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, as conjugated bilirubin cannot be directly reduced to urobilinoid conjugates—unconjugated bilirubin is reduced much faster. 2
Enterohepatic Circulation
After formation in the intestine, 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 intestinal epithelium is virtually impermeable to conjugated bilirubin but can reabsorb lipid-soluble unconjugated bilirubin and urobilinogen, ensuring this metabolic pathway functions efficiently. 5
The portion of urobilinogen not reabsorbed undergoes further bacterial reduction to urobilin, stercobilin, and dipyrrolmethenes, which are excreted in feces, giving stool its characteristic brown color. 5
Urinary Excretion
Urobilinogen that enters the systemic circulation is filtered by the kidneys and excreted in urine, making it detectable on routine urinalysis dipstick testing. 1, 6
Normal urine contains small amounts of urobilinogen (typically <1-2 mg/dL), but levels can increase with hemolysis, liver disease, or conditions affecting the enterohepatic circulation. 6
Clinical Significance
Decreased urobilinogen in urine and feces occurs with complete biliary obstruction, as no conjugated bilirubin reaches the intestine for bacterial conversion. 1
Increased urinary urobilinogen suggests hemolysis (increased bilirubin production) or liver disease with impaired hepatic reuptake from the enterohepatic circulation. 6
Antibiotic use can decrease urobilinogen production by suppressing intestinal bacterial flora, as demonstrated by studies showing decreased urobilinogen and fecal tryptic activity following antibiotic treatment. 1
Recent research suggests urobilin may serve as a biomarker for Cardiovascular-Kidney-Metabolic (CKM) Syndrome, as elevated urinary urobilin is frequently found in persons with cardiovascular disease and may contribute to metabolic dysfunction. 3
Diagnostic Utility
Urine urobilinogen testing has moderate sensitivity (43-74%) and specificity (77-87%) for detecting liver function test abnormalities, with positive predictive values of 83-86% for detecting at least one LFT abnormality. 6
The optimal threshold for clinical utility is 2.0/4.0 mg/dL (normal/abnormal), with negative predictive values of 85% for serum bilirubin elevations but lower for other liver function tests. 6
Urobilinogen testing is most useful as a screening tool when combined with urine bilirubin testing, as the pattern of results helps differentiate between hemolytic, hepatic, and obstructive causes of jaundice. 6