Gut microbiota and systemic immunity in health and disease

Abstract

The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. Although the influence of the gut microbiota on intestinal physiology and immunity is well known, mounting evidence suggests a key role for intestinal symbionts in controlling immune cell responses and development outside the gut. Although the underlying mechanisms by which the gut symbionts influence systemic immune responses remain poorly understood, there is evidence for both direct and indirect effects. In addition, the gut microbiota can contribute to immune responses associated with diseases outside the intestine. Understanding the complex interactions between the gut microbiota and the host is thus of fundamental importance to understand both immunity and human health.

Keywords: inflammatory disease; intestinal bacteria; metabolites; microbiome; systemic immune responses.

Fig. 1.

Potential direct microbial mechanisms in systemic immunity. The gut microbiota can contribute to immune responses at distant sites through direct mechanisms such as the translocation of gut microbes and/or their components or their metabolites to the blood circulation and systemic organs. BM, bone marrow; DP, double positive; MΦ, macrophage; ROS, reactive oxygen species; VEGF-B, vascular endothelial growth factor B.

Fig. 2.

The gut microbiota regulates hematopoiesis and immunity. The microbiota controls bone marrow (BM) hematopoiesis through several processes. Flt3L, FMS-like tyrosine kinase 3 ligand; SCF, stem cell factor; THPO, thrombopoietin.

Fig. 3.

Indirect effects of the gut microbiota on systemic immunity. The intestinal microbiota can modulate host systemic immunity through several indirect mechanisms via local stimulation of epithelial and immune cells which are then communicated to distal sites. GALT, gut-associated lymphoid tissue; MATE, microbial adhesion-triggered endocytosis.