Diana is working with Dr. Zul Merali on the launch of a new Brain and Mind Institute, which serves South Asia and East Africa in the areas of neurosciences and mental health. In connection with this week’s article, she spoke with Dr. Merali who serves as the Institute’s Founding Scientific Director.
Dr. Merali is Past President/CEO and Scientific Director of the University of Ottawa Institute of Mental Health Research. He is also full professor in the faculties of Medicine (Departments of Cellular and Molecular Medicine and Psychiatry) and Social Sciences (Psychology) at the University of Ottawa, as well as research professor at the Institute of Neuroscience at Carleton University. He has studied the body’s response to stressful and appetitive events, and the relationship of stressors (including early-life trauma) to mood and anxiety disorders. Another focus of his research is also to determine how pharmacological interventions (pharmaceutical and nutraceutical) may attenuate stress-induced pathophysiology. In this vein, he and his colleagues have been attempting to isolate anti-anxiety compounds from a variety of rare plants. He has published over a hundred scientific papers, more than 20 book chapters and over 100 conference presentations.
Diana Gifford-Jones: Dr. Merali, how would you characterize the relationship between the gut and the brain?
Dr. Merali: You can think of it like a marriage. The gut and the brain are in constant communication with each other. Just like in a marriage, sometimes the communication is good and sometimes it’s not that good. What really surprised me when I started looking into the area is that the gut microbiome is enormous. It is home to trillions of microbial cells, including bacteria – these microbial cells in fact outnumber the human cells in the body. You can’t have such a vast number of foreign cells in your body and expect them to be doing nothing.
Diana: We usually think of our digestive system as a processing unit for food. It’s quite different to imagine our gut as a partner to our brain – and a host for so many independent residents and visitors. And how are they all getting along?
Dr. Merali: The gut microbiome, as an entity, is in harmony with your body. That state is called eubiosis. It comes from Greek eu meaning good and biosis meaning life – in other words, a balanced ecosystem. But you can have something called dysbiosis where disruption in the balance results in a bit of a tiff between the brain and gut. This is when you start having issues. There could be digestive issues or problems with the absorption of nutrients. And the imbalance can affect communication with the brain. When the brain interprets things that are disharmonious, this is essentially how the brain perceives stress. Anything not in a harmonious state is like a stress to the brain, and this can lead to what any other stressor would trigger – ill health, including mental ill health, for example.
Diana: What’s the mechanism for the communication between the brain and gut?
Dr. Merali: There are many channels of communication between the gut and the brain.
First, the gut itself has its own nervous system, called the enteric nervous system. Because it is so large, it is sometimes referred to as the second brain. The enteric nervous system controls the regulation and functioning of the gut and it can function independently of the brain. But one major channel of communication between the gut and the brain uses the one of the biggest nerves, the vagus nerve, connecting the gut to the brain. And there are other smaller neural connections.
Second, there are indirect ways of communication. For example, your endocrine system uses chemical messengers that can trigger the brain to release of certain hormones, such as cortisol. This will have an impact on the nervous system within the gut. It can indirectly influence the functioning of the gut.
The third channel is the immune system. The gut has its own way of dealing with immune parameters. Don’t forget, when you eat different food, you may ingest some things that might be dangerous and other things that might be beneficial. Sometimes the gut senses a problem that might evoke very noticeable reactions that lead you to be sick to your stomach. This sensory system within the gut is very alert to foods you are ingesting. If you ingest things that are potentially dangerous, it will provoke aversive responses, including an immune response when required.
When the immune system is activated, it releases a whole system of chemicals called cytokines. These are chemical agents that serve an immune function. But when they travel into the brain, the brain perceives a stressor and kicks into gear. It is of interest to note that the gut often uses the same chemicals as the brain. Serotonin, for example, the hormone that stabilizes your mood, is a factor we talk about in the treatment of depression. Serotonin was discovered in the gut, and there is a lot of it in there.
There’s so much going on in our gut that its been called the second brain. There are so many systems, and they all influence each other. That’s why I say it’s like a marriage. If things are balanced, it’s a good marriage with all systems working well together. But occasionally, there are disruptions, either through the brain or the gut, and there can be ramifications for other organs too.
Diana: How well do we understand the factors that affect the balance and how the systems interact?
Dr. Merali: Although people have been suspecting the importance of this gut-brain relationship for a long time, we are at the dawn of discovery. There were therapies that people used to use that disrupted the gut function to influence people’s behaviour. But it was anecdotal research. Now that we are able to characterize the genes so well, we are then also able to genetically characterize the microbiome. Although we still don’t understand the full extent of it. There are so many different kinds of bacteria in there. We are only beginning to understand what the good bacteria are, what the bad bacteria are, how do we measure them. Our next step is to understand more fully the composition of the microbiome. It will become clear that everyone is unique in composition. We will get to the point where the treatment of gut disorders becomes highly personalized medicine. But we are at the very early stages of understanding what is the exact make-up of the microbiome and how to identify and ‘correct’ the disrupted microbiome.
