An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus

Chen, Beidi; Jia, Xiaoyun; Xu, Jiayue; Li, Zhao; Ji, Junyi; Wu, Bingxuan; Ma, Yue; Hao, Li; Zuo, Xiaoxia; Pan, Wei; Wang, Xiaohan; Ye, Shuang; Tsokos, George C.; Wang, Jun; Zhang, Xuan

doi:10.1002/art.41511

Cited by 132 publications

(151 citation statements)

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“…Important research efforts focusing on how human commensal microbes trigger systemic autoimmunity have been made over the last decade [212]. Gut microbial composition and function are markedly altered in untreated SLE patients compared with HCs, having an autoimmunogenic and proinflammatory profile characterized by a consistently reduced Firmicutes-to-Bacteroidetes ratio [213,214].…”

Section: Analysis and Modulation Of Microbiotamentioning

confidence: 99%

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

Quaglia

Merlotti

Andrea

et al. 2021

Viruses

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A causal link between viral infections and autoimmunity has been studied for a long time and the role of some viruses in the induction or exacerbation of systemic lupus erythematosus (SLE) in genetically predisposed patients has been proved. The strength of the association between different viral agents and SLE is variable. Epstein–Barr virus (EBV), parvovirus B19 (B19V), and human endogenous retroviruses (HERVs) are involved in SLE pathogenesis, whereas other viruses such as Cytomegalovirus (CMV) probably play a less prominent role. However, the mechanisms of viral–host interactions and the impact of viruses on disease course have yet to be elucidated. In addition to classical mechanisms of viral-triggered autoimmunity, such as molecular mimicry and epitope spreading, there has been a growing appreciation of the role of direct activation of innate response by viral nucleic acids and epigenetic modulation of interferon-related immune response. The latter is especially important for HERVs, which may represent the molecular link between environmental triggers and critical immune genes. Virus-specific proteins modulating interaction with the host immune system have been characterized especially for Epstein–Barr virus and explain immune evasion, persistent infection and self-reactive B-cell “immortalization”. Knowledge has also been expanding on key viral proteins of B19-V and CMV and their possible association with specific phenotypes such as antiphospholipid syndrome. This progress may pave the way to new therapeutic perspectives, including the use of known or new antiviral drugs, postviral immune response modulation and innate immunity inhibition. We herein describe the state-of-the-art knowledge on the role of viral infections in SLE, with a focus on their mechanisms of action and potential therapeutic targets.

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Section: Analysis and Modulation Of Microbiotamentioning

confidence: 99%

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

Quaglia

Merlotti

Andrea

et al. 2021

Viruses

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“…Microbial dysbiosis has been shown to be associated with several autoimmune disorders, such as systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis (Zhang et al, 2015;Cosorich et al, 2017;Vich Vila et al, 2018;Chen et al, 2020). Disturbance in microbiota can affect host immune response, involving maturation and balance of immune cells, the release of various cytokines and chemokines, protection against pathogens, and absorption and metabolism of medicine and nutrients (Belkaid and Hand, 2014).…”

Section: Introductionmentioning

confidence: 99%

Potential Roles of Oral Microbiota in the Pathogenesis of Immunoglobin A Nephropathy

Zhou

Hou

et al. 2021

Front. Cell. Infect. Microbiol.

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Disturbance in microbiota affects the mucosal immune response, and it is gradually recognized to be associated with the Immunoglobin A nephropathy (IgAN). This study aims to explore the potential roles of oral microbiota in disease pathogenesis. Saliva samples were collected from 31 patients with IgAN and 30 controls for 16S rRNA gene sequencing. The evenness, diversity, and composition of oral microbiota were analyzed. Moreover, sub-phenotype association analysis was conducted. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to investigate microbiota functions. Compared to healthy controls, microbial diversity tended to decrease in IgAN, and the microbial profiles were remarkably distinguished. The relative abundance of Capnocytophaga and SR1_genera_incertae_sedis were enriched, whereas 17 genera, such as Rothia, were significantly reduced in IgAN. Variable importance in projection scores showed that 12 genera, including Capnocytophaga, Rothia, and Haemophilus, could discriminate between the two groups. In the sub-phenotype correlation analysis, the relative abundance of Capnocytophaga and Haemophilus was positively associated with levels of proteinuria and serum IgA, respectively. Further metabolic pathway analysis showed 7 predictive functional profiles, including glycosphingolipid biosynthesis, oxidative phosphorylation, and N-glycan biosynthesis were enriched in IgAN. In conclusion, disturbance in oral microbiota was observed to be associated with IgAN and its sub-phenotypes, which may shed novel insights into disease pathogenesis from a microbiome perspective.

