Dataset Information

Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus.

ABSTRACT:

Objectives

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved.

Methods

Fecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), and their gut microbiome and gene expression in recipients' colons were examined by NGS. The anti-double stranded DNA (anti-dsDNA) antibodies in recipients were determined using an enzyme-linked immunosorbent assay (ELISA). The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real-time PCR (qRT-PCR).

Results

The fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti-dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes.

Conclusions

SLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti-dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice.

SUBMITTER: Ma Y

PROVIDER: S-EPMC6676588 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus.

Ma Yiyangzi Y Xu Xiaoxue X Li Mengtao M Cai Jun J Wei Qiang Q Niu Haitao H

Molecular medicine (Cambridge, Mass.) 20190801 1

<h4>Objectives</h4>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved.<h4>Methods</h4>Fecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), an ...[more]

PMID: 31370803

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Project description:IntroductionDespite recent developments in our comprehension of how the gut microbiota and systemic lupus erythematosus (SLE) are related. The mycobiome: which is a small but crucial part of the gut microbiota and is involved in hosts' homeostasis and physiological processes, remained unexplored in SLE.MethodsWe profiled the gut fungal mycobiota based on internal transcribed spacer region 1 (ITS1) sequencing for the gut microbial DNA from the SLE individuals with lupus nephritis (LN) (n = 23), SLE without LN (n = 26) and healthy controls (n = 14) enrolled in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School.ResultsThe ITS sequencing generated a total of 4.63 million valid tags which were stratified into 4,488 operational taxonomic units (OTUs) and identified about 13 phyla and 262 genera. Patients with SLE were characterized with unique fungal flora feature. The fungal microbiomes of the three groups displayed distinct beta diversity from each other. Compared with HC group, the abundance of fungal dysbiosis was reflected in a higher ratio of opportunistic fungi in SLE or LN group, as well as the loss of Rhizopus and Malassezia. The main principal components of the flora between the SLE and LN group were generally consistent. The relative abundance of Vanrija in the fecal fungal community was higher in LN group, while the relative abundance of Fusarium was higher in SLE group. Moreover, our data revealed superior diagnostic accuracy for SLE with the fungal species (e.g. Candida, Meyerozyma). Correlations between gut fungi and clinical parameters were identified by Spearman's correlation analysis. Interestingly, Aspergillus in SLE patients was positively correlated with ACR, 24 h proteinuria, proteinuria, anti-dsDNA, ANA, and SLEDAI, while Rhizopus was negatively correlated with lymphocytes and Hb. Finally, we successfully cultured the fungi and identified it as Candida glabrata by microscopic observation and mass spectrometry.DiscussionWe first explored the highly significant gut fungal dysbiosis and ecology in patients with SLE, and demonstrated the applicability of fungal species as SLE diagnostic tools, signifying that the gut fungal mycobiome-host interplay can potentially contribute in disease pathogenesis.

Project description:Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera Odoribacter and Blautia and an unnamed genus in the family Rikenellaceae) and was less diverse, with increased representation of Gram-negative bacteria. The Firmicutes/Bacteroidetes ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort.IMPORTANCE SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a group of SLE patients with active disease.

Project description:BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes.MethodsA total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann-Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation.ResultsCompared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4.ConclusionGut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.

Dataset Information

Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus.

Objectives

Methods

Results

Conclusions

Publications

Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus.

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