Case Control Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2025; 16(4): 102970
Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.102970
Characteristic dysbiosis in patients with type 2 diabetes and hyperuricemia, and the effect of empagliflozin on gut microbiota
Xin-Ru Deng, Yu-Jia Zhai, Xiao-Yang Shi, Sha-Sha Tang, Yuan-Yuan Fang, Hong-Yan Heng, Ling-Yun Zhao, Hui-Juan Yuan
Xin-Ru Deng, Yu-Jia Zhai, Xiao-Yang Shi, Sha-Sha Tang, Yuan-Yuan Fang, Hong-Yan Heng, Ling-Yun Zhao, Hui-Juan Yuan, Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
Co-first authors: Xin-Ru Deng and Yu-Jia Zhai.
Author contributions: Deng XR and Zhai YJ contributed equally to this work; Deng XR contributed to conceptualization, methodology, data collection, formal analysis, writing and reviewing; Zhai YJ contributed to data collection, data curation, parameters measurement and reviewing; Shi XY was involved in supervision, funding acquisition and data curation; Tang SS, Fang YY, Heng HY and Zhao LY contributed to data collection and reviewing; Yuan HJ contributed to conceptualization, supervising, funding acquisition, methodology and reviewing; All authors contributed to the interpretation of the study and approved the final version to be published.
Supported by the National Natural Science Foundation of China, No. 82270865; the Henan Provincial Key Research and Development Projects, No. 231111313200; the Henan Provincial Medical Science and Technology Research Program-the Provincial and Ministerial Major Projects, No. SBGJ202301002; and the Scientific and Technological Project in Henan Province, No. LHGJ20190614.
Institutional review board statement: The study approved by the Ethics Committee and Committee for Clinical Investigation of Henan Provincial People’s Hospital (Henan Province, China), approval No. 2018[48] and No. 2019[13].
Informed consent statement: All participants provided written informed consent.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The raw Illumina sequence data generated during and/or analyzed during the current study are available in the sequence read archive at NCBI under accession No. SRP513322. The other data generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui-Juan Yuan, MD, Professor, Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, Henan Province, China. hjyuan@zzu.edu.cn
Received: November 5, 2024
Revised: January 4, 2025
Accepted: February 5, 2025
Published online: April 15, 2025
Processing time: 116 Days and 4.5 Hours
Abstract
BACKGROUND

Gut microbiota play a crucial role in metabolic diseases, including type 2 diabetes (T2DM) and hyperuricemia (HUA). One-third of uric acid is excreted into the intestinal tract and further metabolized by gut microbiota. Thus, the gut microbiota might be a new therapeutic target for HUA. Empagliflozin significantly lowers serum uric acid levels and contributes to cardiovascular benefits which are partly attributed to altered gut microbiota. We hypothesize that gut dysbiosis in patients with diabetes and HUA, and the reduction of uric acid by empagliflozin, may be mediated by gut microbiota.

AIM

To investigate dysbiosis in patients with T2DM and HUA, and the effect of empagliflozin on gut microbiota associated with purine metabolism.

METHODS

In this age and sex-matched, case-control study, we recruited 30 patients with T2DM and HUA; 30 with T2DM; and 30 healthy controls at the Henan Provincial People’s Hospital between February 2019 and August 2023. Nine patients with T2DM and HUA were treated with empagliflozin for three months. Gut microbiota profiles were assessed using the 16S rRNA gene.

RESULTS

Patients with T2DM and HUA had the highest total triglycerides (1.09 mmol/L in heathy control vs 1.56 mmol/L in T2DM vs 2.82 mmol/L in T2DM + HUA) and uric acid levels (302.50 μmol/L in heathy control vs 288.50 μmol/L in T2DM vs 466.50 μmol/L in T2DM + HUA) among the three groups. The composition of the gut microbiota differed significantly between patients with T2DM and HUA, and those with T2DM/healthy controls (P < 0.05). Notably, patients with T2DM and HUA demonstrated a deficiency of uric acid-degrading bacteria such as Romboutsia, Blautia, Clostridium sensu stricto 1 (P < 0.05). Empagliflozin treatment was associated with significantly reduced serum uric acid levels and purine metabolism-related pathways and genes in patients with T2DM and HUA (P < 0.05).

CONCLUSION

Gut dysbiosis may contribute to the pathogenesis of HUA in T2DM, and empagliflozin may partly restore the gut microbiota related to uric acid metabolism.

Keywords: Type 2 diabetes; Hyperuricemia; Uric acid; Empagliflozin; Gut microbiota

Core Tip: Patients with type 2 diabetes (T2DM) have a significantly higher prevalence of hyperuricemia (HUA) than non-diabetic patients and are more likely to suffer from cardiovascular diseases. In recent years, the gut microbiota has been shown to play a crucial role in metabolic diseases, including T2DM and HUA. Thus, the gut microbiota may be a new therapeutic target for HUA. Empagliflozin significantly lowers serum uric acid levels and contributes to cardiovascular benefits which are partly attributed to altered gut microbiota. This study revealed that empagliflozin administered to patients with characteristic dysbiosis due to T2DM and HUA, may have gut microbiota involved in purine metabolism partially restored.