{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:25:10Z","timestamp":1787034310279,"version":"build-2736575974"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013317","name":"Shanxi Provincial Key Research and Development Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013317","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004480","name":"Natural Science Foundation of Shanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004480","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Background<\/jats:title>\n Aneurysmal subarachnoid hemorrhage (aSAH) is frequently followed by persistent cognitive impairment, characterized by a complex and multifactorial pathological mechanism. While the role of the \u201cmicrobiota-gut-brain axis\u201d in neurocognition has garnered increasing attention, the specific ways in which gut microbiota and their derived metabolites might be associated with the development and progression of post-aSAH cognitive impairment remain largely undefined. Consequently, there remains a lack of systematic multi-omics evidence to elucidate these potential underlying associations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this prospective observational study, we enrolled 48 patients with intracranial aneurysms. Among them, patients with aSAH (\n n<\/jats:italic>\n = 33) were divided into a cognitive impairment group (aSAH-CI,\n n<\/jats:italic>\n = 18) and a group without cognitive impairment (aSAH-WCI,\n n<\/jats:italic>\n = 15) based on a 6-month longitudinal neurocognitive assessment. Patients with unruptured intracranial aneurysms (UIA,\n n<\/jats:italic>\n = 15) served as the control group. We integrated a multi-omics approach encompassing fecal metagenomics, untargeted metabolomics, and serological profiles of inflammation, oxidative stress, and apoptosis to explore the potential correlations between the host and the microbiome, as well as to identify early diagnostic biomarkers.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Fecal metagenomics revealed distinct gut dysbiosis in aSAH-CI patients, characterized by reduced alpha diversity, depletion of beneficial commensals (e.g.,\n Agathobacter<\/jats:italic>\n ), and expansion of opportunistic pathogens (e.g.,\n Enterococcus<\/jats:italic>\n ). Functional and metabolomic analyses identified a significant alteration in aromatic amino acid biosynthesis. Specifically, tyrosine metabolism was altered, marked by reduced levels of neurotransmitter precursors and elevated neurotoxic trace amines (tyramine and phenylethylamine). Serologically, aSAH-CI patients exhibited heightened systemic inflammation, oxidative stress, and apoptosis. Integrated multi-omics network analysis underscored a strong correlation between elevated trace amines, depleted\n Agathobacter<\/jats:italic>\n , and systemic pathological indices. Notably,\n Agathobacter rectalis<\/jats:italic>\n and tyramine demonstrated robust potential as early diagnostic biomarkers for cognitive impairment following aSAH.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our findings suggest a potential dual-hit correlative signature via the microbiota-gut-brain axis in cognitive impairment following aSAH. We hypothesize that the depletion of aromatic amino acid-producing microbiota correlates with reduced neurotransmitter precursors, theoretically impairing synaptic repair. Concurrently, observed associations among opportunistic pathogens, trace amines, and systemic inflammatory and oxidative stress markers suggest a synergistic effect potentially linked to further neuronal damage.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1870309","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:36:32Z","timestamp":1787031392000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota dysbiosis and aromatic amino acid metabolism alterations: a multi-omics analysis of cognitive impairment following aneurysmal subarachnoid hemorrhage"],"prefix":"10.3389","volume":"17","author":[{"given":"Wentian","family":"Zhang","sequence":"first","affiliation":[{"name":"The First Clinical School of Medicine, Shanxi Medical University","place":["Taiyuan, China"]},{"name":"Department of Neurosurgery, Cardiovascular Hospital Affiliated to Shanxi Medical University","place":["Taiyuan, China"]},{"name":"Shanxi Key Laboratory of Heart Failure Precision Medicine","place":["Taiyuan, China"]},{"name":"Department of Neurosurgery, The First Hospital of Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Academy of Medical Sciences, Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Public Health, Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guopeng","family":"Kuang","sequence":"additional","affiliation":[{"name":"The First Clinical School of Medicine, Shanxi Medical University","place":["Taiyuan, China"]},{"name":"Department of Neurosurgery, The First Hospital of Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Cardiovascular Hospital Affiliated to Shanxi Medical University","place":["Taiyuan, China"]},{"name":"Shanxi Key Laboratory of Heart Failure Precision Medicine","place":["Taiyuan, China"]},{"name":"Department of Neurosurgery, The First Hospital of Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.1016\/j.cell.2021.03.022","article-title":"SnapShot: The microbiota-gut-brain axis.","volume":"184","author":"Agirman","year":"2021","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.chom.2021.11.001","article-title":"Human gut bacterial metabolism drives Th17 activation and colitis.","volume":"30","author":"Alexander","year":"2022","journal-title":"Cell Host Microbe"},{"key":"B3","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1093\/neuros\/nyy045","article-title":"White blood cell count improves prediction of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.","volume":"84","author":"Al-Mufti","year":"2019","journal-title":"Neurosurgery"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.conb.2019.11.009","article-title":"The microbiome-gut-brain axis in acute and chronic brain diseases.","volume":"61","author":"Benakis","year":"2020","journal-title":"Curr. Opin. Neurobiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e70142","DOI":"10.1002\/trc2.70142","article-title":"Cognitive effects of dopaminergic treatment in Alzheimer\u2019s disease: Systematic review and meta-analysis.","volume":"11","author":"Bonet Olivares","year":"2025","journal-title":"Alzheimers Dement."