September 28, 2022

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Diarrhea (Intestinal inflammation) can make you stupid?

Diarrhea (Intestinal inflammation) can make you stupid?



 

Diarrhea (Intestinal inflammation) can make you stupid?

Science: Intestinal inflammation causes changes in the structure of the brain barrier and induces mental symptoms!

 

Almost everyone has had such an experience: abdominal cramps, gurgles accompanied by intestinal peristalsis, the red alarm that “the city gate is about to fall” sounded at a high decibel level in the mind, there is no moment like now, attention Completely concentrated in one place, a toilet, a squatting pit, even a grass!

 

The despair of diarrhea is too deep, especially on the highway, there is a saying: When you have a stomachache, don’t believe any fart… Once you can’t control it, depending on the current scene, how many people are around, according to strangers, relatives, friends , the object of secret love, etc., have caused different degrees of indelible trauma to people’s spirit, sight, and hearing.

 

If this makes you despair, how are those who suffer from repeated diarrhea and abdominal pain, which seriously affects their daily life, work and study, and whose disease course is prolonged and even lasts a lifetime?

 

They are inflammatory bowel disease patients.

 

Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory bowel disease of unknown etiology, mainly including Crohn’s disease and ulcerative colitis. Epidemiological data show that the incidence of IBD in China has shown a rapid upward trend in recent years, and the number of patients has reached 3.44/100,000, ranking first in Asia .

 

Inflammatory bowel disease patients not only suffer from abdominal pain and diarrhea, research shows that 40% of IBD patients are also accompanied by anxiety, depression symptoms, and even impaired cognitive function. In colitis mice, anxiety, depressive behavior, and changes in the limbic system were also observed . However, the mechanism by which enteritis causes psychiatric symptoms is unclear.

 

Instead of simply attributing anxiety and depression symptoms in IBD patients to the suffering of the disease, scientists are looking at the gut-brain connection. A recent study published in Science started from the gut-cerebrovascular axis and revealed the key mechanism by which intestinal inflammation causes psychiatric symptoms.

 

Diarrhea (Intestinal inflammation) can make you stupid?

 

We know that in the state of intestinal inflammation, the leakage of the intestinal vascular barrier increases, and bacterial toxins in the intestinal lumen also enter the blood circulation, causing a systemic systemic inflammatory response.

 

Because the central nervous system has complex vascular barriers, including the blood-brain barrier and the blood-cerebrospinal fluid barrier, under normal circumstances, the cerebrovascular barrier will restrict the entry of macromolecules in the blood into the brain and maintain a stable environment in the brain tissue.

 

However, the researchers observed that during the acute phase of colitis in mice, the number of macrophages in the mouse brain increased, and at the same time, microglia, the main immune surveillance cells of the nervous system, were also activated, indicating that intestinal inflammation can Rapidly triggers an inflammatory response in the brain .

 

So, in the state of intestinal inflammation, how do bacterial toxins from the gut and inflammatory factors in the blood enter the brain?

 

To this end, the researchers injected 70KDa dextran with fluorescent probes into the retro-orbital venous plexus of mice in the normal state, acute enteritis period, and enteritis recovery period, respectively, and observed changes in the permeability of the cerebral vascular barrier.

Since the blood-brain barrier can only pass through 500 Da fat-soluble substances, the 70KDa fluorescent molecules are more likely to enter the brain through the blood-cerebrospinal fluid barrier.

 

The researchers observed that on the first day of acute enteritis, the permeability of the cerebral vascular barrier was enhanced, fluorescent molecules aggregated and infiltrated into the choroid plexus area of ​​the brain, and fluorescent molecules could also be found in the cerebrospinal fluid.

Completely blocked from the cerebrovascular barrier, the fluorescent molecules could not enter the brain again until the enteritis recovered.

 

This indicates that the structure of the cerebrovascular barrier changes in the state of acute enteritis. Although the permeability of the cerebral vascular barrier in the choroid plexus region is temporarily enhanced at the initial stage, the cerebrovascular barrier is rapidly closed and does not reopen until the enteritis recovers .

 

Diarrhea (Intestinal inflammation) can make you stupid?

 

 

Intraperitoneal injection of bacterial endotoxin-lipopolysaccharide LPS into mice can also observe changes similar to acute colitis in the brain of mice – the closure of the choroid plexus blood-cerebrospinal fluid barrier, indicating that the presence of bacterial endotoxin affects Changes in the structure of the cerebrovascular barrier.

 

The research has progressed to this point. We already know that in the state of acute enteritis, the permeability of the intestinal vascular barrier increases, the endotoxin produced by intestinal bacteria enters the blood circulation, reaches the brain, changes the structure of the cerebrovascular barrier, and the brain barrier closes…

 

Wait, it seems to be a little different from what you imagined. Since the brain barrier is closed, it stands to reason that harmful substances cannot enter the brain, and should not have further effects on the brain, so how are anxiety, depression, and even cognitive decline? produced?

 

Is it because of the increased permeability of the cerebrovascular barrier on the first day of acute enteritis that harmful substances in the circulation enter the brain? Or does the daily diarrhea make the mice and patients feel distressed?

 

The most wonderful step is here. The researchers designed a gene-edited mouse that can close the cerebrovascular barrier without intestinal inflammation and disease pain after injecting inducing drugs. mouse behavior.

 

The researchers found that when the brain-vascular barrier was closed, the mice exhibited anxiety-like behaviors, impaired episodic memory, and no depressive behaviors. It turns out that mental symptoms, at least the key to the appearance of some mental symptoms, lie in the closed cerebrovascular barrier!

 

So far, all events can finally be linked together: in the state of intestinal inflammation, harmful substances enter the blood, and the cerebrovascular barrier feels this “threat” and chooses to close to prevent the entry of harmful substances and maintain brain homeostasis, However, if the external communication is isolated, harmful substances cannot enter, and beneficial substances cannot enter, and the garbage generated in the brain cannot be transported out either. At this time, mental symptoms will occur .

 

Finally, there is still a problem: although we only see anxiety-like symptoms and cognitive decline after closing the vascular barrier in mice, if the cerebral vascular barrier is repeatedly induced for a long time, can depression symptoms be observed?

 

Secondly, in animal models, the researchers observed that the changes in the cerebral vascular barrier can also return to the original state after the recovery of enteritis.

If it is a long-term recurrent enteritis, such as clinical IBD patients, the changes in the structure of the brain barrier are still temporary. Is it sexual, and will it change permanently? These issues remain to be further studied by scientists.

 

 

references:

1. Ng, SC, et al., Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn’s and colitis epidemiology study. Gastroenterology, 2013. 145(1): p. 158-165.e2.

2.Byrne, G., et al., Prevalence of Anxiety and Depression in Patients with Inflammatory Bowel Disease. Can J Gastroenterol Hepatol, 2017. 2017: p. 6496727.

3. Dempsey, E., et al., Persistent central inflammation and region specific cellular activation accompany depression- and anxiety-like behaviours during the resolution phase of experimental colitis. Brain Behav Immun, 2019. 80: p. 616-632.

4. Carloni, S., et al., Identification of a choroid plexus vascular barrier closing during intestinal inflammation. Science, 2021. 374(6566): p. 439-448.

Diarrhea (Intestinal inflammation) can make you stupid?

(source:internet, reference only)


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