title: Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells.
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.
authors.affiliation: *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.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Reigstad
authors.affiliation: *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.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Salmonson
authors.affiliation: *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.
authors.forename: John F
authors.initials: JF
authors.lastname: Rainey
authors.affiliation: *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.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Szurszewski
authors.affiliation: *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.
authors.forename: David R
authors.initials: DR
authors.lastname: Linden
authors.affiliation: *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.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Sonnenburg
authors.affiliation: *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.
authors.forename: Gianrico
authors.initials: G
authors.lastname: Farrugia
authors.affiliation: *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.
authors.forename: Purna C
authors.initials: PC
authors.lastname: Kashyap
mesh_terms: D000818:Animals; D002452:Cell Count; D002460:Cell Line; D053379:Chromogranin A / Q000235:genetics; D003106:Colon / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D004064:Digestive System / Q000382:microbiology*; D004759:Enterochromaffin Cells / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005260:Female; D005769:Gastrointestinal Motility; D005856:Germ-Free Life; D006801:Humans; D008297:Male; D051379:Mice; D064307:Microbiota; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis*; D015398:Signal Transduction; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D053379:Chromogranin A; D005232:Fatty Acids, Volatile; D012333:RNA, Messenger; C506155:chromogranin A, mouse; D012701:Serotonin; C497467:TPH1 protein, human; C487801:Tph1 protein, mouse; D014365:Tryptophan Hydroxylase
keywords: 5-hydroxytryptamine; gnotobiotic; gut motility; host-microbe interaction; microbiome