{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:43:01Z","timestamp":1792784581391,"version":"4.5.0"},"reference-count":80,"publisher":"American Chemical Society (ACS)","issue":"41","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"National Natural Science Foundation of China (NSFC)","award":["42677347,42277269"],"award-info":[{"award-number":["42677347,42277269"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The widespread use of antibiotics has resulted in their frequent occurrence in marine environments, yet their ecological risks remain poorly understood. Enrofloxacin (ENR) is one of the most frequently detected antibiotics in aquatic ecosystems. However, its toxicological mechanisms in marine fish remain unclear. Here, multiomics, Vibrio parahemolyticus infection, short chain fatty acid supplementation and germ-free fish models were integrated to investigate ENR induced neurotoxicity and the role of gut microbiota. The results showed that ENR exposure impaired intestinal function in marine medaka (Oryzias melastigma), accompanied by behavioral abnormalities, neurotoxicity, and liver injury. ENR also induced gut microbiome dysbiosis and altered SCFAs levels. Furthermore, SCFAs supplementation and germ-free fish experiments provided complementary and supportive evidence that gut microbial dysbiosis and altered SCFAs levels may be involved in ENR neurotoxic responses. Moreover, ENR pretreated fish showed increased susceptibility to V. parahemolyticus challenge, which further disrupted the gut microbiome and aggravated neurological dysfunction. Collectively, these findings suggest that ENR induced neurotoxicity is linked to disruption of the microbiome\u2013gut\u2013brain axis and increased susceptibility to subsequent pathogenic stress. This study provides new insights into antibiotic toxicity in marine fish and supports ecological risk assessment of ENR in marine aquaculture.<\/jats:p>","DOI":"10.1021\/acs.est.6c06063","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:01:40Z","timestamp":1791396100000},"page":"29299-29312","source":"Crossref","is-referenced-by-count":0,"title":["Enrofloxacin Disrupts\nMicrobiota\u2013Gut\u2013Brain\nAxes in Marine Medaka: Mechanistic Insights from Multiomics and Germ-Free\nModels"],"prefix":"10.1021","volume":"60","author":[{"given":"Bian-Hao","family":"Zeng","sequence":"first","affiliation":[{"name":"Shandong University , , , ,","place":["Weihai, Shandong, China, 264209"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Weihai, Shandong, China, 264209"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Weihai, Shandong, China, 264209"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengzhou","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Weihai, Shandong, China, 264209"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Yin","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Weihai, Shandong, China, 264209"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Sun","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Weihai, Shandong, China, 264209"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Weihai, Shandong, China, 264209"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6484-657X","authenticated-orcid":true,"given":"Zhi-Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Weihai, Shandong, China, 264209"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"issue":"3","key":"2026102007524467200_cit1","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1016\/j.watres.2010.10.032","article-title":"Evaluating environmental\nimpact of STPs situated on streams in the Czech Republic: An integrated\napproach to biomonitoring the aquatic environment","volume":"45","author":"Li","year":"2011","journal-title":"Water Res."},{"key":"2026102007524467200_cit2","doi-asserted-by":"publisher","first-page":"127338","DOI":"10.1016\/j.envpol.2025.127338","article-title":"Comprehensive profiling\nof quinolone\nantibiotics in the Bohai Sea: Occurrence, source apportionment, and\nenvironmental risks","volume":"387","author":"Wen","year":"2025","journal-title":"Environ. Pollut."