If you’ve read that bacteria in our guts influence our moods and have wondered how that works, here’s a new clue towards solving this piece of the recently enlivened mind/body axis puzzle.
THE NEUROTRANSMITTERS GABA & GLUTAMATE
The amino acid called GABA (Gamma Aminobutyric Acid) is the principal INHIBITORY neurotransmitter in the mammalian central nervous system, sending chemical messages through the brain and nervous system and helping regulate communication between brain cells.
GABA’s chief role is to reduce the activity of nerve cells. It plays an important role in behavior, cognition, and how we respond to stress. Research suggests that GABA helps control fear and anxiety when neurons become overexcited. Below normal GABA levels in the brain have been linked to depression, anxiety, sleep disorders, and schizophrenia.
Pharmaceuticals called benzodiazepines bind to the same receptors as GABA, mimicking GABA’s natural calming effects. Examples of popular benzodiazepines for anxiety and insomnia are Valium (diazepam) and Ativan (lorazepam). They slow down the body’s central nervous system and cause sleepiness. (Konkel, 2015)
Glutamate (also called L-glutamate or glutamic acid)) is another important amino acid neurotransmitter released by nerve cells in the brain. It is involved in most aspects of normal brain functioning, including cognition, memory and learning. It is the major mediator of EXCITATORY signals in the mammalian central nervous system. (Danbolt, 2001)
GABA & GLUTAMATE IN BALANCE
Calming GAMBA restrains the release of excitatory glutamate. So you can see that a balance between GABA and glutamate production is needed for proper functioning. It’s a Goldilocks situation: The brain needs to release just the right amount of both GABA and glutamate. Too much or too little of one or the other causes problems.
IT TURNS OUT THAT A TYPE OF BACTERIA IN THE GUT LIVES ON GABA
Researchers have now observed gut bacteria consuming the brain chemical GABA. They found that a type of recently discovered gut bacteria, called KLE1738, can survive and reproduce only if it has GABA molecules to feed on. The researchers tried providing KLE1738 with other types of neurotransmitters but the bacteria couldn’t survive on anything but GABA. Without GABA, these bacteria die.
This is an important clue about how our gut bacteria influence our mood. “GABA acts by inhibiting signals from nerve cells, calming down the activity of the brain, so it’s surprising to learn that a gut bacterium needs it to grow and reproduce. Having abnormally low levels of GABA is linked to depression and mood disorders, and this finding adds to growing evidence that our gut bacteria may affect our brains.” (Coghlan, 2016)
An earlier experiment, in 2011, demonstrated that a different type of gut bacteria, Lactobacillus rhamnosus, dramatically altered GABA activity in the brains of mice as well as affected how well they responded to stress.
When the researchers surgically removed the vagus nerve, the communication pathway between the gut and the brain, the effect on the mice disappeared – more evidence on how gut bacteria influence the brain. (Coghlan, 2016)
The research team, led by Philip Strandwitz at Northeastern University in Boston, is now searching for other gut bacteria that consume or even produce GABA. They plan to test their effect on the brains and behavior of animals. Such work may eventually lead to new treatments for mood disorders like depression or anxiety.
“Due to this unique growth requirement, we provisionally name KLE1738 Evtepia gabavorous. Using growth of E. gabalyticus as an indicator, we then identified novel GABA producing bacteria from the gut microbiome. Reduced levels of GABA are associated with depression, and we found fewer GABA producers in a human cohort of depressed individuals. By modulating the level of GABA, microbial producers and consumers of this neurotransmitter may be influencing host behavior.” (Strandwitz et al, 2016)
Researchers are just at the beginning of looking into the many ways the gut microbiome influences, if not regulates, many bodily processes and how unbalance in the gut microbiome eventually leads to poor health.
This finding of a dependence of a type of gut bacteria on the neurotransmitter GABA doesn’t mean you should start yourself on one of the GABA supplements you’ll find for sale online. But do stay tuned! Neurotransmitters and specific microbes may become the treatment of choice for mood disorders – or, even better, for preventing mood disorders in the first place.
Keep your gut microbiome health, keep your body healthy.
Danbolt, N.C. (2001). Glutamate as a Neurotransmitter – An overview. Center for Molecular Biology & Neuroscience, The Neurotransporter Group – Dynamics of extracellular transmitter amino acids. See: http://neurotransporter.org/glutamate.html
Very good news! An exciting new field of medicine is on the horizon: PSYCHOBIOTICS.
