Abstract
PurposeExposure to antibiotics in early life exerts profound impacts on the gut microbiota and is linked to various diseases. This study investigated the association between long-term or recurrent antibiotics use during early life(LRAU), genetic risk and urolithiasis incidence using a large-scale cohort.MethodsParticipants in the UK Biobank who completed digestive health questionnaire were included in this cohort study. Multivariable Cox proportional hazards regression models were used to estimate the risk of incident urolithiasis for LRAU and polygenic risk score (PRS). Additionally, the potential interaction effects were assessed.ResultsOver a median follow-up of 51 years, 3011 of the 121,746 participants developed urolithiasis. Compared to non-LRAU participants, those with LRAU exhibited higher risks of urolithiasis with HRs of 1.20 (95% CI 1.09-1.31). This association is still significant at 5-year intervals from ages 35 to 60. Participants with high and moderate PRS demonstrated increased risks of urolithiasis compared with low group, with HRs of 1.78 (95% CI 1.62-1.94) and 1.36 (1.23-1.49). When stratified by PRS, the significance of LRAU was no longer evident, but still could bring additional risk. Results in the sensitivity analyses were highly consistent with the primary analyses.ConclusionBoth LRAU and a higher PRS are associated with an increased risk of urolithiasis. This association is significant for LRAU at 5-year intervals from ages 35 to 60. A dose-response correlation between PRS and urolithiasis incidence was indicated. LRAU could bring additional urolithiasis risk in participants with higher genetic risk.