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Background and Aims The long-term impact of maternal smoking during pregnancy [MSDP] on the risk of Crohn's disease [CD] and ulcerative colitis [UC] in adult offspring remains uncertain. The present study aimed to investigate the individual and combined effects of early life exposure [MSDP], offspring personal behaviour [smoking], and genetic risk on the development of CD and UC in adult offspring. Methods We conducted a prospective cohort study using UK Biobank data, including 334 083 participants recruited between 2006 and 2010, with follow-up until December 31, 2021. Multivariable Cox regression models were used to evaluate the associations of genetic factors, maternal and personal smoking, and their combination with CD and UC. Results Participants exposed to MSDP had an 18% increased risk of CD compared to those without MSDP (hazard ratio [HR] = 1.18, 95% confidence interval [CI] = 1.01–1.39). However, no significant association was found between MSDP and UC risk [HR = 1.03, 95% CI = 0.92–1.16]. Personal smoking increased the risk of CD and UC, and had a numerically amplified effect with MSDP. Participants with high genetic risk and MSDP had a 2.01-fold [95% CI = 1.53–2.65] and a 2.45-fold [95% CI = 2.00–2.99] increased risk of CD and UC, respectively, compared to participants without MSDP and with low genetic risk. Conclusions Our prospective cohort study provides evidence that MSDP increases the risk of CD in adult offspring, whereas no evidence supports their causal association. Additionally, smoking and genetic susceptibility had a numerically amplified effect with MSDP on CD and UC, but the interaction lacked statistical significance. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that bile acids are essential in irritable bowel syndrome (IBS) pathology, and cholecystectomy has direct effects on bile acid metabolism. However, whether cholecystectomy increases the risk of IBS remains unclear. We aimed to investigate the association between cholecystectomy and IBS risk in the UK Biobank (UKB). Methods: This study is a prospective analysis of 413,472 participants who were free of IBS, inflammatory bowel disease, cancer, or common benign digestive tract diseases. We identified incidents of IBS through self-reporting or links to primary healthcare and hospitalization data. We evaluated hazard ratios (HRs) adjusted for sociodemographic characteristics, health behaviours, comorbidities, and medications. Results: During a median follow-up period of 12.7 years, we observed 15,503 new cases of IBS. Participants with a history of cholecystectomy had a 46% higher risk of IBS than those without (HR = 1.46, 95% CI: 1.32-1.60), and further subtype analysis showed that the risk of IBS with diarrhoea was significantly higher than the risk of IBS without diarrhoea (HR = 1.71, 95% CI: 1.30-2.25 vs. HR = 1.42, 95% CI: 1.28-1.58). The overall covariate-adjusted HRs for IBS were similar between the group with both cholecystectomy and gallstones (HR = 1.45, 95% CI: 1.32-1.58) and the group with cholecystectomy without gallstones (HR = 1.50, 95% CI: 1.36-1.67) when the group without both cholecystectomy and gallstones was used as a reference. The overall covariate-adjusted HR was not significantly different in the group without cholecystectomy with gallstones (HR = 1.18, 95% CI: 0.95-1.47). The positive association of cholecystectomy with IBS risk did not change when stratifying the data based on age, sex, BMI, smoking, alcohol consumption, healthy diet, quality sleep, physical activity, type 2 diabetes, hypertension, hyperlipidaemia, mental illness, NSAID intake, or acid inhibitor intake. Sensitivity analyses, including propensity score matching analysis and lagging the exposure for two or four years, indicated that the effects were robust. Conclusion: Cholecystectomy was associated with a higher risk of IBS, especially IBS with diarrhoea. Additional prospective randomized controlled and experimental studies are warranted to further validate the association and to explore the relevant biological mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Tian, Xia, Mi, He, Yang, Wang, Wu, Li, Zhang, Zhang, Yue, Lin, Zhao, Zhang, Ma, Jiang, Li, Yuan, Nie, Lu and Meng.)