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

Suhee Kim; Sung Hak Chun; Hee Jin Park; Sang-Il Lee

doi:10.4078/jrd.2019.26.4.235

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Kim, Chun, Park, and Lee: Systemic Sclerosis and Microbiota: Overview of Current Research Trends and Future Perspective

Review Article

J Rheum Dis 2019;26(4):235-247.

Published online: 31 October 2019

DOI: https://doi.org/10.4078/jrd.2019.26.4.235

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

Suhee Kim, Sung Hak Chun, Hee Jin Park, Sang-Il Lee

Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea

Corresponding to: Sang-Il Lee http://orcid.org/0000-0002-8283-7001 Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University and Gyeongsang National University Hospital, 79 Gangnam-ro, Jinju 52727, Korea. E-mail: goldgu@gnu.ac.kr

Received 16 August 201928 August 2019 Accepted 29 August 2019

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 pathoimmuno-logical 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.

Keywords: Microbiota, Systemic sclerosis, Autoimmune disease, Dysbiosis

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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.

Table 1.

The alterations of gastrointestinal microbial composition in SSc patients

Bacterial taxa	Sample	Observation	References
Phylum
Bacteroidetes	Feces	↓ in SSc (vs. HC)	34
Firmicutes	Feces	↑ in SSc (vs. HC)	34,89
Class
γ-Proteobacteria	Colonic lavage	↑ in SSc (vs. HC)	65
Family
Clostridiaceae	Feces	↓ in SSc (vs. HC)	71
U.m. of Lachnospiraceae	Feces	↓ in SSc (vs. HC)	89
Genus
Actinobacillus	Colonic lavage	↑ in severe (vs. less GI symptoms)	65
Akkermansia	Colonic lavage/Feces	↑ in SSc (vs. HC)	34,65,70
	Feces	↑ in SSc/GI+ (vs. SSc/GI-)
Bacteroides	Feces	↓ in SSc (vs. HC)	34,70
		↓ in SSc/GI-(vs. HC)
Bifidobacterium	Colonic lavage/Feces	↑ in SSc (vs. HC)	65,70
Blautia	Feces	↑ in SSc/GI+ (vs. SSc/GI-and HC)	70
Butyricimonas	Feces	↑ in SSc (vs. HC)	89
Clostridium	Colonic lavage/Feces	↓ in SSc (vs. HC)	34,65,70
		↓ in severe (vs. less GI symptoms)
Coprococcus	Feces	↑ in SSc/GI+ (vs. SSc/GI– and HC)	70
Desulfovibrio	Feces	↑ in SSc (vs. HC)	89
		↑ in SSc/GI+ (vs. HC)
Erwinia	Colonic lavage/Feces	↑ in SSc (vs. HC)	34,65
Faecalibacterium	Colonic lavage/Feces	↓ in SSc (vs. HC)	34,65,70
	Feces	↓ in SSc/GI+ (vs. SSc/GI– and HC)
Fusobacterium	Colonic lavage/Feces	↑ in SSc (vs. HC)	34,65
	Colonic lavage	↑ in severe (vs. less GI symptoms)
Lactobacillus	Colonic lavage/Feces	↑ in SSc (vs. HC)	34,65,70,71
	Feces	↑ in SSc/GI+ (vs. HC)
		↓ in severe (vs. less GI symptoms)
Parabacteroids	Feces	↑ in SSc (vs. HC)	34,89
		↑ in severe (vs. less GI symptoms)
Prevotella	Colonic lavage	↑ in SSc (vs. HC)	34,65,70
	Feces	↓ in SSc (vs. HC)
		↓ in SSc/GI+ (vs. HC)
		↑ in severe (vs. less GI symptoms)
Rikenella	Feces	↓ in SSc (vs. HC)	65
Roseburia	Feces	↓ in SSc (vs. HC)	70
		↓ in SSc/GI+ (vs. HC)
Ruminococcus	Colonic lavage/Feces	↑ in SSc (vs. HC)	34,65
Streptococcus	Feces	↑ in SSc (vs. HC)	70
		↑ in SSc/GI– (vs. HC)
Turicibacter	Feces	↓ in SSc (vs. HC)	89

Table 1.

Continued

Bacterial taxa	Sample	Observation	References
Species
Bacteroides fragilis	Colonic lavage	↓ in severe (vs. less GI symptoms)	65
Candidatus arthromitus	Colonic lavage	↓ in severe (vs. less GI symptoms)
Faeclibacterium prausnitzii	Feces	↓ in SSc (vs. HC)	70,71
		↓ in SSc/GI+ (vs. SSc/GI– and HC)
Lactobacillus reuteri	Feces	↑ in SSc/GI+ (vs. HC)	70
Lactobacillus salivaris	Feces	↑ in SSc/GI+ (vs. SSC/GI– and HC)
Roseburia faecis	Feces	↓ in SSc/GI+ (vs. HC)
Streptococcus salivarius	Feces	↑ in SSc/GI– (vs. HC)

SSc: systemic sclerosis, HC: healthy control, GI: gastrointestinal, SSc/GI+: SSc patients with gastrointestinal symptoms, SSc/GI-: SSc patients without gastrointestinal symptoms.

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