Unveiling the gut-eye axis: how microbial metabolites influence ocular health and disease

Abstract

The intricate interplay between the gut microbiota and ocular health has surpassed conventional medical beliefs, fundamentally reshaping our understanding of organ interconnectivity. This review investigates into the intricate relationship between gut microbiota-derived metabolites and their consequential impact on ocular health and disease pathogenesis. By examining the role of specific metabolites, such as short-chain fatty acids (SCFAs) like butyrate and bile acids (BAs), herein we elucidate their significant contributions to ocular pathologies, thought-provoking the traditional belief of organ sterility, particularly in the field of ophthalmology. Highlighting the dynamic nature of the gut microbiota and its profound influence on ocular health, this review underlines the necessity of comprehending the complex workings of the gut-eye axis, an emerging field of science ready for further exploration and scrutiny. While acknowledging the therapeutic promise in manipulating the gut microbiome and its metabolites, the available literature advocates for a targeted, precise approach. Instead of broad interventions, it emphasizes the potential of exploiting specific microbiome-related metabolites as a focused strategy. This targeted approach compared to a precision tool rather than a broad-spectrum solution, aims to explore the therapeutic applications of microbiome-related metabolites in the context of various retinal diseases. By proposing a nuanced strategy targeted at specific microbial metabolites, this review suggests that addressing specific deficiencies or imbalances through microbiome-related metabolites might yield expedited and pronounced outcomes in systemic health, extending to the eye. This focused strategy holds the potential in bypassing the irregularity associated with manipulating microbes themselves, paving a more efficient pathway toward desired outcomes in optimizing gut health and its implications for retinal diseases.

Keywords: bile acids; butyrate; microbiome; ocular diseases; short chain fatty acids.

Figure 1

The gut-eye axis in retinal health and disease. The complex interplay between the gut microbiome (GM) and retinal health. This diagram illustrates the numerous factors influencing the gut-eye axis and its potential role in various retinal diseases. “Created with BioRender.com”.

Figure 2

Gut Microbiota-Derived Metabolite Production. Gut microbiota generates a diverse array of metabolites through distinct pathways: (1) Dietary Fermentation: Here, bacteria “transform” ingested food components, like fibers, into bioactive molecules like short-chain fatty acids (SCFAs) or branched-chain amino acids (BCAAs). (2) Host-Microbial Collaboration: In this interplay, the host produces primary metabolites that gut bacteria refine into potent compounds. (3) Microbial Independence: Some bacteria possess the remarkable ability to “craft” specific metabolites, like trimethylamine-N-oxide (TMAO), entirely from scratch, independent of diet or host precursors. BCAAs: Branched-chain amino acids, SCFAs: Short-chain fatty acids, TMAO: Trimethylamine-N-oxide. “Created with BioRender.com”.

Figure 3

Microbial metabolites, specifically bile acids and butyrate, exert significant influence on retinal health. (A) Bile acids, produced through cholesterol metabolism, impact retinal inflammation, vascular function, and oxidative stress. Meanwhile, (B) butyrate, a short-chain fatty acid, modulates (C–E) immune responses and neuronal survival within the retina. Understanding these metabolites’ roles is crucial for developing targeted therapies to mitigate retinal pathologies. Created with BioRender.com.