title: Impaired butyrate oxidation in ulcerative colitis is due to decreased butyrate uptake and a defect in the oxidation pathway.
abstract: BACKGROUND
  In ulcerative colitis (UC) butyrate metabolism is impaired due to a defect in the butyrate oxidation pathway and/or transport. In the present study we correlated butyrate uptake and oxidation to the gene expression of the butyrate transporter SLC16A1 and the enzymes involved in butyrate oxidation (ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2) in UC and controls.
  
  
  METHODS
  Colonic mucosal biopsies were collected during endoscopy of 88 UC patients and 20 controls with normal colonoscopy. Butyrate uptake and oxidation was measured by incubating biopsies with (14) C-labeled Na-butyrate. To assess gene expression, total RNA from biopsies was used for quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In 20 UC patients, gene expression was reassessed after treatment with infliximab.
  
  
  RESULTS
  Butyrate uptake and oxidation were significantly decreased in UC versus controls (P < 0.001 for both). Butyrate oxidation remained significantly reduced in UC after correction for butyrate uptake (P < 0.001), suggesting that the butyrate oxidation pathway itself is also affected. Also, the mucosal gene expression of SLC16A1, ACSM3, ACADS, ECHS1, HSD17B10, and ACAT2 was significantly decreased in UC as compared with controls (P < 0.001 for all). In a subgroup of patients (n = 20), the gene expression was reassessed after infliximab therapy. In responders to therapy, a significant increase in gene expression was observed. Nevertheless, only ACSM3 mRNA levels returned to control values after therapy in the responders groups.
  
  
  CONCLUSIONS
  The deficiency in the colonic butyrate metabolism in UC is initiated at the gene expression level and is the result of a decreased expression of SLC16A1 and enzymes in the β-oxidation pathway of butyrate.
authors: Translational Research Center for Gastrointestinal Disorders (TARGID) and Leuven Food Science and Nutrition Research Centre (LFoRCe), University Hospital Gasthuisberg, K.U. Leuven, Leuven, Belgium.
authors: Vicky
authors: V
authors: De Preter
authors: Ingrid
authors: I
authors: Arijs
authors: Karen
authors: K
authors: Windey
authors: Wiebe
authors: W
authors: Vanhove
authors: Severine
authors: S
authors: Vermeire
authors: Frans
authors: F
authors: Schuit
authors: Paul
authors: P
authors: Rutgeerts
authors: Kristin
authors: K
authors: Verbeke
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism*; D002087:Butyrates / Q000737:chemistry* / Q000378:metabolism*; D016022:Case-Control Studies; D003066:Coenzyme A Ligases / Q000235:genetics / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003113:Colonoscopy; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002785:Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D000097587:Sterol O-Acyltransferase 2; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D002087:Butyrates; D003066:Coenzyme A Ligases; D000069285:Infliximab; D027501:Monocarboxylic Acid Transporters; D012333:RNA, Messenger; D002785:Sterol O-Acyltransferase; D027981:Symporters; D000097587:Sterol O-Acyltransferase 2; D000099233:Monocarboxylate Transport Protein 1; C108634:HSD17B10 protein, human; C487181:ACSM3 protein, human