That Gut Feeling: How Depression and Constipation Are Linked

Researchers from Columbia describe how depression and gut health are linked by low serotonin.
Jessica Miley

Depression and gastrointestinal distress are well linked, but scientists have not exactly understood why. It is common for people suffering depression to also concurrently endure gut health problems such as constipation.

A new study from Columbia suggests that the two conditions are caused by the same neurological glitch - low serotonin.


The research included a study conducted on mice that demonstrated a lack of serotonin, - also known as the happiness chemical - can cause constipation. Low serotonin levels in the brain may also lead to depression. Increasing serotonin levels in both the brain and the gut have been found to lessen both conditions. More than a third of people diagnosed with depression also suffer from chronic constipation.

Depression and poor gut health linked

Bowel and gut issues are often reported by people with mental health problems as a massive factor in the quality of life. Chronic constipation is uncomfortable and can cause sleeplessness, pain, as well as accompanying feeling of shame and embarrassment. Severe constipation can obstruct the hollow organs from the mouth of the anus known collectively as the GI tract.

Blockage of the GI tract leads to more than 2.5 million physician visits in the U.S alone as well as 100,000 hospitalizations each year. While some antidepressants may cause constipation as a side effect, this drug-induced obstruction does not relate to all cases, and the links between gut health and mental health are clear. Though some antidepressants are known to cause constipation, medication side effects do not explain all cases.

Second brain

“Ultimately, many patients with depression are faced with limited treatment options and have to suffer with prominent GI dysfunction,” says study leader Kara Gross Margolis, MD, associate professor of pediatrics at Columbia University Vagelos College of Physicians and Surgeons. Recent studies have shown just how tightly linked the brain and gut are.

“The gut is often called the body’s ‘second brain,’” says Margolis.

“It contains more neurons than the spinal cord and uses many of the same neurotransmitters as the brain. So it shouldn’t be surprising that the two conditions could be caused by the same process.”

The researchers theorized that because low levels of serotonin in the brain have been linked to depression and serotonin is also used by neurons in the gut; they were keen to find if a serotonin shortage also plays a role in constipation.

Low serotonin leads to constipation

The mice in the study carry a gene mutation that is linked to severe depression in humans that slows the ability of neurons in both the brain and the gut to make serotonin.

By hampering the production of serotonin in the mice's gut, the study found that the mice’s gut lining began to deteriorate which slows the movement of contents through the animal's GI tract causing constipation.

“Basically, the mice were constipated,” Margolis says, “and they showed the same kind of GI changes we see in people with constipation.” Co-authors of the study Marc Caron, Ph.D., and Jacob Jacobsen, Ph.D., of Duke University, also created an experimental drug treatment aimed at raising serotonin levels.

The treatment could alleviate constipation by raising the animal's serotonin levels.

Slow release drug could be key

The drug is a slow release of 5-HTP, a precursor of serotonin, which works by increasing the number of GI neurons in adult mice. The researchers are satisfied they could show that neurogenesis in the gut is possible and can correct abnormalities in the gut.

“Though it’s been known for many years that neurogenesis occurs in certain parts of the brain, the idea that it occurs in the gut nervous system is relatively new,” Margolis says.

Research into the use of slow release 5-HTP as both a drug for constipation relief and for use with people with treatment-resistant depression.

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