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“…They lead to pro-in ammatory response [35][36][37][38] . In addition, abnormally enriched, antigen mimicry and metabolic response of gut microbiota can cause the disorder of immune response [19,39] . Thus, we tried to include as many studies as possible to obtain and extracted experiment results of alpha diversity and some gut microbiota abundance between SLE patients and healthy people, analyzing the changes of gut microbiota in SLE patients by meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Marc JanBonder [17] proposed that gene-diet interaction can regulate the abundance of Bi dobacterium. The experimental results of Chiara Bellocchi [18] and Jingquan He [19] showed there was no signi cant difference in Shannon-wiener diversity index and Chao1 richness estimator between SLE and healthy controls (HCs). Weifang Zhu [20] drew a different experimental result that chao1 richness estimator of SLE was higher and the Shannon-wiener diversity index was lower compared with HCs.…”

Section: Introductionmentioning

confidence: 99%

The Association Between the Gut Microbiota and Systemic Lupus Erythematosus, a Meta-Analysis

Xiang

Qian

et al. 2021

Preprint

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Introduction: Evaluate the changes of gut Microbiota in patients with Systemic Lupus Erythematosus (SLE) and healthy people by meta-analysis. Methods We searched the case-control studies of SLE and healthy controls (HCs) for detecting the diversity of gut Microbiota and the abundance level of some microbiota in the two groups. StataMP16 software was applied for this meta-analysis. The Newcastle-Ottawa quality assessment scale (NOS) was used to assess the quality of the included studies. Results Eleven case-control studies were included. There were 373 SLE patients and 1288 healthy people, involving 5 countries and 9 different cities. Compared with the HCs, the Shannon-wiener diversity index (WMD=-0.22; 95% CI=-0.32 to -0.13; P = 0.000) and Chao1 richness estimator (SMD=-0.62; 95% CI=-1.04 to -0.21; P = 0.003) of gut Microbiota in SLE decreased, and the abundance level of Ruminococcaceae decreased (SMD=--0.48; 95% CI = 0.76 to-0.21; P = 0.001). Enterobacteriaceae (SMD = 0.39,95% CI = 0.11 to 0.66;P = 0.006) and Enterococcaceae (SMD = 0.55; 95% CI = 0.19 to 0.9; P = 0.03) showed higher abundance levels in comparison with HCs. The subgroup analysis showed the abundance level of Ruminococcaceae (SMD=-0.89; 95% CI =-1.34 to -0.45; P = 0.000) was lower and Enterococcaceae was higher (SMD = 0.77; 95% CI = 0.34 to 1.21༛P = 0.001) in Chinese with SLE compared with HCs. In non-Chinese patients with SLE, there were no significant difference between the abundance level of Ruminococcaceae (SMD=-0.22; 95% CI=--0.58 to 0.13; P = 0.216) and Enterococcaceae (SMD=-0.08; 95% CI=-0.49 to 0.32; P = 0.682 ) with HCs. The subgroup analysis also found the level of Enterobacteriaceae was affected by the sample size. Conclusion Compared with the diversity of healthy people, richness and evenness of gut microbiota in patients with SLE are impaired. There is a decrease in the abundance level of beneficial bacteria and an increase in the harmful bacteria. Thus, gut microbiota in patients with SLE appear disorder, which may lead to metabolic imbalance, destruction of the integrity of the small intestine, immune system disorders and pro-inflammatory. Regulating the abundance of gut microbiota can be used as one of the key strategies for treating SLE.

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An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus

Cited by 132 publications

References 50 publications

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

Potential Roles of Oral Microbiota in the Pathogenesis of Immunoglobin A Nephropathy

The Association Between the Gut Microbiota and Systemic Lupus Erythematosus, a Meta-Analysis

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