{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:18:57Z","timestamp":1789435137803,"version":"build-2803163510"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Ecotoxicology and Environmental Safety"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1016\/j.ecoenv.2021.112668","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T20:35:26Z","timestamp":1629837326000},"page":"112668","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":40,"special_numbering":"C","title":["Ammonia exposure causes the imbalance of the gut-brain axis by altering gene networks associated with oxidative metabolism, inflammation and apoptosis"],"prefix":"10.1016","volume":"224","author":[{"given":"Yutao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyin","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houjuan","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ecoenv.2021.112668_bib1","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.3382\/ps\/pez135","article-title":"The evaluation of potential immunotoxicity induced by environmental pollutant ammonia in broilers","volume":"98","author":"An","year":"2019","journal-title":"Poult. Sci."},{"key":"10.1016\/j.ecoenv.2021.112668_bib2","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.atmosenv.2018.06.037","article-title":"Real-time monitoring of atmospheric ammonia during a pollution episode in Madrid (Spain)","volume":"189","author":"Art\u00ed\u00f1ano","year":"2018","journal-title":"Atmos. Environ."},{"issue":"1","key":"10.1016\/j.ecoenv.2021.112668_bib3","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12974-020-01853-x","article-title":"TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K\/Akt pathway after intracerebral hemorrhage in mice","volume":"17","author":"Chen","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.ecoenv.2021.112668_bib4","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jhazmat.2018.12.014","article-title":"Immunosuppression, oxidative stress, and glycometabolism disorder caused by cadmium in common carp (Cyprinus carpio L.): application of transcriptome analysis in risk assessment of environmental contaminant cadmium","volume":"366","author":"Chen","year":"2019","journal-title":"J. Hazard. Mater."},{"key":"10.1016\/j.ecoenv.2021.112668_bib5","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.4049\/jimmunol.181.3.1917","article-title":"IL-2 receptor \u03b2-chain signaling controls immunosuppressive CD4+ T cells in the draining lymph nodes and lung during allergic airway inflammation in vivo","volume":"181","author":"Doganci","year":"2008","journal-title":"J. Immunol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib6","doi-asserted-by":"crossref","first-page":"19228","DOI":"10.1038\/srep19228","article-title":"Transcriptome analyses reveal genotype-and developmental stage-specific molecular responses to drought and salinity stresses in chickpea","volume":"6","author":"Garg","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ecoenv.2021.112668_bib7","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.conb.2020.02.005","article-title":"The diet-microbiome tango: how nutrients lead the gut brain axis","volume":"62","author":"Gili","year":"2020","journal-title":"Curr. Opin. Neurobiol."},{"issue":"6","key":"10.1016\/j.ecoenv.2021.112668_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbagrm.2020.194491","article-title":"Transcriptomic landscape, gene signatures and regulatory profile of aging in the human brain","volume":"1863","author":"Gonz\u00e1lez-Velasco","year":"2020","journal-title":"Biochim. Biophys. Acta Gene Regul. Mech."},{"issue":"9","key":"10.1016\/j.ecoenv.2021.112668_bib9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0223019","article-title":"Neurobehavioral dysfunction in non-alcoholic steatohepatitis is associated with hyperammonemia, gut dysbiosis, and metabolic and functional brain regional deficits","volume":"14","author":"Higarza","year":"2019","journal-title":"PLoS One"},{"key":"10.1016\/j.ecoenv.2021.112668_bib10","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1242\/jeb.01586","article-title":"Chronic and acute ammonia toxicity in mudskippers, Periophthalmodon schlosseri and Boleophthalmus boddaerti: brain ammonia and glutamine contents, and effects of methionine sulfoximine and MK801","volume":"208","author":"Ip","year":"2005","journal-title":"J. Exp. Biol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2019.105716","article-title":"Effect of IL2RA and IL2RB gene polymorphisms on lung cancer risk","volume":"74","author":"Jia","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib12","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s11248-005-0199-x","article-title":"Analysis of substrate specificity of pig CYP2B22 and CYP2C49 towards herbicides by transgenic rice plants","volume":"14","author":"Kawahigashi","year":"2005","journal-title":"Transgenic Res."},{"key":"10.1016\/j.ecoenv.2021.112668_bib13","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1080\/1059924X.2014.886536","article-title":"Evaluation of respiratory symptoms and respiratory protection behavior among poultry workers in small farming operations","volume":"19","author":"Kearney","year":"2014","journal-title":"J. Agromed."