Sodium butyrate ameliorates diabetic retinopathy in mice via the regulation of gut microbiota and related short-chain fatty acids

被引：41
作者：
Huang, Yinhua [1 ,2 ]
Wang, Zhijie [3 ,4 ]
Ye, Bo [5 ]
Ma, Jacey Hongjie [2 ]
Ji, Shangli [2 ]
Sheng, Wang [6 ]
Ye, Suna [2 ]
Ou, Yiwen [1 ,2 ]
Peng, Yanfang [2 ]
Yang, Xu [2 ]
Chen, Jiansu [1 ,2 ,7 ]
Tang, Shibo [1 ,2 ,8 ]
机构：
[1] Cent South Univ, Aier Sch Ophthalmol, Changsha, Peoples R China
[2] Aier Eye Inst, Changsha, Peoples R China
[3] Wenzhou Med Univ, Eye Hosp, State Key Lab Ophthalmol Optometry & Visual Sci, Wenzhou, Peoples R China
[4] Wenzhou Med Univ, Eye Hosp, Natl Clin Res Ctr Ocular Dis, Wenzhou, Peoples R China
[5] Nanchang Aier Eye Hosp, Dept Ophthalmol, Nanchang, Peoples R China
[6] Changsha Xiangjiang Aier Eye Hosp, Dept Ophthalmol, Changsha, Peoples R China
[7] Jinan Univ, Minist Educ, Key Lab Regenerat Med, Guangzhou, Peoples R China
[8] Changsha Aier Eye Hosp, Aier Eye Hosp Grp, Changsha, Hunan, Peoples R China
来源：
JOURNAL OF TRANSLATIONAL MEDICINE | 2023年 / 21卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Diabetic retinopathy; Gut microbiota; Short-chain fatty acids; Sodium butyrate; 4-Methylvaleric acid; Caproic acid; POGOSTONE; INJURY; MODEL; ONSET;
D O I：
10.1186/s12967-023-04259-4
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
BackgroundDiabetic retinopathy (DR) development is associated with disturbances in the gut microbiota and related metabolites. Butyric acid is one of the short-chain fatty acids (SCFAs), which has been found to possess a potential antidiabetic effect. However, whether butyrate has a role in DR remains elusive. This study aimed to investigate the effect and mechanism of sodium butyrate supplementation on DR.MethodsC57BL/6J mice were divided into three groups: Control group, diabetic group, and diabetic with butyrate supplementation group. Type 1 diabetic mouse model was induced by streptozotocin. Sodium butyrate was administered by gavage to the experimental group daily for 12 weeks. Optic coherence tomography, hematoxylin-eosin, and immunostaining of whole-mount retina were used to value the changes in retinal structure. Electroretinography was performed to assess the retinal visual function. The tight junction proteins in intestinal tissue were evaluated using immunohistochemistry. 16S rRNA sequencing and LC-MS/MS were performed to determine the alteration and correlation of the gut microbiota and systemic SCFAs.ResultsButyrate decreased blood glucose, food, and water consumption. Meanwhile, it alleviated retinal thinning and activated microglial cells but improved electroretinography visual function. Additionally, butyrate effectively enhanced the expression of ZO-1 and Occludin proteins in the small intestine. Crucially, only butyric acid, 4-methylvaleric acid, and caproic acid were significantly decreased in the plasma of diabetic mice and improved after butyrate supplementation. The deeper correlation analysis revealed nine genera strongly positively or negatively correlated with the above three SCFAs. Of note, all three positively correlated genera, including norank_f_Muribaculaceae, Ileibacterium, and Dubosiella, were significantly decreased in the diabetic mice with or without butyrate treatment. Interestingly, among the six negatively correlated genera, Escherichia-Shigella and Enterococcus were increased, while Lactobacillus, Bifidobacterium, Lachnospiraceae_NK4A136_group, and unclassified_f_Lachnospiraceae were decreased after butyrate supplementation.ConclusionTogether, these findings demonstrate the microbiota regulating and diabetic therapeutic effects of butyrate, which can be used as a potential food supplement alternative to DR medicine.
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页数：17
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