},{"issue":"2","key":"2026102007524467200_cit3","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2165\/00003495-199958002-00007","article-title":"Toxicity of Quinolones","volume":"58","author":"Stahlmann","year":"1999","journal-title":"Drugs"},{"key":"2026102007524467200_cit4","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.3390\/ph16081105","article-title":"Depressive\nand Other Adverse CNS\nEffects of Fluoroquinolones","volume":"16","author":"Wierzbin\u0301ski","year":"2023","journal-title":"Pharmaceuticals"},{"key":"2026102007524467200_cit5","doi-asserted-by":"publisher","first-page":"131210","DOI":"10.1016\/j.chemosphere.2021.131210","article-title":"Hepatotoxicity in carp (Cyprinus\ncarpio) exposed to environmental levels of norfloxacin (NOR): Some\nlatest evidences from transcriptomics analysis, biochemical parameters\nand histopathological changes","volume":"283","author":"Zhang","year":"2021","journal-title":"Chemosphere"},{"key":"2026102007524467200_cit6","doi-asserted-by":"publisher","first-page":"118541","DOI":"10.1016\/j.envpol.2021.118541","article-title":"Antibiotics in mariculture systems:\nA review of occurrence, environmental behavior, and ecological effects","volume":"293","author":"Wang","year":"2022","journal-title":"Environ. Pollut."},{"key":"2026102007524467200_cit7","doi-asserted-by":"publisher","first-page":"143863","DOI":"10.1016\/j.scitotenv.2020.143863","article-title":"Antibiotics in marine\naquaculture farms surrounding Laizhou Bay, Bohai Sea: Distribution\ncharacteristics considering various culture modes and organism species","volume":"760","author":"Han","year":"2021","journal-title":"Sci. Total Environ."},{"issue":"1","key":"2026102007524467200_cit8","doi-asserted-by":"publisher","first-page":"1926337","DOI":"10.1080\/20964129.2021.1926337","article-title":"Antibiotic residues\nfrom aquaculture farms and their ecological risks in Southeast Asia:\na case study from Malaysia","volume":"7","author":"Thiang","year":"2021","journal-title":"Ecosyst. Health\nSustain."},{"issue":"10","key":"2026102007524467200_cit9","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1002\/etc.4532","article-title":"Occurrence, Distribution,\nand Ecological Risk of Fluoroquinolones\nin Rivers and Wastewaters","volume":"38","author":"Teglia","year":"2019","journal-title":"Environ. Toxicol.\nChem."},{"key":"2026102007524467200_cit10","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.etap.2019.02.002","article-title":"Oxidative stress induced\nby fluoroquinolone enrofloxacin in zebrafish (Danio rerio) can be\nameliorated after a prolonged exposure","volume":"67","author":"Sehonova","year":"2019","journal-title":"Environ.\nToxicol. Pharmacol."},{"key":"2026102007524467200_cit11","doi-asserted-by":"publisher","first-page":"160094","DOI":"10.1016\/j.scitotenv.2022.160094","article-title":"Enrofloxacin exposure\ninduces anxiety-like behavioral responses in zebrafish by affecting\nthe microbiota-gut-brain axis","volume":"858","author":"Tian","year":"2023","journal-title":"Sci. Total Environ."},{"key":"2026102007524467200_cit12","doi-asserted-by":"publisher","first-page":"136888","DOI":"10.1016\/j.jhazmat.2024.136888","article-title":"Hepatotoxicity, developmental\ntoxicity, and neurotoxicity risks associated with co-exposure of zebrafish\nto fluoroquinolone antibiotics and tire microplastics: An in silico\nstudy","volume":"485","author":"Wen","year":"2025","journal-title":"J. Hazard. Mater."},{"issue":"12","key":"2026102007524467200_cit13","doi-asserted-by":"publisher","first-page":"8428","DOI":"10.1021\/acs.est.1c08712","article-title":"Enrofloxacin\nInduces Intestinal Microbiota-Mediated Immunosuppression in Zebrafish","volume":"56","author":"Qiu","year":"2022","journal-title":"Environ. Sci. Technol."},{"issue":"1","key":"2026102007524467200_cit14","doi-asserted-by":"publisher","first-page":"fiae169","DOI":"10.1093\/femsec\/fiae169","article-title":"A review on comparative analysis of marine and freshwater fish gut\nmicrobiomes: insights into environmental impact on gut microbiota","volume":"101","author":"Singh","year":"2025","journal-title":"FEMS Microbiol. Ecol."