Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2023; 14(6): 862-882
Published online Jun 15, 2023. doi: 10.4239/wjd.v14.i6.862
Alteration of intestinal microbiota is associated with diabetic retinopathy and its severity: Samples collected from southeast coast Chinese
Xue-Mei Gu, Chao-Yin Lu, Jian Pan, Jian-Zhong Ye, Qi-Han Zhu
Xue-Mei Gu, Qi-Han Zhu, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Xue-Mei Gu, Qi-Han Zhu, Wenzhou Key Laboratory of Diabetes Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Chao-Yin Lu, Department of Endocrinology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou 318000, Zhejiang Province, China
Jian Pan, Department of Ophthalmology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Jian-Zhong Ye, Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
Author contributions: Gu XM and Lu CY have contributed equally to this work and share first authorship; Gu XM performed data analysis and co-wrote the first draft of the manuscript; Lu CY performed data analysis, specimen collection, and co-wrote the first draft of the manuscript; Pan J performed specimen collection and data collection; Ye JZ performed data analysis, experimental design, co-chief investigator of the study, and co-guarantor of this work; Zhu QH performed data analysis, experimental design, essay modification, co-chief investigator of the study, and co-guarantor of this work; all authors have provided substantial intellectual input and approved the final version for publication.
Supported by Wenzhou Science and Technology Bureau, No. Y20190129 and No. Y2020263.
Institutional review board statement: The studies involving human participants were reviewed and approved by Research Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets presented in this study can be found in online repositories: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA786292. The names of the repository/repositories and accession number(s) can be found below: NCBI SRA (accession: SRP349289).
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: Qi-Han Zhu, MM, Attending Doctor, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, The South of Shangcai Village, Nanbaixiang Town, Ouhai District, Wenzhou 325000, Zhejiang Province, China. dr_zhuqihan@163.com
Received: March 9, 2023
Peer-review started: March 9, 2023
First decision: March 23, 2023
Revised: April 9, 2023
Accepted: April 27, 2023
Article in press: April 27, 2023
Published online: June 15, 2023
Processing time: 98 Days and 0.6 Hours
Abstract
BACKGROUND

Current approaches for the therapy of diabetic retinopathy (DR), which was one of leading causes of visual impairment, have their limitations. Animal experiments revealed that restructuring of intestinal microbiota can prevent retinopathy.

AIM

To explore the relationship between intestinal microbiota and DR among patients in the southeast coast of China, and provide clues for novel ways to prevention and treatment methods of DR.

METHODS

The fecal samples of non-diabetics (Group C, n = 15) and diabetics (Group DM, n = 30), including 15 samples with DR (Group DR) and 15 samples without DR (Group D), were analyzed by 16S rRNA sequencing. Intestinal microbiota compositions were compared between Group C and Group DM, Group DR and Group D, as well as patients with proliferative diabetic retinopathy (PDR) (Group PDR, n = 8) and patients without PDR (Group NPDR, n = 7). Spearman correlation analyses were performed to explore the associations between intestinal microbiota and clinical indicators.

RESULTS

The alpha and beta diversity did not differ significantly between Group DR and Group D as well as Group PDR and Group NPDR. At the family level, Fusobacteriaceae, Desulfovibrionaceae and Pseudomonadaceae were significantly increased in Group DR than in Group D (P < 0.05, respectively). At the genera level, Fusobacterium, Pseudomonas, and Adlercreutzia were increased in Group DR than Group D while Senegalimassilia was decreased (P < 0.05, respectively). Pseudomonas was negatively correlated with NK cell count (r = -0.39, P = 0.03). Further, the abundance of genera Eubacterium (P < 0.01), Peptococcus, Desulfovibrio, Acetanaerobacterium and Negativibacillus (P < 0.05, respectively) were higher in Group PDR compared to Group NPDR, while Pseudomonas, Alloprevotella and Tyzzerella (P < 0.05, respectively) were lower. Acetanaerobacterium and Desulfovibrio were positively correlated with fasting insulin (r = 0.53 and 0.61, respectively, P < 0.05), when Negativibacillus was negatively correlated with B cell count (r = -0.67, P < 0.01).

CONCLUSION

Our findings indicated that the alteration of gut microbiota was associated with DR and its severity among patients in the southeast coast of China, probably by multiple mechanisms such as producing short-chain fatty acids, influencing permeability of blood vessels, affecting levels of vascular cell adhesion molecule-1, hypoxia-inducible factor-1, B cell and insulin. Modulating gut microbiota composition might be a novel strategy for prevention of DR, particularly PDR in population above.

Keywords: Intestinal microbiota; Diabetic retinopathy; Occurrence; Progression; Southeast coast of China

Core Tip: Current approaches for the therapy of diabetic retinopathy (DR) have their limitations. Our study revealed that alteration of gut microbiota was associated with DR and its progression, and further, this association was mediated by multiple mechanisms including producing short-chain fatty acids, influencing permeability of blood vessels, affecting levels of vascular cell adhesion molecule-1, hypoxia-inducible factor-1, B cell and insulin. Hence, reconstruction of gut microbiota might be a promising strategy for prevention of DR.