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Regulation of gut luminal serotonin by commensal microbiota in mice
Open accessAbstract
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.
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“gut bacteria were shown to deconjugate host-produced catecholamines via the β-glucuronidase enzyme pathway, and thus generate free luminal 5-HT (Asano et al., 2012;Hata et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hata et al., 2017
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“Likewise, 5-HT concentrations in the cecal and colonic lumens are significantly reduced in GF mice (Hata et al., 2017).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hata et al., 2017
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“Moreover, in the same study, the conjugated, biologically inactive form of 5-HT was found at a higher percentage in GF mice, whereas the unconjugated, biologically-active form of 5-HT was found in greater concentration in conventionalized GF mice.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hata et al., 2017
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“the gut microbiota are understood to impact the host GI serotonergic system (Hata et al., 2017;O'Mahony et al., 2015).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hata et al., 2017
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“The conventionalization of GF mice with a microbiota resulted in increased concentrations of intestinal luminal 5-HT.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Hata et al., 2017
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“In a rodent study, it was found that mice without an enteric microbiome had only half the amount of serotonin in the circulation when compared to mice with normal gut microbiota [48].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [48]
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Metadata
- Authors
- Hata, T., Asano, Y., Yoshihara, K., Kimura-Todani, T., Miyata, N., Zhang, X.-T., Takakura, S., Aiba, Y., Koga, Y., & Sudo, N.
- Affiliations
- Kyushu University (JP)
- Tokai University (JP)
- Corresponding author
- Sudo, Nobuyuki
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-07-06
- Volume
- 12
- Issue
- 7
- Pages
- e0180745
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5500371
- OpenAlex
- W2725296099
- Cited by
- 211
- References
- 39
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 26 · 2023: 22 · 2022: 30 · 2021: 35 · 2020: 33 · 2019: 30 · 2018: 9 · 2017: 2
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kyushu University Institutional Repository (QIR) (Kyushu University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (16H05278, 16K15413)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- commensal microbiota, enterochromaffin cells, serotonin, glucuronidation, bacterial enzymes, gnotobiotic mice, germ-free mice, fecal microbiota transplantation, gut-brain axis, peristalsis
- MeSH terms
- Animals, Chromatography, High Pressure Liquid, Germ-Free Life, Intestinal Mucosa, Intestines, Mice, Inbred BALB C, Serotonin, Reverse Transcriptase Polymerase Chain Reaction, Mice, Microbiota
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