Metabolite-Related Evidence Linking Metabolic Measures to Patient-Reported Outcomes in Inflammatory Bowel Disease: A Critical Narrative Review.

Abstract

Background/objectives: Patient-reported outcomes (PROs) capture important dimensions of inflammatory bowel disease (IBD), including fatigue, questionnaire-defined mood-related symptom burden, pain, sleep disturbance, bowel urgency and impaired health-related quality of life, yet these outcomes are incompletely explained by conventional inflammatory markers. Metabolite-related measures may capture host-microbe co-metabolism relevant to patient-reported burden.

Methods: This critical narrative review synthesized adult IBD literature linking metabolite-related measures with patient-reported symptom domains. PubMed/MEDLINE, Embase.com, Scopus and Web of Science Core Collection were searched through 11 June 2026; purposive source selection supported critical narrative synthesis rather than exhaustive enumeration.

Results: Our structured search identified only a small number of human studies, mainly in fatigue and questionnaire-defined mood-related symptom burden. Studies included serum, plasma or fecal metabolite measurements, exploratory multi-omics, inferred microbial metabolic functions and interventional pathway testing. Fatigue was associated with serum amino-acid-related changes, plasma lipidomic alterations and fecal untargeted metabolomic and microbiome differences; inferred microbial functional modules were also reported. Mood-related burden was associated with serum and fecal metabolomic changes, bile-acid profiles and microbiota-derived functional signals. Within our search and eligibility criteria, no human studies paired measured metabolites with sleep-, pain- or urgency-specific patient-reported outcome measures (PROMs); evidence for multidimensional clusters was insufficient.

Conclusions: We did not identify a metabolite-related signature for the assessment of patient-reported burden that had undergone both analytical and clinical validation; findings support candidate associations and exploratory signatures. Future work requires longitudinal, phenotype-stratified cohorts, validated PROMs, rigorous metabolomics methodology, causal modeling, inflammatory and dietary metadata, multiple-testing control and independent validation for clinical translation.