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Irritable Bowel Syndrome: HELP
Articles by Eric W. Klee
Based on 3 articles published since 2010
(Why 3 articles?)
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Between 2010 and 2020, Eric W. Klee wrote the following 3 articles about Irritable Bowel Syndrome.
 
+ Citations + Abstracts
1 Article Pilot study of small bowel mucosal gene expression in patients with irritable bowel syndrome with diarrhea. 2016

Camilleri, Michael / Carlson, Paula / Valentin, Nelson / Acosta, Andres / O'Neill, Jessica / Eckert, Deborah / Dyer, Roy / Na, Jie / Klee, Eric W / Murray, Joseph A. ·Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and camilleri.michael@mayo.edu. · Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota; and. · 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. ·Am J Physiol Gastrointest Liver Physiol · Pubmed #27445342.

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.

2 Article RNA sequencing shows transcriptomic changes in rectosigmoid mucosa in patients with irritable bowel syndrome-diarrhea: a pilot case-control study. 2014

Camilleri, Michael / Carlson, Paula / Acosta, Andres / Busciglio, Irene / Nair, Asha A / Gibbons, Simon J / Farrugia, Gianrico / Klee, Eric W. ·Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) and camilleri.michael@mayo.edu. · Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) and. · Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. ·Am J Physiol Gastrointest Liver Physiol · Pubmed #24763552.

ABSTRACT: Our aim was to conduct a pilot case-control study of RNA expression profile using RNA sequencing of rectosigmoid mucosa of nine females with -diarrhea-predominant irritable bowel syndrome (IBS-D) with accelerated colonic transit and nine female healthy controls. Mucosal total RNA was isolated and purified, and next-generation pair-end sequencing was performed using Illumina TruSeq. Analysis was carried out using a targeted approach toward 12 genes previously associated with IBS and a hypothesis-generating approach. Of the 12 targeted genes tested, patients with IBS-D had decreased mRNA expression of TNFSF15 (fold change controls to IBS-D: 1.53, P = 0.01). Overall, up- and downregulated mRNA expressions of 21 genes (P = 10(-5) to 10(-8); P values with false detection rates are shown) were potentially relevant to IBS-D including the following: neurotransmitters [P2RY4 (P = 0.001), vasoactive intestinal peptide (VIP, P = 0.02)]; cytokines [CCL20 (P = 0.019)]; immune function [C4BPA complement cascade (P = 0.0187)]; interferon-related [IFIT3 (P = 0.016)]; mucosal repair and cell adhesion [trefoil protein (TFF1, P = 0.012)], retinol binding protein [RBP2 (P = 0.017)]; fibronectin (FN1, P = 0.009); and ion channel functions [guanylate cyclase (GUCA2B, P = 0.017), PDZ domain-containing protein 3 (PDZD3, P = 0.029)]. Ten genes associated with functions related to pathobiology of IBS-D were validated by RT-PCR. There was significant correlation in fold changes of the selected genes (Rs = 0.73, P = 0.013). Up- or downregulation of P2RY4, GUC2AB, RBP2, FNI, and C4BPA genes were confirmed on RT-PCR, which also revealed upregulation of farnesoid X receptor (FXR) and apical sodium-coupled bile acid transporter (IBAT/ASBT). RNA-Seq and RT-PCR analysis of rectosigmoid mucosa in IBS-D show transcriptome changes that provide the rationale for validation studies to explore the role of mucosal factors in the pathobiology of IBS-D.

3 Article Irritable bowel syndrome-diarrhea: characterization of genotype by exome sequencing, and phenotypes of bile acid synthesis and colonic transit. 2014

Camilleri, Michael / Klee, Eric W / Shin, Andrea / Carlson, Paula / Li, Ying / Grover, Madhusudan / Zinsmeister, Alan R. ·Mayo Clinic, Charlton 8-110, 200 First St. S.W., Rochester, MN 55905. camilleri.michael@mayo.edu. ·Am J Physiol Gastrointest Liver Physiol · Pubmed #24200957.

ABSTRACT: The study objectives were: to mine the complete exome to identify putative rare single nucleotide variants (SNVs) associated with irritable bowel syndrome (IBS)-diarrhea (IBS-D) phenotype, to assess genes that regulate bile acids in IBS-D, and to explore univariate associations of SNVs with symptom phenotype and quantitative traits in an independent IBS cohort. Using principal components analysis, we identified two groups of IBS-D (n = 16) with increased fecal bile acids: rapid colonic transit or high bile acids synthesis. DNA was sequenced in depth, analyzing SNVs in bile acid genes (ASBT, FXR, OSTα/β, FGF19, FGFR4, KLB, SHP, CYP7A1, LRH-1, and FABP6). Exome findings were compared with those of 50 similar ethnicity controls. We assessed univariate associations of each SNV with quantitative traits and a principal components analysis and associations between SNVs in KLB and FGFR4 and symptom phenotype in 405 IBS, 228 controls and colonic transit in 70 IBS-D, 71 IBS-constipation. Mining the complete exome did not reveal significant associations with IBS-D over controls. There were 54 SNVs in 10 of 11 bile acid-regulating genes, with no SNVs in FGF19; 15 nonsynonymous SNVs were identified in similar proportions of IBS-D and controls. Variations in KLB (rs1015450, downstream) and FGFR4 [rs434434 (intronic), rs1966265, and rs351855 (nonsynonymous)] were associated with colonic transit (rs1966265; P = 0.043), fecal bile acids (rs1015450; P = 0.064), and principal components analysis groups (all 3 FGFR4 SNVs; P < 0.05). In the 633-person cohort, FGFR4 rs434434 was associated with symptom phenotype (P = 0.027) and rs1966265 with 24-h colonic transit (P = 0.066). Thus exome sequencing identified additional variants in KLB and FGFR4 associated with bile acids or colonic transit in IBS-D.