Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases

Abstract

Purpose of review: The authors present evidence published during the past 2 years of the roles of commensal and pathogenic bacteria in the pathogenesis of the inflammatory bowel diseases.

Recent findings: Rodent models conclusively implicate commensal enteric bacteria in chronic, immune-mediated, experimental colitis, and genetically determined defects in bacterial killing by innate immune cells are found in a subset of patients with Crohn's disease. There is no evidence that a single pathogen, including Mycobacterium avium subspecies paratuberculosis, causes Crohn's disease or ulcerative colitis. However, adherent/invasive Escherichia coli are associated with ileal Crohn's disease, with the mechanisms and genetics of adherent/invasive E. coli virulence being elucidated. Molecular characterization of the microbiota in patients with inflammatory bowel diseases reveals decreased biodiversity of commensal bacteria, most notably the phyla Bacteroidetes and Firmicutes, including the clinically relevant Faecalibacterium prausnitzii, and increased E. coli concentrations. VSL#3 is one probiotic preparation shown to be efficacious in certain clinical situations in small clinical trials.

Summary: Further characterization of altered microbiota in patients with inflammatory bowel diseases and linking dysbiosis with host genetic alterations in immunoregulation, innate microbial killing and barrier function are critical, so that individualized treatments to increase beneficial commensals and their metabolic products (probiotic and prebiotic administration) and diminish deleterious species such as adherent/invasive E. coli can be tailored for defined patient subsets.

Figure 1. Defective containment of commensal bacteria in IBD

Crohn’s disease genes that affect bacterial killing result in defective containment of commensal bacteria. NOD2 polymorphisms result in defective α-defensin production and clearance of intracellular bacteria. Overgrowth of mucosal bacteria occurs with defective secretion of antimicrobial peptides (NOD2 and ATG16L1 polymorphisms) or secretory IgA. Inefficient killing of phagocytosed bacteria (NOD2, ATG16L1, NCF4 and IGRM polymorphisms) results in persistent intracellular bacteria and ineffective clearance of bacterial antigens. Increased mucosal permeability leads to overwhelming exposure of bacterial TLR ligands and antigens that activate pathogenic innate and T-cell immune responses. Modified from ref and used with permission of Elsevier Publishing Company.