{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T07:01:32Z","timestamp":1762326092990,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Vienna","award":["P32303"],"award-info":[{"award-number":["P32303"]}]},{"name":"Austrian Science Fund","award":["P32303"],"award-info":[{"award-number":["P32303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In addition to their role in lipid absorption, bile acids (BAs) are also known for several relevant (endocrine) activities including contributing to the regulation of energy homeostasis and some non-communicable diseases (NCDs). Furthermore, moderately elevated unconjugated bilirubin levels, as observed in Gilbert\u2019s syndrome (GS), may protect against NCDs. We therefore hypothesized that the BA profile in GS subjects differs from that of normo-bilirubinemic individuals. To test this, we performed a human case-control study, in which GS (n = 60) and controls (n = 60) were matched for age and gender, and serum BA concentrations were measured by liquid-chromatography mass spectrometry (LC\u2013MS). Despite analyzing a comprehensive panel of BAs, no significant differences between the two groups were observed. These data suggest that bile acid concentrations are similar between groups, indicating that altered bilirubin metabolism unlikely influences their transport into the blood.<\/jats:p>","DOI":"10.3390\/ijms26062475","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T12:02:59Z","timestamp":1741608179000},"page":"2475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bilirubin Metabolism Does Not Influence Serum Bile Acid Profiles According to LC\u2013MS: A Human Case-Control Study"],"prefix":"10.3390","volume":"26","author":[{"given":"Tamara Christina","family":"Stelzer","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Doctoral School for Pharmaceutical, Nutritional and Sport Sciences (PhaNuSpo), University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1904-8621","authenticated-orcid":false,"given":"Ralf","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, 76131 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1769-6799","authenticated-orcid":false,"given":"Paola Gloria","family":"Ferrario","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, Federal Research Institute of Nutrition and Food, 76131 Karlsruhe, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8015-7774","authenticated-orcid":false,"given":"Christine","family":"M\u00f6lzer","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna General Hospital, W\u00e4hringer G\u00fcrtel 18-20, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-8697","authenticated-orcid":false,"given":"Marlies","family":"Wallner","sequence":"additional","affiliation":[{"name":"Institute of Dietetics and Nutrition, University of Applied Sciences FH JOANNEUM, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1772-6695","authenticated-orcid":false,"given":"Rodrig","family":"Marculescu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Doberer","sequence":"additional","affiliation":[{"name":"Vienna Health Care Group, Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Bruenner Stra\u00dfe 68, 1210 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew Cameron","family":"Bulmer","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences, Griffith University, Southport, QLD 4215, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-7265","authenticated-orcid":false,"given":"Karl-Heinz","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"G619","DOI":"10.1152\/ajpgi.00308.2020","article-title":"Metabolic consequences of ileal interruption of the enterohepatic circulation of bile acids","volume":"319","author":"Verkade","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R85","DOI":"10.1530\/JOE-15-0469","article-title":"The role of bile acids in metabolic regulation","volume":"228","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"van der Schoor, L.W.E., Verkade, H.J., Bertolini, A., de Wit, S., Mennillo, E., Rettenmeier, E., Weber, A.A., Havinga, R., Val\u00e1\u0161kov\u00e1, P., and Ja\u0161prov\u00e1, J. (2021). Potential of therapeutic bile acids in the treatment of neonatal Hyperbilirubinemia. