The central role of the gut microbiota in chronic inflammatory diseases

Abstract

The commensal microbiota is in constant interaction with the immune system, teaching immune cells to respond to antigens. Studies in mice have demonstrated that manipulation of the intestinal microbiota alters host immune cell homeostasis. Additionally, metagenomic-sequencing analysis has revealed alterations in intestinal microbiota in patients suffering from inflammatory bowel disease, asthma, and obesity. Perturbations in the microbiota composition result in a deficient immune response and impaired tolerance to commensal microorganisms. Due to altered microbiota composition which is associated to some inflammatory diseases, several strategies, such as the administration of probiotics, diet, and antibiotic usage, have been utilized to prevent or ameliorate chronic inflammatory diseases. The purpose of this review is to present and discuss recent evidence showing that the gut microbiota controls immune system function and onset, development, and resolution of some common inflammatory diseases.

Figure 1

Schematic representation of the pulmonary allergic response induced by gastrointestinal (GI) immune cells and two microbiota-related conditions (a healthy gut microbiota and a reduced gut microbiota following antibiotic treatment). Microbes in the intestines are sampled by Toll-like receptors (TLRs) on DCs either directly in the lumen or in the gut-associated lymphoid tissue (GALT). In the healthy gut microbiota, polymorphonuclear development (PMN) is normal and DCs become regulatory DCs (DCr) that promote development of Tregs and/or Th1 cells and natural killer (NK) cells. These NK cells inhibit Th2 inflammation. Antibiotic treatment kills a large proportion of healthy microbiota, leading to a reduced gut microbiota and an inflammatory environment without DCs, Th1 cells or NK cells. In this environment, an unhealthy microbiota elevates serum immunoglobulin E (IgE) levels, increases circulating basophil populations, and exacerbates basophil-mediated Th2 responses (adapted from Forsythe [110]).

Figure 2

Schematic representation of a complex mucosal immune system composed of epithelial and hematopoietic cells that are able to react to pathogenic insults. Development of IBD occurs mainly when epithelial cells are damaged and/or the intestinal microbiota composition is not healthy.

Figure 3

Effects of a high-fat diet. The altered microbial community of obese animals and humans promotes adiposity and decreased levels of short chain fatty acids and influences metabolic processes such as storage and metabolism of lipids in adipose tissue, muscle, and liver.