title: Lubiprostone decreases mouse colonic inner mucus layer thickness and alters intestinal microbiota.
abstract: BACKGROUND
  Lubiprostone has been used to treat constipation through its effects to stimulate Cl(-) secretion, resulting in water and electrolyte secretion.
  
  
  OBJECTIVE
  Potential associated changes in intestinal mucus and the colonizing bacteria (microbiome) have not been studied. As mucus obstructions may play a role in cystic fibrosis, the hypothesis that lubiprostone alters intestinal mucus and the microbiome was investigated.
  
  
  METHODS
  Ion transport studies were performed ex vivo. For mucus and microbiome studies, mice were gavaged daily with lubiprostone or vehicle. Mucin from intestinal sections was analyzed in Carnoy's fixed tissues stained with Alcian blue. Microbiome composition was analyzed by 16S rRNA gene-based sequencing.
  
  
  RESULTS
  Lubiprostone stimulated short circuit current in all mouse intestinal segments after both serosal and mucosal additions, albeit at lower concentrations in the latter. Current was Cl-dependent and blocked by mucosal diphenylcarboxylic acid, serosal bumetanide, and serosal Ba(++). The CFTR inhibitor CFTRinh172 had a marginal effect. Mucus near epithelial cells (inner layer mucus) was not present in the small intestine of any mice. Proximal colon inner mucus layer was thicker in ∆F/∆F compared with +/∆F and +/+ mice. Lubiprostone decreased inner mucus layer thickness in both proximal and distal colon of all mice. Furthermore, lubiprostone altered the intestinal microbiome by increasing abundance of Lactobacillus and Alistipes.
  
  
  CONCLUSIONS
  Lubiprostone activates non-CFTR Cl(-) secretion and alters the colonic inner mucus layer, which is associated with changes in the composition of the enteric microbiome.
authors: Division of Biological Sciences, Department of Medicine, The University of Chicago, 900 E. 57th St., Chicago, IL 60637, USA.
authors: Mark W
authors: MW
authors: Musch
authors: Yunwei
authors: Y
authors: Wang
authors: Erika C
authors: EC
authors: Claud
authors: Eugene B
authors: EB
authors: Chang
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism; D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D003106:Colon / Q000187:drug effects* / Q000382:microbiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D000068238:Lubiprostone; D051379:Mice; D018181:Mice, Inbred CFTR; D010802:Phylogeny; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism
chemical_list: D000838:Anions; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000068238:Lubiprostone; D000527:Alprostadil