},{"issue":"1","key":"2026102007524467200_cit15","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1186\/s40168-021-01113-x","article-title":"Host habitat\nis the major determinant of the gut microbiome\nof fish","volume":"9","author":"Kim","year":"2021","journal-title":"Microbiome"},{"issue":"15","key":"2026102007524467200_cit16","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1080\/10643389.2022.2142033","article-title":"Controlling factors and toxicokinetic\nmodeling of antibiotics bioaccumulation in aquatic organisms: A review","volume":"53","author":"Zhu","year":"2023","journal-title":"Crit. Rev. Environ. Sci. Technol."},{"key":"2026102007524467200_cit17","doi-asserted-by":"publisher","first-page":"123079","DOI":"10.1016\/j.envpol.2023.123079","article-title":"Micro(nano)plastics in marine medaka:\nEntry pathways and cardiotoxicity with triphenyltin","volume":"342","author":"Liu","year":"2024","journal-title":"Environ. Pollut."},{"issue":"22","key":"2026102007524467200_cit18","doi-asserted-by":"publisher","first-page":"10879","DOI":"10.1021\/acs.est.5c01615","article-title":"The Gut Microbiome\nCausally Contributes\nto Interspecific Differences in Pesticide Sensitivity","volume":"59","author":"Theys","year":"2025","journal-title":"Environ. Sci. Technol."},{"key":"2026102007524467200_cit19","doi-asserted-by":"publisher","first-page":"117751","DOI":"10.1016\/j.envpol.2021.117751","article-title":"Triphenyltin exposure causes changes in health-associated gut microbiome\nand metabolites in marine medaka","volume":"288","author":"He","year":"2021","journal-title":"Environ. Pollut."},{"issue":"1","key":"2026102007524467200_cit20","doi-asserted-by":"publisher","first-page":"7748","DOI":"10.1038\/s41467-025-62989-z","article-title":"The soil-plant-human\ngut microbiome\naxis into perspective","volume":"16","author":"Ma","year":"2025","journal-title":"Nat. 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Hepatol."},{"issue":"12","key":"2026102007524467200_cit23","doi-asserted-by":"publisher","first-page":"6571","DOI":"10.1111\/are.15528","article-title":"Enrofloxacin induces\nintestinal disorders of metabolome and microbiome\nin American shad (Alosa sapidissima)","volume":"52","author":"Du","year":"2021","journal-title":"Aquacult.\nRes."},{"key":"2026102007524467200_cit24","doi-asserted-by":"publisher","first-page":"653025","DOI":"10.3389\/fimmu.2021.653025","article-title":"Mechanisms\nUsed by Probiotics to Confer Pathogen Resistance to Teleost Fish","volume":"12","author":"Simo\u0301n","year":"2021","journal-title":"Front. Immunol."},{"key":"2026102007524467200_cit25","doi-asserted-by":"publisher","first-page":"114966","DOI":"10.1016\/j.marpolbul.2023.114966","article-title":"Short-term\nexposure to enrofloxacin causes hepatic metabolism disorder\nassociated with intestinal flora dysbiosis in adult marine medaka\n(Oryzias melastigma)","volume":"192","author":"Wang","year":"2023","journal-title":"Mar. Pollut. Bull."},{"issue":"6","key":"2026102007524467200_cit26","doi-asserted-by":"publisher","first-page":"127","DOI":"10.11758\/yykxjz.20160905001","article-title":"Simultaneous Determination\nof Seventeen Quinolones in Aquaculture\nSeawater Using Solid-Phase Extraction and Liquid Chromatography Tandem\nMass Spectrometry","volume":"38","author":"Xiao","year":"2017","journal-title":"Prog. Fish. Sci."