title: Activated fluid transport regulates bacterial-epithelial interactions and significantly shifts the murine colonic microbiome.
abstract: Within the intestinal mucosa, epithelial cells serve multiple functions to partition the lumen from the lamina propria. As part of their natural function, intestinal epithelial cells actively transport electrolytes with passive water movement as a mechanism for mucosal hydration. Here, we hypothesized that electrogenic Cl(-) secretion, and associated mucosal hydration, influences bacterial-epithelial interactions and significantly influences the composition of the intestinal microbiota. An initial screen of different epithelial secretagogues identified lubiprostone as the most potent agonist for which to define these principles. In in vitro studies using cultured T84 cells, lubiprostone decreased E. coli translocation in a concentration-dependent manner (p < 0.001) and decreased S. typhimurium internalization and translocation by as much as 71 ± 6% (p < 0.01). Such decreases in bacterial translocation were abolished by inhibition of electrogenic Cl(-) secretion and water transport using the Na/K/Cl(-) antagonist bumetanide (p < 0.01). Extensions of these findings to microbiome analysis in vivo revealed that lubiprostone delivered orally to mice fundamentally shifted the intestinal microbiota, with notable changes within the Firmicutes and Bacteroidetes phyla of resident colonic bacteria. Such findings document a previously unappreciated role for epithelial Cl(-) secretion and water transport in influencing bacterial-epithelial interactions and suggest that active mucosal hydration functions as a primitive innate epithelial defense mechanism.
authors.affiliation: Mucosal Inflammation Program, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Keely
authors.forename: Caleb J
authors.initials: CJ
authors.lastname: Kelly
authors.forename: Thomas
authors.initials: T
authors.lastname: Weissmueller
authors.forename: Adrianne
authors.initials: A
authors.lastname: Burgess
authors.forename: Brandie D
authors.initials: BD
authors.lastname: Wagner
authors.forename: Charles E
authors.initials: CE
authors.lastname: Robertson
authors.forename: J Kirk
authors.initials: JK
authors.lastname: Harris
authors.forename: Sean P
authors.initials: SP
authors.lastname: Colgan
mesh_terms: D000284:Administration, Oral; D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification; D018988:Bacterial Translocation; D044822:Biodiversity; D001826:Body Fluids / Q000378:metabolism*; D002460:Cell Line; D065101:Chloride Channel Agonists; D002713:Chlorine / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology*; D000068238:Lubiprostone; D051379:Mice; D008810:Mice, Inbred C57BL; D014867:Water / Q000378:metabolism
chemical_list: D065101:Chloride Channel Agonists; D004573:Electrolytes; D014867:Water; D002713:Chlorine; D000068238:Lubiprostone; D000527:Alprostadil