Appendix and Ulcerative Colitis: a Key to Explaining the Pathogenesis and Directing Novel Therapies?

Abstract

The vermiform appendix is generally considered a redundant organ, but recent evidence suggests that the appendix could contribute to the pathogenesis of inflammatory bowel diseases, in particular ulcerative colitis (UC), and may even have a therapeutic role; however, mechanisms of the appendix involvement remain unclear. Here, we highlight current evidence on the link between the appendix and UC and consider plausible therapeutic implications. A literature search was conducted using PubMed and PubMed Central from inception to Nov 2021 using the terms "Appendix", "UC", "Appendix & UC," "Appendectomy", and "Peri-appendicular patch," including only articles published in English. Reference lists from the selected studies were manually searched and reviewed to gather additional related reports. Inflammation around the appendix ("peri-appendicular patch") has been frequently observed in UC patients without other cecal involvement, and this inflammation can even precede the onset of UC. Epidemiologic studies propose that appendectomy reduces the risk of developing UC or even the risk of flare after UC is diagnosed, although this remains controversial. We reviewed studies showing altered host-microbe interactions in the appendix in UC, which suggest that the appendix could act as a priming site for disease via alterations in the immune response and changes in microbiota carried distally to the colon. In summary, recent literature suggests a possible role for microbes and immune cells within the appendix; however, the role of the appendix in the pathogenesis of UC remains unclear. Further research could clarify the therapeutic potential related to this organ.

Keywords: appendectomy; microbiome; peri-appendicular patch.

Figure 1.

A schematic illustration of the appendix and colon layers with their lymphoid tissues and commensal microbes. The appendix and colon layers consist of serosa, muscularis externa, submucosa, lamina propria, and mucosa. In contrast to the colon, the appendix has more abundant and pronounced lymphoid follicles and likely a different microbiome. This figure is created with BioRender.com.

Figure 2.

The immune link between the appendix and ulcerative colitis. Interleukin (IL)-13, IL-17, INFγ, and TNFα, produced by NKT cells, lead to inflammation. Dendritic (DC) cells activate naïve T cells to T helper 2 cells, which could suppress or regulate the immune system. Follicular dendritic cells (FDCs) in interaction with B cells promote humoral immunity. Secretory IgA in the appendix is produced by B cells, resulting in the formation of biofilms. B cells can migrate to the colon, as well. This figure is created with BioRender.com.

Figure 3.

Microbial and immunological links between the appendix and UC. The appendix and its biofilms are considered a safe house for resident bacteria, possibly seeding the colon with pathobionts in UC. Additionally, the appendix is rich in immune cells and can act as a priming site for UC, triggering inflammation. This figure is created with BioRender.com.