Abstract
The observational association between gut microbiome and systemic lupus erythematosus (SLE) has been well documented. However, whether the association is causal remains unclear. The present study used publicly available genome-wide association study (GWAS) summary data to perform two-sample Mendelian randomization (MR), aiming to examine the causal links between gut microbiome and SLE. Two sets of MR analyses were conducted. A group of single nucleotide polymorphisms (SNPs) that less than the genome-wide statistical significance threshold (5 × 10-8) served as instrumental variables. To obtain a comprehensive conclusion, the other group where SNPs were smaller than the locus-wide significance level (1 × 10-5) were selected as instrumental variables. Based on the locus-wide significance level, the results indicated that there were causal effects of gut microbiome components on SLE risk. The inverse variance weighted (IVW) method suggested that Bacilli and Lactobacillales were positively correlated with the risk of SLE and Bacillales, Coprobacter and Lachnospira were negatively correlated with SLE risk. The results of weighted median method supported that Bacilli, Lactobacillales, and Eggerthella were risk factors for SLE and Bacillales and Coprobacter served as protective factors for SLE. The estimates of MR Egger suggested that genetically predicted Ruminiclostridium6 was negatively associated with SLE. Based on the genome-wide statistical significance threshold, the results showed that Actinobacteria might reduce the SLE risk. However, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) detected significant horizontal pleiotropy between the instrumental variables of Ruminiclostridium6 and outcome. This study support that there are beneficial or detrimental causal effects of gut microbiome components on SLE risk.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease involving multiple organs, and it presents with a range of clinical symptoms, including skin rash, pericarditis, nephritis, and neurological and hematological involvement
inverse variance weighted (IVW) is essentially a meta-analysis method, which converts to a weighted regression of the outcome effects of instrumental variables on the exposure effects to obtain an overall estimate of the impact of gut microbiome on the risk of SLE, where the intercept is limited to zero [14]
Heterogeneity and horizontal pleiotropy could not be examined due to the limited number of included SNPs. This two-sample MR study suggested that the levels of Bacillales, Coprobacter, Lachnospira, and Actinobacteria were negatively related to the risk of SLE, and Bacilli, Lactobacillales, and Eggerthella might be the risk factors for SLE onset
Summary
Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease involving multiple organs, and it presents with a range of clinical symptoms, including skin rash, pericarditis, nephritis, and neurological and hematological involvement. Loss of tolerance to autoantigens is one of the hallmarks of SLE. Hormonal, and environmental factors interact in susceptible individuals, resulting in autoantibodies deposition and abnormal production of proinflammatory cytokines [1]. Ultraviolet light and infections induce DNA damage and apoptosis which increase exposure to autoantigens are potential triggers for SLE as well [2]. The current treatment strategy is mainly the use of non-selective immunosuppressive agents. Long-term use of immunosuppressants weakens the immunity and results in severe infections [3]. It is imperative to explore the etiology of SLE to facilitate the development of treatment strategies with low damage or even no side effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
