Alterations of the Gut Microbiota in Patients With Diabetic Nephropathy and Its Association With the Renin-Angiotensin System Publisher



Zali F^{1, 2} ; Absalan A³ ; Bahramali G⁴ ; Mousavi Nasab SD⁵ ; Esmaeili F¹ ; Ejtahed HS^{6, 7} ; Nasliesfahani E⁸ ; Siadat SD⁹ ; Pasalar P² ; Emamgholipour S^{1, 2} ; Razi F² Show Affiliations
Source: Journal of Diabetes and Metabolic Disorders Published:2025

Abstract

Significant alterations in gut microbiota, with reduced butyrate-producing genera, were found in T2DM and DN patients. Altered microbiota correlated with increased expression of RAS-related genes and inflammatory markers. Dysbiosis was tied to renal dysfunction markers like lower eGFR and higher creatinine. Modulating gut microbiota may reduce RAS activation and slow DN progression. The study highlights gut microbiota’s role in DN, offering insights for future research. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2025.; 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. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2025.