Causal effects of gut microbiota on the risk of chronic kidney disease: a Mendelian randomization study

Abstract

BackgroundPrevious studies have reported that gut microbiota is associated with an increased risk of chronic kidney disease (CKD) progression. However, whether gut microbiota has a causal effect on the development of CKD has not been revealed. Thus, we aimed to analyze the potential causal effect of gut microbiota on the risk of CKD using mendelian randomization (MR) study.Materials and MethodsIndependent single nucleotide polymorphisms closely associated with 196 gut bacterial taxa (N = 18340) were identified as instrumental variables. Two-sample MR was performed to evaluate the causal effect of gut microbiota on CKD (N = 480698), including inverse-variance-weighted (IVW) method, weighted median method, MR-Egger, mode-based estimation and MR-PRESSO. The robustness of the estimation was tested by a series of sensitivity analyses including Cochran’s Q test, MR-Egger intercept analysis, leave-one-out analysis and funnel plot. Statistical powers were also calculated.ResultsThe genetically predicted higher abundance of order Desulfovibrionales was causally associated with an increased risk of CKD (odds ratio = 1.15, 95% confidence interval: 1.05-1.26; p = 0.0026). Besides, we also detected potential causalities between nine other taxa (Eubacterium eligens group, Desulfovibrionaceae, Ruminococcaceae UCG-002, Deltaproteobacteria, Lachnospiraceae UCG-010, Senegalimassilia, Peptostreptococcaceae, Alcaligenaceae and Ruminococcus torques group) and CKD (p < 0.05). No heterogeneity or pleiotropy was detected for significant estimates.ConclusionWe found that Desulfovibrionales and nine other taxa are associated with CKD, thus confirming that gut microbiota plays an important role in the pathogenesis of CKD. Our work also provides new potential indicators and targets for screening and prevention of CKD.

Genome-wide association analysis of gut microbiome and serum metabolomics identifies heart failure therapeutic targets

“…Our study found that out of 211 classes of gut microbiota, 6 classes of gut microbes were causally associated with increased risk of HF, namely genus Eubacterium eligens group, class Negativicutes, genus Eubacterium oxidoreducens group, genus Flavonifractor, genus Ruminococcaceae UCG009, and order Selenomonadales, whereas four groups of gut microbes can act as defense factors against HF, namely class Bacteroidia, genus Anaerostipes, order Bacillales, and order Bacteroidales.Huajie Dai 43 and others found that genus Eubacterium eligens group was causally associated with an increased risk of HF, which is consistent with our ndings.A previous study reported 44 that in pregnant women in pregnancy class Negativicutes abundance was signi cantly increased and causally associated with higher BMI in pregnant women, and a meta-analysis by Fatin Umirah et al 45 found a moderate to strong signi cant positive correlation between class Negativicutes and IL-6, and in addition, MR analysis by Feihong Ren et al 46 further showed a causal relationship between elevated class Negativicutes abundance and higher CRP levels. Multiple MR analyses 47,48 showed that genus Eubacterium eligens group increased the risk of CKD, in addition to a causal relationship with visceral adipose tissue (VAT) accumulation.Weiheng Yan et al 49 found that genus Ruminococcaceae UCG009 was associated with an OSA associated with an increased risk of morbidity. Taken together, our ndings suggest that targeting gut microbes that increase the risk of HF may be a promising strategy for the prevention of HF in clinical practice.…”

Integration of Urinary Peptidome and Fecal Microbiome to Explore Patient Clustering in Chronic Kidney Disease

“…Further, the genus Enterorhabdus has been negatively correlated with IL-10 and IL-4 inflammation factors [ 54 ], while the genus Butyricicoccus has been positively correlated with eGFR [ 55 ]. In a Mendelian randomization study, the genus Senegalimassilia was found relevant in the context of CKD [ 56 ]. Further, a species of the genus Haemophilus displayed an increased trend in CKD compared to Non-CKD participants [ 57 ].…”

Unraveling the Causal Nexus: Exploring the Relationship between Gut Microbiota and Aortic Dissection

“…Firstly, based on previous research experience 20 , we selected SNPs strongly associated with the risk factor using a signi cance threshold of P < 1x10 − 5 for analysis. Secondly, to avoid violating assumption one, we calculated the F-statistic for each SNP, de ning SNPs with F-statistic < 10 as weak instrumental variables and removing them 21 .To ensure that the impact of linkage disequilibrium (LD) was eliminated, an LD coe cient (r 2 ) threshold of 0.001 and a genetic distance of 10,000 kb were applied to remove SNPs in LD.…”