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Toxicol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>1-Nitropyrene (1-NP), a prevalent nitro-polycyclic aromatic hydrocarbon, is increasingly recognized as a potential metabolic disruptor, yet its systemic biological effects remain insufficiently characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigated the metabolic, immunological, hepatic, and microbiome alterations induced by chronic 1-NP exposure in rats and assessed whether ferroptosis inhibition via Fer-1 could mitigate these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Although body weight was not significantly altered overall, high-dose exposure impaired growth from week 4. Exposed groups exhibited progressively elevated fasting blood glucose and impaired glucose tolerance, indicating significant disruption of glucose homeostasis. Serum biochemistry revealed dose-dependent reductions in HDL and total cholesterol, while histopathology confirmed hepatocyte ballooning, inflammation, and steatosis consistent with NAFLD-like progression. Hematological changes, including shifts in neutrophil and lymphocyte populations, suggested chronic inflammatory activation. Untargeted metabolomics identified extensive alterations in pathways related to glycolysis, tryptophan metabolism, glycerophospholipid metabolism, and ABC transporters. Gut microbiota analysis demonstrated reduced richness and significant compositional shifts, with functional predictions linking dysbiosis to xenobiotic degradation, lipid metabolism, and phosphotransferase systems. Integrated microbiome\u2013metabolome analysis revealed coordinated disruptions in host\u2013microbial metabolic networks. Fer-1 intervention modified specific metabolic and microbial signatures but did not substantially alleviate major toxic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, chronic 1-NP exposure causes widespread metabolic injury driven by combined effects on host metabolism, immune regulation, hepatic function, and gut microbial ecology. These findings highlight 1-NP as a potent environmental metabolic disruptor and underscore the need for further mechanistic studies to inform mitigation strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/ftox.2026.1771766","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T22:10:22Z","timestamp":1773353422000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated microbiome-metabolome analysis reveals multiorgan toxicity of 1-nitropyrene and the limited efficacy of ferroptosis inhibitor Fer-1 in rats"],"prefix":"10.3389","volume":"8","author":[{"given":"Ning","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Jinan Central Hospital, Shandong University","place":["Jinan, China"]},{"name":"Department of Endocrinology, Zibo Central Hospital","place":["Zibo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Jinan Central Hospital, Shandong University","place":["Jinan, China"]},{"name":"Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Changqing District People\u2019s Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongcui","family":"Diao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-spectrometric exploration of proteome structure and function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"167450","DOI":"10.1016\/j.scitotenv.2023.167450","article-title":"Environmental hormesis: new developments","volume":"906","author":"Agathokleous","year":"2024","journal-title":"Sci. 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