA). Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique known to exert anti-inflammatory, prokinetic, and neuroregulatory effects in various conditions; however, its application for managing postoperative complications in AD remains unexplored. This study aims to evaluate the efficacy and safety of taVNS in regulating the GBA among postoperative AD patients through a randomized controlled trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a single-center, randomized, investigator-blinded, sham-controlled randomized controlled trial. A total of 50 patients aged 18\u201375 years with postoperative Stanford Type A or B AD will be enrolled and randomly assigned in a 1:1 ratio to either the active taVNS group or the sham control group. Both groups will receive standard postoperative care. The experimental group will additionally receive active taVNS targeting the vagus nerve-innervated auricular area (15 Hz, 200 \u03bcs pulse width), while the control group will receive sham stimulation at a non-vagus innervated site without electrical current. The intervention will be administered for 30 min, twice daily, over 7 consecutive days, with follow-up assessments continuing until 24 weeks post-surgery. Primary outcomes include changes in gut microbiota diversity\/abundance and brain function (assessed via functional near-infrared spectroscopy). Secondary outcomes encompass inflammatory markers, plasma neurotransmitter levels, intestinal function recovery, and relevant psychometric scale scores. Safety will be monitored through vital signs, laboratory tests, and recording of any adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This study is the first to innovatively integrate taVNS with the GBA theory, investigating its multi-target mechanisms through a comprehensive set of biomarkers and clinical endpoints. If proven effective, taVNS could offer a safe and cost-effective non-pharmacological adjunctive therapy for managing postoperative complications in AD. Furthermore, the findings have the potential to elucidate the role of the GBA in the recovery trajectory of patients following major cardiovascular surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      Chinese Clinical Trial Registry (ChiCTR,\n                      <jats:ext-link>http:\/\/www.chictr.org.cn<\/jats:ext-link>\n                      ), No. ChiCTR2500102345, Date: May 13, 2025.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1692356","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:17:29Z","timestamp":1766063849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical efficacy and mechanisms of transcutaneous auricular vagus nerve stimulation targeting the gut-brain axis for postoperative complications of aortic dissection: study protocol for a randomized controlled trial"],"prefix":"10.3389","volume":"12","author":[{"given":"Bo","family":"Ning","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangbin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feisheng","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzuo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Bo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjun","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihai","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/S0140-6736(22)01970-5","article-title":"Acute aortic dissection","volume":"401","author":"Carrel","year":"2023","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3538","DOI":"10.1093\/eurheartj\/ehae179","article-title":"2024 ESC guidelines for the management of peripheral arterial and aortic diseases","volume":"45","author":"Mazzolai","year":"2024","journal-title":"Eur Heart J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e334","DOI":"10.1161\/CIR.0000000000001097","article-title":"2022 ACC\/AHA guideline for the diagnosis and management of aortic disease: a report of the American heart association\/American college of cardiology joint committee on clinical practice guidelines","volume":"146","author":"Isselbacher","year":"2022","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1093\/eurheartj\/ehad534","article-title":"The activator protein-1 complex governs a vascular degenerative transcriptional programme in smooth muscle cells to trigger aortic dissection and rupture","volume":"45","author":"Luo","year":"2024","journal-title":"Eur Heart J"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmatsci.2024.101363","article-title":"Mechanisms of aortic dissection: from pathological changes to experimental and in silico models","author":"Rolf-Pissarczyk","year":"2025","journal-title":"Prog Mater Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1093\/eurheartj\/ehac757","article-title":"Acute aortic dissection: evidence, uncertainties, and future therapies","volume":"44","author":"Rylski","year":"2023","journal-title":"Eur Heart J"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1126\/science.abi6087","article-title":"Signaling