Introduction:
Physical activity (PA) has a significant impact on gallstone formation, but the relationship is still unclear, and the patterns of PA have received little attention. This study aims to reveal the potential association between PA patterns and gallstone disease (GSD).

Material and methods:
This study conducted two-sample Mendelian randomization (MR) analyses to assess the causal relationships between PA and GSD, cholecystectomy, and biliary tract disorders. The inverse variance weighting (IVW) method was employed as the primary reference, supplemented with sensitivity tests. Subsequently, validation was performed using data from the National Health and Nutrition Examination Survey (NHANES) for the period 2017-2020, from which four PA patterns (no activity, insufficient exercise, weekend warrior, regular exercise) were derived to investigate the association between weekend warrior and the risk of GSD and cholecystectomy.

Results:
The MR analysis showed significant causal relationships between PA and GSD (OR = 0.97, 95% CI = 0.94-0.99, p = 0.01), cholecystectomy, and biliary tract diseases, passing rigorous sensitivity tests. In NHANES analysis, adjusted covariate survey-weighted logistic regression demonstrated that weekend warrior (OR = 0.57, 95% CI = 0.35-0.94, p = 0.03) and regular exercise (OR = 0.74, 95% CI = 0.56-1.00, p = 0.047) had equivalent protective effects against GSD. Similarly, weekend exercise and regular exercise significantly reduced the risk of cholecystectomy.

Conclusions:
The negative causal relationship between PA and GSD was observed. Both weekend warrior and regular exercise were found to effectively reduce the risk of GSD.