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How the Gut Microbiome affects the Brain and Mind

One summer afternoon when Doctor Martin Blaser was still a medical student, he went to see an eleven-year-old boy who had suddenly become ill and was hospitalized.

He was perfectly fine until two days earlier when he suddenly developed a fever and an upset stomach. The next day the fever worsened, and on the third day, the boy developed small purplish dots on his body.

The emergency room doctors quickly realized the boy had Rocky Mountain spotted fever, something caused by a bite from a tick infected with a type of bacteria called rickettsia. This bacterium multiplies within cells lining blood vessels, invoking an aggressive immune response.

Since this involves the brain’s blood vessels, it caused a form of encephalitis, a swelling of the brain provoking a massive headache. When Blaser accompanied doctors to see the boy, the room was darkened as the light hurt his eyes, his body was covered with purple spots, and he was thrashing around in his bed covered in sweat.

He was yelling incoherently as loud as he could while hallucinating. As Dr. Blaser explains in his book “Missing Microbes,” the boy was started on an antibiotic called tetracycline and after just five days, he was discharged from the hospital.

Especially considering the Gut Microbiome is the big topic in health and science recently, you may know that not all microbes are bad. While there are pathogenic microbes like these just mentioned, at all times there are 500 to 1000 different species of bacteria in the human body.

And the importance of their function is becoming more apparent as we learn new things about them. However, it’s hard to picture how tiny microbes in our gut contribute to our day to day cognition and brain function. In the case of rocky mountain spotted fever it may not be surprising that the introduction of a deadly pathogen could induce drastic changes in a person’s mental state.

However, the relationship between the microbes normally residing in the gut and how our brain operates becomes apparent when we take them out. Scientists observing microbe-free mice living in sterile bubbles quickly noticed that these mice have a personality that is distinct from mice with gut microbes.

Microbe-free mice were found to be more prone to taking risks and they freely explore their environment. Risk taking might be good if you’re a young entrepreneur, but the kind of risk these mice engage in is wandering further out in an open field. For a mouse, this is an excellent strategy for quickly getting killed by a predator.

Not only are the mice unusually reckless, scientists also noticed that these microbe-free mice have memory-related defects. The book “The Good Gut” by Erica and Justin Sonnenburg describes how a group of researchers put normal and microbe free mice through some memory tests.

First, the mice were given five minutes to explore two new objects, a small smooth ring and a large checkered ring. Then the objects were removed for twenty minutes. After that, the large checkered ring and a new object, a star-shaped cookie cutter, were put in the cages.

Predictably, the mice with the normal microbiota checked out the cookie cutter and paid less attention to the checkered ring because they already knew what it was. The microbiota free mice, explored the new cookie cutter, but spent just as much time checking out the old object - the checkered ring.

It seemed that these mice had completely forgotten an object they had just seen twenty minutes earlier. The forgetfulness in these mice may be explained by the fact that the microbe free mice have lower levels of BDNF. BDNF, brain-derived neurotrophic factor is a powerful protein important for learning and memory.

It stimulates the production of new brain cells and strengthens existing ones. Low levels of BDNF are linked to depression and anxiety. Since making microbe-free humans would be quite unethical, such experiments haven’t been repeated in humans, but… you may have heard of the woman who, after receiving a fecal microbiota transplant, became obese.

The fecal microbiota transplant or FMT is just as it sounds, it’s taking the poop from one healthy person and putting it into another person, in order to share the healthy microbiota of the donor.

FMT is not a common practice, but it’s the most effective treatment for a Clostridium difficile infection, which causes diarrhea and abdominal pain for weeks. In this case, the woman’s donor was her 16 year old overweight but otherwise healthy daughter. The transplant went smoothly and successfully cured the woman’s issues. But, over a period 16 months, the woman gained 34 pounds.

And this happened despite persistent diet and exercise efforts. She even went on a medically supervised liquid protein diet and still could not get the weight off. On the flipside of this, it’s been found that putting the microbiota of lean mice into other mice protects them from gaining weight.

So it looks like a microbiota transplant can transplant body types, but what about personality? In 2011, a research group at McMaster University did an experiment with two different types of lab mice. One type had a personality that was the mouse equivalent of anxious and the other type was sociable and extroverted.

To set a metric for how nervous the mice were, they put them on an elevated platform and recorded how long it took for them to step down. The mice with the anxious personality spent an average of four and a half minutes slowly and carefully making their way off the platform. The “extroverted” mice jumped down in seconds.

Then, the scientists switched the microbiota of the two types of mice and did the platform test again. The mice with the extroverted personality, after receiving the microbes of the anxious mice, now took over a minute to get off the platform.

On the other hand, after getting the microbes from the extroverted mice, the “anxious” mice got off of the platform a whole minute quicker. What this group showed was that in these mice, behavior and levels of anxiety were dependent on which microbes were living in their gut.

