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FASEB J. 2015 Apr;29(4):1395-403. doi: 10.1096/fj.14-259598. Epub 2014 Dec 30.

Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells.

Author information

1
*Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA; and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
2
*Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA; and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA kashyap.purna@mayo.edu.

Abstract

Gut microbiota alterations have been described in several diseases with altered gastrointestinal (GI) motility, and awareness is increasing regarding the role of the gut microbiome in modulating GI function. Serotonin [5-hydroxytryptamine (5-HT)] is a key regulator of GI motility and secretion. To determine the relationship among gut microbes, colonic contractility, and host serotonergic gene expression, we evaluated mice that were germ-free (GF) or humanized (HM; ex-GF colonized with human gut microbiota). 5-HT reduced contractile duration in both GF and HM colons. Microbiota from HM and conventionally raised (CR) mice significantly increased colonic mRNAs Tph1 [(tryptophan hydroxylase) 1, rate limiting for mucosal 5-HT synthesis; P < 0.01] and chromogranin A (neuroendocrine secretion; P < 0.01), with no effect on monoamine oxidase A (serotonin catabolism), serotonin receptor 5-HT4, or mouse serotonin transporter. HM and CR mice also had increased colonic Tph1 protein (P < 0.05) and 5-HT concentrations (GF, 17 ± 3 ng/mg; HM, 25 ± 2 ng/mg; and CR, 35 ± 3 ng/mg; P < 0.05). Enterochromaffin (EC) cell numbers (cells producing 5-HT) were unchanged. Short-chain fatty acids (SCFAs) promoted TPH1 transcription in BON cells (human EC cell model). Thus, gut microbiota acting through SCFAs are important determinants of enteric 5-HT production and homeostasis.

KEYWORDS:

5-hydroxytryptamine; gnotobiotic; gut motility; host-microbe interaction; microbiome

PMID:
25550456
PMCID:
PMC4396604
DOI:
10.1096/fj.14-259598
[Indexed for MEDLINE]
Free PMC Article

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