Gong Haijun, Zuo Haoyu, Wu Keling, Gao Xinbo, Lan Yuqing, Zhao Ling
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Ophthalmology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Nutrients. 2025 Jul 18;17(14):2363. doi: 10.3390/nu17142363.
Early neurovascular unit (NVU) impairment plays a critical role in the pathogenesis of diabetic retinopathy (DR), often preceding clinically detectable changes. Butyrate, a short-chain fatty acid (SCFA) derived from gut microbiota, has shown promising metabolic and anti-inflammatory effects. : This study investigated the protective potential of oral butyrate supplementation in a mouse model of early type 2 diabetes mellitus (T2DM) induced by a high-fat diet and streptozotocin. Mice (C57BL/6J) received sodium butyrate (5 g/L in drinking water) for 12 weeks. Retinal NVU integrity was assessed using widefield swept-source optical coherence tomography angiography (WF SS-OCTA), alongside evaluations of systemic glucose and lipid metabolism, hepatic steatosis, visual function, and gut microbiota composition via 16S rRNA sequencing. Butyrate supplementation significantly reduced body weight, fasting glucose, serum cholesterol, and hepatic lipid accumulation. Microbiome analysis demonstrated a partial reversal of gut dysbiosis, characterized by increased SCFA-producing taxa (Ruminococcaceae, Oscillibacter, Lachnospiraceae) and decreased pro-inflammatory, lipid-metabolism-related genera (Rikenella, Ileibacterium). KEGG pathway analysis further revealed enrichment in microbial lipid metabolism functions (fabG, ABC.CD.A, and transketolase). Retinal vascular and neurodegenerative alterations-including reduced vessel density and retinal thinning-were markedly attenuated by butyrate, as revealed by WF SS-OCTA. OKN testing indicated partial improvement in visual function, despite unchanged ERG amplitudes. Butyrate supplementation mitigates early NVU damage in the diabetic retina by improving glucose and lipid metabolism and partially restoring gut microbial balance. This study also underscores the utility of WF SS-OCTA as a powerful noninvasive tool for detecting early neurovascular changes in DR.
早期神经血管单元（NVU）损伤在糖尿病视网膜病变（DR）的发病机制中起关键作用，通常先于临床可检测到的变化出现。丁酸盐是一种源自肠道微生物群的短链脂肪酸（SCFA），已显示出有前景的代谢和抗炎作用。本研究调查了在高脂饮食和链脲佐菌素诱导的早期2型糖尿病（T2DM）小鼠模型中口服补充丁酸盐的保护潜力。小鼠（C57BL/6J）饮用含丁酸钠（5 g/L）的水，持续12周。使用广角扫频源光学相干断层扫描血管造影（WF SS-OCTA）评估视网膜NVU完整性，同时通过16S rRNA测序评估全身葡萄糖和脂质代谢、肝脏脂肪变性、视觉功能和肠道微生物群组成。补充丁酸盐显著降低了体重、空腹血糖、血清胆固醇和肝脏脂质积累。微生物组分析表明肠道菌群失调得到部分逆转，其特征是产生SCFA的分类群（瘤胃球菌科、颤杆菌属、毛螺菌科）增加，促炎、脂质代谢相关属（理研菌属、艾氏杆菌属）减少。KEGG通路分析进一步揭示了微生物脂质代谢功能（fabG、ABC.CD.A和转酮醇酶）的富集。WF SS-OCTA显示，丁酸盐显著减轻了视网膜血管和神经退行性改变，包括血管密度降低和视网膜变薄。视动性眼震测试表明视觉功能有部分改善，尽管视网膜电图振幅未变。补充丁酸盐通过改善葡萄糖和脂质代谢以及部分恢复肠道微生物平衡，减轻糖尿病视网膜早期NVU损伤。本研究还强调了WF SS-OCTA作为检测DR早期神经血管变化的强大非侵入性工具的实用性。
