Abstract
AbstractMetabolism of haem by-products such as bilirubin by humans and their gut microbiota is essential to human health, as excess serum bilirubin can cause jaundice and even neurological damage. The bacterial enzymes that reduce bilirubin to urobilinogen, a key step in this pathway, have remained unidentified. Here we used biochemical analyses and comparative genomics to identify BilR as a gut-microbiota-derived bilirubin reductase that reduces bilirubin to urobilinogen. We delineated the BilR sequences from similar reductases through the identification of key residues critical for bilirubin reduction and found that BilR is predominantly encoded by Firmicutes species. Analysis of human gut metagenomes revealed that BilR is nearly ubiquitous in healthy adults, but prevalence is decreased in neonates and individuals with inflammatory bowel disease. This discovery sheds light on the role of the gut microbiome in bilirubin metabolism and highlights the significance of the gut–liver axis in maintaining bilirubin homeostasis.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Intramural Research Program, National Institutes of Health
Startup funding, University of Maryland
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Microbiology (medical),Genetics,Applied Microbiology and Biotechnology,Immunology,Microbiology