ROLE OF GUT MICROBIOTA IN THE EPISODIC NATURE OF SYMPTOMS IN IRRITABLE BOWEL SYNDROME

Abstract

Irritable Bowel Syndrome (IBS) is a gut-brain-axis disorder with a prevalence of 5.8% in Canada and 3.8% globally. Despite evidence suggesting complex interactions among neural, immune, and epithelial cells, influenced by factors such as diet, microbiota, and stress, the pathophysiology of IBS remains incompletely understood. Key knowledge gaps include the irregular nature of symptoms and the specific bacterial taxa responsible for symptom generation. Therefore, this thesis aims to perform an integrated analysis of a longitudinal study to investigate the relationship between IBS symptom dynamics, gut microbiota composition, and metabolite profiles, to determine whether temporal changes in microbiota predict or drive IBS symptoms. Clustering analysis identified distinct patterns in symptom occurrence and progression, categorizing samples into clusters that captured changes in both gut and mood symptoms, and distinguishing between symptom flares and remission. Subjects with constipation-predominant IBS exhibited consistently higher levels of symptoms while diarrhea-predominant IBS subjects showed varying symptom levels among abnormal stool weeks and normal stool weeks. Examining parallel changes in symptom scores and microbiota beta diversity over time, we found a significant correlation between the two in only 25% of IBS subjects in our cohort. This suggests a potential link between microbiota composition and symptom variability in specific subsets of patients, highlighting the heterogeneity in the microbiota-symptom relationship. Integrated microbiota-metabolite analysis revealed signatures linked to IBS subtypes, with bacteria such as Lachnoclostridium and Olsenella ,and metabolites like chenodeoxycholic acid among others identified as key nodes in network analysis. In conclusion, this study offers comprehensive insights into the episodic nature and heterogeneity of IBS, revealing dynamic symptom patterns and persistent burdens across subtypes. The findings highlight the complex relationship between microbiota composition changes and symptom variation, as well as the microbiota-metabolite axis in IBS patients.