The cecal appendix: one more immune component with a function disturbed by post-industrial culture

This review assesses the current state of knowledge regarding the cecal appendix, its apparent function, and its evolution. The association of the cecal appendix with substantial amounts of immune tissue has long been taken as an indicator that the appendix may have some immune function. Recently, an improved understanding of the interactions between the normal gut flora and the immune system has led to the identification of the appendix as an apparent safe-house for normal gut bacteria. Further, a variety of observations related to the evolution and morphology of the appendix, including the identification of the structure as a "recurrent trait" in some clades, the presence of appendix-like structures in monotremes and some non-mammalian species, and consistent features of the cecal appendix such as its narrow diameter, provide direct support for an important function of the appendix. This bacterial safe-house, which is likely important in the event of diarrheal illness, is presumably of minimal importance to humans living with abundant nutritional resources, modern medicine and modern hygiene practices that include clean drinking water. Consistent with this idea, epidemiologic studies demonstrate that diarrheal illness is indeed a major source of selection pressure in developing countries but not in developed countries, whereas appendicitis shows the opposite trend, being associated with modern hygiene and medicine. The cecal appendix may thus be viewed as a part of the immune system that, like those immune compartments that cause allergy, is vital to life in a "natural" environment, but which is poorly suited to post-industrialized societies.