{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:58:45Z","timestamp":1790776725063,"version":"4.1.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Repeated low-dose sevoflurane exposure may affect cognition, but the relationship between such exposure, gut microbial composition, and circulating metabolites remains unclear. This study examined an experimental proof-of-concept exposure model and treated microbiota-metabolite findings as exploratory associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were exposed to 100 ppm sevoflurane for 2 h\/day over 7 consecutive days, followed by Morris water maze testing without a long-term recovery follow-up. Gut microbiota and serum metabolites were profiled by shotgun metagenomic sequencing and LC-MS metabolomics, respectively, and machine-learning analyses were used only for exploratory feature ranking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sevoflurane-exposed mice exhibited poorer Morris water maze performance (Day 6 escape latency: 28.6 \u00b1 3.4 s vs. 12.5 \u00b1 1.8 s in controls, p &amp;lt; 0.01), although interpretation is limited by unequal behavioral sample sizes. Serum metabolomics suggested nominal and exploratory alterations in bile acid- and sphingolipid-related pathways. Shotgun metagenomics (n = 3\/group) identified preliminary relative-abundance shifts, including a lower\n                      <jats:italic>Bacteroidota\/Bacillota<\/jats:italic>\n                      ratio and lower relative abundance of\n                      <jats:italic>Akkermansia<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this proof-of-concept model, repeated low-dose sevoflurane exposure was associated with impaired spatial learning and memory and with exploratory serum metabolic and gut microbial alterations. The findings do not establish persistent long-term deficits, routine occupational risk, or causal microbiota-metabolite mediation. Larger cage-aware studies, an ambient-air comparison group, targeted validation, and interventional experiments are required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1869293","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:19:32Z","timestamp":1790774372000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory microbiota-metabolite alterations associated with cognitive impairment after repeated low-dose sevoflurane exposure in mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Hui","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Lijiang People\u2019s Hospital","place":["Lijiang, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.bjane.2017.04.008","article-title":"Comparison of waste anesthetic gases in operating rooms with or without a scavenging system in a Brazilian university hospital","volume":"67","author":"Braz","year":"2017","journal-title":"Rev. Bras. Anestesiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1177\/0960327120938840","article-title":"Effect of inhaled waste anaesthetic gas on blood and liver parameters among hospital staff","volume":"39","author":"Emara","year":"2020","journal-title":"Hum. Exp. Toxicol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.lfs.2017.11.025","article-title":"Repeated exposure to sevoflurane impairs the learning and memory of older male rats","volume":"192","author":"Guo","year":"2018","journal-title":"Life Sci."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.633527","article-title":"Effects of sevoflurane inhalation anesthesia on the intestinal microbiome in mice","volume":"11","author":"Han","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"10500","DOI":"10.1007\/s12035-024-04229-x","article-title":"Dysregulation of the gut microbiota contributes to sevoflurane-induced cognitive dysfunction in aged mice by activating the NLRP3 inflammasome","volume":"61","author":"Han","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8831535","article-title":"Effects of occupational exposure to waste anesthetic gas on oxidative stress and DNA damage","volume":"2021","author":"Hua","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1007\/s12035-024-04322-1","article-title":"The role of the intestinal flora and its derivatives in neurocognitive disorders: a narrative review from a surgical perspective","volume":"62","author":"Huang","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s00420-017-1287-y","article-title":"Environmental and biological measurements of isoflurane and sevoflurane in operating room personnel","volume":"91","author":"Jafari","year":"2018","journal-title":"Int. Arch. Occup. Environ. Health"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-021-01305-w","article-title":"Effects of sevoflurane exposure on apoptosis and cell cycle of peripheral blood lymphocytes, and immunologic function","volume":"21","author":"Ji","year":"2021","journal-title":"BMC Anesthesiol."},{"key":"B10","article-title":"Evaluation of Waste Anesthetic Gas Exposure at a Veterinary Hospital","volume-title":"Niosh Health Hazard Evaluation Report 2022-0032-3399","author":"Kobos","year":"2024"},{"key":"B11","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.bja.2023.06.059","article-title":"Sevoflurane anaesthesia induces cognitive impairment in young mice through sequential tau phosphorylation","volume":"131","author":"Liang","year":"2023","journal-title":"Br. J. Anaesth."},{"key":"B12","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jalz.2018.07.217","article-title":"Altered bile acid profile associates with cognitive impairment in Alzheimer's disease: an emerging role for the gut microbiome","volume":"15","author":"MahmoudianDehkordi","year":"2019","journal-title":"Alzheimers Dement"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD012317.pub2","article-title":"Intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery","volume":"8","author":"Miller","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"B14","doi-asserted-by":"publisher","first-page":"10436","DOI":"10.1007\/s11356-020-11684-1","article-title":"Spontaneous abortion in women occupationally exposed to inhalational anesthetics: a critical systematic review","volume":"28","author":"Oliveira","year":"2021","journal-title":"Environ. Sci. pollut. Res. Int."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.170069","article-title":"Sphingolipids: membrane microdomains in brain development, function and neurological diseases","volume":"7","author":"Olsen","year":"2017","journal-title":"Open Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1007\/BF03021623","article-title":"Behavioural effects of chronic exposure to subanesthetic concentrations of halothane, sevoflurane and desflurane in rats","volume":"53","author":"Ozer","year":"2006","journal-title":"Can. J. Anaesth."},{"key":"B17","first-page":"647","article-title":"The gender difference in the effect of sevoflurane exposure on cognitive function and hippocampal neuronal apoptosis in rats","volume":"19","author":"Xie","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1093\/toxsci\/kfad071","article-title":"Tbx2 knockdown alleviated sevoflurane-induced cognitive disorder and neuron damage in aged rats by suppressing oxidative stress and ferroptosis","volume":"195","author":"Xu","year":"2023","journal-title":"Toxicol. Sci."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8639618","article-title":"Honokiol-mediated mitophagy ameliorates postoperative cognitive impairment induced by surgery\/sevoflurane by inhibiting activation of the NLRP3 inflammasome in the hippocampus","volume":"2019","author":"Ye","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2026.116278","article-title":"Gut microbiota mediates repeated sevoflurane-induced cognitive impairment via the gut-brain axis","volume":"513","author":"Zhang","year":"2026","journal-title":"Behav. Brain Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.neuroscience.2023.01.031","article-title":"Luteoloside prevents sevoflurane-induced cognitive dysfunction in aged rats by maintaining mitochondrial function and dynamics in hippocampal neurons","volume":"516","author":"Zhang","year":"2023","journal-title":"Neuroscience"},{"key":"B22","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1093\/jnen\/nlae026","article-title":"Syringaresinol attenuates tau phosphorylation and ameliorates cognitive dysfunction induced by sevoflurane in aged rats","volume":"83","author":"Zheng","year":"2024","journal-title":"J. Neuropathol. Exp. Neurol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1869293\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:19:33Z","timestamp":1790774373000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1869293\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":22,"alternative-id":["10.3389\/fcimb.2026.1869293"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1869293","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1869293"}}