Researchers identify the microbial enzyme responsible for the yellow color of urine

Researchers from the University of Maryland and the National Institutes of Health have identified the microbial enzyme responsible for yellowing urine, according to a new study published in the journal Nature Microbiology on January 3, 2024.

The discovery of this enzyme, called bilirubin reductase, paves the way for further research into the role of the gut microbiome in diseases such as jaundice and inflammatory bowel disease.

This enzyme discovery finally unravels the mystery behind the yellow color of urine. It is remarkable that an everyday biological phenomenon has remained unexplained for so long, and our team is excited to be able to explain it.”

Brantley Hall, lead author of the study, assistant professor in the Department of Cell Biology and Molecular Genetics at the University of Maryland

When red blood cells break down after their six-month lifespan, a bright orange pigment called bilirubin is produced as a byproduct. Bilirubin is typically secreted into the intestine, where it is destined for excretion but can also be partially reabsorbed. Excessive reabsorption can lead to a build-up of bilirubin in the blood and can cause jaundice – a condition that results in yellowing of the skin and eyes. Once in the gut, flora can convert bilirubin into other molecules.

“Gut microbes encode the enzyme bilirubin reductase that converts bilirubin into a colorless byproduct called urocholinegen,” explained Hall, who holds a joint appointment at the University of Maryland Institute for Advanced Computer Studies. “Urocholinogen is then spontaneously degraded into a molecule called urobilin, which is responsible for the yellow color we all know.”

Urobilin has long been linked to the yellow hue of urine, but the research team’s discovery of the enzyme responsible answers a question that has eluded scientists for more than a century.

In addition to solving a scientific mystery, these findings could have important health implications. The research team found that bilirubin reductase is present in almost all healthy adults, but is often lacking in newborns and people with inflammatory bowel disease. They hypothesize that the absence of bilirubin reductase may contribute to infant jaundice and the formation of melanocytic gallstones.

“Now that we have identified this enzyme, we can begin to investigate how the bacteria in our gut affect circulating bilirubin levels and related conditions such as jaundice,” said study co-author and NIH researcher Xiaofang Jiang. “This discovery lays the foundation for understanding the gut-liver axis.”

In addition to jaundice and inflammatory bowel disease, the gut microbiome has been linked to a variety of diseases and conditions, from allergies to arthritis to psoriasis. This latest discovery brings researchers closer to achieving a holistic understanding of the role of the gut microbiome in human health.

“The multidisciplinary approach we were able to take—thanks to the collaboration between our labs—was key to solving the physiological puzzle of why our urine looks yellow,” Hall said. “It is the culmination of many years of work by our team and highlights yet another reason why our gut microbiome is so vital to human health.”

This article was adapted from text provided by Brantley Hall and Sophia Levy.

In addition to Hall, UMD-affiliated authors included Stephenie Abeysinghe (BS ’23, public health science); Domenick Braccia (Ph.D. ’22, biological sciences); biological sciences Maggie Grant; biochemistry Ph.D. student Conor Jenkins; of biological sciences Ph.D. students Gabriela Arp (BS ’19, public health science, BA ’19, Spanish), Madison Jermain, Sophia Levy (BS ’19, chemical engineering, BS ’19, biological sciences), and Chih Hao Wu (BS ’21, biological sciences); Glory Minabou Ndjite (BS ’22, public health science); and Ashley Weiss (BS ’22, biological sciences).

Their paper, “Discovery of a gut microbial enzyme that reduces bilirubin to urocholinerogen,” was published in the journal Nature Microbiology on January 3, 2024.