Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses

Abstract

BACKGROUND & AIMS Multiple environmental factors have been associated with development of inflammatory bowel diseases (IBD). We performed an umbrella review of meta-analyses to summarize available epidemiologic evidence and assess its credibility. METHODS We systematically identified and appraised meta-analyses of observational studies examining environmental factors and risk of IBD (Crohn's disease [CD] or ulcerative colitis [UC]). For each meta-analysis we considered the random-effects estimate, its 95% CI, the estimates of heterogeneity and small-study effects, and graded the evidence according to prespecified criteria. Methodologic quality was assessed using AMSTAR 2. RESULTS We examined 183 estimates in 53 meta-analyses of 71 environmental factors related to lifestyles and hygiene, surgeries, drug exposures, diet, microorganisms, and vaccinations. We identified 9 factors that increase risk of IBD: smoking (CD), urban living (CD and IBD), appendectomy (CD), tonsillectomy (CD), antibiotic exposure (IBD), oral contraceptive use (IBD), consumption of soft drinks (UC), vitamin D deficiency (IBD), and non-Helicobacter pylori-like enterohepatic Helicobacter species (IBD). We identified 7 factors that reduce risk of IBD: physical activity (CD), breastfeeding (IBD), bed sharing (CD), tea consumption (UC), high levels of folate (IBD), high levels of vitamin D (CD), Helicobacter pylori infection (CD, UC, and IBD). Epidemiologic evidence for all these associations were of high to moderate strength; we identified another 11 factors associated with increased risk and 16 factors associated with reduced risk with weak credibility. Methodologic quality varied considerably among meta-analyses. Several associations were based on findings from retrospective studies, so it is not possible to determine if these are effects of IBD or results of recall bias. CONCLUSIONS In an umbrella review of meta-analyses, we found varying levels of evidence for associations of different environmental factors with risk of IBD. High-quality prospective studies with analyses of samples from patients with recent diagnoses of IBD are needed to determine whether these factors cause or are results of IBD, and their pathogenic mechanisms.