Through dynamic bidirectional communication along the gut-brain axis, the gut microbiota interacts with the host to regulate the development and optimal function of all body systems, (digestive and extra-digestive) (Chaudhry et al., 2023). This communication network involves a complex interplay of neural, hormonal and immune signaling mechanisms, connecting the gut and the brain (Zheng et al., 2023). Imbalance between gut microbial communities, or dysbiosis, and alterations in the processes of this network of signaling pathways via inflammatory, metabolic and oxidative stress mechanisms, etc., have been implicated in a number of human health disorders. Recent advances in microbiota research have unveiled intricate connections between the gut microbiota composition and the pathogenesis of systemic diseases, including metabolic disorders, autoimmune conditions, and neurological disorders including developmental and degenerative conditions of the nervous system (Intili et al., 2023; Ullah et al., 2023). In parallel, studies have begun to unravel the potential implications of gut microbiota dysbiosis in the context of eye health and disease. In fact, the microbiota-retina axis emerged as a concept when a network analysis was conducted to highlight the likely role of gut microbiota disruption in the development of retinal damages (Rowan et al., 2017; Rinninella et al., 2018). Rowan’s study found that age-related macular degeneration (AMD) can be prevented or reversed by using a diet that induces changes in the gut microbiota. The potential link between the gut microbiota as well as the ocular surface microbiota and ocular health has recently been broadened (Scuderi et al., 2022; Spörri et al., 2024). Therefore, the pathogenesis of several eye diseases, including AMD, diabetic retinopathy (DR), glaucoma, uveitis and newly inherited retinal degenerations (Douglas et al., 2023), etc.… has recently been associated with a larger concept termed the gut-eye axis (Floyd and Grant, 2020).

This mini-review of the literature aims to provide an overview of the current understanding of the gut-eye axis and the potential mechanisms underlying this axis, to offer insights into the biological basis of this relationship. It aims to disclose the role of the gut microbiota in the development, progression and management of retinopathies as well as other degenerative eye diseases including glaucoma and uveitis; and finally to elucidate challenges to target the gut microbiota to improve the prevention and treatment of these eye diseases.

The gut microbiota is involved in digestion, vitamin production, and the synthesis of short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate. It also protects against harmful bacteria, supports immune system development, and helps regulate T-cell populations like regulatory T cells (Tregs), T helper 1 (Th1) cells, and Th17 cells. These effects are mediated by the microbiota and their byproducts, such as SCFAs from microbes like Bacteroides that regulate Tregs and Th17 cells (Kho and Lal, 2018; Zeng and Chi, 2015).

The gut microbiota comprises more than 100 trillion microorganisms associated with multiple functions, from nutrient metabolism to protection against pathogens. Each individual encompasses a unique gut microbiota profile that changes over time, depending on certain variables such as lifestyle, physical exercise, body mass index, and dietary habits. Advances in sequencing technology, have played a key role in determining the composition of microbiota, which has been found to be mainly dominated by Proteobacteria, followed by Actinobacteria, Firmicutes, and Bacteroidetes (Xue et al., 2021).

A healthy gut microbiota maintains a balance between beneficial and harmful bacteria, and imbalances are linked to autoimmune intestinal diseases like Crohn’s disease and ulcerative colitis (Hornef and Pabst, 2016; Viladomiu et al., 2017). Disruptions in the gut microbiota are associated with various conditions, including irritable bowel syndrome, inflammatory bowel disease, obesity, diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and neurodegenerative diseases, some of which can have serious effects on eye health (Rajilić-Stojanović et al., 2015; Sheehan et al., 2015; Aron-Wisnewsky and Clément, 2016).

Since the introduction of the gut-retina axis concept by Rowan et al., the importance of gut microbes as regulators of ocular disease has gained significant attention (Rowan et al., 2017; Jayasudha et al., 2020). Research has shown that diet, probiotics, and antibiotics can influence the gut microbiota and, in turn, affect the development of ocular diseases (Bringer et al., 2022). In addition, the gut microbiota has been increasingly recognized as a factor influencing the onset and progression of multiple ocular diseases, including uveitis, dry eye, macular degeneration, diabetic retinopathy and glaucoma (Fu et al., 2023). In this bibliometric study, Fu et al. found a total of 284 relevant publications from 2009 to 2023 about gut microbiota and eye diseases. There were few studies in the first 5 years, but the number has increased steadily since 2016. These studies involved 1,376 authors from 41 countries. The top journal and the most cited journal were both Investigative Ophthalmology & Visual Science. The author concluded that emerging findings suggest the existence of a gut-eye axis, wherein gut dysbiosis may be an important factor influencing the onset and progression of multiple ocular diseases (Fu et al., 2023). The gut microbiota has a metabolic activity similar to that exhibited by other organs of the human body (Xue et al., 2021) and produces various metabolites, which can affect the host’s physiology and pathology. These metabolites can enter the systemic circulation and reach the eye, where they can modulate the function of the eye and contribute to the development of ocular diseases (Napolitano et al., 2021; Zhang et al., 2023).