},{"key":"B6","doi-asserted-by":"publisher","first-page":"971048","DOI":"10.3389\/fimmu.2022.971048","article-title":"Sex hormones, intestinal inflammation, and the gut microbiome: Major influencers of the sexual dimorphisms in obesity.","volume":"13","author":"Brettle","year":"2022","journal-title":"Front. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.pharmthera.2009.11.005","article-title":"The vascular effects of trace amines and amphetamines.","volume":"125","author":"Broadley","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1227\/00006123-198204000-00021","article-title":"Neurotransmitter precursors and brain function.","volume":"10","author":"Conlay","year":"1982","journal-title":"Neurosurgery"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis.","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3488","DOI":"10.3390\/jcm14103488","article-title":"Distinct gut microbiota profiles in unruptured and ruptured intracranial aneurysms: Focus on butyrate-producing bacteria.","volume":"14","author":"Csecsei","year":"2025","journal-title":"J. Clin. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1001\/jamaneurol.2019.0006","article-title":"Worldwide incidence of aneurysmal subarachnoid hemorrhage according to region, time period, blood pressure, and smoking prevalence in the population: A systematic review and meta-analysis.","volume":"76","author":"Etminan","year":"2019","journal-title":"JAMA Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/s41579-020-0433-9","article-title":"Gut microbiota in human metabolic health and disease.","volume":"19","author":"Fan","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"105722","DOI":"10.1016\/j.neubiorev.2024.105722","article-title":"Cognition and gut microbiota in schizophrenia spectrum and mood disorders: A systematic review.","volume":"162","author":"Frileux","year":"2024","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1097\/00006123-199206000-00011","article-title":"Blood-Brain barrier permeability changes after experimental subarachnoid hemorrhage.","volume":"30","author":"German\u00f3","year":"1992","journal-title":"Neurosurgery"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.1038\/s41380-025-02939-9","article-title":"Neuroinflammatory fluid biomarkers in patients with Alzheimer\u2019s disease: A systematic literature review.","volume":"30","author":"Heneka","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic Diagramming Platform (GDP): A comprehensive database of high-quality biomedical graphics.","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"102015","DOI":"10.1016\/j.rehab.2025.102015","article-title":"Social cognition and behavioral problems persist after subarachnoid hemorrhage: A longitudinal cohort study.","volume":"68","author":"Jorna","year":"2025","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1161\/strokeaha.121.034792","article-title":"Dysbiosis of gut microbiome is associated with rupture of cerebral aneurysms.","volume":"53","author":"Kawabata","year":"2022","journal-title":"Stroke"},{"key":"B19","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3389\/fncel.2015.00392","article-title":"Breaking down the barriers: The gut microbiome, intestinal permeability and stress-related psychiatric disorders.","volume":"9","author":"Kelly","year":"2015","journal-title":"Front. Cell Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"122356","DOI":"10.1016\/j.lfs.2023.122356","article-title":"Important roles of linoleic acid and alpha-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia.","volume":"337","author":"Kim","year":"2024","journal-title":"Life Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites.","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.chom.2024.04.020","article-title":"Enterococcus-derived tyramine hijacks alpha(2A)-adrenergic receptor in intestinal stem cells to exacerbate colitis.","volume":"32","author":"Li","year":"2024","journal-title":"Cell Host Microbe"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1648800","DOI":"10.3389\/fimmu.2025.1648800","article-title":"The Microbiota-gut-brain axis in vascular cognitive impairment: Unraveling the mysterious link and therapeutic prospects.","volume":"16","author":"Liu","year":"2025","journal-title":"Front. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1016\/j.freeradbiomed.2025.12.059","article-title":"Inhibition of the SGLT2\/NHE-1\/NLRP3 signaling axis attenuates neuroinflammation and oxidative stress to ameliorate seizures and cognitive impairment in epileptic mice.","volume":"246","author":"Liu","year":"2026","journal-title":"Free Radical Biol. