Data Sheet 1_Gut microbiota and health-related quality of life in paediatric inherited metabolic disorders: a narrative review and conceptual framework.docx

For PKU, controlled studies report reduced microbial diversity and depletion of butyrate-producing taxa associated with long-term dietary treatment. For the remaining disorders, direct paediatric microbiome data are sparse or absent, and proposed links rely on mechanistic extrapolation from non-IMD populations. We present the gut microbiota–metabolism–quality of life axis as a conceptual framework that integrates microbial metabolites, intestinal barrier function, immune signalling, and patient-reported outcomes, while emphasising that direct causal evidence linking microbiota alterations to HRQoL in paediatric IMDs is currently lacking.

Microbiota-directed interventions remain preliminary. Future multicentre longitudinal studies integrating microbiome profiling, multi-omics technologies, and validated patient-reported outcomes are needed to clarify causal mechanisms and therapeutic potential. Importantly, the available evidence is heterogeneous: direct paediatric microbiome evidence is strongest for PKU, whereas evidence for other IMDs is sparse and often observational, preclinical, or extrapolated from non-IMD populations.

The proposed microbiota–metabolism–HRQoL axis is therefore presented as a hypothesis-generating framework rather than an established causal pathway.</p>