Machine learning to phenotype pain and predict response to pain interventions among young adults with irritable bowel syndrome

Introduction

Irritable bowel syndrome (IBS) is a prevalent disorder whose most debilitating symptom is pain. The complex, multifactorial nature of IBS pain leads to highly variable and often inadequate responses to self-management, underscoring the urgent need for personalized prediction models.

Methods

This ancillary analysis of a randomized controlled trial ( NCT03332537 ) utilized data from 80 young adults with IBS. We applied the Bayesian Additive Regression Trees machine learning algorithm to develop 27 distinct predictive models for pain severity, pain interference, and quality of life (QOL) at baseline and post-intervention. Predictors included a comprehensive, multi-domain set of variables spanning genetics, quantitative sensory testing, gut microbiota, psychosocial factors, and food intake.

Results

Model performance was strong, with area under the curve (AUC) values ranging from 0.753 to 0.981. A consistent hierarchy of predictors emerged. The COMT rs4680 polymorphism was the most significant predictor, featuring in 26 models, followed by ADRA1D rs1556832 in 24 models. The mechanical pain threshold was a key predictor of pain severity, while psychosocial factors, particularly pain catastrophizing, were crucial for pain interference and QOL. Gut microbiota features and food intake were also consistently important.

Discussion

This study establishes a comprehensive, multi-omics framework that explains individual differences in IBS pain and treatment response. The identified predictors provide a practical tool for advancing precision medicine. By classifying patients based on their distinct profiles, clinicians can proactively customize self-management strategies, potentially transforming care for this complex condition.

WHAT IS KNOWN

• IBS pain involves complex, dysregulated gut-brain interactions.

• Treatment response is highly variable and difficult to predict.

• Machine learning can help phenotype complex pain conditions.

WHAT IS NEW HERE

• Machine learning based hierarchical models identify a core neurogenetic predisposition for IBS pain.

• Machine learning based prediction of individual response to self-management before treatment begins.

• This provides a direct pathway to precision pain management in IBS.