Dietary and commensal derived nutrients: shaping mucosal and systemic immunity

Abstract

The intestine serves as the primary site of nutrient absorption in the body while also harboring the highest burden of commensal microflora and representing a major portal of pathogen exposure. As such, the immune network of the intestine relies on both dietary and commensal derived signals to guide appropriate function. Recent advances highlight the role of dietary derived nutrients and commensal derived metabolites in shaping gastrointestinal immunity. In particular, vitamin A has been shown to have dominant and pleiotropic effects in the intestine. In addition, dietary derived AHR ligands and commensal derived metabolites are now emerging as important players in mucosal immunity. Thus nutrition, commensal microflora and the mucosal immune system are all intimately connected.

Figure 1. Dietary derived influences on intestinal immunity

Dietary derived factors and nutrients have dominant influences on intestinal immunity. Vitamin A derived retinoic acid can act either on T cells or dendritic cells to promote mucosal immune responses. Vitamin D has been shown to promote IEL development and macrophage antimicrobial peptide secretion [50,36]. Dietary derived AHR ligands regulate IEL maintenance and Lti development[39,40]. Fiber contained in the diet promotes commensal bacteria metabolism of short chain fatty acids (SCFA) which restrain neutrophil function and reinforce epithelial barrier [3,41]. Folate receptor is expressed on immune cells of the GI tract, but the role of folate sensing remains unclear [38].

Figure 2. Interdependence of diet, immune and commensal interactions

Evidence now exists for bidirectional communication between the three key factors in the GI tract: Diet, immuninty and commensal microflora. Diet can have profound influences on the immune system (Vit A, Vit D, AHR ligands and Folate), while immunodeficiency impairs energy absorption [45]. Diet also has dominant influence on the composition and metabolic capacity of commensal bacteria, while this, in turn, influences nutrient absorption and energy harvest [43]. The immune system is able to exert control over both commensal composition and localization via recognition of TLR5 ligands and secretion of IL-22 as well as effector mechanisms including IgA production and paneth cell derived antimicrobial peptides (AMP), RegIIIγ and alpha defensins [,–55]. Conversely, commensal signals are critical for development and maintenance of the intestinal immune system including the production of short chain fatty acids (SCFA), activation of innate immunity via NOD and TLR ligands and the induction of CD4+ T cell and IgA+ B cell responses [2,41].