Fig. 1
Interplay between different factors involved in gut immunity and permeability. a The intestinal epithelial cells containing Paneth cells, goblet cells, enterocytes and enteroendocrine cells coordinate with intra-epithelial lymphocytes to generate a functional immune response. Paneth cells secrete antimicrobial peptides and goblet cells produce mucus to cover the epithelial layer. This mucus layer prevents adhesion of microbes to the epithelial cells. Lamina propria situated under the mucus layer contains Peyer’s patches and immune cells including antigen presenting cells (APCs) like dendritic cells (DCs), T cells and B cells. Pattern recognition receptors (PRRs) such as toll-like receptors (TLRs) on epithelial cells interact with microbe-derived pathogen-associated-molecular patterns (PAMPs) such as lipopolysaccharide (LPS) to activate MYD88-dependent signaling. DCs travel to mesenteric lymph nodes (mLN) and promote the differentiation of naïve T cells to regulatory T (Treg) cells that migrate to other sites. Treg cells secrete IL-10 to elicit an anti-inflammatory response. b Dysbiosis decreases mucus layer thickness and short-chain fatty acid (SCFAs) production. This affects the secretion of antimicrobial peptides and allows microbes to come in close proximity to the epithelial cells. Reduction in SCFAs influences gut barrier dysfunction. As a result, the gut luminal content also translocated and spreaded through the systemic circulation to trigger local and systemic immune responses. In addition to PAMPs, DAMPs released from damaged intestinal epithelium interact with PRRs to facilitate expression of macrophages and maturation of DCs. Mature DCs promote the differentiation of naïve T cells to effector T cells such as T helper cells (Th1, Th2, Th17). Th1 release TNFα and IFNγ, and Th17 secrete IL-17 to recruit polymorphonuclear neutrophils (PMNs). These cytokines create a pro-inflammatory condition