Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

TLR2 and interleukin-10 are involved in Bacteroides fragilis-mediated prevention of DSS-induced colitis in gnotobiotic mice

“…The pathogenesis of UC is associated with a complex interplay of genetic, immune system, microbial, and environmental factors [3]. It is generally accepted that IBDs are associated with dysregulation of the mucosal immune system in the native gut microbiota in genetically susceptible individuals.…”

MAHMI database: a comprehensive MetaHit-based resource for the study of the mechanism of action of the human microbiota

“…In this regard, some species have been found to be underrepresented in the faecal microbiota of patients suffering from IBD, such as the butyrate producing bacteria Faecalibacterium praustnizii , which has been postulated as a biomarker or even as a potential therapeutic agent (16, 17). However, it should be taken into account that several studies point to the involvement of genetic predisposition due to IBD-promoting gene mutations (18, 19). …”

Methodological Quality Assessment of Meta-Analyses and Systematic Reviews of Probiotics in Inflammatory Bowel Disease and Pouchitis

“…IBD includes Crohn’s disease (CD) and ulcerative colitis (UC). The etiology of IBD is still unclear; however, there is some evidence to suggest that immune dysregulation, environmental factors, and genetic polymorphisms contribute to the multifactorial nature of the disease [2]. A dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under an altered or impaired immune response [2].…”