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Understanding the Basics of the Gut-Brain Connection

July 14, 2020

Have you experienced nausea or cramping in your stomach during an anxious moment? Or felt butterflies in your belly?

Researchers are working to better understand this phenomenon and the underlying mechanisms that might also contribute to more serious conditions. It may be that your diet affects your mood and your mood affects your digestion. “We still don’t quite know how nutritional microbes control us yet, but food is at the center of who we are,” explained Dr. Bohorquez in an interview with NC State University. The interaction of vagal neurons, neuropods, gut bacteria, and neuropeptide hormones contributes to brain activity and gut health. Scientists are currently investigating ways to promote healthy communication between the gut and the brain, as well as identify what hinders their relationship.

“We still don’t quite know how nutritional microbes control us yet, but food is at the center of who we are,” explained Dr. Bohorquez in an interview with NC State University.

Understanding the Basics of the Gut-Brain Connection
The Gut-Brain Axis (GBA), also known as the Gut-Brain Connection, refers to the bidirectional communication between the central nervous system and the enteric nervous system that connects cognitive and digestive behavior. The enteric nervous system has been described as a second brain in the gastrointestinal tract that regulates digestion (Carabotti et al, 2015). Not only is the GBA responsible for the butterflies in your stomach, but it may also be the underlying factor for some psychiatric, gastrointestinal, and neurological conditions such as Major Depressive Disorder, Irritable Bowel Syndrome and Parkinson’s Disease.

So how do the gut and brain communicate? Scientists have identified several physiological components that contribute to their relationship.

The Vagus Nerve is the Central Communications Superhighway

There are 500 million neurons in the gastrointestinal tract. However, our understanding of the gut is primitive compared to other sensory organs like the tongue and nose. The vagus nerve is the major pathway that connects the brain to the gut. It runs from the brain, through the lungs, heart, spleen, liver, kidneys, and down to the intestines. Interestingly, if severed, the intestines can still function without direction from the central nervous system (Briet et al, 2018).

Neuropod Cells are Specialized Messengers in the Gut

According to the research of Duke University neuroscientist Dr. Diego Bohorquez, specialized neuropod cells in the lining of the intestinal wall communicate with vagal neurons upon stimulation by molecules in the gut, such as the nutrients present in food particles, bacteria or pathogens. This communication can occur within seconds. In a 2018 study, Bohorquez and his fellow researchers explain, “Sensory cues that stimulate the gut could potentially be manipulated to influence specific brain functions and behavior, including those linked to food choices.” This has great implications for future applications in the management of obesity. (Kaelberer et al, 2018).

Diversity in the Gut Microbiome is an Indicator of Mental Health

The gut microbiome is made up of trillions of bacteria in the gut. The microbiome weighs more than the brain – over 4 pounds! Bacterial strains in the gut produce neurotransmitters and short-chain fatty acids that stimulate the nervous system. Specific types of bacteria have been found to enhance memory and regulate stress (Ferranti et al, 2014). In recent years, there’s been increasing interest in the study of psychobiotics, specific bacteria that have mental health benefits when ingested, and the practice of fecal transplants (Sarkar et al, 2016).

Neurons in the Gut Release Gastrointestinal Hormones

Neuroendocrine signaling occurs when bacteria in the gut trigger enteroendocrine cells in the lining of the intestinal wall to release neuropeptides like cholecystokinin which is a well-studied satiety hormone (Hirokazu et al, 2018). Additionally, more than ninety percent of serotonin, a hormone that helps increase feelings of happiness, is made in the gut. Serotonin plays an important role in regulating mood (Yano et al, 2015).


