Gut-Brain Axis

Imagine this:

You wake up that one day and notice that your legs fell somehow weird. You try to walk it off but instead of getting better it only gets worse and slowly you start losing the feeling in your legs completly. The scenario I just described is common for patients who develop an onset of the autoimmune disease multiple sclerosis.

In his book “Brain Maker”, Dr. David Perlmutter describes the case of Carlos. One morning at the age of 27, Carlos woke up and felt “drunk and dizzy” even though he didn’t go out last night and should have had enough sleep. He went to see a Neurologist and who performed a MRI on his brain. but without any findings. Two weeks after that, while exercising, Carlos suddenly felt like ants crawling up his back. This time he went to see a Naturopath, who gave him nutritional supplements. And Carlos health improved a little bit and the symptoms mostly disappeared. Three years later, he felt a numbness in both his legs. Again he was given a new round of supplementation but this time he improved only slowly with some kind of relapse two years later.

In 2010, his health became worse when he suddenly got problems with his balance. This time no supplementation could show any improvement. And by 2014, he went through another round of test with Neurologist, including a MRI with the result that he got diagnosed with an onset of Multiple Sclerosis.

 

 
Multiple Sclerosis.jpg
 

Multiple Sclerosis is an autoimmune disease in which the body’s own immune cells start to attack the insulating cover that protects the neurons. The myelin. Researchers still do not completely understand which factors play into developing Multiple Sclerosis and how the disease starts.

Certainly, genetic components play into this.

But statistics show us that MS is on a rise. Since 1990 there is an increase of 2.4%  annually in the MS cases in women and also in men it is rising with a steady pace.

                                    Incidence and prevalence of multiple sclerosis in the UK 1990–2010 [1]

                                   Incidence and prevalence of multiple sclerosis in the UK 1990–2010 [1]

 

A study published in 2013 actually showed us that the risk to develop MS was reduced by more than 40% in people who were breast-fed as babies [2], which gives us a hint that also environmental factors can have a big role in the development of this disease.

MS is just one example of the many brain disorders that are on a rise.

- ADHD rates have increased over 50% just in the last 15 years .

- The death rates of Alzheimer's disease have doubled during the same time period.

- Depression rates are rising, as the suicide rates have increased by 24%.

- Autism in children have more than doubled for during the last years.

By now we have evidence that most of these diseases have a certain origin and that in some cases they can be averted. The connection I am talking about is the health of the billions of tiny microbes living inside your body; 

YOUR MICROBIOME

And even if it sounds odd at the beginning that some bacteria in your gut have such a power over your brain I want to show you how we can improve our mental health with some smart tricks in our diet.
But before we jump into the scientific evidences, let’s go back to Carlos:
By the time Carlos met Dr. Perlmutter, Carlos could barely walk anymore. After some initial examinations, Dr. Perlmutter gave Carlos a nutritional plan, high in fiber and good fats and also probiotics to re-introduce healthy microbes. Only two weeks later Carlos health already improved and started walking again. To further improve Carlos health, Dr. Perlmutter suggested a “new” form a microbiome reset –called fecal microbiota transplantation. It basically transfers the microbiome from a healthy person to a person with a disrupted microbiome. After the microbiome transplantations, Carlos improved drastically, and he could walk without assistance again. Carlos case is far from extraordinary. In my series about the microbiome and the immune system, you can learn more about it.

So let’s right jump into the scientific literature out there.

 

Serotonin

gut-brain-axis and serotonin production_OMahony 2014.PNG

 

People with depression often lack optimal stimulation of their brains with the neurotransmitter Serotonin – the happiness hormone. One of the most prescribed drugs for depression are Selective serotonin reuptake inhibitor which are believed to increase serotonin levels. However, what most people don’t know is that actually 95% of the serotonin is produced and released in the gut [3].

 For the production of serotonin, our body needs tryptophan and unlike our own cells, bacteria can synthesize tryptophan. The bacteria often found in probiotics, such as lactobacilli species, streptococcus thermophilus or bifidobacterium infantis are excellent serotonin producer.

Scientist who published in the journal of Psychiatric Research fed rats with the probiotic bacterium “bifidobacterium infantis” and found that the tryptophan concentration in the blood of probiotica-fed rats was almost twice as high as control group [4].

