The Gut-Brain Axis

What if I told you that you have tiny organisms living inside you influencing your brain?

What sounds like something out of an 80s science fiction movie is actually a topic currently at the forefront of scientific research! Scientists are discovering how the microbes that live in your gut influence your brain. Your human microbiome has a metabolic capacity that exceeds the liver, and these microbes produce molecules that can have effects all throughout your body, including your brain.

Microbiome controls behaviors

To analyse the influence of our gut microbiome on our behaviour, researchers used two characteristic extremes of mice [1].
For simplicity’s sake, we will call them the brave mice and the shy mice.
These characteristics were defined by a so-called step-down test. A mouse was placed in the center of an elevated platform and the time the mouse needs to step down was measured.

The brave mice usually needed less than 20 seconds to jump down while the shy mice needed three times as much time for the same task.

To identify whether these behaviors had anything to do with the microbiome, they fed the mice antibiotics to deplete their microbes.
After they killed off their whole microbiome, they specifically reintroduced in the one set of brave mice the microbiome from the shy mice and repeated the step-down test.

The results were astonishing:
The brave mice, who harbored the microbiome from shy mice suddenly needed the same time to step-down as the shy mice needed before.
Based on the results, the microbes seem to influence the characteristic traits of the mice.

 
Intestinal microbiota transfer differentially affects behavior of recipient mice [modified after Bercik et al., Gastroenterology, 2011]

Intestinal microbiota transfer differentially affects behavior of recipient mice [modified after Bercik et al., Gastroenterology, 2011]

 

Our Happiness is influenced by our Microbiome

Your happiness might also be dependent on your microbes.

People with depression often lack optimal stimulation of their brains with the neurotransmitter Serotonin – the happiness hormone. Some of the most prescribed drugs for depression are selective serotonin reuptake inhibitors, which are believed to increase serotonin concentration in the tissue fluid of the brain.

gut-brain-axis and serotonin production_OMahony 2014.PNG

However, what most people don’t know is that 95% of the body’s serotonin is produced and released by cells lining the gut [2].

Tryptophan is an essential amino acid and the precursor for serotonin production. Human cells do not produce tryptophan. However, ingesting tryptophan is not the only way humans obtain this essential amino acid. Unlike human cells, bacteria can synthesis tryptophan and there are even a few specific bacterial strains that produce serotonin, including some Lactobacilli species, Streptococcus thermophilus, and Bifidobacterium infantis [3, 4].

In one study scientist fed rats with the probiotic bacterium bifidobacterium infantis and found that the tryptophan concentration in the blood of probiotic-fed rats was almost twice as high as for the control group [5].

Another paper published in 2015 in the journal Cell showed that the serotonin concentration is reduced by 50% in mice without a microbiome [4].

Stress Response depends on the Gut Bacteria

Chronic stress can lead to many health issues such as stroke, depression, cancer or inflammatory diseases

Stress response in germ-free mice_Clarke 2013.PNG

In a study published in 2013, scientist looked into the stress response of germ-free mice [6]. Germ-free animals are animals that are virtually sterile, which means they don’t possess a microbiome. The researchers found two things:

  1. First, even without any stressful situation, the corticosterone levels, which is the stress hormone of mice, was higher in germ-free mice than in the normal mice.

  2. And second, the germ-free mice had almost a 2 times higher stress response than normal mice after some stress was induced.

Memory and Microbes

Memory is not something we would associate with our intestines. But even here seems to be some kind of connection.
To test if a disruption of a healthy microbiome has an impact on memory functions in mice, scientists infected the mice with a pathogen that infects the gastrointestinal tract of mice [7].

Gut-brain-axis_spatial memory_Gareau 2014.PNG

Half of the infected mice were given a probiotic supplement, containing two different strains of Lactobacilli, to restore the group’s microbiome. The other half did not receive the supplement.

To test each groups’ cognitive function, the mice were placed in a maze to test their spatial memory.
The group of mice which were infected and did NOT receive the probiotics exhibited memory dysfunctions. However, the group that did receive the probiotics did not show memory impairment. Therefore, the scientist concluded that:

“Memory dysfunction was prevented by daily treatment of infected mice with probiotics".

The Gut Microbiome influences BDNF levels

BDNF in germ-free mice Sudo 2004.PNG

The Brain-derived neurotrophic factor (BDNF) is a protein responsible for the survival of neurons and stimulates the growth and differentiation of new neurons.
Levels of BDNF decrease with aging and people with Alzheimer’s disease have generally lower levels of BDNF.

To test whether the microbiome influences BDNF levels, scientist treated mice with antibiotics and checked for their BDNF levels in different parts of the brain [8].
The scientist found that BDNF levels in antibiotic-treated mice were lower in the hippocampus region of the brain.

-> The hippocampus is the region that plays a role in consolidating information from short-term to long-term memory, suggesting that a healthy microbiome might be important to protect our memory.

It is amazing to me how these microbes can have an impact not just on our physiological health but also our mental health and how we can improve both with some smart changes in our diet.
Even though this field of research is still in its infancy, I am excited about its current and future findings.


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 References

  1. Bercik et al., The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice, Gastroenterology, 2011

  2. Berger et al., The Expanded Biology of Serotonin, Annu Rev Med, 2009

  3. O'Mahony et al., Serotonin, tryptophan metabolism and the brain-gut-microbiome axis, Behavioural Brain Research, 2015

  4. Yano et al., Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis, Cell 2015

  5. Desbonnet et al., The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat, Journal of psychiatric research, 2009

  6. Clarke et al., The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner, Molecular Psychiatry, 2013

  7. Gareau et al., Bacterial infection causes stress-induced memory dysfunction in mice, Gut Microbiota, 2014

  8. Sudo et al., Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice, J Physiol, 2004

  9. Brain Maker by Dr. David Perlmutter

Neurologist Dr. Perlmutter explains how your gut influences your brain:

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