A Nexus Between Appendectomy and a Higher Risk of IBD: Insights From a Comprehensive Systematic Review and Meta-analysis

Background: Inflammatory bowel disease (IBD) represents a group of chronic gastrointestinal disorders with rising global prevalence. Crohn’s disease (CD) and ulcerative colitis (UC) are subtypes of IBD, significantly affecting patients’ quality of life. The etiology of IBD is multifactorial, involving genetic and environmental factors. The mucosa and gut-associated lymphoid tissue (MALT/GALT), comprising structures like the appendix, plays a pivotal role in immune regulation and gut microbiota balance. While dysbiosis has been reported in IBD patients, a direct association remains unclear. This study investigates the relationship between appendectomy and IBD. The primary objective of this article is to assess the relation between appendectomy (MALT surgery) and the risk of developing Crohn’s disease (CD) and ulcerative colitis (UC). Methods: Employing a systematic review and meta-analysis approach, we meticulously adhered to PRISMA and MOOSE guidelines. PubMed was searched for articles relating to IBD and MALT surgeries, including appendectomy using following keywords:((“Inflammatory Bowel Disease”[Title/Abstract] OR “IBD”[Title/Abstract] OR “Crohn’s disease”[Title/Abstract] OR “Ulcerative colitis”[Title/Abstract]) AND (“adenoidectomy”[Title/Abstract] OR “MALT-ectomy”[Title/Abstract] OR “appendicectomy”[Title/Abstract] OR “tonsillectomy”[Title/Abstract] OR “lymphoid tissue”[Title/Abstract] OR “GALT-ectomy”[Title/Abstract]. Inclusion criteria encompassed observational studies involving IBD patients who had undergone these surgeries. Exclusions comprised non-human, non-English, and non-full-text studies. Eligible articles were screened, and data were independently extracted. We employed random-effects models using inverse variance analysis considering interstudy heterogeneity. For outcomes, pooled odds ratios with 95% CI and forest plots were calculated and derived. Results: From a vast pool of 114,537 articles addressing IBD and mucosa-associated lymphoid tissue (MALT) surgeries, 23 observational studies met the stringent eligibility criteria. Subsequently, our quantitative analysis included six studies that conformed to the highest standards. The meta-analysis revealed a statistically significant 53% elevated risk of CD following appendicectomy (pooled OR: 1.57, 95% CI: 1.01 - 2.43; p < 0.00001). However, substantial heterogeneity was observed (93%). Turning our attention to UC, we examined five studies, revealing a noteworthy 40% reduction in UC risk following appendicectomy (pooled OR: 0.60, 95% CI: 0.24 - 1.47; p < 0.00001). However, this apparent protective effect was accompanied by a high level of heterogeneity (96%). Conclusions: This systematic review and meta-analysis indicate a significant association between appendectomy and Crohn’s disease, with an increased risk, while ulcerative colitis appears to be inversely associated with appendectomy. These findings contribute to our understanding of the relationship between mucosa-associated lymphoid tissue surgery and IBD; however, the high heterogeneity highlights the need for further research to elucidate the underlying mechanisms and potential biases in existing data.