Association between sphingomyelin levels and gut microbiota abundance: a two-sample Mendelian randomization study

Abstract Background Several previous observational studies have shown that abnormal sphingomyelin metabolism may be implicated in the pathogenesis of Alzheimer's disease. To determine the causal relationship between sphingolipid abundance and gut microbiota abundance at the genetic level, we conducted a Mendelian randomization (MR) investigation. Methods We first used the TwoSampleMR and MRPRESSO packages for conducting two-sample MR studies. Second, we utilized random effect inverse variance weighting (IVW) as the principal method of analysis and used MR‒Egger, the weighted median, the simple mode and the weighted mode as supplementary methods. Finally, we performed tests for heterogeneity and horizontal pleiotropy. These analyses were also conducted to evaluate the impact of individual SNPs on the outcomes of our analysis. Results The results showed that the level of sphingomyelin was correlated with the abundance of 6 gut microbiota species, among which 2 were positively correlated with the family Alcaligenaceae (p = 0.006, beta 95% CI = 0.103 [0.029, 0.178]) and the species Ruminococcus callidus (p = 0.034, beta 95% CI = 0.197 [0.015, 0.378]). There were negative correlations with the abundances of 4 gut microbiota abundencegenera, such as the genus Flavonifractor (p = 0.026, beta 95%CI = -0.218 [-0.411, -0.026]) and the genus Streptococcus (p = 0.014, beta 95% CI = -0.096 [-0.172, -0.019]). The results presented a normal distribution with no anomalous values, heterogeneity or horizontal pleiotropic effects detected. Conclusions This two-sample Mendelian randomization study revealed a causal relationship between sphingomyelin levels and gut microbiota abundance.