journal article·2026-05-27Open access

Canagliflozin Alleviates Diabetic Glomerular Endothelial Injury via Melibiose in a Microbiota‐Dependent Manner

Wei Zhang, Yi Song, Changkun Li, Yuanyuan Luo, Mingwei Shao, Feng Guo, Fangyi Wei, Xunjie Fan, Wenwen Guo, Fengmei Xu, Yanhong Sang, Dongming Zhang, Yanhong Zhou, Lianwei Wang, Zhiqiang Kang, Yingjun Yang, Chunhua Song, Yanxia Liu, Xiaojun Ma, Jiao Wang, Chong Li, Shengnan Ma, Lin Zhao, Zhi Qin, Guolan Xing, Qiubo Zhao, Jun Li, Shumin Song, Dan Zhao, Ting Huang, Qingzhu Wang, Yanyan Zhao, Guijun Qin

Abstract

ABSTRACT Canagliflozin reduces albuminuria in patients with diabetic kidney disease (DKD) beyond its glucose‐lowering effect, but the mechanisms remain unclear. We analyzed 85 patients treated with canagliflozin and 85 controls over 26 weeks to explore whether the gut microbiome and its metabolites contribute to renoprotection. Canagliflozin remodeled the gut microbiota, notably enriching Roseburia intestinalis and increasing plasma melibiose levels. In mice, canagliflozin alleviated glomerular endothelial injury and albuminuria. Similar effects were replicated by fecal microbiota transplantation, Roseburia intestinalis , or melibiose administration. Mechanistically, melibiose bound to and activated glyoxalase 1, reduced methylglyoxal, and suppressed the AGE‐RAGE pathway, preserving glomerular endothelial integrity. Furthermore, oral melibiose precursor supplementation reduced albuminuria in patients with early‐stage DKD. These findings suggest the involvement of a gut‐kidney axis in the renoprotective effects of canagliflozin and indicate that melibiose may serve as a potential therapeutic strategy for DKD.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Gut microbiota and health · Diabetes Treatment and Management · Chronic Kidney Disease and Diabetes

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Endocrinology and Metabolism The First Affiliated Hospital of Zhengzhou University Zhengzhou China

Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou China

Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic Diseases Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

Department of Endocrinology and Metabolism Hebi Coal Industry (Group) Co., Ltd General Hospital Hebi China

Department of Endocrinology and Metabolism The Fifth Affiliated Hospital of Zhengzhou University Zhengzhou China

Department of Endocrinology and Metabolism The Second Affiliated Hospital of Zhengzhou University Zhengzhou China

Department of Endocrinology Xinxiang Central Hospital Xinxiang China

Department of Endocrinology Zhumadian Central Hospital Zhumadian China

Department of Endocrinology and Metabolism Zhengzhou Central Hospital Zhengzhou China

Department of Endocrinology and Geriatrics The Seventh People's Hospital of Zhengzhou Zhengzhou China

Department of Epidemiology and Statistics College of Public Health Zhengzhou University Zhengzhou China

Department of Thoracic Surgery The First Affiliated Hospital of Zhengzhou University Zhengzhou China

Department of Nephrology The First Affiliated Hospital of Zhengzhou University Zhengzhou China

Department of Nuclear Medicine The First Affiliated Hospital of Zhengzhou University Zhengzhou China

Henan Provincial Center For Diabetes Prevention and Control Zhengzhou China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Henan Province

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