Diet and host-microbial crosstalk in postnatal intestinal immune homeostasis

Abstract

Neonates face unique challenges in the period following birth. The postnatal immune system is in the early stages of development and has a range of functional capabilities that are distinct from the mature adult immune system. Bidirectional immune-microbial interactions regulate the development of mucosal immunity and alter the composition of the microbiota, which contributes to overall host well-being. In the past few years, nutrition has been highlighted as a third element in this interaction that governs host health by modulating microbial composition and the function of the immune system. Dietary changes and imbalances can disturb the immune-microbiota homeostasis, which might alter susceptibility to several autoimmune and metabolic diseases. Major changes in cultural traditions, socioeconomic status and agriculture are affecting the nutritional status of humans worldwide, which is altering core intestinal microbial communities. This phenomenon is especially relevant to the neonatal and paediatric populations, in which the microbiota and immune system are extremely sensitive to dietary influences. In this Review, we discuss the current state of knowledge regarding early-life nutrition, its effects on the microbiota and the consequences of diet-induced perturbation of the structure of the microbial community on mucosal immunity and disease susceptibility.

Figure 1 |

The ‘diet hypothesis’. Diet, gut microbiota and host immunity are intimately connected and their bidirectional communication is central to maintaining intestinal and metabolic homeostasis. The commensal bacteria determine the nutritional value of food by fermenting dietary components to usable energy sources and by affecting nutrient uptake. Specific bacteria and microbial by-products influence the development and function of key components of mucosal immunity. The mucosal immune system shapes the commensal composition and location. Immune–microbial interactions via pattern-recognition receptors (TLRs, NODs) result in secretion of antimicrobial peptides, mucins and IgA, which maintains intestinal homeostasis and barrier function. The mucosal innate immune system also influences dietary energy absorption. Finally, perturbation of microbial community structure leads to dysbiosis, which can precipitate immune-mediated disorders such as IBD and metabolic diseases such as type 2 diabetes. Abbreviations: ILC, innate lymphoid cell; NOD, nucleotide oligomerization domain; T_H17 cell, type 17 T helper cell; TLR, Toll-like receptor; T_REG cell, regulatory T cell.

Figure 2 |

Diet, gut microbiota and dysbiosis. Several features regulate the establishment and composition of the microbiota and their effect on the health and immune function of the host. Eubiosis or a normal microflora structure that protects against infections educates the immune system and contributes to nutrient digestion. Energy harvest is established by early intestinal colonization with specific microbes immediately after birth. An ordered process of subsequent colonization and expansion shaped by diet results in the establishment of distinct ‘enterotypes’, or clusters of microbial communities, that remains fairly stable in adults. Perturbations in the microbial community structure or dysbiosis are induced by factors such as diet, use of antibiotics or infection, which can alter susceptibility to several diseases.

Figure 3 |

The intestinal barrier. The intestinal barrier is made up of a single layer of epithelium consisting of intestinal epithelial cells and specialized Goblet cells, M cells and Paneth cells (present only in small intestine). Peyer’s patches (found specifically in the ileum) and mesenteric lymph nodes develop prenatally when LTi are recruited to sites of the developing intestines called cryptopatches. Cryptopatches mature into isolated lymphoid follicles when pattern-recognition receptors (TLRs) are triggered by MAMPs, which then release IgA-producing plasma cells into the lamina propria. Dendritic cells in the Peyer’s patches access microbes through M cells or directly from the lumen by extending dendrites through intestinal epithelial cells. These antigen-loaded dendritic cells can induce T-cell differentiation or T-cell-dependent B-cell maturation into germinal centres. Naive T cells (T_H0 cells) can differentiate into effector T_H1, T_H2 or T_H17 cells or into regulatory FOXP3⁺ T_REG cells or Tr1 cells. Microbial sensing by intestinal epithelial cells also marks the release of antimicrobial peptides and stimulation of intestinal epithelial cell proliferation in crypts. Abbreviations: IEL, intraepithelial lymphocyte; LTi, lymphoid tissue inducer cell; MAMP, microbe-associated molecular pattern; M cell, microfold cell; T_H, T helper cell; TLR, Toll-like receptor; Tr1, type 1 regulatory T cell; T_REG, regulatory T cell.

Figure 4 |

Development and maturation of the intestinal mucosal barrier and mucosal immune system. Developmental changes in the prenatal, postnatal and adult intestine are summarized. Intestinal microbial colonization, as well as dietary components, induces maturation of the intestinal epithelium and initiates development of the mucosal immune system. Complex bidirectional interactions between gut microbiota, diet and the immune system itself regulate the establishment and maintenance of intestinal homeostasis and barrier function. Abbreviations: CRAMP, cathelin-related antimicrobial peptide; CRS, cryptidin-related sequence; TLR, Toll-like receptor; ±, cells might or might not be present; +, ++, +++, ++++, relative numbers of indicated cells.