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Published on: May 2, 2025
Blood Metabolites Mediate the Effects of Gut Microbiota on Diabetic Nephropathy: A Mendelian Randomization Study
Weiwei Zhang1, Yun Zhang2, Huijuan Yuan2
1Department of Endocrinology, Henan Provincial People's Hospital, Xinxiang Medical University, Xinxiang, Henan, China, xxmu.edu.cn.
Background:
The gut microbiota (GM) might be related to diabetic nephropathy (DN). The role of blood metabolites, immune cells, and plasma lipidomes in mediating the impact of GM on DN remains unexplored.
Methods:
412 GM, 1400 blood metabolites, 731 immune cells, 179 plasma lipidomes, and DN were identified through genome-wide association study (GWAS) datasets. We employed Mendelian randomization (MR) to investigate the relationship among GM, blood metabolomes, immune cells, plasma lipidomes, and DN. Furthermore, we conducted mediation analyses to ascertain if the blood metabolomes, immune cells, and plasma lipidomes function as mediators.
Results:
Our research identified suggestive causal linkages among 15 GM, 27 immune cells, 27 plasma lipidomes, and 55 blood metabolites associated with DN. Mediation analysis showed that advanced glycation end products (AGEs) pyrraline may mediate the causal relationship between s_Bacteroides_eggerthii and DN, with a mediation percentage of 39.96% (p = 0.015). Furthermore, immune cells and plasma lipidomes do not appear to play a mediating role.
Conclusion:
Gut microbiota, blood metabolomes, immune cells, and plasma lipidomes were causally linked to DN. The blood metabolite pyrraline may act as a potential mediator by which s_Bacteroides_eggerthii influences the risk of developing DN.
