title: Genotype-dependency of butyrate efficacy in children with congenital chloride diarrhea.
abstract: BACKGROUND
  Congenital chloride diarrhea (CLD) is an autosomal recessive disorder characterized by life-long, severe diarrhea with intestinal Cl- malabsorption. It results from a reduced activity of the down regulated in adenoma exchanger (DRA), due to mutations in the solute carrier family 26, member 3 (SLC26A3) gene. Currently available therapies are not able to limit the severity of diarrhea in CLD. Conflicting results have been reported on the therapeutic efficacy of oral butyrate.
  
  
  METHODS
  We investigated the effect of oral butyrate (100 mg/kg/day) in seven CLD children with different SLC26A3 genotypes. Nasal epithelial cells were obtained to assess the effect of butyrate on the expression of the two main Cl- transporters: DRA and putative anion transporter-1 (PAT-1).
  
  
  RESULTS
  A variable clinical response to butyrate was observed regarding the stool pattern and fecal ion loss. The best response was observed in subjects with missense and deletion mutations. Variable response to butyrate was also observed on SLC26A3 (DRA) and SLC26A6 (PAT1) gene expression in nasal epithelial cells of CLD patients.
  
  
  CONCLUSIONS
  We demonstrate a genotype-dependency for butyrate therapeutic efficacy in CLD. The effect of butyrate is related in part on a different modulation of the expression of the two main apical membrane Cl- exchangers of epithelial cells, members of the SLC26 anion family.
  
  
  BACKGROUND
  Australian New Zealand Clinical trial Registry ACTRN12613000450718.
authors.affiliation: Department of Translational Medical Science - Pediatric Section, and European Laboratory for the Investigation of Food Induced Diseases, University of Naples, "Federico II" Via S, Pansini, 5 80131 Naples, Italy. berni@unina.it.
authors.forename: Roberto Berni
authors.initials: RB
authors.lastname: Canani
authors.forename: Gianluca
authors.initials: G
authors.lastname: Terrin
authors.forename: Ausilia
authors.initials: A
authors.lastname: Elce
authors.forename: Vincenza
authors.initials: V
authors.lastname: Pezzella
authors.forename: Peter
authors.initials: P
authors.lastname: Heinz-Erian
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pedrolli
authors.forename: Chiara
authors.initials: C
authors.lastname: Centenari
authors.forename: Felice
authors.initials: F
authors.lastname: Amato
authors.forename: Rossella
authors.initials: R
authors.lastname: Tomaiuolo
authors.forename: Antonio
authors.initials: A
authors.lastname: Calignano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Troncone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castaldo
mesh_terms: D000293:Adolescent; D002087:Butyrates / Q000627:therapeutic use*; D002648:Child; D027963:Chloride-Bicarbonate Antiporters / Q000235:genetics; D003967:Diarrhea / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008661:Metabolism, Inborn Errors / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D000076988:Sulfate Transporters
chemical_list: D002087:Butyrates; D027963:Chloride-Bicarbonate Antiporters; D026901:Membrane Transport Proteins; C081011:SLC26A3 protein, human; C439529:SLC26A6 protein, human; D000076988:Sulfate Transporters