Reelin protein emerges as promising leaky gut and depression solution

Preclinical research has found that glycoprotein Reelin injections could help heal leaky gut syndrome and severe depression. The study warns that chronic stress can weaken the gut barrier, making it more permeable to harmful bacteria and toxins that can enter and circulate in the bloodstream, which triggers an immune system reaction and inflammation. 

The publication in Chronic Stress explains that chronic stress diminishes Reelin (~50%) and specific immunoreactive cells (~55%) in the small intestine gut lining. However, a single injection of 3 µg of Reelin in Long-Evans rats was found to normalize these deficits. 

Reelin is naturally found throughout the body — in the brain, liver, intestines, and blood.

Nutrition Insight connects with the study’s first author from the University of Victoria, Canada, to learn about the injections nutrition implications and possible therapeutics targeting the gut-brain axis. 

“The microbiome plays a role in maintaining a healthy gut barrier, but the composition and function of the gut microbiome can become disrupted in depression. Likewise, a leaky gut barrier can contribute to dysbiosis,” Ciara Halvorson, Ph.D. candidate, tells us.

“We have shown previously that Reelin has antidepressant-like effects within one hour of administration and that these effects are still present one week after administration. While we have not tested timepoints further than one week after administration, that timeline is still quite promising, as most commonly used antidepressants are taken as daily pills.”

Corresponding author, Hector Caruncho, professor of medical sciences, adds: “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.”

Building on growing evidence

The researchers cite previous studies, which found that people diagnosed with major depressive disorder — as well as rodents exposed to chronic stress — have less Reelin in their brains. Glycoprotein is necessary to renew the gut lining.

A recent review explored the connection between gut and mental health and found the “strongest proof” yet that the microbiome directly affects brain chemistry, stress responses, and behaviors in animal models. It underlines that the gut can potentially improve global mental health with practical diet, stress, and environmental changes to shape gut bacteria.

“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,” says Halvorson.

“Under healthy conditions, the gut lining is renewed every four to five days. This is important as the cells in the gut lining are constantly exposed to damaging factors in the gut,” she adds. “We have not investigated Reelin in the context of obesity or weight management. In cases of obesity accompanied by gastrointestinal disturbances, including leaky gut, Reelin may help mitigate associated symptoms by promoting regeneration of the gut lining.”

Further testing required

The 32 rats in the study came from a subset used in another 2022 study and were kept in rectangular cages. They were injected with vehicle or CORT for 21 days, followed by a recombinant Reelin protein injection. They were anesthetized before the tissue was processed and sliced for immunohistochemical analyses.

The researchers say further studies are required before Reelin is available in clinics. But their research positions it as a promising treatment against depression triggered by leaky gut.

“If Reelin protects against leaky gut by supporting the renewal of the gut lining, Reelin may thereby protect against the worsening of depression symptoms triggered by inflammatory immune responses to leaked gut material,” says Halvorson.

“Through ameliorating the integrity of the gut barrier, Reelin may indirectly normalize or rebalance microbiome composition. There is an emerging body of research showing that symptoms of depression can be ameliorated through the manipulation of the gut environment and microbiome with probiotic supplementation, fecal microbiota transplantations, or dietary changes.”

Mental health and nutrition

Recently, Nutrition Insight spoke to BiOkuris, which found that its synbiotic BK002 benefits gastrointestinal symptoms and significantly reduces anxiety.

Another study suggests that a low-calorie diet may be linked to a higher risk of depressive symptoms, especially among men and those who are overweight.

Meanwhile, clinical research has found that a dose of psilocybin brings sustained reductions in depression and anxiety in cancer patients. One study on psilocybin found that people reported better psychosocial functioning, including a greater sense of meaning in life and psychological connectedness, than those taking standard treatment.