The Brain-Gut Connection An interview with Dr. Emeran Mayer M.D., Director of the University of California Los Angeles’ Center for Neurobiology of Stress.

Welcome to the 11th edition of Probiotics: News You Can Use, an informational bulletin brought to you by the Dannon Probiotics Center.

A growing body of research in recent years has shown a strong, two-way connection between the brain and the digestive system. Scientists now have a greater understanding of how the brain and gut signal to one another, and how this relationship can affect overall well-being. We spoke to Dr. Emeran Mayer about the science behind the brain-gut connection and what we can do to keep it in balance. Dr. Mayer is director of the University of California Los Angeles’ Center for Neurobiology of Stress, specializing in gastroenterology.

What is the relationship between the brain and the gut?

The brain and the gut are closely connected. First, the gut sends information to the brain via the vagus nerve and spinal afferent nerves. The primary function of this gut-to-brain signaling is to provide input to a hierarchy of reflex loops at different levels of the central nervous system, including the spinal cord, brain stem, hypothalamus, and primary interoceptive cortex. Because these mechanisms are so complex, the gut can be considered the largest sensory organ in the body. Through this signaling, the brain receives information not only about what is going on in the gut wall, but also about events in the gut lumen, including the state of our microflora.

At each level, the central nervous system sends information back to the gut to ensure optimal functioning during sleep, fasting, and digestion. The gut has its own branch of the autonomic system—the enteric nervous system—that provides stereotypic response patterns to signals from the brain. This process ensures that what the gut does is always optimally coordinated with a person’s overall situation.

In addition to nerve signals, the gut also emits endocrine signals that reach the brain directly or through stimulation of the sensory nerves. For example, certain gut hormones can transmit sensations of fullness and hunger. During intestinal inflammation, the gut can also trigger brain functions such as pain, fatigue, increased sleep, and a feeling of "being sick."

Does the gut control the brain? If so, how?

The traditional view of gut-to-brain signaling is that most of the gut’s influence on the brain in healthy individuals is mediated within central autonomic nuclei. Less understood is the influence of the gut on higher brain functions and underlying structures, such as the interoceptive cortex, and emotional arousal circuits. Activity within these regions plays a crucial role in our mood and emotions, and possibly in our general sense of wellness or discomfort.

So, in the healthy person, and based on what we currently know, the gut probably has relatively little control over higher brain functions. However, in diseases that affect the gut, such as acute gut infections or chronic inflammation, the gut can exert a major influence on how we feel, how we think, how well we sleep, what our energy level is, and how much pain we experience. For example, nearly everyone has experienced the miserable feeling associated with gastroenteritis and the profound effect this pain can have on other behaviors.

Does the gut-brain connection explain “gut feelings”?

It is not uncommon to hear politicians, business people or even scientists start a sentence with “My gut feeling tells me…” But the term “gut feeling” has different meanings to the medical research community and to the lay person:

For the researcher, it is fairly simple: In healthy individuals, there is almost no conscious awareness of the complex processes between the brain and the gut. Conscious awareness of gut sensations only becomes important when a behavioral response is required. For example, sensations of discomfort or pain in the upper abdomen often are a sign to stop eating; sensations of fullness and urgency in the lower abdomen are a signal to have a bowel movement. While most of these sensations have a negative connotation, we rarely think of the pleasant sensations associated with the gut—for example, the pleasant fullness, warmth, and slight fatigue following a three-course meal.

For the lay person, gut feelings have more to do with instant, intuitive decision-making than the rational, linear process of decision making. Most of us use this term without ever thinking about the possible biological basis to such feelings. However, recent breakthroughs in affective neuroscience have resulted in models of intuition and decision-making that put interoceptive processes and memories at the center of such complex human processes. Since the gut provides the largest input to the primary interoceptive cortex, one would expect that gut sensations play an important role in this process. For example, the uneasy feeling that some of us experience in our bellies in worrisome situations, the knot in the stomach when we feel angry, or the butterflies when we are anxious—all these sensations may get stored in our “interoceptive memory” or “body map,” and always influence our later decisions in similar situations.

How can we improve the relationship between the brain and the gut?

There are a number of lifestyle changes one can make to improve the relationship between the brain and the gut.

For example, eating a healthy diet that is low in fat and refined sugars; high in natural fibers; low in calories; and taken in several small portions during the day should help promote the natural state of homeostasis. In contrast, an oversized, high-fat, high-calorie meal, particularly when eaten late at night when our intestinal tract is supposed to go into its fasting mode, is likely to cause intestinal disturbances, and associated feelings of distress.

Becoming more aware of pleasant gut sensations and learning to think about occasional negative sensations such as fullness, abdominal pain, and discomfort as normal rather than serious, may, over time, shift the focus from associating gut sensations with discomfort to a more accurate “interoceptive memory.” Finally, relaxation exercises, including simple breathing exercises or gut-directed hypnosis, have been used successfully in cognitive behavioral approaches to functional bowel disorders.

What role do probiotics and the intestinal microflora play in the brain-gut connection?

Adding certain probiotics and prebiotics to one’s diet has been shown to help reduce symptoms of bloating and flatulence, and may even influence background emotions of well-being.

This area of research is still in its infancy. However, a growing number of preclinical studies (mainly in rodents) suggest an important role of the microflora in influencing the responsiveness of the stress system, particularly in pain sensitivity, gut inflammation, and possibly in emotion regulation. While these findings are intriguing, it remains to be seen how they will translate into humans. Recent studies in humans have shown that regular intake of certain probiotics can help reduce such gut discomfort as bloating, gas, and visible abdominal distension. Ongoing research is continuing to explore whether regular consumption of certain probiotics in healthy individuals can help increase digestive wellness and gut comfort.

What are some of the emerging topics of research in the brain-gut connection?

Upcoming research topics include the possible role of the microbiota in obesity, inflammatory and functional GI disorders, pain sensitivity, autism, and depression. Beyond the possible role of the microflora in modulating disease activity, it will be important to know if microbiobial gut interactions play a role in background emotions in healthy people.