Scientists Discover Protein That May Repair Leaky Gut, Reduce Depression

Scientists have identified a potential biological connection between chronic stress, gut health, and depression, with a protein called Reelin emerging as a central player. New research from the University of Victoria (UVic), published in Chronic Stress, suggests that therapies targeting Reelin could simultaneously restore gut barrier integrity and reduce depressive symptoms.
The gastrointestinal system, including the stomach and intestines, regulates which nutrients enter the bloodstream. Chronic stress and stress-related conditions, such as major depressive disorder (MDD), can disrupt this balance, leading to increased gut permeability, commonly referred to as “leaky gut.”
Leaky gut allows harmful bacteria and toxins to escape into the bloodstream, triggering inflammation that can exacerbate depressive symptoms. Strengthening the gut barrier may therefore offer a strategy to reduce the severity or risk of MDD.
Reelin is a glycoprotein found throughout the body, including in the brain, blood, liver, and intestines. According to Hector Caruncho, professor of medical sciences at UVic and corresponding author of the study, Reelin may play a key role in maintaining gut and brain health.
In preclinical models, chronic stress reduced Reelin levels in the intestines. Remarkably, a single intravenous injection of 3 µg of Reelin restored these levels to normal. Previous research has also shown that individuals with MDD have lower Reelin levels in the brain, and rodents exposed to chronic stress exhibit similar reductions. In these animals, Reelin administration produced antidepressant-like effects.
Reelin supports the renewal of gut lining cells, which are naturally replaced every four to five days to maintain intestinal integrity. By reinforcing gut barrier function, Reelin may prevent inflammation caused by leaked gut material, potentially reducing depressive symptoms triggered by immune responses.
Ciara Halvorson, a neuroscience PhD student at UVic and first author of the study, emphasizes that these findings could have important implications for individuals living with both depression and gastrointestinal conditions.
Although further research is needed before Reelin-based therapies can be tested in clinical settings, this study highlights a promising new approach to treating depression. By simultaneously targeting the brain and gut, Reelin could offer a more comprehensive strategy for managing mental health conditions associated with chronic stress.
REFERENCE: Ciara S Halvorson, Carla Liria Sánchez-Lafuente, Brady S Reive, Lara S Solomons, Josh Allen, Lisa E Kalynchuk, Hector J Caruncho. An Intravenous Injection of Reelin Rescues Endogenous Reelin Expression and Epithelial Cell Apoptosis in the Small Intestine Following Chronic Stress. Chronic Stress, 2025; 9 DOI: 10.1177/24705470251381456