How Digestive Hormones Affect Mental Health

Christmas and New Year’s are behind us, and most of us spent those days not only surrounded by loved ones but also indulging in delicious food. While this leaves us with a sense of warmth and satisfaction, it can have greater effects on our bodies than just giving our digestion some extra work. Who would have thought that the hormones released during the simple act of eating could directly influence our mental health? Or that something as ordinary as savoring a meal might also shape how our brain processes stress, hunger, or satiety?

At the heart of this intricate connection between food, body, and brain are three key players: ghrelin, cortisol, and cholecystokinin (CCK). These hormones do more than regulate hunger or digestion – they also interact with the brain, sometimes acting like neurotransmitters. But what does that mean? And how can substances that travel through the bloodstream have such a profound impact on our neural communication?

To answer this, it’s essential to understand the roles of neurotransmitters and hormones. Neurotransmitters are the body’s rapid-response messengers. They are released by nerve cells and act locally, sending signals across synapses to other neurons, muscles, or glands. Think of them as instant texts sent from one device to another (University of Queensland, 2024). Hormones, by contrast, are more like letters sent through the postal system. Produced by endocrine glands and released into the bloodstream, they travel across the body to reach their target cells, influencing processes like metabolism, stress response, and growth. Their effects are systemic and slower than the quickfire action of neurotransmitters (Stárka & Dušková, 2020).

But here’s where it gets fascinating: some hormones, like ghrelin, cortisol, and CCK, can blur the lines between these two roles. For example, imagine skipping breakfast and feeling that all-too-familiar growl in your stomach. That’s ghrelin in action. Produced in the stomach, it signals your brain that it’s time to eat. However, ghrelin doesn’t stop at being a hunger hormone; it can also function as a neuroactive molecule, heightening your focus and driving you to prioritize food (Pradhan, Samson, & Sun, 2013).

Now picture yourself recovering from a stressful presentation. Cortisol, released by the adrenal glands, helps your body cope with stress (Knezevic, Nenic, Milanovic, & Knezevic, 2023). But this “stress hormone” also influences neurotransmitters like GABA and glutamate, which affect mood and energy regulation. While cortisol isn’t directly a neurotransmitter, it modulates the brain’s chemical balance, illustrating its dual role (Cleveland Clinic, 2024).

Finally, think about the satisfaction you feel after a hearty meal. That’s cholecystokinin stepping in. Released by the small intestine, it activates digestive enzymes and stimulates the gallbladder (National Institutes of Medicine, 2024). At the same time, it acts as a neurotransmitter in the brain, signaling fullness and encouraging you to stop eating (Rehfeld, 2017).

The multifaceted roles of ghrelin, cortisol, and cholecystokinin (CCK) reveal the intricate connections between our physical and psychological well-being. While they govern crucial functions such as appetite, stress response, and digestive processes, their effects ripple outward to influence behaviors, mood states, and overall mental health. Recognizing these connections highlights how everyday factors, like eating patterns and stress levels, are intricately linked to these hormones and their far-reaching impact.

Ghrelin: More Than Just Hunger’s Alarm Bell

Let’s start with ghrelin, the so-called “hunger hormone.” While its primary function is to tell the brain that it’s time to eat, ghrelin’s reach goes far beyond signaling an empty stomach. This hormone interacts with the brain’s reward systems, particularly in the ventral tegmental area, a key part of the brain associated with motivation and pleasure (Müller et al., 2015). Studies show that ghrelin can amplify the rewarding aspects of food, especially under conditions of stress, pushing us toward comfort eating (Schéle, Bake, Rabasa, & Dickson, 2016). But this same pathway also means ghrelin has a hand in modulating mood and emotional resilience.

For instance, prolonged fasting can lead not only to physical hunger but also to heightened irritability or restlessness – an emotional ripple effect of ghrelin’s activity in the brain (Chuang & Zigman, 2020). Conversely, in the context of chronic stress or anxiety disorders, elevated ghrelin levels can skew the brain’s reward balance, making unhealthy eating habits harder to resist (Müller et al., 2015).

Cortisol: The Stress Regulator with a Hidden Cost

Cortisol, often associated with the body’s “fight or flight” response, is another hormone that bridges the gap between physical and mental health. In small doses, cortisol is invaluable, allowing us to respond to challenges, maintain focus, and recover from stress. But when stress becomes chronic, cortisol shifts from being a helpful regulator to a disruptive force. Prolonged elevation of cortisol can suppress digestion, disrupt gut motility, and even alter the gut microbiome, which is crucial for overall digestive health (Chrousos, 2009).

On the mental health side, elevated cortisol interferes with neurotransmitters like serotonin, a key mood stabilizer. This can lead to symptoms of anxiety, depression, and even cognitive difficulties. Think of those moments when stress leaves you unable to eat or, conversely, craving sugary, high-energy foods: cortisol is working overtime, rewiring both your body’s energy systems and your emotional responses (The Center for Health, 2024).

Cholecystokinin: From Fullness to Emotional Balance

Cholecystokinin may not enjoy the same recognition as ghrelin or cortisol, but its functions are equally intriguing. Released during meals, CCK communicates with the brain to curb appetite and aids in fat digestion (Rehfeld, 2017). Beyond its physical roles, it exerts influence on emotions by engaging the limbic system, fostering feelings of satisfaction and relaxation after eating. Yet, this hormone has its complexities. Increased sensitivity to CCK has been linked to anxiety disorders, as its activation of the limbic system can sometimes lead to heightened emotional responses (Rotzinger & Vaccarino, 2003).

