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

IntroductionIrritable 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. MethodsThis 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. ResultsModel 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. DiscussionThis 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 KNOWNO_LIIBS pain involves complex, dysregulated gut-brain interactions. C_LIO_LITreatment response is highly variable and difficult to predict. C_LIO_LIMachine learning can help phenotype complex pain conditions. C_LI WHAT IS NEW HEREO_LIMachine learning based hierarchical models identify a core neurogenetic predisposition for IBS pain. C_LIO_LIMachine learning based prediction of individual response to self-management before treatment begins. C_LIO_LIThis provides a direct pathway to precision pain management in IBS. C_LI