title: Pilot study of small bowel mucosal gene expression in patients with irritable bowel syndrome with diarrhea.
abstract: Prior studies in with irritable bowel syndrome with diarrhea (IBS-D) patients showed immune activation, secretion, and barrier dysfunction in jejunal or colorectal mucosa. We measured mRNA expression by RT-PCR of 91 genes reflecting tight junction proteins, chemokines, innate immunity, ion channels, transmitters, housekeeping genes, and controls for DNA contamination and PCR efficiency in small intestinal mucosa from 15 IBS-D and 7 controls (biopsies negative for celiac disease). Fold change was calculated using 2((-ΔΔCT)) formula. Nominal P values (P < 0.05) were interpreted with false detection rate (FDR) correction (q value). Cluster analysis with Lens for Enrichment and Network Studies (LENS) explored connectivity of mechanisms. Upregulated genes (uncorrected P < 0.05) were related to ion transport (INADL, MAGI1, and SONS1), barrier (TJP1, 2, and 3 and CLDN) or immune functions (TLR3, IL15, and MAPKAPK5), or histamine metabolism (HNMT); downregulated genes were related to immune function (IL-1β, TGF-β1, and CCL20) or antigen detection (TLR1 and 8). The following genes were significantly upregulated (q < 0.05) in IBS-D: INADL, MAGI1, PPP2R5C, MAPKAPK5, TLR3, and IL-15. Among the 14 nominally upregulated genes, there was clustering of barrier and PDZ domains (TJP1, TJP2, TJP3, CLDN4, INADL, and MAGI1) and clustering of downregulated genes (CCL20, TLR1, IL1B, and TLR8). Protein expression of PPP2R5C in nuclear lysates was greater in patients with IBS-D and controls. There was increase in INADL protein (median 9.4 ng/ml) in patients with IBS-D relative to controls (median 5.8 ng/ml, P > 0.05). In conclusion, altered transcriptome (and to lesser extent protein) expression of ion transport, barrier, immune, and mast cell mechanisms in small bowel may reflect different alterations in function and deserves further study in IBS-D.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and camilleri.michael@mayo.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Paula
authors.initials: P
authors.lastname: Carlson
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Nelson
authors.initials: N
authors.lastname: Valentin
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Andres
authors.initials: A
authors.lastname: Acosta
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Jessica
authors.initials: J
authors.lastname: O'Neill
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Deborah
authors.initials: D
authors.lastname: Eckert
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Roy
authors.initials: R
authors.lastname: Dyer
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and Division of Biomedical Statistic and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jie
authors.initials: J
authors.lastname: Na
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and Division of Biomedical Statistic and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Klee
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Murray
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003967:Diarrhea / Q000209:etiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000378:metabolism*; D008297:Male; D010865:Pilot Projects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger
keywords: barrier; cytokines; immune; secretion