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

Christopher S. Reigstad, Charles E. Salmonson, John F. Rainey, Joseph H. Szurszewski, David R. Linden, Justin L. Sonnenburg, Gianrico Farrugia, Purna C. Kashyap

Research output: Contribution to journalArticlepeer-review

389 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1395-1403
Number of pages9
JournalFASEB Journal
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • 5-hydroxytryptamine
  • Gnotobiotic
  • Gut motility
  • Host-microbe interaction
  • Microbiome

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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