When Gut Bacteria Changes Brain Function

[itchybromusic]

http://www.theatlantic.com/health/archive/2015/06/gut-bacteria-on-the-brain/395918/

Some researchers believe that the microbiome may play a role in regulating how people think and feel.

 

By now, the idea that gut bacteria affects a person’s health is not revolutionary.

Many people know that these microbes influence digestion, allergies, and metabolism.

The trend has become almost commonplace: New books appear regularly detailing

precisely which diet will lead to optimum bacterial health.

 

But these microbes’ reach may extend much further, into the human brains. A

 

growing group of researchers around the world are investigating how the

 

microbiome, as this bacterial ecosystem is known, regulates how people think

 

and feel. Scientists have found evidence that this assemblage—about a

 

thousand different species of bacteria, trillions of cells that together weigh

 

between one and three pounds—could play a crucial role in autism, anxiety,

 

depression, and other disorders.

 

 

“There’s been an explosion of interest in the connections between the

 

microbiome and the brain,” says Emeran Mayer, a gastroenterologist at the

 

University of California, Los Angeles, who has been studying the topic for the

 

past five years.

 

Some of the most intriguing work has been done on autism. For decades,

 

doctors, parents, and researchers have noted that about three-quarters of

 

people with autism also have some gastrointestinal abnormality, like digestive

 

issues, food allergies, or gluten sensitivity. This recognition led scientists to

 

examine potential connections between gut microbes and autism; several

 

recent studies have found that autistic people’s microbiome differs significantly

 

from control groups. The California Institute of Technology microbiologist

 

Sarkis Mazmanian has focused on a common species called Bacteroides

 

fragilis, which is seen in smaller quantities in some children with autism. In

 

a paper published two years ago in the journal Cell, Mazmanian and several

 

colleagues fed B. fragilis from humans to mice with symptoms similar to

 

autism. The treatment altered the makeup of the animals’ microbiome, and

 

more importantly, improved their behavior: They became less anxious,

 

communicated more with other mice, and showed less repetitive behavior.

 

Exactly how the microbes interact with the illness—whether as a trigger or as a

 

shield—remains mostly a mystery. But Mazmanian and his colleagues have

 

identified one possible link: a chemical called 4-ethylphenylsulphate, or 4EPS,

 

which seems to be produced by gut bacteria. They’ve found that mice with

 

symptoms of autism have blood levels of 4EPS more than 40 times higher than

 

other mice. The link between 4EPS levels and the brain isn’t clear, but when

 

the animals were injected with the compound, they developed autism-like symptoms.

 

“We may be able to reverse these ailments. If you turn off the faucet that produces this compound, then the symptoms disappear.”

 

Mazmanian, who in 2012 was awarded a MacArthur grant for his microbiome

 

work, sees this as a “potential breakthrough” in understanding how microbes

 

contribute to autism and other neurodevelopmental disorders. He says the

 

results so far suggest that adjusting gut bacteria could be a viable treatment for

 

the disease, at least in some patients. “We may be able to reverse these

 

ailments,” he says. “If you turn off the faucet that produces this compound,

 

then the symptoms disappear. That’s what we see in the mouse model.”

 

Scientists have also gathered evidence that gut bacteria can influence anxiety

 

and depression. Stephen Collins, a gastroenterology researcher at McMaster

 

University in Hamilton, Ontario, has found that strains of two

 

bacteria, lactobacillus and bifidobacterium, reduce anxiety-like behavior in

 

mice (scientists don’t call it “anxiety” because you can’t ask a mouse how it’s

 

feeling). Humans also carry strains of these bacteria in their guts. In one study,

 

he and his colleague collected gut bacteria from a strain of mice prone to

 

anxious behavior, and then transplanted these microbes into another strain

 

inclined to be calm. The result: The tranquil animals appeared to become anxious.

 

Overall, both of these microbes seem to be major players in the gut-brain axis.

 

John Cryan, a neuroscientist at the University College of Cork in Ireland, has

 

examined the effects of both of them on depression in animals. In a

 

2010 paper published in Neuroscience, he gave mice either bifidobacterium or

 

the antidepressant Lexapro; he then subjected them to a series of stressful

 

situations, including a test which measured how long they continued to swim

 

in a tank of water with no way out. (They were pulled out after a short period of

 

time, before they drowned.) The microbe and the drug were both effective at

 

increasing the animals’ perseverance, and reducing levels of hormones linked

 

to stress. Another experiment, this time using lactobacillus, had similar

 

results. Cryan is launching a study with humans (using measurements other

 

than the forced swim test to gauge subjects’ response).

