Objective: Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods: Mendelian randomization (MR) is a type of instrumental variables (IVs) analysis; MR follows the Mendelian genetic rule of “parental alleles are randomly assigned to offspring” and takes genetic variation as IVs to infer the causal association between exposure factors and study outcome in observational studies. Genome-wide association study (GWAS) summary data of AS were from the FinnGen consortium, and the gut microbiota (Bacteroides, Streptococcus, Proteobacteria, Lachnospiraceae) were from the MiBioGen consortium. The TwoSampleMR and MRPRESSO packages of the R were used to perform a two-sample MR study. Random-effects inverse variance weighted (IVW) was the main analysis method, and MR Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We examined heterogeneity and horizontal pleiotropy, and examined whether the analysis results were influenced by a single SNP. We applied radial variants of the IVW and MR-Egger model for the improved visualization of the causal estimate. We further examined the causal relationship between AS and gut microbiota, and the robustness of the analysis results. Finally, we performed maximum likelihood, penalized weighted median, and IVW (fixed effects) to further identify the potential causal association. Results: The random-effects IVW results showed that Bacteroides (p = 0.965, OR 95% confidence interval [CI] = 0.990 [0.621–1.579]), Streptococcus (p = 0.591, OR 95% CI = 1.120 [0.741–1.692]), Proteobacteria (p = 0.522, OR 95% CI = 1.160 [0.737–1.826]), and Lachnospiraceae (p = 0.717, OR 95% CI = 1.073 [0.732–1.574]) have no genetic causal relationship with AS. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The MR analysis results were not driven by a single SNP. Conclusion: This study showed that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae, four common gut microbiotas associated with AS, had no causal relationship with AS at the genetic level. This study makes a positive contribution to the genetics of AS, but the insufficient number of gut microbiota included is a limitation.

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Several observational studies have indicated the potential associations among calcium, vitamin D (Vit-D), and irritable bowel syndrome (IBS). However, the causal relationship deduced from these studies is subject to residual confounding factors and reverse causation. Therefore, we aimed to explore the bidirectional causal effects among serum calcium, Vit-D, PTH, and IBS at the genetic level by a two-sample Mendelian randomization (MR) analysis of the datasets from IEU OpenGWAS database. Sensitivity analyses were performed to evaluate the robustness. The estimates were presented as odds ratios (ORs) with their 95% confidence intervals (CIs). The results of the inverse variance weighted method did not reveal any causal relationship between the genetically predisposed calcium (OR = 0.92, 95% CI: 0.80–1.06, p = 0.25) and Vit-D (OR = 0.99, 95% CI: 0.83–1.19, p = 0.94) level and the risk of IBS. The bidirectional analysis demonstrated that genetic predisposition to IBS was associated with a decreased level of PTH (beta: −0.19, 95%CI: −0.34 to −0.04, p = 0.01). In conclusion, the present study indicates no causal relationship between the serum calcium and Vit-D concentrations and the risk of IBS. The potential mechanisms via which IBS affects serum PTH need to be further investigated.