{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:00:44Z","timestamp":1793138444964,"version":"4.5.0"},"reference-count":111,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"W2 Helmholtz Association"},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF21OC0066551"],"award-info":[{"award-number":["NNF21OC0066551"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CITEPro"},{"DOI":"10.13039\/501100001656","name":"Helmholtz Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001656","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UFZ CITE TB College"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The gut microbiome is essential for neurodevelopment via bidirectional gut\u2013brain axis signaling, yet environmental chemicals can potentially disrupt this communication by altering community structure and xenobiotic metabolism. In this study, we investigated whether the fungicide azoxystrobin, a known metabolic disruptor, modulates microbiome composition and function to influence neurobehavior. We utilized a simplified human gut microbiota model (SIHUMIx) and a vertebrate host model (larval zebrafish) to elucidate microbiome-mediated mechanisms of xenobiotic neurotoxicity. SIHUMIx was exposed to azoxystrobin for 7\u2009days at 10% of the acceptable daily intake, followed by recovery. Integrated metaproteomic and metabolomic analyses revealed functional reprogramming of the microbiota, characterized by upregulation of vitamin and cofactor biosynthesis, nutrient acquisition, and detoxification pathways, and decreases in carbohydrate fermentation and amino acid turnover, consistent with reduced short-chain fatty acid levels. Microbiome-depleted and SIHUMIx-inoculated larvae were exposed to azoxystrobin at 4\u2009days post fertilization, and neurobehavioral outcomes were assessed after 24\u2009h using the Visual and Acoustic Motor Response assay. Azoxystrobin exposure disrupted non-associative habituation learning independent of microbiome status but induced dark-phase hyperactivity only in colonized larvae, indicating a microbiome-dependent phenotype. Targeted metabolomics revealed lower serotonin levels in microbiome-depleted larvae relative to colonized controls and that azoxystrobin exposure reduced serotonin in colonized larvae toward depleted levels. These results suggest that microbiota-dependent serotonergic signaling may modulate host responses to azoxystrobin. This integrated ex vivo\u2013in vivo approach supports the concept that the microbiome is a key determinant of neurotoxic responses and underscores the importance of incorporating microbiome-mediated effects into chemical risk assessment frameworks.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag022","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:24:20Z","timestamp":1772454260000},"source":"Crossref","is-referenced-by-count":2,"title":["Integration of human microbiota (SIHUMIx) and zebrafish models reveals microbiome-mediated host responses to azoxystrobin"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2289-2441","authenticated-orcid":false,"given":"Chloe","family":"Wray","sequence":"first","affiliation":[{"name":"Department of Ecotoxicology, Chemicals in the Environment Research Section, Helmholtz-Centre for Environmental Research\u2014UFZ , 04318 Leipzig,","place":["Germany"]},{"name":"Biosciences, University 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in the Environment Research Section, Helmholtz-Centre for Environmental Research\u2014UFZ , 04318 Leipzig,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1496-1677","authenticated-orcid":false,"given":"Debjyoti","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Molecular Toxicology, Chemicals in the Environment Research Section, Helmholtz-Centre for Environmental Research\u2014UFZ , 04318 Leipzig,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4420-2185","authenticated-orcid":false,"given":"Siraz","family":"Kader","sequence":"additional","affiliation":[{"name":"Department of Ecotoxicology, Chemicals in the Environment Research Section, Helmholtz-Centre for Environmental Research\u2014UFZ , 04318 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