Life is full of mysteries that we ignore. Why is urine yellow? That’s exactly what it is, right? Rather than flushing the 125-year-old question down the toilet, scientists searched for the answer and discovered that a previously unknown microbial enzyme was to blame.
This enzyme, whose existence was unknown to us for a long time, is now known as bilirubin reductase. It was identified by Brantley Hall, a researcher and assistant professor at the University of Maryland who is part of a team based at the University of Maryland and the National Institutes of Health.
Bilirubin is an orange pigment released after red blood cells die. Gut bacteria then use bilirubin reductase to break down bilirubin into colorless urobilinogen, which is broken down into yellowish urobilin, which gives urine its infamous hue. Urobilin has previously been associated with urine color, but the enzyme that initiates the process that produces urobilinogen was previously unknown.
The research team said, “While it was previously thought that multiple enzymes were involved in the reduction of bilirubin, our results support the finding that the reduction of bilirubin to urobilinogen is carried out by a single enzyme.” “There is,” he said. study Recently published in Nature Microbiology.
intuition
Some gut bacteria were known to reduce bilirubin, so Hall and his team knew where to start, but they weren’t sure which specific species actually do this and how. I wanted to fill in the unknowns by investigating. This meant they had to find the gene that codes for bilirubin reductase.
Previous studies have shown that this species clostridiodes difficile It was able to reduce bilirubin (however, the mechanism was unclear).use C. difficile As a basis for comparison, the research team cultured different species of gut bacteria, exposed them to bilirubin to see if the bacteria could produce urobilinogen, and used a fluorescence assay to detect its presence. .
Using fluorescence assays, Hall and colleagues found nine strains of the species tested that appeared to have the ability to reduce bilirubin, but researchers are not sure how these bacteria break down bilirubin. It was still unclear. After fluorescence assays, the genomes of the most closely related strains were analyzed and found that several strains shared the gene encoding bilirubin reductase, an enzyme that reduces bilirubin.
The bacterial strains that metabolize bilirubin using bilirubin reductase were all derived from species that were found to belong to a single clade (informally referred to by the researchers as the bilirubin reductase clade). Within that clade, most of these species belong to the phylum Clostridium. Firmicutesa bacterial phylum important for gut health.
more than you know
The discovery of bilirubin reductase goes beyond the origin of urine color. After identifying the enzyme, researchers found that while bilirubin reductase is present in healthy adults, newborns and adults with inflammatory bowel disease have a deficiency, which could ultimately impact future treatments. I discovered that there is.
By sequencing the infant gut genome, Hall and his team discovered that bilirubin reductase is often missing during the first few months of life. Excessive buildup of bilirubin in the blood causes the skin and whites of the eyes to turn yellow, a condition known as “bilirubin”. jaundice. Most infants have some degree of jaundice, which usually goes away on its own.
Lack of bilirubin reductase is also associated with pigmented gallstones in adults with inflammatory bowel disease (inflammatory bowel disease, or IBD, is an umbrella term for several different diagnoses). Sequencing of the adult gut genome has shown that this enzyme is deficient in most patients with Crohn’s disease or ulcerative colitis whose gut genomes have been sequenced.
“With knowledge of the species, genes, and enzymes involved in bilirubin reduction, future research can focus on the extent to which bilirubin metabolism in gut bacteria influences the role of bilirubin reduction in health and disease. “It could be done,” the researchers said in the paper. study.
More research is still needed on bilirubin reductase and its effects on health. The research team believes there may be a link between the amount of urobilin produced in the body and insulin resistance, obesity, heart disease, and even heart failure. Next, you finally know why your urine is yellow.
Nature Microbiology, 2023. DOI: 10.1038/s41564-023-01549-x
