Photo courtesy of James Wojcik/Trunk Archive
How Our Gut Affects Our Mood
How Our Gut Affects Our Mood
“Whatever goes on in the emotional parts of our brain is mirrored in the gut, and whatever goes on in our gut influences our brain,” explains Dr. Emeran Mayer. “Even though these bidirectional influences happen in each individual, many people are not aware of them.”
A gastroenterologist, neuroscientist, and the author of The Mind-Gut Connection, Mayer has been studying this interaction for over forty years. He is a professor at the David Geffen School of Medicine at UCLA, where he runs the G. Oppenheimer Center for Neurobiology of Stress and Resilience and codirects the Digestive Diseases Research Center (CURE). Mayer’s research on how the tiny microbes in our gut communicate with our brain shows how an unbalanced communication system can give rise to health issues, whether it’s a digestive disorder and allergies or anxiety and depression.
The gut is not the second brain, according to Mayer. It’s the first. Our gut-based nervous system developed hundreds of millions of years before the human brain. We’d be wise to pay attention to it.
Which is what Mayer helps us do: His work, for example, examines the impact of what we eat, as well as how we eat. By implementing specific dietary interventions, shifting our inner dialogue, and spending time with our communities, Mayer says we can enhance our mind-gut connection, improve our mood and mind-set, boost our immunity, and maybe do even more to stave off the most common diseases.
A Q&A with Emeran Mayer, MD
The gut is a complex organ made up of different, closely interconnected systems. While it’s commonly believed to encompass just our digestive system, it is far more complex. To acknowledge this interconnectedness, scientists have referred to it as “gut connectome.”1
The gut communicates with the brain via different channels, which include:
The immune system: through circulating cytokines and other inflammatory signals.
The endocrine system: comprising hormones produced in the gut, including the satiety hormones that make us feel full after a meal.
The nervous system: comprising the two branches of the vagus nerve, one branch sending signals from the gut to the brain and the other, much bigger one transmitting information from the brain to the gut.
When the gut is inflamed, it can make an individual feel unwell or fatigued or similarly cause an individual to feel nauseated after consuming a meal high in fats. When the gut is empty for a long period of time, one may begin to crave food. On the other hand, if you eat healthy, nutritious food, it can often lead to decreased feelings of anxiety and an enhanced mood. These are a few examples of the way the gut sends signals across a branch to the brain.
On the other hand, the brain can also send signals to the gut that reflect our emotional states and the degree to which we feel stressed. These signals travel via a different branch of the vagus nerve, which is much smaller than the sensory branch. For example, when you’re angry or stressed, your stomach may feel cramped or as if it’s tied up in knots. And when you are excited, you may feel butterflies in your stomach. All these gut reactions reflect how your brain influences the different aspects of your gut, including contractions, blood flow, and secretion.
Whatever goes on in the emotional parts of our brain is mirrored in the gut—and whatever goes on in our gut, in response to what we eat, influences our brain. Even though these bidirectional influences happen in each individual, many people are not aware of them. There are others, though, who are overly sensitive and develop hypersensitivities to various foods or feelings of anxiety and may develop symptoms of irritable bowel syndrome.
While the term “the second brain” has become popular to describe the enteric nervous system (ENS)—or the collection of nerves found in the gut—this gut-based nervous system is really our first brain. The ENS developed hundreds of millions of years before the human brain, and most of the neurotransmitters and signaling molecules in the brain are derived from molecules that originated in the nervous system of the gut.
The gut is in constant interaction with the 70 trillion microorganisms that live within us. In addition to containing more than 150 million nerve cells, the gut also makes up the largest part of our immune and endocrine (hormonal) system. Much of the information generated in our gut is sent to the brain through the vagus nerve, highlighting the wealth of information that our bodies collect from our intestines. This explains why the gut plays such an important role in regulating so many functions in the body. It also explains why the gut has been implicated in so many health issues, from neurodegenerative diseases, like Alzheimer’s and Parkinson’s, to our emotional well-being, allergies, and autoimmune diseases, like inflammatory bowel diseases, multiple sclerosis, and rheumatoid arthritis.
While the brain is responsible for the ways we interact with the world around us through our senses of sight, sound, smell, and touch, our gut governs the ways we interact with the food we consume and with the microbial world inside of us.
The gut microbiome represents the vast community comprising hundreds of trillions of microorganisms that make up a complex ecosystem inside of our intestines. They are responsible for the stability and resilience against foreign insults and perturbations to our bodies. They are in intimate contact with the major information-gathering systems in our body—specifically the immune and endocrine systems. Because these communities of microbes reside throughout our intestines, this strategic location allows them to listen in when the brain signals to the gut how stressed, happy, anxious, or angry you are, even when you’re not fully aware of these emotions. On the other hand, they are in a perfect position to strongly influence our emotions by sending signals back to the brain.
We have good reason to believe, based on studies in mice, that the gut microbiome also plays a role in our emotional and social behaviors. While there are fewer studies that support the close link in humans, my team and other researchers have demonstrated that there is a relationship between the types of microbes that live in your gut and brain structure and function. Alterations in the composition and function of the gut microbiota have been identified in many brain disorders, including depression, anxiety, autism spectrum disorders, Alzheimer’s, and Parkinson’s disease.
