Expert: New Research Helps Understanding of the Gut-Brain Axis and Motivational Behavior

Pharmacy Times interviewed American Diabetes Association Scientific Sessions speaker Ivan de Araujo, MSc, DPhil, associate professor of psychiatry at Yale University School of Medicine, who explains the complex and varied signals the brain processes in order to regulate food intake. de Araujo also discusses recent research that demonstrates how the gut-brain axis both suppresses appetite and enhances motivation to eat by rewarding the brain.

Pharmacy Times: Can you explain the concept of “food noise”, its key mechanisms, and how it relates to satiety responsiveness and motivation processing in the brain?

Ivan de Araujo: I think 1 way to understand what the expression "food noise" means is to think of the multiple source of inputs to the central nervous system that controls a particular behavior. So, food intake is controlled by a number of factors simultaneously [such as] the taste, the odor of the food, the time of the day, whether or not you're experienced with that food, and also your physiological internal parameters. And in some way, the brain is going to filter out some of these factors and favor others, for example, nutritional value over taste, depending on how hungry you are, so this multiple source of inputs...correspond to a "noisy" source of information to the brain, and the brain is going to make the appropriate comparisons and judgments and decide which factor is potentially more important. And 1 of the factors we will be interested in discussing is the inputs that come from the gut, from the gastrointestinal tract to the brain via neuronal and hormonal pathways. So, that's the food noise idea, I think, it's this complex set of inputs that go from the periphery to the brain that is going to be computed in such a way that a decision is made in terms of whether we should eat or not eat something.

Pharmacy Times: Can you discuss the research findings that have advanced our understanding of how gut-brain signaling affects motivational behavior related to food?

de Araujo: So there has been an enormous interest in the gut-brain axis recently. So, I would say over the last 10 [or] 12 years, there has been a number of these studies trying to understand exactly how the gastrointestinal tract impacts the brain to change behavior and change decisions about food intake. And traditionally, the role of the gut had been restricted to the idea that some gut cells release hormones, these hormones get into the blood, and then eventually to the brain, and this result[s] in a suppression of food intake. So, the role of the gut has always been believed to be a negative one—let us say—it's a factor that suppresses appetite via satiation and nausea.

But, more recently, what we have been finding is that—in addition to this satiation or anorectic factors—the gut plays a huge role in providing rewarding information to the brain, meaning [that] the signals from the gut also increase motivation to eat. And this is because the gut wants to detect nutrients and because nutrients are advantages to survival, then the gut will use nerve pathways—especially the vagus nerve—to transmit that information to the reward processing areas of the brain [such as parts] of the brain that represent pleasure, motivation, effort, and so on. So, the gut is producing rewards [and] making the brain learn that eating a particular food is advantageous to the organism and that this behavior is more likely to be repeated later because the gut is basically telling your brain that you did the right thing, you acquired nutrients.

So, the research on the role of the gut-brain axis in food intake has been—let us say—completely turned upside down by this idea that the vagus nerve is actually a reward-related nerve, not a sickness or bloating type of nerve that people have always believed to be the case.

Pharmacy Times: What are psychological and physiological factors that influence an individual’s satiety responsiveness, and how do they work?

de Araujo: Yeah so, in humans especially—but you see this also in preclinical research—the psychological factors, such as familiarity and the previous experience, play a huge role in determining what the animal is about to do and what choices humans make in terms of their preferences and their regulation of food intake. So...when an organism [for the first time meets] a new food and if this new food happens to be nutritional, then the gut is going to transmit that information to the brain and this information is going to be...recorded in the brain via the reward system. So, the more often this happens, the more likely it is that a strong memory will be formed for that particular food, forming some sort of habit that is, in many ways, unconscious because these nerve pathways from the gut reach the brain in areas that are...subcortical, not allowing for a conscious evaluation or perception of the choices you are making. So basically, the previous experience of a subject with the food, the familiarity, and how nutrition areas is a huge factor in influencing choices, even if these factors are not necessarily available to conscious perception.

Pharmacy Times: How does this topic relate to diabetes and what is its significance?

de Araujo: In my field, there are 2 links to diabetes. One is that the gut-brain axis has been, let us say, co-opted or involved in the treatment of diabetes itself because some of the gut factors, the so-called hormones that are being released by gut cells actually seem to help with treating or alleviating some of the diabetic issues when used in pharmacological doses. So, even if it's not an entirely physiological effect in pharmacological doses, [for example, the GLP-1 agonists], are very effective in ameliorating some aspects of diabetes, including blood glucose levels. So, there is a potential clinical application directly that involves gut signals that communicate to the brain via the nervous system, or even via hormonal pathways. This is 1 side of the story where we can use it clinically.

But there is another side of it—which relates to what I said before—which is the role of the gut-brain axis in forming preferences for foods, right? So, 1 issue with diabetes is the control of food intake, of what kind of choices for foods that patients make on a daily basis. And because we animals were born with this evolutionarily-selected mechanism that detects highly caloric compounds in the gut and tells the brain that this is good, then we have to take this into consideration—this pathway from the gut to the brain—when thinking about interventions or approaches to curb excess caloric intake. So, the gut-brain axis is, in addition to potential applications in hyperglycemia for example, is also critical to the mechanisms by which food intake control is regulated.

So, we have these 2 aspects and the latter maybe has not been as fully appreciated as the the potential clinical applications, but it's absolutely the key to prevent overconsumption, especially off of carbohydrates, because we now know from a number of studies that the gut-brain axis is critical for linking sugar intake to the parts of the brain that form this memory and cause some sort of compulsive behavior towards sugars.