Assessing the relationship between gut microbiota ( family, orders, classes,and phyla) and gestational diabetes mellitus : a two-sample Mendelian randomization analysis

Abstract Background Previous studies have shown that gut microbiota (GM) are associated with gestational diabetes mellitus (GDM). Although it is unclear if the association is causative. This study used Mendelian randomization (MR) to systematically examine whether the gut microbiota was causally linked to GDM .There have been numerous Mendelian randomization (MR) studies that between the gut microbiota abundance (genus) and gestational diabetes mellitus (GDM). However, the gut microbiota abundance(family, orders, classes,and phyla)have yet to be fully investigated.This study used Mendelian randomization (MR) to systematically examine whether several gut microbiota taxa was causally linked to GDM. Methods Genetic instrumental variables for the gut microbiota were identified from a genome-wide association study (GWAS) involving 14306 participants. Summary statistics for gestational diabetes mellitus(GDM)were drawn from another GWAS, which included 6033 cases and 110330 controls.Maximum likelihood (ML), MR-Egger regression, weighted median, inverse variance weighted(IVW), and weighted model were used to investigate the causal association between gut microbiota and GDM. To examine the causal association, several methods were utilized, including inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS. We further conducted a series of sensitivity analyses to confirm the robustness of the primary results of the MR analyses.Reverse MR analysis was performed on the bacterial taxa that were reported to be causally linked to GDM risk in forwarding MR analysis to evaluate the possibility of reverse causation. Furthermore, sensitivity analyses were performed to identify any potential heterogeneity and horizontal pleiotropy. Results MR analysis revealed that phylum Tenericutes (OR: 0.717 95%CI: 0.573–0.896, P = 0.003), class Mollicutes (OR: 0.717, 95%CI: 0.573–0.896, P = 0.003)were related to a lower risk of GDM, and family Lactobacillaceae(OR: 1.303, 95%CI: 1.001–1.697, P = 0.049)were positively associated with the risk of GDM. Additional sensitivity analyses confirmed the robustness of the association between specific gut microbiota composition and GDM. In the reverse Mendelian randomization (MR) analysis, we did not find evidence that these was statistically significant associations between GDM and these three bacterial traits. Conclusions Our systematic analysis provides evidence to explore the causal associations among GM and GDM. More studies are needed to clarify how the gut microbiota(family, orders, classes,and phyla) affects the development of GDM.