Evidence for the involvement of infectious agents in the pathogenesis of Crohn's disease.
Many advances have been made in the understanding of Crohn's disease (CD) pathogenesis during the last decade. CD is currently seen as a predominantly T-lymphocyte-driven disease characterized by the presence of a complex cocktail of interacting cytokines, chemokines and other mediators produced by a variety of cell types. Prevailing theories of CD pathogenesis suggest that patients' T-lymphocytes are inappropriately activated in the setting of an immune imbalance, which is itself caused by an unfortunate confluence of genetic and environmental factors. The T-cell response then leads to the chronic inflammation characteristic for the disease. Various environmental factors may play a role in the development of CD, but microbes are most consistently implied. This theory is based on epidemiological, clinicopathological, genetic and experimental evidence. Despite the abundance of arguments for the implication of bacteria in the aetiopathogenesis of CD, the precise role of bacteria in this disease still remains elusive. Three not necessarily mutually exclusive theories have been proposed: (1) an unidentified persistent pathogen; (2) an abnormally permeable mucosal barrier leading to excessive bacterial translocation; and (3) a breakdown in the balance between putative "protective" versus "harmful" intestinal bacteria ("dysbiosis"). At present, one cannot exclude with certainty any of these three proposed hypotheses; they may all apply to CD to a certain extent.
De Hertogh
Gert
G
Department of Pathology, University Hospitals KULeuven, Minderbroedersstraat 12, Leuven 3000, Belgium.
Aerssens
Jeroen
J
Geboes
Karen P
KP
Geboes
Karel
K
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001419:Bacteria / Q000276:immunology / Q000472:pathogenicity; D003424:Crohn Disease / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology; D006801:Humans; D019936:Probiotics / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
D000900:Anti-Bacterial Agents