                     Increased Tryptophan concentration by  Bifidobacterium infantis  supplementation [4]

                     Increased Tryptophan concentration by Bifidobacterium infantis supplementation [4]

 

Stress

Chronic stress can lead to many diseases such as strokes, depression, cancer or inflammatory diseases. And as we all now; stress upsets the stomach. But it also works the other way round:
In a study published in 2013, scientist looked into the stress response of germ-free mice [5]. Germ-free animals are animals that are virtually sterile – they don’t possess a microbiome. The researchers found two things:
1. First, GF mice showed an almost double as high stress response than normal mice after some stress was induced and
2. Second, the baseline stress level without any stimulus were already higher in mice without microbes.

Your microbes influence your character

The next study I wanna show is one of my favorite studies I’ve read so far!
Imagine this: Not just between humans but also between mice there are different characters. For an experiment, researchers used the two extremes of mice. For simplicity, we will call them the brave mice and the shy mice. The characteristics are defined by a so-called step-down test. A mouse is placed in the center of an elevated platform and the time the mouse needs to step down is measured. The brave mice usually needed less than 20 seconds to jump down while the shy mice needed three times as much time to find the courage to do so [6].

To identify whether these behaviors have anything to do with the microbiome, they fed the mice antibiotics to deplete their microbes. After they killed of the whole microbiome with antibiotics, they specifically reintroduced in the brave mice the microbiome from the shy mice or they gave the brave mice their "old" microbes back.
Next, they repeated the step down test and the results were astonishing:

- the brave mice, who now harbors the microbiome from shy mice suddenly needs the same time to step-down as the shy mice needed before.

It is like the microbes would have carried over the characteristic traits of the mice. 

Our microbes control our emotions

By now researchers even think that our microbiome influences the way we process emotions. A study conducted by a research group of the UCLA divided healthy women into three groups [7];
- one group received a fermented milk product, containing different probiotic cultures.
- the second group got non-fermented milk
- the third one nothing.

Each group consumed the product twice daily for 4 weeks and to test the emotional responsiveness, the people were then set in front of a screen and the participants viewed a series of pictures of angry or frightened people while their brain activity was measured.

What the functional brain scan showed was that the women on probiotics showed a decrease in parts of the brain that are related to emotions. The researchers concluded that :

“A modulation of the gut flora can provide novel targets for the treatment of patients with abnormal pain and stress responses.”

Microbes and Memory

Memory is nothing we would necessarily connect 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, scientist infected the mice with a pathogen that infects the gastrointestinal tract of mice. Half of the infected mice recieved a probiotica supplement, containing two different strains of Lactobacilli [8].

To test their cognitive function, the mice were placed into a maze to test their spatial memory. The group of mice which were infected and did not receive the probiotics, exhibited memory dysfunctions. The memory dysfunction that "was prevented by daily treatment of infected mice with probiotics".

Brain-derived neurotrophic factor

The Brain-derived neurotrophic factor (BDNF) is a protein responsible for the survival of neurons and stimulates the growth and differentiation of new neurons. The levels of BDNF decrease while aging and people with Alzheimer’s disease have generally lower levels of BDNF. Considering this, it might be a good idea to keep your BDNF levels up.

To test if the microbiome somehow influences BDNF levels, scientist treated mice with antibiotics and checked for their BDNF levels in different parts of the brain [9]. 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.

What can we do with this knowledge?

It is amazing to me how these tiny 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.

 

References

  1. Mackenzie et al., Incidence and prevalence of multiple sclerosis in the UK 1990–2010: a descriptive study in the General Practice Research Database, BMJ, 2013
  2. Conradi et al., Breastfeeding is associated with lower risk for multiple sclerosis, Mult Scler, 2013
  3. Berger et al., The expended biology of serotonin, Annuv Rev Med, 2009
  4. Desbonnet et al., The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat, Joural of Psychiatric Research, 2009
  5. Clarke et al., The microbiome-gut-brain axis during early life regulates the
    hippocampal serotonergic system in a sex-dependent manner, Molecular Psychiatry, 2013
  6. Bercik et al., The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice, Gastroenterology, 2011
  7. Tilisch et al., Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity, Gastroenterology, 2013
  8. Gareau et al., Bacterial infection causes stress-induced memory dysfunction in mice, Gut Microbioate, 2010
  9. Sudo et al., Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice, J Physiol, 2004