Pathogenesis of Crohn’s disease: Bug or no bug

Table 1 Microorganisms involved in inflammatory bowel disease

Microorganism	Main features
Bacteria
Adherent-invasive Escherichia coli	The AIEC has adherente and invasive properties. They are found in macrophages of ileal CD tissue. It adheres with a type 1 pili to CEACAM6 receptors (increased in ileal tissue). Invasion is facilitated by endomasplic reticulum expresion of Gp96 AIEC promotes translocation of bacteria and stimulates TNF production, promoting granuloma formation. CD mutations enhance intracellular replication. AIEC is very similar to the urologic UPEC
Mycobacterium aviumparatuberculosis	MAP causes CD-like disease in animals. It has been found un blood and intestinal tissue of CD patients, mainly in spheroplast form (cell-wall deficient form which may take up to 18 mo to culture in special stains). Blood MAP DNA has been found in higher levels in controls, as a sign of exposure in the general population and maybe due to the treatment IBD patients receive, which has been shown to inhibit MAP. MAP antibodies have been found in IBD sera. MAP is a source for ASCA. In vitro, MAP impair macrophages to kill E. coli. Several CD genetic alterations can favor MAP infection
H. pylori	Epidemiological studies have observed an inverse correlation between IBD and HP, that cannot only be explained by coincidence or by previous antibiotic treatment. It has been shown that HP’s DNA has the capacity to reduce type I IFN
C. difficile	Up to 10% of the IBD patients will develop C. difficile infections, 40% of them without having had previous antibiotic treatment. It is considered a risk factor for exacerbations and should be screened in every IBD patient hospitalized for a flare
Campylobacter and salmonella	The risk of IBD after a Campylobacter or Salmonella positive test is high, but it is also high if a stool test has been done and it was negative, suggesting that IBD patients undergo stool tests in the years before diagnosis
Virus
Measles and mumps	Implication of these virus and their vaccines in the pathogenesis is uncertain, specially with respect to measles
Rubella	No relationship has been found
Cytomegalovirus	It reactivates underlying inflammatory disease. The intensity in which CMV is expressed in the intestinal mucosa relates to the severity of the inflammation
Epstein-Barr virus	Like CMV, it has a modulating function, not an ethiological implication

AIEC: Adherent-invasive Escherichia coli; MAP: Mycobacterium avium paratuberculosis; IBD: Inflammatory bowel disease; CD: Crohn’s disease; ASCA: Antibodies against saccharomyces cerevisiae; CMV: Cytomegalovirus.