J Rheum Dis.  2019 Oct;26(4):235-247. 10.4078/jrd.2019.26.4.235.

Systemic Sclerosis and Microbiota: Overview of Current Research Trends and Future Perspective

• Kim S
• Chun SH
• Park HJ
• Lee SI

• KMID: 2459448
• DOI: http://doi.org/10.4078/jrd.2019.26.4.235

Abstract

The commensal microbiota contributes to the maintenance of immune homeostasis in the human body. Autoimmunity can be aggravated or alleviated by the microbiota, which affects both innate and adaptive immune cells. Many studies have demonstrated the role of gut dysbiosis, the alteration of the gut microbiome, in the development and progression of numerous autoimmune diseases. Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue and is characterized by skin and lung fibrosis, as well as injuries in small arteries. Recent studies have shown variable degrees of dysbiosis in SSc patients and the effect of probiotics on these patients, providing evidence for the potential link between microbiota and SSc. However, further research is needed to elucidate the key microorganisms and the mechanisms through which they affect the pathoimmunological process of SSc. This review summarizes the current knowledge regarding the association between microbiota and SSc, and discusses the changing perspectives and potential therapy strategies based on the microbiota and its products.

Keyword

Microbiota; Systemic sclerosis; Autoimmune disease; Dysbiosis

MeSH Terms

Arteries
Autoimmune Diseases
Autoimmunity
Connective Tissue
Dysbiosis
Fibrosis
Gastrointestinal Microbiome
Homeostasis
Human Body
Humans
Lung
Microbiota*
Probiotics
Scleroderma, Systemic*
Skin

Figure

• 

  Figure 1. Potential effects of microbiota-targeted challenges in systemic sclerosis (SSc). Probiotics, prebiotics, and dietary fibers can help produce microbial metabolites, such as short-chain fatty acids (SCFAs), via the recovery of commensal bacteria. SCFAs bind to G protein-coupled receptors (GPCRs) on intestinal epithelial cells and immune cells. In turn, SCFAs regulate intestinal barrier integrity by inducing secretion of interleukin (IL)-18 by epithelial cells, differentiation of T cells into regulatory T (Treg) cells, and proinflammatory cytokine production by macrophages. Dendritic cells (DCs) also regulate T cell differentiation by both SCFAs and microbe-associated molecular patterns (MAMPs) sensing through pattern-recognition receptors (PRRs). Presumably, the circulation of SCFAs and anti-inflammatory cytokines might prevent fibrosis by modulating the dysregulated immune system in SSc. TGF-β: transforming growth factor-β, TLR: toll-like receptor, ECM: extracellular matrix, pDC: plasmacytoid DC, TNF-α: tumor necrosis factor-α.

• 

  Figure 2. Detection of disease-specific bacterial species using bacterial antibody microarray. (A) Representative images of gut bacterial antibody microarray in serum. (B) Differential expression at the bacterial species level between healthy controls and patients. (C) Species abundance analysis between healthy controls (n=11) and patients (n=8). Green and red col-ors indicate high and low expression of bacterial antibodies, respectively. *p<0.01.

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