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Written | The two-way communication between Xueyue's intestines and brain can have a great impact on body health and diseases
.
The factors that affect the two-way communication between the two mainly include environmental factors and peripheral factors.
An important aspect of this is the intestinal flora factor
.
Studies on stress coping, anxiety, and social behavior have found that the flora contributes to the development and function of the brain and the formation of behavior
.
The specific intestinal flora will play an important role in the formation of various behaviors in mice
.
The impact of host-microbe interactions on complex behaviors needs more research
.
Studies have found that in neuropsychiatric diseases related to changes in social behavior, such as patients with autism, gut microbes will change
.
Studies in rodents have also shown that lack of intestinal flora leads to reduced social behavior
.
Autism model mice will have changes in the composition of the intestinal flora, and correcting these changes will also improve the symptoms of autism
.
Although the influence of intestinal flora on complex behaviors has been gradually discovered, how the microbiome regulates the neural circuits related to social behaviors has not yet been clarified
.
On June 30, 2021, Wei-Li Wu from the California Institute of Technology and others jointly published an article entitled Microbiota regulate social behaviour via stress response neurons in the brain on Nature
.
This study provides the neurological basis for the influence of intestinal flora on social activities in mice: specific intestinal flora inhibits the HPA axis (The hypothalamic–pituitary–adrenal axis, HPA or HTPA axis) The mediated production of corticosterone promotes social activities in mice
.
The author first validated the previous research in sterile mice (GF mice)
.
The social behavior of sterile mice was significantly reduced, and other non-social behaviors were unchanged compared with SPF mice
.
This phenomenon also appeared in antibiotic-treated mice (ABX mice)
.
The authors further verified that the lack of intestinal flora that impairs the social activities of mice is not the result of olfactory dysfunction, anxiety or changes in movement
.
Next, the authors used the immediate early gene c-Fos as a marker of neuron activation and found that the paraventricular nucleus (PVN), stria terminalis nucleus (BNST) and hippocampus of the GF mice and ABX mice after social activities in the brain Neurons in the dentate gyrus (DG) and basolateral amygdala (BLA) are activated
.
The influence of gut bacteria on the social behaviors studied is unlikely to be mediated by vasopressin, and the oxytocin-dependent pathway cannot be completely ruled out
.
Studies have shown that the intestinal flora can regulate the HPA axis (the hypothalamic–pituitary–adrenal axis, HPA or HPA axis) produced by corticosterone
.
So the authors tested the changes of corticosterone in GF mice and ABX mice
.
The results showed that compared with SPF mice, GF and ABX mice had a more significant increase in serum corticosterone levels after brief social contact, and this change was not affected by the circadian rhythm
.
The author used pharmacological methods and removal of the adrenal glands to inhibit the production of corticosterone
.
Injection of corticosterone synthesis blocker MET (metyrapone MET) can increase the social behavior of ABX mice
.
ABX mice with adrenalectomy (adrenalectomy ADX) showed similar levels of social behavior as the sham operation group
.
The author next injected AAV-hSyn-Cre-GFP into specific brain regions of Nr3c1f/f (Nr3c1 gene encoding glucocorticoid receptor) to knock out glucocorticoid receptor
.
Knockout of Nr3c1 in DG or BNST will increase the level of social behavior in ABX mice
.
Glucocorticoid receptor signal blocker RU-486 can also increase the social activities of ABX mice
.
Injecting AAV-hSyn-Cre-GFP into the hypothalamic area will reduce the social behavior of ABX mice, and the expression of corticosterone in serum and c-Fos in DG will increase significantly
.
And this change only appeared in ABX mice
.
It shows that the glucocorticoid receptor in the hypothalamus plays a negative role in the HPA axis
.
These results indicate that glucocorticoid receptors have different functions in different brain regions and can regulate corticosterone levels and social behaviors affected by the flora
.
The author then injected the hM4Di-expressing AAV virus on the PVN of Crh-cre mice to specifically inhibit the activity of PVN neurons.
