Intestinal Microbial Metabolites in Ankylosing Spondylitis

Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by inflammation of axial joints and the pelvis. It is known that intestinal dysbiosis may exert direct pathogenic effects on gut homeostasis and may act as a triggering factor for the host innate immune system to activate and cause inflammation in extraintestinal sites in the so-called "gut-joint axis", contributing to AS pathogenesis. However, although the intestinal microbiota's influence on the clinical manifestation of AS is widely accepted, the mechanisms mediating the cross-talk between the intestinal lumen and the immune system are still not completely defined. Recent evidence suggests that the metabolism of microbial species may be a source of metabolites and small molecules participating in the complex network existing between bacteria and host cells. These findings may give inputs for further research of novel pharmacological targets and pave the way to applying dietary interventions to prevent the onset and ameliorate the clinical presentation of the disease. In this review, we discuss the role of some of the biological mediators of microbial origin, with a particular focus on short-chain fatty acids, tryptophan and vitamin B derivatives, and their role in barrier integrity and type 3 immunity in the context of AS.

Keywords: SCFA; ankylosing spondylitis; dysbiosis; immunometabolism; interleukin 17; microbial metabolism; microbiota.

Figure 1

Schematic view of the effects of microbial metabolites on intestinal and immune cells. From left to right: vitamin B2 and B9 metabolites respectively activate and inhibit MAIT cells function; tryptophane metabolite kynurenine activates aryl hydrocarbon receptor (AhR) on iNKT and ILC3 cells and induces IL-22 production; SCFAs produced from microbic metabolism of dietary fibers interact with intestinal epithelial cells and promote mucine production and decrease paracellular permeability; absorbed SCFAs promote FoxP3 and IL-10 expression in regulatory T-cells (Tregs) and decrease RORϒt expression in Th17 lymphocytes, as well as Th17 activity; SCFAs block DC differentiation, decrease production of nitric oxide (NO) and IL-6 in macrophages, and inhibit neutrophil function and promote their apoptosis.