Study shows how serotonin and a popular antidepressant affect intestinal microbiota

A new study in mice led by UCLA biologists strongly suggests that serotonin and serotonin-targeting drugs, such as antidepressants, can have a major effect on the gut microbiota – about 100 trillion bacteria and other microbes present in the body. human body. intestines.

Serotonin – a neurotransmitter or chemical messenger that sends messages between cells – performs many functions in the human body, including playing a role in emotions and happiness. It is estimated that 90% of serotonin is produced in the intestine, where it influences intestinal immunity.

The team, led by lead author Elaine Hsiao and lead author Thomas Fung, a postdoctoral fellow, identified a specific intestinal bacterium that can detect and transport serotonin into bacterial cells. When the mice received an antidepressant, fluoxetine, or Prozac, biologists found that it reduced the transport of serotonin in their cells. This bacterium, about which we know little, calls Turicibacter sanguinis. The study is published this week in the journal Microbiology of nature.

"Our previous work has shown that some intestinal bacteria help the gut produce serotonin, and in this study we wanted to know why they could do this," said Hsiao, UCLA Assistant Professor of Integrative Biology and Physiology, and microbiology, immunology and molecular genetics at UCLA; and digestive diseases at the David Geffen School of Medicine at UCLA.

Hsiao and his research group reported in the newspaper Cell in 2015 than in mice, a specific mixture of bacteria, composed mainly of Turicibacter sanguinis and Clostridia, produces molecules that signal to intestinal cells to increase serotonin production. When the Hsiao team raised mice without bacteria, they lacked more than 50% of the intestinal serotonin. The researchers then added the mixture of bacteria composed mainly of Turicibacter and Clostridiaand their serotonin has increased to a normal level.

This study has led the team to wonder why bacteria report to our intestinal cells to produce serotonin. Do microbes use serotonin, and if so, for what?

In this new study, researchers added serotonin to the drinking water of some mice and elevated others with a mutation (created by modification of a specific serotonin transporter gene) increasing levels serotonin in their intestines. After studying the microbiota of mice, researchers found that Turicibacter and Clostridia increased significantly when there was more serotonin in the intestine.

If these bacteria increase in the presence of serotonin, they may have a cellular mechanism to detect serotonin, speculated researchers. In collaboration with study partner Lucy Forrest and her team at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, researchers discovered a protein in several species of Turicibacter with a structural similarity with a protein that transports serotonin in mammals. When they grew up Turicibacter sanguinis in the laboratory, they discovered that the bacterium was importing serotonin into the cell.

In another experiment, the researchers added the antidepressant fluoxetine, which normally blocks the serotonin transporter in mammals, to a tube containing Turicibacter sanguinis. They discovered that the bacteria carried a lot less serotonin.

The team discovered that the exhibition Turicibacter sanguinis Serotonin or fluoxetine has influenced the ability of the bacteria to grow in the gastrointestinal tract. In the presence of serotonin, the bacterium reached high concentrations in the mouse, but when exposed to fluoxetine, it reached only low concentrations in mice.

"Previous studies from our lab and others have shown that specific bacteria promote serotonin levels in the intestine," said Fung. "Our new study tells us that some intestinal bacteria can react to serotonin and drugs that influence serotonin, such as antidepressants.This is a unique form of communication between bacteria and our own cells by the intermediary of molecules traditionally recognized as neurotransmitters. "

The team's research on Turicibacter aligns with a growing number of studies indicating that antidepressants can alter the gut microbiota. "For the future," said Hsiao, "we want to know if microbial interactions with antidepressants have consequences for health and disease." Hsiao wrote a blog post for the newspaper on the new research.