Gut Feeling: Curing the Mind Through the Stomach?

(Editor’s note: This article from a past issue of Brain World magazineIf you enjoy this article, consider a print or digital subscription!)

Many cultures recognize the importance of gut health — but recently it’s attracted the attention of the medical world as well. Scientists are now discovering that the gut may influence our thinking, behavior, and even mental well-being. The state of our insides could in fact shape the way we interact with the outside world.

GATEWAY TO THE BRAIN?

The gastrointestinal tract contains about 500 million neurons, as many as are in the spinal cord. Called the “second brain” by Michael Gershon, M.D., the GI tract houses the enteric nervous system (ENS). The ENS contains many of the same neurotransmitters as the brain, including 95 percent of serotonin, the “feel-good” neurotransmitter, as well as neurons and proteins. The gut has a “mind” of its own, and it may be as powerful as the one in your head.

Linking the central nervous system and the ENS is the vagus (“wandering”) nerve, a two-way street between the brain and abdomen. Most signals do not travel from the head to the gut, but from the gut to the head. About 90 percent of messages are conveyed from the vagal receptors to the CNS. The gut also contains 70 percent of immune cells, along with various chemicals and microbes.

Many inflammatory disorders have been linked to changes in the gut ecosystem, or microbiome (the 100 trillion bugs living on our skin, in our mouths, gut, and elsewhere on our bodies). Gut bacteria are essential to our immunity, aid digestion, support metabolism, and ward off harmful invaders. Stress, pollution, and processed food can upset the bacterial balance, causing the immune system to release chemicals that trigger inflammation and can lead to disease. If communication is bidirectional, stress-related changes to the microbiome may affect brain function and behavior.

This raises the possibility that adding “good” bacteria could restore gut harmony and mental well-being. “A new class of probiotics could be used to address neurodevelopmental, behavioral, and perhaps even neurodegenerative disorders,” says Sarkis Mazmanian, Ph.D., a microbiologist at the California Institute of Technology.

UNDER THE INFLUENCE OF BUGS

Everyone is born with a pristine gut. Colonization during birth and shortly afterward helps program one’s responses to stress, and may even influence a person’s behavior.

In 2004, Nobuyuki Sudo, Ph.D., and colleagues at Kyushu University in Japan discovered that introducing bacteria to mice with a sterile gut altered brain chemistry and behavior. They found that germ-free mice were more anxious. Adding the probiotic Bifidobacterium to their gut flora had calming effects on the mice and lowered corticosterone (the stress hormone) levels.

Over the next 10 years, scientists uncovered further evidence of the interplay between the brain and gut. Mazmanian shifted his earlier focus from immunity to how intestinal bacteria interact with the brain. “Gut microbes were communicating with the nervous system and potentially with the brain itself,” he says. In a 2013 study, Mazmanian and neuroscientist Elaine Hsiao investigated behavior in mice that were bred to exhibit symptoms of autism. Altering bacterial composition reduced gut permeability and caused noticeably profound changes in the behavior of mice that were influenced by the microbiome.

At McMaster University in Ontario, the gastroenterologist Premysl Bercik, M.D., found that harmful bacteria can increase anxiety while beneficial bacteria can reduce it. In one study, Bercik and colleagues replaced the gut bacteria in a timid strain of germ-free mice with microbes from fearless mice. Resultantly, the fearful mice were transformed into more adventurous creatures, while the bold mice grew anxious after getting microbes from the timid mice.

Yet, how the gut talks to the brain remains largely uncertain. Scientists at the University College Cork, Ireland, severed the vagus nerve in mice before giving them probiotics. The mice had lower anxiety levels — but only if the vagus nerve was intact. The results suggest its importance, but stop short of explaining how bacteria actually influences the brain.

The endocrinologist Mark Lyte, Ph.D., suggested that gut microbes speak to the brain using their own neurotransmitters. Gut bacteria produce and respond to the same chemicals the brain uses to govern mood (e.g., serotonin, dopamine, and GABA). Presumably, the brain might monitor — and react to — “gut feelings” in order to control outside influences. Probiotics may alleviate anxiety by producing anti-inflammatory molecules, such as serotonin, or reducing activity of the hypothalamic-pituitaryadrenal axis, a set of organs whose interaction helps regulate stress.

TREATING THE GUT TO TREAT THE BRAIN

The beneficial effects of prebiotics and probiotics on digestive health in humans are well-known. However, there are not too many studies on how they affect the brain.

One research team, led by the neuroscientist Philip Burnet, Ph.D., at the University of Oxford, tested the effects of prebiotics on anxiety in 45 healthy adults. Prebiotics are carbohydrates (fibers) that feed beneficial bacteria already found in the gut. Participants received either a prebiotic supplement or placebo every day for three weeks. The results were recently published in the Journal of Psychopharmacology.

“People who are depressed tend to focus on negative information,” says Burnet. To test emotional processing, the researchers performed several computerized assessments, such as eliciting responses to positive and negative words. “After using prebiotics people focused more on positive stimuli than negative information,” says Burnet. Saliva cortisol levels were also lower in the prebiotic group than in controls, indicating diminished anxiety.

The reduction in anxiety is likely due to the anti-inflammatory effects of gut bacteria, according to Burnet. The gut responds to stress or infection by releasing inflammatory cytokines, these in effect disturb brain chemistry and increase susceptibility to anxiety or depression. Prebiotics may increase bacterial diversity, which alters the gut ecosystem and helps put out the fire. “The results suggest prebiotics could work on mechanisms that affect mental health,” Burnet says.

A recent study, led by psychologist Laura Steenbergen from the Leiden Institute of Brain and Cognition in the Netherlands, investigated the potential effects of probiotics on depression. For four weeks, 40 healthy participants received either a multistrain probiotic or placebo. The results appeared in the April 2015 issue of Brain, Behavior, and Immunity. “Rumination is one of the most predictive vulnerability markers of depression,” said Steenbergen in a statement. “Persistent ruminative thoughts often precede and predict episodes of depression.” At the end of the study, the probiotic users had fewer negative thoughts than the placebo group, suggesting that beneficial bacteria have the power to brighten up a dark mood.

Probiotics have also been linked to activation of certain brain areas. A 2013 study by Kirsten Tillisch, M.D., and colleagues used functional MRI to measure changes in resting brain activity and emotion recognition. They gave 36 healthy women probiotics twice daily for four weeks. Twelve consumed a probiotic yogurt, 11 had a nonprobiotic yogurt, and 13 received no intervention. The fMRI results showed that probiotics led to reduced reactivity in the brain regions associated with anxiety (including the insula and somatosensory cortex) in response to images of angry or frightened faces. Their research was an important step in demonstrating the influence of gut health on brain circuitry.

Perhaps one day a drug remedying the gut could treat the brain? Most scientists agree it’s too soon to tell. “Probiotics and prebiotics offer a natural option without the side effects of drugs that target the brain, but it is unlikely that they will replace traditional therapies,” cautions Burnet. “They could improve brain function overall, and therefore improve the response to a drug in treatment-resistant patients.”

Good for Your Gut — And Head

  • Probiotics: KIMCHI, SOME YOGURTS, KEFIR, TEMPEH, OLIVES
  • Prebiotics: ASPARAGUS, GARLIC, ENDIVE, WHEAT, OATS
  • Anti-inflammatories: GINGER, TURMERIC, FISH OIL, CAYENNE, GREEN TEA

(Editor’s note: This article from a past issue of Brain World magazineIf you enjoy this article, consider a print or digital subscription!)

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