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Ahem, guys, do you remember δ-valerobetaine (δ-VB)? Singularity cake to show you the way-I am a portal
.
Yes, just a few days ago, a study published in the journal Nature Metabolism found that this δ-VB, as a metabolite of the intestinal flora, would pile up fat in our body and cause obesity.
And liver steatosis [1]
.
You said that by coincidence, on the same day, an article published in "Nature · Aging" also accused the crime of δ-VB in our body-δ-VB will also erode our cognition! Thomas Blank from the University of Freiburg, Germany, and his colleagues found that as we age, the more delta-VB produced by the metabolism of the intestinal flora, which causes the delta-VB levels in serum and brain to rise
.
It has been observed in mice that δ-VB impairs cognition and does not depend on microglia [2]
.
This explains how the gut flora induces age-related cognitive decline
.
The screenshot of the paper's homepage should say that age-related cognitive dysfunction is inseparable from the intestinal flora (intestinal bacteria seem to be inseparable from anything)
.
Not long ago, there was research that realized the "age-inverse" change in cognitive function in mice.
Transplanting fecal bacteria from young mice to aging mice can significantly improve the cognitive behavior of mice [3]
.
However, although the correlation and various appearances have been observed, we still have a little understanding of the mechanism-how the intestinal flora induces age-related cognitive impairment
.
Not to mention how many secrets of the intestinal microbiota we don’t know.
We can't finish reading about the cognitive function alone.
If we want to fully understand the intricate connections between the brain and the intestinal microbiota, It's still enough for scientists to work on it for a long time
.
This time, Blank and his colleagues can be regarded as squeezing out δ-VB
.
They first used fecal bacteria transplantation (FMT) to make different hands and feet on a bunch of aging mice (C57BL/6J SPF, 15-16 months)
.
yFMTiAged mice: Aging mice that received intestinal flora transplantation from young mice (C57BL/6J SPF, 8 weeks)
.
oFMTiAged mice: Aging mice that received intestinal flora transplantation from other aging mice (C57BL/6J SPF, 15-16 months)
.
It was found that compared with normal aging mice, the cognitive function of oFMTiAged mice remained unchanged; while the cognitive function of yFMTiAged mice was reversed, which was similar to that of young mice
.
This is also in line with the research results mentioned at the beginning [3].
Only the transplantation of fecal bacteria from young mice can significantly improve the cognitive function of aging mice, and once again proves that the intestinal flora can indeed be associated with age-related cognition.
Related to the decline in levels
.
The intestinal flora of young mice can restore the cognitive function of aging mice.
In order to investigate the gap between the "young" and "aging" intestinal flora, the researchers decided to start with metabolites
.
They obtained serum and brain samples from young mice, aging mice, yFMTiAged mice, and oFMTiAged mice for metabolomics analysis
.
The analysis results showed that there were 633 metabolites in mouse serum and 466 metabolites in brain
.
Among them, δ-VB exists in mouse serum and brain, and the level increases with the age of mice.
At the same time, it also shows obvious level difference in yFMTiAged mice and oFMTiAged mice that have received fecal bacteria transplantation
.
However, it cannot be said at this time that the change in the level of δ-VB is entirely caused by the metabolism of the intestinal flora
.
Therefore, the researchers looked for sterile mice (GF) without intestinal flora for comparison
.
The results found that sterile mice without intestinal flora are "relaxed", no matter how old they are, the levels of δ-VB in the brain and blood are maintained at extremely low levels, and there is no significant change with age
.
In other words, the delta-VB in mouse serum and brain is indeed mainly derived from the intestinal flora
.
And compared with young mice, the intestinal flora of aging mice can produce more δ-VB
.
Without the intestinal flora, the delta-VB levels in the brain and serum of the mice would not rise.
In addition, they also identified 11 bacterial genera related to changes in delta-VB levels
.
Bilophila, Holdemanella, and Lachnospiraceae are positively correlated; Barnesiella, Allobaculum, and Eisenbergiella are negatively correlated
.
With these findings in mice, Blank and his colleagues obtained data on a total of 9,842 human serum samples from metabolites from two clinical study cohorts [4,5]
.
The results found that not only mice, but also in our serum, the level of δ-VB is also significantly positively correlated with age
.
The metabolites of human serum samples from two clinical research cohorts were analyzed to find the relationship between intestinal flora and age-related cognition.
The pathway of metabolite δ-VB seems to work! In order to verify the effect of δ-VB on impairing cognitive function, Blank and his colleagues injected δ-VB into the intraperitoneal cavity of young mice
.
By observing the cognitive behavior of mice, they found that the cognitive function of young mice injected with δ-VB was reduced, and the performance of cognitive behaviors such as learning and memory ability was similar to that of aging mice
.
On the other hand, they also explored the direct effects of δ-VB on the brain of mice, and recorded electrophysiological records of neurons in the prefrontal cortex of mice
.