After injection of CNO, it can acutely increase the social behavior of ABX mice and reduce the level of cortisol.
.
Inhibition of neuronal activity in BNST or DG did not change the social behavior of mice
.
In GF and ABX mice, cholera toxin B subunit (CTB) was used to reverse the upstream circuit of PVN and found that their upstream circuit connection did not change significantly
.
Therefore, the authors infer that the main mechanism for the reduction of social behavior in GF and ABX mice is the activation of neurons in PVN, rather than its upstream neural circuits
.
However, the author did not rule out whether other circuits in the brain are also involved in this process
.
The authors next tried to find out which gut flora would affect the social activities of mice
.
The authors treated SPF mice with different antibiotics and found that bacteria sensitive to neomycin could affect the social behavior of mice and the expression of c-Fos in PVN
.
Using a quantitative microbiome sequencing method, the authors found that there was a bacterium belonging to the Enterococcus genus in antibiotic-treated mice without neomycin, but it did not exist in mice treated with antibiotics containing neomycin.
The main bacterial strain is E.
faecalis
.
So the author colonized E.
faecalis in ABX mice
.
Compared with E.
faecalis before colonization, ABX mice containing E.
faecalis significantly increased social activities and decreased the expression of c-Fos in the brain
.
This phenomenon has also been verified in GF mice
.
The author also pointed out that this result does not exclude that other bacteria can also affect the social activities of mice
.
This study found that removing the adrenal glands and suppressing glucocorticoid receptor signals with drugs can restore the social activities of mice lacking intestinal flora, providing a neurological basis for how the intestinal flora affects the social activities of mice
.
Future research will aim to discover the key microbial molecules responsible for regulating social activities and target host cell types and receptors, and to clarify the regulatory mechanisms in more detail
.
Original link: https://doi.
org/10.
1038/s41586-021-03669-y Platemaker: Instructions for reprinting on the 11th [Original article] BioArt original article, personal forwarding and sharing are welcome, reprinting without permission is prohibited, all published The copyright of the work is owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
.
The factors that affect the two-way communication between the two mainly include environmental factors and peripheral factors.
An important aspect of this is the intestinal flora factor
.
Studies on stress coping, anxiety, and social behavior have found that the flora contributes to the development and function of the brain and the formation of behavior
.
The specific intestinal flora will play an important role in the formation of various behaviors in mice
.
The impact of host-microbe interactions on complex behaviors needs more research
.
Studies have found that in neuropsychiatric diseases related to changes in social behavior, such as patients with autism, gut microbes will change
.
Studies in rodents have also shown that lack of intestinal flora leads to reduced social behavior
.
Autism model mice will have changes in the composition of the intestinal flora, and correcting these changes will also improve the symptoms of autism
.
Although the influence of intestinal flora on complex behaviors has been gradually discovered, how the microbiome regulates the neural circuits related to social behaviors has not yet been clarified
.
On June 30, 2021, Wei-Li Wu from the California Institute of Technology and others jointly published an article entitled Microbiota regulate social behaviour via stress response neurons in the brain on Nature
.
This study provides the neurological basis for the influence of intestinal flora on social activities in mice: specific intestinal flora inhibits the HPA axis (The hypothalamic–pituitary–adrenal axis, HPA or HTPA axis) The mediated production of corticosterone promotes social activities in mice
.
The author first validated the previous research in sterile mice (GF mice)
.
The social behavior of sterile mice was significantly reduced, and other non-social behaviors were unchanged compared with SPF mice
.
This phenomenon also appeared in antibiotic-treated mice (ABX mice)
.
The authors further verified that the lack of intestinal flora that impairs the social activities of mice is not the result of olfactory dysfunction, anxiety or changes in movement
.
Next, the authors used the immediate early gene c-Fos as a marker of neuron activation and found that the paraventricular nucleus (PVN), stria terminalis nucleus (BNST) and hippocampus of the GF mice and ABX mice after social activities in the brain Neurons in the dentate gyrus (DG) and basolateral amygdala (BLA) are activated
.