 

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http://cdn.theatlantic.com/static/mt/assets/food/138851785_1f0ede5370_omain2.jpg

In Autism, the Importance of the Gut

So far, most microbiome-based brain research has

 

been in mice. But there have already been a few studies

 

involving humans. Last year, for example, Collins

 

transferred gut bacteria from anxious humans into

 

“germ-free” mice—animals that had been raised (very

 

carefully) so their guts contained no bacteria at all.

 

After the transplant, these animals also behaved more

 

anxiously.

 

Other research has examined entire humans, not just their bugs.

 

A paper published in the May 2015 issue of Psychopharmacology by the

 

Oxford University neurobiologist Phil Burnet looked at whether a prebiotic—a

 

group of carbohydrates that provide sustenance for gut bacteria—affected

 

stress levels among a group of 45 healthy volunteers. Some subjects were fed

 

5.5 grams of a powdered carbohydrate known as galactooligosaccharide, or

 

GOS, while others were given a placebo. Previous studies in mice by the same

 

scientists had shown that this carb fostered growth

 

of Lactobacillus and Bifidobacteria; the mice with more of these microbes also

 

had increased levels of several neurotransmitters that affect anxiety, including

 

one called brain-derived neurotrophic factor.

 

In this experiment, subjects who ingested GOS showed lower levels of a key

 

stress hormone, cortisol, and in a test involving a series of words flashed

 

quickly on a screen, the GOS group also focused more on positive information

 

and less on negative. This test is often used to measure levels of anxiety and

 

depression, since in these conditions anxious and depressed patients often

 

focus inordinately on the threatening or negative stimuli. Burnet and his

 

colleagues note that the results are similar to those seen when subjects take

 

anti-depressants or anti-anxiety medications.

 

Perhaps the most well-known human study was done by Mayer, the UCLA

 

researcher. He recruited 25 subjects, all healthy women; for four weeks, 12 of

 

them ate a cup of commercially available yogurt twice a day, while the rest

 

didn’t. Yogurt is a probiotic, meaning it contains live bacteria, in this case

 

strains of four

 

species, bifidobacterium, streptococcus, lactococcus, and lactobacillus. Before

 

and after the study, subjects were given brain scans to gauge their response to a

 

series of images of facial expressions—happiness, sadness, anger, and so on.

 

“This was not what we expected, that eating yogurt twice a day for a few weeks would do something to your brain.”

 

To Mayer’s surprise, the results, which were published in 2013 in the

 

journal Gastroenterology, showed significant differences between the two

 

groups; the yogurt eaters reacted more calmly to the images than the control

 

group. “The contrast was clear,” says Mayer. “This was not what we expected,

 

that eating a yogurt twice a day for a few weeks would do something to your

 

brain.” He thinks the bacteria in the yogurt changed the makeup of the

 

subjects’ gut microbes, and that this led to the production of compounds that

 

modified brain chemistry.

 

 

It’s not yet clear how the microbiome alters the brain. Most researchers agree

 

that microbes probably influence the brain via multiple mechanisms. Scientists

 

have found that gut bacteria produce neurotransmitters such as serotonin,

 

dopamine and GABA, all of which play a key role in mood (many

 

antidepressants increase levels of these same compounds). Certain organisms

 

also affect how people metabolize these compounds, effectively regulating the

 

amount that circulates in the blood and brain. Gut bacteria may also generate

 

other neuroactive chemicals, including one called butyrate, that have been

 

linked to reduced anxiety and depression. Cryan and others have also shown

 

that some microbes can activate the vagus nerve, the main line of

 

communication between the gut and the brain. In addition, the microbiome is

 

intertwined with the immune system, which itself influences mood and

 

behavior.

 

This interconnection of bugs and brain seems credible, too, from a

 

evolutionary perspective. After all, bacteria have lived inside humans for

 

millions of years. Cryan suggests that over time, at least a few microbes have

 

developed ways to shape their hosts’ behavior for their own ends. Modifying

 

mood is a plausible microbial survival strategy, he argues that “happy people

 

tend to be more social. And the more social we are, the more chances the

 

microbes have to exchange and spread.”

 

As scientists learn more about how the gut-brain microbial network operates,

 

Cryan thinks it could be hacked to treat psychiatric disorders. “These bacteria

 

could eventually be used the way we now use Prozac or Valium,” he says. And

 

because these microbes have eons of experience modifying our brains, they are

 

likely to be more precise and subtle than current pharmacological approaches,

 

which could mean fewer side effects. “I think these microbes will have a real

 

effect on how we treat these disorders,” Cryan says. “This is a whole new way to

 

modulate brain function.”

[Harry Bootlace]

VERY interesting

[Canarchist]

MMM, who's doing the thinking, the intelligent bacteria or the dumb human host! What if 'we' are actually the bacteria...

[cardrona]

Nice i have thought about the history and links of this a lot

 

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