The results showed that when delta-VB was injected, the neuronal activity related to cognitive behavior changed significantly, and the key processes of movement, sensation and memory formation in mice were affected
.
Sure enough, δ-VB does induce cognitive impairment in mice
.
It is worth mentioning that studies have shown that the microglia in the brain are very sensitive to the metabolites of the intestinal flora
.
Microglia are an indispensable part of physiological processes such as cognitive regulation and nerve support, and intestinal flora metabolites will affect the maturation and physiological functions of microglia [6]
.
But here the researchers found that the cognitive impairment induced by delta-VB does not depend on microglia
.
In a brief and concise description of the research methods and results, Blank and his colleagues found that the delta-VB produced by the metabolism of the intestinal flora can impair cognitive function without relying on microglia
.
And as we age, the intestinal flora will metabolize to produce more δ-VB, which leads to the increase of δ-VB levels in our brain and serum
.
Regarding delta-VB, the researchers said, "beautiful boy, you have successfully attracted our attention", and hope that through more in-depth research, the therapy targeting delta-VB can be used in clinical applications
.
They also hypothesized that since δ-VB does not induce cognitive impairment by acting on microglia, it may have an effect on cardiomyocytes, such as causing β-oxidation of fatty acids
.
For δ-VB, the singularity cake has to say-you are playing with fat in my liver, and you have to trample on cognition in the brain.
Your crime is too numerous to write! References: [1] Liu KH, et al.
Microbial metabolite delta-valerobetaine is a diet-dependent obesogen.
Nat Metab.
2021 Dec;3(12):1694-1705.
doi: 10.
1038/s42255-021-00502-8 .
Epub 2021 Dec 20.
PMID: 34931082.
[2]Mossad, O.
, Nent, E.
, Woltemate, S.
et al.
Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline .
Nat Aging 1, 1127–1136 (2021).
https://doi.
org/10.
1038/s43587-021-00141-4[3]Boehme, M.
, Guzzetta, KE, Bastiaanssen, TFS et al.
Microbiota from young mice counteracts selective age-associated behavioral deficits.
Nat Aging 1, 666–676 (2021).
https://doi.
org/10.
1038/s43587-021-00093-9[4]Shin, SY et al.
An atlas of genetic infuences on human blood metabolites.
Nat.
Genet.
46, 543–550 (2014).
[5]Long, T.
et al.
.
Yes, just a few days ago, a study published in the journal Nature Metabolism found that this δ-VB, as a metabolite of the intestinal flora, would pile up fat in our body and cause obesity.
And liver steatosis [1]
.
You said that by coincidence, on the same day, an article published in "Nature · Aging" also accused the crime of δ-VB in our body-δ-VB will also erode our cognition! Thomas Blank from the University of Freiburg, Germany, and his colleagues found that as we age, the more delta-VB produced by the metabolism of the intestinal flora, which causes the delta-VB levels in serum and brain to rise
.
It has been observed in mice that δ-VB impairs cognition and does not depend on microglia [2]
.
This explains how the gut flora induces age-related cognitive decline
.
The screenshot of the paper's homepage should say that age-related cognitive dysfunction is inseparable from the intestinal flora (intestinal bacteria seem to be inseparable from anything)
.
Not long ago, there was research that realized the "age-inverse" change in cognitive function in mice.
Transplanting fecal bacteria from young mice to aging mice can significantly improve the cognitive behavior of mice [3]
.
However, although the correlation and various appearances have been observed, we still have a little understanding of the mechanism-how the intestinal flora induces age-related cognitive impairment
.
Not to mention how many secrets of the intestinal microbiota we don’t know.
We can't finish reading about the cognitive function alone.
If we want to fully understand the intricate connections between the brain and the intestinal microbiota, It's still enough for scientists to work on it for a long time
.
This time, Blank and his colleagues can be regarded as squeezing out δ-VB
.
They first used fecal bacteria transplantation (FMT) to make different hands and feet on a bunch of aging mice (C57BL/6J SPF, 15-16 months)
.
yFMTiAged mice: Aging mice that received intestinal flora transplantation from young mice (C57BL/6J SPF, 8 weeks)
.
oFMTiAged mice: Aging mice that received intestinal flora transplantation from other aging mice (C57BL/6J SPF, 15-16 months)
.
It was found that compared with normal aging mice, the cognitive function of oFMTiAged mice remained unchanged; while the cognitive function of yFMTiAged mice was reversed, which was similar to that of young mice
.
This is also in line with the research results mentioned at the beginning [3].
Only the transplantation of fecal bacteria from young mice can significantly improve the cognitive function of aging mice, and once again proves that the intestinal flora can indeed be associated with age-related cognition.
Related to the decline in levels
.
The intestinal flora of young mice can restore the cognitive function of aging mice.
