Extensive antibiotic use during early life and risk of frailty: a population-based cohort study in the UK biobank

Early-life antibiotic exposure has been shown to disrupt gut microbiota, impair immune function, and perturb metabolic health. These are pathways known to contribute to frailty, yet direct evidence connecting antibiotic use to frailty is notably limited. We aimed to examine the association between extensive antibiotic use during early life and the subsequent risk of frailty among middle-aged and older-aged adults.

We used data from the UK Biobank, a population-based cohort study that recruited adults aged 40-70 years during 2006 and 2010 across 22 centres in England, Scotland and Wales. "Extensive antibiotic use during early life" was self-reported as long-term or recurrent antibiotic courses (≥ 3 per year) during childhood or adolescence. To comprehensively capture frailty's multidimensional nature and validate the robustness of associations, we applied three validated measures each targeting distinct frailty dimensions: frailty phenotype for physical frailty, hospital frailty risk score for multimorbidity-related frailty, and frailty index for comprehensive cumulative deficit frailty. Multivariable logistic regression models were used to explore the relationships between extensive antibiotic use during early life and risk of frailty.

A total of 156,401 participants were included in this study, among whom 22,692 participants self-reported extensive antibiotic use during early life. Compared to people without extensive antibiotic use during early life, those with this exposure had increased odds of physical frailty, hospital frailty and comprehensive frailty. The corresponding odd ratio (95% confidence interval were 1.36 (1.32-1.41), 1.42 (1.37-1.48) and 1.86 (1.80-1.92), respectively. Subgroup analyses were consistent with the main results.

Our findings indicate that extensive antibiotic use during early life is associated with elevated risk of frailty in middle and older adulthood. They highlight the importance of prudent antibiotic use in early life and the need for additional studies to explore the underlying causal pathways.