FODMAP availability modulates the influence of the microbiota on visceral afferent neuron activation
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Authors
Baker, Corey
Date
Type
thesis
Language
eng
Keyword
Microbiota , Pain , IBS , FODMAP , Protease
Alternative Title
Abstract
Abdominal pain is commonly observed in gastrointestinal diseases such as irritable bowel syndrome (IBS). However, it is unclear what role the microbiota plays in the development of abdominal pain. It has been shown that fecal samples from IBS patients excites afferent nerves, but when the same patients are placed on a low fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) diet the fecal samples cause inhibition. It is not clear whether these effects were driven by host derived or bacterial mediators. It was hypothesized that culturing stool microbial communities from IBS patients in vitro will help discriminate between microbial and host contributions to the development of visceral pain by removing host contributions entirely. The fecal cultures were exposed to low concentrations of FODMAPs to simulate a low FODMAP diet, a common treatment for IBS symptoms, to determine whether a reduction of FODMAPs alters production of bacterial neuroactive mediators in vitro. The culture supernatant was collected and perfused through murine colonic preparations while the activation of spinal afferent axons within the mesentery was recorded using extracellular electrodes. Afferent nerve recordings showed no difference between the effects of the original patient stool supernatant and the supernatant obtained after 15 days in culture (N=3 IBS patients). This suggests the cultured stool bacteria produce similar mediators to those contained in the original IBS patient stool samples. When the FODMAP content of the media was reduced, the culture supernatant reduced action potential discharge by 40% (p=0.0008) compared to discharge during a control distention. This inhibitory effect was blocked by intraluminal perfusion of the protease activated receptor 4 antagonist ML354 (10µM). This work suggests that a popular dietary therapy for IBS may act by altering gut microbiota metabolite secretion.
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This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivs 3.0 United States
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivs 3.0 United States