Higher Plasma Levels of Valerate Produced by Gut Microbiota May Have a Beneficial Impact on Renal Function

Abstract

Objective

Observational studies have evaluated the relationships among plasma short chain fatty acids (SCFA) produced by gut microbiota, renal function, and risk of chronic kidney disease (CKD). In the present study, Mendelian Randomization (MR) analysis was applied to obtain unconfounded estimates of the casual association of genetically determined plasma valerate (an SCFA) with kidney function and risk of CKD.

Method

MR was performed by using summary-level data from the largest genome-wide association studies (GWAS) conducted on plasma valerate, CKD, and estimated glomerular filtration rate (eGFR; separately in diabetic and nondiabetic individuals). Inverse variance weighted method (IVW), weighted median–based method, MR-Egger, as well as MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. Sensitivity analysis was conducted using the leave-one-out method.

Results

No significant association was observed between plasma valerate and CKD (IVW: β = 0.234, p = 0.744). In contrast, plasma valerate was positively associated with eGFR in the total population (IVW: β = 0.049, p = 0.022) and among nondiabetic individuals (IVW: β = 0.058, p = 0.009), but not in the diabetic population (IVW: β = −0.052, p = 0.603). None of the estimated associations was subjected to significant level of heterogeneity. Furthermore, MR-PRESSO analysis did not show any chance of outlier for all estimates. The pleiotropy test, with very a negligible intercept and insignificant p value, also indicated no chance of pleiotropy for all of our estimations (all p > 0.539). The results of the MR-Robust Adjusted Profile Score were identical with the IVW estimates, highlighting again no possibility of pleiotropy. Results of the leave-one-out method demonstrated that the links were not driven by single-nucleotide polymorphisms.

Conclusions

Individuals with higher plasma valerate levels had better renal function, defined by eGFR. This finding was observed in the total population and in nondiabetic subjects, but not in those with diabetes. Further research is needed to elucidate the links among plasma valerate, kidney function, and CKD.

Keywords:

• Mendelian randomization
• valerate
• chronic kidney disease
• glomerular filtration rate
• short chain fatty acids
• gut microbiota

Conflict of interest

NK has given talks, attended conferences, and participated in trials sponsored by Amgen, AstraZeneca, Bausch Health, Boehringer Ingelheim, Elpen, Mylan, Novo Nordisk, Sanofi, and Servier. The other authors have no conflict of interest to declare.

Financial disclosure

None.

Acknowledgments

None.