Moody microbes? Gut bacteria found to play key role in serotonin production

By Nathan Gray

- Last updated on GMT

“The finding that gut microbes modulate serotonin levels raises the interesting prospect of using them to drive changes in biology," says senior author Dr Elaine Hsiao of Caltech.
“The finding that gut microbes modulate serotonin levels raises the interesting prospect of using them to drive changes in biology," says senior author Dr Elaine Hsiao of Caltech.

Related tags Bacteria

Our gut microbiota may play a vital role in driving our mood by regulating the production of serotonin in the intestines and blood, say researchers.

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.

Serotonin study

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.”

Source: Cell
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

Related topics Research

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Gut serotonin

Posted by Dr. Jacob L. Driesen, MB Chb (Medicine-UK), D.Phil. (Clinical Neuroscience),

The state of the gut is intimately related to mental states. To believe that a neurotransmitter has only one function is to seriously misunderstand their role in behavior.

The state of the gut, neurotransmitters, and bacteria is intimately related to the brain in a feedback loop.

If one recognizes the nonlinear nature of bodily functions, one cannot assign one purpose to what goes on in the body.

The gut alerts the immune system through such mechanisms as mentioned here by feedback loops. The immune system is also intimately connected to mood, both directly and through the activity in the gut.

To present this as a linear process where action in the gut is only about defense, is to utterly fail to understand how the body works in reality.

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The role of serotonin production in the gut

Posted by Rob Wotring,

Serotonin in produced and stored in massive quantities by enterochromaffin cells in the wall of the gut. Compared to other cells lining the gut, these cells express a much higher density of special receptors that enable them to 'sense' bacteria. Serotonin is released into the wall of the gut when the TLRs 2 and 4 bind to peptidoglycan or lipopolysaccharide, which are found in the cell walls of gram negative and positive bacteria, respectively. Basically, this is a way for the body to monitor the amount of bacteria that has made it past the normally impenetrable gel mucus layer. The serotonin released here is a kind of early warning system, alerting the body that it's first line of defense has been breached. In stark contrast to the elevated mood associated with serotonin production and release in the brain, serotonin in the gut certainly does not cause one to feel better. Rather, increasing levels of serotonin secretion in the gut wall lead to diarrhea and abdominal discomfort, followed eventually by nausea and vomiting.

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