The influence of gut bacteria on the social behaviors studied is unlikely to be mediated by vasopressin, and the oxytocin-dependent pathway cannot be completely ruled out
.
Studies have shown that the intestinal flora can regulate the HPA axis (the hypothalamic–pituitary–adrenal axis, HPA or HPA axis) produced by corticosterone
.
So the authors tested the changes of corticosterone in GF mice and ABX mice
.
The results showed that compared with SPF mice, GF and ABX mice had a more significant increase in serum corticosterone levels after brief social contact, and this change was not affected by the circadian rhythm
.
The author used pharmacological methods and removal of the adrenal glands to inhibit the production of corticosterone
.
Injection of corticosterone synthesis blocker MET (metyrapone MET) can increase the social behavior of ABX mice
.
ABX mice with adrenalectomy (adrenalectomy ADX) showed similar levels of social behavior as the sham operation group
.
The author next injected AAV-hSyn-Cre-GFP into specific brain regions of Nr3c1f/f (Nr3c1 gene encoding glucocorticoid receptor) to knock out glucocorticoid receptor
.
Knockout of Nr3c1 in DG or BNST will increase the level of social behavior in ABX mice
.
Glucocorticoid receptor signal blocker RU-486 can also increase the social activities of ABX mice
.
Injecting AAV-hSyn-Cre-GFP into the hypothalamic area will reduce the social behavior of ABX mice, and the expression of corticosterone in serum and c-Fos in DG will increase significantly
.
And this change only appeared in ABX mice
.
It shows that the glucocorticoid receptor in the hypothalamus plays a negative role in the HPA axis
.
These results indicate that glucocorticoid receptors have different functions in different brain regions and can regulate corticosterone levels and social behaviors affected by the flora
.
The author then injected the hM4Di-expressing AAV virus on the PVN of Crh-cre mice to specifically inhibit the activity of PVN neurons.
After injection of CNO, it can acutely increase the social behavior of ABX mice and reduce the level of cortisol.
.
Inhibition of neuronal activity in BNST or DG did not change the social behavior of mice
.
In GF and ABX mice, cholera toxin B subunit (CTB) was used to reverse the upstream circuit of PVN and found that their upstream circuit connection did not change significantly
.
Therefore, the authors infer that the main mechanism for the reduction of social behavior in GF and ABX mice is the activation of neurons in PVN, rather than its upstream neural circuits
.
However, the author did not rule out whether other circuits in the brain are also involved in this process
.
The authors next tried to find out which gut flora would affect the social activities of mice
.
The authors treated SPF mice with different antibiotics and found that bacteria sensitive to neomycin could affect the social behavior of mice and the expression of c-Fos in PVN
.
Using a quantitative microbiome sequencing method, the authors found that there was a bacterium belonging to the Enterococcus genus in antibiotic-treated mice without neomycin, but it did not exist in mice treated with antibiotics containing neomycin.
The main bacterial strain is E.
faecalis
.
So the author colonized E.
faecalis in ABX mice
.
Compared with E.
faecalis before colonization, ABX mice containing E.
faecalis significantly increased social activities and decreased the expression of c-Fos in the brain
.
This phenomenon has also been verified in GF mice
.
The author also pointed out that this result does not exclude that other bacteria can also affect the social activities of mice
.
This study found that removing the adrenal glands and suppressing glucocorticoid receptor signals with drugs can restore the social activities of mice lacking intestinal flora, providing a neurological basis for how the intestinal flora affects the social activities of mice
.
Future research will aim to discover the key microbial molecules responsible for regulating social activities and target host cell types and receptors, and to clarify the regulatory mechanisms in more detail
.
Original link: https://doi.
org/10.
1038/s41586-021-03669-y Platemaker: Instructions for reprinting on the 11th [Original article] BioArt original article, personal forwarding and sharing are welcome, reprinting without permission is prohibited, all published The copyright of the work is owned by BioArt
.
BioArt reserves all statutory rights and offenders must be investigated
.
