354 A comparative analysis of gut microbiota between systemic lupus erythematosus patients and non-autoimmune controls: a single centrecenter cohort experience

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease with disturbance of lymphocyte subpopulations1. Growing experimental and clinical evidence suggests that chronic inflammatory response induced by gut microbiome critically contribute to the development of SLE2 3.Objectives:To investigate the characteristics of gut microbiome and the associations between flora and peripheral lymphocyte subpopulations in SLE patients.Methods:A total of 19 SLE patients who fulfilled the 2019 American college of Rheumatology (ACR) and European League Against Rheumatism (EULAR) classification criteria and 16 age- and sex- matched healthy controls (HC) were enrolled in this study. The peripheral T lymphocyte subsets of these participants were assessed by flow cytometry and the gut microbiota were investigated via 16s rRNA. Indicators of disease activity such as erythrocyte sedimentation rate (ESR), complement C3 and C4 were recorded at the same time. Mann-Whitney U test was applied to compare T lymphocyte subsets between SLE patients and HC. Spearman analysis was used for calculating correlation between T subsets and highly expressed differential flora as well as their correlation with disease activity indicators. All P-values reported herein were two-tailed and P-value<0.05 was taken as statistically significant.Results:SLE patients had higher proportions of Th17 cells (P=0.020) and γδT cells (P=0.018) but lower levels of Treg cells (P=0.001), Tfh cells (P=0.018) and Naïve CD4+T cells (P=0.004) (Figure 1a-e). The diversity and relative abundance of intestinal flora in patients with SLE were significantly different from those in HCs. Detailly, the α-diversity was decreased in SLE (P<0.05) (Figure 2a-c). Compared with HC, 11 species of flora were discovered to be distinctly different(P<0.05) (Figure 2d-e). Moreover, there was a significant positive correlation between Treg levels and Ruminococcus2 (P=0.042), Th17 and Megamonas (P=0.009), γδT and Streptococcus (P=0.004) as well as Megamonas (P=0.003), Tfh and Bacteroides (P=0.040). Whereas Th1 levels and Bifidobacterium were negatively correlated in these participants (P=0.005). As for clinical disease measures, there were negative correlations not only between ESR and Treg cells (P=0.031) but also C4 and the amount of Unclassified Ruminococcaceae (P=0.032).Conclusion:Abnormality of T cell subsets, especially the level of Naïve CD4+T, γδT, Tfh, Treg, and Th17 cells contributes to the occurrence and progression of SLE, which may be related to the disturbance of gut microbiota. Therefore it is necessary to attach importance to the alteration of gut microbiota to prevent the outbreak of inflammation and maybe they can be identified as biomarkers predicting disease activity.References:[1]Katsuyama T, Tsokos GC, Moulton VR. Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus. Front Immunol 2018;9:1088. doi: 10.3389/fimmu.2018.01088 [published Online First: 2018/06/06][2]López P, de Paz B, Rodríguez-Carrio J, et al. Th17 responses and natural IgM antibodies are related to gut microbiota composition in systemic lupus erythematosus patients. Sci Rep 2016;6:24072. doi: 10.1038/srep24072 [published Online First: 2016/04/06][3]Esmaeili SA, Mahmoudi M, Momtazi AA, et al. Tolerogenic probiotics: potential immunoregulators in Systemic Lupus Erythematosus. J Cell Physiol 2017;232(8):1994-2007. doi: 10.1002/jcp.25748 [published Online First: 2016/12/21]Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared.

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Comparative analysis of the sensitivity and specificity of the classification criteria and correlation with prognosis of disease in patients with Systemic Lupus Erythematosus

Mediterranean Journal of Rheumatology ◽

10.31138/mjr.29.4.232 ◽

2018 ◽

Vol 29 (4) ◽

pp. 232-235

Author(s):

Christina damichou ◽

Dionysios Nikolopoulos ◽

Emmanouil Papastefanakis ◽

Eleni Kalogiannaki ◽

Irini Gergianaki ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Comparative Analysis ◽

Sensitivity And Specificity ◽

Lupus Erythematosus ◽

Classification Criteria ◽

Systemic Lupus

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Altered Profile of Fecal Microbiota in Newly Diagnosed Systemic Lupus Erythematosus Egyptian Patients

International Journal of Microbiology ◽

10.1155/2021/9934533 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Marian A. Gerges ◽

Noura E. Esmaeel ◽

Wafaa K. Makram ◽

Doaa M. Sharaf ◽

Manar G. Gebriel

Keyword(s):