However, it remains to be seen if these correlations reflect a causal role of certain microbes in these disorders, if they result from altered signals that the brain sends to the gut in these conditions, or if there are other factors—such as lifestyle, diet, medications—that underlie these associations. If a causal role of altered gut microbes in human brain disorders can be established, it would open up exciting new treatment options aimed at normalizing the microbiome and curing the disease. Such future options could include specific dietary interventions, personalized pre- and probiotics, and even new ways of doing fecal microbial transplants. Unfortunately, oftentimes such interventions are recommended in the absence of scientific evidence.
There is mounting evidence that a healthy microbiome—high in diversity and beneficial microbes—plays an important role in keeping our gut healthy. This is reflected in an optimal gut barrier, or minimal “leakiness”; little gut-based and systemic immune activation; regular gut contractions and transit; and secretion of mucus and water.
The crucial period of microbiome development is in the first thousand days of life. Many crucial factors play a role during this period, such as the pregnant mother’s diet, her levels of stress, the mode of delivery, the duration of breastfeeding. Other factors include a newborn’s exposure to any early life stressors and their exposure to pets and environmental microbes. Since there are many factors that can contribute to the health of the infant’s microbiome, it’s difficult to identify the impact of any single one of them.
For example, the Yanomami—the largest relatively isolated tribe of indigenous people living along the upper Orinoco River in Venezuela—have the highest diversity and abundance of gut microbes of any individuals in the world. This can already be seen in their infants. A few factors that may be responsible for this are the fact that Yanomami mothers nurse their infants for up to three years, that they consume a largely plant-based food diet, that their newborns are exposed to an abundance of healthy microbes in their environment from the day they’re born, and that they’re not exposed to antibiotics.
After that early programming phase, the basic community structure of the gut microbes is fairly stable throughout one’s life. After that, it can be influenced to a limited degree by diet, medication intake, and chronic stress or emotional states, among other factors. When it comes to your diet, by taking pre- and probiotics, you can improve your gut microbial composition and function within a certain limit, so long as you also stick to a healthy, low-inflammatory diet. If not, the microbiome will return to its original state as soon as you stop taking them.
While there have been studies that illustrate the large influence genes have on the mouse microbiome, in humans, the effect is much more limited and indirect. For example, the composition of breast milk is partially determined by the mother’s genes and by the mother’s diet. In particular, a certain group of large, nonabsorbable molecules called human milk oligosaccharides were naturally designed to be a specific source of food for gut microbes. That said, overall, early environmental influences starting during pregnancy and continuing through the first thousand days of life play a much bigger role than the parents’ genes.
We know a lot about genetic and epigenetic influences on the developing brain. For example, traits like anxiety, depression, and stress responsiveness have a strong genetic as well as epigenetic basis. Epigenetic influences can be triggered by adverse early life events occurring in the first eighteen to twenty-five years of life. An unstable family environment, a mother’s chronic illness, marital discord, and verbal or emotional or sexual abuse can all alter the ability of genes to express their genetic information.
Typically, the combination of genetic and epigenetic effects greatly increases the stress responsiveness of the brain and the vulnerability to developing a range of chronic disorders, including brain disorders as an adult. As mentioned, a brain that’s hyperreactive to stress or a chronic negative emotional state influences the gut and its microbes through the autonomic nervous system, including the vagus nerve. In brief, genetic and particularly epigenetic factors have a strong influence on brain-gut microbiome communication throughout life.
It’s best to conceptualize the interactions between our brain and our gut and its microbiome as a circular system. When viewed this way, there is almost always a combination of altered gut function with any brain or mental disorder—in particular in anxiety, depression, autism spectrum disorders, and Parkinson’s disease.
I believe that for many mental disorders, the initial aberrant signal comes from the brain, which is shaped by genetic and epigenetic factors, which then affect the gut and its microbes, which give feedback to the brain. On the other hand, we now know that we can positively influence brain disorders, like anxiety, depression, autism, epilepsy, and possibly cognitive decline, through gut-targeted therapies, in particular dietary interventions.
A common underlying theme in dietary interventions is to reduce the activation of the gut-based immune system, strengthen the intestinal barrier, and deliver anti-inflammatory molecules. For example, a diet high in a wide variety of plant-based fibers has consistently been shown to increase the diversity and abundance of the gut microbes, to reduce “leakiness” of the gut, and to reduce immune activation in the gut. Similarly, an increase in the amount of plant-derived molecules called polyphenols (contained in largest amounts in dark berries, dark chocolate, olives, pomegranate, and red wine) increases the abundance of good gut microbes. And the microbes in turn metabolize these molecules into health-promoting substances that are absorbed in the large intestine and contribute to brain health. High contents of fiber and polyphenols are some of the most important factors underlying the unequivocal health benefits of Mediterranean-type diets.
