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. 2023 May 2:13:1171517.
doi: 10.3389/fcimb.2023.1171517. eCollection 2023.

Causal effects between gut microbiota and IgA nephropathy: a bidirectional Mendelian randomization study

Feihong Ren  1   2 , Qiubai Jin  1 , Tongtong Liu  1 , Xuelei Ren  1 , Yongli Zhan  1
Affiliations

Causal effects between gut microbiota and IgA nephropathy: a bidirectional Mendelian randomization study

Feihong Ren et al. Front Cell Infect Microbiol. .

Abstract

Background: Therapeutic approaches that target the gut microbiota (GM) may be helpful in the potential prevention and treatment of IgA nephropathy (IgAN). Meanwhile, relevant studies demonstrated a correlation between GM and IgAN, however, these confounding evidence cannot prove a causal relationship between GM and IgAN.

Methods: Based on the data from the GM genome-wide association study (GWAS) of MiBioGen and the IgAN GWAS data from the FinnGen research. A bi-directional Mendelian randomization (MR) study was performed to explore the causal relationship between GM and IgAN. We used inverse variance weighted (IVW) method as the primary method to determine the causal relationship between exposure and outcome in our MR study. Besides, we used additional analysis (MR-Egger, weighted median) and sensitivity analysis (Cochrane's Q test, MR-Egger and MR-PRESSO) to select significant results, followed by Bayesian model averaging (MR-BMA) to test the results of MR study. Finally, a reverse MR analysis was conducted to estimate the probability of reverse causality.

Results: At the locus-wide significance level, the results of IVW method and additional analysis showed that Genus Enterorhabdus was a protective factor for IgAN [OR: 0.456, 95% CI: 0.238-0.875, p=0.023], while Genus butyricicoccus was a risk factor for IgAN [OR: 3.471, 95% CI: 1.671-7.209, p=0.0008]. In the sensitivity analysis, no significant pleiotropy or heterogeneity of the results was found.

Conclusion: Our study revealed the causal relationship between GM and IgAN, and expanded the variety of bacterial taxa causally related to IgAN. These bacterial taxa could become novel biomarkers to facilitate the development of targeted therapies for IgAN, developing our understanding of the "gut-kidney axis".

Keywords: Bayesian model averaging; IgA nephropathy; causality; gut microbiota; pathogenesis; two-sample mendelian randomization.

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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
The study design and major assumptions of the Two-sample MR study. LD r2, r2 in linkage disequilibrium; SNPs, single nucleotide polymorphisms; IgAN, IgA nephropathy; MR-PRESSO, Mendelian Randomization Pleiotropy RESidual Sum and Outlier; IV, instruments variable; MR-BMA, MR Bayesian Model Averaging.
Figure 2
Figure 2
MR results of GM taxa with nominal significance causal relationships to IgAN.
Figure 3
Figure 3
Leave-one-out analysis of the causal association between GM and IgAN. (A) Leave-one-out analysis of the causal association between Butyricicoccus and IgAN; (B) Leave-one-out analysis of the causal association between Enterorhabdus and IgAN; (C) Leave-one-out analysis of the causal association between Peptococcaceae and IgAN; (D) Leave-one-out analysis of the causal association between Prevotellaceae and IgAN.
Figure 4
Figure 4
The present MR study reveals that GM may causally influences IgAN.
See this image and copyright information in PMC

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