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. 2023 Mar 31:13:1142140.
doi: 10.3389/fcimb.2023.1142140. eCollection 2023.

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

Mingli Luo  1   2 , Jiahao Cai  3 , Shulu Luo  4 , Xiaosi Hong  5 , Lingxin Xu  6 , Honghong Lin  7 , Xiong Chen  1 , Wen Fu  1
Affiliations

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

Mingli Luo et al. Front Cell Infect Microbiol. .

Abstract

Background: Previous 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 methods: Independent 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.

Results: The 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.

Conclusion: We 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.

Keywords: CKD; Mendelian randomization; chronic kidney disease; gut microbiota; nutrition.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study design. An overview of the study design. SNP, single nucleotide polymorphisms; IVW, inverse-variance weighted.
Figure 2
Figure 2
Preliminary MR estimates for the associations between gut microbiota and the risk of CKD. From the inner to outer circles, they represent the estimates of: mode-based estimation, weighted median, MR-Egger, MR-PRESSO and inverse-variance weighted methods, respectively. And the shades of color reflect the magnitude of the p-value.
Figure 3
Figure 3
Scatter plots of the MR analyses for the association of 10 gut bacterial taxa and the risk of chronic kidney disease. (A) Causal effect of Desulfovibrionales on CKD; (B–J) Potential causal effect of nine other gut bacterial taxa on CKD. SNP, single nucleotide polymorphisms; MR, mendelian randomization; CKD, chronic kidney disease.
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References

    1. GBD Chronic Kidney Disease Collaboration .(2020). Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the global burden of disease study 2017. Lancet 395 (10225), 709–733. doi: 10.1016/S0140-6736(20)30045-3 - DOI - PMC - PubMed
    1. Bowden J., Davey Smith G., Burgess S. (2015). Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression. Int. J. Epidemiol. 44 (2), 512–525. doi: 10.1093/ije/dyv080 - DOI - PMC - PubMed
    1. Bowden J., Davey Smith G., Haycock P. C., Burgess S. (2016). Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol. 40 (4), 304–314. doi: 10.1002/gepi.21965 - DOI - PMC - PubMed
    1. Burgess S. (2014). Sample size and power calculations in mendelian randomization with a single instrumental variable and a binary outcome. Int. J. Epidemiol. 43 (3), 922–929. doi: 10.1093/ije/dyu005 - DOI - PMC - PubMed
    1. Burgess S., Davies N. M., Thompson S. G. (2016). Bias due to participant overlap in two-sample mendelian randomization. Genet. Epidemiol. 40 (7), 597–608. doi: 10.1002/gepi.21998 - DOI - PMC - PubMed

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