This research contributes to a growing body of evidence that suggests that the GBA is a promising target for medical therapies in the treatment of some disorders. Here are a few things you can do to improve the relationship between your brain and your gut:

  1. The Mediterranean Diet, high in polyphenols and omega-3 fatty acids, has been shown to improve the GBA in systematic reviews of multiple clinical trials (Morkl et al, 2018).
  2. Consider adding food that is high in fiber to feed the healthy bacteria in your gut and fermented food that contains beneficial bacteria that contribute to the diversity of your gut microbiome.
  3. Improve vagal tone  and the GBA with deep breathing exercises. Engage your diaphragm and inhale slowly from the depths of your lungs to the count of five. Then exhale slowly to the count of five and repeat. Meditation and physical activity have also been found to improve vagal tone and the GBA.
  4. Avoid caffeine which can amplify nervousness and anxiety and agitate bowel discomfort. Try swapping your coffee for herbal teas that have less caffeine and drink plenty of water.
  5. Listen to your gut! If you’re experiencing a digestive disorder, consider your state of mind. You might be able to improve your gut health by addressing your mental health.


Breit, S., Kupferberg, A., Rogler, G., & Hasler, G. (2018). Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Frontiers in Psychiatry.

Carabotti, M., Scirocco, A., Maselli, M., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annal of Gastroenterology, 28(2), 203–209.

Ferranti, E., Dunbar, S., Dunlop, A., & Corwin, E. (2014). 20 Things You Didn’t Know About the Human Gut Microbiome. Journal of Cardiovascular Nursing, 29(6), 479–481.

Hirokazu, F., Xu, X., & Miwa, H. (2018). Role of Gut Microbiota-Gut Hormone Axis in the Pathophysiology of Functional Gastrointestinal Disorders. Journal of Neurogastroenterology and Motility, 24(3), 367–386.

Kaelberer, M., Buchanan, K., Klein, M., Barth, B., Montoya, M., & Shen, X. (2018). A Gut-Brain Neural Circuit for Nutrient Sensory Transduction. Science.

Morkl, S., Wagner-Skacel, J., Lahousen, T., Lackner, S., Holasek, S., & Bengesser, S. (2018). The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the Literature. Neuropsychobiology, 1–9.

Sarkar, A., Lehto, S., Harty, S., Dinan, T., Cryan, J., & Burnet, P. (2016). Psychobiotics and the Manipulation of Bacteria–Gut-Brain Signals. Trents in Neurosciences, 39(11), 763–781.

Terlouw, J. (2020, January 17). Tummy Talk: Dr. Diego Bohorquez and The Neuroscience of The Gut.

Yano, J., Yu, K., Donaldson, G., Ismagilov, R., Mazmanian, S., & Hsiao, E. (2015). Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell, 161(2), 264–276.

These resources were developed by Lauren Fiabane, Intern at the Duke Diet & Fitness Center and the Duke Health & Well-Being Nutrition team:

Duke Diet & Fitness Center
Elisabetta Politi, RD, MPH, LDN, CDE – Nutrition Director
Christine B. Tenekjian, MPH, RD, LDN – Clinical Dietitian

Duke Health & Fitness Center
Kara Mitchell – Wellness Manager, Exercise Physiologist & Dietitian/Nutritionist
Samantha Mendelowitz – Dietitian/Nutritionist – Clinical Dietitian
Jenni Biggs – Dietitian/Nutritionist – Clinical Dietitian, Certified Diabetes Educator

Duke Integrative Medicine
Joanne Gardner, MS, RDN, LDN – Integrative Dietitian / Nutritionist
Jill Brown, MS, RDN, IFNCP, CLT – Integrative Dietitian / Nutritionist
Gretchen L. Hofing, MPH, RD

About Duke Health & Well-Being Nutrition & Lifestyle Services

Our individualized nutrition services are utilized to treat specific health conditions, manage weight healthfully, and to attain optimal vitality through a wholesome diet. Our nutritionists understand that getting on the right path toward your health goals is a process that requires support, adjustment, and taking small steps to make lasting and positive changes. Work with a nutritionist to discover the connection between food, movement, stress, and rest and make strategic changes to your diet that will help you achieve your goals.

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