Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul;169(1):104-118.e4.
doi: 10.1053/j.gastro.2025.01.246. Epub 2025 Feb 18.

Psychological Stress-Induced Local Immune Response to Food Antigens Increases Pain Signaling Across the Gut in Mice

Javier Aguilera-Lizarraga  1 , Cintya Lopez-Lopez  2 , Josue Jaramillo-Polanco  2 , Morgane V Florens  1 , Yang Yu  2 , Quentin K Tsang  2 , Ananya Chakraborty  2 , Sofie De Gand  1 , Fedrica Pia  1 , Runze Quan  1 , María Cuende-Estévez  1 , Samuel Van Remoortel  1 , Jessica Strid  3 , Alan E Lomax  2 , M Cecilia Berin  4 , Andrew W Craig  5 , Eva Kaufmann  2 , Mark L Ormiston  5 , Stephen J Vanner  2 , Hind Hussein  1 , Guy E Boeckxstaens  1 , David E Reed  6
Affiliations
Free article

Psychological Stress-Induced Local Immune Response to Food Antigens Increases Pain Signaling Across the Gut in Mice

Javier Aguilera-Lizarraga et al. Gastroenterology. 2025 Jul.
Free article

Abstract

Background & aims: We recently showed that a bacterial infection can break oral tolerance to food and lead to immunoglobulin E (IgE)-dependent mast cell activation and food-induced abdominal pain, which could constitute an important pathogenic mechanism in postinfectious irritable bowel syndrome (IBS). Here, we investigated whether similar immune mechanisms in response to psychological stress lead to food-evoked pain signaling, and thus potentially explain the pathophysiology in a larger group of patients with IBS.

Methods: Mice were exposed to ovalbumin (OVA) during water avoidance stress (WAS) and re-exposed to OVA 5 weeks later. Nociception was evaluated by visceromotor responses and afferent nerve recordings to intestinal distension, and patch-clamp recordings of sensory neurons incubated with intestinal supernatants. The role of IgE and type 2 immunity was evaluated using pharmacologic and genetic approaches.

Results: Re-exposure to OVA increased pain signaling in the colon and small intestine only in mice exposed to OVA during WAS, in the absence of systemic allergy. OVA-induced increases in pain responses depended on mast cells, IgE, and signal transducer and activator of transcription 6 signaling. Notably, incubation of sensory neurons with ileum and colon supernatants from WAS/OVA+OVA mice lowered their threshold of excitability. Finally, treatment with histamine receptor H1 antagonist pyrilamine blocked the increased sensory neuron excitability, and reduced ileal afferent nerve firing to distension in WAS/OVA+OVA mice.

Conclusions: Psychological stress induces a type 2 immune response to food antigens, with IgE-mediated mast cell activation and increased pain signaling in the small intestine and colon in response to food. These findings may explain the potential role of psychological stress in food-induced symptoms in IBS.

Keywords: Abdominal Pain; IgE; Irritable Bowel Syndrome; Mast Cells; Psychological Stress.

PubMed Disclaimer

MeSH terms