Antibiotic consumption, genetic risk and incidence of metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

INTRODUCTION AND

OBJECTIVES

The association between antibiotic consumption and the risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD) remains ambiguous. This study aimed to investigate this relationship within a large prospective cohort from the UK Biobank.

PATIENTS AND

METHODS

We conducted a prospective cohort study of 143,279 adults aged 40 to 70 years, among whom 1477 were diagnosed with MASLD for the first time. Multivariate Cox proportional hazards regression models were employed to assess the data. The genetic risk score (GRS) for MASLD was derived from five single-nucleotide variants, and mediation analysis was performed to evaluate the role of metabolic syndrome (MetS).

RESULTS

Our findings demonstrated that individuals with antibiotic exposure during childhood or adolescence exhibited a significantly higher risk of developing MASLD compared to those without antibiotic exposure (P < 0.001, HR 1.39; 95 % CI 1.21-1.59). No significant interaction was observed between antibiotic consumption and genetic predisposition for MASLD. Mediation analysis revealed that MetS and central obesity accounted for 21.98 % and 13.55 % of the association between early-life antibiotic exposure and MASLD, respectively (P < 0.001), particularly in women (P for interaction = 0.031).

CONCLUSIONS

Long-term antibiotic exposure in early life was significantly associated with a higher risk of developing MASLD, and this association persisted after adjustment for genetic predisposition factors.