# The gut-retina axis in age-related macular degeneration: immune crosstalk and metabolite production

## TL;DR

This paper explores how gut health influences eye diseases like AMD through immune and metabolite interactions, suggesting dietary and microbiome-based treatments.

## Contribution

The paper provides a comprehensive review of the gut-retina axis in AMD, emphasizing microbial-immune crosstalk and novel therapeutic strategies.

## Key findings

- Dysbiosis in the gut microbiome contributes to AMD progression through immune activation and pro-angiogenic cytokines.
- Metabolites like short-chain fatty acids and bile acids modulate host immunity and AMD risk.
- Dietary changes and fecal microbiota transplantation show potential in reducing AMD severity.

## Abstract

Current therapies slow down advanced features but do not halt or reverse degeneration and neovascularization in dry and wet age-related macular degeneration (AMD). Recent research implicates the gastrointestinal microbiome as a potential critical modulator in AMD pathogenesis through the gut-retina axis. Dysbiosis, characterized by imbalanced microbial diversity, composition and function, can exacerbate systemic and retinal inflammation through microglial priming, inflammasome activation, and secretion of pro-angiogenic cytokines (IL-6, IL-1β, TNF-α, VEGF). Additionally, microbiome-derived metabolites such as short-chain fatty acids and bile acids may exert modulatory roles in host immunity and homeostasis. Their depletion in conjunction with enrichment of specific microbial taxa have been linked to progression of advanced AMD. Together, these complex systems of immune crosstalk in relation to dysbiosis highlight the gut-retina axis as a promising therapeutic target. Dietary modifications, particularly Mediterranean and high-fiber diets, enhance production of protective metabolites and are associated with decreased AMD progression risk compared to Western dietary patterns. Experimental strategies such as fecal microbiota transplantation in animal models and drug repurposing strategies show promise in modulating disease severity. This review synthesizes current mechanistic insights into microbial-immune crosstalk in AMD, emphasizing the interplay of dysbiosis, immune activation, and metabolite signaling.