},{"issue":"5","key":"2026102007524467200_cit27","doi-asserted-by":"publisher","first-page":"421","DOI":"10.3390\/toxics11050421","article-title":"Occurrence\nand distribution of antibiotics in a tropical mariculture\narea of Hainan, China: implications for risk assessment and management","volume":"11","author":"Qin","year":"2023","journal-title":"Toxics"},{"key":"2026102007524467200_cit28","doi-asserted-by":"publisher","first-page":"136365","DOI":"10.1016\/j.jhazmat.2024.136365","article-title":"Multigenerational effects of combined\nexposure of triphenyltin and micro\/nanoplastics on marine medaka (Oryzias\nmelastigma): From molecular levels to behavioral response","volume":"480","author":"Feng","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"2026102007524467200_cit29","doi-asserted-by":"publisher","first-page":"100655","DOI":"10.1016\/j.bbih.2023.100655","article-title":"Chronic early life\nstress alters the neuroimmune profile and functioning of the developing\nzebrafish gut","volume":"31","author":"Graves","year":"2023","journal-title":"Brain, Behav., Immun.:Health"},{"issue":"10","key":"2026102007524467200_cit30","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1093\/bioinformatics\/btv033","article-title":"MEGAHIT:\nan ultra-fast single-node solution for large and complex metagenomics\nassembly via succinct de Bruijn graph","volume":"31","author":"Li","year":"2015","journal-title":"Bioinformatics"},{"issue":"1","key":"2026102007524467200_cit31","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/1471-2105-11-119","article-title":"Prodigal: prokaryotic\ngene recognition and translation\ninitiation site identification","volume":"11","author":"Hyatt","year":"2010","journal-title":"BMC Bioinf."},{"issue":"13","key":"2026102007524467200_cit32","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1093\/bioinformatics\/btl158","article-title":"Cd-hit: a fast program for clustering and comparing\nlarge sets of protein or nucleotide sequences","volume":"22","author":"Li","year":"2006","journal-title":"Bioinformatics"},{"issue":"23","key":"2026102007524467200_cit33","doi-asserted-by":"publisher","first-page":"3150","DOI":"10.1093\/bioinformatics\/bts565","article-title":"CD-HIT: accelerated\nfor clustering the next-generation sequencing data","volume":"28","author":"Fu","year":"2012","journal-title":"Bioinformatics"},{"issue":"12","key":"2026102007524467200_cit34","doi-asserted-by":"publisher","first-page":"5825","DOI":"10.1093\/molbev\/msab293","article-title":"eggNOG-mapper v2: Functional Annotation,\nOrthology\nAssignments, and Domain Prediction at the Metagenomic Scale","volume":"38","author":"Cantalapiedra","year":"2021","journal-title":"Mol. Biol. Evol."},{"issue":"4","key":"2026102007524467200_cit35","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides\nfast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"2026102007524467200_cit36","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.crimmu.2021.08.003","article-title":"Short chain\nfatty acids (SCFAs) improves TNBS-induced colitis in zebrafish","volume":"2","author":"Morales Fe\u0301nero","year":"2021","journal-title":"Curr. Res. Immunol."},{"key":"2026102007524467200_cit37","doi-asserted-by":"publisher","first-page":"536225","DOI":"10.1101\/2023.04.10.536225","article-title":"Breaking the mold:\nThe first report on germ-free adult\nmarine medaka (Oryzias melastigma) models","author":"Jia","year":"2023","journal-title":"bioRxiv"},{"key":"2026102007524467200_cit38","doi-asserted-by":"publisher","first-page":"742889","DOI":"10.1016\/j.aquaculture.2025.742889","article-title":"The effect\nof enrofloxacin exposure\non energy metabolism and the ARGs transmission in grass carp: Potential\ncontribution of microbiota-gut-liver axis","volume":"610","author":"Li","year":"2026","journal-title":"Aquaculture"},{"issue":"2","key":"2026102007524467200_cit39","doi-asserted-by":"publisher","first-page":"fiaa255","DOI":"10.1093\/femsec\/fiaa255","article-title":"microeco: an R package for data mining\nin microbial community ecology","volume":"97","author":"Liu","year":"2021","journal-title":"FEMS Microbiol.\nEcol."},{"key":"2026102007524467200_cit40","doi-asserted-by":"crossref","unstructured":"Bastian, M.; Heymann, S.; Jacomy, M.\n          Gephi: An Open\nSource Software for Exploring and Manipulating Networks.  Proceedings of the International AAAI Conference on Web\nand Social Media; AAAI,2009; Vol. 3(1), pp 361\u2013362.10.1609\/icwsm.v3i1.13937.","DOI":"10.1609\/icwsm.v3i1.13937"},{"issue":"2","key":"2026102007524467200_cit41","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1152\/physrev.00018.2022","article-title":"The enteric nervous system","volume":"103","author":"Sharkey","year":"2023","journal-title":"Physiol.