Infectious agents are still thought to be involved in the origin of inflammatory bowel disease. The focus in recent years has been more on Mycobacterium avium subsp paratuberculosis, adherent-invasive Escherichia coli or yeasts.
A metaanalysis has shown a significant association of M. avium subsp paratuberculosis and Crohn's disease and a large randomized placebo-controlled trial reported an absence of sustained beneficial effects of combined antibiotic therapy on remission of active Crohn's disease. Adherent-invasive E. coli adhere via type 1 pili to carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), abnormally expressed by intestinal epithelial cells in Crohn's disease patients. Both colonization of the ileal mucosa and stimulation of ileal epithelial cells by tumour necrosis factor-α induce overexpression of CEACAM6, leading to an amplification loop of colonization and inflammation. Anti-Saccharomyces cerevisiae mannan antibodies are the most prevalent serologic marker in Crohn's disease. Major oligomannose epitopes supporting antibody formation are expressed by Candida albicans in human tissues, suggesting that a loss of tolerance to C. albicans could lead to antibody formation in a subset of Crohn's disease patients who are genetically predisposed.
M. avium subsp paratuberculosis, adherent-invasive E. coli and Candida are good candidates for an infectious aetiology of Crohn's disease on the basis of genetic susceptibility, which relates to impaired function in the defence against intracellular bacteria.
aClinic of Digestive Disorders and Nutrition, Hôpital Claude Huriez, CHRU Lille, France
bLaboratory of Parasitology and Microbiology, INSERM U799, CHRU Lille, France
cDepartment of Intestinal Tract and Bacterial Pathogenesis, Université d'Auvergne, USC INRA 2018, Clermont-Ferrand, France
Correspondence to Arlette Darfeuille-Michaud, Pathogénie Bactérienne Intestinale, Laboratoire de Bactériologie, CBRV, 28 place Henri Dunant, 63001 Clermont-Ferrand, France Tel: +33 4 73 17 79 97; fax: +33 4 73 17 83 71; e-mail: firstname.lastname@example.org