Optimal communication within the brain-gut-microbiome axis means that brain and gut and microbes are in a harmonious state. The brain is in a relaxed, positive emotional state, free of negative emotions, such as anger, fear, disgust, envy, high stress reactivity, etc. And therefore the brain sends positive signals to the gut. These positive signals lead to high barrier function (the opposite of leaky gut), regular contractions and secretion of fluids and electrolytes, and a normal mucus layer, among other factors.
The microbiome is in an optimal state when it has a high diversity of beneficial microorganisms and a high percentage of microbes contributing to a healthy mucus layer. This optimal state is associated with minimal immune activation, minimal leakiness of the gut, optimal cognitive function, and a sense of well-being.
Disturbances to this balanced state can occur in response to an unhealthy diet, such as one consisting of high fat, high sugar, and low fiber, and also as a result of chronic stress or trauma. The latter will reduce the gut barrier, increase its leakiness, reduce the number of beneficial microbes in the gut, and promote signals to the gut that reinforce the emotional imbalance.
I recommend a personalized and integrative approach targeted at the microbiome, the brain, and the gut. In my practice, we focus on stress management, including mindfulness-based stress reduction, relaxation techniques, and short-term cognitive behavioral therapy, sometimes in combination with brain-targeted medications (aimed at reducing stress hyperresponsiveness), if necessary.
We also target the gut and microbiome through a plant-based diet, anti-inflammatory foods, and natural bowel habit-regulating interventions. These natural interventions may include foods that promote intestinal fluid secretion and transit, such as rhubarb root extract, aloe vera, and flaxseed.
Each program is tailored to each patient, depending on what the underlying problem could be, and I’ve found most patients follow the recommendations successfully. While I view stress-attenuating medications as a temporary intervention to “reset the system,” dietary, mind-targeted, and exercise-related recommendations are considered long-term lifestyle changes.
Studies on the benefits of the Mediterranean diet have shown that social factors—in particular having communal meals with family and friends—play an important role in the documented health benefits of such diets, over and above the benefits from the largely plant-based dishes. There is an ancient connection between positive emotional events—like weddings, birthdays, holidays, even funerals—and sharing a meal. Most cultures recognize this close connection and try to maintain and nurture this tradition.
However, modern lifestyles in many parts of the world—in particular in the US—make it more and more difficult to maintain these social and emotional connections. As a result, people often end up eating mindlessly, without any connection to what they eat, with whom they eat, or in which context they eat. Even though there are few, if any, studies that identify the mechanisms underlying the beneficial effect of communal eating, it is most likely connected to the emotional signals the brain generates in such situations and sends to the gut and its microbes.
How we eat is as important as what we eat. I advise people to try to eat meals with friends and family—and not in front of the TV screen—three times a week at the very minimum.
We have several ongoing research projects, all studying brain-gut-microbiome interactions, some of which have been completed and are currently being written up for publication. We are writing up the results of a study we completed on the effect of cognitive behavioral therapy in patients with irritable bowel syndrome. As expected, CBT significantly improved symptoms in close to 60 percent of patients. This improvement was associated with a change in brain structure and function, as well as in the composition and function of the gut microbiome.
In another study, we examined the associations between a history of adverse life events before the age of eighteen and the gut microbiome. We found that such a history has a profound influence both on the composition of gut microbes and on the metabolites that they produce when the person is an adult. We are also working on several other exciting projects that we hope will shed light on other aspects of the brain-gut relationship, including:
Correlations between gut microbial composition and function, and brain networks and clinical symptoms in 1,000 individuals for whom we have comprehensive information in our database.
Effect of a dietary intervention, specifically one with high polyphenol content, such as berries and nuts, on stress reactivity, brain function, and gut microbiome in a student population.
The effects of a dietary intervention, or Mediterranean-style diet, on brain function and symptoms in cognitive decline.
Changes in brain-gut-microbiome interactions in patients with ulcerative colitis.
While it’s hard to predict the outcome, there are some great ongoing research efforts in the gut microbiome science field, such as the identification of ways to reverse negative early programming of the gut microbiome in the first thousand days of life. This may include selective transplants of microbes that are missing in an infant’s microbiome and targeted pre- and probiotic interventions in early life. Another ongoing study involving a big human population is seeking to demonstrate a causative role of gut microbial alterations in disease pathophysiology. If these studies are positive, it will become possible to identify subtypes of patients who may benefit from microbiome-targeted therapies like pre- and probiotics, selective antibiotics, or fecal microbial transplants.
We can also look out for animal studies identifying the precise mechanisms underlying the influence of altered microbial function on the brain and behavior. This data can then be used to develop specific therapies targeted at the brain and/or gut microbiota.
These studies and others will help us better understand the vital relationship between the health of our gut and our brain and the way this relationship helps shape our thoughts and feelings. I hope we can discover more about the way the microbial universe inside us affects our experience of the world we live in.
Emeran Mayer, MD, is a gastroenterologist, a neuroscientist, and the author of The Mind-Gut Connection. He is the executive director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience and a codirector of CURE: Digestive Diseases Research Center at UCLA. He has been studying brain-gut microbiome interactions for the past forty years, and much of his research has been supported by the NIH. He is currently researching the role of the gut microbiota and brain interactions in chronic pain and emotional regulation.
This article is for informational purposes only, even if and to the extent that it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of goop.