ICVS Researcher Nuno Dinis Alves Explored the Role of Gut Serotonin in Treating Depression and Anxiety While Reducing Side Effects of Classic Antidepressants
Researchers have revealed that modulating serotonin levels in the gut could offer a promising strategy to treat depression and anxiety, potentially avoiding common side effects of classic antidepressants, such as anxiety and digestive issues. These antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are widely prescribed and work by influencing serotonin availability in both the brain and the gut. Additionally, this approach shows potential to prevent negative effects of antidepressant use during pregnancy on both mother and child.
The study, published in Gastroenterology, demonstrates that increasing serotonin specifically in the intestinal epithelium—the thin layer of cells lining the small and large intestines—can alleviate symptoms of anxiety- and depression-like symptoms in rodents. Researchers also found that the use of classic antidepressants during pregnancy increases the risk of constipation in babies during their first year of life.
“Results from both rodent and human studies suggest that selectively targeting antidepressants to the intestinal epithelium may offer clear advantages for patients”, explains Nuno Dinis Alves, an ICVS researcher from the School of Medicine and first author of this publication.
Nuno Dinis Alves
Mental health problems like depression and anxiety are becoming increasingly common, and individuals with mood disorders often experience digestive issues, such as irritable bowel syndrome and constipation. According to Nuno Dinis Alves, “Addressing one issue may help resolve the other.”
SSRIs work by blocking a transport protein that ‘recycles’ serotonin back into neurons, increasing serotonin levels. However, most serotonin is produced in the gut, and the serotonin transporter is also present in intestinal epithelium.
In this study, researchers used various mouse models where the serotonin transporter was removed or blocked. Nuno Dinis Alves explains, “Removing the serotonin transporter from the intestinal epithelium increased serotonin levels and consistently reduced anxiety and depression-like behaviors.”
How is the Gut-Brain Connection Made?
The researchers also identified that the vagus nerve, the “two-way highway” connecting the gut and the brain, is used by serotonin in the intestinal epithelium to influence mood. Cutting this connection in one direction—from the gut to the brain—prevented improvements in anxiety and depression.
In the clinical study, researchers analyzed the use of antidepressants during pregnancy in over 400 mothers, about a quarter of whom were taking antidepressants.
This research resulted from a collaboration between researchers from the NYU Pain Research Center, Columbia University, Université de Sherbrooke in Quebec, Pennsylvania State College of Medicine, Duke University School of Medicine, Baylor College of Medicine, and Albert Einstein College of Medicine.
