Lifechanging new protein treats both 'leaky gut' and depression

view original post

Stress has always been an ugly word, and for good reason. In addition to causing people headaches and sleeplessness, ongoing stress can quietly damage the gut—the body’s complex doorway between food and what is absorbed into the bloodstream.

Scientists have known for decades that prolonged stress degrades that barrier, making it more penetrable. New research at the University of Victoria suggests that an injection of a naturally occurring protein called Reelin may heal that damage in a single dose.

The Gut Under Stress

Under normal circumstances, the lining of the intestines functions like a security checkpoint, letting nutrition in but not toxic bacteria and toxins. If that breaks down, the gut is “leaky” and lets foreign particles pour into the blood. This leads to inflammation and, in turn, worsens mental health conditions such as depression and anxiety.

Researchers led by neuroscience PhD student Ciara Halvorson and professor Hector Caruncho wondered if Reelin—a large glycoprotein found all over the body—could repair this stress-induced damage in the gut. In their study, they conducted research with rats to see how chronic stress affects intestinal health and if an intravenous injection of Reelin could undo some of that harm.

Reelin’s Secret Skill

Reelin is best known for its role in the brain, where it helps guide neuron growth and connectivity. But it also shows up in the gut, being released from cells within a layer called the lamina propria. It helps guide new intestinal cells from the crypts at the bottom of the villi—small, finger-shaped projections to absorb nutrients—up to their tips, where older cells die and shed.

This steady rhythm keeps the gut barrier strong. Under chronic stress, though, Reelin levels decrease, slowing down the process of renewal and tearing down the lining of the gut. The researchers hypothesized that boosting Reelin would return normal rhythm to the gut if tested.

The experiment employed 32 male Long Evans rats that were divided into two control groups and two under chronic stress. The stressed rodents were given daily injections of corticosterone, which is a hormone mimicking the action of long-term stress, for 21 days.

On the final day, rats received a single intravenous injection of either 3 or 9 micrograms of recombinant Reelin, or a dummy injection. The researchers then examined tissue from the rats’ small intestine and brain, including Reelin-positive cells and markers for cell death—normal gut cell turnover.

The results were startling. Admittedly stressed rats had roughly half the number of Reelin-positive cells in their guts as controls. But in stressed rats that had been administered a one-shot 3 µg injection of Reelin, those numbers restored to near-normal. Reelin also appeared to restore the tips of the villi to normal levels of cell death, so the lining of the gut was able to rebuild itself.

A Protein With Two Jobs

Those findings are supported by earlier research showing Reelin plays the same healing role in the brain. In earlier experiments, stressed rats given the same amount of Reelin had fewer behavioral symptoms of hopelessness and better results on standard behavior tests. This study connects the dots: stress damages both the gut and the brain, and Reelin seems to draw both tighter.

“Combined, these results may have important implications for the treatment of major depressive disorder,” said Halvorson. “This is especially true for individuals who co-occur with both depression and gastrointestinal disease.”

That overlap is not uncommon—about 70% of people with depression also have gut issues. The “gut-brain axis,” that two-way conversation between your gut and your nervous system, may hold the secret to understanding why mental and digestive health are so interconnected.

Why the Findings Matter

In healthy individuals, the gut lining is replaced every four or five days. That rapid turnover protects against the constant erosion of digestion. When chronic stress retards the process, the gut becomes vulnerable to inflammation and bacterial leakage. Those leaks can send distress signals through the bloodstream that, in turn, affect mood and brain function.

The new findings suggest Reelin could be functioning as a kind of biological band-aid, enabling the gut to mend and maintain its protective lining. “The gut-brain axis is becoming central to our understanding of many psychiatric disorders, such as depression,” said Caruncho.

Despite the fact that the study didn’t find a direct connection between gut content of Reelin and brain, the results hint at a fascinating possibility: treating the gut might indirectly benefit the brain.

Limitations and Next Steps

They caution that the study was conducted in rats, and human physiology is far more complex. The scientists also note that they did not measure actual leakiness or inflammatory cytokines in the gut, which would indicate the beneficial effect of Reelin. Further studies will most likely examine whether repeated injections or multiple concentrations of Reelin could result in more potent or longer effects.

It’s also doubtful whether Reelin-based therapies would even reduce symptoms of depression in humans directly. But the potential is encouraging, given that reduced Reelin expression has already been observed in humans who have major depressive disorder.

This study was to discover how Reelin works in the gut, especially under conditions of chronic stress,” Caruncho explained. “While further studies are needed before Reelin will reach the clinic, these findings put it on the map as a possible new drug treatment for depression that targets processes in both the brain and the gut.”

Practical Implications of the Research

The discovery that a single intravenous dose of Reelin can restore damage to the gut caused by stress holds out new promise for treatments that cure both mind and body. In repairing the gut barrier, Reelin could reduce the inflammatory chain reaction that generally links chronic stress to depression and other psychiatric disease.

If these results hold up in subsequent human trials, Reelin-based treatments could potentially bring relief to millions of individuals suffering from both gut and mood disorders. The study also highlights just how interconnected the body systems are—treatment for the gut may not only relieve digestive upset but also settle the mind.

Research findings are available online in the journal Chronic Stress.

Related Stories

Like these kind of feel good stories? Get The Brighter Side of News’ newsletter.