Alterations of the gut microbiota in patients with diabetic nephropathy and its association with the renin-angiotensin system

Affiliations

¹ Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
³ Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
⁴ Hepatitis, AIDS and Bloodborne Diseases Department, Pasteur Institute of Iran, Tehran, Iran.
⁵ Department of Arboviruses and Viral Hemorrhagic Fevers (National Ref Lab), Pasteur Institute of Iran, Tehran, Iran.
⁶ Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁸ Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁹ Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran.

^# Contributed equally.

PMID: 39989880
PMCID: PMC11842656 (available on 2026-02-20)
DOI: 10.1007/s40200-025-01579-8

Alterations of the gut microbiota in patients with diabetic nephropathy and its association with the renin-angiotensin system

Fatemeh Zali et al. J Diabetes Metab Disord. 2025.

. 2025 Feb 20;24(1):69.

doi: 10.1007/s40200-025-01579-8. eCollection 2025 Jun.

Authors

Affiliations

¹ Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
³ Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
⁴ Hepatitis, AIDS and Bloodborne Diseases Department, Pasteur Institute of Iran, Tehran, Iran.
⁵ Department of Arboviruses and Viral Hemorrhagic Fevers (National Ref Lab), Pasteur Institute of Iran, Tehran, Iran.
⁶ Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁸ Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁹ Department of Mycobacteriology and Pulmonary Research, Microbiology Research Center, Pasteur Institute of Iran, Tehran, Iran.

^# Contributed equally.

PMID: 39989880
PMCID: PMC11842656 (available on 2026-02-20)
DOI: 10.1007/s40200-025-01579-8

Abstract

Objective: Type 2 Diabetes Mellitus (T2DM) is a global health concern, with complications such as diabetic nephropathy (DN) affecting 16.6% of patients and contributing to end-stage renal failure. Emerging research suggests that gut microbial communities may influence DN progression, potentially through mechanisms involving the renin-angiotensin system (RAS). This study aimed to evaluate changes in specific microbial genera in individuals with T2DM, both with and without DN, and to explore their associations with renal function markers and RAS activation.

Methods: A total of 120 participants were categorized into three groups: healthy controls, T2DM without DN, and T2DM with DN. Microbial abundances of genera including Escherichia, Prevotella, Bifidobacterium, Lactobacillus, Roseburia, Bacteroides, Faecalibacterium, and Akkermansia were quantified using qPCR targeting the bacterial 16 S rRNA gene. Gene expression levels of RAS-associated markers (ACE, AGT1R, AT2R, and Ang II) and inflammation-related genes (TNF-α, TLR4) were analyzed in peripheral blood mononuclear cells via qPCR.

Results: The study identified significant alterations in microbial composition. Genera such as Faecalibacterium, Akkermansia, Roseburia (butyrate producers), and Bifidobacterium (a potential probiotic) were markedly reduced in T2DM and DN groups compared to controls. Increased mRNA expression of RAS-related genes, including ACE, AGT1R, and Ang II, was observed in these groups. We also foun correlations between altered microbial genera, RAS gene expression, and clinical markers of renal dysfunction.

Conclusion: The findings suggest that specific microbial genera may influence the pathogenesis of DN through RAS activation and inflammatory pathways. These insights highlight potential therapeutic targets for mitigating DN progression in T2DM patients.

Keywords: Diabetes mellitus; Diabetic nephropathy; Microbiota; Renin-angiotensin system.

© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2025. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

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Conflict of interest statement

Competing interestsThe authors declare that they have no conflict of interest.

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Alterations of the gut microbiota in patients with diabetic nephropathy and its association with the renin-angiotensin system

Affiliations

Alterations of the gut microbiota in patients with diabetic nephropathy and its association with the renin-angiotensin system

Authors

Affiliations

Abstract

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources

Miscellaneous