New research from Caltech, published in the April 9 issue of the journal Cell, has shown that certain bacteria in the gut are important in producing peripheral (non-brain-derived) serotonin.
“More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviours,” explained study lead author Elaine Hsiao, a Research Assistant Professor of Biology and Biological Engineering. “We are interested in how microbes communicate with the nervous system. To start, we explored the idea that normal gut microbes could influence levels of neurotransmitters in their hosts.”
To find out whether gut microbes have any effect on the production of peripheral serotonin in the digestive tract, Hsiao and her colleagues measured its levels in mice with normal gut microbiota and their counterparts without the resident germs.
What they found was that the enterochromaffin cells (the major manufacturers of serotonin in the gut) of the germ-free mice produced 60% less serotonin than did their peers with conventional bacterial colonies. When the mice were re-colonized with normal intestinal microbes, their peripheral serotonin production went right back up.
Next, the researchers went on to test whether specific species or groups of known gut bacteria are more important in producing serotonin than others. It turned out that a group of approximately 20 species of spore-forming bacteria elevated serotonin levels in germ-free mice. This group of microorganisms also increased gastrointestinal motility and produced changes in the activation of blood platelets that are know to use serotonin to promote clotting.
Hsiao et. al. also succeeded in identifying the mechanism responsible for this collaboration. They discovered several particular metabolites – products of the microbes’ metabolism – that were regulated by spore-forming bacteria and that elevated serotonin from enterochromaffin cells in culture.
These findings disprove previous research that has indicated gut microbes can make serotonin by themselves.
“While the connections between the microbiome and the immune and 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,” said study co-author Sarkis K. Mazmanian, a Luis B. and Nelly Soux Professor of Microbiology. “This work elegantly extends previous seminal research from Caltech in this emerging field.”
While serotonin is important for many aspects of human health, Hsiao says more research is needed before these findings become useful for clinical purposes:
“We identified a group of bacteria that, aside from increasing serotonin, likely has other effects yet to be explores. Also, there are conditions where an excess of peripheral serotonin appears to be detrimental.”
Hsiao and her team are now investigating whether this mechanism might be playing a part in the developing brain.