Dysbiosis and Implication of the Gut Microbiota in Diabetic Retinopathy

Abstract

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.

Altered Fecal Microbiome and Metabolome in a Mouse Model of Choroidal Neovascularization

“…Recent studies demonstrated the alterations and possible application prospects of the gut microbiome in patients with other ocular neovascular diseases, such as DR (Das et al, 2021;Huang et al, 2021) and retinopathy of prematurity (Skondra et al, 2020). Das et al (2021) recognized a reduction in anti-inflammatory, probiotic and other bacteria that could be pathogenic in the microbiomes of patients with both diabetes mellitus and DR, compared to the healthy controls, and the changes observed in DR patients were more pronounced.…”

“…Das et al (2021) recognized a reduction in anti-inflammatory, probiotic and other bacteria that could be pathogenic in the microbiomes of patients with both diabetes mellitus and DR, compared to the healthy controls, and the changes observed in DR patients were more pronounced. Huang et al (2021) indicated the potential use of gut microbiota as a biomarker of DR, which could be helpful for diagnosis in clinical applications. Moreover, it has been suggested that the effect of antihyperglycemic drugs might be involved in the connection between the gut microbiota and DR, and targeting the gut microbiome could be novel therapeutic strategies in treating DR (Rowan and Taylor, 2018).…”

“…Changes in the intestinal microbiota significantly affect barrier function and metabolic pathways and gradually regulate the host immune system (Cerf-Bensussan and Gaboriau-Routhiau, 2010), and loss of gut microbiota diversity affects age-related changes (O'Toole and Jeffery, 2015). Recently, numerous studies have indicated that the gut microbiome is involved in ophthalmic diseases, such as diabetic retinopathy (DR) (Huang et al, 2021), Vogt-Koyanagi-Harada disease (Ye et al, 2020), and glaucoma (Gong et al, 2020). Zinkernagel et al (2017) revealed enrichment of the genera Anaerotruncus and Oscillibacter as well as Ruminococcus torques and Eubacterium ventriosum in nAMD patients; on the other hand, Bacteroides eggerthii was enriched in controls compared to patients.…”

Recent Insights into the Role of Gut Microbiota in Diabetic Retinopathy

“…LPS derived from Bacteroidetes and Desulfobacterota could generate inflammatory injuries, trigger abnormal equilibrium of metabolism, and inhibit endotoxin tolerance, all of which are related to the pathogenesis of retinopathy. 18 , 60 Influence of endotoxin-mediated retinal inflammation on phenotype of diabetic retinopathy. Additionally, Vagaja et al revealed that endotoxin-mediated retinal inflammation may have impact on phenotype of DR, that is, the systemic LPS exposure in Ins2 Akita mice could accelerate the damage of retinal capillary endothelium and attenuation of the retina.…”

“… 16 , 17 However, little has been understood regarding the molecular mechanisms of intestinal dysbiosis and how they induce retinopathy in patients with DM. Recently, data indicate that changes in the gut microbiome act as a key internal environmental modulator which favorably affects the pathogenetic processes underlying the micro-complications of DM such as DR. 18 …”