Adverse Impact of Spp. and Beneficial Role of Spp. on Renal Function: Insights from a Mendelian Randomization Analysis

Background: The microbiota composition is now considered as one of the main modifiable risk factors for health. No controlled study has been performed on the association between microbiota composition and renal function. We applied Mendelian randomization (MR) to estimate the casual impact of eight microbiota genera on renal function and the risk of chronic kidney disease (CKD).

Methods: MR was implemented by using summary-level data from the largest-ever genome-wide association studies (GWAS) conducted on microbiota genera, CKD and renal function parameters. The inverse-variance weighted method (IVW), weighted median (WM)-based method, MR-Egger, MR-Robust Adjusted Profile Score (RAPS), MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. A sensitivity analysis was conducted using the leave-one-out method.

Results: The genus was associated with higher estimated glomerular filtration rate (eGFR) in the overall population (IVW: β = 0.003, = 0.021) and non-diabetes mellitus (DM) subgroup (IVW: β = 0.003, = 0.033), while it had a non-significant association with the risk of CKD and eGFR in DM patients. Subjects with higher abundance of spp. had a significantly lower level of eGFR (IVW: β = -0.001, = 0.035); the same results were observed in non-DM (IVW: β = -0.001, = 0.007) subjects. , , , , and had no significant association with eGFR in the overall population, DM and non-DM subgroups (IVW: > 0.105 for all groups); they also presented no significant association with the risk of CKD (IVW: > 0.201 for all groups). Analyses of MR-PRESSO did not highlight any outlier. The pleiotropy test, with very negligible intercept and insignificant -value, also indicated no chance of pleiotropy for all estimations. The leave-one-out method demonstrated that the observed links were not driven by single single-nucleotide polymorphism.

Conclusions: Our results suggest an adverse association of spp. and a beneficial association of spp. with eGFR. Further studies using multiple robust instruments are needed to confirm these results.