National Library of Medicine | The Enzyme That Makes Urine Yellow (Audio Described Version) @NLMNIH | Uploaded March 2024 | Updated October 2024, 8 hours ago.
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.
pubmed.ncbi.nlm.nih.gov/38172624
nature.com/articles/s41564-023-01549-x
nlm.nih.gov/research/researchstaff/JiangXiaofang.html
Video Transcript
00:00:05:10 - 00:00:11:03
[Jiang] It all started because we were interested in what kind of functions gut bacteria can do.
00:00:11:08 - 00:00:16:13
And it turned out we found this one function that were important for human physiology
00:00:16:13 - 00:00:20:13
is the reduction of Bilirubin to Urobilinogen.
00:00:20:13 - 00:00:23:23
Urobilinogen was then converted to Urobilin.
00:00:23:23 - 00:00:27:02
Which causes the urine color to be yellow.
00:00:27:22 - 00:00:31:22
One of the projects our lab have been working on
is to identify this enzyme,
00:00:31:22 - 00:00:36:10
that is a mystery enzyme
that has not been characterized before
00:00:36:10 - 00:00:41:14
and this enzyme is responsible
for converting Bilirubin to Urobilinogen.
00:00:41:16 - 00:00:44:18
And this is preformed by the gut bacteria.
00:00:45:10 - 00:00:49:10
[Dufault-Thompson] The importance of this enzyme, Bilirubin
reductase, is that it helps our body
00:00:49:10 - 00:00:52:15
break down heme
and convert it into products
00:00:52:15 - 00:00:57:18
that we can get rid of as just part of our
normal healthy course of life.
00:00:57:21 - 00:01:00:02
But in order to understand
00:01:00:02 - 00:01:03:01
what microbes are doing
that, the first step that we needed to do
00:01:03:01 - 00:01:08:15
was actually find the mystery gene
that performs this function.
00:01:08:23 - 00:01:14:23
We had a really collaborative effort
with the Hall Lab to identify, first,
00:01:14:23 - 00:01:19:05
a group of bacteria
that could reduce Bilirubin, in the lab.
00:01:19:05 - 00:01:23:07
And then, our side, we were able to look
at the genomes of those bacteria
00:01:23:18 - 00:01:26:14
and eventually identify likely enzymes
00:01:26:14 - 00:01:29:07
that we were
then able to confirm their functions
00:01:29:19 - 00:01:33:02
and then look at bigger picture
trends like the relationship
00:01:33:02 - 00:01:36:20
of that gene
to different kinds of diseases.
00:01:37:01 - 00:01:42:11
Very commonly in infants,
we'll see a buildup of excess Bilirubin,
00:01:42:11 - 00:01:46:03
which then can cause the coloring
of the skin
00:01:46:03 - 00:01:49:08
and eyes, cause
a little bit of pain for them, and fevers.
00:01:49:08 - 00:01:53:15
And then more severe cases, lead to brain
damage and
00:01:53:20 - 00:01:56:12
you know hearing loss
and more severe effects.
00:01:56:17 - 00:02:01:01
Once we had an idea of what enzyme
was involved in this, we were then able
00:02:01:01 - 00:02:06:17
to go into these large, publicly available
data sets from young infants,
00:02:06:17 - 00:02:09:15
healthy adults, and patients with IBD.
00:02:09:15 - 00:02:12:13
And so we were able to kind of
for the first time show that
00:02:12:13 - 00:02:16:13
these young infants, in the first
30 to 60 days of life,
00:02:16:13 - 00:02:20:17
are often missing this gene, while
healthy adults almost always have it.
00:02:20:17 - 00:02:22:03
We were also able to see
00:02:22:03 - 00:02:27:09
that about 30% of IBD
patients were also missing that gene.
00:02:27:09 - 00:02:32:15
Now that we have a much better understanding of what bacteria are involved
00:02:32:15 - 00:02:37:18
this can hopefully lead to some better outcomes, in terms of the infants that develop jaundice.
00:02:38:00 - 00:02:40:04
[Jiang] Bilirubin reductase is just tip of
00:02:40:04 - 00:02:45:03
iceberg of the many functions our
gut bacteria perform
00:02:45:03 - 00:02:50:09
and we want to further characterize
more enzymes like it to understand
00:02:50:09 - 00:02:53:05
the role of the gut microbiome
00:02:53:05 - 00:02:55:05
perform in our human health.
