Alteration in gut microbiota is associated with dysregulation of cytokines and glucocorticoid therapy in systemic lupus erythematosus

ABSTRACT A growing corpus of evidence implicates the involvement of the commensal microbiota and immune cytokines in the initiation and progression of systemic lupus erythematosus (SLE). Glucocorticoids have been widely used in the treatment of SLE patients, however, glucocorticoid treatment carries a higher risk of other diseases. Using the 16S rRNA technique, we investigated the differences between the gut microbiota associated with the immune cytokines of SLE and relevant glucocorticoid treatment in a female cohort of 20 healthy control subjects (HC), 17 subjects with SLE (SLE-G), and 20 SLE patients having undergone glucocorticoid treatment (SLE+G). We observed that the diversity and structure of the microbial community in SLE+G patients were significantly changed compared to that of SLE-G patients, whereas the gut microbial community of the SLE+G group showed a similarity with the HC group, which implicate that the shift in the gut microbiome could represent a return to homeostasis. Furthermore, the up-regulations of immune cytokines in SLE-G were identified as closely related to gut dysbiosis, which indicates that the overrepresented genera in SLE patients may play roles in regulating expression level of these immune cytokines. This associated analysis of gut microbiota, glucocorticoid therapy, and immune factors might provide novel and insightful clues revealing the pathogenesis of SLE patients.

[1]  Systemic Lupus Erythematosus Disease Activity Index , 2020, Definitions.

[2]  A. M. Eren,et al.  B cell superantigens in the human intestinal microbiota , 2019, Science Translational Medicine.

[3]  Zhixing He,et al.  Alterations of the Gut Microbiota Associated With Promoting Efficacy of Prednisone by Bromofuranone in MRL/lpr Mice , 2019, Front. Microbiol..

[4]  B. Rovin,et al.  Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal , 2019, Annals of the rheumatic diseases.

[5]  C. Dehner,et al.  A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity. , 2019, Cell host & microbe.

[6]  N. Minato,et al.  Microbiota - an amplifier of autoimmunity. , 2018, Current opinion in immunology.

[7]  G. Ruiz-Irastorza,et al.  Glucocorticoids and antimalarials in systemic lupus erythematosus: an update and future directions , 2018, Current opinion in rheumatology.

[8]  J. Raes,et al.  Regional variation limits applications of healthy gut microbiome reference ranges and disease models , 2018, Nature Medicine.

[9]  Vaishali R. Moulton,et al.  Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus , 2018, Front. Immunol..

[10]  F. Zhao,et al.  Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus , 2018, Gut.

[11]  P. Fu,et al.  Gut microbiota–derived short-chain fatty acids and kidney diseases , 2017, Drug design, development and therapy.

[12]  M. Petri,et al.  Epidemiology of systemic lupus erythematosus: an update , 2017, Current opinion in rheumatology.

[13]  M. Petri,et al.  The Risk Benefit Ratio of Glucocorticoids in SLE: Have Things Changed over the Past 40 years? , 2017, Current Treatment Options in Rheumatology.

[14]  Hongfu Zhang,et al.  Zinc Oxide Nanoparticles Influence Microflora in Ileal Digesta and Correlate Well with Blood Metabolites , 2017, Front. Microbiol..

[15]  Weili Zhang,et al.  Gut microbiota dysbiosis contributes to the development of hypertension , 2017, Microbiome.

[16]  Zhijun Xie,et al.  Alterations of the gut microbiome in Chinese patients with systemic lupus erythematosus , 2016, Gut Pathogens.

[17]  E. Rosser,et al.  A clinical update on the significance of the gut microbiota in systemic autoimmunity. , 2016, Journal of autoimmunity.

[18]  A. Cava,et al.  Regulatory T Cells in SLE: Biology and Use in Treatment , 2016, Current Rheumatology Reports.

[19]  J. Anaya,et al.  The Autoimmune Ecology , 2016, Front. Immunol..

[20]  A. Margolles,et al.  Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients , 2016, Scientific Reports.

[21]  Renan Corrêa-Oliveira,et al.  Regulation of immune cell function by short-chain fatty acids , 2016, Clinical & translational immunology.

[22]  N. Câmara,et al.  Innate Sensing of the Gut Microbiota: Modulation of Inflammatory and Autoimmune Diseases , 2016, Front. Immunol..

[23]  P. Gaffney,et al.  Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity , 2016, eLife.

[24]  S. Mani,et al.  Microbial control of intestinal innate immunity , 2015, Oncotarget.

[25]  K. Moudgil Interplay among cytokines and T cell subsets in the progression and control of immune-mediated diseases. , 2015, Cytokine.

[26]  H. Young,et al.  Does the microbiota play a role in the pathogenesis of autoimmune diseases? , 2014, Gut.

[27]  F. Turroni,et al.  Intestinal Dysbiosis Associated with Systemic Lupus Erythematosus , 2014, mBio.

[28]  G. Triadafilopoulos Glucocorticoid therapy for gastrointestinal diseases , 2014, Expert opinion on drug safety.

[29]  Jesse R. Zaneveld,et al.  Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences , 2013, Nature Biotechnology.

[30]  Katherine H. Huang,et al.  Structure, Function and Diversity of the Healthy Human Microbiome , 2012, Nature.

[31]  H. El‐Serag,et al.  Epidemiology of viral hepatitis and hepatocellular carcinoma. , 2012, Gastroenterology.

[32]  Hsin-Jung Wu,et al.  The role of gut microbiota in immune homeostasis and autoimmunity , 2012, Gut microbes.

[33]  Bernard Henrissat,et al.  Recognition and Degradation of Plant Cell Wall Polysaccharides by Two Human Gut Symbionts , 2011, PLoS biology.

[34]  C. Huttenhower,et al.  Metagenomic biomarker discovery and explanation , 2011, Genome Biology.

[35]  William A. Walters,et al.  QIIME allows analysis of high-throughput community sequencing data , 2010, Nature Methods.

[36]  P. Lawson,et al.  Reclassification of Clostridium coccoides, Ruminococcus hansenii, Ruminococcus hydrogenotrophicus, Ruminococcus luti, Ruminococcus productus and Ruminococcus schinkii as Blautia coccoides gen. nov., comb. nov., Blautia hansenii comb. nov., Blautia hydrogenotrophica comb. nov., Blautia luti comb. nov , 2008, International journal of systematic and evolutionary microbiology.

[37]  B. White,et al.  Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis , 2008, Nature Reviews Microbiology.

[38]  D. Gladman,et al.  Systemic lupus erythematosus disease activity index 2000. , 2002, The Journal of rheumatology.

[39]  M. Hochberg,et al.  Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. , 1997, Arthritis and rheumatism.