The role of FODMAP-microbiota interactions in IBS-related visceral pain
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Authors
Ables, Samantha
Date
Type
thesis
Language
eng
Keyword
gut microbiota , irritable bowel syndrome , calcium imaging , clinical study , abdominal pain , dorsal root ganglia
Alternative Title
Abstract
Background: Irritable bowel syndrome (IBS) causes abdominal pain, which is more severe in females. IBS pathophysiology is multifactorial, including an altered gut microbiota composition and low-grade inflammation, which produces pro-nociceptive luminal mediators. Moreover, estrogen can increase inflammatory mediators and neuronal activity, potentially causing sex differences in IBS. In some IBS patients, a low FODMAP diet (LFD) or a Lactobacillus probiotic reduce symptoms. Both interventions can modulate the gut microbiota and low-grade inflammation, but whether this alters neuroactive luminal mediators to reduce abdominal pain is unclear. I hypothesize that 1) the LFD and Lactobacillus probiotic improve symptoms in IBS patients and reduce luminal mediator-induced neuronal activity and 2) female neurons are more susceptible to sensitization by luminal mediators.
Methods: IBS patients followed a LFD, then were challenged with i) a high FODMAP drink (HFD), and ii) a HFD + Lactobacillus probiotic, while continuing the LFD. Participants completed symptom and stress questionnaires and provided stool samples. Mouse dorsal root ganglia neurons were incubated with IBS patient fecal supernatant (FS). Capsaicin-induced Ca2+ influx was quantified to measure neuronal activity.
Results: IBS patient FS increased neuronal excitability compared to healthy controls (HC) FS. Four participants were LFD responders (clinically significant symptom reduction compared to baseline). LFD FS from two LFD responders reduced neuronal activity. While one participant was a probiotic symptom-responder, their probiotic FS did not reduce neuronal activity. Conversely, probiotic FS from two probiotic symptom non-responders reduced neuronal activity. Stress and IBS symptoms correlated in two participants; during high stress, their FS increased neuronal activity. Interestingly, FS from HC, IBS, and LFD conditions caused
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differences in neuronal activity in neurons from female mice, but not males. Additionally, untreated neurons from female mice during peak estrogen levels of the estrous cycle had greater activity than neurons from males, low-estrogen females, and ovariectomized females.
Conclusion: The LFD and Lactobacillus probiotic improve symptoms in some IBS patients and alter luminal mediator-treated neuronal activity. However, alternative mechanisms, including stress, also affect symptoms and luminal mediators. Additionally, increased activity and sensitization by luminal mediators in female neurons may contribute to more severe abdominal pain in female IBS patients.
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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.