{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:59:30Z","timestamp":1787029170039,"version":"build-2736575974"},"reference-count":223,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["722619"],"award-info":[{"award-number":["722619"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects.<\/jats:p>","DOI":"10.3390\/nu12123709","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T20:10:22Z","timestamp":1606767022000},"page":"3709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-1471","authenticated-orcid":false,"given":"Piero","family":"Portincasa","sequence":"first","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Biomedical Sciences &amp; Human Oncology, University of Bari Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5476-7376","authenticated-orcid":false,"given":"Agostino","family":"Di Ciaula","sequence":"additional","affiliation":[{"name":"Clinica Medica \u201cA. Murri\u201d, Department of Biomedical Sciences &amp; Human Oncology, University of Bari Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Garruti","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Department of Emergency and Organ Transplantations, University of Bari \u201cAldo Moro\u201d Medical School, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0813-169X","authenticated-orcid":false,"given":"Mirco","family":"Vacca","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze del Suolo, Della Pianta e Degli Alimenti, Universit\u00e0 degli Studi di Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2010-884X","authenticated-orcid":false,"given":"Maria","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze del Suolo, Della Pianta e Degli Alimenti, Universit\u00e0 degli Studi di Bari Aldo Moro, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-7651","authenticated-orcid":false,"given":"David Q.-H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"s4","DOI":"10.5604\/01.3001.0010.5493","article-title":"Bile acid physiology","volume":"16","author":"Garruti","year":"2017","journal-title":"Ann. 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