title: Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier.
abstract: Production of short-chain fatty acids (SCFA) in the intestinal lumen may play an important role in the maintenance of the intestinal barrier. However, overproduction/accumulation of SCFA in the bowel may be toxic to the intestinal mucosa and has been hypothesized to play a role in the pathogenesis of neonatal necrotizing enterocolitis (NEC). By using a Caco-2 cell monolayer model of intestinal barrier, we report here that the effect of butyrate on the intestinal barrier is paradoxical. Butyrate at a low concentration (2 mM) promotes intestinal barrier function as measured by a significant increase in transepithelial electrical resistance (TER) and a significant decrease in inulin permeability. Butyrate at a high concentration (8 mM) reduces TER and increases inulin permeability significantly. Butyrate induces apoptosis and reduces the number of viable Caco-2 cells in a dose-dependent manner. Intestinal barrier function impairment induced by high concentrations of butyrate is most likely related to butyrate-induced cytotoxicity due to apoptosis. We conclude that the effect of butyrate on the intestinal barrier is paradoxical; i.e. whereas low concentrations of butyrate may be beneficial in promoting intestinal barrier function, excessive butyrate may induce severe intestinal epithelial cell apoptosis and disrupt intestinal barrier.
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Luying
authors.initials: L
authors.lastname: Peng
authors.forename: Zhenjuan
authors.initials: Z
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Ian R
authors.initials: IR
authors.lastname: Holzman
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects*; D007444:Inulin / Q000378:metabolism; D008954:Models, Biological; D010539:Permeability / Q000187:drug effects
chemical_list: D002087:Butyrates; D007444:Inulin