Short-Chain Fatty Acids and the Gut-Retina Connection: A Systematic Review

The interplay between gut microbiota and retinal health, known as the gut--retina axis, has gained increasing attention in recent years. Short-chain fatty acids (SCFAs), metabolites produced by gut microbiota, have been identified as key mediators of gut-retina communication. This systematic review explores the role of SCFAs in retinal health and their potential impact on the development and progression of retinal diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. A literature search was conducted across multiple databases, including PubMed, Google Scholar, and Science Direct, to identify studies published between 2014 and December 2024. Studies were included if they investigated the effects of SCFAs on retinal structure, function, or disease pathogenesis in animal models or human subjects. The review included 10 original articles spanning both preclinical and clinical studies. Evidence suggests that SCFAs play a crucial role in maintaining retinal homeostasis through anti-inflammatory and neuroprotective mechanisms. Dysbiosis of the gut microbiota, leading to altered SCFA production, was associated with increased retinal inflammation, oxidative stress, and vascular dysfunction. Furthermore, reduced SCFA levels were linked to the progression of retinal diseases, such as diabetic retinopathy and age-related macular degeneration. Modulation of gut microbiota and SCFA levels through dietary interventions or probiotics may represent a novel therapeutic strategy for preventing or managing retinal diseases. Further research is needed to elucidate the precise molecular mechanisms underlying SCFA-mediated retinal protection and to evaluate the efficacy of targeted therapies in clinical settings.