{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:23:33Z","timestamp":1790223813470,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd\u2010induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd\u2010induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry\u2010based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd\u2010induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine\u2010specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd\u2010exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut\u2010derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro\u2010\u03b2\u2010muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd\u2010exposed mice. However, MT could not ameliorate Cd\u2010induced liver damage and fibrosis in Abx\u2010treated mice. Conversely, MT still exerted a protective effect on Cd\u2010induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd\u2010exposed intestinal epithelial cell\u2010specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd\u2010induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR\u2010mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice.<\/jats:p>","DOI":"10.1111\/jpi.70005","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T07:35:49Z","timestamp":1731915349000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Melatonin Ameliorates Cadmium\u2010Induced Liver Fibrosis Via Modulating Gut Microbiota and Bile Acid Metabolism"],"prefix":"10.1111","volume":"76","author":[{"given":"Xianjiao","family":"Liu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Nanjing Agricultural University Nanjing China"},{"name":"Institute of Animal Nutritional Health Nanjing Agricultural University Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine Nanjing Agricultural University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weili","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Nanjing Agricultural University Nanjing China"},{"name":"Institute of Animal Nutritional Health Nanjing Agricultural University Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine Nanjing Agricultural University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Nanjing Agricultural University Nanjing China"},{"name":"Institute of Animal Nutritional Health Nanjing Agricultural University Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine Nanjing Agricultural 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Agricultural University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Nanjing Agricultural University Nanjing China"},{"name":"Institute of Animal Nutritional Health Nanjing Agricultural University Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine Nanjing Agricultural University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Del Pilar Abreo","family":"Medina","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Nanjing Agricultural University Nanjing China"},{"name":"Institute of Animal Nutritional Health Nanjing Agricultural University Nanjing China"},{"name":"MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine Nanjing Agricultural University 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