The bacterial flora in inflammatory bowel disease: Current insights in pathogenesis and the influence of antibiotics and probiotics

The pathogenesis of inflammatory bowel disease (IBD) remains unknown. altho ugh in recent years more data have become available. The contribution of ge netic and environmental factors is evident. and the luminal bacterial flora plays a major role in the initiation and perpetuation of chronic IBD. Annu al models of IBD) have shown that colitis does not occur in a germ-free env ironment. In human IBD. inflammation is present in parts of the gut contain ing the highest bacterial concentrations. Moreover, the terminal ileum. cae cum and rectum are areas of relative stasis. providing prolonged mucosal co ntact with luminal contents. Enhanced mucosal permeability may play a pivotal role in maintaining a chro nic inflammatory state. due to a genetic predisposition or as a result of d irect contact with bacteria or their products. A defective epithelial barri er may cause a loss of tolerance to the normal enteric flora. Furthermore. an increased mucosal absorption of viable bacteria and bacterial products i s found in IBD. Serum and secreted antibodies are increased and mucosal T-l ymphocytes that recognize luminal bacteria are present. However. there is e vidence that the immune system reacts over aggressively towards the normal luminal flora rather than the flora being altered in IBD. Several approache s have been used in attempts to discover a specific microbial agent in the cause of IBD). These include demonstration of the presence of organisms or specific antigens in affected tissues. culture of microbes fron) the affect ed tissues. demonstration of serological responses to several agents, and l ocalization and detection of individual pathogen-specific nucleic acid sequ ences in affected tissue by in situ hybridization and polymerase chain reac tion. So far. no specific micro-organism has been directly associated with the pathogenesis of IBD. Analysis of the luminal enteric flora. however. ha s revealed differences in the composition of this flora compared to healthy controls. In Crohn disease. concentrations of Bacteroides, Eubacteria and Peptostreptococcus are increased. whereas Bifidobacteria numbers are signif icantly reduced. Furthermore. in ulcerative colitis, concentrations of facu ltative anaerobic bacteria are increased. The arrival of new molecular tech niques qualifying and quantifying the complex intestinal flora has induced a revival of interest in this microflora. Therapeutic approaches geared towards changing the environment at the mucos al border have been attempted by the use of elemental diets, total parenter al nutrition, surgical diversion of the faecal stream and antibiotics. Over the past few years, the use of probiotics in IBD and other intestinal diso rders has gained attention. Strengthened by promising experimental data and commercial interests, research in this field is rapidly expanding. Manipul ation of the colonic bacteria with antibiotic drugs and probiotic agents ma y prove to be more effective and better tolerated than immunosuppresants in the future.