Gut microbes important for serotonin production

Serotonin is probably best known as a brain chemical that affects emotions and behavior, an imbalance of which is thought to contribute to depression. Less well-known is that scientists estimate 90% of serotonin is made in the gut, and imbalances in this peripheral serotonin have been linked to diseases ranging from irritable bowel syndrome and cardiovascular disease, to osteoporosis.

90% of serotonin is made in the gut.
Image credit: E. Hsiao/Caltech

Now, researchers from the California Institute of Technology (Caltech) in Pasadena report a study in the journal Cell that shows certain bacteria in the gut play an important role in the production of peripheral serotonin.

Senior author Elaine Hsiao, research assistant professor of biology and biological engineering at Caltech, says studies of mice and other lab animals are increasingly showing that changes in gut microbes affect behavior.

She explains that she and her colleagues were interested in finding out more about how gut microbes and the nervous system talk to each other, and:

"To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts."

In the gut, there are three types of cell we know of that produce serotonin: immune cells, nerve cells or neurons, and enterochromaffin (EC) cells.

Gut microbes appear to influence serotonin production by EC cells

For their study, Prof. Hsiao and colleagues wanted to find out which cells the gut microbes might be influencing to have an effect on serotonin levels.

In the first part of the study, they compared peripheral serotonin levels produced from these cells in two groups of mice: one with normal gut microbes and another group of germ-free mice without gut bacteria.

The team found that in the germ-free mice, their EC cells produced around 60% less serotonin than the mice with normal gut bacteria.

And when they restored bacteria colonies in the gut of the germ-free mice, their EC cells began producing normal levels of serotonin - showing the effect on the EC cells can be reversed.

In the next part of the study the team set out to find which bacteria in particular were interacting with the EC cells to make serotonin.

They introduced single species and groups of gut microbes one by one into the germ-free mice, and found that serotonin levels went up when there was a certain mix of about 20 species of spore-forming bacteria.

Introducing this particular bacterial mix into the germ-free mice increased the movement of food through their digestive tract. It also changed activity in their blood platelets, which use serotonin to boost clotting.

Bacteria control gut microbiota metabolites to influence serotonin production

Further exploration in cell cultures revealed some of the molecular mechanisms underpinning the findings. The team found several metabolic byproducts of gut bacteria are controlled by the mix of spore-forming bacteria and act on EC cells to alter serotonin production.

When the researchers increased these metabolic byproducts in germ-free mice, it increased their levels of peripheral serotonin.

Other investigations have shown bacteria can make serotonin on their own. The researchers say their study suggests a lot of the serotonin in the body relies on the interaction between bacteria and host cells.

Prof. Hsiao says a lot more research needs to be done before findings like theirs are ready for clinical use, and offers a word of caution:

"We identified a group of bacteria that, aside from increasing serotonin, likely has other effects yet to be explored. Also, there are conditions where an excess of peripheral serotonin appears to be detrimental."

She and her team now plan to find out how their findings may apply to the human brain.

Researchers are also discovering other surprising things about serotonin in the body. For example, Medical News Today recently learned how a previously unknown source of serotonin could affect antidepressant activity.

One of the main drawbacks of SSRIs (selective serotonin reuptake inhibitors - a class of antidepressants that prevent reuptake of serotonin by increasing levels of it outside cells) is that they take a while to kick in. A study led by the University of Florence found that the source of this extracellular serotonin is not what experts have assumed, and finding out more about it should help improve drugs that target serotonin.