Altered Gut Microbiome Composition by Appendectomy Contributes to Colorectal Cancer

Colorectal cancer (CRC) is one of the most common cancer worldwide. Initiation and progression of CRC involve complex interactions among genetic, epigenetic and environmental factors. Given that hereditary and familial CRC only accounts for 2% to 5% of cases, environmental factors are the key triggers of CRC. Emerging evidence has indicated that gut microbes are an important environmental factor promoting CRC development. Gut dysbiosis has been shown to promote colorectal carcinogenesis in mice. Several individual bacterial species, such as the enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum and Peptostreptococcus anaerobius, could exert carcinogenic effects by inducing direct DNA damage, oxidative damage and activating oncogenic signaling pathways. Recent studies have shown that the appendix plays an important role in maintaining homeostasis and biodiversity of gut microbiome by providing an ideal ecological niche for commensal bacteria and production of immunoglobulin A. Considering the key role of microorganisms in gastrointestinal pathophysiology, absence of appendix may result in disruption of microbiome homeostasis, which could potentially influence the risk of developing CRC. In terms of epidemiological evidence, the association of appendectomy with the risk of CRC development has been controversial, and to date no consensus has been attained. Although gut microorganisms could be a crucial pivot between appendectomy and risk of subsequent CRC development, the direct contribution of appendectomy and the underlying mechanisms are still largely unexplored. In this study, we aim to study

1. the association between appendectomy and colorectal cancer, and
2. the role of appendectomy in CRC risk through causing gut microbial dysbiosis.