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Evolutionary
The low incidence of pathogens within modern societies are thought to have contributed to Inflammatory Bowel Disease vulnerability. This has been known as the Hygiene Hypothesis. Humanity has been exposed to a wide range of bacteria and viruses with the advent of agriculture. The increase of the rates in IBD has been coincided with the increase in hygiene. Infectious vectors that have co-evolved with humans are thought to had conferred protection against auto-immune disorders. In the modern society, improved sanitation and medicine has lowered pathogen exposure. This leads to an evolutionary mismatch between adaptation and environment where the low pathogen exposure increases susceptibility to Inflammatory Bowel Disease. This is a result of an inappropriate response from the immune system that has not been exposed to many pathogens.

A mechanism of the hygiene hypothesis that has been suggested is the T-helper type 1 (Th1)/Th2 imbalance. Th1 is associated with the inflammatory response while Th2 is associated with the allergic response. It is suggested that the low microbial exposure early in life has predisposed hosts to allergy. For example, helminthic infection is shown to modulate a strong Th2 response. The increase in Th2 decreases the Th1 response which is associated with auto-immune and Crohn's Disease. Newer perspectives have lessened the impact of this mechanism as autoimmune diseases have also shown to protect the Th1 response.

Another mechanism that has been proposed is the dysregulation of the immune system. Problems in the inability to terminate inappropriate inflammatory cytokines has been implicated in IBD etiology. Regulatory T-cells (Treg) are made in response to "pseudo-commensal" microbial agents such as helminths and have been suggested to reduce the inflammatory response. Taken together, these suggest that the active immune system is mismatched in the modern, low pathogen setting and may be a reason for vulnerability to IBD.