Studies indicate that elevated CCK activity, particularly through the CCK-B receptor, can provoke anxiety and even panic in vulnerable individuals (Rotzinger & Vaccarino, 2003). For instance, research has shown that administering CCK-related compounds can elicit panic-like reactions in those predisposed to such symptoms. This reveals the dual nature of CCK: while it plays a vital role in regulating appetite and digestion, dysregulation in its signaling can contribute to mood disorders like generalized anxiety and panic disorder. These findings emphasize the intricate connection between digestive processes and mental health, underscoring the gut-brain axis as a vital area for continued research.

In conclusion, the interplay between ghrelin, cortisol, and cholecystokinin (CCK) extends beyond hunger and emotional regulation to significantly impact the digestive system. Ghrelin, which stimulates appetite and promotes gastric motility, primes the body for food intake (Pradhan, Samson, & Sun, 2013). Cortisol, a stress hormone, disrupts digestion when chronically elevated, slowing gut motility and altering the gut microbiome, which can lead to digestive problems (Chrousos, 2009). Meanwhile, cholecystokinin, released after eating, supports digestion by stimulating bile release and digestive enzymes, while signaling to the brain that satiety has been achieved (Rehfeld, 2017). As these hormones play pivotal roles in both digestion and emotional regulation, their influence on the digestive system can directly affect mood, stress levels, and overall mental health, highlighting the profound connection between our gut and brain.

By understanding these mechanisms, we can make more informed decisions regarding our eating habits, stress management, and overall health. Small adjustments in how we address these interconnected systems can lead to profound improvements in both physical and mental well-being, emphasizing the importance of maintaining a balanced gut-brain connection for optimal health.

On the 17th, 18th, 24th and 25th of January 2025, you will have the opportunity to consult our experts and discuss any doubts you may have about the impact of your microbiota on your mental health.

Remember that during the exhibition, our experts will not give a presentation, but will simply be present so that you can talk to them about your thoughts.

We will be announcing details of a more formal microbiota and psychobiome awareness day at a later date.

Check out our schedule and which expert will be assisting when HERE. Apply now!

References

Chrousos, G. P. (2009). Stress and disorders of the stress system. Nature Reviews Endocrinology, 5(7), 374-381. https://doi.org/10.1038/nrendo.2009.106

Chuang, J., & Zigman, J. M. (2010). Ghrelin’s roles in stress, mood, and anxiety regulation. International Journal of Peptides, 2010, 1–5. https://doi.org/10.1155/2010/460549

Cleveland Clinic. (2024). The cortisol connection. Retrieved from

https://consultqd.clevelandclinic.org/the-cortisol-connection?utm_source=chatgpt.co m

Knezevic, E., Nenic, K., Milanovic, V., & Knezevic, N. N. (2023). The role of cortisol in chronic stress, neurodegenerative diseases, and psychological disorders. Cells, 12(23), 2726. https://doi.org/10.3390/cells12232726

Müller, T., Nogueiras, R., Andermann, M., Andrews, Z., Anker, S., Argente, J., Batterham, R., Benoit, S., Bowers, C., Broglio, F., Casanueva, F., D’Alessio, D., Depoortere, I., Geliebter, A., Ghigo, E., Cole, P., Cowley, M., Cummings, D., Dagher, A., … Tschöp, M. (2015). Ghrelin. Molecular Metabolism, 4(6), 437-460.https://doi.org/10.1016/j.molmet.2015.03.00

Okonkwo, O., Zezoff, D., & Adeyinka, A. (2023, May 1). Biochemistry, cholecystokinin. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK534204/

Pradhan, G., Samson, S. L., & Sun, Y. (2013). Ghrelin: Much more than a hunger hormone. Current Opinion in Clinical Nutrition & Metabolic Care, 16(6), 619-624. https://doi.org/10.1097/MCO.0b013e328365b9be

Rehfeld, J. F. (2017). Cholecystokinin – from local gut hormone to ubiquitous messenger. Frontiers in Endocrinology, 8, 47. https://doi.org/10.3389/fendo.2017.00047

Cholecystokinin receptor subtypes: role in the modulation of anxiety-related and reward-related behaviours in animal models. (2003, May 1). PubMed. https://pubmed.ncbi.nlm.nih.gov/12790157/

Schéle, E., Bake, T., Rabasa, C., & Dickson, S. L. (2016). Centrally administered ghrelin acutely influences food choice in rodents. PLoS ONE, 11(2), e0149456. https://doi.org/10.1371/journal.pone.0149456

Stárka, L., & Dušková, M. (2020). What is a hormone? Physiological Research, S183–S185. https://doi.org/10.33549/physiolres.934509

The Center for Health. (2024). Cortisol and stress. Retrieved from

https://www.thecenterforhas.com/increase-serotonin-by-improving-gut-health/

University of Queensland. (2024). What are neurotransmitters? Retrieved from

https://qbi.uq.edu.au/brain/brain-functions/what-are-neurotransmitters

Jana Isabel Vicente @neuropsyblog

Nieves López-Brea Serrat
Psicóloga Sanitaria
Experta en Neuropsicología Clínica Infanto-Juvenil