Research progress of diabetic retinopathy and gut microecology

Abstract

According to the prediction of the International Diabetes Federation, global diabetes mellitus (DM) patients will reach 783.2 million in 2045. The increasing incidence of DM has led to a global epidemic of diabetic retinopathy (DR). DR is a common microvascular complication of DM, which has a significant impact on the vision of working-age people and is one of the main causes of blindness worldwide. Substantial research has highlighted that microangiopathy and chronic low-grade inflammation are widespread in the retina of DR. Meanwhile, with the introduction of the gut-retina axis, it has also been found that DR is associated with gut microecological disorders. The disordered structure of the GM and the destruction of the gut barrier result in the release of abnormal GM flora metabolites into the blood circulation. In addition, this process induced alterations in the expression of various cytokines and proteins, which further modulate the inflammatory microenvironment, vascular damage, oxidative stress, and immune levels within the retina. Such alterations led to the development of DR. In this review, we discuss the corresponding alterations in the structure of the GM flora and its metabolites in DR, with a more detailed focus on the mechanism of gut microecology in DR. Finally, we summarize the potential therapeutic approaches of DM/DR, mainly regulating the disturbed gut microecology to restore the homeostatic level, to provide a new perspective on the prevention, monitoring, and treatment of DR.

Keywords: diabetic retinopathy; gut microbiota; gut microecology; gut-retinal axis; metabolite.

Figure 1

Changes in the structure of the GM flora in DM/DR patients.

Figure 2

Production and mechanism of GM flora metabolites. (A) Promote inflammatory response. As shown in Figure 1, the GM flora of DR is disordered, and a large number of GM gram-negative bacteria accumulate to produce LPS. GM flora lyses choline and gradually oxidizes through the liver portal vein to produce TMAO, which binds to TLR4 and NLRP3 on the surface of blood vessels and the retina through IEC with impaired barrier function, activating the NF-κB pathway, up-regulates inflammatory cytokines and releases them into the retinal microenvironment. Probiotic supplementation and DHA diet can inhibit the above pathways to reduce inflammation and oxidative stress. (B) Inhibition of inflammatory response. The liver and GM flora gradually produce secondary BAs, Faecalibacterium/Akkermansia/ Phascolarctobacterium and other GM flora to produce SCFAs, which are absorbed through the gut and combined with TGR5 and GRP to maintain IEC homeostasis, promote the secretion of GLP-1 in the blood, reduce NO levels, induce DCs to activate Treg cells and inhibit Th17 cells, up-regulate anti-inflammatory factors and down-regulate pro-inflammatory factors to act synergistically on the retina to maintain gut and retinal homeostasis. Supplementation with BAs and SCFAs can improve the immune system, the metabolism, and the anti-inflammatory capacity of the organism.