In order to investigate the gap between the "young" and "aging" intestinal flora, the researchers decided to start with metabolites
.
They obtained serum and brain samples from young mice, aging mice, yFMTiAged mice, and oFMTiAged mice for metabolomics analysis
.
The analysis results showed that there were 633 metabolites in mouse serum and 466 metabolites in brain
.
Among them, δ-VB exists in mouse serum and brain, and the level increases with the age of mice.
At the same time, it also shows obvious level difference in yFMTiAged mice and oFMTiAged mice that have received fecal bacteria transplantation
.
However, it cannot be said at this time that the change in the level of δ-VB is entirely caused by the metabolism of the intestinal flora
.
Therefore, the researchers looked for sterile mice (GF) without intestinal flora for comparison
.
The results found that sterile mice without intestinal flora are "relaxed", no matter how old they are, the levels of δ-VB in the brain and blood are maintained at extremely low levels, and there is no significant change with age
.
In other words, the delta-VB in mouse serum and brain is indeed mainly derived from the intestinal flora
.
And compared with young mice, the intestinal flora of aging mice can produce more δ-VB
.
Without the intestinal flora, the delta-VB levels in the brain and serum of the mice would not rise.
In addition, they also identified 11 bacterial genera related to changes in delta-VB levels
.
Bilophila, Holdemanella, and Lachnospiraceae are positively correlated; Barnesiella, Allobaculum, and Eisenbergiella are negatively correlated
.
With these findings in mice, Blank and his colleagues obtained data on a total of 9,842 human serum samples from metabolites from two clinical study cohorts [4,5]
.
The results found that not only mice, but also in our serum, the level of δ-VB is also significantly positively correlated with age
.
The metabolites of human serum samples from two clinical research cohorts were analyzed to find the relationship between intestinal flora and age-related cognition.
The pathway of metabolite δ-VB seems to work! In order to verify the effect of δ-VB on impairing cognitive function, Blank and his colleagues injected δ-VB into the intraperitoneal cavity of young mice
.
By observing the cognitive behavior of mice, they found that the cognitive function of young mice injected with δ-VB was reduced, and the performance of cognitive behaviors such as learning and memory ability was similar to that of aging mice
.
On the other hand, they also explored the direct effects of δ-VB on the brain of mice, and recorded electrophysiological records of neurons in the prefrontal cortex of mice
.
The results showed that when delta-VB was injected, the neuronal activity related to cognitive behavior changed significantly, and the key processes of movement, sensation and memory formation in mice were affected
.
Sure enough, δ-VB does induce cognitive impairment in mice
.
It is worth mentioning that studies have shown that the microglia in the brain are very sensitive to the metabolites of the intestinal flora
.
Microglia are an indispensable part of physiological processes such as cognitive regulation and nerve support, and intestinal flora metabolites will affect the maturation and physiological functions of microglia [6]
.
But here the researchers found that the cognitive impairment induced by delta-VB does not depend on microglia
.
In a brief and concise description of the research methods and results, Blank and his colleagues found that the delta-VB produced by the metabolism of the intestinal flora can impair cognitive function without relying on microglia
.
And as we age, the intestinal flora will metabolize to produce more δ-VB, which leads to the increase of δ-VB levels in our brain and serum
.
Regarding delta-VB, the researchers said, "beautiful boy, you have successfully attracted our attention", and hope that through more in-depth research, the therapy targeting delta-VB can be used in clinical applications
.
They also hypothesized that since δ-VB does not induce cognitive impairment by acting on microglia, it may have an effect on cardiomyocytes, such as causing β-oxidation of fatty acids
.
For δ-VB, the singularity cake has to say-you are playing with fat in my liver, and you have to trample on cognition in the brain.
Your crime is too numerous to write! References: [1] Liu KH, et al.
Microbial metabolite delta-valerobetaine is a diet-dependent obesogen.
Nat Metab.
2021 Dec;3(12):1694-1705.
doi: 10.
1038/s42255-021-00502-8 .
Epub 2021 Dec 20.
PMID: 34931082.
[2]Mossad, O.
, Nent, E.
, Woltemate, S.
et al.
Microbiota-dependent increase in δ-valerobetaine alters neuronal function and is responsible for age-related cognitive decline .
Nat Aging 1, 1127–1136 (2021).
https://doi.
org/10.
1038/s43587-021-00141-4[3]Boehme, M.
, Guzzetta, KE, Bastiaanssen, TFS et al.
Microbiota from young mice counteracts selective age-associated behavioral deficits.
Nat Aging 1, 666–676 (2021).
https://doi.
org/10.
1038/s43587-021-00093-9[4]Shin, SY et al.
An atlas of genetic infuences on human blood metabolites.
Nat.
Genet.
46, 543–550 (2014).
[5]Long, T.
et al.
