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Deciphering the causal link between gut microbiota and membranous nephropathy: insights into potential inflammatory
Jianbo Qing1,2,3, Changqun Li1, Nan Jiao2,3,4,5
1Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background:
Membranous nephropathy (MN), a leading cause of adult nephrotic syndrome and renal failure, has been linked to gut microbiota (GM) and their metabolites. However, direct causal relationships and therapeutic implications remain unclear.
Methods:
We utilized a comprehensive GWAS dataset that encompasses GM, metabolites, and MN through two-sample Mendelian randomization (MR) analyses, bidirectional MR evaluations, and detailed sensitivity tests.
Results:
We identified strong causal associations between nine specific types of GM, including class Clostridia (OR = 1.816, 95%CI: 1.021-3.236, p = .042), class Melainabacteria (OR = 0.661, 95%CI: 0.439-0.996, p = .048), order Gastranaerophilales (OR = 0.689, 95%CI: 0.480-0.996, p = .044), genus Alistipes (OR = 0.480, 95%CI: 0.223-0.998, p = .049), genus Butyricicoccus (OR = 0.464, 95%CI: 0.216-0.995, p = .048), genus Butyrivibrio (OR = 0.799, 95%CI: 0.639-0.998, p = .048), genus Ruminococcaceae UCG003 (OR = 0.563, 95%CI: 0.362-0.877, p = .011), genus Streptococcus (OR = 0.619, 95%CI: 0.393-0.973, p = .038), and genus Oscillibacter (OR = 1.90, 95%CI: 1.06-3.40, p = .031). Additionally, the metabolite tryptophan also exhibited a significant causal influence on MN (OR = 0.852, 95%CI: 0.754-0.963, p = .010). Sensitivity and reverse MR analyses confirmed the robustness of these findings. Further exploration using gutMGene database suggests that GM may influence MN by affecting the release of inflammatory factors and modulating inflammatory pathways.
Conclusion:
This study offers a comprehensive understanding of the causal links between GM, their metabolites, and MN, which highlight potential pathways for developing new preventive and therapeutic strategies for this condition.
Insights
This study reveals causal links between gut microbiota (GM) and membranous nephropathy (MN). Specific GM types and the metabolite tryptophan influence MN development, suggesting new therapeutic targets.
Area of Science:
- Genetics and Microbiology
- Nephrology
- Metabolomics
Background:
- Membranous nephropathy (MN) is a primary cause of nephrotic syndrome and kidney failure in adults.
- The gut microbiota (GM) and its metabolites are implicated in MN, but direct causal links and therapeutic potential are not fully understood.
Purpose of the Study:
- To investigate the causal relationship between gut microbiota, metabolites, and membranous nephropathy using genetic data.
- To identify specific gut bacteria and metabolites that causally influence the risk of developing MN.
Main Methods:
- Utilized a comprehensive genome-wide association study (GWAS) dataset.
- Performed two-sample Mendelian randomization (MR) analyses, including bidirectional MR and sensitivity tests.
- Analyzed associations between nine specific gut microbial types, metabolites, and MN.
Main Results:
- Identified significant causal associations between nine gut microbial taxa (e.g., class Clostridia, genus Alistipes) and MN.
- Found that the metabolite tryptophan causally influences MN.
- Confirmed findings through sensitivity and reverse MR analyses, suggesting GM impacts MN via inflammatory pathways.
Conclusions:
- Established causal links between specific gut microbiota, tryptophan, and membranous nephropathy.
- Highlights potential for novel preventive and therapeutic strategies targeting the gut microbiome for MN treatment.
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