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 deconjugate host-produced catecholamines via the β-glucuronidase enzyme pathway, and thus generate free luminal 5-HT.
“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
The Introduction and Discussion say bacterial β-glucuronidase deconjugates catecholamines, but they describe free luminal 5-HT as arising, in part, from deconjugation of 5-HT-O-glucuronide—not from catecholamines. The Results support a microbial contribution to free luminal 5-HT in mice, while the specific deconjugation mechanism remains a proposed explanation. (LLM, conf=0.89)
Experimental — accuracy not yet measured5-HT concentrations in the cecal and colonic lumens are significantly reduced in GF mice.
“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
In GF mice, conjugated biologically inactive 5-HT is found at a higher percentage, whereas unconjugated biologically active 5-HT is found in greater concentration in conventionalized GF mice.
“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
The gut microbiota impact the host GI serotonergic system.
“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
Conventionalization of GF mice with a microbiota increases intestinal luminal 5-HT concentrations.
“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
In a rodent study, mice without an enteric microbiome had only half the amount of serotonin in the circulation compared to mice with normal gut microbiota.
“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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- 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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