Interactions between Intestinal Microbiota and Host Immune Response in Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Although the etiology and pathogenesis of IBD remain unclear, both genetic susceptibility and environmental factors are implicated in the initiation and progression of IBD. Recent studies with experimental animal models and clinical patients indicated that the intestinal microbiota is one of the critical environmental factors that influence nutrient metabolism, immune responses, and the health of the host in various intestinal diseases, including ulcerative colitis and Crohn's disease. The objective of this review is to highlight the crosstalk between gut microbiota and host immune response and the contribution of this interaction to the pathogenesis of IBD. In addition, potential therapeutic strategies targeting the intestinal micro-ecosystem in IBD are discussed.

Keywords: epithelial cells; host immune response; inflammatory bowel disease; intestinal barrier function; intestinal microbiota.

Figure 1

Host immune responses to intestinal microbiota. Several immune mechanisms work in concert to the intestinal microbiota and contribute to intestinal homeostasis. Goblet cells secret mucin glycoproteins, plasma cells secret IgA, and epithelial cells secrete antimicrobial proteins through toll-like receptors (TLRs), or nucleotide-binding oligomerization domain-containing protein 2 (NOD2)-dependent mechanisms. Dendritic cells (DCs) take up bacteria migrate to Peyer’s patches and mesenteric lymph nodes where B cells are differentiated into IgA-secreting plasma cells. In addition, sampling of polysaccharide A (PSA) from Bacteroides fragilis by intestinal DCs leads to induction of regulatory T (Treg), which is responsible for the production of IL-10. In addition, the antimicrobial proteins secreted by the host cells can modulate the composition of the microbiota. IL-10, interleukin 10; M cell, microfold cell; MYD88, myeloid differentiation primary-response protein 88; REG3γ, C-type lectin regenerating islet-derived protein 3γ.

Figure 2

Interactions between microbiota and host genetic and environmental factors contribute to the pathogenesis of IBD. Under healthy conditions (left panel), pathogens are suppressed by beneficial commensal bacteria through the induction of antimicrobial proteins, such as IL-10 and REG3γ, thus maintaining homeostasis. In IBD (right panel), a combination of genetic factors and environmental factors (such as stress, diet, and antibiotic) lead to dysbiosis, which in turn affects barrier integrity, innate, and adaptive immunity, resulting in uncontrolled chronic inflammation and hyper-activation of T helper 1 (Th1) and Th17 cells, increase in tight junction permeability, reduction in regulatory T (Treg) cells, and decrease in REG3γ and IL-10. ATG16L, autophagy-related 16-like; CARD9, caspase recruitment domain family member 9; FUT2, fucosyltransferase 2; IBD, inflammatory bowel disease; IL-10, interleukin 10; IRGM, immunity-related GTPase M; NOD2, nucleotide-binding oligomerization domain-containing protein 2; REG3γ, C-type lectin regenerating islet-derived protein 3γ.

Figure 3

Mechanisms involved in probiotic-induced protection against intestinal dysbiosis. Probiotics suppress pathogens through various actions, including lowering luminal pH, production of antimicrobial proteins, inhibition of adhesion and translocation of flora, competitive exclusion of pathogens, improvement of epithelial barrier, enhancement of adhesion of commensal bacteria to the intestinal mucosa, and modulation of gastrointestinal mucosal immune system.