Systemic Lupus Erythematosus ◽

Gut Microbiota ◽

Disease Activity ◽

Lupus Erythematosus ◽

Healthy Subjects ◽

Fecal Microbiota ◽

Healthy Controls ◽

Newly Diagnosed ◽

Systemic Lupus ◽

Egyptian Patients

Background. Dysbiosis of gut microbiota could promote autoimmune disorders including systemic lupus erythematosus (SLE). Clarifying this point would be of great importance in understanding the pathogenesis and hence the development of new strategies for SLE treatment. Aim. This study aimed to determine the fecal microbiota profile in newly diagnosed SLE patients compared to healthy subjects and to investigate the correlation of this profile with disease activity. Methods. Newly diagnosed SLE patients who fulfilled at least four of the American College of Rheumatology (ACR) criteria were enrolled during the study period. Patients with lupus were matched to healthy subjects. SLE activity was evaluated using the Systemic Lupus Disease Activity Index (SLEDAI-2K). Fresh fecal samples were collected from each subject. Genomic DNA was extracted from fecal samples. Quantitative real-time PCR was applied for quantitation of Firmicutes phylum, Bacteroidetes phylum, and Lactobacillus genus in comparison to the total fecal microbiota. Results of patients’ samples were compared to those of healthy subjects and were correlated to patients’ SLEDAI-2K score. Results. Twenty SLE patients’ samples were compared with 20 control samples. There was a significant alteration in SLE patients’ gut microbiota. A significantly lower ( p ≤ 0.001 ) Firmicutes/Bacteroidetes (F/B) ratio in SLE patients (mean ratio: 0.66%) compared to healthy subjects (mean ratio: 1.79%) was found. Lactobacillus showed a significant decrease in SLE patients ( p = 0.006 ) in comparison to healthy controls. An inverse significant correlation between SLEDAI-2K scores for disease activity and F/B ratio (r = −0.451; p = 0.04 ) was found. However, an inverse nonsignificant correlation between SLEDAI-2K scores for disease activity and Lactobacillus (r = −0.155; p = 0.51 ) was detected. Conclusion. Compared to healthy controls, recently diagnosed SLE Egyptian patients have an altered fecal microbiota profile with significant lowering of both F/B ratio and Lactobacillus abundance, which is weakly correlated with disease activity.

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Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice

Arthritis Research & Therapy ◽

10.1186/s13075-021-02620-w ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Mingzhu Wang ◽

Zhengyang Zhu ◽

Xiaoying Lin ◽

Haichang Li ◽

Chengping Wen ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Side Effects ◽

Gut Microbiota ◽

Lupus Erythematosus ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Therapeutic Effects ◽

Systemic Lupus ◽

Therapeutic Efficiency ◽

Dose Dependent

Abstract Background Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs. Methods Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone. Results The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella. Conclusions These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.

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Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies

Frontiers in Immunology ◽

10.3389/fimmu.2021.799788 ◽

2021 ◽

Vol 12 ◽

Author(s):

Quanren Pan ◽

Fengbiao Guo ◽

Yanyan Huang ◽

Aifen Li ◽

Shuxian Chen ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Epithelial Cells ◽

Gut Microbiota ◽

Lupus Erythematosus ◽

Intestinal Epithelial Cells ◽

Therapeutic Strategies ◽

Oral Antibiotic ◽

Intestinal Epithelial ◽

Systemic Lupus ◽

Gut Microbiota Dysbiosis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that was traditionally thought to be closely related to genetic and environmental risk factors. Although treatment options for SLE with hormones, immunosuppressants, and biologic drugs are now available, the rates of clinical response and functional remission of these drugs are still not satisfactory. Currently, emerging evidence suggests that gut microbiota dysbiosis may play crucial roles in the occurrence and development of SLE, and manipulation of targeting the gut microbiota holds great promises for the successful treatment of SLE. The possible mechanisms of gut microbiota dysbiosis in SLE have not yet been well identified to date, although they may include molecular mimicry, impaired intestinal barrier function and leaky gut, bacterial biofilms, intestinal specific pathogen infection, gender bias, intestinal epithelial cells autophagy, and extracellular vesicles and microRNAs. Potential therapies for modulating gut microbiota in SLE include oral antibiotic therapy, fecal microbiota transplantation, glucocorticoid therapy, regulation of intestinal epithelial cells autophagy, extracellular vesicle-derived miRNA therapy, mesenchymal stem cell therapy, and vaccination. This review summarizes novel insights into the mechanisms of microbiota dysbiosis in SLE and promising therapeutic strategies, which may help improve our understanding of the pathogenesis of SLE and provide novel therapies for SLE.

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