The Gut-Eye Axis: Lessons Learned from Murine Models

Jason L Floyd, Maria B Grant, Jason L Floyd, Maria B Grant

Abstract

A healthy gut microbiota is essential in maintaining the human body in a homeostatic state by its functions in digestion and immune tolerance. Under states of aberrant microbial composition or function (dysbiosis), the gut microbiota induces systemic inflammation that can lead to the onset of many diseases. In this review, we describe some evidence, largely from rodent studies, that supports the possible role of a dysbiotic gut microbiota in the onset and exacerbation of ocular diseases, primarily diabetic retinopathy, age-related macular degeneration, choroidal neovascularization, and uveitis. Furthermore, we examine several potential therapeutic measures that show promise in restoring the gut microbiota to a eubiotic state, preventing the aforementioned disease pathologies.

Keywords: Age-related macular degeneration; Choroidal neovascularization; Diabetic retinopathy; Diet; Fecal microbiota transplant; Glaucoma; Gut microbiota; Intermittent fasting; Probiotic; Uveitis.

Figures

Fig. 1
Fig. 1
The effects of gut dysbiosis. A dysbiotic gut microbiota, typically associated with an increased Firmicutes/Bacteroidetes (F/B) ratio, results in thinning of the intestinal mucus layer and disruption of the gut–vascular barrier. Together, loss of these physiological barriers allows for translocation of gut commensal bacteria and bacterial products into the circulation, where they travel to tissues and induce pathological inflammation
Fig. 2
Fig. 2
The effects of cellular and nutritional therapies on the prevention of diabetic retinopathy. a In a model of type 1 diabetes with ACE2 deficiency (ACE2−/y-Akita), intraperitoneal injection of FACS-sorted wild-type (WT) bone marrow myeloid angiogenic cells (MACs) was shown to restructure the gut microbiota and repair the gut–vascular barrier (GVB). The intact GVB resulted in a decrease in the levels of systemic peptidoglycan (PGN), inhibiting a noncanonical TLR2-mediated signaling cascade in the retina, reducing retinal barrier dysfunction. b In a model of type 2 diabetes (db/db), intermittent fasting on an alternate-day regimen was shown to restructure the gut microbiota and activate production of beneficial secondary bile acids, specifically tauroursodeoxycholate (TUDCA), in the liver. TUDCA prevented progression of DR via activation of its receptor, TGR5, in the neural retina
Fig. 3
Fig. 3
The gut–eye axis in ocular diseases. Alterations in the gut microbiota have been shown to be associated with multiple ocular diseases, including diabetic retinopathy, age-related macular degeneration, choroidal neovascularization, and uveitis. Various groups have shown that restructuring the gut microbiota by cellular and antibiotic therapies, intermittent fasting, and dietary intervention have potential therapeutic benefits in preventing/treating ocular diseases

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