},{"key":"10.1016\/j.ecoenv.2021.112668_bib14","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.etap.2019.02.001","article-title":"Toxic effects of nitrogenous compounds (ammonia, nitrite, and nitrate) on acute toxicity and antioxidant responses of juvenile olive flounder, Paralichthys olivaceus","volume":"67","author":"Kim","year":"2019","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.tox.2011.01.017","article-title":"Ferulic acid protects against carbon tetrachloride-induced liver injury in mice","volume":"282","author":"Kim","year":"2011","journal-title":"Toxicology"},{"key":"10.1016\/j.ecoenv.2021.112668_bib16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1089\/jir.2010.0107","article-title":"The oligoadenylate synthetase family: an ancient protein family with multiple antiviral activities","volume":"31","author":"Kristiansen","year":"2011","journal-title":"J. Interferon Cytokine Res."},{"key":"10.1016\/j.ecoenv.2021.112668_bib17","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.yexcr.2015.09.019","article-title":"The small chemical enzyme inhibitor 5-phenylnicotinic acid\/CD13 inhibits cell migration and invasion of tartrate-resistant acid phosphatase\/ACP5-overexpressing MDA-MB-231 breast cancer cells","volume":"339","author":"Krumpel","year":"2015","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.ecoenv.2021.112668_bib18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.abb.2015.02.010","article-title":"Cytochrome P450 1B1: an unexpected modulator of liver fatty acid homeostasis","volume":"571","author":"Larsen","year":"2015","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.ecoenv.2021.112668_bib19","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/ni.2535","article-title":"OASL1 inhibits translation of the type I interferon-regulating transcription factor IRF7","volume":"14","author":"Lee","year":"2013","journal-title":"Nat. Immunol."},{"issue":"7","key":"10.1016\/j.ecoenv.2021.112668_bib20","article-title":"Serum substance P levels and early mortality of spontaneous intracerebral haemorrhage patients","volume":"29","author":"Lorente","year":"2020","journal-title":"J. Stroke Cereb. Dis."},{"issue":"3","key":"10.1016\/j.ecoenv.2021.112668_bib21","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.jad.2011.11.016","article-title":"Increased autoimmune activity against 5-HT: A key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression","volume":"136","author":"Maes","year":"2012","journal-title":"J. Affect. Disord."},{"issue":"1","key":"10.1016\/j.ecoenv.2021.112668_bib22","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.fsi.2015.02.037","article-title":"Di (2-ethylhexyl) phthalate inhibits B cell proliferation and reduces the abundance of IgM-secreting cells in cultured immune tissues of the rainbow trout","volume":"44","author":"Martins","year":"2015","journal-title":"Fish. Shellfish Immunol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib23","first-page":"889","article-title":"Hepatotoxicity of paraquat on common carp (Cyprinus carpio L.)","volume":"616\u2013617","author":"Ma","year":"2017","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.ecoenv.2021.112668_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.gene.2020.144700","article-title":"Associations of IL6 rs1800795, BLK rs13277113, TIMP3 rs9621532, IL1RL1 rs1041973 and IL1RAP rs4624606 single gene polymorphisms with laryngeal squamous cell carcinoma","volume":"747","author":"Pasvenskaite","year":"2020","journal-title":"Gene"},{"key":"10.1016\/j.ecoenv.2021.112668_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2019.110078","article-title":"Ammonia inhalation impaired immune function and mitochondrial integrity in the broilers bursa of fabricius: Implication of oxidative stress and apoptosis","volume":"190","author":"Shah","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.ecoenv.2021.112668_bib26","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.envpol.2008.03.013","article-title":"Ammonia in the environment: from ancient times to the present","volume":"156","author":"Sutton","year":"2008","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.ecoenv.2021.112668_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2020.139917","article-title":"High ammonia exposure regulates lipid metabolism in the pig skeletal muscle via mTOR pathway","volume":"740","author":"Tang","year":"2020","journal-title":"Sci. Total Environ."},{"issue":"3","key":"10.1016\/j.ecoenv.2021.112668_bib28","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.cmet.2020.02.008","article-title":"When rhythms meet the blues: circadian interaction with the microbiota-gut-brain axis","volume":"31","author":"Teichman","year":"2020","journal-title":"Cell Metab."},{"key":"10.1016\/j.ecoenv.2021.112668_bib29","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2020.111050","article-title":"Ammonia exposure causes lung injuries and disturbs pulmonary circadian clock gene network in a pig study","volume":"205","author":"Wang","year":"2020","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.ecoenv.2021.112668_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2020.140532","article-title":"The inflammatory injury of heart caused by ammonia is realized by oxidative stress and abnormal energy metabolism activating inflammatory pathway","volume":"742","author":"Wang","year":"2020","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.ecoenv.2021.112668_bib31","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1039\/C8MT00234G","article-title":"Arsenite renal apoptotic effects in chickens co-aggravated by oxidative stress and inflammatory response","volume":"10","author":"Wang","year":"2018","journal-title":"Metallomics"},{"key":"10.1016\/j.ecoenv.2021.112668_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2020.111473","article-title":"Zinc offers splenic protection through suppressing PERK\/IRE1-driven apoptosis pathway in common carp (Cyprinus carpio) under arsenic stress","volume":"208","author":"Wang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.ecoenv.2021.112668_bib33","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.chemosphere.2019.06.235","article-title":"Ammonia inhalation-mediated mir-202-5p leads to cardiac autophagy through PTEN\/AKT\/mTOR pathway","volume":"235","author":"Xing","year":"2019","journal-title":"Chemosphere"},{"key":"10.1016\/j.ecoenv.2021.112668_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2019.116749","article-title":"An orally administered magnoloside A ameliorates functional dyspepsia by modulating brain-gut peptides and gut microbiota","volume":"233","author":"Xue","year":"2019","journal-title":"Life Sci."