Enzyme that helps make urine yellow may lead to insights on gut microbiome

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Researchers have long known that a blood byproduct gives urine its yellow hue. But identifying the full chain of events that leads red blood cells to degrade into yellow urine has always proved elusive. Until now.

In a new study, scientists say they’ve discovered a missing link in the transformative process – bilirubin reductase, a microbial enzyme that causes urine’s yellow pigment – and that it may open doors to more research on the gut microbiome’s role in certain illnesses.

The analysis, published in Nature Microbiology, answers long-standing questions about urine production. The process begins when red blood cells degrade in the body at the end of their six-month life cycle.

These cells produce heme, the precursor of the hemoglobin that delivers oxygen to the body’s tissues. Heme then degrades into a bright orange pigment known as bilirubin, which passes through the liver and degrades first into urobilinogen and then further into urobilin, which is excreted in both urine and feces. An excess of bilirubin can lead to jaundice, which can cause a yellowish discoloration of the skin and eyes.

In the newly released study, researchers managed to isolate the enzyme that causes bilirubin to become urobilin. They named it bilirubin reductase and identified a potential genetic marker.

When the researchers analyzed a large data set of genomes, they found the marker in most healthy adults. But in some adults with inflammatory bowel disease and many infants, it was missing, and an analysis of infant gut microbiomes found it is often completely absent in newborns. That absence may contribute to jaundice, the researchers hypothesize.

Urobilin’s existence has been known since pioneering studies in the 1890s. But the discovery of the new enzyme fleshes out a part of the process that has long remained hidden.

“It’s remarkable that an everyday biological phenomenon went unexplained for so long,” Brantley Hall, an assistant professor in the University of Maryland’s Department of Cell Biology and Molecular Genetics and the paper’s lead author, said in a news release.

There’s more to learn about the process, the researchers write. They call for more research on the role of bilirubin in health and disease.