Does appendix removal raise risk of Crohn’s disease?

Individuals who have undergone an appendectomy may be at heightened risk of Crohn’s disease, according to the results of a systematic review and meta-analysis.

The surgical removal of the appendix was associated with a 53-percent greater odds of subsequent Crohn’s disease (pooled odds ratio [OR], 1.57, 95 percent confidence interval [CI], 1.01–2.43; p=0.00001). [AIBD 2023, abstract S150]

On the bright side, a notable 40-percent reduction in the likelihood of developing ulcerative colitis following appendectomy was seen (pooled OR, 0.60, 95 percent CI, 0.24–1.47; p=0.00001).

From a vast pool of 114,537 articles addressing inflammatory bowel disease (IBD) and mucosa-associated lymphoid tissue surgeries, 23 observational studies met the stringent eligibility criteria, noted lead study investigator Dr Suprada Vinyak of Ballad Health in Norton, Virginia, US.

“Subsequently, our quantitative analysis included six studies that conformed to the highest standards,” Vinyak added.

However, the investigator acknowledged that the estimates for both Crohn’s disease and ulcerative colitis accompanied a substantial level of heterogeneity—93 percent and 96 percent, respectively.

Appendix’s role in gut health

IBD, an umbrella term for various chronic conditions affecting the gastrointestinal system, is spreading across the globe, according to Vinyak. People with Crohn’s disease and ulcerative colitis have a decreased quality of life.

“The aetiology 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,” Vinyak said.

Evidence shows that the appendix is packed with lymphoid tissues, which in turn act as a “safe house” for good bacteria. The special environment inside the appendix protects beneficial microbes against digestive juices and other harsh conditions. As such, the bacteria stored in the appendix can repopulate the gut after dysbiosis and restore balance. [J Theor Biol 2007;249:826-831; mBio 2013;4:e00366–12; Cell 2017;171:1481-1493]

Researchers believe that appendectomy might disrupt the gut’s delicate balance by affecting its immune system and microbiota. This could create conditions that may trigger excessive immune reactions, disrupt homeostasis, damage tissues, thin the protective mucus layer, or allow harmful bacteria to dig deeper into the gut wall—events that characterize IBD. [Cell Immunol 1997;182:29-37; Front Microbiol 2018;9:2247]

While the findings of the present meta-analysis provide insights into the relationship between mucosa-associated lymphoid tissue surgery and IBD, Vinyak stressed the need for further research to establish underlying mechanisms, validate the protective effect of appendectomy on ulcerative colitis, and address potential biases in existing data.