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.
Highlights
Immunometabolism has recently became an appealing area of translational research; metabolic cues regulate cell survival and differentiation and modulate the activity of a plethora of immune responses against microbes, cancer cells, and toward the self [1]
Microbial metabolism has been recognized as a source of small molecules influencing the behaviour of host immune cells contributing to the cross-talk between microbiota and host immune response [2]
One possible interpretation of these data is that either quantitative/qualitative alteration in short-chain fatty acids (SCFAs) content or an impaired signaling downstream GPR43 in patients with Ankylosing spondylitis (AS) may contribute to an impaired Treg function. This alteration could be behind the unbalanced type 3 immune response, resulting in the activation of IL23-IL17/22 axis and of the mucosal cell involved in type 3 immunity and regulated by RORγt such as ILC3, invariant natural killer T cells, mucosal-associated invariant T (MAIT) cells, and γδ-T cells [14]
Summary
Immunometabolism has recently became an appealing area of translational research; metabolic cues regulate cell survival and differentiation and modulate the activity of a plethora of immune responses against microbes, cancer cells, and toward the self [1]. The initial trigger of the dysbiosis is still not fully explained, multiple animal and human studies demonstrated an active role for the microbiota in the initiation and perpetuation of the inflammatory pathways behind the intestinal inflammation observed in AxSpA and in SpA more in general [8,17,18]. The study of the bacterial metabolic pathways and their bioproducts could offer another key to interpreting the maladaptive cross-talk existing between intestinal epithelial cells and mucosa immune cells and their immunometabolism which could be deeply helpful in deciphering the etiopathogenesis of these conditions. The biological activity of microbial bioproducts will be summarized in the context of AxSpA pathogenesis, discussing their role in linking intestinal epithelial barrier inflammation and arthritis. The future therapeutic perspective harnessing microbial metabolic activity will be summarized
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