Tuesday 24 December 2019

Spilling the guts with the gut-brain axis

The relationship between our guts (intestines) and brains can be seen through the phrases used in our daily conversation from spilling our guts to having the guts to do something. Most people are also familiar with how mental states like nervousness can lead to gastrointestinal (GI) discomfort. It has been recently shown how this connection is much more than just an upset stomach before a major interview or exam.

There is a separate branch of nervous system that is present in the GI tract called as the enteric nervous system (ENS) that can function independent of the brain and the spinal cord (Central Nervous System or CNS). ENS also has connections with the CNS via a specific nerve called as the Vagus nerve. The major function of ENS is to make sure that the GI tract muscles can contract and relax so as to ensure a smooth passage for food along with the timely release of gastric juices and enzymes that aid in digestion. ENS send signals to CNS via Vagus nerve and usually they go unnoticed by us unless they are causing a feeling of nausea or bloating. The intestine is also host to a wide range of microrgansisms that include bacteria and fungi. Surprisingly, our bodies have more bacterial cells than normal body cells, which together constitute the microbiota. The specific types of bacteria that are present in the intestines constitute the gut microbiota. 

The exposure of brain to toxins can affect the ENS and vice versa. Many of the disease causing pathogens can enter the brain via this gut brain connection i.e., the vagus nerve. Besides pathogens, other molecules can enter the brain via this connection. This is also evident in the infectious brain degenreative diseases like Creutzfeldt-Jakob disease and spongiform encephalopathy (brain dissection on autopsy show spongy structure), where the infectious protein particles enter the brain utilizing this very connection.
Recently it has also been shown that the gut bacteria can affect the development of certain other diseases like Depression, Anxiety, neurodevelopmental disorders like Autism and neurodegenerative disorders like Parkinson's Disease (PD). This is a surprising finding because it changes the way we look at many of these CNS diseases. 


But how do diseases like anxiety and depression occur due to the gut microbiota? These bacteria release substances that influences neurons and affects levels of different neurotransmitters in the brain, which have the potential to modulate our mood and behaviour. Although, the exact mechanisms are still not clear. Some of the known mechanisms and proposed hypotheses are:

1. Infectious protein particles enter brain via gut, as described above. Braak hypothesis suggests that infectious pathogens can enter the brain via the gut brain connection (like the Rabies and Polio virus) and can lead to death of neurons as seen in PD and AD. 

2. Leaky gut suggests that the epithelial lining of the GI tract is not intact which can lead to entry of bacteria, and other macromolecules into the brain. This is suggested as a possible mechanism for the development of Autism.

3. Certain bacteria affect stress circuit in brain.
The first study that showed gut microbiota can affect the brain, showed how stress response was affected in rats. It was found that the GF rats, which did not have any bacteria in their gut (called as germ free or GF rats), were more stressed.

4. Infection and inflammation of the gut
Specific bacterial infections of the gut have shown to result in inflammation of the gut followed by increased anxiety. This again was experimentally studied in rats.

So, there are still human studies lacking which would show that these proposed mechanisms would be true for us. Thus, there is a potential for the gut-brain connection to be a diagnosis cum treatment cum prevention site as can be seen by the following examples:

1. Early diagnosis 
For diseases like Autism and PD it has been shown that there are GI symptoms present in many of the patients. For many PD patients such symptoms are present even before the classical CNS related symptoms of PD emerge. Thus the assessment of GI symptoms can help in early detection of neurodegenerative diseases like PD. 

2. Potential treatment
Since, now we know that gut microbiota can influence these diseases, it is possible to use it to our advantage by providing the kind of bacteria that would help in reversing the symptoms. This has been shown by reversing some of the sypmtoms of Autism that were considered to be irreversible. Treatment for anxiety and depression are too looking in this direction for alternatives other than the current drugs in use.

3. Prevention
The most exciting discovery would be if we can prevent some of these CNS diseases from occuring in the first place by altering the gut microbioata of the susceptible individuals.



Does this mean that taking all those probiotics is going to acually save you from developing devastating neurodegenerative diseases in old age? To be honest, there is a lot of research that would go into creating the kind of probiotic that can someday be a cure for all sorts of diseases that we are fighting today. For now, its just a safe precaution to keep your gut healthy (by eating curd and avoiding unnecessary antibiotics) and wait for that day to arrive!

Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005185/

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