Researchers at the University of Victoria have discovered that the protein Reelin could help repair leaky gut caused by chronic stress and alleviate depression symptoms. A single injection restored Reelin levels in preclinical models, showing antidepressant effects. The findings highlight the gut-brain connection in mental health.
Chronic stress disrupts the gut barrier, leading to increased permeability known as leaky gut, which allows harmful bacteria and toxins into the bloodstream and triggers inflammation that can exacerbate major depressive disorder (MDD). A study from the University of Victoria, published in the journal Chronic Stress in 2025, identifies Reelin—a glycoprotein present in the brain, blood, liver, and intestines—as a key player in maintaining gut health and supporting brain function.
In preclinical models, chronic stress reduced Reelin levels in the intestines. However, administering a single intravenous injection of 3 µg of Reelin normalized these levels and promoted healthy renewal of the gut lining, which typically replaces cells every four to five days. Previous research has linked low Reelin in the brain to MDD in humans and rodents, and similar injections in stressed animals produced antidepressant-like effects.
Hector Caruncho, professor of medical sciences at UVic and the study's corresponding author, emphasized the gut-brain axis: "This study aimed to understand the role of Reelin in the gut, especially under conditions of chronic stress. The gut-brain axis is becoming essential to understanding many psychiatric disorders, including depression."
Ciara Halvorson, the lead author and a neuroscience PhD student at UVic, noted the broader implications: "Taken together, these results may have important implications for the management of major depressive disorder. This is especially true for people who live with both depression and gastrointestinal conditions."
The research, supported by the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC), suggests Reelin-based therapies could target both gut integrity and depressive symptoms, though further studies are needed before clinical applications. The full study, titled "An Intravenous Injection of Reelin Rescues Endogenous Reelin Expression and Epithelial Cell Apoptosis in the Small Intestine Following Chronic Stress," is available with DOI: 10.1177/24705470251381456.
