Journal
FASEB JOURNAL
Volume 29, Issue 4, Pages 1395-1403Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.14-259598
Keywords
5-hydroxytryptamine; gnotobiotic; gut motility; host-microbe interaction; microbiome
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Funding
- U.S. National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [K08 DK100638, P30DK84567, R01 DK085025]
- Global Probiotic Council
- Minnesota Partnership for Biotechnology and Genomics
- Center for Individualized Medicine, Mayo Clinic
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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 gutmicrobiota). 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.
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