PROBIOTICS are micro-organisms that have beneficial effects on the body when consumed.
Ted Dinan, Catherine Stanton, and John Cryan, pioneering researchers in the field, define a PSYCHOBIOTIC as “a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness”. (Dinan, Stanton & Cryan, 2013)
Scientists are discovering that some probiotic micro-organisms living in our guts are also psychoactive. That is, they deliver neuroactive substances such as gamma-aminobutyric acid (GABA) and serotonin that influence the brain via the gut-brain axis.
I’d say that the field of psychobiotics in the not so distant future will be understood more broadly to include all of us, not just those with diagnosable mental illnesses. For example, we’ll be able to fine tune our anxiety levels day to day – by taking particular probiotics before events we know make us anxious (public speaking, flying, big dates, exams). And, even better, we’ll be able to AVOID depression’s deep troughs of despair and the exhausting paralysis of anxiety by nourishing healthy populations of the appropriate probiotics in our guts.
As we understand the gut-brain axis at this point, communications between the gut and the brain (and vice versa) travel via the long vagus nerve, spinal cord, and/or neuroendocrine systems to mediate various physical and mental states – including anxiety, depression, obsessive-compulsive thoughts and behaviors, autism, chronic fatigue syndrome, and irritable bowel syndrome.
Here’s a diagram of the vagus nerve’s path, showing the organs it connects between the brain at its top end and the intestines at its bottom end. You can see what an important communication highway it provides for the body, allowing the brain, lungs, heart, spleen, liver, kidneys, pancreas, stomach, and intestines to ‘talk’ to one another.
THE VAGUS NERVE
It runs from the brain stem down each side of the neck, across the chest, down through the abdomen allowing the brain, lungs, heart, spleen, liver, pancreas, kidneys, stomach and intestines to communicate bi-directionally along its network.
“So far, psychobiotics have been most extensively studied in … patients with irritable bowel syndrome, where positive benefits have been reported for a number of organisms including Bifidobacterium infantis. Evidence is emerging of benefits in alleviating symptoms of depression and in chronic fatigue syndrome. Such benefits may be related to the anti-inflammatory actions of certain psychobiotics and a capacity to reduce hypothalamic-pituitary-adrenal axis activity. ” (Dinan, Stanton & Cryan, 2013)
Did you notice the mention of the anti-inflammatory actions of probiotics in the quote above?
Most physical and mental diseases have inflammation as their root cause. The vast majority of our immune system, about 70% of it, is located in the gut microbiome. Unbalance in the composition of microbes there creates inflammation inside the intestinal linings, increasing gut permeability, leading to chronic inflammation elsewhere in the body – and disease.
This is my short hand explanation for how the connection works:
Chronic imbalance of microbes in the gut –> chronic inflammation in the gut –>increased gut permeability –> chronic inflammation elsewhere in the body –> diseases in the gut and/or elsewhere in the body
These signaling irregularities affect our emotions, mental abilities, behaviors, and perception of and reactions to pain (nociception). The whole system is something like an enormous, highly complex switchboard. If something interferes with signaling somewhere in the system, a circuit can malfunction and perhaps cause the entire switchboard to break down.
Chronic imbalances in our gut bacteria that lead to gut-brain axis signaling irregularities can also lead to a wide variety of other health problems – including diabetes, heart disease, stroke, migraines, thyroid problems, dental issues, cancers, degenerative neurological diseases, obesity, ADD/ADHD, allergies, asthma, autism, rheumatoid arthritis, chronic Lyme disease … and many, many more. And they all begin with the health of the several pounds of miniscule critters living in our gut microbiomes.
