THE MICROBIOME SUMMIT : The New Path to Health
Brain-Gut-Microbiome Connection: Stress Impacts
Dr. Emeran Mayer, MD, PhD
Stress has been found to impact the gut microbiome. Dr. Emeran Mayer is an expert in the gut-brain axis, and yet also embraces balance, wisdom, philosophy, culture and ancient healing traditions. In this interview, Dr. Mayer offers thought provoking ideas, as well as practical suggestions on how to better handle stress – such as abdominal breathing and dietary changes.
- Tracey:
- Hi, Emeran. Thank you for joining me today.
- Emeran:
- Hello.
- Tracey:
- In your book The Mind Gut Connection, you really elaborate on the role of the how stress impacts our lives through the brain gut microbiome axis. Can you explain that to us?
- Emeran:
- So, let me start off with the definition the way I understand stress in this context. It’s really in scientific terms a perturbation of the homeostasis or the balance within the system and the body is a system that always will try to re-establish the original balance state. And so, stress in this definition can happen at the brain level of perturbation of your normal emotional state. Or it can happen that the gut-level with a gut infection, unhealthy meal or overeating such as a variety of things, toxins getting into our gut. So, both of these will perturb the brain gut microbiome interaction and the system then will try to respond to that trying to re-establish the original balance. Most stresses do not have a permanent damage on the system because it bounces back so resilience is a very important concept in this context. But some stresses severe or chronic or repeated can actually lead to reorganization of the entire brain gut microbiome axis leading to the chronic stress related illnesses. So, let’s start with the psychological stress and that is the world that we live in today in western developed societies is that most of us are fortunate not be exposed to life-threatening stressors, which would trigger the classic fight or flight response. But we are exposed to a very large number of constantly recurring mild stressors that all of us are basically struggling with our daily lives. The system has been really well studied both at the brain level – what the chemicals being released; what circuitry in the brain are being affected; what outputs from the brain in terms of the sympathetic nervous system and the hypothalamic pituitary axis cortisol system how they react. And we also know at the gut level a lot of what happens during stressful many mouse models and also human studies now that we can put the two together. If anybody is psychologically stressed it will generate a somewhat of a stereotype response. So, one is that our sensitivity with our gut increases often just the gut but other systems as well. But if it happens that happens at the gut-level people feel the contractions, distensions -all these activities regarding the gut which cause unpleasant sensations and we also know that the nerve signals that go down to the gut change. For example, during stress we slow down the activities in our stomach and the emptying of food from the stomach and accelerate the transit through the intestine increase the contractions in our sigmoid colon, which generates a typical cramps that people get. So we know pretty much what happens with psychological stress all the way down to the gut. Now, we also just in the last few years we have learned the stress also affects the microbes directly. Both directly and indirectly. The indirect effect is if things move faster through the intestine if there’s more mucus secretion and fluid secretion it will change the habitat of the microbes, and they will adapt to this by changing the composition in there. But even more fascinating in some are stress mediators, neurotransmitters like norepinephrine it will affect the microbes directly will activate receptors on the microbes that then change the gene expression and their function. What’s being studied in many microorganism both in vitro in a – glass tube but also in a test G.I. tract that makes it many of the microbes more aggressive. So, they start turning against the host and contributing to the imbalances within the whole brain gut microbiome axis. So, stress is something that we know from the molecule’s corticotropin releasing factor molecules in the hypothalamus all the way down to how norepinephrine changes the behavior of microbes. We know that pretty well. What we have not found are medications that are particularly effective in normalizing such a response with big hopes that an antagonist should this stress molecule in the brain this CRF would be the miracle drug to attenuate the stress response and people that have a sensitized system. But that has not been been successful. On the other hand, interventions or mind-based interventions, mind-body interventions are quite effective certainly more effect than most of the drugs that we know starting with a simple maneuver that in my clinic I recommend to teach all patients is the abdominal breathing for it’s one of those few viscera within our bodies that we can influence consciously so they don’t just run on autopilot where we can pace our breathing instead of the diaphragmatic breathing where our chest expands and contracts. We focus on the abdomen, the belly and breathing into the belly. It’s hard to understand why this would be good for your stress levels but we know now that it affects signaling of the vagus nerve that innervates our abdominal organs into the brain, and it forces the brain to get into a relaxed mode because abdominal breathing occurs during sleep. It occurs in young people and in infants. So, it’s a natural breathing for the relaxed state. If you can induce that consciously you will force the brain to switching to a relaxed state and with many beneficial consequences from decreased pain sensitivity to decrease stress responsiveness. Thanks to the vagus nerve and thanks to our ability that we can consciously change from stress pattern to a relaxed pattern. We have pretty well one of the most effective systems for counteracting the stress-induced activation of the brain gut microbiome axis.
- Tracey:
- Right.
