Serotonin and the Microbiome

Although serotonin (also known as 5-HT) is well known as a brain neurotransmitter, it is estimated that 90 percent of the body's serotonin is made in the digestive tract.

In fact, altered levels of this serotonin have been linked to diseases such as irritable bowel syndrome, cardiovascular disease, and osteoporosis.

New research at Caltech, published in the April 9 issue of the journal "Cell," shows that certain bacteria in the gut are important for the production of serotonin.

More and more studies are showing that model organisms (mice, dogs etc) with changes in their gut microbes exhibit altered behaviors. We are still researching how microbes communicate with the nervous system, and explored the idea that normal gut microbes could influence levels of neurotransmitters in the body.

Serotonin is produced in the digestive tract by enterochromaffin (EC) cells and also by particular types of immune cells and neurons.

The researchers tested mice with full healthy gut microbiome, and mice without any microbiome and found that the EC cells from germ-free (no microbiome) mice produced approximately 60 percent less serotonin than the other mice with full healthy gut microbiomes. 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 EC cells are rich sources of serotonin produced in the gut. In this experiment they appear to depend on microbes to make serotonin—or at least a large portion of it.

The researchers next wanted to find out whether specific species of bacteria, out of the diverse pool of microbes that inhabit the gut, are interacting with EC cells to make serotonin.

After testing several different single species and groups of known gut microbes, researchers observed that one condition elevated serotonin levels in germ free mice —the presence of a group of approximately 20 species of spore-forming bacteria.

The mice that were treated with repopulating the miccrobiome, showed an increase in gastrointestinal motility compared to their still germ-free counterparts, and changes in the activation of blood platelets, which are known to use serotonin to promote clotting.

Wanting to home in on mechanisms that could be involved in this interesting collaboration between microbe and host, the researchers began looking for molecules that might be key. They identified several particular metabolites, (the by-products of the microbes' metabolism) that were regulated by spore-forming bacteria, and that elevated serotonin from EC cells in germ cultures. Furthermore, increasing these metabolites in germ-free mice increased their serotonin levels.

Previous work in the field indicated that some bacteria can make serotonin all by themselves. However, this new study suggests that much of the body's serotonin relies on particular bacteria that interact with the individual to produce serotonin.

While the connections between the microbiome, the immune system, and the metabolic systems are well appreciated, research into the role gut microbes play in shaping the nervous system is an exciting frontier in the biological sciences.

Serotonin is important for many aspects of human health, but much more research is needed before any of these findings can be translated into the clinic setting.

They identified a group of bacteria that, aside from increasing serotonin, likely has other effects yet to be explored and there are conditions where an excess of serotonin appears to be detrimental as well. Although this study was limited to serotonin in the gut, researchers are now investigating how this mechanism might also be important for the developing brain.

Recent studies revealed that Serotonin also plays a pivotal role in immune cell activation and generation/perpetuation of inflammation in the gut. In addition to its various roles in the gut, there are now emerging evidences that suggest an important role of gut-derived serotonin in other biological processes beyond the gut; such as bone remodeling and metabolic homeostasis.

In conclusion, serotonin is an important neurotransmitter and hormone that is involved in a variety of biological processes. The finding that gut microbes modulate serotonin levels raises the interesting prospect of using them to drive changes in biology such as healing inflammatory bowel disease.

Love and Light,

Happy Healing