As your knowledge about the gut microbiota grows, you may be aware that the gut microbiota is connected with multiple body organs such as the liver, forming the gut-liver axis. More particularly, the liver produces various molecules to help us digest, such as biliary acids, and the gut microbiota transforms them into different compounds that can be reabsorbed by the liver or excreted in the feces, playing an essential role in maintaining gut health. This is the case for bilirubin.
You might have encountered the word ‘bilirubin’ in your blood analysis, but what does it stand for? The cells in our body are constantly recycled; when a cell is too old or malfunctioning, it is eliminated, and all constituents are recycled to create new cells, such as iron from our red blood cells. Bilirubin is a byproduct of the recycling of heme from our red blood cells by macrophages. It is taken up by the liver where bilirubin is being conjugated and, via bile, excreted into the intestine. Here, gut bacteria deconjugate for reabsorption or conversion into urobilinogens that are eliminated via feces or urine while giving these excretions their typical colors. Elevated bilirubin levels can indicate liver diseases and lead to jaundice1. Researchers are exploring the relationship between gut bacteria involved in bilirubin conversion into urobilinogen and the development of liver diseases.
The objective of Dr. Xiaofang Jiang’s team from the National Library of Medicine, National Institutes of Health, Bethesda in the United States, was to pinpoint the bacterial enzyme responsible for converting bilirubin into urobilinogen and comprehend the connection between microbial bilirubin metabolism and human health. To achieve this, the researchers investigated the presence and absence of the enzyme capable of converting bilirubin into urobilinogen within the gut microbiota of infants during their first year of life2.
BilR, the enzyme that converts bilirubin into urobilinogen
Bilirubin reductase (BilR), the enzyme responsible for converting bilirubin into urobilinogen, was a mystery until recent findings of the research team. Dr. Xiaofang Jiang’s research team successfully identified this enzyme within bacterial species such as Roseburia intestinalis, Roseburia inulinivorans, and Faecalibacterium prausnitzii.
BilR is often absent in the gut microbiota of infants
The absence of BilR in the gut microbiota of infants is an important discovery by the research team. During the vulnerable period of infancy, characterized by a heightened risk of jaundice, BilR is often lacking. The correlation between the absence of BilR and the elevated risk of jaundice underscores a strong link between the microbiome composition and the development of jaundice in infants during this critical timeframe.
The conversion of bilirubin into urobilinogen plays part in gut health
When the authors looked at patients with Inflammatory Bowel Disease (IBD) compared to healthy individuals, they found that those with IBD had lower levels of urobilin and higher levels of bilirubin which was explained in part by the absence of the BilR enzyme within their gut microbiota. This emphasizes a direct link between the composition shift of the gut microbiota observed in IBD individuals and alterations in the gut microbiome bilirubin metabolism. This finding suggests that there might be a potential disruption of bilirubin metabolism in IBD patients.
In conclusion, the discovery of the bacterial enzyme responsible for converting bilirubin into urobilinogen has unveiled a significant connection between the gut microbiota and the liver. Particularly, the absence of BilR within the gut microbiota of neonates is linked to the highest incidence of neonatal jaundice. Beyond its involvement in jaundice, BilR may also play a role in bowel diseases, further emphasizing its profound implications for broader aspects of human health.
References:
- Hamoud, A.R., Weaver, L., Stec, D.E., et Hinds, T.D. Bilirubin in the Liver–Gut Signaling Axis. Trends in Endocrinology & Metabolism 29:3, 140 – 150 (2018). https://doi.org/10.1016/j.tem.2018.01.002
- Hall, B., Levy, S., Dufault-Thompson, K. et al. BilR is a gut microbial enzyme that reduces bilirubin to urobilinogen. Nat Microbiol 9, 173–184 (2024). https://doi.org/10.1038/s41564-023-01549-x