One other thing: remember BDNF, the protein that we should like to have more of for better brain function? Well, the microbiota switch that made the “anxious” mice more “confident” also increased their levels of BDNF. The change in microbiota not only made observable changes in behavior, but in brain chemistry as well. In fact, there’s all kinds of chemistry going on in the gut that can affect the brain.

There’s even research identifying which specific microbes produce which neurotransmitters. For example it’s estimated that 90% of our serotonin is produced in the gut, and it’s been found that some of this serotonin is produced by these four microbes.

These two microbes produce gamma-Aminobutyric acid or “GABA” - our chief inhibitory neurotransmitter which has relaxing and anti-anxiety effects. And these two (Bacillus and Serratia) produce our motivation neurotransmitter, dopamine.

[R] So we basically have this huge mass of little drug factories sitting in our gut pumping out different substances that affect our brain. In fact the gut and its microbes appears to affect the brain so much that preclinical research in rodents suggested that certain probiotics have antidepressant and anti-anxiety effects.

Probiotics are basically substances you can take orally to stimulate the growth of microbes. One study even found that a Bifidobacterium infantis probiotic had anti-depressive effects on par with that of the anti-depressant drug citalopram. I used to think that the only benefit of fiber was that it helped you poop.

However, considering dietary fiber isn’t food for us but for our microbes, a diet rich in fiber from a variety of sources should also be good for our mental health. This information about the gut microbiome makes you start to wonder how many mental afflictions could be traced back to disruptions in gut health from, for example, diets rich in fiberless processed foods and refined carbohydrates, or from the unmitigated use of antibiotics.

Antibiotics can be a life saver when absolutely necessary as we saw at the start of the video, but the most commonly prescribed antibiotic - a wide-spectrum antibiotic doesn’t just kill the offending bacteria, but all kinds of other bacteria get caught in the crossfire. This is like poisoning your cat along with a bunch of cockroaches you’re trying to kill.

In the United States alone, tens of millions of people are prescribed antibiotics for minor afflictions. 60 to 80 percent of children taken to the doctor complaining of bad sore throats or ear pain will walk out with an antibiotic.

It’s estimated that people will take 30 courses of antibiotics by the age of 40. But, the highest prescription rate was for children under the age of two with 1,365 courses per 1000 babies. So, could all these antibiotics affect the young gut microbiome and the brain development of these children?

A 2012 paper by Dr. Derrick MacFabe describes what happens when rats are injected with something called Propionic Acid or PPA. The PPA injection provoked peculiar changes in the rats’ brains like neuroinflammation, increased oxidative stress, and glutathione depletion.

The rats also displayed abnormal movements, repetitive interests, cognitive deficits, and impaired social interactions. Basically, the results of this injection were very similar to autism spectrum disorders. And, PPA is a fermentation product of bacteria, namely Desulfovibrio, Bacteroidetes and Clostridia.

It was found that patients with autism have many more species of the clostridium bacteria and have high levels of PPA in their feces. It’s estimated that in one third of patients, autism doesn’t show up until around 18 to 24 months.

Several reports from parents say that their children were developing normally until they received antibiotics for upper respiratory or ear infections. According to Dr. Sydney Finegold, antibiotics wipe out or suppress several organisms in the gut, but Clostridia is one of the ones that persists.

A CBC program titled “The Autism Enigma” features Ellen Bolte who explains how her son Andrew’s behavior changed drastically after 6 courses of antibiotics over a 2 to 3 ½ month period for an ear infection.

After this, he was diagnosed with severe autism. Digging into the research, Ellen came across information about the Clostridia bacteria, so she started searching for a doctor who would be willing to try an antibiotic called “vancomycin” on Andrew. Vancomycin is specifically designed to target the Clostridia bacteria.

After she finally found a doctor who agreed to test her theory, they tried the antibiotic and it had impressive effects. “The results were astounding. Within a matter of just a few weeks, he became calm. He was aware of his environment… he’s putting puzzles together…”

The antibiotic brought out improvements in Andrew that were transient but drastic. This case lead to a pilot study with Dr. Finegold and a Dr. R Sandler who found that out of 10 autistic children treated with vancomycin, 8 of them had again transient but significant improvements.

Now, jumping to conclusions about the cause autism has not been… helpful in the past… but this idea that autism could be the result of a disturbed gut is gathering more and more data. A disturbed gut ecosystem would also explain the very common gastrointestinal issues autistic children suffer.

Some estimates say that as high as 70% of children with autism spectrum disorders also have gastrointestinal issues. Autism is just one of the disorders that can be linked to a disruption in gut health, and research on the gut microbiome is growing quickly. About 3600 related articles on this topic were published between 2010 and 2015.

At this point, saying the gut microbiome is important to health is an understatement. Dr. Martin Blaser says that “losing your entire microbiome outright would be nearly as bad as losing your kidneys or liver.” Unlike the kidneys or liver however, you can change the makeup of your microbiome with what you put into your mouth.

I guess Hippocrates knew what he was talking about when he said “All disease begins in the gut,” and “Let food be thy medicine.”