Can long-term diarrhoea make a person stupid?
Editor’s Recommendation: Does diarrhea (inflammation of the gut) make you stupid?Diarrhea desperation is so deep, especially on the highway, there’s a saying: When your stomach hurts, don’t trust a fart…Once uncontrollable, depending on the situation at that time, how many people around, there are strangers, relatives, friends, there are unloved objects and so on, have caused indelible trauma to different degrees of people’s spirit, vision and hearing.If this makes you feel hopeless, what about those with recurrent diarrhea and abdominal pain that severely affect daily life, work and school, and prolong their course or even last a lifetime?They have inflammatory bowel disease.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 been increasing rapidly in recent years, and the number of patients has reached 3.44/100,000, ranking the first in Asia.IBD patients not only suffer from abdominal pain and diarrhea, studies show that 40% of IBD patients also suffer from anxiety, depression and even impaired cognitive function.Changes in anxiety, depressive behavior and the limbic system were also observed in mice with colitis.However, the mechanism by which enteritis causes psychiatric symptoms remains unclear.Rather than simply blaming ibD for symptoms of anxiety and depression, scientists are studying the connection between the gut and the brain.A recent study published in the journal Science reveals a key mechanism by which intestinal inflammation leads to psychiatric symptoms, starting with the enteric-cerebrovascular axis.We know that in the inflammatory state of the gut, the leakage of the intestinal vascular barrier increases, and bacterial toxins in the gut also enter the bloodstream, causing inflammation throughout the body.Because of the complex vascular barriers of the central nervous system, including the blood-brain barrier and the Blood-cerebrospinal fluid barrier, cerebrovascular disorders normally limit the entry of large molecules from the blood into the brain and maintain a stable environment in brain tissues.However, the researchers found that during the acute phase of the mice with colitis, the number of macrophages in their brains increased, while microglias, the main immune-monitoring cells of the nervous system, were also activated, suggesting that intestinal inflammation can quickly trigger an inflammatory response in the brain.So how do bacterial toxins from the gut and inflammatory factors in the blood get into the brain in an inflammatory state of the gut?To investigate the changes of cerebrovascular barrier permeability, we injected 70KDa dextran fluorescent probe into the posterior orbital venous plexus of mice in normal state, acute enteritis stage and recovery stage respectively.Since the BBB can only pass through 500da of fat-soluble material, 70KDa fluorescent molecules are more likely to enter the brain through the BBB.Researchers observed that acute enteritis on the first day, the cerebrovascular barrier permeability enhancement, fluorescent molecules gathered and infiltrated to the choroid plexus area of the brain, cerebrospinal fluid can also be found in fluorescent molecules.These fluorescent molecules are completely blocked by the cerebrovascular barrier and cannot re-enter the brain until the enteritis has healed.The cerebral vascular barrier structure changes in acute enteritis.Although the permeability of the cerebrovascular barrier in the choroid plexus area was temporarily enhanced at the initial stage, the barrier was quickly closed and reopened after the enteritis recovered.The intraderitoneal injection of bacterial endotoxin-lipopolysaccharide LPS also produced changes similar to those observed in the brains of mice with acute colitis — shutting down the choroid plexus blood-cerebrospinal fluid barrier, suggesting that the presence of bacterial endotoxin affects structural changes in 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, the brain barrier closes…Wait, this is a little different than you thought.Since the brain barrier is closed, it stands to reason that harmful substances cannot enter and should not have further effects on the brain, so what about anxiety, depression and even cognitive decline?The production?Be because of acute enteritis the barrier of cerebrovascular vessel of the first day appear sex increased, the harmful material in circulation entered cerebrum?Or is it the daily diarrhea that makes rats and patients miserable?The best part is right here.The researchers engineered gene-edited mice to turn off the blood-vessel barrier without intestinal inflammation and disease pain by injecting induced drugs.The behavior of rats.The researchers found that when the cerebrovascular barrier was closed, the mice showed anxiety-like behavior, impaired episodic memory, and no depressive behavior.It turns out that the key to mental symptoms, at least some of them, is a blocked cerebrovascular barrier!So far, all the events can finally be connected:In intestinal inflammation, harmful substances enter the blood and cerebrovascular disorders feel this “threat”, choose to shut down to prevent harmful substances from entering and maintain brain homeostasis, however, if the external communication is isolated, harmful substances can not enter and beneficial substances can not enter, the waste generated in the brain can not be transported out.At this point, psychiatric symptoms will appear.One final question: Although we only see anxiety-like symptoms and cognitive decline in mice after the barrier is closed, can depressive symptoms be observed if the barrier is repeatedly induced over a long period of time?Second, in animal models, the researchers observed that changes in the cerebrovascular barrier could return to their original state after enteritis returned.In patients with long-term recurrent enteritis, such as clinical IBD, the changes in the brain barrier structure are still temporary.Is it sexual?Will it change forever?These questions remain to be further studied by scientists.Reference:1. Ng, SC, et al., Incidence and phenotype of inflammatory bowel disease based on results from the Asia-Pacific Crohn’s and colitisepidemiology 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.Disclaimer: Kanga is committed to the dissemination of health knowledge, the content is edited according to public information, copyright belongs to the original author;If there is infringement please delete online message.The article is intended to introduce the progress of health science, not as a treatment plan;For precise health guidance, please go to a regular hospital for diagnosis and treatment.