Our gut microbiome, the 100 trillion micro-organisms (500-1,000 species of bacteria, fungi, viruses, and other tiny life forms) living in our intestinal linings, is so important to the proper functioning of the entire body that many scientists now regard it as an organ in and of itself. The theory is that these micro-organisms communicate with the nervous system using some of the same neurochemicals the body uses to relay messages in the brain. (Smith, 2015)
These several pounds of micro-organisms in our guts secrete a large number of neurochemicals, including dopamine, serotonin, and gamma-aminobutyric acid (GABA), the very same chemicals our neurons use to communicate and regulate mood – and chemicals that also play a role in GI disorders, which, not strangely, are associated with high levels of depression and anxiety. (Smith, 2015)
ANXIETY, OBSESSIVE BEHAVIOR, LEAKY GUT AND BACTEROIDES FRAGILIS
In 2013, microbiology researchers Mazmanian and Hsiao published research results that linked a specific variety of probiotic bacteria with anxious behaviors in mice. The mice were known to have alterations in their gut microbiota and GI barrier defects (increased gut permeability, AKA leaky gut) and also exhibited anxious, obsessive behaviors (such as obsessively burying marbles). When they were given oral doses of one of two strains of the bacterium Bacteroides fragilis (probiotic bacteria found in normal gut flora), both their GI problems and maladaptive behaviors improved. (Hsiao et al, 2013) (Smith, 2015)
STRESS, DEPRESSION AND THE PROBIOTICS LACTOBACILLUS AND BIFIDOBACTERIUM
A recent study found that a combination of the probiotics Lactobacillus helveticus and Bifidobacterium longum (probiotic bacteria found in healthy human gut microbiomes) reduced anxiety, depression, and stress levels and improved coping strategies. (Messaoudi, 2011)
Our psychological and physiological reactions to fear and stress play a large role in depression. People suffering from major depression also have elevated levels of cortisol, the stress hormone our adrenals release to get us ready to fight for our lives or flee from the danger. Back when we frequently encountered predatory animals and were often in a fight or flight situation, this elevated release of cortisol was a very useful thing.
What often happens now is that we live in a state of chronic cortisol overproduction, over stimulated, afraid, unable to calm down, wearing out our adrenals. Chronically elevated cortisol production interferes with learning and memory, lowers immune functioning, decreases bone density, increases weight gain, raises blood pressure and cholesterol levels, leads to heart disease, increases risk for depression and anxiety, decreases resilience – and is generally exhausting. A combination of the probiotics, Lactobacillus helveticus and Bifidobacterium longum, was found to reduce cortisol levels. (Berglund, 2013) (Davidson, 2014)
GABA (gamma-Aminobutyric acid) is our central nervous system’s chief inhibitory neurotransmitter, playing a central role in reducing neuronal excitability throughout the body and regulating muscle tone. (Wikipedia, 2015)
Many physiological and psychological processes associated with depression, including negative ruminations, can be traced to a deficiency in the neurotransmitter GABA. Microbes that actively secrete GABA in the gut have been identified by researchers. Chief among them are strains of Lactobacillus and Bifidobacterium.
Bifidobacterium longum has anti-inflammatory, anti-carcinogenic, and antimutagenic properties and may protect you from developing colon cancer. It’s present in breast milk and is one of the first probiotics to colonize a newborn’s gut.
Swiss and Emmenthaler cheeses contain Lactobacillus helveticus. (We’re talking about real cheeses, not the tasteless, processed kinds often found prepackaged in the US.)
Bifodobacterium longum is found in unprocessed yogurts, various types of fermented dairy foods (kefir’s a good choice), and fermented vegetables such as sauerkraut.
Good news for those of us who love dark chocolate: The plentiful polyphenols in dark chocolate serve as PREbiotics, nourishing the beneficial Lactobacillus and Bifidobacterium in our guts. (Davidson, 2014) The higher the cacao and lower the sugar content the better. Organic and fair trade also if possible.
Both L. helveticus and B. longum can also be taken as supplements.
MOOD, OXYTOCIN AND LACTOBACILLUS REUTERI
A team of biologists at MIT found that another probiotic strain, Lactobacillus reuteri, improved mood, restored a youthful appearance to the skin, and promoted general health by increasing levels of oxytocin, the love hormone. (Davidson, 2015)
L. reuteri is one of the fastest colonizing probiotic bacteria available. This is a good thing – colonizing probiotic strains of bacteria in your gut can restore your health.
Lactobacillus rhamnosus is a bacterial strain that has been shown to reduce anxiety and depression in anxious mice.
GABA, the central nervous system’s principal inhibitory neurotransmitter, regulates many physiological and psychological processes in the body. Alterations in GABA receptor expression are linked to the the development of anxiety and depression.
Study results published in 2011 shed light on exactly how L. rhamnosus in the gut impacts the brain’s chemistry.
The researchers found that the probiotic L. rhamnosus markedly affected GABA levels in certain brain regions and lowered the stress-induced hormone corticosterone, resulting in reduced anxiety- and depression-related behavior.
When the vagus nerve was severed, GABA receptor levels and the animals’ behavior remained unchanged after treatment with L. rhamnosus, confirming that the vagus nerve is most likely the primary pathway of communication between the bacteria in the gut and the brain.
