The Brain-Gut Connection: A Q&A with Dr. Emeran Mayer

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Dr. Emeran Mayer has been studying medicine at the Ludwig Maximilian University, in Munich,
Germany, where he received his M.D. and Ph.D. He went on to complete his residency in Internal Medicine at the Vancouver General Hospital, in Vancouver, Canada. Upon arriving in the United States, Dr. Mayer took up residence in Los Angeles, where he has been serving as executive director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience, as well as the co-director of the CURE: Digestive Diseases Research Center at UCLA. He is a professor of medicine, psychiatry, and physiology at the David Geffen School of Medicine at UCLA.

Hailed as a pioneer of brain and gut research, Mayer has published hundreds of original manuscripts as well as co-edits and chapter contributions. He is a specialist in mind-brain-body interactions, and focuses on the interactions of the brain and the digestive system specifically. He has received long-term support for his research from the National Institutes of Health. Brain World had a conversation with Mayer.

Brain World: Could you tell us a little bit about how you got so interested in this topic?

Dr. Emeran Mayer: My interest goes back a long time; it’s probably the reason I went to medical school. My initial research interest was in the interactions between the brain and heart. I did my dissertation on it, but being a physician, I preferred the clinical side of gastroenterology to clinical cardiology, so I switched my interest to studying brain-gut interactions.

The most obvious disorder at the time for such studies was irritable bowel syndrome (IBS). Most of the studies that I did over the last 25 years or so were on IBS, and this area of research was greatly expanded by the realization of the importance of the gut microbiome in brain-gut interactions during the past decade. My interest in brain-gut interactions has also led me to studying the connections between the brain and the gut in inflammatory bowel disorders where it’s pretty obvious to a clinician that there is a close relationship of disease activity and severity with the mind.

Patients who suffer from these chronic inflammatory disorders feel their symptoms not only come from the gut but also from the brain, in the form of fatigue, “brain fog,” and chronic pain. We’ve also looked at brain-gut interactions related to food intake and obesity, particularly related to a behavior, which is called “food addiction.” The brain obviously has mechanisms that drive us to seek out highly palatable food, and if this drive is not adequately constrained by satiety signals from the gut, it leads to food ingestion beyond our metabolic needs. So in a nutshell, I went from an early, general interest in brain and body interactions, to looking at several dimensions and clinical applications of brain and gut microbiome interactions.

BW: So do we know if this gut-brain connection starts in the womb?

EM: There’s increasing scientific evidence that the placenta is not as sterile as had been assumed until a couple of years ago. Interestingly, the microorganisms that have been discovered in the placenta are similar to the ones we have in our oral cavity in the mouth. But then there are also the gut microbes of the mother, which produce thousands of signaling molecules that can cross the placenta and influence the child’s brain development. So brain development in an infant is most likely in part related to what metabolites the microbes of the mother produce. In addition, other studies have shown that if the mother is stressed during pregnancy, it can change her vaginal microbes, which in turn can influence the infant’s developing gut microbiota.

There is also the question of how the mode of delivery — C-section versus vaginal delivery — affects the development of the gut-brain of people that we had filmed several decades ago. The investigators had analyzed gut microbes and their metabolites from the Yanomami, and compared them to age-and-sex-matched people living in North American cities — both their infants but also the adults. The most consistent difference was the diversity of the gut microbes. There was a 40 percent loss of this diversity in people living in the U.S. as opposed to those living in the rainforest. And that was already seen in really young infants, suggesting it is not only the difference in adult dietary habits that are responsible for the findings.

The presentation, and the published paper about their findings, really intrigued me because we had lived with them for six weeks in the middle of these almost uncontacted people living a lifestyle unchanged for thousands of years. We’d filmed and observed and written down what they ate, a diet very high in various plant-based foods with a relatively small amount of animal-based products: mainly fish, birds, and every once in a while a large animal — importantly, these are all animals with a very low amount of fat. We can conclude from these observations that humans have optimally been adapted to such a diet for thousands of years.

On the way to the uncontacted tribes, we encountered villages where missionaries had already influenced the lifestyle and dietary habits of the natives. Many of these “Westernized” individuals develop the typical Western diseases, including obesity and diabetes, emphasizing the important protective role of their unique dietary habits.

One fascinating idea for me is that humans have not evolved to be either meat eaters, or vegetarians, or vegans, but really omnivores. Evolution has endowed us with a system that has a brain-gut axis, even as an infant. What the mother eats during pregnancy and during breastfeeding is obviously very important, not only in terms of the nutrients but in terms of the signaling molecules that the microbes produce. So the gut-microbe-brain connection really starts developing in pregnancy and this development continues during the first few years of life.

It is a fascinating story because through these microbes you have this almost continuous connection of the developing human organism with what the mother does, how she feels, and the food she eats … it’s this continuous trail of connections. When I look at an adult patient in the clinic with symptoms of an altered brain-gut axis, I pay attention to this whole developmental history. My patients often tell me that they got repeated doses of antibiotics for minor infections in childhood, or the mother was taking antibiotics. Realizing these connections is not only scientifically interesting, it’s really clinically relevant when you get to talk to your patient.

BW: How would you describe what we call the “gut” feeling?

EM: This is a difficult topic, which has many dimensions. The biological one is that essentially every emotion that you have is always a mirror image of your gut activity. The brain stores all this information, like a supercomputer, from the earliest days. From the first time the infant gets pleasure from being breastfed or gets upset because it didn’t like something that went through the stomach or the mouth. These emotional memories are being encoded in our brain from the day we are born. Later in life you basically have two ways to make a rational decision. One is to use your prefrontal cortex to make rational decisions, a time consuming process that sequentially goes through pros and cons before making a decision. Or you go directly to the intuitive, nonlinear mechanism based on your database of gut feelings. In my book I’ve expanded on this, and compared the gut feeling based decision-making to the process used by the search engines of Google, Amazon, and Netflix.

All these databases have stored a vast amount of personal information about your tastes and preferences, and they can instantly pick out something that is important to you. I propose that you build up trillions of little emotional moments that are always associated with a gut sensation and over a lifetime — and as an adult, particularly if you’re trained to access your gut feeling — you can access that and you can make decisions that are most appropriate for you. Not for your neighbor or somebody [else], because everyone has a different bank of memories.

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