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Causal Relationships Between Gut Microbiota, Metabolites, and Diabetic Nephropathy: Insights from a Two-Sample Mendelian Randomization Analysis

Year: 2024

Type: article

Abstract: Background: Previous studies have established a correlation between gut microbiota, metabolites, and diabetic nephropathy (DN). However, the inherent limitations of observational studies, including reverse causality and confounding factors, made this relationship uncertain. Methods: In this study, we compiled summary statistics from a genome-wide association study (GWAS) conducted on gut microbiota, metabolites, and DN. We employed a two-sample Mendelian randomization (MR) approach, utilizing inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods. Results: We detected the protective nature of genetically predicted representatives from the family Bacteroidaceae (OR: 0.716, 95% CI: 0.516– 0.995, p = 0.046), family Victivallaceae (OR: 0.871, 95% CI: 0.772– 0.982, p = 0.026), genus Bacteroides (OR: 0.716, 95% CI: 0.516– 0.995, p = 0.046), genus Coprococcus 2 (OR: 0.745, 95% CI: 0.576– 0.963, p = 0.025), and genus Lactococcus (OR: 0.851, 95% CI: 0.730– 0.992, p = 0.039) against the development of DN. Conversely, we identified a positive correlation between the incidence of DN and entities, such as Phylum Bacteroidetes (OR: 1.427, 95% CI: 1.085– 1.875, p = 0.011), class Bacteroidia (OR: 1.304, 95% CI: 1.036– 1.641, p = 0.024), order Bacteroidales (OR: 1.304, 95% CI: 1.035– 1.641, p = 0.028), genus Catenibacterium (OR: 1.312, 95% CI: 1.079– 1.594, p = 0.006), genus Lachnoclostridium (OR: 1.434, 95% CI: 1.129– 1.821, p = 0.003), and genus Parasutterella (OR: 1.270, 95% CI: 1.070– 1.510, p = 0.006). In our analysis, none of the gut metabolites demonstrated a causal relationship with DN. Conclusion: Our results substantiated the potential causal association between specific gut microbiota and DN. Therefore, our study offers novel insight into the mechanisms underlying DN. This finding provides a theoretical foundation for the future development of targeted strategies for the prevention and treatment of DN. Keywords: Gut microbiota, diabetic nephropathy, gut metabolites, Mendelian randomization

Source: International Journal of Nephrology and Renovascular Disease

DOI: 10.2147/ijnrd.s489074

Authors: Xixi Song, Jingqiu Cui, Shiwei Li, Bo Huang

Institutions: Tianjin Medical University General Hospital, Baoding No.1 Central Hospital, Tianjin Medical University

Language: English

Topic: Gut microbiota and health

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,320