},{"key":"10.1016\/j.ecoenv.2021.112668_bib35","first-page":"78","article-title":"Projections of NH3 emissions from manure generated by livestock production in China to 2030 under six mitigation scenarios","volume":"607\u2013608","author":"Xu","year":"2017","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.ecoenv.2021.112668_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2019.114869","article-title":"miR-187-5p\/apaf-1 axis was involved in oxidative stress-mediated apoptosis caused by ammonia via mitochondrial pathway in chicken livers","volume":"388","author":"Xu","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib37","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1046\/j.1471-4159.2003.02069.x","article-title":"GABAC receptor agonist suppressed ammonia-induced apoptosis in cultured rat hippocampal neurons by restoring phosphorylated BAD level","volume":"87","author":"Yang","year":"2003","journal-title":"J. Neurochem."},{"key":"10.1016\/j.ecoenv.2021.112668_bib38","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1016\/j.molimm.2010.02.005","article-title":"LFA-1 defect-induced effector\/memory CD8+T cell apoptosis is mediated via Bcl-2\/Caspase pathways and associated with downregulation of CD27 and IL-15R","volume":"47","author":"Ye","year":"2010","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib39","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.molimm.2020.03.022","article-title":"S100A12 promotes inflammation and cell apoptosis in sepsis-induced ARDS via activation of NLRP3 inflammasome signaling","volume":"122","author":"Zhang","year":"2020","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib40","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.fsi.2012.05.001","article-title":"Effects of dietary mannan oligosaccharide on growth performance, gut morphology and stress tolerance of juvenile Pacific white shrimp, Litopenaeus vannamei","volume":"33","author":"Zhang","year":"2012","journal-title":"Fish. Shellfish Immunol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12953-015-0067-4","article-title":"Proteome changes in the small intestinal mucosa of broilers (Gallus gallus) induced by high concentrations of atmospheric ammonia","volume":"13","author":"Zhang","year":"2015","journal-title":"Proteome Sci."},{"key":"10.1016\/j.ecoenv.2021.112668_bib42","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.fsi.2018.05.036","article-title":"Effects of acute ammonia toxicity on oxidative stress, immune response and apoptosis of juvenile yellow catfish Pelteobagrus fulvidraco and the mitigation of exogenous taurine","volume":"79","author":"Zhang","year":"2018","journal-title":"Fish. Shellfish Immunol."},{"key":"10.1016\/j.ecoenv.2021.112668_bib43","doi-asserted-by":"crossref","DOI":"10.1016\/j.ecoenv.2019.109582","article-title":"Taxifolin alleviates apoptotic injury induced by DEHP exposure through cytochrome P450 homeostasis in chicken cardiomyocytes","volume":"183","author":"Zhang","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"10.1016\/j.ecoenv.2021.112668_bib44","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2020.143054","article-title":"Environmentally relevant concentration of cypermethrin or\/and sulfamethoxazole induce neurotoxicity of grass carp: Involvement of blood-brain barrier, oxidative stress and apoptosis","volume":"762","author":"Zhao","year":"2021","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.ecoenv.2021.112668_bib45","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.chemosphere.2018.09.002","article-title":"Hydrogen sulfifide exposure induces jejunum injury via CYP450s\/ROS pathway in broilers","volume":"214","author":"Zheng","year":"2019","journal-title":"Chemosphere"}],"container-title":["Ecotoxicology and Environmental Safety"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0147651321007806?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0147651321007806?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T05:46:15Z","timestamp":1758951975000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0147651321007806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":45,"alternative-id":["S0147651321007806"],"URL":"https:\/\/doi.org\/10.1016\/j.ecoenv.2021.112668","relation":{},"ISSN":["0147-6513"],"issn-type":[{"value":"0147-6513","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ammonia exposure causes the imbalance of the gut-brain axis by altering gene networks associated with oxidative metabolism, inflammation and apoptosis","name":"articletitle","label":"Article Title"},{"value":"Ecotoxicology and Environmental Safety","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ecoenv.2021.112668","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"112668"}}