Infectious etiopathogenesis of Crohn’s disease

Abstract

Important advances during the last decade have been made in understanding the complex etiopathogenesis of Crohn’s disease (CD). While many gaps in our knowledge still exist, it has been suggested that the etiology of CD is multifactorial including genetic, environmental and infectious factors. The most widely accepted theory states that CD is caused by an aggressive immune response to infectious agents in genetically predisposed individuals. The rise of genome-wide association studies allowed the identification of loci and genetic variants in several components of host innate and adaptive immune responses to microorganisms in the gut, highlighting an implication of intestinal microbiota in CD etiology. Moreover, numerous independent studies reported a dysbiosis, i.e., a modification of intestinal microbiota composition, with an imbalance between the abundance of beneficial and harmful bacteria. Although microorganisms including viruses, yeasts, fungi and bacteria have been postulated as potential CD pathogens, based on epidemiological, clinicopathological, genetic and experimental evidence, their precise role in this disease is not clearly defined. This review summarizes the current knowledge of the infectious agents associated with an increased risk of developing CD. Therapeutic approaches to modulate the intestinal dysbiosis and to target the putative CD-associated pathogens, as well as their potential mechanisms of action are also discussed.

Keywords: Crohn’s disease, Intestinal microbiota, Dysbiosis, Adherent-invasive Escherichia coli, Probiotics, Antibiotics, Fecal microbiota transplantation

Core tip: Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract of which the etiopathogenesis is not fully understood. Increasing evidence has shown that the etiology of CD is multifactorial involving genetic, environmental and infectious factors. A dysbiosis with an increase in the abundance of putative pathogenic bacteria and a decrease in that of potentially beneficial bacteria has been observed in CD patients, revealing the involvement of intestinal microbiota in such disease. This review aims to summarize the current knowledge of the infectious etiology of CD and to discuss therapeutic approaches to modulate intestinal dysbiosis and to target CD-associated pathogens.