Abstract
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.
Highlights
Enterochromaffin (EC) cells are located within the gut epithelia and store the largest pool of serotonin (5-hydroxytryptamine: 5-HT) in the body [1,2,3]
The presence of substantial contaminants inhibited the precise evaluation of luminal catecholamine-related metabolite levels; luminal 5-HT could be clearly identified as a unique peak
In support of this interaction, the present study showed that EX-GF mice, which were GF mice reconstituted with specific pathogen-free (SPF) microbiota, had higher levels of luminal 5-HT in the cecum and colon, as well as whole-colon 5-HT levels compared with the GF mice
Summary
Enterochromaffin (EC) cells are located within the gut epithelia and store the largest pool of serotonin (5-hydroxytryptamine: 5-HT) in the body [1,2,3]. A significant amount of 5-HT is released into the gut lumen in response to various stimuli [1, 4,5,6,7]. EC cells release 5-HT into the lumen in response to mechanical stimuli on the side of the gut mucosa, which enhances peristaltic reflexes [5, 8, 9]. The influence of the gut microbiota on various aspects of human health and diseases has become a hot topic in the field of medical research.
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