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Microorganisms in Pathogenesis and Management of Systemic Lupus Erythematosus (SLE)

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Role of Microorganisms in Pathogenesis and Management of Autoimmune Diseases

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Abstract

Systemic lupus erythematosus (SLE) is a type of multisystem involved autoimmune inflammatory disease with high heterogenous clinical manifestation and various etiologies, featuring overexpressed pathogenic autoantibodies and overactivation of autoreactive immune cells. Genetic, environmental, and hormonal factors all contribute to the pathogenesis of SLE. Over decades, alteration of the diversity and composition of microbiota, as well as microbiota-derived metabolites, has been found in lupus-like spontaneous and/or inducible mouse models and SLE patients. Among them, gut microbial dysbiosis, generally a lower Firmicutes/Bacteroidetes ratio, has been reported to correlate with autoantibody production and activation of immune cells. Accumulated studies have focused on the interaction of the host and microbiota and the mechanisms of microbiota-triggered autoimmunity. However, the underlying mechanisms of microbiota in the pathogenesis of SLE remain a matter of debate. In this chapter, we elaborated patterns and functions of microbiota in physiological conditions and summarized the association of intestinal, oral, cutaneous, and plasma microbiota with the pathogenesis of SLE, especially intestinal microbiota. Intestinal microbiota plays a crucial role in the occurrence and progression of SLE through three major mechanisms including leaky gut and gut microbiota translocation, molecular mimicry, and metabolites like short-chain fatty acids (SCFAs) and microbial tryptophan catabolites, suggesting the potential efficacy of intervention of gut microbiota in the management of SLE. Numerous microbiota-related treatments of SLE covering dietary intervention, probiotics, antibiotics, and drugs, as well as fecal microbiota transplantation (FMT), have been explored and preliminarily applied in the assessment of SLE and intended to repair the aberrant intestinal microbiota environment and reduce the adverse influence caused by gut microbial dysbiosis.

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Abbreviations

AhR:

Aryl hydrocarbon receptor

AMP :

Antimicrobial protein

ANA :

Antinuclear antibody

APC :

Antigen-presenting cell

ARDs :

Autoimmune rheumatic diseases

B. fragilis :

Bacteroides fragilis

bDMARD :

Biological disease-modifying antirheumatic drug

Breg :

Regulatory B cell

COVID-19 :

Coronavirus disease 2019

CQ :

Chloroquine

CSR :

Class switch recombination

DMARDs :

Disease-modifying antirheumatic drugs

dsDNA :

Double-strand DNA

DSS :

Dextran sulfate solution

EBNA1 :

Epstein-Barr virus nuclear antigen-1

eDNA :

Extracellular DNA

FMT :

Fecal microbiota transplantation

GALT :

Gut-associated lymphoid tissue

GC :

Germinal center

GF :

Germ-free

HCQ :

Hydroxychloroquine

HDAC :

Histone deacetylation

HU1:

Histone-like protein 1

IFN :

Interferon

IL :

Interleukin

IMQ :

Imiquimod

LC40 :

Lactobacillus fermentum CECT5716

lpr:

Lymphoproliferation

LPS :

Lipopolysaccharide

MLN :

Mesenteric lymph node

MS :

Multiple sclerosis

NAC :

N -acetylcysteine

NLR:

Nucleotide-binding and oligomerization domain-like receptor

NOD :

Nonobese diabetic

NSAIDs :

Nonsteroidal anti-inflammatory drugs

PAMP:

Pathogen-associated molecular pattern

PBMC:

Peripheral blood mononuclear cell

pDC:

Plasmacytoid dendritic cell

PRR :

Pattern recognition receptor

RA :

Rheumatoid arthritis

RCT :

Randomized controlled trial

rDNA:

Ribosomal DNA

RG :

Ruminococcus gnavus

RG2 :

RG strain CC55_001C

RMDs :

Rheumatic and musculoskeletal diseases

RS :

Resistant starch

SARS-CoV-2 :

Severe acute respiratory syndrome coronavirus 2

SCFA:

Short-chain fatty acid

SHM :

Somatic hypermutation

sIgA :

Secretory immunoglobulin A

SLE :

Systemic lupus erythematosus

SNF1:

(SWR × NZB) F1

TC:

B6.Sle1.Sle2.Sle3 triple congenic

Tfh:

Follicular helper T

Tg:

Transgenic

TGF-β:

Transforming growth factor-β

Th:

T helper

TLR :

Toll-like receptor

TPC :

A conjugate of tuftsin and PC

Treg :

Regulatory T cell

tsDMARD :

Targeted synthetic disease-modifying antirheumatic drug

vWFA :

von Willebrand factor type A domain protein

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Authors and Affiliations

  1. Department of Dermatology, Second Xiangya Hospital, Hunan Key Laboratory of Medical Epigenomics, Central South University, Changsha, China

    Ping Yi, Ming Zhao & Qianjin Lu

  2. Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China

    Qianjin Lu

Authors
  1. Ping Yi
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  2. Ming Zhao
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  3. Qianjin Lu
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Corresponding author

Correspondence to Qianjin Lu .

Editor information

Editors and Affiliations

  1. C.G. Bhakta Institute of Biotechnology, Uka Tarsadia University, Surat, Gujarat, India

    Mitesh Kumar Dwivedi

  2. C.G. Bhakta Institute of Biotechnology, Uka Tarsadia University, Surat, Gujarat, India

    N. Amaresan

  3. Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

    E. Helen Kemp

  4. Zabludowizc Center for Autoimmunity, Sheba Medical Center, Tel-Hashomer, Israel

    Yehuda Shoenfeld

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Yi, P., Zhao, M., Lu, Q. (2022). Microorganisms in Pathogenesis and Management of Systemic Lupus Erythematosus (SLE). In: Dwivedi, M.K., Amaresan, N., Kemp, E.H., Shoenfeld, Y. (eds) Role of Microorganisms in Pathogenesis and Management of Autoimmune Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-19-1946-6_20

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