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I’d just gotten used to the idea that I’m a walking mountain of microbes. The sizzling field of research into the microbiome — our full complement of bugs — is casting new light on our role as homes to the trillions of bacteria that inhabit each of us. At least most of them are friendly, I figured.
But now comes the next microbial shift in my self-image, courtesy of the new book “The Mind-Gut Connection.” My trillions of gut microbes, it seems, are in constant communication with my brain, and there’s mounting evidence that they may affect how I feel — not just physically but emotionally.
Does this mean — gulp — that maybe our bugs are driving the bus? I spoke with the book’s author, Dr. Emeran Mayer, professor of medicine and psychiatry at UCLA, executive director of the Oppenheimer Center for Neurobiology of Stress and Resilience and expert in brain-gut microbiome interactions. Edited excerpts:
So we’re not only packed with trillions of gut microbes but they’re in constant cross-talk with our brains — that’s the picture?
First of all, you have to realize that these are invisible creatures. So even though there are 100 trillion of them living in our gut, you wouldn’t be able to see them with the naked eye. It’s not like something tangible sitting inside of you, like another organ.
These minuscule creatures live in different parts of your gut, most of them sitting at the mucus layer that is just on top of your gut surface. That allows them to be just microns away from receptors and sensors with which your gut records the chatter that goes on between them and measures what goes on inside.
And yes, they can communicate. Interestingly enough, they have the same signaling molecules that we’re quite familiar with, neurotransmitters and hormones, that are the main means of biological communication in our bodies and brains. The microbes use very similar molecules, and in fact, we probably got the genes to produce these signaling molecules from the microbes millions of years ago.
When you’re stressed, for example, the main stress molecule that we secrete, norepinephrine, gets to the microbes, changes their gene expression pattern, and makes them secrete different things, which results in a change in their behavior. So the microbes know what state of mood you’re in, and at the same time, our brain knows the signals that microbes send up to us. It’s a communication that we are totally unaware of, yet it plays such an important role.
So is there reason to think that the biggest effect of stress is on the gut or through the gut?
When you’re stressed, the stress response reaches pretty much every cell and organ in your body, including the gut. However, the gut is very complex — it has the largest number of immune cells, the largest number of nerve cells outside the brain and spinal cord, the largest number of hormonal or endocrine cells. So yes, you can imagine the effect of stress on this very complex system is probably larger than on any other part of the body.
Mild stress is always a good thing for everybody, to enhance physical and mental performance. If anything, excitement can optimize digestion. However, if the stress intensity increases, and becomes chronic, it can mess up normal gut function in a lot of people, which can result in diarrhea, bloating and constipation, typical symptoms of the irritable bowel syndrome. And if the stress is severe enough to result in a major fight-or-flight response, it results in a major shift in all the functions of every cell in the gut, including the microbes.
You write about patients who had both gut problems and mental health problems like anxiety or depression. Is it clear which is more the chicken or the egg?
I can’t give you a definitive answer to this question. There are epidemiological studies where, in half of the patients who present with both gut and emotional symptoms, the problem started with abdominal pain, and in the other half, they started with anxiety and depression.
When I take a history of a patient, in 90 percent, the first symptoms can be identified in childhood, sometimes in infancy. So symptoms often start very early in life. Half of the patients would say their symptoms started with anxiety, the other ones remember constipation or stomach cramps as first symptoms. So one can view it as two different disturbances within the brain-gut axis: one can be top down, starting in the brain, the other can be bottom up starting in the gut.
How would you contrast typical treatment for such patients with what you do?
The typical response of our health-care system to such a patient is frustration. Many patients are seen by gastroenterologists who have neither the training nor the interest nor the expertise to deal with their symptoms. And a physician hates nothing more than a situation where they can’t really do anything.
So instead of trying to treat the symptoms, they do diagnostic endoscopic procedures, often multiple times. And then they typically give the patient a medication that we know has very limited effect in the majority of patients. In my career in the last 35 years, very few medications have been developed that are much better than a placebo pill.