The researchers allow that the vagus nerve is the obvious communication route but perhaps not the only one, that messaging may also occur via other nerves or chemicals in the blood.
If you doubt there’s a direct connection between the health of the gut microbiome and mental health, keep in mind that functional bowel disorders and mood disorders such as anxiety and depression are generally comorbid (they generally occur together).
Strains of L. rhamnosus are found in some dairy products such as live culture yogurts, cheeses (eg, real Parmigiano Reggiano), and kefir. They’re also found in fermented dry sausages and some fermented soy cheeses. (Panyko, 2015)
PAIN, CHRONIC FATIGUE, DEPRESSION, ANXIETY AND LACTOBACILLUS ACIDOPHILUS
Lactobacillus acidophilus improves the functioning of canabinoid receptors in the spinal cord that are important for regulating pain perception. (Davidson, 2014)
A 2009 study to see if treatment with live L. acidophilus was helpful for chronic fatigue syndrome and the depression that’s part of it showed promising results. When the researchers supplemented chronic fatigue syndrome sufferers with a live casie strain of L. acidophilus for two months, they saw a significant decrease in the subjects’ depression, anxiety, and general emotional distress. (Rao et al, 2009)
Food sources of L. acidophilus include live culture yogurt and other fermented foods such as sauerkraut, sauerkraut juice, kimchi, miso, chutneys, and kefir.
SEROTININ, CHRONIC INFLAMMATION AND BIFIDOBACTERIUM INFANTIS
A number of microbes can produce other neurotransmitters, such as norepinephrine, serotonin, and dopamine. For example, Bifidobacterium infantis, taken as an probotic, alters serotonin levels – just like Prozac but without the undesirable side effects. (Davidson, 2014)
Bifidobacterium infantis has been clinically demonstrated to be very good at reducing the symptoms caused by chronic immune activation in the gut, autoimmune diseases, and excessive cortisol release. So it, along with some other probiotic bacteria, is a good choice for people with leaky gut, IBS, IBD, celiac disease, and Crohn’s disease. (Nootriment, 2015)
Infantis in this bacteria’s name indicates that it’s a strain vitally important for infant health. B. infantis is usually one of the first probiotics mothers pass on to their babies during vaginal births. Many scientists and doctors therefore recommend that pregnant women take it as a supplement.
The main benefit from B. infantis is to improve digestion and protect us against infection and sickness. It has also been shown to fight allergies and prevent kidney stones. It accomplishes all this by producing large amounts of acid to make our digestive tracts and vaginas inhospitable to pathogenic bacteria and parasites. (Jerkunica, 2015)
If you’ve decided to add ready-made fermented foods like sauerkraut or pickles to your diet for their probiotic benefits, remember it’s only the truly fermented versions that are helpful. The ones made with vinegar, although they may say ‘pickled’ on their labels, aren’t actually fermented and don’t offer any probiotic or enzymatic benefits. Look for the fermented versions in the refrigerated areas in stores.
Fermented foods contain living cultures. Refrigeration slows down the fermentation process. The brine may be cloudy – full of lactic acid bacterial growth (the desirable probiotics) created during fermentation. The jar lids may be slightly swollen from the ongoing fermentation process. Fermented pickles have a complex taste – they’re alive on your tongue. Pickles made with vinegar taste like vinegar.
Years ago, when I was living in Cambridge, MA, my neighborhood grocery store was Savenor’s. Mrs Savenor kept a huge, wooden pickle barrel next to the checkout counter. The top of the barrel was open. The brine was cloudy, sometimes scummy looking, and every once in a while the barrel emitted a big belch of gas. I thought the whole thing was unsanitary and never bought her pickles. Now I wish I’d known then what I’ve since learned about the benefits of that living culture.
Savenor’s was also where Julia Child shopped for her meats. The Childs lived in the neighborhood of beautiful big houses on the north side of Kirkland Street. I was in the neighborhood of old apartment buildings on the south side of Kirkland, where students and other people with little money lived.
Here’s a fond memoir about Mrs Savenor by one of her grandsons, Alan Savenor: How a Matriarch Ran Savenor’s. She was a character. Reputedly, she’d smuggled her young boys out of Lithuania by walking across the border with them under her voluminous, floor length skirt when the Nazis set about exterminating all the Jews there.
