Most of us never think about why urine is yellow. A study published in Nature Microbiology in 2024 finally identified the enzyme responsible. For urologists, the colour of urine matters for a practical reason: a change to red can be the first sign of a serious problem. This article explains the discovery and why blood in the urine, or a raised PSA, is best investigated in a rapid diagnostic clinic.
Why urine is yellow
Professor Prokar Dasgupta remembers being taught in biology classes at school in India that urine is yellow because of a by-product of bile called urobilin. Bilirubin from bile is converted by bacteria in the gut into urobilinogen, which then breaks down into urobilin. Problems with this process can cause jaundice.
Although urobilin was identified as the yellow pigment more than 125 years ago, the enzyme that drives the key step had eluded scientists until now. It had been thought that several different enzymes were involved.
The discovery of BilR
Using biochemical analysis and comparative genomics, the researchers identified a single enzyme, which they named bilirubin reductase, or BilR. It is produced by bacteria in the gut, mainly species known as Firmicutes, and is found in almost all healthy adults. They profiled its presence in 7,960 genetic samples from the gut.
BilR is often missing in newborn babies, who commonly develop jaundice, and is reduced in people with inflammatory bowel disease. Advances in genome sequencing made the discovery possible, as many gut bacteria are difficult to study in the laboratory.
When urine turns red
Blood in the urine, known as haematuria, is an alarming symptom. Sometimes there is a harmless explanation: eating a lot of beetroot can turn urine red, for example. Even so, red urine should always be checked. The NHS explains the causes of blood in urine and when to see a GP.
The main concern is a cancer of the urinary tract. A systematic review of 44 studies, including 229,701 patients, found bladder cancer in 17% of people with visible blood in the urine and 3.3% of those with blood found only on testing. Kidney cancers were much less common. Being male and having smoked increased the risk, particularly for bladder cancer.
These figures also mean that most people with haematuria do not have cancer, and many can be reassured quickly after investigation. A newer urine test for bladder cancer is described in our article on the GALEAS Bladder test.
The one-stop clinic
Many patients with haematuria are now seen in rapid diagnostic clinics, where assessment, imaging and a cystoscopy take place in a single visit. This avoids repeated appointments and the anxiety of waiting for results between them.
The other common reasons for referral are a raised PSA test and a lump in a testicle, which can usually be assessed by examination and an ultrasound scan.
Rapid diagnosis for a raised PSA
A pathway called RAPID was evaluated in 2,130 patients across three centres. It combined an MRI scan of the prostate with a biopsy through the skin behind the scrotum, under local anaesthetic or sedation. Around 43% of patients avoided an immediate biopsy because their MRI was not suspicious, and clinically significant cancer was found in 26%. Satisfaction was high, with half of those surveyed preferring to have their tests on a single day. Our overview of prostate cancer describes the tests involved, and our page on benign prostatic enlargement explains another common cause of a raised PSA.
Looking ahead
As urological tests become quicker and more accurate, rapid pathways are likely to become the norm. They can also help reduce the long waiting times many patients have faced since the pandemic. Cancer Research UK has more information on bladder cancer symptoms and diagnosis, and our article on smart screening explains a structured approach to prostate checks.
If you have noticed blood in your urine or have a raised PSA, please contact the clinic to arrange a prompt assessment.