Crohn's disease is the result of an abnormal immune response of the gut mucosa 
triggered by one or more environmental risk factors in people with predisposing 
gene variations, including CARD15 mutations. Epidemiological data allow 
assessment of familial environmental risk factors related to western lifestyle, 
diet, bacteria, and domestic hygiene. All findings point to refrigeration as a 
potential risk factor for Crohn's disease. Furthermore, cold-chain development 
paralleled the outbreak of Crohn's disease during the 20th century. The cold 
chain hypothesis suggests that psychrotrophic bacteria such as Yersinia spp and 
Listeria spp contribute to the disease. These bacteria have been identified in 
Crohn's disease lesions and we discuss their pathogenic properties with respect 
to our knowledge of the disease. From a molecular perspective, we postulate that 
the disease is a result of a defect in host recognition by pathogenic bacterial 
components that usually escape the immune response (eg, Yop molecules), which 
results in an excessive host response to these bacteria.