title: Correlated gene expression encoding serotonin (5-HT) receptor 4 and 5-HT transporter in proximal colonic segments of mice across different colonization states and sexes.
abstract: The production and handling of serotonin (5-HT) is an important determinant of colonic motility and has been reported to be altered in gastrointestinal (GI) disorders such as irritable bowel syndrome (IBS). Recent studies suggest that the intestinal microbiota and sex of the host can influence expression of genes involved in 5-HT biosynthesis and signaling. While expression of genes in serotonergic pathways has been shown to be variable, it remains unclear whether genes within this pathway are coregulated. As a first step in that direction, we investigated potential correlations in relative mRNA expression of serotonergic genes, in the proximal colon isolated from male and female mice in different states of microbial association: germ-free (GF), humanized (ex-germ-free colonized with human gut microbiota, HM), and conventionally raised (CR) mice. Among the 10 pairwise comparisons conducted between five serotonergic transcripts, Tph1, Chga, Maoa, Slc6a4, and Htr4, we found a strong, positive correlation between colonic expression of Slc6a4 and Htr4 across different colonization states and sexes. We also identified a positive correlation between the expression of Tph1 and Chga; however, there were no correlations observed between any other tested pair of 5-HT-related transcripts. These data suggest that correlated expression of Slc6a4 and Htr4 likely involves coregulation of genes located on different chromosomes which modulate serotonergic activity in the gut. Further work will need to be done to understand the pathways and cell types responsible for this correlated expression, given the important role of 5-HT in gastrointestinal physiology.
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.|Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.|Department of Natural Sciences and Geography, Concordia University Chicago, River Forest, IL, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Reigstad
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Linden
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.|Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Szurszewski
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Sonnenburg
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.|Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
authors.forename: G
authors.initials: G
authors.lastname: Farrugia
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.|Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.|Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Kashyap
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D043183:Irritable Bowel Syndrome / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D044422:Receptors, Serotonin, 5-HT4
keywords: Htr4; SERT; Slc6a4; Tph1; microbiota; visceral hypersensitivity