Altered gut microbial functional pathways in people with Irritable Bowel Syndrome enable precision health insights

Abstract

AbstractFunctional gastrointestinal disorders present diagnostic and therapeutic challenges, and there is a strong need for molecular markers that enable early detection and intervention. Herein, we present an approach to assess an abnormal gut microbiome associated with irritable bowel syndrome using stool-based gut metatranscriptome data from a large adult human population (n= 80,570). We develop a suite of eight gut microbial functional pathway scores, each of which represents the activity of a set of interacting microbial functional features (based on KEGG orthology) relevant to known gut biochemical activities. We use a normative approach within a subpopulation (n= 9,350) to define “Good” and “Not Optimal” activities for these functional pathway scores. We hypothesize that Not Optimal scores are associated with irritable bowel syndrome (IBS) and its subtypes (i.e., IBS-Constipation, IBS-Diarrhea, IBS-Mixed Type). We show that Not Optimal functional pathway scores are associated with higher odds of IBS or its subtypes within an independent cohort (n= 71,220) using both the Rome IV Diagnostic Questionnaire as well as self-reported phenotypes. Rather than waiting to diagnose IBS after symptoms appear, these functional scores can help to provide early health insights into molecular pathways that may lead to IBS. These molecular endpoints could also assist with measuring the efficacy of practical interventions, developing related algorithms, providing personalized nutritional recommendations, diagnostics, and treatments for gastrointestinal disorders like IBS.Graphical Abstract