A58 ALTERATIONS IN INTESTINAL MOTILITY AND BARRIER FUNCTION AFTER ANTIBIOTIC TREATMENT IN MALE AND FEMALE MICE: THE ROLE OF ENTERIC GLIA

BACKGROUND: Recent studies suggest that the gut microbiota may contribute to the regulation of gastrointestinal (GI) motility. Alterations in motility are commonly associated with gastrointestinal disorders, which are linked to intestinal dysbiosis. However, the mechanisms through which the microbiota regulates GI motility remain to be fully characterized. It has recently been reported that the distribution of enteric glial cells (EGC) are altered in the context of changes in the microbiota. AIMS: Given the role that EGC play in contributing to modulation of gut motility, we hypothesized that alterations in the microbiota may trigger dysmotility through altering EGC distribution and/or function. METHODS: To test this hypothesis, we depleted the intestinal microbiota in adult C57Bl/6 mice (male and female) administering antibiotics (ABX) for three weeks, and subsequently assessed gut motility through assays including: quantifying fecal pellet output; measuring whole gut and small intestine transit time (Evan’s blue dye); and assessing colonic bead propulsion. Intestinal permeability was assessed using fluorescein sulfonic acid (FSA). Lastly, EGC morphology and distribution was assessed by immunohistochemistry using an anti-S100β antibody. RESULTS: We observed an increase in whole gut transit time in the ABX-treated male and female mice. Both male and female ABX-treated mice exhibited an increased small intestinal transit time, with no alterations in motility of the colon. The number of fecal pellets expelled per hour was not affected by ABX treatment, however, this regimen led to a greater water content in the fecal pellets. Intestinal permeability was equally increased in ABX-treated mice of both sexes. Finally, to our surprise we found no differences in the morphology or distribution of EGC in the mucosa or myenteric plexus of ABX-treated mice. CONCLUSIONS: In summary, depletion of gut microbiota led to alterations in motility in both male and female mice. The increased whole gut transit time in ABX-treated mice was associated with increased small intestinal transit time, however, we cannot rule out the contribution of changes in gastric emptying at this time. While the motility and permeability changes were striking in ABX-treated mice, we found no associated changes in the distribution of EGC. Further investigation is required to identify the underlying mechanisms through which the microbiota regulates intestinal motility and whether ABX treatment altered the function of EGC. FUNDING AGENCIES: CIHRNational Counsel of Technological and Scientific Development (CNPq – Brazil).