#humanhealth #jaundice #guthealth #microbiome #urine #audiodescription
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.
pubmed.ncbi.nlm.nih.gov/38172624
nature.com/articles/s41564-023-01549-x
nlm.nih.gov/research/researchstaff/JiangXiaofang.html
Video Transcript
00:00:05:10 - 00:00:11:03
[Jiang] It all started because we were interested in what kind of functions gut bacteria can do.
00:00:11:08 - 00:00:16:13
And it turned out we found this one function that were important for human physiology
00:00:16:13 - 00:00:20:13
is the reduction of Bilirubin to Urobilinogen.
00:00:20:13 - 00:00:23:23
Urobilinogen was then converted to Urobilin.
00:00:23:23 - 00:00:27:02
Which causes the urine color to be yellow.
00:00:27:22 - 00:00:31:22
One of the projects our lab have been working on
is to identify this enzyme,
00:00:31:22 - 00:00:36:10
that is a mystery enzyme
that has not been characterized before
00:00:36:10 - 00:00:41:14
and this enzyme is responsible
for converting Bilirubin to Urobilinogen.
00:00:41:16 - 00:00:44:18
And this is preformed by the gut bacteria.
00:00:45:10 - 00:00:49:10
[Dufault-Thompson] The importance of this enzyme, Bilirubin
reductase, is that it helps our body
00:00:49:10 - 00:00:52:15
break down heme
and convert it into products
00:00:52:15 - 00:00:57:18
that we can get rid of as just part of our
normal healthy course of life.
00:00:57:21 - 00:01:00:02
But in order to understand
00:01:00:02 - 00:01:03:01
what microbes are doing
that, the first step that we needed to do
00:01:03:01 - 00:01:08:15
was actually find the mystery gene
that performs this function.
00:01:08:23 - 00:01:14:23
We had a really collaborative effort
with the Hall Lab to identify, first,
00:01:14:23 - 00:01:19:05
a group of bacteria
that could reduce Bilirubin, in the lab.
00:01:19:05 - 00:01:23:07
And then, our side, we were able to look
at the genomes of those bacteria
00:01:23:18 - 00:01:26:14
and eventually identify likely enzymes
00:01:26:14 - 00:01:29:07
that we were
then able to confirm their functions
00:01:29:19 - 00:01:33:02
and then look at bigger picture
trends like the relationship
00:01:33:02 - 00:01:36:20
of that gene
to different kinds of diseases.
00:01:37:01 - 00:01:42:11
Very commonly in infants,
we'll see a buildup of excess Bilirubin,
00:01:42:11 - 00:01:46:03
which then can cause the coloring
of the skin
00:01:46:03 - 00:01:49:08
and eyes, cause
a little bit of pain for them, and fevers.
00:01:49:08 - 00:01:53:15
And then more severe cases, lead to brain
damage and
00:01:53:20 - 00:01:56:12
you know hearing loss
and more severe effects.
00:01:56:17 - 00:02:01:01
Once we had an idea of what enzyme
was involved in this, we were then able
00:02:01:01 - 00:02:06:17
to go into these large, publicly available
data sets from young infants,
00:02:06:17 - 00:02:09:15
healthy adults, and patients with IBD.
00:02:09:15 - 00:02:12:13
And so we were able to kind of
for the first time show that
00:02:12:13 - 00:02:16:13
these young infants, in the first
30 to 60 days of life,
00:02:16:13 - 00:02:20:17
are often missing this gene, while
healthy adults almost always have it.
00:02:20:17 - 00:02:22:03
We were also able to see
00:02:22:03 - 00:02:27:09
that about 30% of IBD
patients were also missing that gene.
00:02:27:09 - 00:02:32:15
Now that we have a much better understanding of what bacteria are involved
00:02:32:15 - 00:02:37:18
this can hopefully lead to some better outcomes, in terms of the infants that develop jaundice.
00:02:38:00 - 00:02:40:04
[Jiang] Bilirubin reductase is just tip of
00:02:40:04 - 00:02:45:03
iceberg of the many functions our
gut bacteria perform
00:02:45:03 - 00:02:50:09
and we want to further characterize
more enzymes like it to understand
00:02:50:09 - 00:02:53:05
the role of the gut microbiome
00:02:53:05 - 00:02:55:05
perform in our human health.
#humanhealth #jaundice #guthealth #microbiome #urine #audiodescription