We take a different approach: Instead of just giving a pill that targets the gut to treat diarrhea or constipation but doesn't affect the rest of the brain-gut axis and the overall wellbeing of a patient, our group has always believed that an integrative approach works best.
First of all, we explain to the patients the concept of the brain-gut interactions: In this view, the brain dimension is not psychological or imagined or hysterical — but the brain must be viewed as the main regulatory organ in our body, which interacts closely with the gut. That takes off a lot of anxiety and frustration from the patient, because they’ve been told many times that ’It’s in your head.’
Secondly, we offer patients what we call mind-based therapies. So abdominal breathing, which sends signals to the brain which forces it to switch the stress response to a relaxation response. Or we teach them mindfulness-based stress reduction — a very effective intervention for these conditions. In more severe cases, we recommend some form of Cognitive Behavioral Therapy.
Thirdly, we talk about the dietary dimension of their symptoms. In my career, I’ve seen many of such diets come and go, from high fiber to low fiber to various elimination diets such as the gluten free or the sugar free diets. I personally believe what’s best is to have the patients themselves find out what agrees with them and what reliably causes symptoms, using food diaries. This approach empowers them that they can find their optimal, individualized diet themselves. I do recommend probiotics, not just in dairy products and pill form but also by increasing the consumption of various fermented foods.
And I also do use medications, but it’s just one arm of a multi-pronged approach, and it may only be necessary for a certain time. The medications can act on the brain or they can act on the gut or on both, depending on what domain the manifestations are in. Overall, I would say that even though the patients that come to me are a selected group of the most severe and refractory patients who have wandered from one specialist to another, we have a success rate of between 50 and 75 percent,.
Do you have particular concerns about other treatments?
Many patients are now recommended to go on one or several courses of antibiotics for their symptoms, which I think, given our knowledge of the gut microbiome today, is probably the most irresponsible thing you can do.
In general, I’m worried by the lack of recognition that for many patients it’s not just a gut issue, but that symptoms are a reflection that your brain-gut microbiome axis has gone out of balance.
On diets: I’ve always been amazed — and particularly now, after going through the literature while working on this book — how often the recommended diets for gut issues have come and gone.
You write about the role of gut microbes in translating what we eat into how it makes us feel. So could they be the reason that certain foods are comforting, or that we get addicted to certain foods?
Most of the microbes in our bodies live in the large intestine. The part of the food that gets there because we weren’t able to digest and absorb it, is the natural food for the microbes. Bacteria in the large intestine break it down into many molecules, including short-chain fatty acids. These signaling molecules, which can be regarded as the language of the microbes, will now act on a wide range of receptors that line the inside of our gut — for example, receptors on cells that contain hormones, which when released make you feel full and make you stop eating, the so-called satiety hormones.
So the microbes sit on this interface between food coming in and the sensors in our gut that pick up the signals from the microbes. That’s definitely one way that the emotional aspect of food intake is translated into a feeling of fullness, bloating or comfort. It’s probably not the only way.
If you ask me, how much your microbes contribute to how you feel after a meal, I’d say it depends on what kind of meal you eat, and it probably varies between different individuals. Some people feel good, others bloated or gassy or other don't feel anything. We all have very different sets or communities of microbes; comparing one person with another, the sets of microbes that each of us harbors actually differ more than our genes differ from person to person.
But so are we being manipulated by our microbes? The way, say, it’s been shown that toxoplasmosis gondii can manipulate rats into going near cats and thus spreading them farther?
This is a really interesting and I would say unanswered question. A big part in our brain is the reward system, dopamine being the main signaling molecule, which basically motivates us to do things —makes us eat certain things or buy something to eat. If there is a communication between our gut microbes and this reward system, the microbes could manipulate us to seek out what is best for them.
However, this research is really just beginning. In our studies, where we try to correlate the populations of microbes, and the molecules they produce with the size and function of brain regions, it turns out that the brain reward system, the basal ganglia and the nucleus accumbens, are the ones that show the best correlations with microbial communities. So I would not rule out that at some point, we’ll be able to demonstrate that the gut microbes can motivate us to do and eat things that are best for their own wellbeing.
