Altered gut microbiome composition by appendectomy contributes to colorectal cancer

Area of Science:

• Microbiome research
• Gastroenterology
• Oncology

Background:

• Appendectomy is known to impact gut microbiome homeostasis.
• Gut microbial dysbiosis is implicated in colorectal cancer (CRC) development.
• The specific role of appendectomy-induced dysbiosis in CRC risk requires further investigation.

Purpose of the Study:

• To investigate the association between appendectomy and colorectal cancer (CRC) risk.
• To elucidate the role of appendectomy-induced gut microbial dysbiosis in CRC pathogenesis.
• To identify specific bacterial alterations following appendectomy and their correlation with CRC risk.

Main Methods:

• A population-based longitudinal cohort study (n=129,155) analyzed CRC risk over 20 years post-appendectomy.
• Shotgun metagenomic sequencing of fecal samples (n=314) characterized gut microbial composition in appendectomy patients versus controls.
• In vivo mouse models were used to confirm appendectomy's effect on colorectal tumorigenesis and gut barrier function.

Main Results:

• Appendectomy was associated with a 73.0% increased risk of CRC (SHR 1.73, P < 0.001).
• Appendectomy subjects exhibited gut microbial dysbiosis, with enrichment of 7 CRC-promoting bacteria (e.g., Bacteroides fragilis) and depletion of 5 beneficial commensals.
• Microbial network analysis revealed increased correlations among enriched bacteria and oncogenic pathways, with B. fragilis as a central node.

Conclusions:

• Appendectomy significantly elevates colorectal cancer risk, mediated by gut microbial dysbiosis.
• Appendectomy-induced dysbiosis involves an increase in CRC-promoting bacteria and a decrease in beneficial commensals.
• The gut microbiome plays a critical role in the development of colorectal cancer following appendectomy.