Antibiotics are powerful modifiers of the gut microbiota, and antibiotic perturbations in early life may have long-lasting metabolic consequences. Using the UK Biobank adult cohort, we will investigate whether retrospectively reported long-term or recurrent antibiotic use during childhood or adolescence is associated with an increased risk of multi-organ metabolic disease in adulthood, and whether blood metabolomic pathways help explain these associations. Experimental evidence suggests that antibiotic-driven microbial disruption can lead to persistent changes in host metabolism, including altered lipid and energy metabolism and increased adiposity, but population-based evidence integrating metabolomic intermediates remains limited.
We hypothesise that blood metabolomic profiles partly mediate the relationship between long-term or recurrent antibiotic use in childhood or adolescence and later metabolic disorders affecting multiple organs (including liver, thyroid and kidney conditions), and that these relationships are modified by lifestyle factors and genetic susceptibility relevant to microbiome-metabolism pathways. Our objectives are to (1) examine and characterise associations between early-life antibiotic exposure and subsequent metabolic outcomes in adulthood using linked health records and follow-up data; (2) identify specific circulating metabolites and metabolomic signatures most strongly implicated as intermediate pathways; and (3) develop and validate machine-learning-based risk prediction models that integrate early-life antibiotic exposure, metabolomic signatures and key covariates to stratify future risk.
By clarifying metabolome-related mechanisms and improving risk prediction for common metabolic diseases, this study will provide population-level evidence on potential long-term consequences of intensive antibiotic use earlier in life and may inform targeted prevention strategies and more evidence-based antibiotic stewardship policies.
