Gut microbiota may mediate the causality of statins on diabetic nephropathy: a mediation Mendelian randomization study.

IF 1.8 4区 医学 Q3 UROLOGY & NEPHROLOGY
International Urology and Nephrology Pub Date : 2025-04-01 Epub Date: 2024-12-10 DOI:10.1007/s11255-024-04321-0
Xiaoli Wen, Gaosi Xu
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引用次数: 0

Abstract

Background: Increasing evidence indicates that statins may increase the risk of developing diabetic nephropathy (DN). As the gut-kidney axis concept gains traction, it remains unclear whether statins contribute to the onset and progression of DN by modulating gut microbiota.

Objective: To investigate the association between statins and DN and the proportion of this association mediated through gut microbiota.

Method: This study utilized a two-sample Mendelian randomization (MR) approach and a cross-sectional observational design to investigate the causal relationships among statins, 473 gut microbiota, and DN. Furthermore, mediation MR analysis was employed to explore the potential mediating effects of gut microbiota in the statins-DN relationship.

Results: HMGCR inhibitors were causally linked to the increased incidence of DN (odds ratio [OR]: 0.732, 95% confidence interval [CI] 0.647, 0.828, PFDR = 0.000004). Supporting results from a cross-sectional study based on the Medical Information Marketplace in Intensive Care (MIMIC-IV) database also indicated this association (OR: 0.74, 95% CI: 0.61, 0.91, P = 0.004). Among the 473 identified gut microbiota species, 13 (PFDR < 0.05) were causally associated with DN. The mediation MR analysis revealed that 10 gut microbiota mediated the relationship between statins and DN, acting as either protective or risk factors (P < 0.05). In addition, HMGCR and related proteins may be involved in lipid metabolism, insulin resistance, and AMPK signaling pathway.

Conclusion: Statins may become a risk factor for DN by increasing or decreasing the abundance of specific gut microbiota. These specific gut bacteria have the potential to become a new indicator for guiding the clinical use of statins in diabetic patients.

肠道微生物群可能介导他汀类药物对糖尿病肾病的因果关系:一项介导孟德尔随机研究。
背景:越来越多的证据表明,他汀类药物可能增加发生糖尿病肾病(DN)的风险。随着肠肾轴概念的发展,他汀类药物是否通过调节肠道微生物群参与DN的发病和进展尚不清楚。目的:探讨他汀类药物与DN的关系,以及该关系通过肠道菌群介导的比例。方法:本研究采用双样本孟德尔随机化(MR)方法和横断面观察设计来研究他汀类药物、473种肠道微生物群和DN之间的因果关系。此外,采用中介MR分析来探讨肠道微生物群在他汀类药物- dn关系中的潜在中介作用。结果:HMGCR抑制剂与DN发病率增加有因果关系(优势比[OR]: 0.732, 95%可信区间[CI] 0.647, 0.828, PFDR = 0.000004)。一项基于重症监护医疗信息市场(MIMIC-IV)数据库的横断面研究的支持结果也表明了这种关联(OR: 0.74, 95% CI: 0.61, 0.91, P = 0.004)。结论:他汀类药物可能通过增加或减少特定肠道菌群的丰度而成为DN的危险因素。这些特异性肠道细菌有可能成为指导糖尿病患者临床使用他汀类药物的新指标。
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来源期刊
International Urology and Nephrology
International Urology and Nephrology 医学-泌尿学与肾脏学
CiteScore
3.40
自引率
5.00%
发文量
329
审稿时长
1.7 months
期刊介绍: International Urology and Nephrology publishes original papers on a broad range of topics in urology, nephrology and andrology. The journal integrates papers originating from clinical practice.
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