A recent study analyzed publications from the Web of Science Core Collection database and identified articles related to gut microbiota and ocular diseases, with an increasing trend in the number of publications over time (Moon et al., 2020a). The most studied and described microbiota dysbiosis is in the bacterial microbiota, but other agents, such as viral and fungal communities, also reside in the intestine and can lead to various eye diseases when deregulated (Moon et al., 2020a,b). The gut-eye axis hypothesis suggests that dysbiosis of the intestinal microbiota or disruption in the intestinal barrier may result in translocation of intestinal microbes and further impact the eye, which is remotely located from the gut (Moon et al., 2020c; Deng et al., 2021). The gut microbiota and their metabolites may serve as endogenous culprits of ocular diseases, exerting their function through molecular mimicry and integrated immunological pathways (Deng et al., 2021).

The specific mechanisms through which gut microbiota, considered as a modulator of systemic health, including ocular health, influence pathogenic processes in ocular diseases are the following:

Our literature review has identified a growing body of evidence supporting the influence of the gut microbiota on ocular health and disease. Research has demonstrated variations in the gut microbiota composition among individuals with certain eye diseases compared to healthy controls. Furthermore, preclinical studies have highlighted potential mechanisms by which the gut microbiota may regulate ocular immune responses, inflammation, and neuro-degeneration, thereby affecting the pathogenesis of eye diseases. However, the precise mechanisms of the gut-eye axis remain incompletely understood, necessitating further investigation.

Targeting the gut microbiota to prevent and manage eye diseases represents a promising frontier in medical research, expanding our understanding of the intricate relationship between gut health and ocular function.

As we have already seen, recent investigations have highlighted how dysbiosis, or imbalance in gut microbial communities, can contribute to the development and progression of eye conditions such as AMD, DR, glaucoma, and uveitis. In fact, the gut microbiota, comprising trillions of microorganisms, plays an important role beyond digestive functions, influencing systemic inflammation, immune modulation, and even neurologic processes.

The therapeutic potential of targeting the gut microbiota lies in its ability to modulate these inflammatory and metabolic pathways. Interventions such as dietary modifications, probiotics, fecal microbiota transplantation, or microbial-derived therapies hold promise in restoring microbial balance, reducing systemic inflammation, and improving outcomes in ocular diseases. By understanding and manipulating these microbial communities, clinicians may potentially personalize treatments to mitigate disease progression and enhance therapeutic efficacy (Parker et al., 2022).

Moreover, ongoing research efforts are exploring the identification of microbial biomarkers predictive of ocular disease risk or progression, which could revolutionize early diagnosis and intervention strategies (Wang et al., 2023; Khan et al., 2021). In a recent study, genetic analyses have determined that gut microbiota is causally associated with myopia risk. Furthermore, transplantation of fecal microbiota from healthy donors into a mouse model of myopia results in increased plasma 3-IAA levels and a simultaneous delay in myopia progression, as well as improved maintenance of type I alpha 1 collagen (COL1A1) expression in the sclera. The authors suggest new strategies for intervening in high myopia by remodeling the intestinal microbiota and supplementing with indole (Li et al., 2024). This multidisciplinary approach not only integrates microbiology and ophthalmology but also underscores the importance of systemic health in maintaining optimal eye function. As our understanding of the gut-eye axis continues to evolve, so too does the potential for innovative therapies that harness the power of the gut microbiota to promote ocular health.

While this review provides a comprehensive summary of the existing literature on the gut-eye axis and its implications for retinal and ocular degenerative diseases, a more robust critical analysis is necessary to enhance its impact.

To address these limitations and advance the field, future research should focus on the following directions:

By addressing these critical areas, future research can contribute to a more nuanced understanding of the gut-eye axis and facilitate the development of targeted, effective therapeutic interventions for retinal and ocular degenerative diseases.

These findings of the literature review underscore the complex interplay between gut microbiota and ocular health, suggesting potential avenues for therapeutic interventions and disease management.

Modulation of gut microbiota represents a promising approach for targeting systemic inflammation and immune dysregulation associated with certain eye diseases. Additionally, the identification of microbial biomarkers predictive of ocular disease risk or progression may facilitate early diagnosis and personalized treatment strategies.

Nonetheless, several challenges and unanswered questions persist, warranting continued research efforts to unravel the intricacies of the gut-eye axis and its therapeutic implications.