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/gps.2101","article-title":"Cross validation of the montreal cognitive assessment in community dwelling older adults residing in the Southeastern US.","volume":"24","author":"Luis","year":"2009","journal-title":"Intern. J. Geriatric Psychiatry"},{"key":"B26","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrneurol.2013.246","article-title":"Delayed neurological deterioration after subarachnoid haemorrhage.","volume":"10","author":"Macdonald","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1161\/strokeaha.119.025997","article-title":"Treatment of spontaneous subarachnoid hemorrhage.","volume":"51","author":"Maher","year":"2020","journal-title":"Stroke"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2870","DOI":"10.1161\/STROKEAHA.121.038035","article-title":"Sex hormones and risk of aneurysmal subarachnoid hemorrhage: A mendelian randomization study.","volume":"53","author":"Molenberg","year":"2022","journal-title":"Stroke"},{"key":"B29","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/s41579-020-00460-0","article-title":"The gut microbiota\u2013brain axis in behaviour and brain disorders.","volume":"19","author":"Morais","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The montreal cognitive assessment, MoCA: A brief screening tool for mild cognitive impairment.","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"B31","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.tim.2020.11.001","article-title":"The interplay of sex steroids, the immune response, and the intestinal microbiota.","volume":"29","author":"Pace","year":"2021","journal-title":"Trends Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/978-1-4939-7643-0_9","article-title":"Untargeted GC-MS metabolomics.","volume":"1738","author":"Papadimitropoulos","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.3390\/nu13041125","article-title":"Antioxidant vitamins and prebiotic FOS and XOS differentially shift microbiota composition and function and improve intestinal epithelial barrier In Vitro.","volume":"13","author":"Pham","year":"2021","journal-title":"Nutrients"},{"key":"B34","doi-asserted-by":"publisher","first-page":"987","DOI":"10.3389\/fphar.2017.00987","article-title":"The case for TAAR1 as a modulator of central nervous system function.","volume":"8","author":"Rutigliano","year":"2017","journal-title":"Front. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev.neuro.22.1.197","article-title":"Monoamine oxidase: From genes to behavior.","volume":"22","author":"Shih","year":"1999","journal-title":"Annu. Rev. Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"4416","DOI":"10.3390\/nu16244416","article-title":"Update on fatty acids and the brain.","volume":"16","author":"Sinclair","year":"2024","journal-title":"Nutrients"},{"key":"B37","doi-asserted-by":"publisher","first-page":"7428","DOI":"10.1523\/jneurosci.1114-16.2016","article-title":"Microbiota dysbiosis controls the neuroinflammatory response after stroke.","volume":"36","author":"Singh","year":"2016","journal-title":"J. Neurosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1136\/gutjnl-2024-332245","article-title":"Integrated metagenomic and metabolomic analysis reveals distinctive stage-specific gut-microbiome-derived metabolites in intracranial aneurysms.","volume":"73","author":"Sun","year":"2024","journal-title":"Gut"},{"key":"B39","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1007\/s12975-019-00740-9","article-title":"The stabilization of central sympathetic nerve activation by renal denervation prevents cerebral vasospasm after subarachnoid hemorrhage in rats.","volume":"11","author":"Takemoto","year":"2020","journal-title":"Transl. Stroke Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1007\/s10741-022-10261-7","article-title":"Cardiovascular disease associated with methamphetamine use: A review.","volume":"27","author":"Tobolski","year":"2022","journal-title":"Heart Fail Rev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"e71023","DOI":"10.1002\/alz.71023","article-title":"The microbiota\u2013gut\u2013brain axis in mild cognitive impairment and Alzheimer\u2019s disease: A scoping review of human studies.","volume":"22","author":"Warren","year":"2026","journal-title":"Alzheimer\u2019s Dement."},{"key":"B42","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/978-3-319-22533-3_26","article-title":"Early cognitive domain deficits in patients with aneurysmal subarachnoid hemorrhage correlate with functional status","volume":"122","author":"Wong","year":"2016","journal-title":"Acta Neurochir. Suppl."},{"key":"B43","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1186\/s12884-022-04923-5","article-title":"Dynamics of gut microbiota during pregnancy in women with TPOAb-positive subclinical hypothyroidism: A prospective cohort study.","volume":"22","author":"Wu","year":"2022","journal-title":"BMC Preg. Childbirth"},{"key":"B44","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1186\/s12866-021-02286-z","article-title":"Disturbed microbial ecology in Alzheimer\u2019s disease: Evidence from the gut microbiota and fecal metabolome.","volume":"21","author":"Xi","year":"2021","journal-title":"BMC Microbiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"111184","DOI":"10.1016\/j.isci.2024.111184","article-title":"Multiple omics reveal link between the microbiota-gut-brain axis and intracranial aneurysm rupture.","volume":"27","author":"Xu","year":"2024","journal-title":"iScience"},{"key":"B46","doi-asserted-by":"publisher","first-page":"6081","DOI":"10.1021\/acsnano.3c01005","article-title":"Foodborne carbon dot exposure induces insulin resistance through gut microbiota dysbiosis and damaged intestinal mucus layer.","volume":"17","author":"Zhang","year":"2023","journal-title":"ACS Nano"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1870309\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:36:33Z","timestamp":1787031393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1870309\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":46,"alternative-id":["10.3389\/fmicb.2026.1870309"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1870309","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"article-number":"1870309"}}