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This study investigated the effects of Chlorogenic acid (CGA) and VX765 on DON-induced enterohepatic injury. A total of 48 female mice were divided into four groups: control (normal saline), DON (1 mg\/kg.bw), CGA (100 mg\/kg.bw CGA + 1 mg\/kg.bw DON), and VX765 (100 mg\/kg.bw VX765 + 1 mg\/kg.bw DON). After 28-day gavage period, the results showed that CGA and VX765 reduced DON-induced intestinal barrier damage. Metabolomics data revealed that CGA and VX765 restored cecal microbiota structure and alleviated DON-induced hepatic injury and lipid metabolic disorders by reshaping intestinal microbiota. Retrograde endocannabinoid signaling was identified as a critical pathway for cecal microbial metabolism and hepatic lipid regulation mediated by CGA and VX765. Additionally, CGA and VX765 reversed the upregulation of IMPA, CDS2, DGKA, NDUFS8, and MAPK1 mRNA and protein expression levels induced by DON via the microbiota-gut-liver axis.<\/jats:p>","DOI":"10.3390\/toxins17090467","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:24:25Z","timestamp":1758198265000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Chlorogenic Acid and VX765 Alleviate Deoxynivalenol-Induced Enterohepatic Injury and Lipid Metabolism Disorders by Improving Intestinal Microecology"],"prefix":"10.3390","volume":"17","author":[{"given":"Tao","family":"Wen","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Zoonoses, College of Animal Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirui","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Zoonoses, College of Animal Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-7479","authenticated-orcid":false,"given":"Huijun","family":"Guo","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Zoonoses, College of Animal Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Zoonoses, College of Animal Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Zoonoses, College of Animal Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6707-2274","authenticated-orcid":false,"given":"Chunyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Zoonoses, College of Animal Veterinary Medicine, Shandong Agricultural University, Tai\u2019an 271018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Abraham, N., Schroeter, K.L., Zhu, Y., Chan, J., Evans, N., Kimber, M.S., Carere, J., Zhou, T., and Seah, S.Y.K. 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