Role of the intestinal flora in gastrointestinal diseases

Abstract

B ecause of their high incidence and potential severity, adenocarcinoma of the colon and cryptogenetic inflammatory bowel diseases (Crohn's disease and ulcerative colitis) ~ are a priority for gastroenterologists in more-developed nations. A French citizen has, during his or her lifetime, a one in 25 chance of getting colon cancer and a one in 1000 chance of developing cryptogenetic inflammatory bowel disease. New treatment options--eg, chemotherapy and monoclonal antibodies to cytokines and adhesion molecules--are being developed. These treatments are increas ingly effective but, a t the same time, increasingly costly. Much attention is also being given to preventive measures. For several reasons, there has been a renewed interest in the role of the bowel flora as cause for these disorders. First, epidemiological and experimental studies consistently show that the bowel flora has a major role in colon cancer. Some colonising organisms are more favourable than others. For example, increased fermentation acidifies the contents of the colon thereby inhibiting the transformation of primary bile acids into carcinogenic secondary bile acids. Butyrate, a by-product of fermentation, aroused researchers' interest because it modulates cellular proliferation and differentiation of colonic cells. Other basic-research studies show that some still poorly identified elements of the intestinal flora might exacerbate inflammatory bowel diseases, in particular Crohn's disease, in both laboratory animals and humans. Second, there have been methodological advances in the study of the intestinal flora. Previous problems of identification because of the difficulties in growing certain micro-organisms on culture media--many intestinal micro-organisms cannot yet be cultivated--have been overcome by detecting molecular markers of their presence or activity. In particular, 16S DNA sequences specific for groups or species of bacteria, sometimes even specific for a given strain, can be identified. Such methods, along with DNA electrophoresis in a temperature gradient, have recently been applied to the human digestive tract, thus allowing previously impossible descriptions of complex ecosystems. A better understanding of the flora helps us to understand the interactions between enteric bacterial flora and mucosal immunity. Experimental models suggest that the inflammatory response in inflammatory bowel diseases is the result of abnormal immunological reactivity to normal flora in genetically-susceptible hosts. The mucosal immune system senses and interprets the local microenvironment, and under normal circumstances it exhibits a restrained response to commensal flora (tolerance), coupled with the capacity to react effectively to pathogenic bacteria (immunity). In susceptible individuals, inflammatory bowel diseases can result from a breakdown of the immunological tolerance to the normal flora. Third, the bowel ecosystem may be modulated by something other than antibiotics. There is industrial Role of the intestinal flora in gastrointestinal diseases