- Emeran:
- If you look at the gut component of this, what can we do to decrease perturbation or increase resilience at the gut level? So for example, if you have a gastroenteritis and it messes up the normal composition microbes, or equally important if we take an antibiotic which causes widespread damage to the microbial composition. What can we do to make the system bounce back to its normal state? So after the gut related stressor and clearly food plays a role here and probiotics have received a lot of attention and some people have even coined the term psychobiotics. Which I’m still a little bit skeptical because this does work in mouse models. So, but really not been demonstrated convincingly in humans. What we can do there is to stick to a diet that we think is beneficial both for the main parameters by which we measure the health the gut microbial system and that will be it’s diversity and the abundance of different organisms present and it’s resilience. So foods that are ideal for the microbes high in plant-based foods on lowering the things that we now know have a negative effect such as high concentrations of animal fats and related products. And in many of the products that are already in processed foods from artificial sweeteners to emulsifiers to there’s a whole range of things that is being added to some of the food that we eat. So, if you want to treat the stress of our gut, and the gut microbiome, I think goes into the direction of eating a healthy diet and if it goes into the brain part of the stress response. I think as we talked about mind-based therapies are probably the most effective at the moment.
- Tracey:
- Right. I think it’s interesting with the diaphragmatic breathing it was explained to me once that you can’t be in sympathetic and parasympathetic at the same time. It’s sort of like this pulling. So, in a way you’re doing diaphragmatic breathing, you’re kind of pulling yourself into the parasympathetic state.
- Emeran:
- That is true and anybody who does that. I do this on a daily basis even for a short times in the car or whatever. If your stressed it and you not really well trained in doing this it’s hard to switch the system around. So, it’s not like someone tells you okay do diaphragmatic breathing and then next time you – you get stressed you can do it. But you’re completely right and the two states cannot exist at the same time similar to that you can’t be depressed and happy at the same time.
- Tracey:
- Yes.
- Emeran:
- But training of that system is definitely the way to do it. If you are good in being able to switch this when you are relaxed and when you are in a good state and do it on a daily basis, at some point you become so effective in doing this. So, you can do it also when you’re really stressed.
- Tracey:
- I think that’s a very important point. I’ve read some research that suggests that perhaps if people did it twenty minutes a day that can be enough to teach them that learned response. So, when they are in a very stressful situation, they can pull them self into a parasympathetic easier.
- Emeran:
- Absolutely, it’s a conditioning. So the stress response you don’t to have to learn because that’s really built into our brain for thousands – hundred thousands of years. The relaxation response is not something that’s hardwired that you really need to learn so you have to train your brain to do it. The only time you know we treat it with relaxation responses during sleep really, where do it naturally. But it’s something you have to learn, and I should also say and just like you have to learn the relaxation response. If you want to treat your stressed gut taking something or eating something once is not gonna make any difference on the system. It has to become your lifestyle you know. These systems are so effective in doing what they are programmed to do in human evolution for a million years’ that you have to do something on a regular basis. It has to affect your lifestyle both in terms of what to eat, but also how you trigger this relaxation response in order to be useful. It’s not like a Valium that you can pop instantaneously to get the benefits. It’s a fundamentally different way of treating of dysregulation in that system.
- Tracey:
- So, what do we know about the effects of stress in the perinatal period, and in your book, you talk a little bit about stress being transferred from one generation to the next. Can you explain that to us?
- Emeran:
- Yes. Let me start with the stress in the perinatal period. So there’s been a lot of focus, several prominent Canadian investigators like Michael Meaney has really studied this a lot, early life stress and how it affects in the postnatal period the programming of the stress axis. So the maternal separation model in mice so we take that litter away its mom for a limited period of time and then the behavior of the offspring, after being exposed to two weeks of this stress, changes fundamentally the way their stress system is activated when they’re grown-up animals. The mother’s behavior is actually the main player here. So, when you separate the pups from the mother the stress mom changes her behavior towards the pups and that basically changes then the behavior of the offspring. What we know from more recent experiments, there’s other channels by which prenatal stress can affect this system and so an example recently done by an investigator with a stressed – actually with a mild stressed or pregnant mice and what the stress did it changed the microbial composition of the vagina of these mothers so when the pups are born and they go through the birth canal and they’re exposed to this stress altered vaginal microbiome which plays a big role in seeding or programming the infants’ microbiome. And these animals then when they grow up, because they also had altered intestinal microbiomes because of stress in the mother, it did affect the brain development in these animals. So, there was a direct link from the stress of the mother and the stressors changed the mother’s vaginal microbiome. The transmission of this abnormal microbiome to the offspring, colonizing their gut and then the influence of that altered gut microbiome in the infants on the brain development. So, I meant that’s pretty amazing. If that happens in humans, it would be quite a novel and impressive way of how prenatal stress. In addition to all these other mechanisms like the maternal separation type stress and how it changes brain function and now we know microbial function.
- Tracey:
- Yes.
