Abstract
Lay Summary To assess reproducibility in inflammatory bowel disease microbiome research, we performed a meta-analysis of 13 inflammatory bowel disease studies, measuring effects of disease and sample type. Crohn's disease studies were more heterogeneous than ulcerative colitis studies, and sample type variation was a major contributor to inconsistency.
Background Numerous studies have examined the gut microbial ecology of patients with Crohn's disease (CD) and ulcerative colitis, but inflammatory bowel disease-associated taxa and ecological effect sizes are not consistent between studies. Methods We systematically searched PubMed and Google Scholar and performed a meta-analysis of 13 studies to analyze how variables such as sample type (stool, biopsy, and lavage) affect results in inflammatory bowel disease gut microbiome studies, using uniform bioinformatic methods for all primary data. Results Reduced alpha diversity was a consistent feature of both CD and ulcerative colitis but was more pronounced in CD. Disease contributed significantly variation in beta diversity in most studies, but effect size varied, and the effect of sample type was greater than the effect of disease. Fusobacterium was the genus most consistently associated with CD, but disease-associated genera were mostly inconsistent between studies. Stool studies had lower heterogeneity than biopsy studies, especially for CD. Conclusions Our results indicate that sample type variation is an important contributor to study variability that should be carefully considered during study design, and stool is likely superior to biopsy for CD studies due to its lower heterogeneity.