Upon seeing the word neurotransmitter, most of us would conjure up some brain centric image or think about its deficiency in some psychological condition. However, it has been estimated that 90% of the serotonin produced within the human body is derived from the digestive tract. Furthermore, aberrant levels of peripheral serotonin have been linked to diseases such as osteoporosis and irritable bowel syndrome. Now, new research from scientists at the California Institute of Technology (Caltech) shows the importance of gut bacteria in the production of peripheral serotonin.   

“More and more studies are showing that mice or other model organisms with changes in their gut microbes exhibit altered behaviors,” explained Elaine Hsiao, Ph.D., research assistant professor of biology and biological engineering at Caltech and senior author on the study. “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.”

The results from this study were published recently in Cell through an article entitled “Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis.”

In addition to neurons and a certain set immune cells, serotonin is produced within the digestive tract by enterochromaffin cells (EC). Dr. Hsiao and her team wanted to determine if the gut microbiota had an effect on serotonin production along the digestive tract. In order to measure serotonin levels, the researchers observed the molecule’s production in mice with normal populations of gut bacteria and compared them to germ-free mice lacking resident microbes.

Interestingly, Dr. Hsiao’s team found that EC cells from germ-free mice produced approximately 60% less serotonin than their microbe laden counterparts. Additionally, the investigators found that they could rescue the normal phenotype by recolonizing the germ-free mice with normal gut bacteria.

“EC cells are rich sources of serotonin in the gut. 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,” said Jessica Yano, research technician in Dr. Hsiao's lab and first author on the paper.

Excited by their initial findings, the Caltech team wanted to see if they could determine the specific species of bacteria that may be effecting the EC cells serotonin production. What they found, after testing an array of different gut microbes, was about 20 species of spore forming bacteria that were responsible for elevating serotonin levels when added to germ-free mice.

“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 Sarkis K. Mazmanian, Ph.D., professor of microbiology at Caltech and a coauthor on the study.

Dr. Hsiao team also found several key metabolites produced by the spore forming bacteria that they observed elevating serotonin production within EC cells in vitro. Moreover, the researchers found that the metabolites, when added to germ-free mice, also increased their peripheral serotonin levels.

“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,” concluded Dr. Hsiao.

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