While serotonin is well known as a brain neurotransmitter, it is also known that as much as 90% of the body's serotonin is made in the digestive tract. In fact, altered levels of this ‘peripheral serotonin’ have been linked to illnesses and disease states including irritable bowel syndrome (IBS), heart disease, and osteoporosis.
Now, new research published in Cell has found that certain bacteria in the gut play a central role in regulating the production of peripheral serotonin – and suggests that altering the microbiota could help to manage conditions related to serotonin.
"More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviours," noted senior author Dr Elaine Hsiao of Caltech.
"We are interested in how microbes communicate with the nervous system,” said Hsiao. “To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts."
Using a combination of mouse research and in vitro cell culture the team found that enterochromaffin (EC) cells, which produce serotonin (5-hydroxytryptamine, 5-HT) in the gut, are largely regulated by spore-forming bacteria and their metabolites.
"EC cells are rich sources of serotonin in the gut,” said Jessica Yano, first author of the research paper. “What we saw in this experiment is that they appear to depend on microbes to make serotonin--or at least a large portion of it.”
"Our work demonstrates that microbes normally present in the gut stimulate host intestinal cells to produce serotonin," said Yano.
The Caltech scientists found that native spore-forming bacteria from the mouse and human microbiota promote serotonin (5-HT) production from intestinal EC cells - which are known to supply serotonin to the mucosa, lumen, and circulating platelets.
“Importantly, microbiota-dependent effects on gut 5-HT significantly impact host physiology, modulating GI motility and platelet function,” wrote Hsiao and her team.
Hsiao and her colleagues first wanted to know if gut microbes have any effect on serotonin production in the gut and, if so, in which types of cells. They began by measuring peripheral serotonin levels in mice with normal populations of gut bacteria and also in germ-free mice that lack these resident microbes.
The researchers found that the EC cells from germ-free mice produced approximately 60 percent less serotonin than did their peers with conventional bacterial colonies.
When these germ-free mice were recolonized with normal gut microbes, the serotonin levels went back up - showing that the deficit in serotonin can be reversed.
The researchers next wanted to find out whether specific species of bacteria were interacting with EC cells to make serotonin. After testing several different single species and groups of known gut microbes, the authors found that one condition - the presence of a group of approximately 20 species of spore-forming bacteria - elevated serotonin levels in germ-free mice.
Indeed, mice treated with this group also showed an increase in gastrointestinal motility compared to their germ-free counterparts, and changes in the activation of blood platelets, which are known to use serotonin to promote clotting.
Hsiao and her team also identified several microbial metabolites that were regulated by spore-forming bacteria, which were found to elevate serotonin from EC cells in in vitro culture tests.
Although this study was limited to serotonin in the gut, Hsiao and her team are now investigating how this mechanism might also be important for the developing brain.
"Serotonin is an important neurotransmitter and hormone that is involved in a variety of biological processes,” said Hsiao. “The finding that gut microbes modulate serotonin levels raises the interesting prospect of using them to drive changes in biology.”
Volume 161, Issue 2, 9 April 2015, Pages 264–276, doi: 10.1016/j.cell.2015.02.047
“Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis”
Authors: Jessica M. Yano, et al