Mendelian randomization analysis reveals a shared protective role of gut microbiota genus Alloprevotella in spontaneous abortion and rheumatoid arthritis

Previous studies to date have demonstrated a significant relationship between spontaneous abortion (SA) and rheumatoid arthritis (RA). Moreover, positive links between gut microbiota and SA, RA have been discussed in observational studies. However, observational studies are prone to bias and result in the causality between gut microbiota and the comorbidity of SA and RA remaining unclear. We therefore aimed to investigate this using a two-sample Mendelian randomization study. A total gut microbiota-related sample size of 18,340 participants from genome-wide association studies was obtained. The summary statistics data for SA (98,453 subjects) and RA (1,53,457 subjects) were obtained from the MRC integrative epidemiology unit genome-wide association studies database as the outcome of gut microbiota. Inverse variance weighted, weighted median, weighted mode, MR-Egger and simple mode were used to assess the causal effects. Sensitivity analyses were applied using the Cochran's Q-statistic, MR-Egger, the leave-one-out analysis, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO). In addition, the statistical power was calculated to evaluate the cause-and-effect. We identified genus Alloprevotella as a shared protective factor for both SA (odds ratio [OR] = 0.903, 95% CI: 0.817-0.997, P = .043) and RA (OR = 0.826, 95% CI: 0.722-0.945, P = .005). In addition, increased abundance of genera Actinomyces (OR = 1.213, 95% CI: 1.025-1.435, P = .025), Subdoligranulum (OR = 1.208, 95% CI: 1.036-1.408, P = .016), and Veillonella (OR = 1.167, 95% CI: 1.003-1.358, P = .046) was causally associated with a higher risk of SA. For RA, decreased abundance of genera ChristensenellaceaeR (OR = 0.736, 95% CI: 0.570-0.950, P = .018), Enterorhabdus (OR = 0.806, 95% CI: 0.684-0.950, P = .010), Prevotella7 (OR = 0.895, 95% CI: 0.808-0.991, P = .032) and Hungatella (OR = 0.818, 95% CI: 0.691-0.970, P = .021), along with increased abundance of the Ruminococcus gauvreauii group (OR = 1.406, 95% CI: 1.112-1.777, P = .004), was linked to elevated disease risk. Sensitivity analyses, including MR-PRESSO, MR-Egger, and Cochran's Q-statistic, revealed no evidence of heterogeneity or pleiotropy. Furthermore, leave-one-out analysis confirmed the robustness of the causal estimates. Our study identified several gut microbiota genera with putative causal effects on SA (4 genera) and RA (6 genera). Notably, Alloprevotella emerged as a shared protective factor for both conditions. These findings suggest that gut microbiota, particularly Alloprevotella, may play a causal, protective role in the shared etiology of SA and RA, highlighting a potential common therapeutic target for future research and clinical management.