{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:59:53Z","timestamp":1790312393934,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012899","name":"Key Research and Development Programme of Gansu Province","doi-asserted-by":"publisher","award":["25YFFA028"],"award-info":[{"award-number":["25YFFA028"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012899","name":"Key Research and Development Programme of Gansu Province","doi-asserted-by":"publisher","award":["25JRRA1273"],"award-info":[{"award-number":["25JRRA1273"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Gansu Province","award":["25JRRA668"],"award-info":[{"award-number":["25JRRA668"]}]},{"DOI":"10.13039\/100012899","name":"Central Universities\u2019 Fundamental Scientific Research Operating Costs","doi-asserted-by":"publisher","award":["lzujbky-2024-it21"],"award-info":[{"award-number":["lzujbky-2024-it21"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Low-molecular-weight polycyclic aromatic hydrocarbons (LMW-PAHs) are ubiquitous dietary contaminants in grilled, smoked, and thermally processed foods, yet their hepatotoxic mechanisms remain poorly understood. We established a rat model co-exposed to fluorene (Flu) and phenanthrene (Phe) at low, medium, and high doses, validated by urinary metabolites and colonic AHR\/CYP1A1. We assessed colonic barrier integrity, gut microbiota (GM) composition, lipopolysaccharide (LPS) translocation, hepatic inflammation, oxidative stress, lipid metabolism, and gut\u2013liver metabolomic profiles. Flu\/Phe co-exposure reduced tight junction proteins and altered GM composition\u2014characterized by increased Gram-negative bacteria and reduced gut health indices\u2014facilitating LPS translocation and upregulating the hepatic TLR4\/MyD88\/NLRP3 signaling axis, which was associated with inflammation, oxidative stress, and lipid metabolic disorders. The medium-dose group exhibited the most pronounced effects, suggesting a possible non-monotonic dose\u2013response relationship. Metabolomic analysis revealed bile secretion as the most significantly enriched pathway common to colon and liver. Mechanistically, combined Flu\/Phe exposure disrupted bile acid homeostasis by suppressing FXR\/SHP while upregulating CYP7A1 and CYP8B1. Collectively, these findings demonstrate that LMW-PAHs induce liver injury through two distinct mechanisms: GM dysbiosis-driven LPS\/TLR4 signaling and FXR\/SHP-mediated bile acid dysregulation. The gut\u2013liver axis thus provides candidate molecular nodes for LMW-PAH dietary risk assessment, though validation at dietary-relevant doses is required given the high-dose mechanistic design of this study.<\/jats:p>","DOI":"10.3390\/foods15193387","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:09:08Z","timestamp":1790161748000},"page":"3387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Gut\u2013Liver Axis Mediates Liver Injury Induced by Low-Molecular-Weight Polycyclic Aromatic Hydrocarbons Through TLR4-Dependent Inflammation and Bile Acid Dysregulation"],"prefix":"10.3390","volume":"15","author":[{"given":"Shiyao","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1518-0249","authenticated-orcid":false,"given":"Jiali","family":"Qin","sequence":"additional","affiliation":[{"name":"School of Public Health, Southeast University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Yunting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"given":"Xiuxia","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Yixuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Kefan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Haitao","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2168-4515","authenticated-orcid":false,"given":"Zhengyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1676-5345","authenticated-orcid":false,"given":"Chengyun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9761-8821","authenticated-orcid":false,"given":"Junling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.38212\/2224-6614.3429","article-title":"Recent advances in the analysis of polycyclic aromatic hydrocarbons in food and water","volume":"30","author":"Chen","year":"2022","journal-title":"J. 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