DISMICROBISM IN INFLAMMATORY BOWEL DISESE AND COLORECTAL CANCER: CHANGES IN RESPONSE OF COLOCYTES

Abstract

Patients with inflammatory bowel disease (IBD) have an increased risk of 10%-15% developing colorectal cancer (CRC) that is a common disease of high economic costs in developed countries. the CRC has been increasing in recent years and its mortality rates are very high. Multiple biological and biochemical factors are responsible for the onset nad progression of this pathology. moreover, it appears absolutely necessary to investigate the environmental factors favoring the onset of CRC and the production of colonic healt. the gut microflora, or microbiota, has an extensive diversity both quantitatively and qualitatively. in utero, the intestine of the mammalian fetus is sterile. Al birth, the intestinal microbiota in acquired by ingestion maternal anal or vaginal organisms, ultimately developing into a stable community, with marked variations in microbial composition between individuals. the development of IBD is often associated with qualitative and quantitative disorders of the intestinal microbial flora (dysbiosis). the healthy human gut arbours about 10 different bacterial species distributed in colony forming units which colonize the gastrointestinal tract. The intestinal microbiota plays a fundamental role in helath and the progeression of diseases such as IBD and CRC. in Healthy subjects, the main control of intestinal bacterial colonization occurs through gastric acidity but other factors such as endoluminal temperature, competition between different bacterial strains, peristalsis and drugs can influence the intestinal microenvironment. the microbiota exerts diverse physiological functions to include; growth inhibition of pathogenic microrganisms, synthesis of compounds useful for the trophysm of colonic mucosa, regulation of the intestinal lymphoid tissue and synthesis of amino acids. furthermopre, mucus seems to play an important role in protecting the intestinal mucosa and maintaining its integrity. changes in the microbiota composition are mainly influenced by diet and age, as well as genetic factors. Increasing evidence indicates that dysbiosis favors the production of genotoxins and metabolities associated with carcinogeneasis and induces dysregulation of the immune response wich promotes and sustains inflammation in IBD leading to carcinogenesis. a disequilibrium in gut microflora composition leads to the specific activation of gut associated lymphoid tissue. the associated chronic inflammatory process associated increases the risk of developing CRC. Ulcerative colitis and Crohn's diasease are the two major IBDs characterized by an early onset and extraintestinal manifestations, such as rheumatoid arthtritis. the pathogenesis of both diseases is complex and not yet fully known. however, it is widely accepted that an inappropriate immune response to microbial flora can play a pivotal role in IBD pathogenesis.