Mecanismos patogénicos del microbioma en la enfermedad inflamatoria intestinal: rol de la actividad proteolítica bacteriana

Abstract

nflammatory bowel disease is an immune mediated condition that includes Crohn’s disease and ulcerative colitis and causes chronic inflammation of the gastrointestinal tract. Although the exact cause for inflammatory bowel disease is unknown, there is consensus that a combination of genetic, environmental, and immune factors participate in its pathogenesis. To date, all the studies have been focused on alterations that occur once IBD has developed, however, the causes triggering the onset of the disease are still unclear. There is an evident genetic basis in which multiple genes involved in intestinal homeostasis are affected, such as NOD2, ATG16L1 and XBP1. However, these genetic factors are not sufficient for disease onset and additional environmental factors such as those related to dysregulation of gut microbiota and the immune system are required. A lower microbial diversity and a decrease in the relative abundance of Firmicutes, as well as an increase in Proteobacteria, have been described in patients with inflammatory bowel disease, but are not found in all studies. In addition to variations in microbial composition, functional changes have also been observed in cross-sectional studies. Longitudinal cohorts in patients at risk for inflammatory bowel disease have recently been conducted allowing us to interrogate whether specific microbial communities and functions could be influencing the onset of the disease. Indeed, a translational study performed in a cohort of at-risk individuals for inflammatory bowel disease (GEM cohort) showed an increased fecal proteolytic activity, associated with microbial composition changes, before the onset of ulcerative colitis. These findings may help develop new non-invasive diagnostic techniques, as well as new therapeutical approaches for inflammatory bowel disease.