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REVIEW article

Front. Endocrinol.

Sec. Diabetes: Molecular Mechanisms

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1621968

This article is part of the Research TopicWorld Diabetes Day 2024: Exploring Mechanisms, Innovations, and Holistic Approaches in Diabetes CareView all 11 articles

Targeting Gut Microbiota for Diabetic Nephropathy Treatment: Probiotics, Dietary Interventions, and Fecal Microbiota Transplantation

Provisionally accepted
Xiaoran  WangXiaoran Wang1*Xinyin  LiuXinyin Liu2Fanghong  GongFanghong Gong1Yan  JiangYan Jiang1Canwei  ZhangCanwei Zhang1Wei  ZhouWei Zhou1*Wen  ZhangWen Zhang3,4*
  • 1Department of Nephrology, The First People’s Hospital of Hangzhou Lin’an District, Hangzhou, China
  • 2Department of Traditional Chinese Medicine, Jiande First People’s Hospital, Jiande, Hangzhou, China
  • 3The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China
  • 4Zhejiang Key Laboratory of Research and Translation for Kidney Deficiency-Stasis-Turbidity Disease, Hangzhou, China

The final, formatted version of the article will be published soon.

Diabetic nephropathy (DN) stands as a prominent microvascular complication of diabetes mellitus and presents a significant global health challenge. Despite advancements in glycemic control and renin-angiotensin system inhibition, current treatments merely delay disease progression without targeting fundamental pathological processes. This review explores gut microbiota modulation as a promising treatment strategy for DN through probiotic supplementation, dietary interventions, and fecal microbiota transplantation(FMT) protocols. The gut microbiota, integral to the "gut-kidney axis," is critically implicated in DN pathogenesis. DN is associated with gut dysbiosis-characterized by reduced microbial diversity, depletion of beneficial short-chain fatty acid (SCFA)-producing bacteria, and proliferation of opportunistic pathogens. This dysbiosis impairs gut barrier integrity, fostering systemic inflammation and the accumulation of uremic toxins like indoxyl sulfate. Furthermore, translocated bacterial lipopolysaccharides activate Toll-like receptors and the NLRP3 inflammasome, exacerbating kidney damage and fibrosis.Interventions targeting the microbiota, including dietary strategies (e.g., enhancing fermentable fibers, low-protein diets) and FMT, show promise in preclinical and early clinical studies, though FMT requires stringent safety and donor screening protocols. Significant challenges persist, such as managing inter-individual microbiota variability for personalized therapies, fully elucidating molecular mechanisms like SCFA-GPR43 signaling, and leveraging multiomics for biomarker discovery. Advancing microbiota-focused interventions for DN towards microbiome-centered precision medicine necessitates addressing standardization, deepening mechanistic understanding, and validating combination therapies, heralding a potential shift from traditional nephroprotective approaches.

Keywords: Diabetic kidney disease, Gut Microbiota, Short-chain fatty acids (SCFAs), Probiotics, fecal microbiota transplantation (FMT)

Received: 02 May 2025; Accepted: 03 Jun 2025.

Copyright: © 2025 Wang, Liu, Gong, Jiang, Zhang, Zhou and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Xiaoran Wang, Department of Nephrology, The First People’s Hospital of Hangzhou Lin’an District, Hangzhou, China
Wei Zhou, Department of Nephrology, The First People’s Hospital of Hangzhou Lin’an District, Hangzhou, China
Wen Zhang, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China

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