Adverse Impact of <i>Desulfovibrio</i> spp. and Beneficial Role of <i>Anaerostipes</i> 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...

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Main Authors: Mohsen Mazidi, Niloofar Shekoohi, Adrian Covic, Dimitri P. Mikhailidis, Maciej Banach
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Nutrients
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Online Access:https://www.mdpi.com/2072-6643/12/8/2216
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author Mohsen Mazidi
Niloofar Shekoohi
Adrian Covic
Dimitri P. Mikhailidis
Maciej Banach
author_facet Mohsen Mazidi
Niloofar Shekoohi
Adrian Covic
Dimitri P. Mikhailidis
Maciej Banach
author_sort Mohsen Mazidi
collection DOAJ
description 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 <i>Anaerostipes</i> genus was associated with higher estimated glomerular filtration rate (eGFR) in the overall population (IVW: β = 0.003, <i>p</i> = 0.021) and non-diabetes mellitus (DM) subgroup (IVW: β = 0.003, <i>p</i> = 0.033), while it had a non-significant association with the risk of CKD and eGFR in DM patients. Subjects with higher abundance of <i>Desulfovibrio</i> spp. had a significantly lower level of eGFR (IVW: β = −0.001, <i>p</i> = 0.035); the same results were observed in non-DM (IVW: β = −0.001, <i>p</i> = 0.007) subjects. <i>Acidaminococcus</i>, <i>Bacteroides</i>, <i>Bifidobacterium</i>, <i>Faecalibacterium</i>, <i>Lactobacillus</i> and <i>Megamonas</i> had no significant association with eGFR in the overall population, DM and non-DM subgroups (IVW: <i>p</i> > 0.105 for all groups); they also presented no significant association with the risk of CKD (IVW: <i>p</i> > 0.201 for all groups). Analyses of MR-PRESSO did not highlight any outlier. The pleiotropy test, with very negligible intercept and insignificant <i>p</i>-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 <i>Desulfovibrio</i> spp. and a beneficial association of <i>Anaerostipes</i> spp. with eGFR. Further studies using multiple robust instruments are needed to confirm these results.
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spelling doaj.art-d99019d93650475ca8e709193d939c8b2023-11-20T07:55:22ZengMDPI AGNutrients2072-66432020-07-01128221610.3390/nu12082216Adverse Impact of <i>Desulfovibrio</i> spp. and Beneficial Role of <i>Anaerostipes</i> spp. on Renal Function: Insights from a Mendelian Randomization AnalysisMohsen Mazidi0Niloofar Shekoohi1Adrian Covic2Dimitri P. Mikhailidis3Maciej Banach4Department of Twin Research and Genetic Epidemiology, King’s College London, St Thomas’ Hospital, Strand, London SE1 7EH, UKDepartment of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 14155-6446, IranNephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, and ‘Grigore T. Popa’ University of Medicine, 700469 Iasi, RomaniaDepartment of Clinical Biochemistry, Royal Free Campus, University College London Medical School, University College London (UCL), London NW3 2QG, UKDepartment of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, 93-338 Lodz, PolandBackground: 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 <i>Anaerostipes</i> genus was associated with higher estimated glomerular filtration rate (eGFR) in the overall population (IVW: β = 0.003, <i>p</i> = 0.021) and non-diabetes mellitus (DM) subgroup (IVW: β = 0.003, <i>p</i> = 0.033), while it had a non-significant association with the risk of CKD and eGFR in DM patients. Subjects with higher abundance of <i>Desulfovibrio</i> spp. had a significantly lower level of eGFR (IVW: β = −0.001, <i>p</i> = 0.035); the same results were observed in non-DM (IVW: β = −0.001, <i>p</i> = 0.007) subjects. <i>Acidaminococcus</i>, <i>Bacteroides</i>, <i>Bifidobacterium</i>, <i>Faecalibacterium</i>, <i>Lactobacillus</i> and <i>Megamonas</i> had no significant association with eGFR in the overall population, DM and non-DM subgroups (IVW: <i>p</i> > 0.105 for all groups); they also presented no significant association with the risk of CKD (IVW: <i>p</i> > 0.201 for all groups). Analyses of MR-PRESSO did not highlight any outlier. The pleiotropy test, with very negligible intercept and insignificant <i>p</i>-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 <i>Desulfovibrio</i> spp. and a beneficial association of <i>Anaerostipes</i> spp. with eGFR. Further studies using multiple robust instruments are needed to confirm these results.https://www.mdpi.com/2072-6643/12/8/2216mendelian randomizationmicrobiotachronic kidney disease
spellingShingle Mohsen Mazidi
Niloofar Shekoohi
Adrian Covic
Dimitri P. Mikhailidis
Maciej Banach
Adverse Impact of <i>Desulfovibrio</i> spp. and Beneficial Role of <i>Anaerostipes</i> spp. on Renal Function: Insights from a Mendelian Randomization Analysis
Nutrients
mendelian randomization
microbiota
chronic kidney disease
title Adverse Impact of <i>Desulfovibrio</i> spp. and Beneficial Role of <i>Anaerostipes</i> spp. on Renal Function: Insights from a Mendelian Randomization Analysis
title_full Adverse Impact of <i>Desulfovibrio</i> spp. and Beneficial Role of <i>Anaerostipes</i> spp. on Renal Function: Insights from a Mendelian Randomization Analysis
title_fullStr Adverse Impact of <i>Desulfovibrio</i> spp. and Beneficial Role of <i>Anaerostipes</i> spp. on Renal Function: Insights from a Mendelian Randomization Analysis
title_full_unstemmed Adverse Impact of <i>Desulfovibrio</i> spp. and Beneficial Role of <i>Anaerostipes</i> spp. on Renal Function: Insights from a Mendelian Randomization Analysis
title_short Adverse Impact of <i>Desulfovibrio</i> spp. and Beneficial Role of <i>Anaerostipes</i> spp. on Renal Function: Insights from a Mendelian Randomization Analysis
title_sort adverse impact of i desulfovibrio i spp and beneficial role of i anaerostipes i spp on renal function insights from a mendelian randomization analysis
topic mendelian randomization
microbiota
chronic kidney disease
url https://www.mdpi.com/2072-6643/12/8/2216
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