For those of you interested in improving your gut microbiomes and overall health by eating probiotic-rich foods, here’s a good article on Probiotics & Fermented Foods written by the Sacramento Natural Foods Coop.
YOUR BRAIN ON BUGS
This is what pioneering Integrative Health doc J. E. Williams, OMD, has to say about psychobiotics and how best to get them into your body:
“Microbiota, those microscopic bugs that live in your body—mainly in the gut—can influence brain chemistry and consequently behavior. We know that Clostridium difficile, the nasty gut hospital-based gut infection that kills 14,000 people each year in the U.S., is associated with depression and dementia. Two antidepressants, mirtazapine (Remeron) and fluoxetine (Prozac), are linked to a nearly 50 percent increased risk for Clostridium difficile infection.
“Doctors have long known that foods and changes in the gastrointestinal system are associated with mood changes. Does the pathway to happiness actually exist in your gut?
Sources of Psychobiotics
“Probiotics come in a variety of forms, from powders and capsules to foods such as yogurt, dairy drinks, infant formulas, cheese, and even some energy snack bars. Any of these forms may be effective for digestive problems as long as they contain the right kind of beneficial organisms in adequate numbers.
“In my clinical experience, I’ve found that supplements with live friendly bacteria in high dosages are more effective for treatment of depression, immune deficiency, and gastrointestinal problems then consuming yogurt or fermented vegetables alone.
“We’re finding that most diseases, including psychiatric illnesses, have inflammation as their root cause. Inflammation is associated with immune system imbalance and disruption of hormone activity. Probiotics may also influence how your genes work. Psychobiotics could target genes responsible influencing neurotransmitters like GABA that have a strong connection to mood and behavior.
“We know that “gluten brain” is a type of mental fog common in people with gluten sensitivity. People with gluten sensitivity feel better when eliminating wheat, but the benefit is limited. If you have tried the gluten-free diet and wonder what’s next, consider psychobiotics
“The autonomic nervous system links the brain and gut largely through the vagus nerve. More than 90 percent of the body’s serotonin, a feel good neurotransmitter, lies within the gut. In fact, your gut has a mind of its own and it’s called the enteric nervous system.
“Changes in diet have immediate effects on the bacterial composition in your gut. Antibiotics have disastrous effects on gut bacteria. Now we have good research and more than enough clinical evidence that specialized probiotic bacteria are essential for health, and also profoundly influence mood.
“So, it’s not surprising that when your gut is healthier, so is your brain and mood. Your immune system works better too, so you have fewer episodes of the cold and/or flu.”
– Williams, 2014
IS YOUR FATE IN YOUR GENES?: GENETICS VS EPIGENETICS
If there’s been mental illness – say depression, anxiety or panic disorder, OCD, autism, schizophrenia – in your family as far back as anyone can remember, you needn’t feel that you or your children are doomed. Genetics is the study of genes, heredity, and genetic variation in living organisms. Epigenetics is the study of factors that turn genes on and off and affect how cells read genes.
Your genetics account for only 25% of the chance you’ll develop a disease. The other 75% is environmental (both internal and external) and therefore largely up to you. So take very good care of your gut microbiome. Provide it with lots of good microbes (probiotics and psychobiotics) to keep a good balance in there and avoid the bad ones (bacterial pathogens and other toxins) as much as possible.
This is also true of genetic predispositions for heart disease, diabetes, Alzheimer’s, cancer, and pretty much every other illness. You are not a prisoner of your genes. Probiotics influence activity in our genes, allowing them to express their contents in a positive, disease-fighting manner.
Research has shown that probiotic bacteria produce positive changes in the mucosal lining of the small intestines which affect gene activity and cellular reactions.
“Consumption of a dairy drink containing three strains of probiotic bacteria was associated with changes in the activity of hundreds of genes, with the changes resembling the effects of certain medicines in the human body, including medicines that positively influence the immune system and those for lowering blood pressure.”
– Mercola, 2010
STAY TUNED! There’s lots of good research being done now on the relationship between probiotics in the gut, mood – and pretty much every other working of the body.
Many thanks to both Liz Poirier and Alex Tatusian for pointing me to the New York Times Magazine article by Peter Andrey Smith, which prompted this post: Can the Bacteria in Your Gut Explain Your Mood? It’s very good and I recommend reading it.
Messaoudi, M. et al. (2011). Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition, 105:5, 755-64. See
Rao, A.V. et al. (2009). A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathogens, 1:6. See: http://www.gutpathogens.com/content/1/1/6