Dowrick JMRoy NCCarco CJames SCHeenan PEFrampton CMAFraser KYoung WCooney JTrower TKeenan JIMcNabb WCMullaney JABayer SBTalley NJGearry RBAngeli-Gordon TR2026-01-112026-12-31Dowrick JM, Roy NC, Carco C, James SC, Heenan PE, Frampton CMA, Fraser K, Young W, Cooney J, Trower T, Keenan JI, McNabb WC, Mullaney JA, Bayer SB, Talley NJ, Gearry RB, Angeli-Gordon TR. (2026). Integrated multi-omic and symptom clustering reveals lower-gastrointestinal disorders of gut-brain interaction heterogeneity. Gut Microbes. 18. 1.1949-0976https://mro.massey.ac.nz/handle/10179/74006Rome IV disorders of gut-brain interaction (DGBI) subtypes are known to be unstable and demonstrate high rates of non-treatment response, likely indicating patient heterogeneity. Cluster analysis, a type of unsupervised machine learning, can identify homogeneous sub-populations. Independent cluster analyses of symptom and biological data have highlighted its value in predicting patient outcomes. Integrated clustering of symptom and biological data may provide a unique multimodal perspective that better captures the complexity of DGBI. Here, integrated symptom and multi-omic cluster analysis was performed on a cohort of healthy controls and patients with lower-gastrointestinal tract DGBI. Cluster stability was assessed by considering how frequently pairs of participants appeared in the same cluster between different bootstrapped datasets. Functional enrichment analysis was performed on the biological signatures of stable DGBI-predominant clusters, implicating disrupted ammonia handling and metabolism as possible pathophysiologies present in a subset of patients with DGBI. Integrated clustering revealed subtypes that were not apparent using a singular modality, suggesting a symptom-only classification is prone to capturing heterogeneous sub-populations.CC BY 4.0(c) 2025 The Author/shttps://creativecommons.org/licenses/by/4.0/Cluster analysisdisorders of gut-brain interactionmetagenomicsmetabolomicsunsupervised machine learningirritable bowel syndromefunctional constipationfunctional diarrheaJournal article10.1080/19490976.2025.26048711949-0984journal-article2604871