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

1
Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas’ Hospital, Strand, London SE1 7EH, UK
2
Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 14155-6446, Iran
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Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, and ‘Grigore T. Popa’ University of Medicine, 700469 Iasi, Romania
4
Department of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London NW3 2QG, UK
5
Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, 93-338 Lodz, Poland
6
Polish Mother’s Memorial Hospital Research Institute (PMMHRI), 93-338 Lodz, Poland
7
Cardiovascular Research Centre, University of Zielona Gora, 65-046 Zielona Gora, Poland
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(8), 2216; https://doi.org/10.3390/nu12082216
Received: 2 July 2020 / Revised: 13 July 2020 / Accepted: 22 July 2020 / Published: 25 July 2020
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 Anaerostipes genus was associated with higher estimated glomerular filtration rate (eGFR) in the overall population (IVW: β = 0.003, p = 0.021) and non-diabetes mellitus (DM) subgroup (IVW: β = 0.003, p = 0.033), while it had a non-significant association with the risk of CKD and eGFR in DM patients. Subjects with higher abundance of Desulfovibrio spp. had a significantly lower level of eGFR (IVW: β = −0.001, p = 0.035); the same results were observed in non-DM (IVW: β = −0.001, p = 0.007) subjects. Acidaminococcus, Bacteroides, Bifidobacterium, Faecalibacterium, Lactobacillus and Megamonas had no significant association with eGFR in the overall population, DM and non-DM subgroups (IVW: p > 0.105 for all groups); they also presented no significant association with the risk of CKD (IVW: p > 0.201 for all groups). Analyses of MR-PRESSO did not highlight any outlier. The pleiotropy test, with very negligible intercept and insignificant p-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 Desulfovibrio spp. and a beneficial association of Anaerostipes spp. with eGFR. Further studies using multiple robust instruments are needed to confirm these results. View Full-Text
Keywords: mendelian randomization; microbiota; chronic kidney disease mendelian randomization; microbiota; chronic kidney disease
MDPI and ACS Style

Mazidi, M.; Shekoohi, N.; Covic, A.; Mikhailidis, D.P.; Banach, M. Adverse Impact of Desulfovibrio spp. and Beneficial Role of Anaerostipes spp. on Renal Function: Insights from a Mendelian Randomization Analysis. Nutrients 2020, 12, 2216.

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