Table_6_Dysbiosis and Implication of the Gut Microbiota in Diabetic Retinopathy.xlsx

The pathogenesis of type 2 diabetes mellitus (T2DM) is commonly associated with altered gut bacteria. However, whether the microbial dysbiosis that exists in human diabetic patients with or without retinopathy is different remains largely unknown. Here, we collected clinical information and fecal samples from 75 participants, including 25 diabetic patients without retinopathy (DM), 25 diabetic patients with retinopathy (DR), and 25 healthy controls (HC). The gut microbial composition in the three groups was analyzed using 16S ribosomal RNA (rRNA) gene sequencing. Microbial structure and composition differed in the three groups. The α and β diversities in both the DM and DR groups were reduced compared with those in the HC group. Blautia was the most abundant genus, especially in the DM group. In addition, increased levels of Bifidobacterium and Lactobacillus and decreased levels of Escherichia-Shigella, Faecalibacterium, Eubacterium_hallii_group and Clostridium genera were observed in the DM and DR groups compared with the HC group. Furthermore, a biomarker set of 25 bacterial families, which could distinguish patients in the DR group from those in the DM and HC groups was identified, with the area under the curve values ranging from 0.69 to 0.85. Of note, Pasteurellaceae, which was increased in DM and decreased in DR compared with HC, generated a high AUC (0.74) as an individual predictive biomarker. Moreover, 14 family biomarkers were associated with fasting blood glucose levels or diabetes, with most of them being negatively correlated. In summary, our study establishes compositional alterations of gut microbiota in DM and DR, suggesting the potential use of gut microbiota as a non-invasive biomarker for clinical and differential diagnosis, as well as identifying potential therapeutic targets of diabetic retinopathy.

2型糖尿病（type 2 diabetes mellitus, T2DM）的发病机制多与肠道菌群失衡相关。然而，伴或不伴视网膜病变的糖尿病患者体内存在的微生物群失调是否存在差异，目前仍尚不明确。本研究收集了75名受试者的临床资料与粪便样本，其中包括25名无视网膜病变的糖尿病患者（DM组）、25名伴视网膜病变的糖尿病患者（DR组）以及25名健康对照者（HC组）。采用16S核糖体RNA（rRNA）基因测序技术对三组受试者的肠道菌群组成进行分析。结果显示，三组受试者的肠道菌群结构与组成均存在显著差异。与HC组相比，DM组与DR组的α多样性及β多样性均有所降低。布劳特氏菌属（Blautia）为丰度最高的菌属，尤其在DM组中优势更为明显。此外，相较于HC组，DM组与DR组的双歧杆菌属（Bifidobacterium）和乳杆菌属（Lactobacillus）丰度显著升高，而埃希氏菌-志贺氏菌属（Escherichia-Shigella）、粪杆菌属（Faecalibacterium）、优杆菌hallii群（Eubacterium_hallii_group）以及梭菌属（Clostridium）的丰度则明显下降。本研究进一步鉴定出一套包含25个细菌科的生物标志物集，可有效区分DR组患者与DM组及HC组患者，其曲线下面积（area under the curve, AUC）值介于0.69至0.85之间。值得关注的是，相较于HC组，在DM组中丰度升高、DR组中丰度降低的巴斯德菌科（Pasteurellaceae）作为单一预测生物标志物时，展现出较高的AUC值（0.74）。此外，14个菌群科生物标志物与空腹血糖水平或糖尿病状态显著相关，其中多数呈负相关关系。综上，本研究明确了DM与DR患者肠道菌群的组成改变，提示肠道菌群可作为无创生物标志物用于临床鉴别诊断，同时也为糖尿病视网膜病变的潜在治疗靶点提供了新的研究方向。