inflammation across the gut-brain axis","volume":"374","author":"Agirman","year":"2021","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1146\/annurev-immunol-101921-042929","article-title":"Neuroimmune interactions in the intestine","volume":"42","author":"Wallrapp","year":"2024","journal-title":"Annu Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.amjcard.2024.03.001","article-title":"Nature of neurological complications and outcome after surgery for Type A aortic dissection","volume":"219","author":"Biancari","year":"2024","journal-title":"Am J Cardiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"10861","DOI":"10.1007\/s12035-024-04228-y","article-title":"Emerging insights into postoperative neurocognitive disorders: the role of signaling across the gut-brain axis","volume":"61","author":"Yu","year":"2024","journal-title":"Mol Neurobiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1007\/s12264-020-00619-y","article-title":"Transcutaneous auricular vagus nerve stimulation: from concept to application","volume":"37","author":"Wang","year":"2021","journal-title":"Neurosci Bull"},{"key":"B12","doi-asserted-by":"publisher","first-page":"499","DOI":"10.3390\/biom15040499","article-title":"Heart rate variability, microvascular dysfunction, and inflammation: exploring the potential of taVNS in managing heart failure in type 2 diabetes mellitus","volume":"15","author":"Thal","year":"2025","journal-title":"Biomolecules"},{"key":"B13","doi-asserted-by":"publisher","first-page":"106440","DOI":"10.1016\/j.nbd.2024.106440","article-title":"Ameliorating effects of transcutaneous auricular vagus nerve stimulation on a mouse model of constipation-predominant irritable bowel syndrome","volume":"193","author":"Liu","year":"2024","journal-title":"Neurobiol Dis"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1016\/j.brs.2021.06.006","article-title":"Transcutaneous auricular vagus nerve stimulation influences gastric motility: a randomized, double-blind trial in healthy individuals","volume":"14","author":"Steidel","year":"2021","journal-title":"Brain Stimul"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1016\/j.jtcvs.2021.11.091","article-title":"The society of thoracic surgeons\/American association for thoracic surgery clinical practice guidelines on the management of Type b aortic dissection","volume":"163","author":"MacGillivray","year":"2022","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B16","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1055\/s-0042-1759494","article-title":"Guideline for the treatment of thoracic aortic dissection Type A: summary of the s2k guideline","volume":"70","author":"Kallenbach","year":"2022","journal-title":"Thorac Cardiovasc Surg"},{"key":"B17","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.brs.2023.02.008","article-title":"Transcutaneous auricular vagus nerve stimulation reduces cytokine production in sepsis: an open double-blind, sham-controlled, pilot study","volume":"16","author":"Wu","year":"2023","journal-title":"Brain Stimul"},{"key":"B18","doi-asserted-by":"publisher","first-page":"521","DOI":"10.14309\/ajg.0000000000002548","article-title":"Transcutaneous auricular vagal nerve stimulation is effective for the treatment of functional dyspepsia: a multicenter, randomized controlled study","volume":"119","author":"Shi","year":"2024","journal-title":"Am J Gastroenterol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1537515","DOI":"10.3389\/fmed.2025.1537515","article-title":"Neuroregulatory and clinical efficacy of auricular vagus nerve stimulation in elderly patients with chronic insomnia comorbid with functional dyspepsia: protocol for a randomized controlled trial","volume":"12","author":"Zhou","year":"2025","journal-title":"Front Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1016\/j.jtcvs.2024.07.015","article-title":"The burden of major complications on failure to rescue after surgery for acute Type A aortic dissection: analysis of more than 19,000 patients","volume":"169","author":"Diaz-Castrillon","year":"2025","journal-title":"J Thorac Cardiovasc Surg"},{"key":"B21","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/s41575-023-00890-0","article-title":"Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota-gut-brain axis","volume":"21","author":"Aburto","year":"2024","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/s41392-023-01673-4","article-title":"Gut liver brain axis in diseases: the implications for therapeutic interventions","volume":"8","author":"Yan","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B23","doi-asserted-by":"publisher","first-page":"15228","DOI":"10.1038\/s41598-017-15079-0","article-title":"Clinical parameters and gut microbiome changes before and after surgery in thoracic aortic dissection in patients with gastrointestinal complications","volume":"7","author":"Zheng","year":"2017","journal-title":"Sci