Researchers Identify Complete Bacterial Pathway for Converting Bilirubin to Urobilinogen in Human Gut
Researchers have mapped the full two-step enzymatic pathway by which gut bacteria convert bilirubin — a byproduct of heme breakdown — into urobilinogen, identifying a previously unknown enzyme called bilinoid vinyl reductase (BilV). The study clarifies that the recently discovered bilirubin reductase (BilR) alone is insufficient for this conversion, and that a second enzyme acting on vinyl groups is also required. This finding is significant because bilirubin and its derivatives are linked to inflammatory and metabolic diseases, and understanding their microbial metabolism could open new avenues for treatment.
A new preprint study on bioRxiv reports the complete elucidation of the bacterial pathway that converts bilirubin into urobilinogen within the human gut. The researchers found that the process requires two distinct reactions — reducting methine bridges and reducing vinyl groups — which can occur in either order. While the recently characterized enzyme bilirubin reductase (BilR) handles the methine bridge reduction and produces a novel intermediate called divinylurobilinogen, it cannot complete the full conversion on its own. Using transcriptomic profiling, the team identified a second enzyme, bilinoid vinyl reductase (BilV), a flavin-dependent oxidoreductase belonging to the Old Yellow Enzyme superfamily, which reduces the vinyl groups. BilV is broadly distributed across human gut bacteria, though its distribution only partially overlaps with that of BilR, suggesting varied metabolic capacities across individuals' microbiomes. Because bilirubin levels and its downstream derivatives are associated with susceptibility to inflammatory and metabolic disorders, this complete pathway map provides a foundation for mechanistic studies into how gut microbial bilirubin metabolism influences human health and disease.
What's missing
As a preprint, this study has not yet undergone formal peer review, so its findings should be considered preliminary. The study does not address whether individual variation in BilV and BilR distribution across gut microbiomes correlates with measurable differences in human health outcomes, nor does it establish causality between altered bilirubin metabolism and specific diseases. The physiological conditions under which the two reactions preferentially occur in vivo remain unclear.
What different sources said
- bioRxivCenter
Identification of the complete pathway for conversion of bilirubin to urobilinogen by human gut bacteria
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