Reframing precision nutrition in irritable bowel syndrome: a mechanism-informed conceptual framework for responder prediction and clinical translation.

Background: The low-Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is widely used for irritable bowel syndrome (IBS), but response varies markedly across patients. This heterogeneity has shifted the field from testing average efficacy toward forecasting individual benefit and translating microbiome science into practical precision-nutrition tools. Methods: We present a conceptual analysis grounded in evidence mapping from human IBS studies that paired dietary interventions (primarily low-FODMAP pathways) with baseline microbiome and/or multi-omics measurements. Findings are organized within a "microbiome-to-model" roadmap that specifies responder endpoints, candidate data layers (taxa, functions, metabolites and volatile signatures), modeling choices, and the validation and implementation requirements needed for clinical decision support. Results: Three recurring signals emerge across cohorts. Baseline microbial ecology can stratify response, but taxonomic features alone often fail to transport across studies. Functional readouts, including metabolites and volatile signatures, are closer to symptom mechanisms and can improve interpretability; however, clinical deployment is still limited by endpoint heterogeneity, imperfect exposure and adherence measurement, batch effects, and insufficient external validation and calibration. Conclusion: IBS is well suited for microbiome-informed responder prediction, provided that models are developed with deployment in mind. Progress will depend on validation-first study designs, harmonized responder endpoints and adherence capture, robust multi-omics pipelines, and biologically interpretable decision rules that can be prospectively tested and monitored for temporal instability in real-world care.