The Pediatric Microbiome as a Diagnostic Biomarker: Cross-Disease Evidence and the Path to Clinical Translation

Microbiome-derived signatures are increasingly investigated as diagnostic biomarkers in children, yet their clinical readiness remains uncertain because pediatric microbiomes vary substantially with age, development, diet, medication exposure, geography, and sampling context. This narrative review evaluates the diagnostic potential and translational maturity of pediatric microbiome biomarkers across disease domains. A prespecified PubMed search identified 124 curated records evaluating taxonomic, functional, genomic, metabolomic, or composite microbiome-derived signatures. Evidence was examined according to clinical task, biological matrix, analytical platform, comparator selection, modeling strategy, diagnostic performance, and validation maturity. Gastrointestinal and hepatobiliary disorders, particularly inflammatory bowel disease, showed the most developed diagnostic evidence, including clinically relevant comparators and independent validation. Promising signals were also reported in neurodevelopmental, respiratory, immune/allergic, oral, and metabolic disorders, although most studies remained at the discovery or internal-validation stage. High discrimination in case–healthy-control studies frequently weakened when models were tested against symptomatic controls or independent populations, highlighting spectrum bias, overfitting, developmental confounding, and limited transportability. Clinical translation therefore requires prespecified clinical use, leakage-controlled models, independent multicenter validation, comparison with standard care, and prospective evaluation of calibration, feasibility, clinical impact, and cost. Pediatric microbiome diagnostics should be judged by reproducibility and clinical utility rather than by discovery-cohort accuracy alone.