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

Abstract

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.

Systematic Review of the Effects of Exercise and Physical Activity on the Gut Microbiome of Older Adults

“…Erlandson et al (2021) found that after a 24-week of combined exercise intervention with a gradual increase in intensity in sedentary subjects (95% men), there was an increase in the genera Bifidobacterium , Oscillopsira and Anareostipes and a decrease in Oribacterium and Prevotella . While physiological information about the genus Anaerostipes is limited, they are known to be acetate and butyrate producers [ 90 ] and have been found to have a beneficial role in renal function [ 91 ]. As such, based on the limited information available, it appears to be a health-related genus that is also responsive to exercise.…”

Specific alterations in gut microbiota in patients with chronic kidney disease: an updated systematic review

“…A Mendelian randomization analysis of data from genome-wide association studies (GWAS) showed that people with higher abundance of Desulfovibrio spp. had a significantly lower level of estimated glomerular filtration rate (eGFR) [ 49 ], which may support the higher abundance of Desulfovibrio in CKD patients. Acute post-streptococcal glomerulonephritis is a post-infectious immune-mediated kidney disease associated with group A Streptococcus [ 50 ], and enriched gut abundance of Streptococcus in CKD patients may also imply the association between kidney injury and Streptococcus mediated immunity disorder.…”

The Effect of ß-Glucan Prebiotic on Kidney Function, Uremic Toxins and Gut Microbiome in Stage 3 to 5 Chronic Kidney Disease (CKD) Predialysis Participants: A Randomized Controlled Trial

“…The abundance of Desulfovibrio has been associated with a lower GFR [57]. Faecalibacterium was negatively correlated with pCS in the current study; it has been found to be lower in CKD patients and has been found to have a positive correlation with GFR [17,58]. Methanobrevibacter has been reported to be pro-inflammatory, while Peptococcus is considered to be a pathogen [59,60].…”