Diana: How should we think about different approaches to maintaining a healthy microbiome or treatments when we detect evidence of disruptions in the balance?
Dr. Merali: In our attempt to regulate the microbiome, there are many products on the market. You will see a wide variety of probiotics. The difference among them is usually the composition of the bacteria in the formula. The goal is to ingest good bacteria that might take up residence in your gut. Very often, some of them with just go right through.
The other approach is to take prebiotics. Whereas probiotics are bacteria that you are ingesting, prebiotics are nutrients to support the bacteria in your gut. After all, bacteria need nutrition as well. So prebiotics function by providing nutrients that might be promoting the growth of good bacteria in your system. As we gain better understanding of good and bad bacteria, we will be better able to select and promote the growth of either your own bacteria using prebiotics or ingested bacteria in the form or probiotics that you hope are going to stick.
Another technique is a fecal transplant, where a fecal sample from someone who has a good balanced microbiome system is implanted. But remember that the microbiome is extremely complicated. So if you implant a seemingly healthy sample from someone else, there could be hidden problems. In other words, you may be taking on the bad with the good. But this is one way of changing the composition of your microbiome. And people are trying to find other ways of manipulating the microbiome as well.
Probiotics and prebiotics are natural products, which means clinical testing is not as stringent or systematic as they are for pharmaceutical drugs. This means we don’t yet have a deep understanding of their performance in controlled settings. There are so many individual variations in the microbiome that what might be good for one person may not be good for another. So there is a lot of trial and error and individual experimentation going on to try and figure out what works for each person’s circumstances. Some people claim wonders when they take probiotics or prebiotics. Some people don’t respond at all. And some respond negatively. Like anything else, new things should be tried carefully, but for those that might respond positively, people claim it does a lot of positive good for them.
Diana: Generally, when people feel stressed, they tend to reach for comfort food. Should we be redefining comfort food? What would you recommend?
We revert to comfort foods when stressed. Typically, this means high fats or high carbohydrates. Because the gut and the brain talk with each other, you are provoking release of the ‘happy’ chemicals in the brain. By eating comfort foods, you might temporarily provoke release of these chemicals so that you feel good. But the problem is that we are talking about high carbs and high fats. So if you continue to binge on these foods, then you negatively impact your health because you start putting on pounds. That has its own ramifications as weight gain sets up the body for problems such as metabolic syndrome. On an occasional basis, it’s fine to reach for comfort foods. But if stress is a regular problem and you regularly binge, then it becomes an issue. These comfort foods are effectively short circuiting the brain to make you feel better for a short period of time. But then afterwards you feel rotten about it.
Diana: Do you see a scenario where scientists working on the microbiome convince us to set aside the French fries and pick up a pill loaded with probiotics or prebiotics?
Dr. Merali: Yes, but they don’t do what the comfort foods do. Probiotics and prebiotics can sooth the GI system, and bring your entire body, not just your brain, into harmony, which is a good thing. But they will not offer immediate relief from the sense of stress.
Diana: So it’s better to go for a walk?
Dr. Merali: Yes, exercise provokes release of the chemical messenger dopamine that makes you feel good. But you might not be in a state to exercise when you are in a state of stress. Sometimes you don’t care what happens to you because you just want to feel better. You self-medicate, and comfort foods are one easy option.
Diana: What area of research related to the interactions between the gut and the brain do you feel offers promises for the future?
Dr. Merali: One of the biggest things in the future will be a better understanding of the gut microbiome, thanks to rapidly advancing genetic testing. As we have seen with COVID, for example, we were able to identify the COVID virus, produce a vaccine based on the genetics of the virus, and then identify a more virulent form of the virus, all through genetic analysis. In the same way, the gut microbiome is getting better understood through genetic analysis. I can see a future where people may develop profiles of their unique microbiome. And then we will see precision interventions by specific kinds of pro and prebiotics and other interventions. This is the more personalized approach that will be coming as genetic analysis becomes more affordable and doable.
We will also better understand how the gut and brain interact. Some scientists are studying whether certain types of depression are created by bad microbiome systems. They are looking for solutions by trying to disrupt the microbiome. I’ve seen it called the psychobiome! Consider the spectrum of depression. It’s not a single disorder. Depression more like a piazza, a central square within a community that has all kinds of lanes leading to it. Each person’s depression might be arriving along different laneway. One such path might be through the gut. And a solution could be a disrupted gut microbiome. It’s particularly interesting to study the aggravated immune reaction that the microbiome can have. Inflammatory disorders of the gut, for example irritated bowel syndrome, can involve concurrent forms of depression. Conversely, some chemicals that the gut microbiome releases look like anti-depressants themselves. So there is a potential for a negative or a positive impact on someone’s mood. It’s a very exciting area of research right now.
