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Additional support came from the American Cancer Society Center for Innovation in Cancer Research Training","award":["DICR IRG-23\u20131030496-01-IRG"],"award-info":[{"award-number":["DICR IRG-23\u20131030496-01-IRG"]}]},{"DOI":"10.13039\/100011968","name":"CRT","doi-asserted-by":"publisher","award":["POST-BACC-25\u20131361803-01-PBACC"],"award-info":[{"award-number":["POST-BACC-25\u20131361803-01-PBACC"]}],"id":[{"id":"10.13039\/100011968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P36259"],"award-info":[{"award-number":["P36259"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally and is associated with factors, such as obesity, inflammation, and metabolic disorders. Bilirubin, a byproduct of heme degradation, is increasingly recognized as a signaling molecule with antioxidant properties that protect against obesity by reducing oxidative stress, decreasing inflammation, and activating the nuclear receptor PPAR\u03b1, which enhances fat metabolism and utilization. The gut microbiome converts bilirubin to urobilinogen via bilirubin reductase, which is then rapidly oxidized to urobilin, thereby influencing colon cancer outcomes. Urobilin may contribute to CRC by being linked to insulin resistance and inflammation in obese individuals, and it could cause DNA damage. Additionally, it may serve as a biomarker for CRC, obesity, insulin-resistant diabetes, and irritable bowel syndrome. This review covers enzymes in the heme oxygenase pathway (HMOX, BVR, UGT1A1) that regulate bilirubin production and excretion, as well as the microbiome-driven breakdown of bilirubin into urobilinogen and its subsequent oxidation to urobilin. It highlights the inverse relationships among CRC, obesity, and inflammation and suggests that urobilin pathways influence CRC risk. Restoring bilirubin\u2019s protective signaling and reducing circulating urobilin could open new avenues for prevention and treatment.<\/jats:p>","DOI":"10.1093\/gastro\/goag065","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:19:33Z","timestamp":1781612373000},"source":"Crossref","is-referenced-by-count":0,"title":["Microbiome-derived cancer: the catabolism of bilirubin to urobilin in the liver\u2013gut axis and its consequences"],"prefix":"10.1093","volume":"14","author":[{"given":"Jayela M","family":"Davis","sequence":"first","affiliation":[{"name":"Drug Disease & Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine , Lexington, KY 40508,","place":["United States"]},{"name":"Markey Cancer Center, University of Kentucky , Lexington, KY 40508,","place":["United 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