Crohn's disease: the cold chain hypothesis.
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.
Hugot
Jean-Pierre
JP
Laboratoire de Génétique des Maladies Inflammatoires de l'Intestin, Projet Avenir INSERM, Fondation Jean Dausset CEPH, Paris, France. jean-pierre.hugot@rdb.ap-hop-paris.fr
Alberti
Corinne
C
Berrebi
Dominique
D
Bingen
Edouard
E
Cézard
Jean-Pierre
JP
D002352:Carrier Proteins / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D016368:Frameshift Mutation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D047908:Intracellular Signaling Peptides and Proteins; D008957:Models, Genetic; D053473:Nod2 Signaling Adaptor Protein; D012034:Refrigeration / Q000009:adverse effects*; D012307:Risk Factors; D015009:Yersinia Infections / Q000276:immunology / Q000382:microbiology
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein