Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025;28(6):1026-1038.
doi: 10.2174/0113862073311197240425073859.

Exploring the Causal Effects of Gut Microbiota on Diabetic Nephropathy: A Two-Sample Mendelian Randomization Study

Kai Chen  1   2 , Xu Wang  1   2 , Zhihao Shang  1   2 , Qingyue Li  1   2 , Wenqiang Yao  1   2 , Shaobo Guo  1   2 , Yingting Guan  1   2
Affiliations

Exploring the Causal Effects of Gut Microbiota on Diabetic Nephropathy: A Two-Sample Mendelian Randomization Study

Kai Chen et al. Comb Chem High Throughput Screen. 2025.

Abstract

Background: In recent years, an increasing number of studies have indicated a bidirectional relationship between gut microbiota and the kidneys (the gut-kidney axis). Currently, the potential causal relationship between gut microbiota and diabetic nephropathy remains unclear. This study explores the causal effects of gut microbiota on diabetic nephropathy through Mendelian randomization.

Methods: We carried out a comprehensive Mendelian Randomization (MR) analysis, drawing on the Genome-wide Association Study (GWAS) data for 196 varieties of gut microbiota and diabetic nephropathy. The primary analytical approach employed was the inverse-variance weighted, supplemented by the MR-Egger, weighted median, simple mode, and weighted mode. We rigorously assessed heterogeneity with Cochran's Q test and examined pleiotropy via MREgger intercept and MR-PRESSO tests. To ensure the reliability of our findings, we conducted funnel plots and leave-one-out analysis.

Results: Our study indicates a causal relationship between the increased risk of diabetic nephropathy and specific gut microbiota, including the Bacteroidia (P=0.01892; OR=1.593; 95%CI, 1.080-2.350), Bacteroidales (P=0.01892; OR=1.593; 95% CI, 1.080-2.350), and LachnospiraceaeUCG008 (P=0.01350; OR=1.452; 95% CI, 1.080-1.953). Conversely, potential protective factors include the Proteobacteria (P=0.00397; OR=0.528; 95% CI, 0.342-0.815), Gammaproteobacteria (P=0.00965; OR=0.474; 95% CI, 0.270-0.834), Lentisphaeria (P=0.04417; OR=0.756; 95% CI, 0.576-0.993), Victivallales (P=0.04417; OR=0.756; 95% CI, 0.576-0.993), and Dialister (P=0.00118; OR=0.513; 95%CI, 0.343-0.768).

Conclusion: This study confirms the causal effects of gut microbiota on diabetic nephropathy. Identifying the risk and protective factors within the gut microbiota for diabetic nephropathy offers fresh insights and novel approaches for preventing and treating this condition.

Keywords: Gut microbiota; causal effects; diabetic nephropathy; genome-wide association study; mendelian randomization; protective factors.; risk factors.

PubMed Disclaimer

References

    1. Jiang S.; Yu T.; Di D.; Wang Y.; Li W.; Worldwide burden and trends of diabetes among people aged 70 years and older, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. Diabetes Metab Res Rev 2024,40(3),e3745 - DOI - PubMed
    1. Cousin E.; Schmidt M.I.; Ong K.L.; Lozano R.; Afshin A.; Abushouk A.I.; Agarwal G.; Agudelo-Botero M.; Al-Aly Z.; Alcalde-Rabanal J.E.; Alvis-Guzman N.; Alvis-Zakzuk N.J.; Antony B.; Asaad M.; Bärnighausen T.W.; Basu S.; Bensenor I.M.; Butt Z.A.; Campos-Nonato I.R.; Chattu V.K.; Criqui M.H.; Daneshpajouhnejad P.; Dávila-Cervantes C.A.; Denova-Gutiérrez E.; Dharmaratne S.D.; Diaz D.; Filip I.; Gad M.M.; Garcia-Gordillo M.A.; Ghasemi Assl S.; Gopalani S.V.; Guimarães R.A.; Gupta R.D.; Hafezi-Nejad N.; Hashemian M.; Hay S.I.; Kahlon T.; Khubchandani J.; Kimokoti R.W.; Kisa A.; Kuate Defo B.; Landires I.; Miller T.R.; Mokdad A.H.; Morales L.; Morrison S.D.; Nigatu Y.T.; Nuñez-Samudio V.; Olagunju A.T.; Pandi-Perumal S.R.; Patel U.K.; Radfar A.; Rios-Blancas M.; Roever L.; Saadatagah S.; Sanabria J.; Santos I.S.; Sathish T.; Shabani M.; Shafaat O.; Sheikhbahaei S.; Silva D.A.S.; Singh A.; Singh J.A.; Tovani-Palone M.R.; Velazquez D.Z.; Zadey S.; Naghavi M.; Vos T.; Duncan B.B.; Burden of diabetes and hyperglycaemia in adults in the Americas, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Diabetes Endocrinol 2022,10(9),655-667 - DOI - PubMed
    1. Yang X.; Xue C.; Chen K.; Gao D.; Wang H.; Tang C.; Characteristics of elderly diabetes patients: focus on clinical manifestation, pathogenic mechanism, and the role of traditional Chinese medicine. Front Pharmacol 2024,14,1339744 - DOI - PubMed
    1. Sun H.; Saeedi P.; Karuranga S.; Pinkepank M.; Ogurtsova K.; Duncan B.B.; Stein C.; Basit A.; Chan J.C.N.; Mbanya J.C.; Pavkov M.E.; Ramachandaran A.; Wild S.H.; James S.; Herman W.H.; Zhang P.; Bommer C.; Kuo S.; Boyko E.J.; Magliano D.J.; IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 2022,183,109119 - DOI - PubMed
    1. Kanasaki K.; Taduri G.; Koya D.; Diabetic nephropathy: the role of inflammation in fibroblast activation and kidney fibrosis. Front Endocrinol 2013,4,7 - DOI - PubMed

MeSH terms

LinkOut - more resources