Effects of the Gut Microbiota on Intestinal Function

Abstract

A growing emphasis has been placed on the importance of the gut-brain axis (GBA) and its role in normal physiological functions of the body. This bidirectional axis links cognitive functions of the central nervous system (CNS) with a number of peripheral intestinal functions such as intestinal permeability, immune activation, and neuro-endocrine signalling. Studies have highlighted the possibility that the intestinal microbiota could influence the function of the gut-brain axis; however, mechanisms underlying these interactions are currently unknown. In hopes of better understanding how the microbiome may play a role in altering the gut-brain axis, I studied the epithelial barrier of the gut, as it acts as the interface between the microbiome and the gut-brain axis. I investigated whether disrupting the microbiome in vivo with antibiotics, and mimicking a healthy microbiome through the application of a commensal bacterial community (microbial ecosystems therapeutics-1; MET-1) can modulate epithelial barrier functions. Using Ussing chambers, I investigated changes in colonic mucosal epithelial permeability in vitro in both antibiotic-treated animals and following the local application of MET-1 (1:1000). Additionally, I examined the effect of antibiotic treatment on paracellular permeability and intestinal transit in vivo, serotonin bioavailability, epithelial ion secretion, and neurotransmission. Paracellular permeability of the colon was significantly increased in vivo following a 7-day vancomycin treatment, and Veratridine-stimulated (30 µM) ion secretion was significantly diminished in colonic tissue of mice subjected to the treatment compared to controls. Apical application of MET-1 did not enhance epithelial barrier function in vitro. Moreover, no differences in intestinal motility, serotonin bioavailability, and ion secretion were found between antibiotic-treated animals and controls. These results indicate that the modulation of host microbiota leads to changes in mucosal permeability and Veratridine-stimulated ion secretion, which may facilitate the access of microbial metabolites to the nervous system.