A recent study published in the journal Nature Microbiology has identified the microbial enzyme responsible for the yellow color of urine. Researchers from the University of Maryland and the National Institutes of Health made this discovery, paving the way for further research into the role of the gut microbiome in diseases such as jaundice and inflammatory bowel diseases.
„The discovery of this enzyme, called Bilirubin Reductase, finally unveils the mystery behind the yellow color of urine. It is remarkable that this everyday biological phenomenon remained unresolved for so long, and our team is delighted to provide an explanation.“ – Brantley Hall, lead author of the study and Assistant Professor at the Institute for Cell Biology and Molecular Genetics at the University of Maryland
When red blood cells are broken down after their six-month lifespan, a by-product called bilirubin, a bright orange pigment, is produced. Bilirubin is usually excreted into the intestine for elimination but can also be partially absorbed. Excessive reabsorption can lead to bilirubin accumulation in the blood, causing jaundice, a condition that results in yellowing of the skin and eyes. Upon reaching the intestine, the resident flora can convert bilirubin into other molecules.
„Gut microbes encode an enzyme called Bilirubin Reductase, which converts bilirubin into a colorless by-product called Urobilinogen,“ explained Hall, who also holds a joint appointment at the Institute for Advanced Computer Studies at the University of Maryland. „Urobilinogen then spontaneously breaks down into a molecule called Urobilin, which is responsible for the yellow color we all recognize.“
Urobilin has long been associated with the yellow color of urine, and the discovery of the enzyme responsible for this addresses a question that has eluded scientists for over a century.
In addition to solving a scientific puzzle, these findings could have important health implications. The research team found that Bilirubin Reductase is present in nearly all healthy adults but is often absent in newborns and individuals with inflammatory bowel diseases. They speculate that the absence of Bilirubin Reductase could contribute to jaundice in infants and the formation of pigmented gallstones.
„Having identified this enzyme, we can now investigate how the bacteria in our gut affect circulating bilirubin levels and related health conditions such as jaundice,“ said study co-author and NIH researcher Xiaofang Jiang. „This discovery lays the groundwork for understanding the gut-liver axis.“
In addition to jaundice and inflammatory bowel diseases, the gut microbiome has been linked to various diseases and conditions, from allergies to arthritis and psoriasis. This latest discovery brings researchers closer to a holistic understanding of the role of the gut microbiome in human health.
„The multidisciplinary approach that we were able to implement through collaboration between our labs was crucial to solving the physiological puzzle of why our urine appears yellow,“ said Hall. „It is the culmination of our team’s long-standing work, highlighting yet another reason why our gut microbiome is so important for human health.“
This article was adapted from a text by Brantley Hall and Sophia Levy.
UMD co-authors of the study included, along with Hall, Stephenie Abeysinghe (BS ’23, Public Health Science); Domenick Braccia (Ph.D. ’22, Life Sciences); Maggie Grant, Major in Biology; Biochemistry Ph.D. Student Conor Jenkins; Life Sciences Ph.D. students Gabriela Arp (BS ’19, Public Health Sciences; BA ’19, Spanish Language), Madison Jermain, Sophia Levy (BS ’19, Chemical Engineering; BS ’19, Life Sciences) and Chih Hao Wu (BS ’21, Biology). Sciences); Glory Minabou Ndjite (BS ’22, Public Health Science); and Ashley Weiss (BS ’22, Life Sciences).
Their work titled „Discovery of a microbial gut enzyme that reduces bilirubin to urobilinogen“ was published in the journal Nature Microbiology on January 3, 2024.
Hall, B., et al. (2024). BilR is a microbial gut enzyme that reduces bilirubin to urobilinogen. Nature Microbiology. doi.org/10.1038/s41564-023-01549-x.