Here’s another example from our studies in obese patients that undergo weight loss or bariatric surgery: We look at surgery induced changes in microbes and in brain structure and function and look at the correlation of these changes with the patients’ desire to eat and the resulting weight loss.
The first thing that happens after surgery is the food preferences change: All of a sudden, patients no longer crave for sweets or high-calorie things. And this behavioral change happens long before the weight loss kicks in. Interestingly, the microbes and their products change quickly too, suggesting that the microbial changes may affect our brain and eating habits.
Because there is such a dramatic change in the behavior of these individuals following the surgery, and at the same time we see this change in the bacteria, I would not say it’s impossible that the gut bacteria can communicate with our reward system, thereby influencing what we do. This wouldn't be the end of free will, but it could play a role in our eating behavior.
What outstanding questions about the effects of the gut microbiome do you most hope to see answered in the coming years?
We need a lot more science at multiple levels, mainly obtained in human studies, to really understand how many of the early spectacular results obtained in mouse models are actually relevant to human behavior. We have to separate the myths that have evolved around the brain gut microbiome interactions from the relevant and important influences that this system can have on our health.
The whole concept of psychobiotics, the suggestion that you can change your mood and emotions with the intake of a single probiotic, a single strain of microorganisms, like popping a Xanax or Prozac pill. Based on what we know from the millions of people that consume probiotics, I think this concept will turn out to be a myth. Even though such psychobiotic effects have been observed in rats and mice, our brains and our emotions are much more complex and are unlikely to respond in a similar way.
We need to find out which diseases or subtypes of patients with a certain disease actually have an abnormal gut microbiome, and if this abnormality is the cause of the disease or its consequence.
For example, in a patient with a mental disorder like autism spectrum disorder, we do not know if it is the stress that these kids experience on a day-to-day basis that is associated with stress signals being sent to the gut, that causes that observed changes in their microbiota. Or is it some alteration in their microbiome from infancy on that sends the wrong signals to the brain? Or is it a combination of both mechanisms? That’s one of the key questions that need to be addressed before we truly understand the role of gut microbes in the development of brain disorders.
Once you understand that, it opens a very exciting avenue of research and development. A lot of scientists are already pursuing such research now: In patients where we think the altered gut microbiota play a causal role, how can we manipulate or even reverse the alteration with a particular diet? People are now developing consortia or groups of different human probiotics that come from our gut that produce certain molecules like short-chain fatty acids which can help patients with problems like metabolic syndrome and diabetes.
So we’ll open up very exciting avenues of non-pharmacological therapies, partly based on food and partly on directly altering the microbes and their behavior in our guts through ingestion of special probiotics. Such approaches would be a much more natural way of treatment than the pharmaceutical products that we currently use.
And for now? You end the book with sensible good-health prescriptions about eating whole foods and fermented foods like yoghurt, about cutting stress and avoiding animal fats. But what do you tell people who are stressed out by the idea that stress could mess up their gut-brain axis?
I’ve come to realize that the most important period in a person’s life to influence the gut
microbiome and the brain-gut axis is probably the first three years in life, starting with pregnancy. I always tell my patients that yes, your brain gut axis may be messed up from early on, and some of these changes you can’t erase. However, as humans, we can use the phenomenal supercomputer, our brain, to learn strategies and techniques that can put a ‘software patch’ over this messed-up early life programming. There’s a range of behavioral techniques and lifestyle changes that are able to counteract much of the early changes.
Chronic stress is bad for your health, there’s no question about this. But there’s been a revolution, an acceptance of mindfulness-based stress reduction, by millions of people. It’s an easy technique that we know is successful in treating various brain gut disorders, and we now can change these imbalances. We’re currently doing a study to prove that a course of mindfulness-based stress reduction can change both your brain and your gut microbes for the better.
So you should never blame your mother for what she did or didn't do when she was pregnant, for not breastfeeding you long enough, or for not giving you enough affection. You can’t erase the traces of these early life experiences have caused. But as a human, you can do things that are very powerful and can compensate for the early acquired dysregulations of your brain-gut microbiome axis.
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