Mind and body homework

10/27/2016 What Gut Bacteria Does to the Human Brain - The Atlantic

http://www.theatlantic.com/health/archive/2015/06/gut-bacteria-on-the-brain/395918/?utm_source=atlfb 1/7

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

When Gut Bacteria Changes Brain Function

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

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10/27/2016 What Gut Bacteria Does to the Human Brain - The Atlantic

http://www.theatlantic.com/health/archive/2015/06/gut-bacteria-on-the-brain/395918/?utm_source=atlfb 2/7

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 paperpublished 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

10/27/2016 What Gut Bacteria Does to the Human Brain - The Atlantic

http://www.theatlantic.com/health/archive/2015/06/gut-bacteria-on-the-brain/395918/?utm_source=atlfb 3/7

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

10/27/2016 What Gut Bacteria Does to the Human Brain - The Atlantic

http://www.theatlantic.com/health/archive/2015/06/gut-bacteria-on-the-brain/395918/?utm_source=atlfb 4/7

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).

R E L AT E D S T O R Y

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

10/27/2016 What Gut Bacteria Does to the Human Brain - The Atlantic

http://www.theatlantic.com/health/archive/2015/06/gut-bacteria-on-the-brain/395918/?utm_source=atlfb 5/7

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 Psychopharmacologyby 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.

10/27/2016 What Gut Bacteria Does to the Human Brain - The Atlantic

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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,

10/27/2016 What Gut Bacteria Does to the Human Brain - The Atlantic

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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 an 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.”