What is Urobilinogen?
Urobilinogen is a colorless breakdown product of bilirubin formed by bacterial reduction in the intestinal tract, which can be reabsorbed into the enterohepatic circulation and excreted in both bile and urine. 1
Biochemical Formation and Metabolism
Urobilinogen is produced when conjugated bilirubin reaches the intestinal tract and undergoes bacterial reduction by gut microflora, primarily through the enzyme bilirubin reductase (BilR) expressed by intestinal bacteria such as Clostridium perfringens. 2, 3
The reduction process converts bilirubin into urobilinogen species in the intestinal lumen, which can then be further oxidized to urobilin (a pinkish-yellow pigment) and stercobilin. 2, 4, 5
Bacterial reduction of bilirubin to urobilinogen requires prior hydrolysis of bilirubin glucuronides—unconjugated bilirubin is reduced much faster than conjugated forms, and bilirubin diglucuronide cannot be directly reduced to conjugated urobilinoids. 2
Enterohepatic Circulation
After formation in the gut, urobilinogen is partially reabsorbed into the enterohepatic circulation through the hepatic portal vein, where it is taken up by the liver and re-excreted unchanged in bile. 1, 5
The residual urobilinogen that is not reabsorbed undergoes further reduction to urobilin, stercobilin, and dipyrrolmethenes, which are excreted in feces giving stool its characteristic brown color. 5
A small fraction of reabsorbed urobilinogen escapes hepatic uptake and is filtered by the kidneys into urine, where it can be detected by dipstick urinalysis. 1, 6
Clinical Significance
Decreased urobilinogen levels occur when antibiotics suppress gut bacterial flora, as demonstrated by studies showing reduced urobilinogen and fecal tryptic activity following antibiotic treatment, which can be restored after fecal microbiota transplantation. 1
Urobilinogen can be measured in urine using commercially available dipsticks as part of quality control procedures, though its clinical utility as a screening test for liver function abnormalities has limitations. 1, 6
Urine urobilinogen has a sensitivity of 70-74% for detecting serum bilirubin elevations and 43-53% for other liver function test abnormalities, with optimal clinical utility when using a normal/abnormal threshold of 2.0/4.0 mg/dL. 6
Pathophysiological Considerations
Elevated urobilin levels in urine may serve as a biomarker for Cardiovascular-Kidney-Metabolic (CKM) Syndrome, as recent evidence suggests urobilin absorption via the hepatic portal vein contributes to cardiovascular disease through a gut-liver-kidney axis. 3
In Gunn rats (which lack bilirubin UDP-glucuronyltransferases), urobilinogen-i represents the major bilirubin derivative in bile, demonstrating that bilirubin can reach the gut via routes other than biliary excretion. 4
The rapid bacterial reduction of bilirubin to urobilinogen in the intestinal tract makes it unlikely that unconjugated bilirubin is formed and absorbed to an appreciable degree under normal circumstances. 5