Editor’s Note: In this blog we write about the most recent findings from Elaine Hsiao’s lab at Cal Tech. You may remember Professor Hsiao’s previous work, which we wrote about last year. She published the now seminal article that linked autism spectrum symptoms in mice with their gut microbiomes. Diane will be joining us on the Microbiome Podcast, to be released on May 4. If you have any questions about this study on serotonin, or on her work with autism and the microbiome, please call this number 518-945-8583 and leave a voicemail. If possible we will ask her your question during the show.

Serotonin is a crucial multi-purpose hormone in our body that affects our mood, happiness, appetite, and gastrointestinal movement, among other functions. It is produced in a few places around the body, but mostly in the epithelial cells that line the gut. It should come as no surprise then, that Professor Diane Hsiao’s group, out of Cal Tech, recently uncovered a critical role that the gut microbiome has in stimulating the production of this molecule. She published her results in the journal Cell.

The researchers first discovered that germ-free mice produced substantially less serotonin than normal mice in their colons, but not in the small intestines, suggesting the importance of the colon microbiome in serotonin production. The scientists then investigated the levels of each enzyme responsible for serotonin production and pinpointed one called TPH1 that was produced at much lower levels in the germ free mice colons. When the germ-free mice were given TPH1 their serotonin levels returned to normal, and when regular mice were given antibiotics their serotonin levels dropped. Taken together, this suggests that the colon microbiome somehow increase TPH1 levels in the gut.

The researchers then investigated the effects that specific bacteria had on increasing serotonin levels in germ free mice and discovered that spore forming bacteria, especially those belonging to Clostridia, were able to increase the levels of serotonin in the mice. After, they tried to determine specific metabolites that may be produced by Clostridia that increase TPH1 production. They found that deoxycholate, a-tocopherol, p-aminobenzoate, and tyramine all increased serotonin to normal levels when given to germ free mice.

Finally, the scientists colonized germ-free mice with spore producing bacteria and measured the effects on certain traits known to be associated with serotonin. For example, germ free mice colonized with spore producing bacteria had longer food transit times and more frequent bowel movements. In addition, blood platelets function better in mice colonized with spore forming bacteria than in germ-free mice.

Overall this work shows an important connection between serotonin production and the microbiome. Serotonin has been implicated with many critical bodily functions, like bone development, appetite control, heart function, and mental well-being. The fact that a dysbiosis in the microbiome may be responsible for lowering its levels may turn out to be crucial in developing next generation therapeutics.