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-90687-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41575-021-00566-7","article-title":"Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology","volume":"19","author":"Fuchs","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1152\/physrev.00010.2008","article-title":"Role of bile acids and bile acid receptors in metabolic regulation","volume":"89","author":"Lefebvre","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nature04330","article-title":"Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation","volume":"439","author":"Watanabe","year":"2006","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"V\u00edtek, L. (2012). The role of bilirubin in diabetes, metabolic syndrome, and cardiovascular diseases. Front. Pharmacol., 3.","DOI":"10.3389\/fphar.2012.00055"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"154913","DOI":"10.1016\/j.metabol.2021.154913","article-title":"Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert\u2019s syndrome individuals","volume":"125","author":"Hana","year":"2021","journal-title":"Metabolism"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"di Gregorio, M.C., Cautela, J., and Galantini, L. (2021). Physiology and Physical Chemistry of Bile Acids. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041780"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1113\/JP282395","article-title":"Sexual dimorphism: Increased sterol excretion leads to hypocholesterolaemia in female hyperbilirubinaemic Gunn rats","volume":"600","author":"Vidimce","year":"2022","journal-title":"J. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Molzer, C., Wallner, M., Kern, C., Tosevska, A., Schwarz, U., Zadnikar, R., Doberer, D., Marculescu, R., and Wagner, K.H. (2016). Features of an altered AMPK metabolic pathway in Gilbert\u2019s Syndrome, and its role in metabolic health. Sci. Rep., 6.","DOI":"10.1038\/srep30051"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"M\u00f6lzer, C., Wallner, M., Kern, C., Tosevska, A., Zadnikar, R., Doberer, D., Marculescu, R., and Wagner, K.H. (2017). Characteristics of the heme catabolic pathway in mild unconjugated hyperbilirubinemia and their associations with inflammation and disease prevention. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-00933-y"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tosevska, A., Moelzer, C., Wallner, M., Janosec, M., Schwarz, U., Kern, C., Marculescu, R., Doberer, D., Weckwerth, W., and Wagner, K.H. (2016). Longer telomeres in chronic, moderate, unconjugated hyperbilirubinaemia: Insights from a human study on Gilbert\u2019s Syndrome. Sci. Rep., 6.","DOI":"10.1038\/srep22300"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Frommherz, L., Bub, A., Hummel, E., Rist, M.J., Roth, A., Watzl, B., and Kulling, S.E. (2016). Age-Related Changes of Plasma Bile Acid Concentrations in Healthy Adults\u2014Results from the Cross-Sectional KarMeN Study. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153959"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11306-023-02065-z","article-title":"A new statistical workflow (R-packages based) to investigate associations between one variable of interest and the metabolome","volume":"20","author":"Ferrario","year":"2023","journal-title":"Metabolomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1080\/10408363.2018.1428526","article-title":"Diagnostic criteria and contributors to Gilbert\u2019s syndrome","volume":"55","author":"Wagner","year":"2018","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E191","DOI":"10.1152\/ajpendo.00405.2020","article-title":"Bilirubin as a metabolic hormone: The physiological relevance of low levels","volume":"320","author":"Creeden","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Punzo, A., Silla, A., Fogacci, F., Perillo, M., Cicero, A.F.G., and Caliceti, C. (2024). Bile Acids and Bilirubin Role in Oxidative Stress and Inflammation in Cardiovascular Diseases. Diseases, 12.","DOI":"10.3390\/diseases12050103"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"s43","DOI":"10.5604\/01.3001.0010.5496","article-title":"Bile Acids in the Treatment of Cardiometabolic Diseases","volume":"16","year":"2017","journal-title":"Ann. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gordon, D.M., Hong, S.H., Kipp, Z.A., and Hinds, T.D. (2021). Identification of Binding Regions of Bilirubin in the Ligand-Binding Pocket of the Peroxisome Proliferator-Activated Receptor-A (PPARalpha). Molecules, 26.","DOI":"10.3390\/molecules26102975"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1111\/j.1582-4934.2010.01098.x","article-title":"Bile acids decrease intracellular bilirubin levels in the cholestatic liver: Implications for bile acid-mediated oxidative stress","volume":"15","author":"Muchova","year":"2011","journal-title":"J. Cell Mol. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2475\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:50:17Z","timestamp":1760028617000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":21,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26062475"],"URL":"https:\/\/doi.org\/10.3390\/ijms26062475","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,3,10]]}}}