Appendectomy and colorectal cancer: a mini review from the perspective of gut microbiota and mucosal immunity.

The vermiform appendix was long considered a vestigial organ, yet accumulating evidence now supports its role as a component of gut associated lymphoid tissue and as a niche involved in microbial homeostasis and mucosal immune regulation. Against this background, whether appendectomy influences colorectal cancer (CRC) development and progression has become an important question at the intersection of oncology, microbiology, and immunology. Current epidemiological evidence does not support a simple model in which appendectomy uniformly increases long term overall CRC risk. Earlier observational studies, particularly from some Asian and American databases, suggested an increased risk in the short to intermediate period after surgery, but more recent prospective cohorts, molecular pathological epidemiology studies, and Mendelian randomization analyses indicate that this signal is highly dependent on time window and study design, and is more likely to reflect reverse causation and detection bias in the early postoperative period. At the same time, mechanistic and translational studies provide a biologically plausible framework, suggesting that appendectomy may be associated with changes in gut microbial communities, epithelial barrier function, inflammatory signaling, and tumor-associated macrophage-related immune programs, although much of the current evidence remains associative in humans or experimental in nature. Notably, appendectomy may not affect all CRCs in the same way, but may instead influence selected tumor locations and microbe related molecular subtypes, particularly Fusobacterium nucleatum (F. nucleatum) associated tumors. Overall, the relationship between appendectomy and CRC should be interpreted as a complex microbiota and immunity related issue rather than a simple unidirectional carcinogenic model. Future studies should clarify the true effects across different time windows, tumor subtypes, and immune ecological settings.