Gut microbiota-host interactions and juvenile idiopathic arthritis

Abstract

Background: Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease.

Main body: Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself.

Conclusions: The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.

Keywords: Antibiotics; Juvenile arthritis; Microbiota.

Fig. 1

The structure of intestinal mucosal defense and antigen sampling. Primary defense against penetration by luminal microbes is primarily provided by secretory IgA, mucin and antimicrobial peptides. In addition, single layered intestinal epithelial cell are anchored to each other by tight junctions. Goblet cells scattered among the epithelial lining produce mucin, which represents a physical barrier against bacterial access to epithelial cells. Secretory IgA attaches to luminal antigens and protects against invasion of pathogens inhibiting the penetration of harmful antigens. On the epithelial side of the mucin layer, antimicrobial peptides neutralize bacteria that have penetrated through the mucin layer. The Peyer’s patch also contains a specific type of enterocytes, M-cells, which periodically sample the luminal contents, transcytosing luminal antigens. Antigens that have broken through the epithelial barrier to the basolateral lamina propria generate inflammatory responses, while those presented to Peyer’s patches by periodic sampling typically generate regulatory responses [80, 81]. Additionally, T cells activated in mesenteric lymph nodes (not shown) express intestinal homing receptors such as the integrin α4β7, which guide the T cells back to the intestinal mucosa, where they can participate in protective or inflammatory immune responses.