\nRev."},{"key":"2026102007524467200_cit42","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-4939-0897-4_3","article-title":"The Enteric\nNervous System and Gastrointestinal Innervation: Integrated Local\nand Central Control","volume-title":"Microbial Endocrinology:\nThe Microbiota-Gut-Brain Axis in Health and Disease","author":"Furness","year":"2014"},{"issue":"6","key":"2026102007524467200_cit43","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1053\/j.gastro.2010.06.063","article-title":"Chronic Gastrointestinal\nInflammation Induces Anxiety-Like Behavior and Alters Central Nervous\nSystem Biochemistry in Mice","volume":"139","author":"Bercik","year":"2010","journal-title":"Gastroenterology"},{"key":"2026102007524467200_cit44","doi-asserted-by":"publisher","first-page":"110262","DOI":"10.1016\/j.neuropharm.2024.110262","article-title":"Metformin activates\nthe PI3K\/AKT\/BDNF axis to attenuate postoperative cognitive dysfunction","volume":"265","author":"Wu","year":"2025","journal-title":"Neuropharmacology"},{"key":"2026102007524467200_cit45","doi-asserted-by":"publisher","first-page":"126830","DOI":"10.1016\/j.jhazmat.2021.126830","article-title":"Micro\/nano-plastics\ncause neurobehavioral toxicity\nin discus fish (Symphysodon aequifasciatus): Insight from brain-gut-microbiota\naxis","volume":"421","author":"Huang","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"2026102007524467200_cit46","doi-asserted-by":"publisher","first-page":"133463","DOI":"10.1016\/j.jhazmat.2024.133463","article-title":"An azole\nfungicide climbazole damages the gut-brain axis in the grass carp","volume":"465","author":"Lu","year":"2024","journal-title":"J. Hazard. Mater."},{"issue":"4","key":"2026102007524467200_cit47","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/nrmicro2539","article-title":"Modulation of NF-\u03baB\nsignalling by microbial pathogens","volume":"9","author":"Rahman","year":"2011","journal-title":"Nat. Rev.\nMicrobiol."},{"issue":"8","key":"2026102007524467200_cit48","doi-asserted-by":"publisher","first-page":"5653","DOI":"10.4049\/jimmunol.180.8.5653","article-title":"Mechanism of IL-1\u03b2-induced\nincrease in intestinal epithelial tight junction permeability","volume":"180","author":"Al-Sadi","year":"2008","journal-title":"J. Immunol."},{"issue":"3","key":"2026102007524467200_cit49","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.cell.2015.12.023","article-title":"Neuro-immune Interactions Drive Tissue\nProgramming\nin Intestinal Macrophages","volume":"164","author":"Gabanyi","year":"2016","journal-title":"Cell"},{"issue":"2","key":"2026102007524467200_cit50","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.cell.2014.04.050","article-title":"Crosstalk\nbetween Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal\nMotility","volume":"158","author":"Muller","year":"2014","journal-title":"Cell"},{"key":"2026102007524467200_cit51","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.fsi.2020.05.018","article-title":"Effects of inflammation and\/or infection\non the neuroendocrine\ncontrol of fish intestinal motility: A review","volume":"103","author":"Serna-Duque","year":"2020","journal-title":"Fish Shellfish Immunol."},{"issue":"5","key":"2026102007524467200_cit52","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.3390\/nu12051474","article-title":"The Firmicutes\/Bacteroidetes Ratio:\nA Relevant Marker of Gut Dysbiosis in Obese Patients?","volume":"12","author":"Magne","year":"2020","journal-title":"Nutrients"},{"key":"2026102007524467200_cit53","doi-asserted-by":"publisher","first-page":"961703","DOI":"10.3389\/fmed.2022.961703","article-title":"Role of gut microbiota-derived\nsignals in the regulation of gastrointestinal motility","volume":"9","author":"Zheng","year":"2022","journal-title":"Front. 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