Scientists have discovered that psychological stress can induce immune responses to food that can cause symptoms when that food is eaten again, findings that demonstrate the potential role of stress in symptoms of irritable bowel syndrome (IBS), according to a recent study published in Gastroenterology.
“This study highlights the key role that activation of the immune system by food plays in many diseases beyond those that we typically think of as food allergies,” said Cecilia Berin, PhD, the Bunning Professor of Food Allergy Research and a co-author of the study. “This study is really showing the molecular explanation for why food can be a trigger not only for a food allergy, but also pain during irritable bowel syndrome.”
Previous work showed that bacterial infection in mouse models can cause the development of immune responses and allergic reactions to food antigens that cause food-induced abdominal pain, the symptom of irritable bowel syndrome. It is also known that IBS can develop after an infection, but this only explains a small portion of IBS cases, according to Berin.
In the current study, the scientists aimed to determine whether similar immune responses caused by psychological stress could contribute to food-induced pain signaling.
“Psychological stress can have direct effects on the physiology of the gastrointestinal tract,” said Berin, who is also a professor of Medicine in the Division of Allergy and Immunology.
First, the investigators exposed mice to ovalbumin, a protein found in egg whites, during a stressful test called water avoidance stress. After five weeks, the mice were re-exposed to ovalbumin.
The scientists then measured visceromotor responses (contractions of the abdominal muscle) and nerve recordings to intestinal distension (excessive enlargement of the intestines) to determine the mice’s nociception, or the nervous system’s response to harmful stimuli. IgE-antibody responses and type 2 immunity, which is triggered by allergic reactions, were measured using pharmacological and genetic approaches.
In the mice exposed to ovalbumin during the stress test, the scientists found that ovalbumin re-exposure increased pain signaling in the mice’s colon and small intestine. These pain responses were also dependent on mast cells (specialized white blood cells), local IgE antibodies and STAT6 signaling, which plays a role in cell proliferation.
When these mice were treated with pyrilamine, a drug currently used to treat allergic symptoms, the investigators found that the drug inhibited increased sensory neuron activity and also decreased nerve firing, causing intestinal distension.
According to Berin, the findings were particularly surprising in that allergic reactions could change normal gastrointestinal tract function and lead to pain without causing systemic allergic reactions such as anaphylaxis.
“The fact that IgE antibodies that we know trigger allergic reactions were at the heart of these symptoms that were quite distinct from what we see in food allergy I found to be really interesting, the idea that these immune responses could be so localized and still be functional,” Berin said.
Going forward, Berin said next steps include studying gastrointestinal immune cells from patients with IBS to determine if localized food-specific immune responses are also seen in patients.
“Targeting the same pathways that are involved in food allergy effectively reduced pain signaling in the mice. We have a number of tools that target these factors that can be used in humans, so this potentially points to a new way of treating irritable bowel syndrome,” Berin said.
This work was supported by Queen’s Translational Institute of Medicine (TIME) Incubator Grant.
