Scientists have discovered the microbial enzyme responsible for giving urine its yellow color. A team of researchers from the University of Maryland and the National Institutes of Health identified the enzyme, called bilirubin reductase, which paves the way for more research on how the bacteria in our guts impact health problems.

Our bodies produce a bright orange pigment called bilirubin when red blood cells are broken down after their typical lifespan of six months. Bilirubin is normally released into the intestines and eliminated from the body.

But some bilirubin can be reabsorbed back into the bloodstream. Too much reabsorption can cause a buildup in the blood and lead to jaundice – when the skin and eyes take on a yellowish tint.

Desvelan el misterio del color amarillo de la orina
The mystery of the yellow color of urine is unraveled | photo krakenimages.com on depositphotos.com

In the intestines, the bilirubin interacts with the trillions of bacteria living there. The study found these gut bacteria have an enzyme called bilirubin reductase that converts bilirubin into a colorless compound called urobilinogen. Urobilinogen then spontaneously breaks down into urobilin, which gives urine its familiar yellow color.

For over a century, scientists knew urobilin was responsible for yellow urine but didn’t know how it got there. This research team has finally solved the mystery by identifying the crucial bilirubin reductase enzyme made by gut bacteria.

The discovery could help many health problems. Most healthy adults have the bilirubin reductase enzyme, but it’s often missing in newborns and people with inflammatory bowel disease. The researchers believe this may contribute to jaundice in babies and formation of gallstones containing pigment.

a, Illustrated representation of the haem degradation pathway. Key human enzymes are labelled with grey text. b, Diagram of the structures of bilirubin and urobilinogen. The bonds reduced during bilirubin reduction are shown in red. c, Results of fluorescence assay screening of bacterial strains. Measurements from n = 3 independent biological replicates are shown as black points. Bars show the ratios of the samples’ fluorescence to a corresponding abiotic media sample with bilirubin added. Error bars indicate 1 s.e. above and below the mean values. The grey line marks a ratio of 5, above which the sample was considered to be positive for bilirubin reduction | photo Brantley Hall et al.

Going forward, identifying this enzyme allows scientists to study how gut bacteria impact bilirubin levels in the blood and related conditions like jaundice. It provides insight into the complex relationship between the intestines and liver.

The gut microbiome has also been linked to diseases ranging from allergies to arthritis to psoriasis. This finding brings researchers closer to fully understanding how the bacteria in our intestines influence overall human health.

The researchers say their collaborative, multi- disciplinary approach was key to solving this physiological puzzle. The discovery is the culmination of years of effort and highlights again how important our gut bacteria are for well-being.

Sources

University of Maryland | Hall, B., Levy, S., Dufault-Thompson, K. et al. BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen. Nat Microbiol (2024). doi.org/10.1038/s41564-023-01549-x

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