3 years ago

Regulation of gut luminal serotonin by commensal microbiota in mice

Xue-Ting Zhang, Yasuhiro Koga, Tomokazu Hata, Nobuyuki Sudo, Noriyuki Miyata, Kazufumi Yoshihara, Shu Takakura, Yuji Aiba, Tae Kimura-Todani, Yasunari Asano

by Tomokazu Hata, Yasunari Asano, Kazufumi Yoshihara, Tae Kimura-Todani, Noriyuki Miyata, Xue-Ting Zhang, Shu Takakura, Yuji Aiba, Yasuhiro Koga, Nobuyuki Sudo

Gut lumen serotonin (5-hydroxytryptamine: 5-HT) contributes to several gastrointestinal functions such as peristaltic reflexes. 5-HT is released from enterochromaffin (EC) cells in response to a number of stimuli, including signals from the gut microbiota. However, the specific mechanism by which the gut microbiota regulates 5-HT levels in the gut lumen has not yet been clarified. Our previous work with gnotobiotic mice showed that free catecholamines can be produced by the deconjugation of conjugated catecholamines; hence, we speculated that deconjugation by bacterial enzymes may be one of the mechanisms whereby gut microbes can produce free 5-HT in the gut lumen. In this study, we tested this hypothesis using germ-free (GF) mice and gnotobiotic mice recolonized with specific pathogen-free (SPF) fecal flora (EX-GF). The 5-HT levels in the lumens of the cecum and colon were significantly lower in the GF mice than in the EX-GF mice. Moreover, these levels were rapidly increased, within only 3 days after exposure to SPF microbiota. The majority of 5-HT was in an unconjugated, free form in the EX-GF mice, whereas approximately 50% of the 5-HT was found in the conjugated form in the GF mice. These results further support the current view that the gut microbiota plays a crucial role in promoting the production of biologically active, free 5-HT. The deconjugation of glucuronide-conjugated 5-HT by bacterial enzymes is likely one of the mechanisms contributing to free 5-HT production in the gut lumen.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.pone.0180745

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