2. Academic Validation
  3. BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen

BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen

  • Nat Microbiol. 2024 Jan;9(1):173-184. doi: 10.1038/s41564-023-01549-x.
Brantley Hall 1 2,  Sophia Levy 3,  Keith Dufault-Thompson 4,  Gabriela Arp 3,  Aoshu Zhong 5,  Glory Minabou Ndjite 3,  Ashley Weiss 3,  Domenick Braccia 6,  Conor Jenkins 7,  Maggie R Grant 3,  Stephenie Abeysinghe 3,  Yiyan Yang 4,  Madison D Jermain 3,  Chih Hao Wu 8,  Bing Ma 9,  Xiaofang Jiang 10
Affiliations

Affiliations

  • 1 Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA. brantley@umd.edu.
  • 2 Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA. brantley@umd.edu.
  • 3 Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA.
  • 4 National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
  • 5 Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.
  • 6 Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, USA.
  • 7 Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA.
  • 8 Program of Computational Biology, Bioinformatics, and Genomics, University of Maryland, College Park, MD, USA.
  • 9 Institute for Genome Sciences, Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
  • 10 National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. xiaofang.jiang@nih.gov.
PMID: 38172624 DOI: 10.1038/s41564-023-01549-x
Abstract

Metabolism 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.

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