- Emeran:
- Why do we have this mechanisms so it’s probably a very important evolutionary development that the condition that we will grow up in both while we’re in the womb and afterwards programs us for a world that may be as hostile or as dangerous as the one that we were born into. So the entire nervous system and the whole-brain gut microbiome axis is programmed for the future to be ultimately adapted to a hostile world. So, it’s actually a great thing that this developed. Unfortunately, today while we don’t live in this type of hostile world but the stressors on the mother and earlier in life are the same or even greater than before, it becomes maladaptive. So, it’s the basis of many of our brain disorders, many psychiatric disorders and probably also involving IBS. I personally that all of these – I mean most psychiatric disorders – what’s called functional gastrointestinal disorders are developmental in nature and they started in the womb with these stress effects.
- Tracey:
- Wow. That definitely something to give us all to think about. So, in the perinatal period, what a woman could maybe focus on would be the diaphragmatic breathing. I mean that is something that she can control.
- Emeran:
- Yeah. I think being aware of it for mothers is really important. I mean when I see my female colleagues pregnant and working on grants until the last minute exposing themselves to that stress situation. Most of them probably do not think about the consequences that this has on the development of the healthy brain gut microbiome axis. So the first thing is being aware of it and the second one is if you can’t avoid the stressors, use the simple things such as abdominal breathing or other relaxation exercises such as progressive muscle relaxation or autogenic training; which is simple, inexpensive, and you can do it on a regular basis. But those are particularly important during the pregnancy and during the early phase of life. One other thing I should mention. Another channel, by which stress to the mother is transmitted to the offspring is breastmilk. So, breastmilk is the main food for the microbes. It’s responsible for a very important component of the assembly of the healthy microbiome and stress really affects the molecules that are in breastmilk. Both food and stress affects this. A – to realize breastmilk is the main food for the assembly of a healthy microbiome and B, that stress can influence that process in a negative way and so that’s just another thing I think is very important for women to be aware of this stuff.
TRACY: Right. Right. And if there are socioeconomic factors that are affecting a woman in the perinatal period. To sort of give women a break, once a child is born you have lots of opportunity even past the breast-feeding period to feed the microbiome. - Emeran:
- Yeah. Absolutely. I mean there’s a lot of information out there and diet books, and what’s good. I think with the microbiome research that has done, ith as kind of simplified the dietary recommendations. Because if you want to do something good for your microbes, you know what they do primarily so they break down these complex carbohydrates that are in plant based foods. So, the more you feed them this kind of food the more diverse the microbiome becomes and it sort of become accepted now that the diet of the mother during pregnancy and during the early periods of life and then what do you add-on to the diet of the infants all falls into the same category. You know if you want to do something that’s optional for your microbes it’s fairly easy what that is. It’s not high-fat. It’s not high-protein. It’s a high level of this complex carbohydrates.
TRACY: Yes. It’s eat more plants. - Emeran:
- Yeah. So, hopefully this will come out of this research. So, it hasn’t really happened yet because if you look at the best-selling diet books at the moment you know they sell all kinds of recommendations that simply do not make any sense based on the evolving science.
- Tracey:
- Right. Other classes of drugs that we might want to be aware of in terms of stress to that gut?
- Emeran:
- I mean if you look at with this viewpoint, you know, most medications will in some ways, that you ingest orally, will have an effect on this complex system. So, they all are perturbations of the brain gut microbiome axis. And it’s kind of remarkable that our system are so resilient to these stressors that you know most of us can’t get away with it without having the side effects. But I mean the side effects that’s basically what we see as the outcome of the stress. But the antibiotics are definitely the best study system. Some – Martin Blazer who has studied and publicized a lot. Not only has he drawn the awareness of the public to the fact that our infants are exposed to the phenomenal doses of antibiotics for reasons that are not medically indicated. You know mainly for viral infections, and that is particularly damaging, or stressful to the microbiome because it happens to large degrees during the period where the normal microbiome is assembled the architecture, and if you perturb this system at this age repeatedly it will have a permanent effect, a damaging effect on the diversity and the abundance of the organisms then its – no matter how many probiotics will take later in life, and it will not re-establish the same thing. So, that may be true also of many other medications that are given in very large quantities sort of like the antidepressants. If you just think about the Prozac like drugs, serotonin re-uptake inhibitors the more and more given to children, to young children with all kinds of psychiatric symptoms. And since we know the effect these serotonin cells in the gut that are close in connection with the microbes. It’s more likely than not – that’s another one of those drugs that has major effect on the brain gut microbiome axis, so we haven’t even realized yet.
- Tracey:
- Wow. I – didn’t know that.
- Emeran:
- I’m sure there’s many others as well that people have not thought about.
- Tracey:
- Thank you, Emeran for all of the knowledge that you have imparted on us today. I’ve learned so much from you and I really want to thank you for taking the time to explain things in the detail that you have.
- Emeran:
- Thank you. It was a pleasure.