Rep"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e34351","DOI":"10.1161\/JAHA.124.034351","article-title":"Quantitative electroencephalography for predication of neurological dysfunction in Type A aortic dissection: a prospective observational study","volume":"13","author":"Wang","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.1097\/JS9.0000000000002235","article-title":"Developing predictive nomogram models using quantitative electroencephalography for brain function in Type A aortic dissection: a prospective observational study","volume":"111","author":"Wang","year":"2025","journal-title":"Int J Surg"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e3091","DOI":"10.1002\/brb3.3091","article-title":"Quantitative EEG as a diagnostic and prognostic tool in hemispheric stroke patients undergoing Type A aortic dissection surgery","volume":"13","author":"Wang","year":"2023","journal-title":"Brain Behav"},{"key":"B27","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1186\/s12916-025-04126-7","article-title":"Baseline functional connectivity of the basal forebrain-cortical circuit predict taVNS treatment response in primary insomnia: a randomized controlled trial and fMRI study","volume":"23","author":"Qi","year":"2025","journal-title":"BMC Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.neurom.2025.02.003","article-title":"Accelerated transcutaneous auricular vagus nerve stimulation for inpatient depression and anxiety: the iWAVE open label pilot trial","volume":"28","author":"Austelle","year":"2025","journal-title":"Neuromodulation"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1002\/ueg2.70041","article-title":"Effects of transcutaneous auricular vagal nerve stimulation on chronic constipation: a multicenter, randomized controlled study","volume":"13","author":"Liu","year":"2025","journal-title":"United European Gastroenterol J"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1016\/j.brs.2022.09.003","article-title":"The efficacy and safety of transcutaneous auricular vagus nerve stimulation in patients with mild cognitive impairment: a double blinded randomized clinical trial","volume":"15","author":"Wang","year":"2022","journal-title":"Brain Stimul"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.3171\/2024.10.JNS241643","article-title":"Auricular vagus nerve stimulation for mitigation of inflammation and vasospasm in subarachnoid hemorrhage: a single-institution randomized controlled trial","volume":"142","author":"Huguenard","year":"2025","journal-title":"J Neurosurg"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1109\/JBHI.2023.3344176","article-title":"Enhancing motor sequence learning via transcutaneous auricular vagus nerve stimulation (taVNS): an EEG study","volume":"28","author":"Chen","year":"2024","journal-title":"IEEE J Biomed Health Inform"},{"key":"B33","doi-asserted-by":"publisher","first-page":"100462","DOI":"10.1016\/j.ijchp.2024.100462","article-title":"Transcutaneous auricular vagus nerve stimulation enhanced emotional inhibitory control via increasing intrinsic prefrontal couplings","volume":"24","author":"Zhu","year":"2024","journal-title":"Int J Clin Health Psychol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1536056","DOI":"10.3389\/fimmu.2025.1536056","article-title":"Transcutaneous auricular vagus nerve stimulation alleviates inflammation-induced depression by modulating peripheral-central inflammatory cytokines and the Nf-\u03baB pathway in rats","volume":"16","author":"Song","year":"2025","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"247","DOI":"10.3390\/biomedicines10020247","article-title":"Different transcutaneous auricular vagus nerve stimulation parameters modulate the anti-inflammatory effects on lipopolysaccharide-induced acute inflammation in mice","volume":"10","author":"Go","year":"2022","journal-title":"Biomedicines"},{"key":"B36","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1016\/j.brs.2020.03.011","article-title":"Stimulus frequency modulates brainstem response to respiratory-gated transcutaneous auricular vagus nerve stimulation","volume":"13","author":"Sclocco","year":"2020","journal-title":"Brain Stimul"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e70016","DOI":"10.1111\/adb.70016","article-title":"Transcutaneous auricular vagus nerve stimulation restores cognitive impairment in morphine-withdrawn rats: role of BDNF and glial cells in the hippocampus","volume":"30","author":"Nazari","year":"2025","journal-title":"Addict Biol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1692356\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:17:30Z","timestamp":1766063850000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1692356\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":37,"alternative-id":["10.3389\/fmed.2025.1692356"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1692356","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"article-number":"1692356"}}