What’s the Role of Psychological Stress in Food-Induced IBS?

• The researchers modeled stress-associated food exposure using mice — To simulate how stress exposure affects food responses, mice were fed a common dietary protein (ovalbumin) during a 10-day period of psychological stress. The same protein was reintroduced five weeks later to see if the gut would respond differently.

• Only stressed mice given the protein developed hypersensitivity — Mice that consumed the protein during periods of stress later developed gut pain and visceral hypersensitivity when re-exposed to it. In contrast, mice that were only stressed, or only fed the protein without stress, did not develop symptoms. This demonstrates that the pairing of food and stress created the hypersensitive state.

• The pain response was not due to general inflammation or allergy — To rule out systemic allergic reactions, researchers injected the protein under the skin. Unlike true food allergies, this didn’t cause ear swelling or signs of systemic inflammation. The pain response was localized to the gut and driven by changes in how the immune system and nerves interacted.

• Blocking mast cells or IgE eliminated the pain response — Mast cells are immune cells that release histamine and other chemicals during allergic reactions, while IgE is the antibody that signals mast cells to activate.

When researchers gave mice a mast cell stabilizer or used genetically modified mice that lacked IgE antibodies, the hypersensitive response disappeared. This confirmed that both mast cells and IgE were required to create the immune memory that led to pain upon food re-exposure.

• Gut fluid from stressed mice activated nerve cells in healthy tissue — Researchers collected intestinal fluid (supernatants) from the stressed mice and applied it to healthy neurons. These neurons became hyperactive, firing pain signals more easily. This showed that the chemical environment in the stressed gut was enough to disturb normal nerve behavior.

• Both the small intestine and the colon were affected — Increased nerve sensitivity was found in the small intestine and the colon, not just one area. This matches what many IBS patients report of pain throughout different parts of the gut, not just in the lower intestine.

• Histamine signaling was responsible for nerve hypersensitivity — Histamine, a chemical released by mast cells during immune responses, was found to drive nerve excitability. Blocking histamine H1 receptors using pyrilamine, an antihistamine, reversed the hypersensitive response, demonstrating its central role in the pain mechanism.

• A type 2 immune response was activated in the gut — Researchers detected increased levels of IL-13, a cytokine associated with allergic-type immune responses, in lymph nodes after re-exposure to the protein. This suggests that the immune system had shifted into a food-specific, allergy-like state, even though there were no outward allergic symptoms.

• Stress increases mast cell numbers and activity in the gut — According to the review, both acute and chronic stress activate mast cells in the intestinal mucosa. These mast cells accumulate in greater numbers in patients with IBS and are found closer to mucosal nerves. This proximity suggests they may influence visceral pain sensitivity.

• Mast cells are located near mucosal nerves in IBS patients — The paper highlights studies showing a correlation between the number of mast cells near nerves and the severity of abdominal pain in IBS. Mast cells situated less than 5 micrometers from nerve endings were found more frequently in patients reporting higher pain scores.

• Stress activates CRF signaling in the gut — Corticotropin-releasing factor (CRF) is a hormone your body releases during psychological stress. According to the authors, CRF binds to receptors on mast cells and nerves in the gut, which in turn triggers changes in gut function that are commonly seen in IBS, such as increased pain sensitivity and disrupted motility.

• CRF-mast cell activation affects gut permeability and motility — Activation of CRF receptors was associated with mast cell degranulation (a process where mast cells release stored chemicals like histamine that influence nearby tissues), changes in intestinal permeability, and altered motility. These effects may contribute to diarrhea, pain, and other IBS symptoms.

• Stress hormones disrupt gut function and microbial balance — When you’re under stress, your body activates the hypothalamic-pituitary-adrenal (HPA) axis, the central stress response system. This leads to the release of several key hormones, including cortisol, your body’s main stress hormone.

• Animal models show early life stress increases gut sensitivity — Rodent studies cited in the paper showed that early life stress (such as maternal separation) increases visceral sensitivity and CRF expression. These effects persist into adulthood, suggesting long-term programming of gut-brain interactions.

• Calming stress signals and stabilizing immune cells reduce IBS symptoms — The authors suggest that treatments that block stress hormones or prevent mast cells from overreacting help reduce gut pain, urgency, and other IBS symptoms, especially if your flare-ups are triggered by stress. This points to a need for therapies that go beyond digestion and instead focus on calming your gut’s stress-immune response.

1. Lower cortisol by fixing your diet and lifestyle — Chronically elevated cortisol levels keep your immune system in a hyperreactive state. Blood sugar instability, undereating, and poor sleep all keep cortisol high. To learn how to lower it, read my article “Key Strategies to Reduce Your Cortisol Levels.”

2. Exercise regularly — Research shows exercise helps improve the symptoms of IBS.⁸ It also boosts mood and counters the detrimental effects of stress by lowering cortisol levels.⁹ I recommend doing moderate exercises such as walking, as they cannot be overdone.¹⁰ Walking outdoors also provides an opportunity to reconnect with nature and spend time under the sun, which helps further decrease stress levels.¹¹

3. Practice mindfulness — Mindfulness meditation teaches your brain to stop reacting to every stress trigger. A 2022 study in the Chinese Journal of Traumatology¹² found it helped reduce post-traumatic stress disorder (PTSD) symptoms in military personnel. You don’t need complicated routines; just 10 minutes of focused attention can help reset your baseline.

4. Fix your breathing habits — Most people develop dysfunctional breathing patterns after emotional stress. These habits reduce carbon dioxide in the body, which increases nervous system sensitivity. Many popular breathing techniques make this worse. Check out “Why Proper Breathing Is the Key to Optimal Health” to learn how to breathe properly and why it matters.

5. Improve your emotional state with optimism and laughter — Cultivating a more positive mindset changes your brain chemistry and helps reduce stress, while laughter triggers the release of endorphins and relaxes the nervous system. Whether you’re reframing negative thoughts or watching something funny, these emotional resets help lower stress and restore balance.

6. Embrace your creativity — Hobbies like painting, writing, or playing music help process emotion and reduce stress-related cortisol release. They shift your focus away from chronic overthinking and give your nervous system space to settle.

7. Try Emotional Freedom Techniques (EFT) — EFT is a form of psychological acupressure based on the energy meridians used in acupuncture that quickly restores inner balance and healing. In the video below, EFT practitioner Julie Schiffman demonstrates how to tap for stress relief.

8. Prioritize high-quality sleep — Poor sleep keeps cortisol elevated and lowers your ability to handle stress. Create a consistent sleep routine, reduce blue light exposure at night, and keep your room cool to improve sleep quality.

9. Increase physical contact — Physical touch, like hugging, releases oxytocin, which lowers stress and promotes emotional regulation. Daily, consensual physical contact helps bring your body out of a high-alert state and into one that supports healing and digestion.

10. Support gut health to reduce immune overreactions — Once stress is under control, restoring a healthy gut environment helps calm your immune system and prevent hypersensitivity. Focus on removing vegetable oils from your diet, optimize your carbohydrate intake, and consider using Akkermansia supplements. To learn more about these strategies, read “Gut Health’s Impact on Mental Well-Being.”

You’ll also want to support your body’s production of butyrate, a short-chain fat made by gut bacteria that strengthens the intestinal barrier and helps regulate immune activity. Check out “Butyrate’s Impact on Your Immune System” for more information.