Depletion of murine microbiota with broad‐spectrum antibiotics alters intestinal motility, secretion, and mucosal barrier function

Abstract

The commensal microbiota in the gut coevolved with the mammalian host and is essential for many host physiological processes. Alterations in the composition of gut microbiota seem to be a pathogenic component of functional gastrointestinal disorders. The aim of this study is to investigate if a state of antibiotics‐induced intestinal dysbiosis is able to modify intestinal motility, secretion, and mucosal barrier function. C57BL/6 mice received a broad‐spectrum antibiotic cocktail (ampicillin 25mg/kg, vancomycin 10mg/kg, neomycin 25 mg/kg, and metronidazole 25 mg/kg) by oral gavage once a day for two weeks. Gastrointestinal transit was measured using a charcoal meal method. Ussing chamber techniques were used to assess colonic mucosal ion secretion and transepithelial electrical resistance (TER). Intestinal permeability to macromolecules was assessed by the flux of horseradish peroxidase (HRP, 44kD) from mucosa to serosa side of the colonic mucosa/submucosa preparations. Two weeks of antibiotics treatment delayed gastrointestinal transit. Colonic baseline ion secretion was increased in antibiotics‐treated mice. Antibiotics treatment also caused a dramatic increase in intestinal permeability, which was indicated by a significant reduction of TER and an increase in HRP flux from mucosa to serosa side of the colon. The results of this study suggest that depletion of intestinal microbiota with broad‐spectrum antiobiotics reduces gastrointestinal motility, enhances colonic ion secretion, and impairs mucosal barrier function and may contribute to functional gastrointestinal disorders.Support or Funding InformationNIH R15 DK097460‐01A1 (SL) and UW‐L undergraduate research grant (JL)