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Sodium butyrate ameliorates diabetic retinopathy in mice via the regulation of gut microbiota and related short-chain fatty acids
发布日期： 2024-09-03

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Abstract
Background Diabetic 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 efect. However, whether butyrate has a role in DR remains elusive. This study aimed to investigate the efect and mechanism of sodium butyrate supplementation on DR.
Methods C57BL/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.
Results Butyrate decreased blood glucose, food, and water consumption. Meanwhile, it alleviated retinal thinning and activated microglial cells but improved electroretinography visual function. Additionally, butyrate efectively enhanced the expression of ZO-1 and Occludin proteins in the small intestine. Crucially, only butyric acid, 4-methyl valeric acid, and caproic acid were signifcantly 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, Ileibac terium, and Dubosiella, were signifcantly 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, Bifdobacterium, Lachnospiraceae_NK4A136_group, and unclassifed_f_Lachnospiraceae were decreased after butyrate supplementation.
Conclusion Together, these fndings demonstrate the microbiota regulating and diabetic therapeutic efects
of butyrate, which can be used as a potential food supplement alternative to DR medicine. 

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