TY - JOUR
T1 - Bilirubin bioconversion to urobilin in the gut-liver-kidney axis
T2 - A biomarker for insulin resistance in the Cardiovascular-Kidney-Metabolic (CKM) Syndrome
AU - Kipp, Zachary A.
AU - Badmus, Olufunto O.
AU - Stec, David E.
AU - Hall, Brantley
AU - Hinds, Terry D.
N1 - Publisher Copyright:
© 2024
PY - 2025/2
Y1 - 2025/2
N2 - The rising rates of obesity worldwide have increased the incidence of cardiovascular disease (CVD), making it the number one cause of death. Higher plasma bilirubin levels have been shown to prevent metabolic dysfunction and CVD. However, reducing levels leads to deleterious outcomes, possibly due to reduced bilirubin half-life that escalates the production of its catabolized product, urobilinogen, produced by gut bacteria and naturally oxidized to urobilin. Recent findings suggest that the involvement of the microbiome catabolism of bilirubin to urobilin and its absorption via the hepatic portal vein contributes to CVD, suggesting a liver-gut axis involvement. We discuss the studies that demonstrate that urobilin is frequently raised in the urine of persons with CVD and its probable role in acquiring the disease. Urobilin is excreted from the kidneys into the urine and may serve as a biomarker for Cardiovascular-Kidney-Metabolic (CKM) Syndrome. We deliberate on the newly discovered bilirubin reductase (BilR) bacterial enzyme that produces urobilin. We discuss the bacterial species expressing BilR, how they impact CVD, and whether suppressing urobilin production and increasing bilirubin may provide new therapeutic strategies for CKM. Possible therapeutic mechanisms for achieving this goal are discussed.
AB - The rising rates of obesity worldwide have increased the incidence of cardiovascular disease (CVD), making it the number one cause of death. Higher plasma bilirubin levels have been shown to prevent metabolic dysfunction and CVD. However, reducing levels leads to deleterious outcomes, possibly due to reduced bilirubin half-life that escalates the production of its catabolized product, urobilinogen, produced by gut bacteria and naturally oxidized to urobilin. Recent findings suggest that the involvement of the microbiome catabolism of bilirubin to urobilin and its absorption via the hepatic portal vein contributes to CVD, suggesting a liver-gut axis involvement. We discuss the studies that demonstrate that urobilin is frequently raised in the urine of persons with CVD and its probable role in acquiring the disease. Urobilin is excreted from the kidneys into the urine and may serve as a biomarker for Cardiovascular-Kidney-Metabolic (CKM) Syndrome. We deliberate on the newly discovered bilirubin reductase (BilR) bacterial enzyme that produces urobilin. We discuss the bacterial species expressing BilR, how they impact CVD, and whether suppressing urobilin production and increasing bilirubin may provide new therapeutic strategies for CKM. Possible therapeutic mechanisms for achieving this goal are discussed.
KW - Antioxidant
KW - BLVRA
KW - BilR
KW - Bilirubin reductase
KW - Biliverdin reductase
KW - HMOX1
KW - Heme oxygenase
KW - MASLD
KW - Microbiome
KW - Obesity
UR - http://www.scopus.com/inward/record.url?scp=85210139286&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85210139286&partnerID=8YFLogxK
U2 - 10.1016/j.metabol.2024.156081
DO - 10.1016/j.metabol.2024.156081
M3 - Review article
AN - SCOPUS:85210139286
SN - 0026-0495
VL - 163
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
M1 - 156081
ER -