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.

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ObjectivesPeriodontitis (PD) has been linked to arthritis in previous epidemiological observational studies; however, the results are inconclusive. It remains unclear whether the association between PD and arthritis is causal. The purpose of this study was to investigate the causal association of PD with arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA).MethodsWe performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy.ResultsGenetically determined PD did not have a causal effect on OA (OR = 1.06, 95% CI: 0.99-1.15, P = 0.09) and RA (OR = 0.99, 95% CI: 0.87-1.13, P = 0.89). Furthermore, we did not find a significant causal effect of arthritis on PD in the reverse MR analysis. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates according to the sensitivity analysis.ConclusionsOur MR analysis reveals non-causal association of PD with arthritis, despite observational studies reporting an association between PD and arthritis.

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